Abstract
Rickets and osteomalacia are diseases characterized by impaired mineralization of bone matrix. Recent investigations have revealed that the causes of rickets and osteomalacia are quite variable. Although these diseases can severely impair the quality of life of affected patients, rickets and osteomalacia can be completely cured or at least respond to treatment when properly diagnosed and treated according to the specific causes. On the other hand, there are no standard criteria to diagnose rickets or osteomalacia nationally and internationally. Therefore, we summarize the definition and pathogenesis of rickets and osteomalacia, and propose diagnostic criteria and a flowchart for the differential diagnosis of various causes of these diseases. We hope that these criteria and the flowchart are clinically useful for the proper diagnosis and management of these diseases.
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References
Reginato AJ, Coquia JA (2003) Musculoskeletal manifestations of osteomalacia and rickets. Best Pract Res Clin Rheumatol 17:1063–1080
Whyte MP, Thakker RV (2009) Rickets and osteomalacia. Medicine 37:483–488
Prentice A (2013) Nutritional rickets around the world. J Steroid Biochem Mol Biol 136:201–206
Fukumoto S, Martin TJ (2009) Bone as an endocrine organ. Trends Endocrinol Metab 20:230–236
Endo I, Fukumoto S, Ozono K, Namba N, Tanaka H, Inoue D, Minagawa M, Sugimoto T, Yamauchi M, Michigami T, Matsumoto T (2008) Clinical usefulness of measurement of fibroblast growth factor 23 (FGF23) in hypophosphatemic patients: proposal of diagnostic criteria using FGF23 measurement. Bone 42:1235–1239
Kitanaka S, Takeyama K, Murayama A, Sato T, Okumura K, Nogami M, Hasegawa Y, Niimi H, Yanagisawa J, Tanaka T, Kato S (1998) Inactivating mutations in the 25-hydroxyvitamin D3 1α-hydroxylase gene in patients with pseudovitamin D-deficiency rickets. N Engl J Med 338:653–661
Hughes MR, Malloy PJ, Kieback DG, Kesterson RA, Pike JW, Feldman D, O’Malley BW (1988) Point mutations in the human vitamin D receptor gene associated with hypocalcemic rickets. Science 242:1702–1705
Tovey FI, Hall ML, Ell PJ, Hobsley M (1992) A review of postgastrectomy bone disease. J Gastroenterol Hepatol 7:639–645
Collier J (2007) Bone disorders in chronic liver disease. Hepatology 46:1271–1278
Blaine J, Chonchol M, Levi M (2015) Renal control of calcium, phosphate, and magnesium homeostasis. Clin J Am Soc Nephrol. doi:10.2215/CJN.09750913
Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H, Frappier D, Burkett K, Carpenter TO, Anderson D, Garabedian M, Sermet I, Fujiwara TM, Morgan K, Tenenhouse HS, Juppner H (2006) SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. Am J Hum Genet 78:179–192
Lorenz-Depiereux B, Benet-Pages A, Eckstein G, Tenenbaum-Rakover Y, Wagenstaller J, Tiosano D, Gershoni-Baruch R, Albers N, Lichtner P, Schnabel D, Hochberg Z, Strom TM (2006) Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. Am J Hum Genet 78:193–201
Lloyd SE, Pearce SH, Fisher SE, Steinmeyer K, Schwappach B, Scheinman SJ, Harding B, Bolino A, Devoto M, Goodyer P, Rigden SP, Wrong O, Jentsch TJ, Craig IW, Thakker RV (1996) A common molecular basis for three inherited kidney stone diseases. Nature 379:445–449
Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T (2004) FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19:429–435
Jonsson KB, Zahradnik R, Larsson T, White KE, Sugimoto T, Imanishi Y, Yamamoto T, Hampson G, Koshiyama H, Ljunggren O, Oba K, Yang IM, Miyauchi A, Econs MJ, Lavigne J, Juppner H (2003) Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med 348:1656–1663
Yamazaki Y, Okazaki R, Shibata M, Hasegawa Y, Satoh K, Tajima T, Takeuchi Y, Fujita T, Nakahara K, Yamashita T, Fukumoto S (2002) Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia. J Clin Endocrinol Metab 87:4957–4960
Fukumoto S (2014) Anti-fibroblast growth factor 23 antibody therapy. Curr Opin Nephrol Hypertens 23:346–351
Weiss MJ, Cole DE, Ray K, Whyte MP, Lafferty MA, Mulivor RA, Harris H (1988) A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia. Proc Natl Acad Sci U S A 85:7666–7669
Bendik I, Friedel A, Roos FF, Weber P, Eggersdorfer M (2014) Vitamin D: a critical and essential micronutrient for human health. Front Physiol 5:248
Kubota T, Kitaoka T, Miura K, Fujiwara M, Ohata Y, Miyoshi Y, Yamamoto K, Takeyari S, Yamamoto T, Namba N, Ozono K (2014) Serum fibroblast growth factor 23 is a useful marker to distinguish vitamin D-deficient rickets from hypophosphatemic rickets. Horm Res Paediatr 81:251–257
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This study was supported in part by a grant from the Ministry of Health, Labour and Welfare of Japan.
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Fukumoto, S., Ozono, K., Michigami, T. et al. Pathogenesis and diagnostic criteria for rickets and osteomalacia—proposal by an expert panel supported by the Ministry of Health, Labour and Welfare, Japan, the Japanese Society for Bone and Mineral Research, and the Japan Endocrine Society. J Bone Miner Metab 33, 467–473 (2015). https://doi.org/10.1007/s00774-015-0698-7
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DOI: https://doi.org/10.1007/s00774-015-0698-7