What is the likely diagnosis and serum findings for a 25-year-old woman with a 9-year history of generalized bone pain, frequent episodes of loose bulky stools, muscle weakness, extended and distended abdomen, and fracture-like bones in the feet, and what would be the expected levels of calcium, phosphorus, alkaline phosphatase (ALP), and parathyroid hormone (PTH)?

Diagnosis: Osteomalacia Secondary to Malabsorption (Likely Celiac Disease)

This 25-year-old woman with chronic bone pain, malabsorptive diarrhea (loose bulky stools), muscle weakness, distended abdomen, and fractures most likely has osteomalacia secondary to celiac disease, with expected serum findings of low-normal calcium, low phosphorus, elevated alkaline phosphatase, and elevated parathyroid hormone. 1

Clinical Presentation Analysis

The constellation of symptoms strongly suggests osteomalacia with underlying malabsorption:

• Nine-year history of generalized bone pain is a hallmark of osteomalacia, distinguishing it from asymptomatic osteoporosis 1, 2
• Muscle weakness is characteristic of severe vitamin D deficiency and osteomalacia 1, 3, 2
• Loose bulky stools indicate fat malabsorption, most commonly from celiac disease in this age group 1
• Distended abdomen is consistent with celiac disease presentation 1
• Fracture-like bones/pseudofractures (Looser zones) are pathognomonic for osteomalacia 3
• Generalized bone demineralization reflects the chronic mineralization defect 1, 2

Expected Serum Laboratory Findings

The characteristic biochemical profile of osteomalacia includes: 1

• Calcium: Low-normal or low - Due to impaired intestinal calcium absorption from vitamin D deficiency 1, 3
• Phosphorus: Low - Results from secondary hyperparathyroidism and renal phosphate wasting 1, 3
• Alkaline phosphatase (ALP): Elevated - Reflects increased osteoblast activity attempting to mineralize accumulating osteoid 1, 3, 4
• Parathyroid hormone (PTH): Elevated - Secondary hyperparathyroidism develops in response to hypocalcemia and vitamin D deficiency 1, 3

Additional expected findings include severely low 25-hydroxyvitamin D levels and very low urinary calcium excretion 3.

Differential Consideration: X-Linked Hypophosphatemia

While the biochemical profile could superficially resemble X-linked hypophosphatemia (XLH), several features make this diagnosis less likely:

• XLH typically presents in infancy/early childhood with delayed walking and progressive deformities starting around 6 months to 2 years of age 1
• The malabsorptive symptoms (loose bulky stools, distended abdomen) are not features of XLH 1
• In XLH, calcium is typically low-normal with inappropriately normal or low 1,25-dihydroxyvitamin D (not severely low 25-hydroxyvitamin D) 1
• XLH shows elevated FGF23 levels, which would not be expected in malabsorption-related osteomalacia 1, 5

Diagnostic Workup Priority

Immediate laboratory assessment should include: 1

• Serum calcium (corrected for albumin), phosphate, total ALP, and PTH 1
• 25-hydroxyvitamin D level (expected to be severely decreased) 1, 3
• Celiac serologies (tissue transglutaminase antibodies, anti-endomysial antibodies) 1
• Complete blood count and comprehensive metabolic panel 1

Imaging studies:

• Plain radiographs to identify pseudofractures (Looser zones), particularly in pelvis, scapula, and long bones 3
• Dual-energy X-ray absorptiometry (DXA) will show severe demineralization 1, 3

Pathophysiology

In celiac disease, villous atrophy leads to:

1. Impaired vitamin D absorption → Severe vitamin D deficiency 1
2. Reduced calcium absorption → Hypocalcemia 1
3. Secondary hyperparathyroidism develops to maintain serum calcium 1, 3
4. PTH causes renal phosphate wasting → Hypophosphatemia 1
5. Defective bone mineralization occurs due to insufficient calcium and phosphate, leading to osteoid accumulation 2
6. Elevated ALP reflects osteoblast activity attempting to mineralize the unmineralized matrix 1, 4

Critical Management Points

Treatment must address both the underlying malabsorption and the metabolic bone disease: 1

• Strict gluten-free diet is essential for celiac disease and will improve calcium/vitamin D absorption 1
• High-dose vitamin D supplementation (typically 50,000 IU weekly initially) plus calcium (1000-1500 mg daily) 1, 3
• Monitor response with repeat calcium, phosphate, ALP, and PTH at 2-3 months 3
• Expect clinical improvement within 2 months, with resolution of bone pain and ability to ambulate 3

Common pitfall: Do not assume this is simple osteoporosis based on young age—the presence of bone pain and muscle weakness mandates evaluation for osteomalacia 1, 2. Standard osteoporosis treatment with bisphosphonates would be inappropriate until the mineralization defect is corrected 1.