Highlights & Basics
- Osteomalacia is most commonly caused by vitamin D deficiency.
- Patients frequently complain of diffuse bony pain with a history of limited sunlight exposure.
- Proximal muscle weakness, spinal tenderness to percussion, pseudofractures, and skeletal deformities are found commonly.
- Diagnosis is made via laboratory results with a low 25-hydroxyvitamin D level in the setting of low or normal calcium and an elevated intact parathyroid hormone (PTH) level.
- Once the underlying cause is addressed, a successful treatment regimen is possible: increased sunlight exposure, oral vitamin D, and calcium replacement.
Quick Reference
History & Exam
Key Factors
Other Factors
Diagnostics Tests
Treatment Options
Definition
Epidemiology
Etiology
Pathophysiology
Images
Radiograph of the femoral shaft in a patient with osteomalacia demonstrating a "pseudofracture" (also known as Looser zone) on the medial aspect of the mid-femoral shaft
Photomicrography of a normal transilial bone biopsy demonstrating mineralized osteoid (shown in purple)
Photomicrography of a transilial bone biopsy in a patient with osteomalacia demonstrating unmineralized osteoid (shown in purple). The width of the osteoid seams is substantially increased
Citations
Holick MF, Brinkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911-1930.[Abstract][Full Text]
Cystic Fibrosis Trust. European cystic fibrosis bone mineralisation guidelines. Feb 2011 [internet publication].[Abstract][Full Text]
Munns CF, Shaw N, Kiely M, et al. Global consensus recommendations on prevention and management of nutritional rickets. 2016 Feb;101(2):394-415.[Abstract][Full Text]
1. Bischof F, Basu D, Pettifor JM. Pathological long-bone fractures in residents with cerebral palsy in a long-term care facility in South Africa. Dev Med Child Neurol. 2002;44:119-122.[Abstract][Full Text]
2. Dardonville Q, Salguiero E, Rousseau V, et al. Drug-induced osteoporosis/osteomalacia: analysis in the French and Spanish pharmacovigilance databases. Eur J Clin Pharmacol. 2019 Dec;75(12):1705-11.[Abstract]
3. Adamson BB, Gallacher SJ, Byars J, et al. Mineralisation defects with pamidronate therapy for Paget's disease. Lancet. 1993;342:1459-1460.[Abstract]
4. Silve C. Hereditary hypophosphatasia and hyperphosphatasia. Curr Opin Rheumatol. 1994;6:336-339.[Abstract]
5. Luni FK, Khan AR, Prashar R, et al. Fanconi syndrome and antiretrovirals: it is never too late. Am J Ther. 2016;23:e558-e560.[Abstract]
6. Patel SM, Graff-Radford J, Wieland ML. Valproate-induced Fanconi syndrome in a 27-year-old woman. J Gen Intern Med. 2011;26:1072-1074.[Abstract][Full Text]
7. Knights M, Thekkekkara T, Morris A, et al. Sodium valproate-induced Fanconi type proximal renal tubular acidosis. BMJ Case Rep. 2016 Jan 28;2016:.[Abstract][Full Text]
8. Song HR, Kweon SS, Choi JS, et al. High prevalence of vitamin D deficiency in adults aged 50 years and older in Gwangju, Korea: the Dong-gu Study. J Korean Med Sci. 2014 Jan;29(1):149-52.[Abstract][Full Text]
9. Cashman KD, Dowling KG, Škrabáková Z, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr. 2016 Apr;103(4):1033-44.[Abstract][Full Text]
10. Prentice A. Nutritional rickets around the world. J Steroid Biochem Mol Biol. 2013 Jul;136:201-6.[Abstract]
11. Goldacre M, Hall N, Yeates DG. Hospitalisation for children with rickets in England: a historical perspective. Lancet. 2014 Feb 15;383(9917):597-8.[Abstract][Full Text]
12. Priemel M, von Domarus C, Klatte TO, et al. Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res. 2010 Feb;25(2):305-12.[Abstract][Full Text]
13. Harris NS, Crawford PB, Yangzom Y, et al. Nutritional and health status of Tibetan children living at high altitudes. N Engl J Med. 2001 Feb 1;344(5):341-7.[Abstract][Full Text]
14. Sedrani SH. Are Saudis at risk of developing vitamin D deficiency? Saudi Med J. 1986;7:427-433.
15. Drezner MK, McGuire JL, Marks SC. Metabolic bone disease. In: Kelley W, ed. Textbook of internal medicine. 2nd ed. Philadelphia, PA: Lippincott; 1992.
16. Finch PJ, Ang L, Eastwood JB, et al. Clinical and histological spectrum of osteomalacia among Asians in South London. Q J Med. 1992;83:439.[Abstract]
17. 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. B J Nutr. 2010;104:603-611.[Abstract]
18. Holick MF, Brinkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911-1930.[Abstract][Full Text]
19. Eddy RL. Metabolic bone disease after gastrectomy. Am J Med. 1971;50:442.[Abstract]
20. Ziegler O, Sirveaux MA, Brunaud L, et al. Medical follow up after bariatric surgery: nutritional and drug issues. General recommendations for the prevention and treatment of nutritional deficiencies. Diabetes Metab. 2009;35:544-557.[Abstract]
21. Dalcanale L, Oliveira CP, Faintuch J, et al. Long-term nutritional outcome after gastric bypass. Obesity Surg. 2010;20:181-187.[Abstract]
22. Al-Shoha A, Qiu S, Palnitkar S, et al. Osteomalacia with bone marrow fibrosis due to severe vitamin D deficiency after a gastrointestinal bypass operation for severe obesity. Endocr Pract. 2009;15:528-533.[Abstract]
23. Karefylakis C, Näslund I, Edholm D, et al. Vitamin D status 10 years after primary gastric bypass: gravely high prevalence of hypovitaminosis D and raised PTH levels. Obes Surg. 2014;24:343-348.[Abstract]
24. Martin KJ, Slatopolsky E. Renal osteodystrophy. In: Becker KL, Bilezikian JP, Remner WJ, et al., eds. Principles and practice of endocrinology and metabolism. New York, NY: J.B. Lippincott Company; 1990:457-463.
25. Minisola S, Fukumoto S, Xia W, et al. Tumor-induced osteomalacia: a comprehensive review. Endocr Rev. 2023 Mar 4;44(2):323-53.[Abstract][Full Text]
26. 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 Jul 22;307(4):217-21.[Abstract]
27. Ott SM, Maloney NA, Klein GL, et al. Aluminium is associated with low bone formation in patients receiving chronic parenteral nutrition. Ann Intern Med. 1983;98:910.[Abstract]
28. Wang Y, Yin Y, Gilula LA, et al. Endemic fluorosis of the skeleton: radiographic features in 127 patients. AJR Am J Roentgenol. 1994;162:93-98.[Abstract][Full Text]
29. Cystic Fibrosis Trust. European cystic fibrosis bone mineralisation guidelines. Feb 2011 [internet publication].[Abstract][Full Text]
30. Russell JA. Osteomalacic myopathy. Muscle Nerve. 1994;17:578-580.[Abstract]
31. Marie PJ, Pettifor JM, Ross FP, et al. Histological osteomalacia due to dietary calcium deficiency in children. N Engl J Med. 1982;307:584-588.[Abstract]
32. Bishop N. Rickets today: children and sunshine (editorial). N Engl J Med. 1999;341:602.[Abstract]
33. De Prisco C, Levine SN. Metabolic bone disease after gastric bypass surgery for obesity. Am J Med Sci. 2005;329:57.[Abstract]
34. De Boer WA, Tytgat GN. A patient with osteomalacia as single presenting symptom of gluten-sensitive enteropathy. J Intern Med. 1992;232:81.[Abstract]
35. Munns CF, Shaw N, Kiely M, et al. Global consensus recommendations on prevention and management of nutritional rickets. 2016 Feb;101(2):394-415.[Abstract][Full Text]
36. Hyppönen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr. 2007;85:860-868.[Abstract]
37. Reddy Munagala VV, Tomar V. Images in clinical medicine: osteomalacia. N Engl J Med. 2014;370:e10.[Abstract][Full Text]
38. Chen TL, Hirst MA, Cone CM, et al. 1,25-dihydroxyvitamin D resistance, rickets, and alopecia: analysis of receptors and bioresponse in cultured skin fibroblasts from patients and parents. J Clin Endocrinol Metab. 1984;59:383-388.[Abstract]
39. Takeuchi Y, Suzuki H, Ogura S, et al. Venous sampling for fibroblast growth factor-23 confirms preoperative diagnosis of tumor-induced osteomalacia. J Clin Endocrinol Metab. 2004;89:3979.[Abstract][Full Text]
40. Eguchi H, Tsuruta M, Tani J, et al. Hypophosphatemic osteomalacia due to drug-induced Fanconi's syndrome associated with adefovir dipivoxil treatment for hepatitis B. Intern Med. 2014;53:233-237.[Abstract][Full Text]
41. Brow TT. Challenges in the management of osteoporosis and vitamin D deficiency in HIV infection. Top Antivir Med. 2013;21:115-118.[Abstract][Full Text]
42. Clarke BL, Wynne AG, Wilson DM, et al. Osteomalacia associated with adult Fanconi's syndrome: clinical and diagnostic features. Clin Endocrinol (Oxf). 1995;43:479-490.[Abstract]
43. Holick MF. Sunlight, UV-radiation, vitamin D and skin cancer: how much sunlight do we need? Adv Exp Med Biol. 2008;624:1-15.[Abstract]
44. Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC. The National Academies Press. 2011 [internet publication].[Full Text]
45. Holick MF. Vitamin D: a D-lightful solution for health. J Investig Med. 2011;59:872-880.[Abstract]
46. National Osteoporosis Foundation. Get the facts on calcium and vitamin D. http://www.nof.org/ (last accessed 9 May 2016).[Full Text]
47. Scientific Advisory Committee on Nutrition. Jul 2016 [internet publication].[Full Text]
48. Klein GL. Nutritional rickets and osteomalacia. In: Favus M, et al., ed. Primer on metabolic bone disease and disorders of mineral metabolism. Philadelphia, PA: Lippincott-Raven; 1993.
49. Kaur G, Singh P, Mittal N, et al. Resolution of "salt and pepper" appearance of the skull with vitamin D therapy. Indian J Endocrinol Metab. 2013 Oct;17(Suppl 1):S194-7.[Abstract][Full Text]
50. Saghafi M, Azarian A, Hashemzadeh K, et al. Bone densitometry in patients with osteomalacia: is it valuable? Clin Cases Miner Bone Metab. 2013;10:180-182.[Abstract][Full Text]
51. MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985;76:1536-1538.[Abstract][Full Text]
52. Carter T, Nutt J, Simons A, et al. Bilateral femoral neck insufficiency fractures secondary to vitamin D deficiency and concurrent corticosteroid use - a case report. Arch Osteoporos. 2014;9:172.[Abstract]
53. Aloia JF, Dhaliwal R, Shieh A, et al. Calcium and vitamin D supplementation in postmenopausal women. J Clin Endocrinol Metab. 2013;98:E1702-E1709.[Abstract]
54. Frame B, Parfitt AM. Osteomalacia: current concepts. Ann Intern Med. 1978 Dec;89(6):966-82.[Abstract]
55. Bingham CT, Fitzpatrick LA. Noninvasive testing in the diagnosis of osteomalacia. Am J Med. 1993;95:519.[Abstract]
56. Basha B, Rao DS, Han ZH, et al. Osteomalacia due to vitamin D depletion: a neglected consequence of intestinal malabsorption. Am J Med. 2000;108:296.[Abstract]
57. Chong WH, Molinolo AA, Chen CC, et al. Tumor-induced osteomalacia. Endocr Relat Cancer. 2011 Jun 8;18(3):R53-77.[Abstract][Full Text]
58. Carpenter TO, Imel EA, Holm IA, et al. A clinician's guide to X-linked hypophosphatemia. J Bone Miner Res. 2011 Jul;26(7):1381-8.[Abstract][Full Text]
59. Insogna KL, Rauch F, Kamenický P, et al. Burosumab improved histomorphometric measures of osteomalacia in adults with X-linked hypophosphatemia: a phase 3, single-arm, international trial. J Bone Miner Res. 2019 Dec;34(12):2183-91.[Abstract][Full Text]
60. Day AL, Gutiérrez OM, Guthrie BL, et al. Burosumab in tumor-induced osteomalacia: a case report. Joint Bone Spine. 2020 Jan;87(1):81-3.[Abstract]
61. Carpenter TO, Miller PD, Weber TJ, et al. OR29-06 Burosumab improves biochemical, skeletal, and clinical features of tumor-induced osteomalacia syndrome. J Endocr Soc. 2020 May 8;4(Suppl 1):OR29-06.[Full Text]
62. Mulligan GB, Licata A. Taking vitamin D with the largest meal improves absorption and results in higher serum levels of 25-hydroxyvitamin D. J Bone Miner Res. 2010;24;928-930.[Abstract]
63. Trang HM, Cole DE, Rubin LA, et al. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998;68:854.[Abstract]
64. Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. 2008:93;677-81.[Abstract][Full Text]
65. Verge CF, Lam A, Simpson JM, et al. Effects of therapy in X-linked hypophosphatemic rickets. N Eng J Med. 1991 Dec 26;325(26):1843-8.[Abstract][Full Text]
