What is osteomalacia?

Osteomalacia: Definition, Causes, and Management

Osteomalacia is a metabolic bone disease characterized by impaired mineralization of newly formed bone matrix, resulting in soft bones prone to deformities, pain, and fractures. 1, 2

Pathophysiology and Causes

Osteomalacia develops due to several underlying mechanisms:

• Vitamin D deficiency is the most common cause, leading to reduced calcium and phosphate absorption and impaired bone mineralization 3, 4
• Phosphate depletion or renal phosphate wasting syndromes 2
• Aluminum toxicity, particularly in patients with chronic kidney disease (CKD), where aluminum accumulates on bone surfaces and impairs bone formation 1
• Chronic kidney disease, which reduces the conversion of vitamin D to its active form 5
• Malabsorption syndromes affecting vitamin D and mineral absorption 4, 6

Clinical Presentation

Osteomalacia manifests with several characteristic symptoms:

• Dull, localized or generalized bone pain and tenderness 2, 4
• Muscle weakness and cramps 2
• Increased incidence of falls 2
• Difficulty walking 4, 6
• In advanced cases, skeletal deformities may develop, including:
  • Lower limb deformities (varus or valgus) 1
  • Widening of the distal metaphyses at wrist and ankle 1
  • Characteristic fracture patterns (pseudofractures) involving ribs, scapulae, pubic rami, and proximal femurs 3

Diagnostic Evaluation

Diagnosis of osteomalacia is based on clinical, biochemical, and radiological findings:

• Laboratory abnormalities progress through three stages:

  • Initial stage: Normal calcium and phosphate, elevated alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D 3
  • Second stage: Declining calcium and phosphate, further increases in PTH and alkaline phosphatase 3
  • Final stage: Hypocalcemia, hypophosphatemia, and severe secondary hyperparathyroidism 3

• Radiographic findings include:

  • Cupped and flared metaphyses 1
  • Widened and irregular growth plates 1
  • Pseudofractures in advanced cases 1, 3

• Definitive diagnosis may require:

  • Bone biopsy showing reduced or deficient mineralization of the newly synthesized extracellular matrix 2, 4

Treatment

Treatment of osteomalacia depends on the underlying cause:

• For vitamin D deficiency:

  • Vitamin D2 or D3 supplementation to restore normal levels 1
  • If response is inadequate, particularly in CKD patients, active vitamin D sterols may be needed 1
  • Calcium supplementation is often required 2

• For phosphate depletion:

  • Phosphate supplementation with doses adjusted to achieve normal serum phosphorus levels 1, 2

• For aluminum-related osteomalacia in CKD:

  • Prevention by maintaining aluminum concentration in dialysate fluid at <10 μg/L 1
  • Avoiding aluminum-containing compounds 1
  • Treatment with deferoxamine (DFO) if aluminum overload is present 1

• For tumor-induced osteomalacia:

  • Removal of the tumor is curative in most cases 2

Special Considerations

• Osteomalacia is often underrecognized or misdiagnosed as osteoporosis 3
• Not all individuals with vitamin D deficiency develop osteomalacia 4, 6
• Treatment should be continued until clinical indicators of osteomalacia normalize, such as bone alkaline phosphatase activity 1
• In patients with intestinal malabsorption syndromes, parenteral administration of vitamin D and calcium may be necessary 2
• Patients who have undergone bariatric surgery are at increased risk of developing osteomalacia 4, 6