A 38-year-old woman from rural Rajasthan presents with progressive bone pain, muscle weakness, and difficulty climbing stairs for 8 months. She reports minimal sun exposure due to cultural practices. On examination, she has proximal muscle weakness and a waddling gait. Biochemistry shows: serum calcium 7.2 mg/dL, phosphate 2.8 mg/dL, alkaline phosphatase 120 IU/L, 25-hydroxyvitamin D 12 ng/mL. X-rays show loss of sharp cortical margins and Looser's zones in the pelvis and femur. What is the most likely diagnosis?

Explanation

## Diagnosis: Nutritional Osteomalacia ### Clinical Presentation This patient has the classic triad of osteomalacia: 1. **Bone pain** — diffuse, aching quality, worse with weight-bearing 2. **Proximal muscle weakness** — waddling gait, difficulty climbing stairs 3. **Risk factors** — minimal sun exposure (cultural purdah), rural setting with limited dietary fortification ### Biochemical Pattern | Parameter | Finding | Interpretation | |-----------|---------|----------------| | Serum calcium | 7.2 mg/dL | Low (normal 8.5–10.5) | | Phosphate | 2.8 mg/dL | Low (normal 2.5–4.5) | | Alkaline phosphatase | 120 IU/L | Mildly elevated | | 25-OH vitamin D | 12 ng/mL | **Severely deficient** (<20 ng/mL is deficient) | | PTH | Expected elevated | Secondary hyperparathyroidism response | **Key Point:** The 25-hydroxyvitamin D level of 12 ng/mL is the diagnostic hallmark — this is the most specific marker of vitamin D deficiency. ### Radiological Findings **High-Yield:** Looser's zones (pseudofractures) are pathognomonic for osteomalacia. These are bands of radiolucency perpendicular to the bone surface, most common in the pelvis, femur, and tibia. Loss of sharp cortical margins reflects poor mineralization. ### Pathophysiology 1. Vitamin D deficiency → ↓ intestinal calcium absorption 2. Hypocalcemia → secondary hyperparathyroidism 3. PTH mobilizes bone phosphate but cannot compensate for defective mineralization 4. Unmineralized osteoid accumulates → soft bones and muscle weakness **Clinical Pearl:** Osteomalacia in adults presents with bone pain and myopathy; rickets in children presents with growth retardation and skeletal deformities. Both share the same underlying defect: defective mineralization of bone matrix. ### Why Nutritional Osteomalacia? - Severe vitamin D deficiency (12 ng/mL) in a patient with minimal sun exposure - No mention of renal disease, malabsorption, or dietary phosphate restriction - Hypocalcemia and hypophosphatemia (both low) — characteristic of vitamin D deficiency - Looser's zones on imaging — classic radiological sign [cite:Robbins 10e Ch 26]