DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20204270

Management of X-linked hypophosphatemic rickets: a review

Mohammed Azar

Abstract


There are two types of management in X-linked hypophosphatemic rickets (XLH), out of which the main stay of treatment is conventional treatment which includes combination of oral phosphate supplements and active vitamin D (calcitriol or alfacalcidol) after the diagnosis is established. Although, conventional treatment with phosphate supplementation and active vitamin D might improve the rickets and control the renal phosphate excretion but it has significant risk of high calcium excretion in the urine and thereby increases the risk of nephrocalcinosis. The other emerging treatment is burosumab therapy which is human monoclonal IgG1 antibody against fibroblast growth factor 23 (FGF 23) for the treatment of XLH in children ≥1 year of age and in adolescents and is found to be effective in improving rickets without major adverse events. In this review, modalities for XLH treatment over the past and the near future will be discussed along with clinical manifestations and investigations.

 


Keywords


FGF 23, PTH, XLH

Full Text:

PDF

References


Imel EA, Glorieux FH, Whyte MP, Munns CF, Ward LM, Nilsson O, et al. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet. 2019;393(10189):2416-27.

Haffner D, Emma F, Eastwood DM, Duplan MB, Bacchetta J, Schnabel D, et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. Nat Rev Nephrol. 2019;15,435-55

Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL. A clinician's guide to X‐linked hypophosphatemia. J Bone Mineral Res. 2015;30(2):394.

Pettifor JM. What's new in hypophosphataemic rickets? Eur J Pediatr. 2008;167:493-9.

Beck-Nielsen SS, Brock-Jacobsen B, Gram J, Brixen K, Jensen TK. Incidence and prevalence of nutritional and hereditary rickets in southern Denmark Eur J Endocrinol. 2009;160(3):491-7.

Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006;444:770-4.

Rasmussen H, Pechet M, Anast C, Mazur A, Gertner J, Broadus AE. Long-term treatment of familial hypophosphatemic rickets with oral phosphate and 1 alpha-hydroxyvitamin D3. J Pediatr. 1981;99:16-25.

Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res. 2004;19:429-35.

The ADHR Consortium. Autosomal dominant hypophosphatemic rickets is associated with mutations in FGF-23. Nat Genet. 2000;26:345-8.

Farrow EG, White KE. Recent advances in renal phosphate handling. Nat Rev Nephrol. 2010;6:207-17.

Sullivan W, Carpenter TO, Glorieux F, Travers R, Insogna K. A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy on symptomatic adults with X-linked hypophosphatemic rickets. J Clin Endocrinol Metab. 1992 75:879-85.

Tsuru N, Chan JC, Chinchilli VM. Renal hypophosphatemic rickets. Growth and mineral metabolism after treatment with calcitriol (1,25-dihydroxyvitamin D3) and phosphate supplementation. Am J Dis Child. 1987;141:108-10.

Petersen DJ, Boniface AM, Schranck FW, Rupich RC, Whyte MP. X-linked hypophosphatemic rickets: a study (with literature review) of linear growth response to calcitriol and phosphate therapy. J Bone Miner Res. 1992;7:583-90.

Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Investig. 2006;116:2062-72.

Aono Y, Yamazaki Y, Yasutake J, Kawata T, Hasegawa H, Urakawa I, et al. Therapeutic effects of anti-FGF23 antibodies in hypophosphatemic rickets/osteomalacia. J Bone Miner Res. 2009;24:1879-88.

Verge CF, Lam A, Simpson JM, Cowell CT, Howard NJ, Silink M. Effects of therapy in X-linked hypophosphatemic rickets. N Engl J Med. 1991;325:1843-8.

Ward LM, Gaboury IL, Adhani MZ, Lotkin S. Vitamin D-deficiency rickets among children in Canada. Canadian Med Assoc J. 2007;177:161-6.

Thacher TD, Fischer PR, Strand MA, Pettifor JM. Nutritional rickets around the world: causes and future directions. Ann Trop Paediatr. 2006;26:1-16.

Harrell RM, Lyles KW, Harrelson JM, Friedman NE, Drezner MK. Healing of bone disease in X-linked hypophosphatemic rickets/osteomalacia. Induction and maintenance with phosphorus and calcitriol. J Clin Invest. 1985;75:1858-68.

Mughal Z. Rickets in childhood. Semin Musculoskel Radiol. 2002;6:183-90.

Santos F, Fuente R, Mejia N, Mantecon L, Gil-Peña H, Ordoñez FA. Hypophosphatemia and growth. Pediatr Nephrol. 2013;28(4):595-603.

Whyte MP, Carpenter TO, Gottesman GS, Mao M, Skrinar A, San Martin J, et al. Efficacy and safety of burosumab in children aged 1–4 years with X-linked hypophosphataemia: a multicentre, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019;7(3):189-99.

Lamb YN, Burosumab: first global approval. Drugs. 2018;78:707-14.

Linglart A, Biosse-Duplan M, Briot K, Chaussain C, Esterle L, Guillaume-Czitrom S, et al. Therapeutic management of hypophosphatemic rickets from infancy to adulthood. Endocr Connect. 2014;3(1):R13-30.

West CD, Blanton JC, Silverman FN, Holland NH. Use of phosphate salts as an adjunct to vitamin D in the treatment of hypophosphatemic vitamin D refractory rickets. J Pediatr. 1964;64:469-77.