Osteomalacia

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Definition

Osteomalacia is a metabolic bone disease characterized by defective mineralization of newly formed osteoid in mature bone. It represents the adult equivalent of rickets, which affects growing bones in children. The hallmark is accumulation of unmineralized or undermineralized osteoid matrix, resulting in soft, deformable bones with increased fracture risk.

Epidemiology

Prevalence:

• Elderly institutionalized: 30-50% have vitamin D deficiency (less than 50 nmol/L)
• Community-dwelling elderly: 10-15% have deficiency
• Post-bariatric surgery: 25-40% develop deficiency without supplementation
• Dark-skinned populations in high latitudes: 5-10 times higher risk

Demographics:

• Female to male ratio: 3:1 (postmenopausal women at highest risk)
• Age: Risk increases with age (reduced sunlight exposure, decreased skin synthesis)
• Geographic variation: Higher prevalence at latitudes greater than 35 degrees (reduced UVB exposure)

Normal bone mineralization requires adequate calcium, phosphate, and alkaline phosphatase. Vitamin D is essential for intestinal calcium absorption and renal phosphate reabsorption. In osteomalacia, deficiency of vitamin D or phosphate leads to:

Molecular cascade:

1. Reduced calcium and phosphate availability
2. Inadequate hydroxyapatite crystal formation in osteoid
3. Accumulation of unmineralized osteoid (increased osteoid volume)
4. Secondary hyperparathyroidism (compensatory response to hypocalcemia)
5. Further phosphate wasting (PTH-induced renal phosphate loss)
6. Progressive bone softening and deformity

Symptoms

Examination Findings

Musculoskeletal:

• Antalgic or waddling gait - due to bone pain and proximal myopathy
• Bone tenderness - sternal pressure, rib compression, pelvic compression
• Skeletal deformities - leg bowing (varus or valgus), kyphosis
• Reduced muscle power - hip flexion (iliopsoas), knee extension (quadriceps) weakness

Neurological:

• Proximal muscle weakness - grade 3-4 out of 5 in hip flexors, shoulder abductors
• Hyporeflexia - reduced or absent deep tendon reflexes
• Tetany signs (if severe hypocalcemia) - Chvostek's sign (facial twitch), Trousseau's sign (carpopedal spasm)

Biochemistry

Vitamin D Thresholds:

• Severe deficiency: less than 25 nmol/L (less than 10 ng/mL)
• Deficiency: 25-50 nmol/L (10-20 ng/mL)
• Insufficiency: 50-75 nmol/L (20-30 ng/mL)
• Optimal for bone health: 75-125 nmol/L (30-50 ng/mL)

Additional Investigations

• Urinary calcium: low (less than 2.5 mmol per 24 hours)
• Urinary phosphate: elevated in renal phosphate wasting
• FGF23 level: elevated in tumor-induced osteomalacia (oncogenic osteomalacia)
• Renal function: to assess for chronic kidney disease (impaired 1-alpha hydroxylation)
• Liver function: to assess for cholestatic disease (impaired vitamin D absorption)

Radiographic Findings

Bone Densitometry (DXA)

• Low bone mineral density (T-score less than -2.5 at spine or hip)
• Cannot distinguish osteomalacia from osteoporosis on DXA alone
• Biochemistry and clinical context essential for diagnosis

Advanced Imaging

Nuclear Medicine (Bone Scan):

• Increased uptake at sites of pseudofractures
• Multiple symmetric hot spots - "superscan" appearance
• Useful in tumor-induced osteomalacia to localize FGF23-secreting tumor

MRI:

• Bone marrow edema at pseudofracture sites
• Localization of occult tumors in oncogenic osteomalacia
• Sensitivity for small mesenchymal tumors

CT:

• Assessment of bone quality and fracture risk
• 3D reconstruction for surgical planning (prophylactic fixation)

Bone Biopsy (Gold Standard)

Indications:

• Diagnostic uncertainty after clinical, biochemical, radiographic evaluation
• Suspected hypophosphatasia or rare mineralization disorder
• Pre-treatment assessment in oncogenic osteomalacia

Findings:

• Increased osteoid volume (greater than 15% vs normal less than 5%)
• Widened osteoid seams (greater than 12 micrometers)
• Prolonged mineralization lag time (greater than 100 days)
• Tetracycline double-labeling shows delayed mineralization front

Pathological Fractures

High-risk sites:

• Femoral neck - bilateral, often at sites of Looser zones
• Proximal femur - subtrochanteric, intertrochanteric
• Pelvis - pubic rami, sacrum
• Ribs - multiple, painful
• Vertebrae - compression fractures

Management principles:

1. Optimize medical management FIRST - vitamin D and calcium replacement
2. Prophylactic fixation for impending fractures (Looser zones greater than 50% cortical width, symptomatic)
3. Fracture fixation with caution - bone is soft, screw purchase poor
4. Longer immobilization than normal fractures - delayed healing

Arthroplasty Considerations

Preoperative:

• Screen all arthroplasty candidates for vitamin D deficiency
• Optimize vitamin D greater than 75 nmol/L before elective surgery
• Correct calcium and phosphate abnormalities

Intraoperative:

• Risk of periprosthetic fracture during insertion (especially press-fit stems)
• Poor bone quality may favor cemented fixation
• Careful reaming and broaching to avoid fracture

Postoperative:

• Delayed osseointegration of uncemented implants
• Risk of aseptic loosening if vitamin D not repleted
• Periprosthetic fracture risk with minimal trauma
• Continue vitamin D and calcium indefinitely

Expected Response to Treatment

Biochemical:

• Calcium and phosphate normalize by 4-12 weeks
• PTH decreases by 3-6 months (may take longer if severe)
• Alkaline phosphatase declines by 6-12 months (may initially rise as bone heals)

Clinical:

• Bone pain improves by 6-12 weeks
• Muscle weakness reverses by 3-6 months
• Looser zones heal by 6-12 months (radiographic evidence of mineralization)
• Fracture risk decreases once vitamin D greater than 50 nmol/L

Poor prognostic factors:

• Severe, prolonged deficiency - may have permanent skeletal deformities
• Uncontrolled underlying cause (malabsorption, chronic kidney disease)
• Non-compliance with supplementation
• Oncogenic osteomalacia with unresectable tumor

Vitamin D Deficiency Prevalence: Vitamin D deficiency is common in Australia despite high UV exposure, particularly in dark-skinned populations, elderly, institutionalised patients, and those with cultural dress practices limiting sun exposure. Screening is recommended in at-risk groups.

PBS-Subsidised Vitamin D: Cholecalciferol (vitamin D3) preparations are available on PBS for documented deficiency. Colecalciferol 1000 IU daily or 50,000 IU monthly loading doses are standard regimens.

Therapeutic Guidelines: Australian Endocrine Society and Osteoporosis Australia recommend treatment based on serum 25-OH vitamin D levels: deficiency (less than 50 nmol/L), insufficiency (50-75 nmol/L), adequate (greater than 75 nmol/L).

Calcium Supplementation: Calcium carbonate and citrate preparations are PBS-subsidised when used with vitamin D. Dietary calcium intake is preferred where possible through dairy and fortified foods.

Oncogenic Osteomalacia: Rare FGF23-secreting mesenchymal tumours require nuclear medicine imaging (Ga-68 DOTATATE PET/CT) for localisation. Surgical excision is curative when tumour is accessible.