Topic: BusinessManagement

Last updated: January 20, 2020

Impact of Vitamin D Therapy in treating X-linked hypophosphatemic ricketsKate BarrattResearch ProposalFor the degree of Masters by Research (Medical Science)SupervisorsAssociate Professor Paul AndersonProfessor Gerald AtkinsProfessor Howard MorrisOUTLINE:X-Linked Hypophosphatemic Rickets (XLH) is a rare hereditary disorder that is difficult to treat without significant side-effects ADDIN EN.CITE <EndNote><Cite><Author>Lee</Author><Year>2013</Year><RecNum>49</RecNum><DisplayText>(Lee &amp; Imel 2013)</DisplayText><record><rec-number>49</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1523104063″>49</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Lee, J. Y</author><author>Imel, E. A</author></authors></contributors><titles><title>The Changing Face of Hypophosphatemic Disorders in the FGF-23 Era</title><secondary-title>Paediatr Endocrinol Rev.</secondary-title></titles><periodical><full-title>Paediatr Endocrinol Rev.

</full-title></periodical><pages>367-379</pages><volume>10</volume><dates><year>2013</year></dates><urls></urls></record></Cite></EndNote>(Lee & Imel 2013). XLH is caused by a mutation in the osteocyte gene, phosphate-regulating endopeptidase homolog, X-linked (PHEX) 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Linglart et al. 2014). This mutation of PHEX impairs cleavage, and accumulation, of Fibroblast Growth Factor 23 (FGF23) 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 ADDIN EN.

We Will Write a Custom Essay Specifically
For You For Only $13.90/page!


order now

CITE 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 ADDIN EN.CITE.DATA (Murali et al.

2016). Elevated FGF23 levels in XLH causes excessive renal excretion of phosphate leading to hypophosphatemia, and low circulating active vitamin D (1,25(OH)2D) levels due to both inhibited synthesis and excessive catabolism of vitamin D ADDIN EN.CITE <EndNote><Cite><Author>Tenenhouse</Author><Year>1990</Year><RecNum>55</RecNum><DisplayText>(Tenenhouse &amp; Jones 1990)</DisplayText><record><rec-number>55</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1533031688″>55</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Tenenhouse, H.

S</author><author>Jones, G.</author></authors></contributors><titles><title>Abnormal Regulation of Renal Vitamin D Catabolism by Dietary Phosphate in Murine X-linked Hypophosphatemic Rickets</title><secondary-title>J Clin. Invest.

</secondary-title></titles><periodical><full-title>J Clin. Invest.</full-title></periodical><pages>1450-1455</pages><volume>85</volume><dates><year>1990</year></dates><urls></urls></record></Cite></EndNote>(Tenenhouse & Jones 1990). It has been long thought that disturbed renal metabolism of vitamin D is major contributor to the development of undermineralised bone, or rickets ADDIN EN.CITE <EndNote><Cite><Author>Tenenhouse</Author><Year>1990</Year><RecNum>55</RecNum><DisplayText>(Tenenhouse &amp; Jones 1990)</DisplayText><record><rec-number>55</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1533031688″>55</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Tenenhouse, H. S</author><author>Jones, G.

</author></authors></contributors><titles><title>Abnormal Regulation of Renal Vitamin D Catabolism by Dietary Phosphate in Murine X-linked Hypophosphatemic Rickets</title><secondary-title>J Clin. Invest.</secondary-title></titles><periodical><full-title>J Clin. Invest.</full-title></periodical><pages>1450-1455</pages><volume>85</volume><dates><year>1990</year></dates><urls></urls></record></Cite></EndNote>(Tenenhouse & Jones 1990). However, recent evidence suggests that (a) local metabolism of 1,25(OH)2D in bone has an independent and critical role for bone mineralisation ADDIN EN.

CITE <EndNote><Cite><Author>Anderson</Author><Year>2017</Year><RecNum>94</RecNum><DisplayText>(Anderson 2017)</DisplayText><record><rec-number>94</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1534470997″>94</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Anderson, P. H.</author></authors></contributors><auth-address>Musculoskeletal Biology Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5001, Australia. [email protected]

edu.au.</auth-address><titles><title>Vitamin D Activity and Metabolism in Bone</title><secondary-title>Curr Osteoporos Rep</secondary-title></titles><periodical><full-title>Curr Osteoporos Rep</full-title></periodical><pages>443-449</pages><volume>15</volume><number>5</number><edition>2017/08/16</edition><keywords><keyword>25-Hydroxyvitamin D3 1-alpha-Hydroxylase/*metabolism</keyword><keyword>Autocrine Communication</keyword><keyword>Bone Resorption/metabolism</keyword><keyword>Bone and Bones/*metabolism</keyword><keyword>Calcification, Physiologic/physiology</keyword><keyword>Fracture Healing/physiology</keyword><keyword>Humans</keyword><keyword>Receptors, Calcitriol/*metabolism</keyword><keyword>Vitamin D/*analogs &amp; derivatives/metabolism</keyword><keyword>Vitamin D3 24-Hydroxylase/*metabolism</keyword><keyword>Cyp24a1</keyword><keyword>Cyp27b1</keyword><keyword>Mineralisation</keyword><keyword>Osteoblasts</keyword><keyword>Vitamin D</keyword><keyword>Vitamin D receptor</keyword></keywords><dates><year>2017</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1544-2241 (Electronic) 1544-1873 (Linking)</isbn><accession-num>28808890</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/28808890</url></related-urls></urls><electronic-resource-num>10.

1007/s11914-017-0394-8</electronic-resource-num></record></Cite></EndNote>(Anderson 2017) (b) that the inhibition of vitamin D catabolism in disorders of rickets due to FGF23 excess, induces the near-complete healing of rickets without the need to lower FGF23 levels nor rescue the hypophosphatemia 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Bai et al. 2016).

These data, and the importance of finding effective treatments for XLH provide great importance for investigating the following hypothesis and aims:Hypothesis: Raising active vitamin D (1,25D) levels within the bone and/or the intestine (via preventing catabolism) prevents rickets in the Hyp mouse model (the mouse homolog for the disorder of XLH) by increasing mineralisation.Aim 1: To determine whether raising circulating 25-hydroxyvitamin D (25D) levels heal the bone in Hyp mice.Aim 2: To determine whether raising osteocyte levels of active vitamin D (1,25(OH)2D) heals the bone of Hyp mice.LITERATURE REVIEW:416623574295Figure 1: Bone deformities in a severe case of XLH0Figure 1: Bone deformities in a severe case of XLHPrevalence and impact of X-linked Hypophosphatemic Rickets: X-Linked Hypophosphatemia (XLH) is a rare genetic disorder, affecting 1 in 20,000 individuals 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 ADDIN EN.CITE 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 ADDIN EN.

CITE.DATA (Azam et al. 2003). The disease is characterised by the excessive renal excretion of serum phosphate leading to hypophosphatemia ADDIN EN.CITE <EndNote><Cite><Author>Saito</Author><Year>2009</Year><RecNum>28</RecNum><DisplayText>(Saito &amp; Fukumoto 2009)</DisplayText><record><rec-number>28</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519884606″>28</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Saito, T.</author><author>Fukumoto, S.</author></authors></contributors><auth-address>Department of Pediatrics, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

</auth-address><titles><title>Fibroblast Growth Factor 23 (FGF23) and Disorders of Phosphate Metabolism</title><secondary-title>Int J Pediatr Endocrinol</secondary-title></titles><periodical><full-title>Int J Pediatr Endocrinol</full-title></periodical><pages>496514</pages><volume>2009</volume><dates><year>2009</year></dates><isbn>1687-9856 (Electronic) 1687-9848 (Linking)</isbn><accession-num>19956747</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/19956747</url></related-urls></urls><custom2>PMC2775677</custom2><electronic-resource-num>10.

1155/2009/496514</electronic-resource-num></record></Cite></EndNote>(Saito & Fukumoto 2009). Hypophosphatemia is generally considered to result in reduced hydroxyapatite (bone mineral) formation resulting in under-mineralisation of the skeleton or rickets (Figure 1) ADDIN EN.CITE <EndNote><Cite><Author>De Menezes Filho</Author><Year>2006</Year><RecNum>101</RecNum><DisplayText>(De Menezes Filho, De Castro &amp; Damiani 2006)</DisplayText><record><rec-number>101</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1537168877″>101</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>De Menezes Filho, H.</author><author>De Castro, L. C. G.</author><author>Damiani, D.

</author></authors></contributors><titles><title>Hypophosphatemic Rickets and Osteomalacia</title></titles><volume>50</volume><number>4</number><dates><year>2006</year></dates><urls></urls></record></Cite></EndNote>(De Menezes Filho, De Castro & Damiani 2006). XLH usually presents in late infancy as growth retardation, skeletal deformities and rickets become apparent. XLH children display a delay in walking, bowed legs, craniostenosis, dental abscesses, entesopathy, fractures, and bone pain 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Linglart et al.

2014; Makitie et al. 2003). The principal symptoms of XLH in adults are bone pain, joint pain, and stiffness. As patients age, long-term weight bearing on misaligned joints often results in osteoarthritis 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Che et al.

2016). While treatment with oral phosphate and active vitamin D compounds, such as 1,25(OH)2D3, are a common therapy for XLH, treatment from infancy results in the best outcomes for children suffering with XLH ADDIN EN.CITE <EndNote><Cite><Author>Makitie</Author><Year>2003</Year><RecNum>22</RecNum><DisplayText>(Makitie et al.

2003)</DisplayText><record><rec-number>22</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519794285″>22</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Makitie, O.</author><author>Doria, A.</author><author>Kooh, S. W.</author><author>Cole, W. G.

</author><author>Daneman, A.</author><author>Sochett, E.</author></authors></contributors><auth-address>Division of Endocrinology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8.

[email protected]</auth-address><titles><title>Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets</title><secondary-title>J Clin Endocrinol Metab</secondary-title></titles><periodical><full-title>J Clin Endocrinol Metab</full-title></periodical><pages>3591-7</pages><volume>88</volume><number>8</number><keywords><keyword>Age of Onset</keyword><keyword>Body Height/drug effects</keyword><keyword>Bone and Bones/diagnostic imaging</keyword><keyword>Calcitriol/blood</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Growth/*drug effects</keyword><keyword>Humans</keyword><keyword>Hypophosphatemia/blood</keyword><keyword>Hypophosphatemia, Familial/diagnostic imaging/metabolism/*therapy</keyword><keyword>Infant</keyword><keyword>Radiography</keyword><keyword>Retrospective Studies</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2003</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0021-972X (Print) 0021-972X (Linking)</isbn><accession-num>12915641</accession-num><urls><related-urls><url>https://www.ncbi.nlm.

nih.gov/pubmed/12915641</url></related-urls></urls><electronic-resource-num>10.1210/jc.2003-030036</electronic-resource-num></record></Cite></EndNote>(Makitie et al. 2003). However, treatment of XLH patients frequently results either in severe side effects such as hypercalcaemia, or has no positive effects on bone health ADDIN EN.CITE <EndNote><Cite><Author>Makitie</Author><Year>2003</Year><RecNum>22</RecNum><DisplayText>(Makitie et al. 2003)</DisplayText><record><rec-number>22</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519794285″>22</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Makitie, O.

</author><author>Doria, A.</author><author>Kooh, S. W.</author><author>Cole, W. G.</author><author>Daneman, A.</author><author>Sochett, E.

</author></authors></contributors><auth-address>Division of Endocrinology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8. [email protected]</auth-address><titles><title>Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets</title><secondary-title>J Clin Endocrinol Metab</secondary-title></titles><periodical><full-title>J Clin Endocrinol Metab</full-title></periodical><pages>3591-7</pages><volume>88</volume><number>8</number><keywords><keyword>Age of Onset</keyword><keyword>Body Height/drug effects</keyword><keyword>Bone and Bones/diagnostic imaging</keyword><keyword>Calcitriol/blood</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Growth/*drug effects</keyword><keyword>Humans</keyword><keyword>Hypophosphatemia/blood</keyword><keyword>Hypophosphatemia, Familial/diagnostic imaging/metabolism/*therapy</keyword><keyword>Infant</keyword><keyword>Radiography</keyword><keyword>Retrospective Studies</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2003</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0021-972X (Print) 0021-972X (Linking)</isbn><accession-num>12915641</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.

gov/pubmed/12915641</url></related-urls></urls><electronic-resource-num>10.1210/jc.2003-030036</electronic-resource-num></record></Cite></EndNote>(Makitie et al. 2003). While recent developments have provided new therapeutic options, numerous side effects have been reported ADDIN EN.CITE <EndNote><Cite><Author>Carpenter</Author><Year>2011</Year><RecNum>98</RecNum><DisplayText>(Carpenter et al.

2011)</DisplayText><record><rec-number>98</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1536560091″>98</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Carpenter, T. O.</author><author>Imel, E. A.</author><author>Holm, I.

A.</author><author>Jan de Beur, S. M.</author><author>Insogna, K. L.

</author></authors></contributors><auth-address>Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-8064, USA. [email protected]

edu</auth-address><titles><title>A clinician&apos;s guide to X-linked hypophosphatemia</title><secondary-title>J Bone Miner Res</secondary-title></titles><periodical><full-title>J Bone Miner Res</full-title></periodical><pages>1381-8</pages><volume>26</volume><number>7</number><edition>2011/05/04</edition><keywords><keyword>*Familial Hypophosphatemic Rickets/diagnostic</keyword><keyword>imaging/pathology/physiopathology/therapy</keyword><keyword>*Genetic Diseases, X-Linked</keyword><keyword>Humans</keyword><keyword>Practice Guidelines as Topic</keyword><keyword>Radiography</keyword></keywords><dates><year>2011</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1523-4681 (Electronic) 0884-0431 (Linking)</isbn><accession-num>21538511</accession-num><urls><related-urls><url>https://www.ncbi.nlm.

nih.gov/pubmed/21538511</url></related-urls></urls><custom2>PMC3157040</custom2><electronic-resource-num>10.1002/jbmr.

340</electronic-resource-num></record></Cite></EndNote>(Carpenter et al. 2011). Thus, further efforts are required to establish effective therapies which heal the under-mineralised bone disorder without causing significant side effects. 23787102134235Figure 2: XLH Pathophysiology ADDIN EN.CITE <EndNote><Cite><Author>Pharmaceutical</Author><Year>2018</Year><RecNum>102</RecNum><DisplayText>(Pharmaceutical 2018)</DisplayText><record><rec-number>102</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1537171348″>102</key></foreign-keys><ref-type name=”Web Page”>12</ref-type><contributors><authors><author>Ultragenyx Pharmaceutical</author></authors></contributors><titles><title>Burosumab for XLH</title></titles><dates><year>2018</year></dates><urls><related-urls><url><style face=”underline” font=”default” size=”100%”>https://www.ultragenyx.com/pipeline/krn23-xlh/</style></url></related-urls></urls></record></Cite></EndNote>(Pharmaceutical 2018)00Figure 2: XLH Pathophysiology ADDIN EN.

CITE <EndNote><Cite><Author>Pharmaceutical</Author><Year>2018</Year><RecNum>102</RecNum><DisplayText>(Pharmaceutical 2018)</DisplayText><record><rec-number>102</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1537171348″>102</key></foreign-keys><ref-type name=”Web Page”>12</ref-type><contributors><authors><author>Ultragenyx Pharmaceutical</author></authors></contributors><titles><title>Burosumab for XLH</title></titles><dates><year>2018</year></dates><urls><related-urls><url><style face=”underline” font=”default” size=”100%”>https://www.ultragenyx.com/pipeline/krn23-xlh/</style></url></related-urls></urls></record></Cite></EndNote>(Pharmaceutical 2018)The cause of XLH: In XLH, a loss-of-function mutation in the phosphate-regulating endopeptidase homolog, X-linked (PHEX) gene results in excessive levels of the Fibroblast Growth Factor 23 (FGF23) protein 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 ADDIN EN.CITE 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 ADDIN EN.CITE.

DATA (Leifheit-Nestler et al. 2017). Fibroblast Growth Factor 23 (FGF23) is a bone derived hormone that was relatively recently discovered in 2000. FGF23 is mainly produced in two bone cell types, osteoblasts and osteocytes, and is normally produced in response to high levels of circulating phosphorus and active vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) ADDIN EN.CITE <EndNote><Cite><Author>Erben</Author><Year>2017</Year><RecNum>8</RecNum><DisplayText>(Erben 2017)</DisplayText><record><rec-number>8</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519791986″>8</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Erben, R. G.

</author></authors></contributors><auth-address>1 Department of Biomedical Sciences, Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria.</auth-address><titles><title>Pleiotropic Actions of FGF23</title><secondary-title>Toxicol Pathol</secondary-title></titles><periodical><full-title>Toxicol Pathol</full-title></periodical><pages>904-910</pages><volume>45</volume><number>7</number><keywords><keyword>bone</keyword><keyword>bone mineralization</keyword><keyword>cardiovascular system</keyword><keyword>endocrine system</keyword><keyword>mineral metabolism</keyword><keyword>renal</keyword><keyword>transgenic animals</keyword></keywords><dates><year>2017</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1533-1601 (Electronic) 0192-6233 (Linking)</isbn><accession-num>29096595</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.

gov/pubmed/29096595</url></related-urls></urls><electronic-resource-num>10.1177/0192623317737469</electronic-resource-num></record></Cite></EndNote>(Erben 2017). In a feedback mechanism, FGF23 is responsible for promoting the excretion of phosphorus as well as reducing 1,25(OH)2D levels (Figure 2) ADDIN EN.CITE <EndNote><Cite><Author>Portale</Author><Year>2012</Year><RecNum>66</RecNum><DisplayText>(Portale, Perwad &amp; Miller 2012)</DisplayText><record><rec-number>66</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1533032235″>66</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Book Section”>5</ref-type><contributors><authors><author>Portale, Anthony A.</author><author>Perwad, Farzana</author><author>Miller, Walter L.

</author></authors></contributors><titles><title>Rickets Due to Hereditary Abnormalities of Vitamin D Synthesis or Action</title><secondary-title>Pediatric Bone</secondary-title></titles><pages>679-698</pages><dates><year>2012</year></dates><isbn>9780123820402</isbn><urls></urls><electronic-resource-num>10.1016/b978-0-12-382040-2.10025-5</electronic-resource-num></record></Cite></EndNote>(Portale, Perwad & Miller 2012). In XLH, elevated FGF23 levels prevent the renal proximal tubular phosphate reabsorption, by reducing Sodium-Phosphate transporters (NaPi2a and NaPi2c) as well as inhibits the intestinal sodium-phosphate transporter (NaPi2b), resulting in inappropriately high phosphate wasting 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Kido et al.

2013). Excess FGF23 levels also acts to markedly reduce 1,25(OH)2D levels both by supressing the 25-hydroxyvitamin D 1?-hydroxylase enzyme, CYP27B1, which is responsible for the conversion of inactive vitamin D (25(OH)D) to 1,25(OH)2D, and by inducing the 25-hydroxyvitamin D 24-hydroxylase enzyme, CYP24A1, which acts to convert 1,25(OH)2D, as well as 25(OH)D, to inactive metabolites 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Liu et al. 2016).The role of phosphate in XLH: Phosphate, whilst less tightly regulated than calcium, plays a critical role in bone homeostasis including directly contributing to chondrocyte maturation and skeletal mineralisation PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LbzwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJlY051bT41PC9SZWNOdW0+PERpc3BsYXlUZXh0PihLbyBldCBhbC4gMjAxNik8L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+NTwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Inhmd2Z4czl2MnpycGU5ZXIyYTlwd2Q5Znh2NXoydjkyd2U1ZCIgdGltZXN0YW1wPSIxNTE5NzkxNjc3Ij41PC9rZXk+PGtleSBhcHA9IkVOV2ViIiBkYi1pZD0iIj4wPC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5LbywgRi4gQy48L2F1dGhvcj48YXV0aG9yPk1hcnRpbnMsIEouIFMuPC9hdXRob3I+PGF1dGhvcj5SZWRkeSwgUC48L2F1dGhvcj48YXV0aG9yPkJyYWdkb24sIEIuPC9hdXRob3I+PGF1dGhvcj5IdXNzZWluLCBBLiBJLjwvYXV0aG9yPjxhdXRob3I+R2Vyc3RlbmZlbGQsIEwuIEMuPC9hdXRob3I+PGF1dGhvcj5EZW1heSwgTS4gQi48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5FbmRvY3JpbmUgVW5pdCwgTWFzc2FjaHVzZXR0cyBHZW5lcmFsIEhvc3BpdGFsLCBCb3N0b24sIE1BLCBVU0EuJiN4RDtIYXJ2YXJkIE1lZGljYWwgU2Nob29sLCBCb3N0b24sIE1BLCBVU0EuJiN4RDtEZXBhcnRtZW50IG9mIE9ydGhvcGFlZGljIFN1cmdlcnksIEJvc3RvbiBVbml2ZXJzaXR5IFNjaG9vbCBvZiBNZWRpY2luZSwgQm9zdG9uLCBNQSwgVVNBLjwvYXV0aC1hZGRyZXNzPjx0aXRsZXM+PHRpdGxlPkFjdXRlIFBob3NwaGF0ZSBSZXN0cmljdGlvbiBJbXBhaXJzIEJvbmUgRm9ybWF0aW9uIGFuZCBJbmNyZWFzZXMgTWFycm93IEFkaXBvc2UgVGlzc3VlIGluIEdyb3dpbmcgTWljZTwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5KIEJvbmUgTWluZXIgUmVzPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+SiBCb25lIE1pbmVyIFJlczwvZnVsbC10aXRsZT48L3BlcmlvZGljYWw+PHBhZ2VzPjIyMDQtMjIxNDwvcGFnZXM+PHZvbHVtZT4zMTwvdm9sdW1lPjxudW1iZXI+MTI8L251bWJlcj48a2V5d29yZHM+PGtleXdvcmQ+QWRpcG9jeXRlcy9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+QWRpcG9zZSBUaXNzdWUvKnBhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5BbmltYWxzPC9rZXl3b3JkPjxrZXl3b3JkPkJvZHkgQ29tcG9zaXRpb248L2tleXdvcmQ+PGtleXdvcmQ+Qm9uZSBNYXJyb3cvYmxvb2Qgc3VwcGx5LypwYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Qm9uZSBNb3JwaG9nZW5ldGljIFByb3RlaW5zL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+Qm9uZSBSZXNvcnB0aW9uL3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD5DZWxsIERpZmZlcmVudGlhdGlvbjwva2V5d29yZD48a2V5d29yZD5GZW1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5d29yZD5NZXNlbmNoeW1hbCBTdHJvbWFsIENlbGxzL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+TWljZTwva2V5d29yZD48a2V5d29yZD5Pc3Rlb2JsYXN0cy9tZXRhYm9saXNtL3BhdGhvbG9neTwva2V5d29yZD48a2V5d29yZD4qT3N0ZW9nZW5lc2lzPC9rZXl3b3JkPjxrZXl3b3JkPlBob3NwaGF0ZXMvKmRlZmljaWVuY3k8L2tleXdvcmQ+PGtleXdvcmQ+U2lnbmFsIFRyYW5zZHVjdGlvbjwva2V5d29yZD48a2V5d29yZD5Cb25lIGhpc3RvbW9ycGhvbWV0cnk8L2tleXdvcmQ+PGtleXdvcmQ+Qm9uZS1mYXQgaW50ZXJhY3Rpb25zPC9rZXl3b3JkPjxrZXl3b3JkPkRpc29yZGVycyBvZiBjYWxjaXVtIGFuZCBwaG9zcGhhdGUgbWV0YWJvbGlzbTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDE2PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+RGVjPC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MTUyMy00NjgxIChFbGVjdHJvbmljKSYjeEQ7MDg4NC0wNDMxIChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9uLW51bT4yNzMyNDE3NzwvYWNjZXNzaW9uLW51bT48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+aHR0cHM6Ly93d3cubmNiaS5ubG0ubmloLmdvdi9wdWJtZWQvMjczMjQxNzc8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEwMDIvamJtci4yODkxPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB= ADDIN EN.CITE 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 ADDIN EN.

CITE.DATA (Ko et al. 2016).

The main regulator of serum phosphate levels is FGF23. However, Parathyroid Hormone (PTH), and 1,25(OH)2D contribute to the regulation of phosphate levels as well ADDIN EN.CITE <EndNote><Cite><Author>Razzaque</Author><Year>2007</Year><RecNum>62</RecNum><DisplayText>(Razzaque &amp; Lanske 2007)</DisplayText><record><rec-number>62</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1533032213″>62</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Razzaque, M. S.</author><author>Lanske, B.</author></authors></contributors><auth-address>Department of Developmental Biology, Harvard School of Dental Medicine, Research and Education Building, Room # 304, 190 Longwood Avenue, Boston, Massachusetts 02115, USA. [email protected]

harvard.edu</auth-address><titles><title>The emerging role of the fibroblast growth factor-23-klotho axis in renal regulation of phosphate homeostasis</title><secondary-title>J Endocrinol</secondary-title></titles><periodical><full-title>J Endocrinol</full-title></periodical><pages>1-10</pages><volume>194</volume><number>1</number><edition>2007/06/27</edition><keywords><keyword>Animals</keyword><keyword>Bone and Bones/metabolism</keyword><keyword>Fibroblast Growth Factors/genetics/*physiology</keyword><keyword>Glucuronidase/genetics/*physiology</keyword><keyword>Homeostasis</keyword><keyword>Humans</keyword><keyword>Iron/metabolism</keyword><keyword>Kidney/*metabolism</keyword><keyword>Mice</keyword><keyword>Mice, Transgenic</keyword><keyword>Models, Animal</keyword><keyword>Phosphates/metabolism</keyword><keyword>Signal Transduction/*physiology</keyword></keywords><dates><year>2007</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0022-0795 (Print) 0022-0795 (Linking)</isbn><accession-num>17592015</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/17592015</url></related-urls></urls><custom2>PMC2900827</custom2><electronic-resource-num>10.1677/JOE-07-0095</electronic-resource-num></record></Cite></EndNote>(Razzaque & Lanske 2007). As discussed, in XLH, elevated FGF23 levels prevent the renal proximal tubular phosphate reabsorption, by reducing Sodium-Phosphate transporters (NaPi2a and NaPi2c) as well as inhibits the intestinal sodium-phosphate transporter (NaPi2b) 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 ADDIN EN.

CITE 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 ADDIN EN.CITE.DATA (Bowe et al. 2001). When supplemented with phosphate alone, XLH patients show a partial improvement in the rachitic phenotype, but no improvement in endosteal bone mineralisation ADDIN EN.CITE <EndNote><Cite><Author>Marie</Author><Year>1981</Year><RecNum>17</RecNum><DisplayText>(Marie, Travers &amp; Glorieux 1981)</DisplayText><record><rec-number>17</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519793688″>17</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Marie, P.

J.</author><author>Travers, R.</author><author>Glorieux, F.

H.</author></authors></contributors><titles><title>Healing of rickets with phosphate supplementation in the hypophosphatemic male mouse</title><secondary-title>Journal of Clinical Investigation</secondary-title></titles><periodical><full-title>Journal of Clinical Investigation</full-title></periodical><pages>911-914</pages><volume>67</volume><number>3</number><dates><year>1981</year></dates><isbn>0021-9738</isbn><urls></urls><electronic-resource-num>10.1172/jci110110</electronic-resource-num></record></Cite></EndNote>(Marie, Travers & Glorieux 1981).

This effect of phosphate is considered to directly effect chondrocyte differentiation and apoptosis. Phosphate activates the caspase-9-dependant mitochondrial pathway to mediate hypertrophic chondrocyte apoptosis. This activation is critical for growth plate maturation 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 ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TYWJiYWdoPC9BdXRob3I+PFllYXI+MjAwNTwvWWVhcj48UmVjTnVtPjM0PC9SZWNOdW0+PERpc3BsYXlUZXh0PihTYWJiYWdoLCBDYXJwZW50ZXIgJmFtcDsgRGVtYXkgMjAwNSk8L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+MzQ8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ4ZndmeHM5djJ6cnBlOWVyMmE5cHdkOWZ4djV6MnY5MndlNWQiIHRpbWVzdGFtcD0iMTUyMDMwMjYwNCI+MzQ8L2tleT48a2V5IGFwcD0iRU5XZWIiIGRiLWlkPSIiPjA8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlNhYmJhZ2gsIFkuPC9hdXRob3I+PGF1dGhvcj5DYXJwZW50ZXIsIFQuIE8uPC9hdXRob3I+PGF1dGhvcj5EZW1heSwgTS4gQi48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5FbmRvY3JpbmUgVW5pdCwgTWFzc2FjaHVzZXR0cyBHZW5lcmFsIEhvc3BpdGFsLCBIYXJ2YXJkIE1lZGljYWwgU2Nob29sLCBCb3N0b24sIE1BIDAyMTE0LCBVU0EuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+SHlwb3Bob3NwaGF0ZW1pYSBsZWFkcyB0byByaWNrZXRzIGJ5IGltcGFpcmluZyBjYXNwYXNlLW1lZGlhdGVkIGFwb3B0b3NpcyBvZiBoeXBlcnRyb3BoaWMgY2hvbmRyb2N5dGVzPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPlByb2MgTmF0bCBBY2FkIFNjaSBVIFMgQTwvc2Vjb25kYXJ5LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPlByb2MgTmF0bCBBY2FkIFNjaSBVIFMgQTwvZnVsbC10aXRsZT48L3BlcmlvZGljYWw+PHBhZ2VzPjk2MzctNDI8L3BhZ2VzPjx2b2x1bWU+MTAyPC92b2x1bWU+PG51bWJlcj4yNzwvbnVtYmVyPjxrZXl3b3Jkcz48a2V5d29yZD5BbmltYWxzPC9rZXl3b3JkPjxrZXl3b3JkPkFwb3B0b3Npcy8qcGh5c2lvbG9neTwva2V5d29yZD48a2V5d29yZD5CbG90dGluZywgV2VzdGVybjwva2V5d29yZD48a2V5d29yZD5DYWxjaXVtL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+Q2FzcGFzZSA5PC9rZXl3b3JkPjxrZXl3b3JkPkNhc3Bhc2VzLyptZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPkNob25kcm9jeXRlcy9jeXRvbG9neS8qcGh5c2lvbG9neTwva2V5d29yZD48a2V5d29yZD5IeXBvcGhvc3BoYXRlbWlhLypjb21wbGljYXRpb25zPC9rZXl3b3JkPjxrZXl3b3JkPkltbXVub2hpc3RvY2hlbWlzdHJ5PC9rZXl3b3JkPjxrZXl3b3JkPk1pY2U8L2tleXdvcmQ+PGtleXdvcmQ+TWljZSwgSW5icmVkIEM1N0JMPC9rZXl3b3JkPjxrZXl3b3JkPk1pY2UsIEtub2Nrb3V0PC9rZXl3b3JkPjxrZXl3b3JkPk1pdG9jaG9uZHJpYS9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPk11dGF0aW9uL2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPlBIRVggUGhvc3BoYXRlIFJlZ3VsYXRpbmcgTmV1dHJhbCBFbmRvcGVwdGlkYXNlPC9rZXl3b3JkPjxrZXl3b3JkPlBhcmF0aHlyb2lkIEhvcm1vbmUvbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5QaG9zcGhhdGVzLyptZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlByb3RlaW5zL2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPlJpY2tldHMvKmV0aW9sb2d5L2dlbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPlZpdGFtaW4gRC9hbmFsb2dzICZhbXA7IGRlcml2YXRpdmVzL21ldGFib2xpc208L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAwNTwveWVhcj48cHViLWRhdGVzPjxkYXRlPkp1bCA1PC9kYXRlPjwvcHViLWRhdGVzPjwvZGF0ZXM+PGlzYm4+MDAyNy04NDI0IChQcmludCkmI3hEOzAwMjctODQyNCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MTU5NzYwMjc8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJsPmh0dHBzOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzE1OTc2MDI3PC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjxjdXN0b20yPlBNQzExNzIyNDk8L2N1c3RvbTI+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjEwLjEwNzMvcG5hcy4wNTAyMjQ5MTAyPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPn== ADDIN EN.

CITE.DATA (Sabbagh, Carpenter & Demay 2005). The growth plate is responsible for the longitudinal endochondral ossification and determines the final length of the bone PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GdWVudGU8L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFyPjxSZWNOdW0+MzA8L1JlY051bT48RGlzcGxheVRleHQ+KEZ1ZW50ZSBldCBhbC4gMjAxNyk8L0Rpc3BsYXlUZXh0PjxyZWNvcmQ+PHJlYy1udW1iZXI+MzA8L3JlYy1udW1iZXI+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ4ZndmeHM5djJ6cnBlOWVyMmE5cHdkOWZ4djV6MnY5MndlNWQiIHRpbWVzdGFtcD0iMTUyMDIwNzUzNyI+MzA8L2tleT48a2V5IGFwcD0iRU5XZWIiIGRiLWlkPSIiPjA8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkZ1ZW50ZSwgUi48L2F1dGhvcj48YXV0aG9yPkdpbC1QZW5hLCBILjwvYXV0aG9yPjxhdXRob3I+Q2xhcmFtdW50LVRhYmVybmVyLCBELjwvYXV0aG9yPjxhdXRob3I+SGVybmFuZGV6LCBPLjwvYXV0aG9yPjxhdXRob3I+RmVybmFuZGV6LUlnbGVzaWFzLCBBLjwvYXV0aG9yPjxhdXRob3I+QWxvbnNvLUR1cmFuLCBMLjwvYXV0aG9yPjxhdXRob3I+Um9kcmlndWV6LVJ1YmlvLCBFLjwvYXV0aG9yPjxhdXRob3I+U2FudG9zLCBGLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YXV0aC1hZGRyZXNzPkRpdmlzaW9uIG9mIFBlZGlhdHJpY3MsIERlcGFydG1lbnQgb2YgTWVkaWNpbmUuIEZhY3VsdHkgb2YgTWVkaWNpbmUsIFVuaXZlcnNpdHkgb2YgT3ZpZWRvLCBPdmllZG8sIEFzdHVyaWFzLCBTcGFpbi4mI3hEO0RlcGFydG1lbnQgb2YgUGVkaWF0cmljcywgSG9zcGl0YWwgVW5pdmVyc2l0YXJpbyBDZW50cmFsIGRlIEFzdHVyaWFzIChIVUNBKSwgT3ZpZWRvLCBBc3R1cmlhcywgU3BhaW4uJiN4RDtEaXZpc2lvbiBvZiBQZWRpYXRyaWNzLCBEZXBhcnRtZW50IG9mIE1lZGljaW5lLiBGYWN1bHR5IG9mIE1lZGljaW5lLCBVbml2ZXJzaXR5IG9mIE92aWVkbywgT3ZpZWRvLCBBc3R1cmlhcywgU3BhaW4uIGZzYW50b3NAdW5pb3ZpLmVzLiYjeEQ7RGVwYXJ0bWVudCBvZiBQZWRpYXRyaWNzLCBIb3NwaXRhbCBVbml2ZXJzaXRhcmlvIENlbnRyYWwgZGUgQXN0dXJpYXMgKEhVQ0EpLCBPdmllZG8sIEFzdHVyaWFzLCBTcGFpbi4gZnNhbnRvc0B1bmlvdmkuZXMuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+WC1saW5rZWQgaHlwb3Bob3NwaGF0ZW1pYSBhbmQgZ3Jvd3RoPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPlJldiBFbmRvY3IgTWV0YWIgRGlzb3JkPC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+UmV2IEVuZG9jciBNZXRhYiBEaXNvcmQ8L2Z1bGwtdGl0bGU+PC9wZXJpb2RpY2FsPjxwYWdlcz4xMDctMTE1PC9wYWdlcz48dm9sdW1lPjE4PC92b2x1bWU+PG51bWJlcj4xPC9udW1iZXI+PGtleXdvcmRzPjxrZXl3b3JkPkFuaW1hbHM8L2tleXdvcmQ+PGtleXdvcmQ+RmFtaWxpYWwgSHlwb3Bob3NwaGF0ZW1pYyBSaWNrZXRzL2NvbXBsaWNhdGlvbnMvKm1ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+Rmlicm9ibGFzdCBHcm93dGggRmFjdG9ycy8qbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5Hcm93dGggRGlzb3JkZXJzL2RydWcgdGhlcmFweS9ldGlvbG9neS8qbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+KkJvbmU8L2tleXdvcmQ+PGtleXdvcmQ+Kkdyb3d0aDwva2V5d29yZD48a2V5d29yZD4qR3Jvd3RoIHBsYXRlPC9rZXl3b3JkPjxrZXl3b3JkPipIeXBvcGhvc3BoYXRlbWlhPC9rZXl3b3JkPjxrZXl3b3JkPipQaG9zcGhhdGU8L2tleXdvcmQ+PGtleXdvcmQ+KlJpY2tldHM8L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxNzwveWVhcj48cHViLWRhdGVzPjxkYXRlPk1hcjwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjE1NzMtMjYwNiAoRWxlY3Ryb25pYykmI3hEOzEzODktOTE1NSAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjgxMzA2MzQ8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJsPmh0dHBzOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzI4MTMwNjM0PC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDA3L3MxMTE1NC0wMTctOTQwOC0xPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB= ADDIN EN.

CITE 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 ADDIN EN.CITE.DATA (Fuente et al. 2017). In the mouse model of XLH (HYP mice) abnormalities of the growth plate are put down to the role of FGF23 in inhibiting chondrocyte proliferation and differentiation. The marked deformities and alterations in the chondrocyte-ossification margin and primary spongiosa trabeculae in HYP mice strongly mimic the deformed growth plate seen in XLH patients 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 ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GdWVudGU8L0F1dGhvcj48WWVhcj4yMDE4PC9ZZWFyPjxSZWNOdW0+MTA3PC9SZWNOdW0+PERpc3BsYXlUZXh0PihGdWVudGUgZXQgYWwuIDIwMTgpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEwNzwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Inhmd2Z4czl2MnpycGU5ZXIyYTlwd2Q5Znh2NXoydjkyd2U1ZCIgdGltZXN0YW1wPSIxNTM3MTczOTI1Ij4xMDc8L2tleT48a2V5IGFwcD0iRU5XZWIiIGRiLWlkPSIiPjA8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkZ1ZW50ZSwgUi48L2F1dGhvcj48YXV0aG9yPkdpbC1QZW5hLCBILjwvYXV0aG9yPjxhdXRob3I+Q2xhcmFtdW50LVRhYmVybmVyLCBELjwvYXV0aG9yPjxhdXRob3I+SGVybmFuZGV6LUZyaWFzLCBPLjwvYXV0aG9yPjxhdXRob3I+RmVybmFuZGV6LUlnbGVzaWFzLCBBLjwvYXV0aG9yPjxhdXRob3I+SGVybWlkYS1QcmFkbywgRi48L2F1dGhvcj48YXV0aG9yPkFuZXMtR29uemFsZXosIEcuPC9hdXRob3I+PGF1dGhvcj5SdWJpby1BbGlhZ2EsIEkuPC9hdXRob3I+PGF1dGhvcj5Mb3BleiwgSi4gTS48L2F1dGhvcj48YXV0aG9yPlNhbnRvcywgRi48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EaXZpc2lvbiBvZiBQZWRpYXRyaWNzLCBEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBGYWN1bHR5IG9mIE1lZGljaW5lLCBVbml2ZXJzaXR5IG9mIE92aWVkbywgT3ZpZWRvLCBBc3R1cmlhcywgU3BhaW47IEhhcnZhcmQgU2Nob29sIG9mIERlbnRhbCBNZWRpY2luZSwgRGV2ZWxvcG1lbnRhbCBCaW9sb2d5LCBIYXJ2YXJkIFVuaXZlcnNpdHksIEJvc3RvbiwgTUEsIFVTQS4mI3hEO0RlcGFydG1lbnQgb2YgUGVkaWF0cmljcywgSG9zcGl0YWwgVW5pdmVyc2l0YXJpbyBDZW50cmFsIGRlIEFzdHVyaWFzIChIVUNBKSwgT3ZpZWRvLCBBc3R1cmlhcywgU3BhaW4uIEVsZWN0cm9uaWMgYWRkcmVzczogaGdpbHBlbmFAZ21haWwuY29tLiYjeEQ7RGl2aXNpb24gb2YgUGVkaWF0cmljcywgRGVwYXJ0bWVudCBvZiBNZWRpY2luZSwgRmFjdWx0eSBvZiBNZWRpY2luZSwgVW5pdmVyc2l0eSBvZiBPdmllZG8sIE92aWVkbywgQXN0dXJpYXMsIFNwYWluLiYjeEQ7RGVwYXJ0bWVudCBvZiBPdG9sYXJ5bmdvbG9naXN0LCBIb3NwaXRhbCBVbml2ZXJzaXRhcmlvIENlbnRyYWwgZGUgQXN0dXJpYXMsIEluc3RpdHV0byBVbml2ZXJzaXRhcmlvIGRlIE9uY29sb2dpYSBkZWwgUHJpbmNpcGFkbyBkZSBBc3R1cmlhcywgT3ZpZWRvLCBTcGFpbi4mI3hEO0RlcGFydG1lbnQgb2YgUGVkaWF0cmljcywgSG9zcGl0YWwgVW5pdmVyc2l0YXJpbyBDZW50cmFsIGRlIEFzdHVyaWFzIChIVUNBKSwgT3ZpZWRvLCBBc3R1cmlhcywgU3BhaW4uJiN4RDtVbml2ZXJzaXR5IG9mIFp1cmljaCwgSW5zdGl0dXRlIG9mIFBoeXNpb2xvZ3ksIEtpZG5leSBhbmQgQWNpZC1iYXNlIFBoeXNpb2xvZ3kgR3JvdXAsIFp1cmljaCwgU3dpdHplcmxhbmQuJiN4RDtEaXZpc2lvbiBvZiBQZWRpYXRyaWNzLCBEZXBhcnRtZW50IG9mIE1lZGljaW5lLCBGYWN1bHR5IG9mIE1lZGljaW5lLCBVbml2ZXJzaXR5IG9mIE92aWVkbywgT3ZpZWRvLCBBc3R1cmlhcywgU3BhaW47IERlcGFydG1lbnQgb2YgUGVkaWF0cmljcywgSG9zcGl0YWwgVW5pdmVyc2l0YXJpbyBDZW50cmFsIGRlIEFzdHVyaWFzIChIVUNBKSwgT3ZpZWRvLCBBc3R1cmlhcywgU3BhaW4uPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+TWFya2VkIGFsdGVyYXRpb25zIGluIHRoZSBzdHJ1Y3R1cmUsIGR5bmFtaWNzIGFuZCBtYXR1cmF0aW9uIG9mIGdyb3d0aCBwbGF0ZSBsaWtlbHkgZXhwbGFpbiBncm93dGggcmV0YXJkYXRpb24gYW5kIGJvbmUgZGVmb3JtaXRpZXMgb2YgeW91bmcgSHlwIG1pY2U8L3RpdGxlPjxzZWNvbmRhcnktdGl0bGU+Qm9uZTwvc2Vjb25kYXJ5LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkJvbmU8L2Z1bGwtdGl0bGU+PC9wZXJpb2RpY2FsPjxwYWdlcz4xODctMTk1PC9wYWdlcz48dm9sdW1lPjExNjwvdm9sdW1lPjxlZGl0aW9uPjIwMTgvMDgvMTE8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkJvbmU8L2tleXdvcmQ+PGtleXdvcmQ+Q2hvbmRyb2N5dGVzPC9rZXl3b3JkPjxrZXl3b3JkPkdyb3d0aCBwbGF0ZTwva2V5d29yZD48a2V5d29yZD5SaWNrZXRzPC9rZXl3b3JkPjxrZXl3b3JkPlhsaDwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDE4PC95ZWFyPjxwdWItZGF0ZXM+PGRhdGU+QXVnIDg8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4xODczLTI3NjMgKEVsZWN0cm9uaWMpJiN4RDsxODczLTI3NjMgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjMwMDk2NDY4PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwczovL3d3dy5uY2JpLm5sbS5uaWguZ292L3B1Ym1lZC8zMDA5NjQ2ODwvdXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTAxNi9qLmJvbmUuMjAxOC4wOC4wMDQ8L2VsZWN0cm9uaWMtcmVzb3VyY2UtbnVtPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+ ADDIN EN.

CITE.DATA (Fuente et al. 2018). Consistent with the effect of phosphate on the growth plate, phosphate supplementation only works in the children where the activity of growth plate is significant. No benefits of phosphate were observed in adult patients with osteomalacia ADDIN EN.CITE <EndNote><Cite><Author>Marie</Author><Year>1981</Year><RecNum>17</RecNum><DisplayText>(Marie, Travers &amp; Glorieux 1981)</DisplayText><record><rec-number>17</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519793688″>17</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Marie, P.

J.</author><author>Travers, R.</author><author>Glorieux, F. H.

</author></authors></contributors><titles><title>Healing of rickets with phosphate supplementation in the hypophosphatemic male mouse</title><secondary-title>Journal of Clinical Investigation</secondary-title></titles><periodical><full-title>Journal of Clinical Investigation</full-title></periodical><pages>911-914</pages><volume>67</volume><number>3</number><dates><year>1981</year></dates><isbn>0021-9738</isbn><urls></urls><electronic-resource-num>10.1172/jci110110</electronic-resource-num></record></Cite></EndNote>(Marie, Travers & Glorieux 1981). Phosphate plays a critical role in the mineralisation of the skeleton. The formation of hydroxyapatite (HAP) in the skeleton requires a combination of inorganic Phosphate (Pi) with calcium (Ca) (Figure 3) 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Foster et al.

2012). The presentation of inorganic phosphate for combination with calcium is not dependent on serum phosphate levels, but rather by the co-ordinated production by osteoblasts 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 ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gb3N0ZXI8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxSZWNOdW0+MTAzPC9SZWNOdW0+PERpc3BsYXlUZXh0PihGb3N0ZXIgZXQgYWwuIDIwMTIpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjEwMzwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Inhmd2Z4czl2MnpycGU5ZXIyYTlwd2Q5Znh2NXoydjkyd2U1ZCIgdGltZXN0YW1wPSIxNTM3MTcxNTc1Ij4xMDM8L2tleT48a2V5IGFwcD0iRU5XZWIiIGRiLWlkPSIiPjA8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkZvc3RlciwgQi4gTC48L2F1dGhvcj48YXV0aG9yPk5hZ2F0b21vLCBLLiBKLjwvYXV0aG9yPjxhdXRob3I+Tm9jaXRpLCBGLiBILiwgSnIuPC9hdXRob3I+PGF1dGhvcj5Gb25nLCBILjwvYXV0aG9yPjxhdXRob3I+RHVubiwgRC48L2F1dGhvcj48YXV0aG9yPlRyYW4sIEEuIEIuPC9hdXRob3I+PGF1dGhvcj5XYW5nLCBXLjwvYXV0aG9yPjxhdXRob3I+TmFyaXNhd2EsIFMuPC9hdXRob3I+PGF1dGhvcj5NaWxsYW4sIEouIEwuPC9hdXRob3I+PGF1dGhvcj5Tb21lcm1hbiwgTS4gSi48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5MYWJvcmF0b3J5IG9mIE9yYWwgQ29ubmVjdGl2ZSBUaXNzdWUgQmlvbG9neSwgTmF0aW9uYWwgSW5zdGl0dXRlIG9mIEFydGhyaXRpcyBhbmQgTXVzY3Vsb3NrZWxldGFsIGFuZCBTa2luIERpc2Vhc2VzLCBOYXRpb25hbCBJbnN0aXR1dGVzIG9mIEhlYWx0aCwgQmV0aGVzZGEsIE1hcnlsYW5kLCBVbml0ZWQgU3RhdGVzIG9mIEFtZXJpY2EuIGJyaWFuLmZvc3RlckBuaWguZ292PC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+Q2VudHJhbCByb2xlIG9mIHB5cm9waG9zcGhhdGUgaW4gYWNlbGx1bGFyIGNlbWVudHVtIGZvcm1hdGlvbjwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5QTG9TIE9uZTwvc2Vjb25kYXJ5LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPlBMb1MgT25lPC9mdWxsLXRpdGxlPjwvcGVyaW9kaWNhbD48cGFnZXM+ZTM4MzkzPC9wYWdlcz48dm9sdW1lPjc8L3ZvbHVtZT48bnVtYmVyPjY8L251bWJlcj48ZWRpdGlvbj4yMDEyLzA2LzA4PC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5BbGthbGluZSBQaG9zcGhhdGFzZS9kZWZpY2llbmN5L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5DYWxjaWZpY2F0aW9uLCBQaHlzaW9sb2dpYzwva2V5d29yZD48a2V5d29yZD5DZWxsIFByb2xpZmVyYXRpb248L2tleXdvcmQ+PGtleXdvcmQ+Q2VsbHMsIEN1bHR1cmVkPC9rZXl3b3JkPjxrZXl3b3JkPipDZW1lbnRvZ2VuZXNpczwva2V5d29yZD48a2V5d29yZD5Db2xsYWdlbi9iaW9zeW50aGVzaXM8L2tleXdvcmQ+PGtleXdvcmQ+RGVudGFsIENlbWVudHVtLyptZXRhYm9saXNtLypwYXRob2xvZ3kvdWx0cmFzdHJ1Y3R1cmU8L2tleXdvcmQ+PGtleXdvcmQ+RGlwaG9zcGhhdGVzLyptZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPkV4dHJhY2VsbHVsYXIgU3BhY2UvbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5HZW5lIEV4cHJlc3Npb24gUmVndWxhdGlvbiwgRGV2ZWxvcG1lbnRhbDwva2V5d29yZD48a2V5d29yZD5Ib21lb3N0YXNpczwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFuZGlibGUvcGF0aG9sb2d5L3VsdHJhc3RydWN0dXJlPC9rZXl3b3JkPjxrZXl3b3JkPk1pY2U8L2tleXdvcmQ+PGtleXdvcmQ+TWljZSwgSW5icmVkIEM1N0JMPC9rZXl3b3JkPjxrZXl3b3JkPk1pY2UsIEtub2Nrb3V0PC9rZXl3b3JkPjxrZXl3b3JkPk1vZGVscywgQmlvbG9naWNhbDwva2V5d29yZD48a2V5d29yZD5Nb2xhci9tZXRhYm9saXNtL3BhdGhvbG9neS91bHRyYXN0cnVjdHVyZTwva2V5d29yZD48a2V5d29yZD5QaG9zcGhhdGUgVHJhbnNwb3J0IFByb3RlaW5zL2RlZmljaWVuY3kvbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5QaG9zcGhvcmljIERpZXN0ZXIgSHlkcm9sYXNlcy9kZWZpY2llbmN5L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+UHlyb3Bob3NwaGF0YXNlcy9kZWZpY2llbmN5L21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+VGltZSBGYWN0b3JzPC9rZXl3b3JkPjxrZXl3b3JkPlRvb3RoIFJvb3QvbWV0YWJvbGlzbS91bHRyYXN0cnVjdHVyZTwva2V5d29yZD48L2tleXdvcmRzPjxkYXRlcz48eWVhcj4yMDEyPC95ZWFyPjwvZGF0ZXM+PGlzYm4+MTkzMi02MjAzIChFbGVjdHJvbmljKSYjeEQ7MTkzMi02MjAzIChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9uLW51bT4yMjY3NTU1NjwvYWNjZXNzaW9uLW51bT48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+aHR0cHM6Ly93d3cubmNiaS5ubG0ubmloLmdvdi9wdWJtZWQvMjI2NzU1NTY8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGN1c3RvbTI+UE1DMzM2Njk1NzwvY3VzdG9tMj48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTM3MS9qb3VybmFsLnBvbmUuMDAzODM5MzwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A ADDIN EN.CITE.

DATA (Foster et al. 2012). This process is governed by at least three cell membrane associated proteins Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 (NPP1), 3376295435610Figure 3: The mechanism of coordinated bone mineralisation in osteocytes.Figure 3: The mechanism of coordinated bone mineralisation in osteocytes.Progressive Ankylosis Protein (ANK) and Tissue Non-specific Alkaline Phosphatase (TNAP) ADDIN EN.CITE <EndNote><Cite><Author>Harmey</Author><Year>2004</Year><RecNum>104</RecNum><DisplayText>(Harmey et al.

2004)</DisplayText><record><rec-number>104</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1537172106″>104</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Harmey, Dympna</author><author>Hessle, Lovisa</author><author>Narisawa, Sonoko</author><author>Johnson, Kristen A.</author><author>Terkeltaub, Robert</author><author>Millán, José Luis</author></authors></contributors><titles><title>Concerted Regulation of Inorganic Pyrophosphate and Osteopontin by Akp2, Enpp1, and Ank</title><secondary-title>The American Journal of Pathology</secondary-title></titles><periodical><full-title>The American Journal of Pathology</full-title></periodical><pages>1199-1209</pages><volume>164</volume><number>4</number><section>1199</section><dates><year>2004</year></dates><isbn>00029440</isbn><urls></urls><electronic-resource-num>10.1016/s0002-9440(10)63208-7</electronic-resource-num></record></Cite></EndNote>(Harmey et al. 2004). Conversion of pyrophosphate (PPi) to Pi by TNAP is common to mineralising osteoblasts.

A high PPi to Pi ratio has been shown to be inhibitory for HAP formation 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Millan 2013). In the mouse model of XLH (Hyp mice), excessive FGF23 contributes to PPi accumulation, by reducing TNAP expression and decreasing the conversion to Pi 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 ADDIN EN.CITE 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 ADDIN EN.CITE.

DATA (Murali et al. 2016). These data partly explain why elevating serum phosphate levels does not contribute to improving bone mineralisation in XLH. Furthermore, the key to improving bone mineralisation in XLH may lie in reducing PPi:Pi ratio through regulation of one or more osteoblastic genes in the bone mineralisation pathway. 336359512700Figure 4: Basic principles of vitamin D synthesis and catabolism.Figure 4: Basic principles of vitamin D synthesis and catabolism.Vitamin D therapy and XLH: The vitamin D endocrine system is responsible for the maintenance of calcium homoeostasis and skeletal growth ADDIN EN.

CITE <EndNote><Cite><Author>Rowling</Author><Year>2007</Year><RecNum>81</RecNum><DisplayText>(Rowling, Matthew J et al. 2007)</DisplayText><record><rec-number>81</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1533113728″>81</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Rowling, Matthew J</author><author>Gliniak, Christy</author><author>Welsh, JoEllen</author><author>Fleet, James C</author></authors></contributors><titles><title>High dietary vitamin D prevents hypocalcemia and osteomalacia in CYP27B1 knockout mice</title><secondary-title>The Journal of nutrition</secondary-title></titles><periodical><full-title>The Journal of nutrition</full-title></periodical><pages>2608-2615</pages><volume>137</volume><number>12</number><dates><year>2007</year></dates><isbn>0022-3166</isbn><urls><related-urls><url>https://watermark.silverchair.

com/2608.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAcAwggG8BgkqhkiG9w0BBwagggGtMIIBqQIBADCCAaIGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMpmD_KmwRd4sGvFgjAgEQgIIBc6dnUxoCZL1YaBZdkc2ucI5X1-RQfXvPZWKQ02OVcRZZvOFjl1Fz9SCa38bb7d0d5Vcljd1q1Vk8la1MlnM7PMUNOyzIRx45OQEB8TooskRO12tczIL0gsaABrtQppQkj0WZQua03_RzIAmUbsDWE_cdlbotQBj7iAISYqr0c1s7JT8xPz7I3tRf6i2QNLpI106GHBW_VJGveUsgo1UDr3ZvlVx0esTI587hPzZaRYsGaYI6NPZI5RqgjQoCMaIaIOfLdD2wB7r094DMgSOrQLtaGD3HUoBbsaJBgOX_Uq7WA3m4leOAGp2gsvWHh8zXyWH4bzJZP6Rcb_Y1m4T4pRO_jRrFNDOngvpP-REW63Mx55_cj3vzDYXc8J7Erzi-NMh47kE2n53mnes4hDMin3TpPqg0LV9f958aKTvcVHdD1ih-kicgSYa12aDVlKfjb3hpP90p13eZfJh3dvEDS8OmEgBaLHu9TbopBiELK2nrEm-4</url></related-urls></urls></record></Cite></EndNote>(Rowling, Matthew J et al. 2007). Optimal bone health is achieved when adequate vitamin D is metabolised and mediated properly through genes in the intestine, kidney, and bone ADDIN EN.

CITE <EndNote><Cite><Author>Rowling</Author><Year>2007</Year><RecNum>81</RecNum><DisplayText>(Rowling, Matthew J et al. 2007)</DisplayText><record><rec-number>81</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1533113728″>81</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Rowling, Matthew J</author><author>Gliniak, Christy</author><author>Welsh, JoEllen</author><author>Fleet, James C</author></authors></contributors><titles><title>High dietary vitamin D prevents hypocalcemia and osteomalacia in CYP27B1 knockout mice</title><secondary-title>The Journal of nutrition</secondary-title></titles><periodical><full-title>The Journal of nutrition</full-title></periodical><pages>2608-2615</pages><volume>137</volume><number>12</number><dates><year>2007</year></dates><isbn>0022-3166</isbn><urls><related-urls><url>https://watermark.silverchair.com/2608.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAcAwggG8BgkqhkiG9w0BBwagggGtMIIBqQIBADCCAaIGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMpmD_KmwRd4sGvFgjAgEQgIIBc6dnUxoCZL1YaBZdkc2ucI5X1-RQfXvPZWKQ02OVcRZZvOFjl1Fz9SCa38bb7d0d5Vcljd1q1Vk8la1MlnM7PMUNOyzIRx45OQEB8TooskRO12tczIL0gsaABrtQppQkj0WZQua03_RzIAmUbsDWE_cdlbotQBj7iAISYqr0c1s7JT8xPz7I3tRf6i2QNLpI106GHBW_VJGveUsgo1UDr3ZvlVx0esTI587hPzZaRYsGaYI6NPZI5RqgjQoCMaIaIOfLdD2wB7r094DMgSOrQLtaGD3HUoBbsaJBgOX_Uq7WA3m4leOAGp2gsvWHh8zXyWH4bzJZP6Rcb_Y1m4T4pRO_jRrFNDOngvpP-REW63Mx55_cj3vzDYXc8J7Erzi-NMh47kE2n53mnes4hDMin3TpPqg0LV9f958aKTvcVHdD1ih-kicgSYa12aDVlKfjb3hpP90p13eZfJh3dvEDS8OmEgBaLHu9TbopBiELK2nrEm-4</url></related-urls></urls></record></Cite></EndNote>(Rowling, Matthew J et al. 2007). While vitamin D can be obtained through diet and supplements, the predominant source for vitamin D is via skin exposure to UV radiation from the sun. Vitamin D3, formed in the skin, is metabolised further in the liver to form 25-hydroxyvitamin D (25(OH)D), mediated primarily by the hepatic enzymes CYP2R1 and CYP27A1 (Figure 4) ADDIN EN.

CITE <EndNote><Cite><Author>Henry</Author><Year>2011</Year><RecNum>73</RecNum><DisplayText>(Henry 2011)</DisplayText><record><rec-number>73</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1533032276″>73</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Henry, H. L.</author></authors></contributors><auth-address>Department of Biochemistry, University of California, Riverside, CA 92521, USA. [email protected]

edu.</auth-address><titles><title>Regulation of vitamin D metabolism</title><secondary-title>Best Pract Res Clin Endocrinol Metab</secondary-title></titles><periodical><full-title>Best Pract Res Clin Endocrinol Metab</full-title></periodical><pages>531-41</pages><volume>25</volume><number>4</number><edition>2011/08/30</edition><keywords><keyword>24,25-Dihydroxyvitamin D 3/metabolism</keyword><keyword>Animals</keyword><keyword>*Autocrine Communication</keyword><keyword>Calcitriol/metabolism</keyword><keyword>Cholestanetriol 26-Monooxygenase/genetics/metabolism</keyword><keyword>*Feedback, Physiological</keyword><keyword>*Gene Expression Regulation, Enzymologic</keyword><keyword>Humans</keyword><keyword>Kidney/metabolism</keyword><keyword>Liver/metabolism</keyword><keyword>*Paracrine Communication</keyword><keyword>*Signal Transduction</keyword><keyword>Steroid Hydroxylases/genetics/metabolism</keyword><keyword>Vitamin D/*metabolism</keyword><keyword>Vitamin D3 24-Hydroxylase</keyword></keywords><dates><year>2011</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1878-1594 (Electronic) 1521-690X (Linking)</isbn><accession-num>21872796</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/21872796</url></related-urls></urls><electronic-resource-num>10.1016/j.

beem.2011.05.003</electronic-resource-num></record></Cite></EndNote>(Henry 2011). 25(OH)D is the major circulating metabolite of vitamin D and while it is itself inactive, the circulating levels of 25(OH)D is used clinically to determine a person’s vitamin D status ADDIN EN.CITE ;EndNote;;Cite;;Author;Vieth;/Author;;Year;1999;/Year;;RecNum;38;/RecNum;;DisplayText;(Vieth 1999);/DisplayText;;record;;rec-number;38;/rec-number;;foreign-keys;;key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1522565771″;38;/key;;key app=”ENWeb” db-id=””;0;/key;;/foreign-keys;;ref-type name=”Journal Article”;17;/ref-type;;contributors;;authors;;author;Vieth, R.;/author;;/authors;;/contributors;;titles;;title;Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety;/title;;secondary-title;American Journal of Clinical Nutrition ;/secondary-title;;/titles;;periodical;;full-title;American Journal of Clinical Nutrition;/full-title;;/periodical;;pages;842-856;/pages;;volume;69;/volume;;number;5;/number;;dates;;year;1999;/year;;/dates;;urls;;/urls;;/record;;/Cite;;/EndNote;(Vieth 1999).

For vitamin D to exert its activity, 25(OH)D is required to be further metabolised to 1,25(OH)2D, a process that is catalysed by the renal CYP27B1 enzyme. 1,25(OH)2D acts upon many tissues by binding to the vitamin D receptor (VDR) and modulating various systems and tissues 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 ADDIN EN.CITE 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 ADDIN EN.

CITE.DATA (Roizen et al. 2018; Rowling, Matthew J et al. 2007). While the classical action of 1,25(OH)2D is to stimulate intestinal calcium absorption, 1,25(OH)2D has also been shown to regulate several other systems including cardiovascular health, immune system, lung health, anti-neoplastic action in several cancers, skin maturation as well multiple direct roles in bone homeostasis ADDIN EN.CITE ;EndNote;;Cite;;Author;Anderson;/Author;;Year;2017;/Year;;RecNum;94;/RecNum;;DisplayText;(Anderson 2017);/DisplayText;;record;;rec-number;94;/rec-number;;foreign-keys;;key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1534470997″;94;/key;;key app=”ENWeb” db-id=””;0;/key;;/foreign-keys;;ref-type name=”Journal Article”;17;/ref-type;;contributors;;authors;;author;Anderson, P.

H.;/author;;/authors;;/contributors;;auth-address;Musculoskeletal Biology Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5001, Australia. [email protected]

;/auth-address;;titles;;title;Vitamin D Activity and Metabolism in Bone;/title;;secondary-title;Curr Osteoporos Rep;/secondary-title;;/titles;;periodical;;full-title;Curr Osteoporos Rep;/full-title;;/periodical;;pages;443-449;/pages;;volume;15;/volume;;number;5;/number;;edition;2017/08/16;/edition;;keywords;;keyword;25-Hydroxyvitamin D3 1-alpha-Hydroxylase/*metabolism</keyword><keyword>Autocrine Communication</keyword><keyword>Bone Resorption/metabolism</keyword><keyword>Bone and Bones/*metabolism</keyword><keyword>Calcification, Physiologic/physiology</keyword><keyword>Fracture Healing/physiology</keyword><keyword>Humans</keyword><keyword>Receptors, Calcitriol/*metabolism</keyword><keyword>Vitamin D/*analogs &amp; derivatives/metabolism</keyword><keyword>Vitamin D3 24-Hydroxylase/*metabolism</keyword><keyword>Cyp24a1</keyword><keyword>Cyp27b1</keyword><keyword>Mineralisation</keyword><keyword>Osteoblasts</keyword><keyword>Vitamin D</keyword><keyword>Vitamin D receptor</keyword></keywords><dates><year>2017</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1544-2241 (Electronic) 1544-1873 (Linking)</isbn><accession-num>28808890</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.

gov/pubmed/28808890</url></related-urls></urls><electronic-resource-num>10.1007/s11914-017-0394-8</electronic-resource-num></record></Cite></EndNote>(Anderson 2017).In XLH, excessive FGF23 actions results in lower renal 1,25(OH)D production. However, few studies have investigated the vitamin D status, as measured by 25(OH)D levels, in XLH patients. This gap in the knowledge is not unexpected given the XLH disease is considered to be disorder that impacts in renal activation of 1,25(OH)D, and not 25(OH)D production. Thus the focus of current therapies include administering 1,25(OH)2D3 to restore levels, or, to use synthetic vitamin D analogues to mimic 1,25(OH)2D3 activity ADDIN EN.CITE <EndNote><Cite><Author>Makitie</Author><Year>2003</Year><RecNum>22</RecNum><DisplayText>(Makitie et al.

2003)</DisplayText><record><rec-number>22</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519794285″>22</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Makitie, O.</author><author>Doria, A.</author><author>Kooh, S. W.</author><author>Cole, W.

G.</author><author>Daneman, A.</author><author>Sochett, E.</author></authors></contributors><auth-address>Division of Endocrinology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8. [email protected]</auth-address><titles><title>Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets</title><secondary-title>J Clin Endocrinol Metab</secondary-title></titles><periodical><full-title>J Clin Endocrinol Metab</full-title></periodical><pages>3591-7</pages><volume>88</volume><number>8</number><keywords><keyword>Age of Onset</keyword><keyword>Body Height/drug effects</keyword><keyword>Bone and Bones/diagnostic imaging</keyword><keyword>Calcitriol/blood</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Growth/*drug effects</keyword><keyword>Humans</keyword><keyword>Hypophosphatemia/blood</keyword><keyword>Hypophosphatemia, Familial/diagnostic imaging/metabolism/*therapy</keyword><keyword>Infant</keyword><keyword>Radiography</keyword><keyword>Retrospective Studies</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2003</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0021-972X (Print) 0021-972X (Linking)</isbn><accession-num>12915641</accession-num><urls><related-urls><url>https://www.ncbi.

nlm.nih.gov/pubmed/12915641</url></related-urls></urls><electronic-resource-num>10.1210/jc.2003-030036</electronic-resource-num></record></Cite></EndNote>(Makitie et al. 2003). Treatment is often supplied with oral phosphate which can be effective in improving growth, healing, and biochemical parameters in children.

However, many children fail to respond to treatment for reasons that are not clear ADDIN EN.CITE <EndNote><Cite><Author>Makitie</Author><Year>2003</Year><RecNum>22</RecNum><DisplayText>(Makitie et al. 2003)</DisplayText><record><rec-number>22</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519794285″>22</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Makitie, O.</author><author>Doria, A.</author><author>Kooh, S. W.</author><author>Cole, W.

G.</author><author>Daneman, A.</author><author>Sochett, E.</author></authors></contributors><auth-address>Division of Endocrinology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8. outi.

[email protected]</auth-address><titles><title>Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets</title><secondary-title>J Clin Endocrinol Metab</secondary-title></titles><periodical><full-title>J Clin Endocrinol Metab</full-title></periodical><pages>3591-7</pages><volume>88</volume><number>8</number><keywords><keyword>Age of Onset</keyword><keyword>Body Height/drug effects</keyword><keyword>Bone and Bones/diagnostic imaging</keyword><keyword>Calcitriol/blood</keyword><keyword>Child</keyword><keyword>Child, Preschool</keyword><keyword>Growth/*drug effects</keyword><keyword>Humans</keyword><keyword>Hypophosphatemia/blood</keyword><keyword>Hypophosphatemia, Familial/diagnostic imaging/metabolism/*therapy</keyword><keyword>Infant</keyword><keyword>Radiography</keyword><keyword>Retrospective Studies</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2003</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>0021-972X (Print) 0021-972X (Linking)</isbn><accession-num>12915641</accession-num><urls><related-urls><url>https://www.ncbi.

nlm.nih.gov/pubmed/12915641</url></related-urls></urls><electronic-resource-num>10.1210/jc.

2003-030036</electronic-resource-num></record></Cite></EndNote>(Makitie et al. 2003) and side-effects including hypercalcemia, nausea, vomiting, nephrocalcinosis, secondary hyperparathyroidism, and even higher FGF23 levels can occur 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 ADDIN EN.CITE 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 ADDIN EN.

CITE.DATA (Leifheit-Nestler et al. 2017; Liu et al. 2016). In an attempt to overcome some of the side-effects of using 1,25(OH)2D3, vitamin D analogues are frequently used in the treatment of XLH. For example, alphacalcidiol may be useful in normalising biochemical parameters such as PTH in XLH patients. However, hypercalcaemia remains a side-effect of alphacalcidiol treatment which, if sustained, can lead to vascular and other soft tissue calcification PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaW5nbGFydDwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJlY051bT44OTwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oTGluZ2xhcnQgZXQgYWwuIDIwMTQpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxyZWMtbnVtYmVyPjg5PC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0ieGZ3ZnhzOXYyenJwZTllcjJhOXB3ZDlmeHY1ejJ2OTJ3ZTVkIiB0aW1lc3RhbXA9IjE1MzM1Mjc5NTUiPjg5PC9rZXk+PGtleSBhcHA9IkVOV2ViIiBkYi1pZD0iIj4wPC9rZXk+PC9mb3JlaWduLWtleXM+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5MaW5nbGFydCwgQS48L2F1dGhvcj48YXV0aG9yPkJpb3NzZS1EdXBsYW4sIE0uPC9hdXRob3I+PGF1dGhvcj5CcmlvdCwgSy48L2F1dGhvcj48YXV0aG9yPkNoYXVzc2FpbiwgQy48L2F1dGhvcj48YXV0aG9yPkVzdGVybGUsIEwuPC9hdXRob3I+PGF1dGhvcj5HdWlsbGF1bWUtQ3ppdHJvbSwgUy48L2F1dGhvcj48YXV0aG9yPkthbWVuaWNreSwgUC48L2F1dGhvcj48YXV0aG9yPk5ldm91eCwgSi48L2F1dGhvcj48YXV0aG9yPlByaWUsIEQuPC9hdXRob3I+PGF1dGhvcj5Sb3RoZW5idWhsZXIsIEEuPC9hdXRob3I+PGF1dGhvcj5XaWNhcnQsIFAuPC9hdXRob3I+PGF1dGhvcj5IYXJ2ZW5ndCwgUC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5TZXJ2aWNlIGQmYXBvcztFbmRvY3Jpbm9sb2dpZSBldCBEaWFiZXRvbG9naWUgZGUgbCZhcG9zO0VuZmFudCBTZXJ2aWNlIGRlIFBlZGlhdHJpZSBnZW5lcmFsZSAtIENvbnN1bHRhdGlvbiBkZSByaHVtYXRvbG9naWUgU2VydmljZSBkJmFwb3M7RW5kb2NyaW5vbG9naWUgZXQgZGVzIE1hbGFkaWVzIGRlIGxhIFJlcHJvZHVjdGlvbiBTZXJ2aWNlIGQmYXBvcztPUkwgZXQgY2hpcnVyZ2llIGNlcnZpY28tbWF4aWxsby1mYWNpYWxlSG9waXRhbCBCaWNldHJlLCBBUEhQLCA3OCBydWUgZHUgR2VuZXJhbCBMZWNsZXJjLCA5NDI3MCBMZSBLcmVtbGluIEJpY2V0cmUsIEZyYW5jZSBVbml2ZXJzaXRlIFBhcmlzIDExRmFjdWx0ZSBkZSBNZWRlY2luZSwgSG9waXRhbCBCaWNldHJlLCA3MCBydWUgZHUgR2VuZXJhbCBMZWNsZXJjLCA5NDI3MCBMZSBLcmVtbGluLUJpY2V0cmUsIEZyYW5jZSBDZW50cmUgZGUgUmVmZXJlbmNlIGRlcyBNYWxhZGllcyBSYXJlcyBkdSBNZXRhYm9saXNtZSBkdSBDYWxjaXVtIGV0IGR1IFBob3NwaG9yZUxlIEtyZW1saW4tQmljZXRyZSwgRnJhbmNlIFNlcnZpY2UgZCZhcG9zO09kb250b2xvZ2llLU1hbGFkaWVzIFJhcmVzIEhvcGl0YWwgQnJldG9ubmVhdSAyIHJ1ZSBDYXJwZWF1eDc1MDE4IFBhcmlzLCBGcmFuY2UgVW5pdmVyc2l0ZSBQYXJpcyBEZXNjYXJ0ZXMgMTIgUnVlIGRlIGwmYXBvcztFY29sZSBkZSBNZWRlY2luZTc1MDA2IFBhcmlzLCBGcmFuY2UgU2VydmljZSBSaHVtYXRvbG9naWUgQiBIb3BpdGFsIENvY2hpbkFQSFAsIDI3LCBydWUgZHUgRmF1Ym91cmcgU2FpbnQtSmFjcXVlcywgNzUwMTQgUGFyaXMsIEZyYW5jZSBDZW50cmUgZGUgUmVmZXJlbmNlIGRlcyBNYWxhZGllcyBSYXJlcyBkZXMgTWFsYWRpZXMgQXV0by1JbmZsYW1tYXRvaXJlcyBSYXJlcyBkZSBsJmFwb3M7RW5mYW50TGUgS3JlbWxpbiBCaWNldHJlLCBGcmFuY2UgU2VydmljZSBkJmFwb3M7ZXhwbG9yYXRpb25zIGZvbmN0aW9ubmVsbGVzIHJlbmFsZXMgU2VydmljZSBkZSBDaGlydXJnaWUgaW5mYW50aWxlIG9ydGhvcGVkaXF1ZUhvcGl0YWwgTmVja2VyLUVuZmFudHMgTWFsYWRlcywgMTQ5IHJ1ZSBkZSBTZXZyZXMsIDc1MDE1IFBhcmlzLCBGcmFuY2UgQXNzb2NpYXRpb24gZGUgcGF0aWVudHMgUlZSSC1YTEgyMCBydWUgTWVybGluIGRlIFRoaW9udmlsbGUsIDkyMTUwIFN1cmVzbmVzLCBGcmFuY2UuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+VGhlcmFwZXV0aWMgbWFuYWdlbWVudCBvZiBoeXBvcGhvc3BoYXRlbWljIHJpY2tldHMgZnJvbSBpbmZhbmN5IHRvIGFkdWx0aG9vZDwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5FbmRvY3IgQ29ubmVjdDwvc2Vjb25kYXJ5LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkVuZG9jciBDb25uZWN0PC9mdWxsLXRpdGxlPjwvcGVyaW9kaWNhbD48cGFnZXM+UjEzLTMwPC9wYWdlcz48dm9sdW1lPjM8L3ZvbHVtZT48bnVtYmVyPjE8L251bWJlcj48ZWRpdGlvbj4yMDE0LzAyLzIwPC9lZGl0aW9uPjxrZXl3b3Jkcz48a2V5d29yZD5YLWxpbmtlZCBoeXBvcGhvc3BoYXRlbWljIHJpY2tldHM8L2tleXdvcmQ+PGtleXdvcmQ+Ym9uZTwva2V5d29yZD48a2V5d29yZD5jYWxjaXVtPC9rZXl3b3JkPjxrZXl3b3JkPnJhcmUgZGlzZWFzZXMvc3luZHJvbWVzPC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTQ8L3llYXI+PC9kYXRlcz48aXNibj4yMDQ5LTM2MTQgKFByaW50KSYjeEQ7MjA0OS0zNjE0IChMaW5raW5nKTwvaXNibj48YWNjZXNzaW9uLW51bT4yNDU1MDMyMjwvYWNjZXNzaW9uLW51bT48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+aHR0cHM6Ly93d3cubmNiaS5ubG0ubmloLmdvdi9wdWJtZWQvMjQ1NTAzMjI8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGN1c3RvbTI+UE1DMzk1OTczMDwvY3VzdG9tMj48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+MTAuMTUzMC9FQy0xMy0wMTAzPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPgB= ADDIN EN.

CITE 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 ADDIN EN.CITE.DATA (Linglart et al. 2014). Experimentally, Eldecalcitriol (ED71) has been shown in the mouse model for XLH (HYP mice) to improve bone mineral content and serum phosphate levels 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 ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LaWRvPC9BdXRob3I+PFllYXI+MjAxMzwvWWVhcj48UmVjTnVtPjU4PC9SZWNOdW0+PERpc3BsYXlUZXh0PihLaWRvIGV0IGFsLiAyMDEzKTwvRGlzcGxheVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj41ODwvcmVjLW51bWJlcj48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Inhmd2Z4czl2MnpycGU5ZXIyYTlwd2Q5Znh2NXoydjkyd2U1ZCIgdGltZXN0YW1wPSIxNTMzMDMyMTAzIj41ODwva2V5PjxrZXkgYXBwPSJFTldlYiIgZGItaWQ9IiI+MDwva2V5PjwvZm9yZWlnbi1rZXlzPjxyZWYtdHlwZSBuYW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+S2lkbywgUy48L2F1dGhvcj48YXV0aG9yPkthbmVrbywgSS48L2F1dGhvcj48YXV0aG9yPlRhdHN1bWksIFMuPC9hdXRob3I+PGF1dGhvcj5TZWdhd2EsIEguPC9hdXRob3I+PGF1dGhvcj5NaXlhbW90bywgSy48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EZXBhcnRtZW50IG9mIE1vbGVjdWxhciBOdXRyaXRpb24sIFVuaXZlcnNpdHkgb2YgVG9rdXNoaW1hIEdyYWR1YXRlIFNjaG9vbCwgMy0xOC0xNSBLdXJhbW90by1jaG8sIFRva3VzaGltYSwgSmFwYW4uPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+Vml0YW1pbiBEIGFuZCB0eXBlIElJIHNvZGl1bS1kZXBlbmRlbnQgcGhvc3BoYXRlIGNvdHJhbnNwb3J0ZXJzPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkNvbnRyaWIgTmVwaHJvbDwvc2Vjb25kYXJ5LXRpdGxlPjwvdGl0bGVzPjxwZXJpb2RpY2FsPjxmdWxsLXRpdGxlPkNvbnRyaWIgTmVwaHJvbDwvZnVsbC10aXRsZT48L3BlcmlvZGljYWw+PHBhZ2VzPjg2LTk3PC9wYWdlcz48dm9sdW1lPjE4MDwvdm9sdW1lPjxlZGl0aW9uPjIwMTMvMDUvMDk8L2VkaXRpb24+PGtleXdvcmRzPjxrZXl3b3JkPkFic29ycHRpb248L2tleXdvcmQ+PGtleXdvcmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5DYWxjaXRyaW9sL3BoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Q2FsY2l1bSwgRGlldGFyeS90aGVyYXBldXRpYyB1c2U8L2tleXdvcmQ+PGtleXdvcmQ+Q2hyb25pYyBLaWRuZXkgRGlzZWFzZS1NaW5lcmFsIGFuZCBCb25lIERpc29yZGVyL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+RmFtaWxpYWwgSHlwb3Bob3NwaGF0ZW1pYyBSaWNrZXRzL2RpZXQgdGhlcmFweS9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPkZpYnJvYmxhc3QgR3Jvd3RoIEZhY3RvcnMvcGh5c2lvbG9neTwva2V5d29yZD48a2V5d29yZD5HZW5lIEV4cHJlc3Npb24gUmVndWxhdGlvbjwva2V5d29yZD48a2V5d29yZD5HbHVjdXJvbmlkYXNlL3BoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3JkPkh5cG9waG9zcGhhdGVtaWEvcGh5c2lvcGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkludGVzdGluYWwgQWJzb3JwdGlvbjwva2V5d29yZD48a2V5d29yZD5LaWRuZXkgVHVidWxlcy9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPk1pY2U8L2tleXdvcmQ+PGtleXdvcmQ+TWljZSwgS25vY2tvdXQ8L2tleXdvcmQ+PGtleXdvcmQ+UGFyYXRoeXJvaWQgSG9ybW9uZS9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlBob3NwaGF0ZXMvKm1ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+UGhvc3Bob3J1cywgRGlldGFyeS9waGFybWFjb2tpbmV0aWNzPC9rZXl3b3JkPjxrZXl3b3JkPlJlY2VwdG9ycywgQ2FsY2l0cmlvbC9kZWZpY2llbmN5L3BoeXNpb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+U29kaXVtLyptZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPlNvZGl1bS1QaG9zcGhhdGUgQ290cmFuc3BvcnRlciBQcm90ZWlucywgVHlwZSBJSS8qbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5WaXRhbWluIEQvKm1ldGFib2xpc208L2tleXdvcmQ+PC9rZXl3b3Jkcz48ZGF0ZXM+PHllYXI+MjAxMzwveWVhcj48L2RhdGVzPjxpc2JuPjE2NjItMjc4MiAoRWxlY3Ryb25pYykmI3hEOzAzMDItNTE0NCAoTGlua2luZyk8L2lzYm4+PGFjY2Vzc2lvbi1udW0+MjM2NTI1NTI8L2FjY2Vzc2lvbi1udW0+PHVybHM+PHJlbGF0ZWQtdXJscz48dXJsPmh0dHBzOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzIzNjUyNTUyPC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMTU5LzAwMDM0Njc4NjwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A ADDIN EN.

CITE.DATA (Kido et al. 2013), however, ED-71 also causes hypercalcemia in other studies related to osteoporosis-treatment 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Kido et al. 2013). Many studies investigating vitamin D-related treatments for XLH have used the HYP mouse model as a homolog for XLH for proof-of-principle studies.

The biochemical and skeletal responses to phosphate supplementation in HYP are very similar to human XLH patients and are thus a very valuable resource for researching this rare disease ADDIN EN.CITE <EndNote><Cite><Author>Eicher</Author><Year>1976</Year><RecNum>76</RecNum><DisplayText>(Eicher et al. 1976; Marie, Travers &amp; Glorieux 1981)</DisplayText><record><rec-number>76</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1533032419″>76</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Eicher, E. M</author><author>Southard, J.

L</author><author>Scriver, C. R</author><author>Glorieux, F. H.</author></authors></contributors><titles><title>Hypophosphatemia: Mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets</title><secondary-title>Proc Natl Acad Sci USA</secondary-title></titles><periodical><full-title>Proc Natl Acad Sci USA</full-title></periodical><pages>4667-4671</pages><volume>73</volume><number>12</number><dates><year>1976</year></dates><urls></urls></record></Cite><Cite><Author>Marie</Author><Year>1981</Year><RecNum>17</RecNum><record><rec-number>17</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519793688″>17</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Marie, P. J.</author><author>Travers, R.</author><author>Glorieux, F.

H.</author></authors></contributors><titles><title>Healing of rickets with phosphate supplementation in the hypophosphatemic male mouse</title><secondary-title>Journal of Clinical Investigation</secondary-title></titles><periodical><full-title>Journal of Clinical Investigation</full-title></periodical><pages>911-914</pages><volume>67</volume><number>3</number><dates><year>1981</year></dates><isbn>0021-9738</isbn><urls></urls><electronic-resource-num>10.1172/jci110110</electronic-resource-num></record></Cite></EndNote>(Eicher et al. 1976; Marie, Travers & Glorieux 1981). HYP mice display many of the same phenotypic traits such as hypophosphatemia, rickets, high serum alkaline phosphatase, modest hypocalcaemia, and marked reduction in bone growth and mineralisation ADDIN EN.CITE <EndNote><Cite><Author>Eicher</Author><Year>1976</Year><RecNum>76</RecNum><DisplayText>(Eicher et al.

1976; Marie, P.J, Travers, R &amp; Glorieux, F.H 1982)</DisplayText><record><rec-number>76</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1533032419″>76</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Eicher, E. M</author><author>Southard, J. L</author><author>Scriver, C. R</author><author>Glorieux, F. H.

</author></authors></contributors><titles><title>Hypophosphatemia: Mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets</title><secondary-title>Proc Natl Acad Sci USA</secondary-title></titles><periodical><full-title>Proc Natl Acad Sci USA</full-title></periodical><pages>4667-4671</pages><volume>73</volume><number>12</number><dates><year>1976</year></dates><urls></urls></record></Cite><Cite><Author>Marie</Author><Year>1982</Year><RecNum>16</RecNum><record><rec-number>16</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519792889″>16</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Marie, P.J</author><author>Travers, R</author><author>Glorieux, F.H</author></authors></contributors><titles><title>Bone Response to Phosphate and Vitamin D Metabolites in the Hypophosphatemic mouse model</title><secondary-title>Calcified Tissue International</secondary-title></titles><periodical><full-title>Calcified Tissue International</full-title></periodical><pages>158-164</pages><volume>34</volume><number>1</number><dates><year>1982</year></dates><urls></urls></record></Cite></EndNote>(Eicher et al.

1976; Marie, P.J, Travers, R & Glorieux, F.H 1982). FGF23 levels in HYP mice are up to 25-fold higher than in WT mice, and CYP24A1 levels are significantly elevated 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 ADDIN EN.

CITE 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 ADDIN EN.CITE.DATA (Azam et al. 2003). Similarly to XLH patients, HYP mice display an intestinal resistance to vitamin D therapy and defective renal CYP27B1 activity ADDIN EN.CITE <EndNote><Cite><Author>Meyer</Author><Year>1996</Year><RecNum>15</RecNum><DisplayText>(Meyer, Meyer &amp; Morgan 1996)</DisplayText><record><rec-number>15</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519792619″>15</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Meyer, R.A</author><author>Meyer, M. H</author><author>Morgan, P.

L</author></authors></contributors><titles><title><style face=”normal” font=”default” size=”100%”>Effects of Altered Diet on Serum levels of 1,25-Dihydroxyvitamin D and Parathyroid Hormone in X-Linked Hypophosphatemic </style><style face=”italic” font=”default” size=”100%”>(HYP and Gy) </style><style face=”normal” font=”default” size=”100%”>Mice</style></title><secondary-title>Bone</secondary-title></titles><periodical><full-title>Bone</full-title></periodical><pages>23-28</pages><volume>18</volume><number>1</number><dates><year>1996</year></dates><urls></urls></record></Cite></EndNote>(Meyer, Meyer & Morgan 1996). HYP mice have been reported to have low 1,25(OH)2D3 and 25(OH)D3 levels, and indeed, our group has also found this in recent unpublished observations.The majority of interventions on HYP mice have tested the efficacy of either phosphate, 1,25(OH)D3, or a combination of the two. Daily injections of 1,25(OH)2D3 in HYP mice were shown to improve cortical microarchitecture and whole bone biomechanical properties 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 ADDIN EN.CITE 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 ADDIN EN.

CITE.DATA (Liu et al. 2016).

The daily treatment of 1,25(OH)2D3 also led to a decrease in urine phosphate wasting despite the increasing FGF23 levels. Mice had normocalcaemia, normal PTH, and increased serum phosphate levels. The sodium-phosphate transporters in the gut were upregulated, and body weight increased.

The bone growth plate and metaphyseal organisation were improved, along with the lumbar vertebral height, and trabecular structure 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 ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MaXU8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxSZWNOdW0+MzwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oTGl1IGV0IGFsLiAyMDE2KTwvRGlzcGxheVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj4zPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0ieGZ3ZnhzOXYyenJwZTllcjJhOXB3ZDlmeHY1ejJ2OTJ3ZTVkIiB0aW1lc3RhbXA9IjE1MTk3OTE0OTgiPjM8L2tleT48a2V5IGFwcD0iRU5XZWIiIGRiLWlkPSIiPjA8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkxpdSwgRS4gUy48L2F1dGhvcj48YXV0aG9yPk1hcnRpbnMsIEouIFMuPC9hdXRob3I+PGF1dGhvcj5SYWltYW5uLCBBLjwvYXV0aG9yPjxhdXRob3I+Q2hhZSwgQi4gVC48L2F1dGhvcj48YXV0aG9yPkJyb29rcywgRC4gSi48L2F1dGhvcj48YXV0aG9yPkpvcmdldHRpLCBWLjwvYXV0aG9yPjxhdXRob3I+Qm91eHNlaW4sIE0uIEwuPC9hdXRob3I+PGF1dGhvcj5EZW1heSwgTS4gQi48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGF1dGgtYWRkcmVzcz5EaXZpc2lvbiBvZiBFbmRvY3Jpbm9sb2d5LCBEaWFiZXRlcywgYW5kIEh5cGVydGVuc2lvbiwgQnJpZ2hhbSBhbmQgV29tZW4mYXBvcztzIEhvc3BpdGFsLCBCb3N0b24sIE1BLCBVU0EuJiN4RDtFbmRvY3JpbmUgVW5pdCwgTWFzc2FjaHVzZXR0cyBHZW5lcmFsIEhvc3BpdGFsLCBCb3N0b24sIE1BLCBVU0EuJiN4RDtIYXJ2YXJkIE1lZGljYWwgU2Nob29sLCBCb3N0b24sIE1BLCBVU0EuJiN4RDtEaXZpc2lvbiBvZiBOZXBocm9sb2d5LCBVbml2ZXJzaWRhZGUgZGUgU2FvIFBhdWxvLCBTYW8gUGF1bG8sIEJyYXppbC4mI3hEO0RlcGFydG1lbnQgb2YgUGVkaWF0cmljcyBhbmQgQWRvbGVzY2VudCBNZWRpY2luZSwgTWVkaWNhbCBVbml2ZXJzaXR5IFZpZW5uYSwgVmllbm5hLCBBdXN0cmlhLiYjeEQ7RGVwYXJ0bWVudCBvZiBPcnRob3BlZGljcywgQmV0aCBJc3JhZWwgRGVhY29uZXNzIE1lZGljYWwgQ2VudGVyLCBCb3N0b24sIE1BLCBVU0EuPC9hdXRoLWFkZHJlc3M+PHRpdGxlcz48dGl0bGU+MSwyNS1EaWh5ZHJveHl2aXRhbWluIEQgQWxvbmUgSW1wcm92ZXMgU2tlbGV0YWwgR3Jvd3RoLCBNaWNyb2FyY2hpdGVjdHVyZSwgYW5kIFN0cmVuZ3RoIGluIGEgTXVyaW5lIE1vZGVsIG9mIFhMSCwgRGVzcGl0ZSBFbmhhbmNlZCBGR0YyMyBFeHByZXNzaW9uPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkogQm9uZSBNaW5lciBSZXM8L3NlY29uZGFyeS10aXRsZT48L3RpdGxlcz48cGVyaW9kaWNhbD48ZnVsbC10aXRsZT5KIEJvbmUgTWluZXIgUmVzPC9mdWxsLXRpdGxlPjwvcGVyaW9kaWNhbD48cGFnZXM+OTI5LTM5PC9wYWdlcz48dm9sdW1lPjMxPC92b2x1bWU+PG51bWJlcj41PC9udW1iZXI+PGtleXdvcmRzPjxrZXl3b3JkPkFuaW1hbHM8L2tleXdvcmQ+PGtleXdvcmQ+Qm9uZSBEZW5zaXR5LypkcnVnIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+Q2FsY2l0cmlvbC8qcGhhcm1hY29sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkRpc2Vhc2UgTW9kZWxzLCBBbmltYWw8L2tleXdvcmQ+PGtleXdvcmQ+KkZhbWlsaWFsIEh5cG9waG9zcGhhdGVtaWMgUmlja2V0cy9kcnVnIHRoZXJhcHkvbWV0YWJvbGlzbS9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+Rmlicm9ibGFzdCBHcm93dGggRmFjdG9ycy8qbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TUFQIEtpbmFzZSBTaWduYWxpbmcgU3lzdGVtLypkcnVnIGVmZmVjdHM8L2tleXdvcmQ+PGtleXdvcmQ+TWljZTwva2V5d29yZD48a2V5d29yZD5NaXRvZ2VuLUFjdGl2YXRlZCBQcm90ZWluIEtpbmFzZSAzL2dlbmV0aWNzL21ldGFib2xpc208L2tleXdvcmQ+PGtleXdvcmQ+KlNrZWxldG9uL21ldGFib2xpc20vcGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPlNvZGl1bS1QaG9zcGhhdGUgQ290cmFuc3BvcnRlciBQcm90ZWlucywgVHlwZSBJSWEvZ2VuZXRpY3MvbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5CaW9tZWNoYW5pY3M8L2tleXdvcmQ+PGtleXdvcmQ+Qk9ORSBRQ1QvbXVDVDwva2V5d29yZD48a2V5d29yZD5HZW5ldGljIG1vdXNlIG1vZGVsczwva2V5d29yZD48a2V5d29yZD5Hcm93dGggcGxhdGU8L2tleXdvcmQ+PGtleXdvcmQ+UHRoL3ZpdCBkL2ZnZjIzPC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTY8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5NYXk8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4xNTIzLTQ2ODEgKEVsZWN0cm9uaWMpJiN4RDswODg0LTA0MzEgKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjI2NzUxODM1PC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwczovL3d3dy5uY2JpLm5sbS5uaWguZ292L3B1Ym1lZC8yNjc1MTgzNTwvdXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48Y3VzdG9tMj5QTUM0ODYyOTMzPC9jdXN0b20yPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDAyL2pibXIuMjc4MzwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A ADDIN EN.CITE.

DATA (Liu et al. 2016). However, 1,25(OH)2D treatment at this scale in humans would cause hypercalcaemia and nephrocalcinosis.Only one previous study has used the inactive from of vitamin D, 25(OH)D3, to try rescue the bone phenotype ADDIN EN.CITE <EndNote><Cite><Author>Marie</Author><Year>1982</Year><RecNum>80</RecNum><DisplayText>(Marie, P. J, Travers, R &amp; Glorieux, F.

H 1982)</DisplayText><record><rec-number>80</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1533113679″>80</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Marie, P. J</author><author>Travers, R</author><author>Glorieux, F. H</author></authors></contributors><titles><title>Healing of bone lesions with 1, 25-dihydroxyvitamin D3 in the young X-linked hypophosphatemic male mouse</title><secondary-title>Endocrinology</secondary-title></titles><periodical><full-title>Endocrinology</full-title></periodical><pages>904-911</pages><volume>111</volume><number>3</number><dates><year>1982</year></dates><isbn>0013-7227</isbn><urls><related-urls><url><style face=”underline” font=”default” size=”100%”>https://academic.oup.

com/endo/article-abstract/111/3/904/2591271?redirectedFrom=fulltext</style></url></related-urls></urls></record></Cite></EndNote>(Marie, P. J, Travers, R & Glorieux, F. H 1982). Marie et al infused a relatively low dose of 25(OH)D3 into HYP mice over a 3 week period, in addition to phosphate salts in the drinking water. While 25(OH)D3 levels were shown to marginally improve, the underminerlised bone persisted.

This suggested to the authors that there was a specific bone cell resistance to mineral and/or hormonal treatment ADDIN EN.CITE <EndNote><Cite><Author>Marie</Author><Year>1982</Year><RecNum>16</RecNum><DisplayText>(Marie, P.J, Travers, R &amp; Glorieux, F.H 1982)</DisplayText><record><rec-number>16</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519792889″>16</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Marie, P.J</author><author>Travers, R</author><author>Glorieux, F.H</author></authors></contributors><titles><title>Bone Response to Phosphate and Vitamin D Metabolites in the Hypophosphatemic mouse model</title><secondary-title>Calcified Tissue International</secondary-title></titles><periodical><full-title>Calcified Tissue International</full-title></periodical><pages>158-164</pages><volume>34</volume><number>1</number><dates><year>1982</year></dates><urls></urls></record></Cite></EndNote>(Marie, P.

J, Travers, R & Glorieux, F.H 1982). While this conclusion may be true, no further investigations have been performed to elevate 25(OH)D to levels that, more recently, have shown to improve bone mineralisation in other settings. For example, 20,000IU/kg of vitamin D fed to Wild Type (WT) mice resulted in increased bone mineralisation and stronger bones without causing hypercalcemia 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Williamson et al.

2017).The role of vitamin D catabolism in XLHCYP24A1 is the sole enzyme involved in the catabolism of vitamin D. While the classical view is that CYP24A1 limits the tissue activity of 1,25(OH)2D, renal CYP24A1 activity has been shown to regulate circulating 1,25(OH)2D levels which also impacts tissue-level activity as well 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 ADDIN EN.CITE 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 ADDIN EN.

CITE.DATA (Anderson et al. 2004). Furthermore, in bone CYP24A1 activity has been shown to be regulated independently of circulating 1,25(OH)2D levels, indicating that autocrine regulation of 1,25(OH)2D activity in bone is independent of renal vitamin D metabolism regulation ADDIN EN.CITE <EndNote><Cite><Author>Anderson</Author><Year>2005</Year><RecNum>100</RecNum><DisplayText>(Anderson et al. 2005)</DisplayText><record><rec-number>100</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1537164458″>100</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Anderson, P.

H.</author><author>O&apos;Loughlin, P. D.</author><author>May, B. K.</author><author>Morris, H. A.</author></authors></contributors><auth-address>Endocrine Bone Research Laboratory, Hanson Institute, Adelaide, SA, Australia.

[email protected]</auth-address><titles><title>Modulation of CYP27B1 and CYP24 mRNA expression in bone is independent of circulating 1,25(OH)2D3 levels</title><secondary-title>Bone</secondary-title></titles><periodical><full-title>Bone</full-title></periodical><pages>654-62</pages><volume>36</volume><number>4</number><edition>2005/03/23</edition><keywords><keyword>25-Hydroxyvitamin D3 1-alpha-Hydroxylase/*genetics</keyword><keyword>Animals</keyword><keyword>Bone and Bones/anatomy &amp; histology/*enzymology</keyword><keyword>Calcitriol/*blood</keyword><keyword>Cytochrome P-450 Enzyme System/*genetics</keyword><keyword>Female</keyword><keyword>Kidney/enzymology</keyword><keyword>RNA, Messenger/*genetics</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Receptors, Calcitriol/genetics</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Steroid Hydroxylases/*genetics</keyword><keyword>Vitamin D3 24-Hydroxylase</keyword></keywords><dates><year>2005</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>8756-3282 (Print) 1873-2763 (Linking)</isbn><accession-num>15781002</accession-num><urls><related-urls><url>https://www.

ncbi.nlm.nih.gov/pubmed/15781002</url></related-urls></urls><electronic-resource-num>10.1016/j.

bone.2005.01.012</electronic-resource-num></record></Cite></EndNote>(Anderson et al. 2005).

We have recently also demonstrated that the genetic deletion of CYP24A1 in osteocytes using Cre-lox technology, increases bone volume in young mice suggesting that the CYP24A1 in osteocytes plays an inhibitory role on bone mineralisation (Barratt et al, in preparation). In Hyp mice, renal CYP24A1 levels have been shown to be 2-fold higher in HYP mice 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Azam et al.

2003) which contributes to lower circulating 1,25(OH)2D levels. No investigations have yet been performed to demonstrate whether osteocytic CYP24A1 levels are in increased in Hyp mice. However, it is unclear whether the bones of HYP mice have aberrantly high CYP24A1, which would frustrate the anabolic activities of 1,25(OH)2D. It is worth noting however, that low phosphate levels may directly contribute to the high expression of CYP24A1, in osteocytes at least, given that decreasing phosphate levels in media of the osteocyte cell line, IDG-SW3, enhances the induction of Cyp24a1 by 1,25(OH)2D 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Ito et al. 2013). Furthermore, HYP primary osteocytes exposed to 1,25(OH)2D do not induce mRNA levels for vitamin D responsive genes such as VDR or Fgf23 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Miyagawa et al. 2014), perhaps suggesting that excessive CYP24A1 catabolises 1,25(OH)2D. However, the authors of this study did not directly measure CYP24A1 or 1,25(OH)2D clearance (Prof T. Michigami, personal communications). Regardless, these data suggest that Cyp24a1 activity in bone, possibly osteoblasts, osteocytes or chondrocytes during phosphate wasting disorders, may reduce 1,25D activity in bone, resulting in under-mineralisation. A recent key study in investigating the role of CYP24A1 in HYP mice was performed by crossing the global CYP24A1-knockout mice with HYP mice. The hypothesis was that the absence of CYP24A1 would elevate circulating 1,25(OH)2D levels and contribute to the healing of the XLH bone phenotype 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 ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYWk8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxSZWNOdW0+MTwvUmVjTnVtPjxEaXNwbGF5VGV4dD4oQmFpIGV0IGFsLiAyMDE2KTwvRGlzcGxheVRleHQ+PHJlY29yZD48cmVjLW51bWJlcj4xPC9yZWMtbnVtYmVyPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0ieGZ3ZnhzOXYyenJwZTllcjJhOXB3ZDlmeHY1ejJ2OTJ3ZTVkIiB0aW1lc3RhbXA9IjAiPjE8L2tleT48L2ZvcmVpZ24ta2V5cz48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkJhaSwgWC48L2F1dGhvcj48YXV0aG9yPk1pYW8sIEQuPC9hdXRob3I+PGF1dGhvcj5YaWFvLCBTLjwvYXV0aG9yPjxhdXRob3I+UWl1LCBELjwvYXV0aG9yPjxhdXRob3I+U3QtQXJuYXVkLCBSLjwvYXV0aG9yPjxhdXRob3I+UGV0a292aWNoLCBNLjwvYXV0aG9yPjxhdXRob3I+R3VwdGEsIEEuPC9hdXRob3I+PGF1dGhvcj5Hb2x0em1hbiwgRC48L2F1dGhvcj48YXV0aG9yPkthcmFwbGlzLCBBLiBDLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48dGl0bGVzPjx0aXRsZT5DWVAyNCBpbmhpYml0aW9uIGFzIGEgdGhlcmFwZXV0aWMgdGFyZ2V0IGluIEZHRjIzLW1lZGlhdGVkIHJlbmFsIHBob3NwaGF0ZSB3YXN0aW5nIGRpc29yZGVyczwvdGl0bGU+PHNlY29uZGFyeS10aXRsZT5KIENsaW4gSW52ZXN0PC9zZWNvbmRhcnktdGl0bGU+PC90aXRsZXM+PHBlcmlvZGljYWw+PGZ1bGwtdGl0bGU+SiBDbGluIEludmVzdDwvZnVsbC10aXRsZT48L3BlcmlvZGljYWw+PHBhZ2VzPjY2Ny04MDwvcGFnZXM+PHZvbHVtZT4xMjY8L3ZvbHVtZT48bnVtYmVyPjI8L251bWJlcj48a2V5d29yZHM+PGtleXdvcmQ+QW5pbWFsczwva2V5d29yZD48a2V5d29yZD5DeXRvY2hyb21lIFAtNDUwIEVuenltZSBJbmhpYml0b3JzLypwaGFybWFjb2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+RGlzZWFzZSBNb2RlbHMsIEFuaW1hbDwva2V5d29yZD48a2V5d29yZD5GZW1hbGU8L2tleXdvcmQ+PGtleXdvcmQ+Rmlicm9ibGFzdCBHcm93dGggRmFjdG9ycy9nZW5ldGljcy8qbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWljZTwva2V5d29yZD48a2V5d29yZD5NaWNlLCBLbm9ja291dDwva2V5d29yZD48a2V5d29yZD5QaG9zcGhhdGVzLyp1cmluZTwva2V5d29yZD48a2V5d29yZD4qUmVuYWwgSW5zdWZmaWNpZW5jeSwgQ2hyb25pYy9kcnVnIHRoZXJhcHkvZ2VuZXRpY3MvcGF0aG9sb2d5L3VyaW5lPC9rZXl3b3JkPjxrZXl3b3JkPlZpdGFtaW4gRDMgMjQtSHlkcm94eWxhc2UvKmFudGFnb25pc3RzICZhbXA7IGluaGliaXRvcnMvZ2VuZXRpY3MvbWV0YWJvbGlzbTwva2V5d29yZD48a2V5d29yZD4qV2FzdGluZyBTeW5kcm9tZS9kcnVnIHRoZXJhcHkvZ2VuZXRpY3MvcGF0aG9sb2d5L3VyaW5lPC9rZXl3b3JkPjwva2V5d29yZHM+PGRhdGVzPjx5ZWFyPjIwMTY8L3llYXI+PHB1Yi1kYXRlcz48ZGF0ZT5GZWI8L2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4xNTU4LTgyMzggKEVsZWN0cm9uaWMpJiN4RDswMDIxLTk3MzggKExpbmtpbmcpPC9pc2JuPjxhY2Nlc3Npb24tbnVtPjI2Nzg0NTQxPC9hY2Nlc3Npb24tbnVtPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD48c3R5bGUgZmFjZT0idW5kZXJsaW5lIiBmb250PSJkZWZhdWx0IiBzaXplPSIxMDAlIj5odHRwczovL3d3dy5uY2JpLm5sbS5uaWguZ292L3B1Ym1lZC8yNjc4NDU0MTwvc3R5bGU+PC91cmw+PHVybD48c3R5bGUgZmFjZT0idW5kZXJsaW5lIiBmb250PSJkZWZhdWx0IiBzaXplPSIxMDAlIj5odHRwczovL3d3dy5uY2JpLm5sbS5uaWguZ292L3BtYy9hcnRpY2xlcy9QTUM0NzMxMTkzL3BkZi9KQ0k4MTkyOC5wZGY8L3N0eWxlPjwvdXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48Y3VzdG9tMj5QTUM0NzMxMTkzPC9jdXN0b20yPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMTcyL0pDSTgxOTI4PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPn== ADDIN EN.CITE.DATA (Bai et al. 2016). To the surprise of the authors, the absence of CYP24A1 resulted in the complete prevention of growth and mineralisation disorder in HYP mice 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Bai et al. 2016). Interestingly, while growth plate and cortical bone mineral was restored, the key biochemical indices of HYP disorder, namely hypophosphatemia and low 1,25(OH)2D levels, remained low and unchanged 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Bai et al. 2016). These exciting data suggest that the current therapy of correcting blood phosphate and circulating 1,25(OH)2D is not essential to normalise bone health in XLH. Furthermore, these data suggest that CYP24A1 deletion in tissues other than the kidney, play a major role in allowing normal bone mineral levels. Given the evidence for the role of CYP24A1 in bone homeostasis, a key tissue to investigate further is the bone with respect to CYP24A1 and its role in XLH.RESEARCH DESIGN: Aim 1: To determine whether raising circulating 25-hydroxyvitamin D (25D) levels heal the bone in Hyp mice.Rationale: The disorder of XLH, was previously known as vitamin D-resistant rickets owing to the fact the renal conversion of 25(OH)D3 to 1,25(OH)D3 was impeded by FGF23 ADDIN EN.CITE <EndNote><Cite><Author>Saito</Author><Year>2009</Year><RecNum>28</RecNum><DisplayText>(Saito &amp; Fukumoto 2009)</DisplayText><record><rec-number>28</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1519884606″>28</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Saito, T.</author><author>Fukumoto, S.</author></authors></contributors><auth-address>Department of Pediatrics, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.</auth-address><titles><title>Fibroblast Growth Factor 23 (FGF23) and Disorders of Phosphate Metabolism</title><secondary-title>Int J Pediatr Endocrinol</secondary-title></titles><periodical><full-title>Int J Pediatr Endocrinol</full-title></periodical><pages>496514</pages><volume>2009</volume><dates><year>2009</year></dates><isbn>1687-9856 (Electronic) 1687-9848 (Linking)</isbn><accession-num>19956747</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/19956747</url></related-urls></urls><custom2>PMC2775677</custom2><electronic-resource-num>10.1155/2009/496514</electronic-resource-num></record></Cite></EndNote>(Saito & Fukumoto 2009). We know that bone is a major site for local synthesis and activity of 1,25(OH)D3 and is dependent on the circulating supply of 25(OH)D3 ADDIN EN.CITE <EndNote><Cite><Author>Anderson</Author><Year>2017</Year><RecNum>94</RecNum><DisplayText>(Anderson 2017)</DisplayText><record><rec-number>94</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1534470997″>94</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Anderson, P. H.</author></authors></contributors><auth-address>Musculoskeletal Biology Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5001, Australia. [email protected]</auth-address><titles><title>Vitamin D Activity and Metabolism in Bone</title><secondary-title>Curr Osteoporos Rep</secondary-title></titles><periodical><full-title>Curr Osteoporos Rep</full-title></periodical><pages>443-449</pages><volume>15</volume><number>5</number><edition>2017/08/16</edition><keywords><keyword>25-Hydroxyvitamin D3 1-alpha-Hydroxylase/*metabolism</keyword><keyword>Autocrine Communication</keyword><keyword>Bone Resorption/metabolism</keyword><keyword>Bone and Bones/*metabolism</keyword><keyword>Calcification, Physiologic/physiology</keyword><keyword>Fracture Healing/physiology</keyword><keyword>Humans</keyword><keyword>Receptors, Calcitriol/*metabolism</keyword><keyword>Vitamin D/*analogs &amp; derivatives/metabolism</keyword><keyword>Vitamin D3 24-Hydroxylase/*metabolism</keyword><keyword>Cyp24a1</keyword><keyword>Cyp27b1</keyword><keyword>Mineralisation</keyword><keyword>Osteoblasts</keyword><keyword>Vitamin D</keyword><keyword>Vitamin D receptor</keyword></keywords><dates><year>2017</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1544-2241 (Electronic) 1544-1873 (Linking)</isbn><accession-num>28808890</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/28808890</url></related-urls></urls><electronic-resource-num>10.1007/s11914-017-0394-8</electronic-resource-num></record></Cite></EndNote>(Anderson 2017). There have been no previous studies to examine whether raising 25(OH)D3 to high levels through dietary vitamin D administration can heal the bone phenotype more easily than 1,25(OH)D3. Thus, it is valuable to assess whether the HYP bone can be healed through raising the serum 25(OH)D levels either by dietary vitamin D supplementation or direct infusion of 25(OH)D.Model 1: Male HYP (XHypY) mice will be supplemented with vitamin D from 3 weeks of age until 12 weeks of age. Mice (n=12/grp) will receive diets containing 1000 IU/kg (standard) or 20,000IU/kg of vitamin D plus either 0.625% phosphorus (standard) or 1.25% phosphorus (high). These levels of vitamin D should significantly raise 25(OH)D3 levels to an approximate maximum of 200 nmol/L without causing direct activation of the VDR ADDIN EN.CITE <EndNote><Cite><Author>Rowling</Author><Year>2007</Year><RecNum>6750</RecNum><DisplayText>(Rowling, M. J. et al. 2007)</DisplayText><record><rec-number>6750</rec-number><foreign-keys><key app=”EN” db-id=”5ardrpxr60pvfnef52axpsxpptazw02s9pvw” timestamp=”1253599895″>6750</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Rowling, M. J.</author><author>Gliniak, C.</author><author>Welsh, J.</author><author>Fleet, J. C.</author></authors></contributors><auth-address>Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556 4Interdepartmental Nutrition Program and Department of Foods and Nutrition, Purdue University, West Lafayette, IN 47906.</auth-address><titles><title>High Dietary Vitamin D Prevents Hypocalcemia and Osteomalacia in CYP27B1 Knockout Mice</title><secondary-title>J Nutr</secondary-title></titles><pages>2608-15</pages><volume>137</volume><number>12</number><dates><year>2007</year><pub-dates><date>Dec</date></pub-dates></dates><accession-num>18029472</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=18029472</url></related-urls></urls></record></Cite></EndNote>(Rowling, M. J. et al. 2007).Model 2; Male HYP (XHypY) mice will be fed a standard level of phosphorus from 3 weeks of age until 8 weeks of age. At 4 weeks of age, mice will undergo minor surgery to insert a mini osmotic pump (Alzet 1004) subcutaneously containing 25(OH)D3 (100ng or 200ng/day), or saline, at a constant rate over a 4 week period. At time of death, we will collect tissues and employ our suite of established analyses described in previous publications <EndNote><Cite><Author>Anderson</Author><Year>2005</Year><RecNum>100</RecNum><DisplayText>(Anderson et al. 2005; Anderson et al. 2008; Chiang et al. 2009)</DisplayText><record><rec-number>100</rec-number><foreign-keys><key app="EN" db-id="xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d" timestamp="1537164458">100</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Anderson, P. H.</author><author>O&apos;Loughlin, P. D.</author><author>May, B. K.</author><author>Morris, H. A.</author></authors></contributors><auth-address>Endocrine Bone Research Laboratory, Hanson Institute, Adelaide, SA, Australia. paul.anderson@imvs.sa.gov.au</auth-address><titles><title>Modulation of CYP27B1 and CYP24 mRNA expression in bone is independent of circulating 1,25(OH)2D3 levels</title><secondary-title>Bone</secondary-title></titles><periodical><full-title>Bone</full-title></periodical><pages>654-62</pages><volume>36</volume><number>4</number><edition>2005/03/23</edition><keywords><keyword>25-Hydroxyvitamin D3 1-alpha-Hydroxylase/*genetics</keyword><keyword>Animals</keyword><keyword>Bone and Bones/anatomy &amp; histology/*enzymology</keyword><keyword>Calcitriol/*blood</keyword><keyword>Cytochrome P-450 Enzyme System/*genetics</keyword><keyword>Female</keyword><keyword>Kidney/enzymology</keyword><keyword>RNA, Messenger/*genetics</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Receptors, Calcitriol/genetics</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Steroid Hydroxylases/*genetics</keyword><keyword>Vitamin D3 24-Hydroxylase</keyword></keywords><dates><year>2005</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>8756-3282 (Print)&#xD;1873-2763 (Linking)</isbn><accession-num>15781002</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/15781002</url></related-urls></urls><electronic-resource-num>10.1016/j.bone.2005.01.012</electronic-resource-num></record></Cite><Cite><Author>Chiang</Author><Year>2009</Year><RecNum>14</RecNum><record><rec-number>14</rec-number><foreign-keys><key app="EN" db-id="r9a0z5fzo02xtzexaf6v552vztvxfwwfexdp" timestamp="1455686799">14</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chiang, C.</author><author>Chiu, M.</author><author>Moore, A. J.</author><author>Anderson, P. H.</author><author>Ghasem-Zadeh, A.</author><author>McManus, J. F.</author><author>Ma, C.</author><author>Seeman, E.</author><author>Clemens, T. L.</author><author>Morris, H. A.</author><author>Zajac, J. D.</author><author>Davey, R. A.</author></authors></contributors><auth-address>Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.</auth-address><titles><title>Mineralization and bone resorption are regulated by the androgen receptor in male mice</title><secondary-title>J Bone Miner Res</secondary-title></titles><periodical><full-title>J Bone Miner Res</full-title></periodical><pages>621-31</pages><volume>24</volume><number>4</number><edition>2008/12/04</edition><keywords><keyword>Acid Phosphatase/blood</keyword><keyword>Animals</keyword><keyword>Biological Markers/blood</keyword><keyword>Bone Density/*physiology</keyword><keyword>Bone Remodeling</keyword><keyword>Bone Resorption/blood/*metabolism/pathology/*physiopathology</keyword><keyword>Femur/pathology</keyword><keyword>Gene Deletion</keyword><keyword>Integrases/metabolism</keyword><keyword>Isoenzymes/blood</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Knockout</keyword><keyword>Osteoblasts/metabolism</keyword><keyword>Osteocalcin/blood</keyword><keyword>Phenotype</keyword><keyword>Receptors, Androgen/*metabolism</keyword><keyword>Spine/metabolism/pathology</keyword><keyword>Tomography, X-Ray Computed</keyword></keywords><dates><year>2009</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1523-4681 (Electronic)&#xD;1523-4681 (Linking)</isbn><accession-num>19049333</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=19049333</url></related-urls></urls><electronic-resource-num>10.1359/jbmr.081217</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Anderson</Author><Year>2008</Year><RecNum>9</RecNum><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="r9a0z5fzo02xtzexaf6v552vztvxfwwfexdp" timestamp="1455686797">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Anderson, P. H.</author><author>Sawyer, R. K.</author><author>Moore, A. J.</author><author>May, B. K.</author><author>O&apos;Loughlin, P. D.</author><author>Morris, H. A.</author></authors></contributors><auth-address>School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia. paul.anderson@imvs.sa.gov.au</auth-address><titles><title>Vitamin D depletion induces RANKL-mediated osteoclastogenesis and bone loss in a rodent model</title><secondary-title>Journal of Bone and Mineral Research</secondary-title></titles><periodical><full-title>Journal of Bone and Mineral Research</full-title></periodical><pages>1789-97</pages><volume>23</volume><number>11</number><edition>2008/07/04</edition><keywords><keyword>25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics/metabolism</keyword><keyword>Animals</keyword><keyword>Bone Resorption/blood/*complications/*physiopathology</keyword><keyword>Calcification, Physiologic</keyword><keyword>Disease Models, Animal</keyword><keyword>Femur/anatomy &amp; histology/enzymology</keyword><keyword>Gene Expression Regulation, Enzymologic</keyword><keyword>Male</keyword><keyword>Organ Size</keyword><keyword>*Osteogenesis</keyword><keyword>Osteomalacia/blood/complications/physiopathology</keyword><keyword>Parathyroid Hormone/blood</keyword><keyword>RANK Ligand/*metabolism</keyword><keyword>RNA, Messenger/genetics/metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Regression Analysis</keyword><keyword>Vitamin D/analogs &amp; derivatives/blood</keyword><keyword>Vitamin D Deficiency/blood/*complications/*physiopathology</keyword></keywords><dates><year>2008</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1523-4681 (Electronic)</isbn><accession-num>18597628</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=18597628</url></related-urls></urls><electronic-resource-num>10.1359/jbmr.080616</electronic-resource-num><language>eng</language></record></Cite></EndNote>  ADDIN EN.CITE <EndNote><Cite><Author>Anderson</Author><Year>2005</Year><RecNum>100</RecNum><DisplayText>(Anderson et al. 2005; Anderson et al. 2008; Chiang et al. 2009)</DisplayText><record><rec-number>100</rec-number><foreign-keys><key app="EN" db-id="xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d" timestamp="1537164458">100</key><key app="ENWeb" db-id="">0</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Anderson, P. H.</author><author>O&apos;Loughlin, P. D.</author><author>May, B. K.</author><author>Morris, H. A.</author></authors></contributors><auth-address>Endocrine Bone Research Laboratory, Hanson Institute, Adelaide, SA, Australia. paul.anderson@imvs.sa.gov.au</auth-address><titles><title>Modulation of CYP27B1 and CYP24 mRNA expression in bone is independent of circulating 1,25(OH)2D3 levels</title><secondary-title>Bone</secondary-title></titles><periodical><full-title>Bone</full-title></periodical><pages>654-62</pages><volume>36</volume><number>4</number><edition>2005/03/23</edition><keywords><keyword>25-Hydroxyvitamin D3 1-alpha-Hydroxylase/*genetics</keyword><keyword>Animals</keyword><keyword>Bone and Bones/anatomy &amp; histology/*enzymology</keyword><keyword>Calcitriol/*blood</keyword><keyword>Cytochrome P-450 Enzyme System/*genetics</keyword><keyword>Female</keyword><keyword>Kidney/enzymology</keyword><keyword>RNA, Messenger/*genetics</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Receptors, Calcitriol/genetics</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Steroid Hydroxylases/*genetics</keyword><keyword>Vitamin D3 24-Hydroxylase</keyword></keywords><dates><year>2005</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>8756-3282 (Print)&#xD;1873-2763 (Linking)</isbn><accession-num>15781002</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/15781002</url></related-urls></urls><electronic-resource-num>10.1016/j.bone.2005.01.012</electronic-resource-num></record></Cite><Cite><Author>Chiang</Author><Year>2009</Year><RecNum>14</RecNum><record><rec-number>14</rec-number><foreign-keys><key app="EN" db-id="r9a0z5fzo02xtzexaf6v552vztvxfwwfexdp" timestamp="1455686799">14</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Chiang, C.</author><author>Chiu, M.</author><author>Moore, A. J.</author><author>Anderson, P. H.</author><author>Ghasem-Zadeh, A.</author><author>McManus, J. F.</author><author>Ma, C.</author><author>Seeman, E.</author><author>Clemens, T. L.</author><author>Morris, H. A.</author><author>Zajac, J. D.</author><author>Davey, R. A.</author></authors></contributors><auth-address>Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.</auth-address><titles><title>Mineralization and bone resorption are regulated by the androgen receptor in male mice</title><secondary-title>J Bone Miner Res</secondary-title></titles><periodical><full-title>J Bone Miner Res</full-title></periodical><pages>621-31</pages><volume>24</volume><number>4</number><edition>2008/12/04</edition><keywords><keyword>Acid Phosphatase/blood</keyword><keyword>Animals</keyword><keyword>Biological Markers/blood</keyword><keyword>Bone Density/*physiology</keyword><keyword>Bone Remodeling</keyword><keyword>Bone Resorption/blood/*metabolism/pathology/*physiopathology</keyword><keyword>Femur/pathology</keyword><keyword>Gene Deletion</keyword><keyword>Integrases/metabolism</keyword><keyword>Isoenzymes/blood</keyword><keyword>Male</keyword><keyword>Mice</keyword><keyword>Mice, Inbred C57BL</keyword><keyword>Mice, Knockout</keyword><keyword>Osteoblasts/metabolism</keyword><keyword>Osteocalcin/blood</keyword><keyword>Phenotype</keyword><keyword>Receptors, Androgen/*metabolism</keyword><keyword>Spine/metabolism/pathology</keyword><keyword>Tomography, X-Ray Computed</keyword></keywords><dates><year>2009</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1523-4681 (Electronic)&#xD;1523-4681 (Linking)</isbn><accession-num>19049333</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=19049333</url></related-urls></urls><electronic-resource-num>10.1359/jbmr.081217</electronic-resource-num><language>eng</language></record></Cite><Cite><Author>Anderson</Author><Year>2008</Year><RecNum>9</RecNum><record><rec-number>9</rec-number><foreign-keys><key app="EN" db-id="r9a0z5fzo02xtzexaf6v552vztvxfwwfexdp" timestamp="1455686797">9</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Anderson, P. H.</author><author>Sawyer, R. K.</author><author>Moore, A. J.</author><author>May, B. K.</author><author>O&apos;Loughlin, P. D.</author><author>Morris, H. A.</author></authors></contributors><auth-address>School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia. paul.anderson@imvs.sa.gov.au</auth-address><titles><title>Vitamin D depletion induces RANKL-mediated osteoclastogenesis and bone loss in a rodent model</title><secondary-title>Journal of Bone and Mineral Research</secondary-title></titles><periodical><full-title>Journal of Bone and Mineral Research</full-title></periodical><pages>1789-97</pages><volume>23</volume><number>11</number><edition>2008/07/04</edition><keywords><keyword>25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics/metabolism</keyword><keyword>Animals</keyword><keyword>Bone Resorption/blood/*complications/*physiopathology</keyword><keyword>Calcification, Physiologic</keyword><keyword>Disease Models, Animal</keyword><keyword>Femur/anatomy &amp; histology/enzymology</keyword><keyword>Gene Expression Regulation, Enzymologic</keyword><keyword>Male</keyword><keyword>Organ Size</keyword><keyword>*Osteogenesis</keyword><keyword>Osteomalacia/blood/complications/physiopathology</keyword><keyword>Parathyroid Hormone/blood</keyword><keyword>RANK Ligand/*metabolism</keyword><keyword>RNA, Messenger/genetics/metabolism</keyword><keyword>Rats</keyword><keyword>Rats, Sprague-Dawley</keyword><keyword>Regression Analysis</keyword><keyword>Vitamin D/analogs &amp; derivatives/blood</keyword><keyword>Vitamin D Deficiency/blood/*complications/*physiopathology</keyword></keywords><dates><year>2008</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>1523-4681 (Electronic)</isbn><accession-num>18597628</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=18597628</url></related-urls></urls><electronic-resource-num>10.1359/jbmr.080616</electronic-resource-num><language>eng</language></record></Cite></EndNote>  ADDIN EN.CITE.DATA (Anderson et al. 2005; Anderson et al. 2008; Chiang et al. 2009). Biochemical analyses: serum levels of calcium, phosphate, ALP (Kone Chemistry Analyser), 25(OH)D3 and 1,25(OH)D3 (LC-MS/MS), PTH, and intact FGF23 (commercially available ELISA assays). Ex-vivo micro-CT analyses: For Model 1, femoral and vertebral scans will be performs as per laboratory SOPs. This provides a non-destructive 3D image of the inner bone structure and allows for evaluation of the treatment on bone health. Regions of interest (ROI) will be adjusted based on the average femur length for each of the groups. In vivo micro-CT analyses: For Model 2, 2 weeks post-surgery (6 weeks of age), mice will be anaesthetised for a lower-leg micro-CT scan (Skyscan 1276). This provides a non-destructive 3D image of the inner bone structure and allows a mid-treatment evaluation of the treatment on bone health. Tissue histology and histomorphometric analyses: To evaluate mineralisation, sections of the left femur (after microCT scanning) will be embedded in methylmethacrylate before sectioning. Histomorphometry will use Osteomeasure (Osteometrics), in accordance to criteria of the American Society of Bone and Mineral Research ADDIN EN.CITE <EndNote><Cite><Author>Dempster</Author><Year>2013</Year><RecNum>93</RecNum><DisplayText>(Dempster et al. 2013)</DisplayText><record><rec-number>93</rec-number><foreign-keys><key app=”EN” db-id=”xfwfxs9v2zrpe9er2a9pwd9fxv5z2v92we5d” timestamp=”1534470947″>93</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Dempster, D. W.</author><author>Compston, J. E.</author><author>Drezner, M. K.</author><author>Glorieux, F. H.</author><author>Kanis, J. A.</author><author>Malluche, H.</author><author>Meunier, P. J.</author><author>Ott, S. M.</author><author>Recker, R. R.</author><author>Parfitt, A. M.</author></authors></contributors><auth-address>Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY, USA. [email protected]</auth-address><titles><title>Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee</title><secondary-title>J Bone Miner Res</secondary-title></titles><periodical><full-title>J Bone Miner Res</full-title></periodical><pages>2-17</pages><volume>28</volume><number>1</number><edition>2012/12/01</edition><keywords><keyword>Animals</keyword><keyword>Bone and Bones/*anatomy &amp; histology</keyword><keyword>Guidelines as Topic</keyword><keyword>Humans</keyword><keyword>Reference Standards</keyword><keyword>*Research Report</keyword><keyword>*Terminology as Topic</keyword></keywords><dates><year>2013</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1523-4681 (Electronic) 0884-0431 (Linking)</isbn><accession-num>23197339</accession-num><urls><related-urls><url>https://www.ncbi.nlm.nih.gov/pubmed/23197339</url></related-urls></urls><custom2>PMC3672237</custom2><electronic-resource-num>10.1002/jbmr.1805</electronic-resource-num></record></Cite></EndNote>(Dempster et al. 2013), and include measures of bone formation (dual fluorochrome labelling prior to death), osteoid volume and growth plate height (Massons’-Goldner’s Modified Trichrome), osteoblast surface (toluidine blue staining), and osteoclasts (TRAP stain). Messenger RNA analyses: Soft tissues will be snap frozen and RNA extracted using the TRIZOL RNA isolation protocol. cDNA will be synthesised for the purpose of RT PCR’s. Relative expression of CYP24A1, CYP27B1, NaPi2a, NaPi2c, CYP2R1 and CYP24A1 will be reported.Outcomes This study is a necessary dietary intervention for HYP mice that frankly should have been done years ago. It will assess if there is resistance to vitamin D synthesis and activity in the bone of HYP mice, be it due to excessive FGF23 or another factor, even with high circulating levels of 25(OH)D and dietary phosphate supplementation.Aim 2: To determine whether raising osteocyte levels of active vitamin D (1,25(OH)2D) heals the bone of Hyp mice.Rationale: As discussed above, global deletion of CYP24A1 heals the under-mineralised and disturbed growth plate phenotype in HYP mice. This occurs despite the persistence of hypophosphataemia and an even lower serum 1,25(OH)D levels 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Bai et al. 2016). These data demonstrate that low serum phosphate and low circulating 1,25D levels are not primarily responsible for the under-mineralisation. While strongly suggestive, the limitation of this study is the inability to definitively implicate bone CYP24A1. The two most likely candidate cell-types in bone that are responsible for the HYP bone phenotype are osteocytes or chondrocytes. Both cell-types have been shown to produce FGF23, control phosphate homeostasis, and are involved in process of bone formation 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 ADDIN EN.CITE 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 ADDIN EN.CITE.DATA (Masuyama et al. 2006). Thus, to determine whether abrogating Cyp24a1 activity in bone improves the bone phenotype of the HYP mice, conditional knockout mouse models are required. We will utilise Cre-lox systems to delete Cyp24a1 in osteocytes. We have previously created the osteocyte-specific CYP24A1KO mice. These mice will be crossed with HYP mice to determine whether the absence of Cyp24a1 activity in either osteoblast/osteocytes or chondrocytes in HYP mice is capable of promoting mineralisation and overcoming bone under-mineralisation.Model: Our team has previously created the floxed Cyp24a1 (Cyp24a1flox/+) and OcyCYP24KO (OcyCyp24a1-/-) mouse models. Male HYP mice are far less virile that the females so generation of a HYP mouse in which Cyp24a1 has been specifically deleted in osteocytes (HYP/OcyCyp24a1-/-) requires a particular breeding strategy. Heterozygous female HYP (XXHyp) will be crossed with Cyp24a1flox/flox males to obtain HYP/Cyp24a1flox/+ double heterozygous females. Then HYP/Cyp24a1flox/+ females will be crossed with Cyp24a1flox/flox males to generate HYP/Cyp24a1flox/flox females. Finally, HYP/Cyp24a1flox/flox females will be crossed with OcyCyp24a1-/+ males to obtain the osteoblast/osteocyte-specific deletion of Cyp24a1 in HYP mice. Studies will include the following four genotypes: Cyp24a1flox/+ (wild-type equivalent) control, OcyCyp24a1-/-, HYP (XHypY), and compound HYP/OcyCyp24a1-/- male littermates as well as Cyp24a1flox/- and HYP/Cyp24a1flox/- male mice.Male HYP (XHypY) mice will be supplemented with vitamin D from 3 weeks of age until 12 weeks of age (as in Aim 1, Model 1), and infused with 25(OH)D (as in Aim 1, Model 2). At time of death, analyses will include Biochemical analyses, ex-vivo micro-CT analyses, in vivo micro-CT analyses, tissue histology and histomorphometric analyses and messenger RNA analyses as described in Aim 1.Outcomes: Central to the hypothesis of this project is whether the absence of CYP24A1 activity within osteoblasts/osteocytes as well as chondrocytes enhances healing of bone in HYP mice, despite their elevated levels of FGF23. Examining HYP/conditional CYP24A1KO mice in the context of 25(OH)D supplementation, phosphorus supplementation and 1,25(OH)2D administration will reveal the importance of raised 1,25D within the key bone cell types in this context of healing HYP bone. As well, using definitive in vitro cell models will determine whether the absence of osteoblastic/osteocytic or chondrocytic Cyp24a1 activity alters differentiation and/or apoptosis of HYP cells independently of confounding factors that could occur in the in vivo studies. At the same time these in vitro studies will seek to establish whether key players in inhibiting mineralisation (such as ASARM peptides and sclerostin) are modulated by vitamin D, phosphate and/or CYP24A1 deletion. These studies will provide important insights into targeting CYP24A1 activity in bone in the condition of XLH..REFERENCES: ADDIN EN.REFLIST Anderson, PH, O’Loughlin, PD, May, BK & Morris, HA 2004, ‘Determinants of circulating 1,25-dihydroxyvitamin D3 levels: the role of renal synthesis and catabolism of vitamin D’, J Steroid Biochem Mol Biol, vol. 89-90, no. 1-5, May, pp. 111-113.Anderson, PH, O’Loughlin, PD, May, BK & Morris, HA 2005, ‘Modulation of CYP27B1 and CYP24 mRNA expression in bone is independent of circulating 1,25(OH)2D3 levels’, Bone, vol. 36, no. 4, Apr, pp. 654-662.Anderson, PH, Sawyer, RK, Moore, AJ, May, BK, O’Loughlin, PD & Morris, HA 2008, ‘Vitamin D depletion induces RANKL-mediated osteoclastogenesis and bone loss in a rodent model’, Journal of Bone and Mineral Research, vol. 23, no. 11, Nov, pp. 1789-1797.Anderson, PH 2017, ‘Vitamin D Activity and Metabolism in Bone’, Curr Osteoporos Rep, vol. 15, no. 5, Oct, pp. 443-449.Azam, N, Zhang, MY, Wang, X, Tenenhouse, HS & Portale, AA 2003, ‘Disordered regulation of renal 25-hydroxyvitamin D-1alpha-hydroxylase gene expression by phosphorus in X-linked hypophosphatemic (hyp) mice’, Endocrinology, vol. 144, no. 8, Aug, pp. 3463-3468.Bai, X, Miao, D, Xiao, S, Qiu, D, St-Arnaud, R, Petkovich, M, Gupta, A, Goltzman, D & Karaplis, AC 2016, ‘CYP24 inhibition as a therapeutic target in FGF23-mediated renal phosphate wasting disorders’, J Clin Invest, vol. 126, no. 2, Feb, pp. 667-680.Bowe, AE, Finnegan, R, Jan de Beur, SM, Cho, J, Levine, MA, Kumar, R & Schiavi, SC 2001, ‘FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate’, Biochem Biophys Res Commun, vol. 284, no. 4, Jun 22, pp. 977-981.Carpenter, TO, Imel, EA, Holm, IA, Jan de Beur, SM & Insogna, KL 2011, ‘A clinician’s guide to X-linked hypophosphatemia’, J Bone Miner Res, vol. 26, no. 7, Jul, pp. 1381-1388.Che, H, Roux, C, Etcheto, A, Rothenbuhler, A, Kamenicky, P, Linglart, A & Briot, K 2016, ‘Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms’, Eur J Endocrinol, vol. 174, no. 3, Mar, pp. 325-333.Chiang, C, Chiu, M, Moore, AJ, Anderson, PH, Ghasem-Zadeh, A, McManus, JF, Ma, C, Seeman, E, Clemens, TL, Morris, HA, Zajac, JD & Davey, RA 2009, ‘Mineralization and bone resorption are regulated by the androgen receptor in male mice’, J Bone Miner Res, vol. 24, no. 4, Apr, pp. 621-631.De Menezes Filho, H, De Castro, LCG & Damiani, D 2006, ‘Hypophosphatemic Rickets and Osteomalacia’, vol. 50, no. 4.Dempster, DW, Compston, JE, Drezner, MK, Glorieux, FH, Kanis, JA, Malluche, H, Meunier, PJ, Ott, SM, Recker, RR & Parfitt, AM 2013, ‘Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee’, J Bone Miner Res, vol. 28, no. 1, Jan, pp. 2-17.Eicher, EM, Southard, JL, Scriver, CR & Glorieux, FH 1976, ‘Hypophosphatemia: Mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets’, Proc Natl Acad Sci USA, vol. 73, no. 12, pp. 4667-4671.Erben, RG 2017, ‘Pleiotropic Actions of FGF23’, Toxicol Pathol, vol. 45, no. 7, Oct, pp. 904-910.Foster, BL, Nagatomo, KJ, Nociti, FH, Jr., Fong, H, Dunn, D, Tran, AB, Wang, W, Narisawa, S, Millan, JL & Somerman, MJ 2012, ‘Central role of pyrophosphate in acellular cementum formation’, PLoS One, vol. 7, no. 6, p. e38393.Fuente, R, Gil-Pena, H, Claramunt-Taberner, D, Hernandez, O, Fernandez-Iglesias, A, Alonso-Duran, L, Rodriguez-Rubio, E & Santos, F 2017, ‘X-linked hypophosphatemia and growth’, Rev Endocr Metab Disord, vol. 18, no. 1, Mar, pp. 107-115.Fuente, R, Gil-Pena, H, Claramunt-Taberner, D, Hernandez-Frias, O, Fernandez-Iglesias, A, Hermida-Prado, F, Anes-Gonzalez, G, Rubio-Aliaga, I, Lopez, JM & Santos, F 2018, ‘Marked alterations in the structure, dynamics and maturation of growth plate likely explain growth retardation and bone deformities of young Hyp mice’, Bone, vol. 116, Aug 8, pp. 187-195.Harmey, D, Hessle, L, Narisawa, S, Johnson, KA, Terkeltaub, R & Millán, JL 2004, ‘Concerted Regulation of Inorganic Pyrophosphate and Osteopontin by Akp2, Enpp1, and Ank’, The American Journal of Pathology, vol. 164, no. 4, pp. 1199-1209.Henry, HL 2011, ‘Regulation of vitamin D metabolism’, Best Pract Res Clin Endocrinol Metab, vol. 25, no. 4, Aug, pp. 531-541.Ito, N, Findlay, DM, Anderson, PH, Bonewald, LF & Atkins, GJ 2013, ‘Extracellular phosphate modulates the effect of 1alpha,25-dihydroxy vitamin D3 (1,25D) on osteocyte like cells’, J Steroid Biochem Mol Biol, vol. 136, Jul, pp. 183-186.Kido, S, Kaneko, I, Tatsumi, S, Segawa, H & Miyamoto, K 2013, ‘Vitamin D and type II sodium-dependent phosphate cotransporters’, Contrib Nephrol, vol. 180, pp. 86-97.Ko, FC, Martins, JS, Reddy, P, Bragdon, B, Hussein, AI, Gerstenfeld, LC & Demay, MB 2016, ‘Acute Phosphate Restriction Impairs Bone Formation and Increases Marrow Adipose Tissue in Growing Mice’, J Bone Miner Res, vol. 31, no. 12, Dec, pp. 2204-2214.Lee, JY & Imel, EA 2013, ‘The Changing Face of Hypophosphatemic Disorders in the FGF-23 Era’, Paediatr Endocrinol Rev., vol. 10, pp. 367-379.Leifheit-Nestler, M, Kucka, J, Yoshizawa, E, Behets, G, D’Haese, P, Bergen, C, Meier, M, Fischer, DC & Haffner, D 2017, ‘Comparison of calcimimetic R568 and calcitriol in mineral homeostasis in the Hyp mouse, a murine homolog of X-linked hypophosphatemia’, Bone, vol. 103, Oct, pp. 224-232.Linglart, A, Biosse-Duplan, M, Briot, K, Chaussain, C, Esterle, L, Guillaume-Czitrom, S, Kamenicky, P, Nevoux, J, Prie, D, Rothenbuhler, A, Wicart, P & Harvengt, P 2014, ‘Therapeutic management of hypophosphatemic rickets from infancy to adulthood’, Endocr Connect, vol. 3, no. 1, pp. R13-30.Liu, ES, Martins, JS, Raimann, A, Chae, BT, Brooks, DJ, Jorgetti, V, Bouxsein, ML & Demay, MB 2016, ‘1,25-Dihydroxyvitamin D Alone Improves Skeletal Growth, Microarchitecture, and Strength in a Murine Model of XLH, Despite Enhanced FGF23 Expression’, J Bone Miner Res, vol. 31, no. 5, May, pp. 929-939.Makitie, O, Doria, A, Kooh, SW, Cole, WG, Daneman, A & Sochett, E 2003, ‘Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets’, J Clin Endocrinol Metab, vol. 88, no. 8, Aug, pp. 3591-3597.Marie, PJ, Travers, R & Glorieux, FH 1981, ‘Healing of rickets with phosphate supplementation in the hypophosphatemic male mouse’, Journal of Clinical Investigation, vol. 67, no. 3, pp. 911-914.Marie, PJ, Travers, R & Glorieux, FH 1982, ‘Bone Response to Phosphate and Vitamin D Metabolites in the Hypophosphatemic mouse model’, Calcified Tissue International, vol. 34, no. 1, pp. 158-164.Marie, PJ, Travers, R & Glorieux, FH 1982, ‘Healing of bone lesions with 1, 25-dihydroxyvitamin D3 in the young X-linked hypophosphatemic male mouse’, Endocrinology, vol. 111, no. 3, pp. 904-911.Masuyama, R, Stockmans, I, Torrekens, S, Van Looveren, R, Maes, C, Carmeliet, P, Bouillon, R & Carmeliet, G 2006, ‘Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts’, J Clin Invest, vol. 116, no. 12, Dec, pp. 3150-3159.Meyer, RA, Meyer, MH & Morgan, PL 1996, ‘Effects of Altered Diet on Serum levels of 1,25-Dihydroxyvitamin D and Parathyroid Hormone in X-Linked Hypophosphatemic (HYP and Gy) Mice’, Bone, vol. 18, no. 1, pp. 23-28.Millan, JL 2013, ‘The role of phosphatases in the initiation of skeletal mineralization’, Calcif Tissue Int, vol. 93, no. 4, Oct, pp. 299-306.Miyagawa, K, Yamazaki, M, Kawai, M, Nishino, J, Koshimizu, T, Ohata, Y, Tachikawa, K, Mikuni-Takagaki, Y, Kogo, M, Ozono, K & Michigami, T 2014, ‘Dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic Hyp mice’, PLoS One, vol. 9, no. 4, p. e93840.Murali, SK, Andrukhova, O, Clinkenbeard, EL, White, KE & Erben, RG 2016, ‘Excessive Osteocytic Fgf23 Secretion Contributes to Pyrophosphate Accumulation and Mineralization Defect in Hyp Mice’, PLoS Biol, vol. 14, no. 4, Apr, p. e1002427.Pharmaceutical, U 2018, Burosumab for XLH, <https://www.ultragenyx.com/pipeline/krn23-xlh/>.Portale, AA, Perwad, F & Miller, WL 2012, ‘Rickets Due to Hereditary Abnormalities of Vitamin D Synthesis or Action’, Pediatric Bone, pp. 679-698.Razzaque, MS & Lanske, B 2007, ‘The emerging role of the fibroblast growth factor-23-klotho axis in renal regulation of phosphate homeostasis’, J Endocrinol, vol. 194, no. 1, Jul, pp. 1-10.Roizen, JD, Li, D, O’Lear, L, Javaid, MK, Shaw, NJ, Ebeling, PR, Nguyen, HH, Rodda, CP, Thummel, KE, Thacher, TD, Hakonarson, H & Levine, MA 2018, ‘CYP3A4 mutation causes vitamin D-dependent rickets type 3’, J Clin Invest, vol. 128, no. 5, May 1, pp. 1913-1918.Rowling, MJ, Gliniak, C, Welsh, J & Fleet, JC 2007, ‘High dietary vitamin D prevents hypocalcemia and osteomalacia in CYP27B1 knockout mice’, The Journal of nutrition, vol. 137, no. 12, pp. 2608-2615.Rowling, MJ, Gliniak, C, Welsh, J & Fleet, JC 2007, ‘High Dietary Vitamin D Prevents Hypocalcemia and Osteomalacia in CYP27B1 Knockout Mice’, J Nutr, vol. 137, no. 12, Dec, pp. 2608-2615.Sabbagh, Y, Carpenter, TO & Demay, MB 2005, ‘Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes’, Proc Natl Acad Sci U S A, vol. 102, no. 27, Jul 5, pp. 9637-9642.Saito, T & Fukumoto, S 2009, ‘Fibroblast Growth Factor 23 (FGF23) and Disorders of Phosphate Metabolism’, Int J Pediatr Endocrinol, vol. 2009, p. 496514.Tenenhouse, HS & Jones, G 1990, ‘Abnormal Regulation of Renal Vitamin D Catabolism by Dietary Phosphate in Murine X-linked Hypophosphatemic Rickets’, J Clin. Invest., vol. 85, pp. 1450-1455.Vieth, R 1999, ‘Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety’, American Journal of Clinical Nutrition, vol. 69, no. 5, pp. 842-856.Williamson, L, Hayes, A, Hanson, ED, Pivonka, P, Sims, NA & Gooi, JH 2017, ‘High dose dietary vitamin D3 increases bone mass and strength in mice’, Bone Rep, vol. 6, Jun, pp. 44-50.GANTT CHART AND PLANNED PUBLICATIONS:2018 2019 2020Tasks/Milestones M A M J J A S O N D J F M A M J J A S O N D J F MEthics approval process                                                  RESA ‘Continuing to Completing’ series                                                  Literature review                                                  Animal research Aim 1                                                  Data analysis Aim 1                                                  Write up Aim 1                                                  Animal research Aim 2                                                  Data analysis Aim 2                                                  Write up Aim 2                                                  Submission                                                  

x

Hi!
I'm Piter!

Would you like to get a custom essay? How about receiving a customized one?

Check it out