What is osteomalacia?

Osteomalacia: Definition and Clinical Overview

Osteomalacia is a metabolic bone disease characterized by defective mineralization of newly formed bone matrix (osteoid), resulting in soft, weakened bones that manifest clinically with bone pain, muscle weakness, and characteristic pseudofractures. 1, 2

Pathophysiology

Osteomalacia develops when there is insufficient calcium, phosphate, or vitamin D available for proper bone mineralization 3. The disease evolves through three progressive stages 4:

• Stage 1: Normal serum calcium and phosphate with elevated alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D 4
• Stage 2: Declining serum calcium and phosphate, further increases in PTH and alkaline phosphatase, with 1,25(OH)₂D returning to normal or low values 4
• Stage 3: Invariable hypocalcemia and hypophosphatemia with severe secondary hyperparathyroidism 4

Primary Causes

The underlying etiologies include 1, 2:

• Vitamin D deficiency: Due to insufficient sunlight exposure, dietary insufficiency, impaired cutaneous synthesis, or malabsorption 1, 5
• Phosphate wasting syndromes: Including X-linked hypophosphatemia and tumor-induced osteomalacia 1, 2
• Aluminum toxicity: Historically seen in dialysis patients when aluminum accumulates on bone surfaces and impairs bone formation 6
• Chronic kidney disease: Reduced conversion of vitamin D to its active form 3
• Drug-induced: Cytochrome P450 pathway inducers, alcohol 6

Clinical Presentation

Symptoms

Patients typically present with 2, 4:

• Dull, localized or generalized bone pain 2
• Proximal muscle weakness and cramps 2, 4
• Increased incidence of falls, particularly in elderly patients 5, 2

Radiographic Findings

Characteristic imaging features include 1:

• Pseudofractures (Looser's zones): Involving ribs, scapulae, pubic rami, proximal femurs 1, 4
• Bone demineralization 1
• Codfish-type vertebrae 4

Pediatric Manifestations

Children exhibit 1:

• Lower limb deformities
• Widening of metaphyses
• Rachitic rosary
• Harrison's groove

Diagnostic Approach

Laboratory Findings

Key biochemical abnormalities include 2, 4:

• Elevated alkaline phosphatase (typically present and serves as an indicator of osteomalacia activity) 1, 2
• Reduced serum phosphate and/or 25-OH vitamin D₃ levels 2
• Hypocalcemia (in advanced stages) 4

Definitive Diagnosis

Bone biopsy from the iliac crest provides histological confirmation, showing reduced or deficient mineralization of newly synthesized extracellular matrix 6, 2. This is particularly important for diagnosing aluminum-related osteomalacia, as the DFO challenge test can identify aluminum overload but is not specific for bone lesions 6.

Treatment Strategies

Vitamin D Deficiency Osteomalacia

The primary treatment is supplementation with vitamin D₂ or D₃, combined with adequate calcium intake of 1,000-1,500 mg/day 6, 1:

• Start with ergocalciferol or cholecalciferol 6, 1
• If no response occurs, particularly in Stage 5 kidney failure patients, consider active vitamin D sterols (calcitriol) 6, 1
• For malabsorption syndromes, parenteral administration may be necessary 2

Phosphate Depletion Osteomalacia

Phosphate supplementation should be administered with doses adjusted upward until normal serum phosphate levels are achieved 6, 1:

• Administer in 2-4 divided doses 7
• Prefer potassium-based phosphate salts to reduce hypercalciuria risk 7
• Ensure adequate calcium intake (at least 1g/day) 7

Aluminum-Related Osteomalacia

Treatment involves 6:

• Chelation therapy with deferoxamine (DFO) for documented aluminum toxicity 6
• Prevention by maintaining aluminum concentration in dialysate fluid at <10 μg/L 1
• Avoidance of aluminum-containing phosphate binders 8

Tumor-Induced Osteomalacia

Surgical removal of the causative tumor leads to cure in most cases 2. Medical management includes phosphate and vitamin D supplementation as outlined above 7.

Monitoring Treatment Response

Continue treatment until serum alkaline phosphatase normalizes, which serves as the primary indicator of osteomalacia activity 6, 1:

• Monitor serum phosphate levels until normalization 7
• Check 25(OH) vitamin D levels and adjust supplementation accordingly 7
• For patients initiating vitamin D after phosphate control, monitor serum phosphate and calcium levels at least weekly during initial supplementation 8

Important Clinical Pitfalls

Differential Diagnosis Considerations

Osteomalacia can mimic several rheumatic conditions 2:

• Polymyalgia rheumatica
• Rheumatoid arthritis
• Myositis
• Fibromyalgia

The condition is frequently misdiagnosed as osteoporosis, requiring high clinical suspicion based on characteristic symptoms and biochemical patterns 4.

Special Population Considerations

In chronic kidney disease patients with osteomalacia and hyperphosphatemia, correct hyperphosphatemia first before vitamin D supplementation 8. This prevents further complications from elevated calcium-phosphate product 8.

During pregnancy and lactation, monitor 25(OH) vitamin D levels and adjust phosphate supplementation as needed, continuing treatment throughout 7.

In chronic liver disease, comprehensive fat-soluble vitamin supplementation (A, D, E, K) may be necessary 1.