What laboratory tests should be ordered for an older adult or postmenopausal woman with risk factors for osteopenia or osteoporosis?

Laboratory Testing for Osteopenia and Osteoporosis

Essential Baseline Laboratory Tests

All patients being evaluated for osteopenia or osteoporosis should have measurements of 25-hydroxyvitamin D, serum calcium, urine calcium, and renal function testing. 1 These tests identify common treatable causes of bone loss and guide supplementation strategies.

Core Laboratory Panel

• 25-hydroxyvitamin D level: Essential to identify vitamin D deficiency, which is highly prevalent and directly treatable 1
• Serum calcium: Screens for hypercalcemia (suggesting hyperparathyroidism or malignancy) or hypocalcemia (suggesting vitamin D deficiency or malabsorption) 1
• 24-hour urine calcium (or spot urine calcium/creatinine ratio): Identifies hypercalciuria or hypocalciuria, which may indicate underlying metabolic disorders 1
• Serum creatinine or estimated GFR: Assesses renal function, as chronic kidney disease affects bone metabolism and medication choices 1

Additional Testing for Secondary Causes

The decision to pursue additional laboratory testing depends on clinical suspicion for secondary osteoporosis based on history and physical examination findings. 1

When to Suspect Secondary Osteoporosis

Consider expanded testing in patients with: 1

• Premature or severe osteoporosis (T-score ≤-2.5 in patients younger than 50 years or T-score ≤-3.5 at any age)
• Rapid bone loss on serial DXA testing
• Fractures despite adequate treatment
• Clinical features suggesting specific endocrine, gastrointestinal, or hematologic disorders

Expanded Laboratory Evaluation

When secondary causes are suspected, consider: 1

• Complete blood count: Screens for multiple myeloma, mastocytosis, or other hematologic disorders
• Thyroid-stimulating hormone (TSH): Identifies hyperthyroidism, which accelerates bone loss 2
• Parathyroid hormone (PTH): Diagnoses primary hyperparathyroidism when serum calcium is elevated or high-normal
• Serum protein electrophoresis with immunofixation: Screens for multiple myeloma in appropriate clinical contexts
• Tissue transglutaminase antibodies (tTG-IgA): Identifies celiac disease causing malabsorption
• Testosterone level (in men): Detects hypogonadism, a common secondary cause in males 2
• Liver function tests: Identifies chronic liver disease affecting vitamin D metabolism
• Cortisol testing (24-hour urine free cortisol or dexamethasone suppression test): Evaluates for Cushing syndrome if clinically suspected

Laboratory Testing NOT Routinely Recommended

Bone turnover markers (such as serum C-telopeptide, N-telopeptide, or bone-specific alkaline phosphatase) are not recommended for routine screening or diagnosis of osteoporosis. 1, 3 While these markers may have a role in monitoring treatment response in specialized settings, they lack sufficient evidence for routine clinical use in initial evaluation.

Special Population Considerations

Glucocorticoid-Induced Osteoporosis

Patients on chronic glucocorticoid therapy (≥5 mg prednisone equivalent daily for ≥3 months) should have baseline laboratory testing including the core panel above, as glucocorticoids are a major cause of secondary osteoporosis. 2 Baseline DXA should be obtained within 6 months of starting therapy. 4

Men with Osteoporosis

Men require particular attention to secondary causes, as they are more likely than women to have an identifiable underlying disorder. 2 Testosterone measurement is essential in all men with osteoporosis. 2

HIV-Infected Patients

HIV-infected individuals should have bone densitometry performed with consideration for earlier screening (age 50 years) if they have risk factors for premature bone loss. 2 Standard laboratory evaluation should include the core panel, with particular attention to vitamin D status.

Clinical Pitfalls to Avoid

• Do not skip vitamin D testing: Vitamin D deficiency is extremely common and must be corrected before or concurrent with osteoporosis treatment 1
• Do not order extensive secondary workup reflexively: Target additional testing based on clinical suspicion rather than ordering comprehensive panels on all patients 1
• Do not rely on bone turnover markers for diagnosis: These lack sufficient evidence for routine diagnostic use 3
• Do not forget to assess renal function: This is critical for medication selection and dosing 1