Osteomalacia: Definition, Diagnosis, and Treatment
Osteomalacia is a metabolic bone disease characterized by impaired bone mineralization due to vitamin D deficiency, phosphate depletion, or calcium deficiency, requiring treatment with appropriate supplementation based on the underlying cause.
Definition and Pathophysiology
- Osteomalacia literally means "soft bone" and results from undermineralization of newly formed bone matrix (osteoid) due to insufficient calcium, phosphorus, or vitamin D 1, 2
- The condition evolves in three stages when caused by vitamin D deficiency:
- Initial stage: Normal serum calcium and phosphate with elevated alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D 2
- Second stage: Declining serum calcium and phosphate with further increases in PTH and alkaline phosphatase 2
- Final stage: Marked hypocalcemia, hypophosphatemia, and severe secondary hyperparathyroidism 2
Causes
- Vitamin D deficiency due to insufficient sunlight exposure, dietary insufficiency, or impaired cutaneous synthesis (in jaundiced patients) 3, 4
- Malabsorption syndromes affecting vitamin D and calcium absorption 1
- Chronic kidney disease with reduced vitamin D hormone activation 4, 5
- Phosphate wasting syndromes, including X-linked hypophosphatemia 3
- Aluminum toxicity (historically in dialysis patients) 3
- Tumor-induced (oncogenic) osteomalacia 6
Clinical Presentation
- Bone pain (diffuse or localized) and tenderness 4, 1
- Muscle weakness, cramps, and increased fall risk, particularly in the elderly 4, 1
- Characteristic fracture patterns including pseudofractures (Looser's zones) involving ribs, scapulae, pubic rami, and proximal femurs 2
- In children, skeletal deformities may include:
- Lower limb deformities (varus or valgus)
- Widening of metaphyses at wrist and ankle
- Rachitic rosary (beading of ribs)
- Harrison's groove (horizontal groove along lower thorax) 3
Diagnosis
- Laboratory findings:
- Radiographic findings:
- Pseudofractures (Looser's zones)
- Bone demineralization
- In children: cupped and flared metaphyses, widened physes 3
- Bone mineral density (BMD) measurements typically show low values at all sites 7
- Definitive diagnosis may require iliac crest bone biopsy showing deficient mineralization of newly synthesized bone matrix 1
Treatment
Vitamin D Deficiency Osteomalacia
- Supplementation with vitamin D2 (ergocalciferol) or D3 (cholecalciferol) 3, 6
- If no response to standard vitamin D supplementation, consider active vitamin D metabolites (calcitriol) 3, 6
- Ensure adequate calcium intake (1,000-1,500 mg/day) 6, 8
- Monitor serum 25-hydroxyvitamin D levels to guide ongoing supplementation 8
Phosphate Depletion Osteomalacia
- Phosphate supplementation with doses adjusted upward until normal serum phosphate levels are achieved 3, 6
- Administer phosphate in 2-4 divided doses, preferably using potassium-based phosphate salts to reduce hypercalciuria risk 6
- For oncogenic osteomalacia, tumor removal is curative when possible 1
Aluminum-Related Osteomalacia (in Dialysis Patients)
- Prevention by maintaining aluminum concentration in dialysate fluid at <10 μg/L 3
- Avoid aluminum-containing compounds (including sucralfate) 3
- Treatment with deferoxamine (DFO) for established aluminum bone disease 3
- For patients with serum aluminum >200 μg/L, intensive dialysis should precede DFO therapy 3
Treatment Response and Monitoring
- Clinical and biochemical improvements typically occur within a few weeks of starting treatment 7
- Bone mineral density recovery:
- Monitor serum alkaline phosphatase as an indicator of osteomalacia activity 6
- Complete recovery of BMD may take longer than clinical improvement 7
Special Considerations
- In chronic kidney disease, treatment approach depends on the specific type of bone disease present 3
- In pregnancy, monitor 25(OH) vitamin D levels and adjust phosphate supplementation as needed 6
- In patients with chronic liver disease, comprehensive fat-soluble vitamin supplementation (A, D, E, K) may be necessary 8