General Principles

  • Osteomalacia is characterized by defective mineralization of osteoid. Bone biopsy reveals increased thickness of osteoid seams and decreased mineralization rate, assessed by tetracycline labeling.
  • Suboptimal vitamin D nutrition, indicated by plasma 25-hydroxy vitamin D (25[OH]D) levels <30 ng/mL, is very common and contributes to the development of osteoporosis.
  • Etiology
    • Dietary vitamin D deficiency
    • Malabsorption of vitamin D and calcium because of intestinal, hepatic, or biliary disease
    • Disorders of vitamin D metabolism (e.g., renal disease, vitamin D–dependent rickets)
    • Vitamin D resistance
    • Chronic hypophosphatemia
    • Renal tubular acidosis
    • Hypophosphatasia


Clinical Presentation

  • Clinical findings include diffuse skeletal pain, proximal muscle weakness, waddling gait, and propensity to fractures.
  • Osteomalacia should be suspected in a patient with osteopenia, elevated serum alkaline phosphatase, and either hypophosphatemia or hypocalcemia.

Diagnostic Testing

  • Serum alkaline phosphatase is elevated. Serum phosphorus, calcium, or both may be low.
  • Serum 25(OH)D levels may be low, establishing the diagnosis of vitamin D deficiency or malabsorption.
  • Radiographic findings include osteopenia and radiolucent bands perpendicular to bone surfaces (pseudofractures or Looser zones). Bone density is decreased.


  • Dietary vitamin D deficiency can initially be treated with ergocalciferol 50,000 international units (IU) PO weekly for 8 weeks to replete body stores, followed by long-term therapy with cholecalciferol 2000 IU/d.
  • Malabsorption of vitamin D may require continued therapy with high doses such as 50,000 IU PO per week. The dose should be adjusted to maintain serum 25(OH)D levels above 30 ng/mL. Calcium supplements, 1 g PO daily, tid, may also be required. Serum 25(OH)D and serum calcium should be monitored every 6–12 months to avoid hypercalcemia.


  1. Holick MF, Binkley 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.  [PMID:21646368]
  2. Munns CF, Shaw N, Kiely M, et al. Global consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab. 2016;101:394-415.  [PMID:26745253]


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