Epidemiology and etiology of osteomalacia
- Marc K Drezner, MD
Marc K Drezner, MD
- Section Editor — Bone Disease
- Professor of Medicine
- University of Wisconsin Medical School
Osteomalacia is a disorder of decreased mineralization of newly formed osteoid at sites of bone turnover, whereas rickets is a disorder of defective mineralization of cartilage in the epiphyseal growth plates of children. Osteomalacia and rickets can occur together in children (open growth plates), but only osteomalacia occurs in adults (fused growth plates). Several different disorders cause osteomalacia via mechanisms that result in hypocalcemia, hypophosphatemia, or direct inhibition of the mineralization process.
This topic will review the epidemiology, pathogenesis, and different causes of osteomalacia. The clinical manifestations, diagnosis, and treatment of osteomalacia and the etiology and treatment of rickets are discussed separately. (See "Clinical manifestations, diagnosis, and treatment of osteomalacia" and "Etiology and treatment of calcipenic rickets in children".)
There is a growing prevalence of vitamin D deficiency in many countries, which when severe (25-hydroxyvitamin D <10 ng/mL [25 nmol/L]) and prolonged results in hypocalcemia, secondary hyperparathyroidism, secondary hypophosphatemia, and osteomalacia . Nutritional vitamin D deficiency is therefore an increasingly common cause of osteomalacia in adults. Populations at risk include the homebound elderly who have little sun exposure and insufficient dietary calcium and vitamin D, patients with malabsorption related to gastrointestinal bypass surgery or celiac disease, and immigrants to cold climates from warm climates, especially women who wear traditional veils or dresses that prevent sun exposure [2,3]. Hereditary forms of vitamin D deficiency and resistance, which are identified in childhood, are associated with osteomalacia in adults, but these disorders are less common.
Osteomalacia can also occur in patients with primary hypophosphatemia due to one of the hereditary hypophosphatemic rickets syndromes (eg, X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets) or with tumor induced osteomalacia, an acquired paraneoplastic syndrome of renal phosphate wasting. The hereditary hypophosphatemic rickets syndromes present in childhood but persist in adulthood. These disorders are also uncommon. (See "Hereditary hypophosphatemic rickets and tumor-induced osteomalacia".)
Bone remodeling occurs continually on trabecular and Haversian bone surfaces. At any given time, about 7 percent of the bone surface is in the process of forming new bone. The osteoclast begins the cycle by excavating a cavity on the surface followed by refilling of the cavity by activated osteoblasts. New bone formation takes place in two steps:
- Ashwell M, Stone EM, Stolte H, et al. UK Food Standards Agency Workshop Report: an investigation of the relative contributions of diet and sunlight to vitamin D status. Br J Nutr 2010; 104:603.
- Al-Shoha A, Qiu S, Palnitkar S, Rao DS. Osteomalacia with bone marrow fibrosis due to severe vitamin D deficiency after a gastrointestinal bypass operation for severe obesity. Endocr Pract 2009; 15:528.
- Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc 2010; 85:752.
- Bone biopsy and histomorphometry in clinical practice. In: Primer on Metabolic Bone Diseases and Disorders of Mineral Metabolism, Lippincott-Raven, Philadelphia 1993.
- Russell JA. Osteomalacic myopathy. Muscle Nerve 1994; 17:578.
- Reginster JY. The high prevalence of inadequate serum vitamin D levels and implications for bone health. Curr Med Res Opin 2005; 21:579.
- Sommer S, Berndt T, Craig T, Kumar R. The phosphatonins and the regulation of phosphate transport and vitamin D metabolism. J Steroid Biochem Mol Biol 2007; 103:497.
- Clarke BL, Wynne AG, Wilson DM, Fitzpatrick LA. Osteomalacia associated with adult Fanconi's syndrome: clinical and diagnostic features. Clin Endocrinol (Oxf) 1995; 43:479.
- Girgis CM, Wong T, Ngu MC, et al. Hypophosphataemic osteomalacia in patients on adefovir dipivoxil. J Clin Gastroenterol 2011; 45:468.
- Kim du H, Sung DH, Min YK. Hypophosphatemic osteomalacia induced by low-dose adefovir therapy: focus on manifestations in the skeletal system and literature review. J Bone Miner Metab 2013; 31:240.
- Shimizu Y, Hiraoka A, Yamago H, et al. Hypophosphatemia in patients with hepatitis B virus infection undergoing long-term adefovir dipivoxil therapy. Hepatol Res 2014; 44:1081.
- Koenig KF, Kalbermatter S, Menter T, et al. Recurrent bone fractures due to tenofovir-induced renal phosphate wasting. Scand J Infect Dis 2014; 46:221.
- Brenner RJ, Spring DB, Sebastian A, et al. Incidence of radiographically evident bone disease, nephrocalcinosis, and nephrolithiasis in various types of renal tubular acidosis. N Engl J Med 1982; 307:217.
- Fulop M, Mackay M. Renal tubular acidosis, Sjögren syndrome, and bone disease. Arch Intern Med 2004; 164:905.
- Disthabanchong S, Domrongkitchaiporn S, Sirikulchayanonta V, et al. Alteration of noncollagenous bone matrix proteins in distal renal tubular acidosis. Bone 2004; 35:604.
- Cherif E, Ben Hassine L, Kaoueche Z, Khalfallah N. Osteomalacia as inaugural manifestation of Sjögren syndrome. BMJ Case Rep 2013; 2013.
- Adamson BB, Gallacher SJ, Byars J, et al. Mineralisation defects with pamidronate therapy for Paget's disease. Lancet 1993; 342:1459.
- Ott SM, Maloney NA, Klein GL, et al. Aluminum is associated with low bone formation in patients receiving chronic parenteral nutrition. Ann Intern Med 1983; 98:910.
- Vargas JH, Klein GL, Ament ME, et al. Metabolic bone disease of total parenteral nutrition: course after changing from casein to amino acids in parenteral solutions with reduced aluminum content. Am J Clin Nutr 1988; 48:1070.
- Wang Y, Yin Y, Gilula LA, Wilson AJ. Endemic fluorosis of the skeleton: radiographic features in 127 patients. AJR Am J Roentgenol 1994; 162:93.
- Kurland ES, Schulman RC, Zerwekh JE, et al. Recovery from skeletal fluorosis (an enigmatic, American case). J Bone Miner Res 2007; 22:163.
- Mornet, E, Nunes, ME. Hypophosphatasia. In: GeneReviews, Pagon RA, Bird TC, Dolan CR, Stephens K (Eds), University of Washington, Seattle 2010.
- Mornet E. Hypophosphatasia. Best Pract Res Clin Rheumatol 2008; 22:113.
- Whyte MP. Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann N Y Acad Sci 2010; 1192:190.
- Whyte, MP. Enzyme defects and the skeleton. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Seventh Edition, Rosen CJ (Ed), The American Society of Bone and Mineral Research, Washington, DC 2008. p.454.
- Maman E, Borderie D, Roux C, Briot K. Absence of recognition of low alkaline phosphatase level in a tertiary care hospital. Osteoporos Int 2016; 27:1251.
- http://www.sesep.uvsq.fr/03_hypo_mutations.php (Accessed on November 04, 2010).
- Moore CA, Curry CJ, Henthorn PS, et al. Mild autosomal dominant hypophosphatasia: in utero presentation in two families. Am J Med Genet 1999; 86:410.
- Whyte MP, Fallon MD, Murphy WA, Teitelbaum SL. Axial osteomalacia. Clinical, laboratory and genetic investigation of an affected mother and son. Am J Med 1981; 71:1041.
- Whyte, MP. Sclerosing Bone Disorders. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Seventh Edition, Rosen CJ (Ed), American Society of Bone and Mineral Research, Washington, DC 2008. p.412.
- Lang R, Vignery AM, Jensen PS. Fibrogenesis imperfecta ossium with early onset: observations after 20 years of illness. Bone 1986; 7:237.