Which laboratory tests should be obtained when evaluating a post‑menopausal woman or a man over 50 for osteoporosis?

Laboratory Evaluation for Osteoporosis Management

All patients being evaluated for osteoporosis should undergo a core panel of laboratory tests to identify secondary causes of bone loss, which are present in 44-90% of young adults and approximately 75% of older men with osteoporosis. 1, 2

Essential Initial Laboratory Panel

The following tests have 92% sensitivity for detecting secondary causes and should be obtained in all patients with osteoporosis or low bone density 1:

• Serum calcium - to screen for hyperparathyroidism and malabsorption 1, 3, 4
• Serum phosphate - to evaluate for osteomalacia and renal disorders 1, 4
• 25-hydroxyvitamin D level - vitamin D deficiency affects 40-80% of certain populations and must be corrected before bisphosphonate therapy 1, 3, 4
• Serum alkaline phosphatase - elevated levels are 3 times more common in osteoporotic men and suggest osteomalacia or Paget's disease 1, 5, 4
• Complete blood count - to screen for multiple myeloma and other hematologic disorders 1, 4
• Serum creatinine - to assess renal function which affects bone metabolism 1, 4
• Protein electrophoresis - to exclude multiple myeloma 1
• Thyroid-stimulating hormone (TSH) - to detect hyperthyroidism 4

Sex-Specific Testing

• Testosterone level in all males - hypogonadism accounts for 40-60% of secondary osteoporosis cases in men under 50 1, 2
• Estrogen status assessment in premenopausal women - estrogen deficiency accounts for 35-40% of secondary osteoporosis in this population 1

Conditional Testing Based on Initial Results

• Parathyroid hormone (PTH) - only obtain if serum calcium or urinary calcium is abnormal, as PTH measurement is unnecessary with normal calcium levels 1, 4
• 24-hour urine calcium - to identify hypercalciuria if clinically suspected 2, 4
• Spot urine calcium-to-creatinine ratio - alternative to 24-hour collection for hypercalciuria screening 2

Critical Clinical Context

Normal serum calcium does not exclude bone disease - calcium is mobilized from bone to maintain serum levels in secondary osteoporosis, so normal calcium levels can coexist with significant bone pathology 1

Vitamin D deficiency is extremely common and causes osteomalacia when severe, presenting with bone pain, muscle weakness, low calcium and phosphorus, elevated alkaline phosphatase, and elevated PTH 1. This contrasts with osteoporosis, which remains completely asymptomatic until fracture occurs 6.

Age-Specific Considerations

In older men (≥65 years), the yield of routine laboratory testing may be lower, as approximately 60% have at least one laboratory abnormality regardless of osteoporosis status 5. However, vitamin D insufficiency and elevated alkaline phosphatase remain significantly more common in osteoporotic older men 5.

Common Pitfalls to Avoid

• Do not skip vitamin D testing - deficiency must be corrected before initiating bisphosphonate therapy 1
• Do not order PTH reflexively - it is only indicated when calcium abnormalities are present 1
• Do not assume primary osteoporosis - secondary causes are identified in approximately 50% of men initially thought to have primary osteoporosis 2
• Consider Z-score - a Z-score of -2.5 or less strongly suggests secondary osteoporosis and warrants more extensive evaluation 4