What labs should be ordered to rule out secondary causes of osteoporosis in a patient?

Laboratory Workup to Rule Out Secondary Causes of Osteoporosis

Order a complete blood count, comprehensive metabolic panel, and 25-hydroxyvitamin D level as your first-line laboratory tests—this combination achieves 92% sensitivity for detecting secondary causes of osteoporosis. 1, 2, 3

First-Line Laboratory Tests (Order for All Patients)

The following tests should be obtained in every patient being evaluated for secondary osteoporosis:

• Complete blood count (CBC) to screen for hematologic disorders and malignancies 1, 2, 4
• Comprehensive metabolic panel including calcium, phosphate, creatinine, and liver function tests to assess bone metabolism, kidney function, and identify metabolic abnormalities 1, 2, 4
• 25-hydroxyvitamin D level to identify vitamin D deficiency, which is extremely common in osteoporosis 1, 2, 4
• Albumin or total protein to correctly interpret calcium levels 2

This initial panel is critical because secondary causes are present in 44-90% of patients with low bone mineral density, making this workup essential rather than optional. 1, 3

Second-Line Tests Based on Clinical Context

Add these tests when specific risk factors or clinical suspicion exists:

Endocrine Evaluation

• Thyroid-stimulating hormone (TSH) to rule out hyperthyroidism 2, 5, 6
• Intact parathyroid hormone (iPTH) to evaluate for hyperparathyroidism, particularly if calcium is elevated or borderline 2, 5, 6
• Testosterone, SHBG, LH, and FSH in men to identify hypogonadism, which accounts for 40-60% of secondary osteoporosis cases in men 2, 3
• Estradiol, LH, and FSH in premenopausal women to identify hypogonadism and premature ovarian failure 2

Additional Testing for Specific Scenarios

• 24-hour urinary calcium, sodium, and creatinine to assess calcium excretion and identify hypercalciuria 4, 5
• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) if inflammatory conditions like rheumatoid arthritis are suspected 2
• Serum protein electrophoresis if multiple myeloma is a concern, particularly in patients with unexplained anemia or elevated calcium 5

High-Risk Populations Requiring Comprehensive Workup

Prioritize complete secondary evaluation in these patients:

• Glucocorticoid users (>3 months duration), as glucocorticoids account for 40-60% of secondary osteoporosis in men and 35-40% in women 1, 3
• Patients with chronic kidney disease 1
• Patients with type 2 diabetes, rheumatoid arthritis, or hyperparathyroidism 1
• Patients on osteoporosis treatment with declining BMD on follow-up DXA scans 1
• All men and premenopausal women with unexplained bone loss or fragility fractures 5
• Patients with Z-scores ≤ -2.0 (or ≤ -2.5 in some guidelines), as this suggests secondary causes 7, 6

Critical Clinical Pitfalls

Do not skip the initial laboratory panel even in postmenopausal women, as secondary causes are still present in a substantial proportion of these patients and failure to identify them may result in continued bone loss despite pharmacologic treatment. 1, 4

The 92% sensitivity of the first-line tests means you will miss approximately 8% of secondary causes with basic testing alone, so maintain clinical vigilance and add targeted tests when the clinical picture suggests specific disorders. 1, 3

In patients with severe vitamin D deficiency, expect to see low calcium and phosphorus, low 25(OH)D, and elevated alkaline phosphatase and parathyroid hormone levels. 1

Older patients with metabolic disorders associated with secondary osteoporosis have a 2-3 fold higher risk of hip and vertebral fractures, making identification and treatment of these conditions critical for reducing morbidity and mortality. 1, 3