Key Facts

Osteomalacia is a metabolic bone disorder characterised by impaired mineralisation of newly formed osteoid. Unlike osteoporosis (where bone is structurally normal but reduced in quantity), osteomalacia involves qualitatively abnormal bone with excess unmineralised osteoid.

Epidemiology

• Common in elderly, housebound, and institutionalised populations in the UK
• Higher prevalence in South Asian women in the UK
• Increasing incidence linked to indoor lifestyles and sun avoidance
• UK latitude (50-60°N) provides insufficient UVB October–March

Aetiology

• Vitamin D deficiency (most common): dietary insufficiency, malabsorption, lack of sunlight
• Renal disease: impaired 1-alpha-hydroxylation (CKD stages 4-5)
• Hepatic disease: impaired 25-hydroxylation
• Drug-induced: phenytoin, carbamazepine, rifampicin (CYP450 induction)
• Hypophosphataemia: X-linked hypophosphataemic rickets, oncogenic osteomalacia (FGF-23 mediated)
• Renal tubular acidosis: type 1 and type 2
• Aluminium toxicity: in patients on dialysis (historical)

Pathophysiology

• Vitamin D deficiency reduces intestinal calcium and phosphate absorption
• Hypocalcaemia triggers secondary hyperparathyroidism
• PTH mobilises calcium from bone and increases renal phosphate excretion
• Insufficient calcium-phosphate product for mineralisation
• Excess unmineralised osteoid accumulates, producing soft, weak bone

Bone Pain

• Diffuse, dull aching bone pain – pelvis, spine, ribs, legs
• Tenderness on palpation of sternum, tibiae, or pelvis
• Pain worsens with weight-bearing and movement

Proximal Myopathy

• Proximal muscle weakness – difficulty rising from a chair, climbing stairs
• Waddling gait is characteristic
• May be misdiagnosed as polymyalgia rheumatica or fibromyalgia

Fractures

• Pathological fractures, particularly vertebral compression fractures
• Insufficiency fractures of pelvis, femoral neck

Red Flags

• Severe hypocalcaemia: tetany, paraesthesiae, carpopedal spasm, seizures, prolonged QT
• Pathological fracture with minimal trauma
• Failure to respond to standard vitamin D replacement → consider rare causes (oncogenic osteomalacia, genetic forms)

Bedside

• Assess risk factors, mobility, and proximal muscle strength
• Chvostek and Trousseau signs if hypocalcaemic

Bloods

• Serum 25-OH-vitamin D: low (<25 nmol/L)
• Adjusted calcium: low or low-normal
• Phosphate: low
• ALP: raised (bone isoenzyme)
• PTH: raised (secondary hyperparathyroidism)
• FBC, U&Es, LFTs, bone profile
• Consider coeliac screen (tTG antibodies)

Imaging

• X-ray: Looser zones (pseudofractures) – bilateral, symmetrical radiolucent bands, classically at femoral neck, pubic rami, lateral scapulae, ribs
• DEXA scan: may show reduced BMD (can be misdiagnosed as osteoporosis)
• Isotope bone scan: increased uptake at pseudofracture sites

Special Tests

• Bone biopsy (iliac crest, tetracycline-labelled): gold standard – shows increased osteoid seams, reduced mineralisation front. Rarely performed clinically.
• 24-hour urinary calcium: low
• FGF-23: if oncogenic osteomalacia suspected

Non-pharmacological

• Dietary advice: increase oily fish, eggs, fortified foods
• Safe sunlight exposure (10-15 min midday, arms/face)
• Falls prevention programme in elderly

Pharmacological

• Vitamin D deficiency-related osteomalacia:
  • Colecalciferol loading: 50,000 IU weekly for 6-8 weeks
  • Maintenance: 800-2,000 IU daily lifelong
  • Calcium supplementation: 1,000-1,500 mg/day if dietary intake inadequate
• CKD-related osteomalacia (renal osteodystrophy):
  • Alfacalcidol 0.25-1 mcg OD or calcitriol 0.25-0.5 mcg OD
  • Phosphate binders if hyperphosphataemia present
• Tumour-induced osteomalacia: surgical excision of FGF-23-producing tumour, phosphate and calcitriol supplementation
• Drug-induced: consider switching anticonvulsant, supplement with higher dose vitamin D

Referral Criteria

• Refractory disease despite adequate supplementation
• CKD stages 4-5 → nephrology
• Suspected oncogenic osteomalacia or genetic forms → metabolic bone specialist
• Pathological fractures → orthopaedics

• Excellent prognosis when cause is identified and treated
• Biochemical improvement within 4-8 weeks
• Bone pain typically resolves within 3-6 months
• Pseudofractures heal over 6-12 months with treatment
• Proximal myopathy is reversible with vitamin D replacement
• Untreated disease carries significant fracture risk and functional impairment

Osteomalacia vs Osteoporosis

Causes of Raised ALP with Normal Calcium