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Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets/osteomalacia.
J Bone Miner Res. 2009 Nov; 24(11):1879-88.JB

Abstract

X-linked hypophosphatemia (XLH), characterized by renal phosphate wasting, is the most common cause of vitamin D-resistant rickets. It has been postulated that some phosphaturic factor plays a causative role in XLH and its murine homolog, the Hyp mouse. Fibroblast growth factor 23 (FGF23) is a physiological phosphaturic factor; its circulatory level is known to be high in most patients with XLH and Hyp mice, suggesting its pathophysiological role in this disease. To test this hypothesis, we treated Hyp mice with anti-FGF23 antibodies to inhibit endogenous FGF23 action. A single injection of the antibodies corrected the hypophosphatemia and inappropriately normal serum 1,25-dihydroxyvitamin D. These effects were accompanied by increased expressions of type IIa sodium-phosphate cotransporter and 25-hydroxyvitamin-D-1alpha-hydroxylase and a suppressed expression of 24-hydroxylase in the kidney. Repeated injections during the growth period ameliorated the rachitic bone phenotypes typically observed in Hyp mice, such as impaired longitudinal elongation, defective mineralization, and abnormal cartilage development. Thus, these results indicate that excess actions of FGF23 underlie hypophosphatemic rickets in Hyp mice and suggest a novel therapeutic potential of the FGF23 antibodies for XLH.

Authors+Show Affiliations

Pharmacological Research Laboratories, Kyowa Hakko Kirin, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19419316

Citation

Aono, Yukiko, et al. "Therapeutic Effects of anti-FGF23 Antibodies in Hypophosphatemic Rickets/osteomalacia." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 24, no. 11, 2009, pp. 1879-88.
Aono Y, Yamazaki Y, Yasutake J, et al. Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets/osteomalacia. J Bone Miner Res. 2009;24(11):1879-88.
Aono, Y., Yamazaki, Y., Yasutake, J., Kawata, T., Hasegawa, H., Urakawa, I., Fujita, T., Wada, M., Yamashita, T., Fukumoto, S., & Shimada, T. (2009). Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets/osteomalacia. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 24(11), 1879-88. https://doi.org/10.1359/jbmr.090509
Aono Y, et al. Therapeutic Effects of anti-FGF23 Antibodies in Hypophosphatemic Rickets/osteomalacia. J Bone Miner Res. 2009;24(11):1879-88. PubMed PMID: 19419316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets/osteomalacia. AU - Aono,Yukiko, AU - Yamazaki,Yuji, AU - Yasutake,Junichi, AU - Kawata,Takehisa, AU - Hasegawa,Hisashi, AU - Urakawa,Itaru, AU - Fujita,Toshiro, AU - Wada,Michihito, AU - Yamashita,Takeyoshi, AU - Fukumoto,Seiji, AU - Shimada,Takashi, PY - 2009/5/8/entrez PY - 2009/5/8/pubmed PY - 2010/1/7/medline SP - 1879 EP - 88 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 24 IS - 11 N2 - X-linked hypophosphatemia (XLH), characterized by renal phosphate wasting, is the most common cause of vitamin D-resistant rickets. It has been postulated that some phosphaturic factor plays a causative role in XLH and its murine homolog, the Hyp mouse. Fibroblast growth factor 23 (FGF23) is a physiological phosphaturic factor; its circulatory level is known to be high in most patients with XLH and Hyp mice, suggesting its pathophysiological role in this disease. To test this hypothesis, we treated Hyp mice with anti-FGF23 antibodies to inhibit endogenous FGF23 action. A single injection of the antibodies corrected the hypophosphatemia and inappropriately normal serum 1,25-dihydroxyvitamin D. These effects were accompanied by increased expressions of type IIa sodium-phosphate cotransporter and 25-hydroxyvitamin-D-1alpha-hydroxylase and a suppressed expression of 24-hydroxylase in the kidney. Repeated injections during the growth period ameliorated the rachitic bone phenotypes typically observed in Hyp mice, such as impaired longitudinal elongation, defective mineralization, and abnormal cartilage development. Thus, these results indicate that excess actions of FGF23 underlie hypophosphatemic rickets in Hyp mice and suggest a novel therapeutic potential of the FGF23 antibodies for XLH. SN - 1523-4681 UR - https://www.unboundmedicine.com/medline/citation/19419316/Therapeutic_effects_of_anti_FGF23_antibodies_in_hypophosphatemic_rickets/osteomalacia_ L2 - https://doi.org/10.1359/jbmr.090509 DB - PRIME DP - Unbound Medicine ER -