What tests are used to evaluate secondary causes of bone loss?

Comprehensive Laboratory Workup for Secondary Causes of Bone Loss

A thorough laboratory evaluation for secondary causes of bone loss should include complete blood count, comprehensive metabolic panel, 25-hydroxyvitamin D level, parathyroid hormone, thyroid-stimulating hormone, 24-hour urine calcium and creatinine, and sex hormone testing appropriate for the patient's gender. 1

Core Laboratory Tests for All Patients

The following tests should be performed in all patients with suspected or confirmed low bone mineral density:

• Complete blood count (CBC) - To screen for hematologic disorders associated with bone loss
• Comprehensive metabolic panel:
  • Creatinine and blood urea nitrogen - To assess kidney function
  • Total calcium, phosphate, and albumin - To evaluate calcium homeostasis
  • Alkaline phosphatase - May be elevated in high bone turnover states
• Serum 25-hydroxyvitamin D level - To identify vitamin D deficiency
• Parathyroid hormone (PTH) - To screen for hyperparathyroidism
• Thyroid-stimulating hormone (TSH) - To identify thyroid dysfunction
• 24-hour urine test for calcium and creatinine - To assess for hypercalciuria 1

Gender-Specific Testing

• For men: Total and free testosterone levels to identify hypogonadism 1
• For premenopausal women with amenorrhea or irregular periods: Estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels 1

Additional Testing Based on Clinical Suspicion

Depending on clinical presentation and risk factors, consider:

• For patients on tenofovir: Calculate fractional excretion of phosphate using simultaneous serum phosphate, creatinine, spot urine phosphate, and creatinine 1
• For suspected celiac disease: Tissue transglutaminase antibodies
• For suspected multiple myeloma: Serum protein electrophoresis and urine for Bence Jones protein
• For suspected Cushing's syndrome: 24-hour urinary free cortisol or overnight dexamethasone suppression test
• For suspected inflammatory conditions: Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)

Bone Turnover Markers

Bone turnover markers can be useful to assess the rate of bone remodeling and to monitor treatment response:

• Bone formation markers: Procollagen type I N-propeptide (P1NP), bone-specific alkaline phosphatase
• Bone resorption markers: C-terminal telopeptide (CTX), deoxypyridinoline 1

Interpretation of Results

Distinguishing Osteoporosis from Osteomalacia

• Osteoporosis: Generally normal laboratory values
• Osteomalacia: May show low calcium and phosphorus levels, low 25(OH)D levels, and elevated alkaline phosphatase and PTH levels 1, 2

Common Secondary Causes and Associated Laboratory Findings

1. Vitamin D deficiency: Low 25(OH)D level (<20 ng/mL)
2. Hyperparathyroidism: Elevated PTH, high or high-normal calcium
3. Hyperthyroidism: Suppressed TSH, elevated free T4
4. Hypogonadism: Low testosterone (men) or estradiol (women)
5. Hypercalciuria: Elevated 24-hour urine calcium
6. Renal dysfunction: Elevated creatinine, abnormal phosphate metabolism

Clinical Implications

The identification of secondary causes of bone loss is crucial because:

1. Treatment of the underlying condition may be sufficient to reduce fracture risk
2. Some secondary causes may require specific treatment approaches beyond standard osteoporosis therapy
3. Untreated secondary causes may limit the effectiveness of osteoporosis medications 3

Remember that laboratory testing should complement a thorough history and physical examination focused on identifying risk factors for secondary osteoporosis, including medications (especially glucocorticoids), lifestyle factors (smoking, alcohol), and comorbid conditions associated with bone loss 1.