What are the secondary causes of osteoporosis and which laboratory tests should be ordered to evaluate them?

Secondary Causes of Osteoporosis and Laboratory Evaluation

Secondary causes of osteoporosis should be evaluated in all patients with low bone mineral density using a comprehensive laboratory workup that includes complete blood count, comprehensive metabolic panel, and 25-hydroxyvitamin D level, which together have a 92% sensitivity for detecting underlying conditions. 1

Common Secondary Causes of Osteoporosis

• Endocrine disorders:

  • Hypogonadism (accounts for 40-60% of cases in men) 1
  • Estrogen deficiency (accounts for 35-40% of cases in premenopausal women) 1
  • Hyperparathyroidism 2
  • Hyperthyroidism 2
  • Cushing syndrome 3

• Gastrointestinal disorders:

  • Malabsorption syndromes 3
  • Celiac disease 3
  • Inflammatory bowel disease 3
  • Gastric bypass surgery 3

• Renal disorders:

  • Chronic renal failure 3

• Rheumatologic and inflammatory conditions:

  • Rheumatoid arthritis and other inflammatory arthritides 3

• Other conditions:

  • Prolonged immobilization 3
  • Multiple myeloma 3
  • Chronic alcoholism or established cirrhosis 3
  • Eating disorders (anorexia nervosa, bulimia) 3
  • Organ transplantation 3

• Medication-induced:

  • Glucocorticoids (accounts for 40-60% of cases in men and 35-40% in women) 1
  • Other medications known to adversely affect BMD 3

Laboratory Tests for Secondary Causes

First-line Laboratory Tests (92% sensitivity when combined)

• Basic laboratory tests:
  • Complete blood count 1
  • Comprehensive metabolic panel (including serum calcium, phosphate, albumin, creatinine) 1, 2
  • 25-hydroxyvitamin D level 3, 2

Additional Tests Based on Clinical Suspicion

• Endocrine evaluation:

  • Thyroid function tests (TSH) to rule out hyperthyroidism 2
  • Intact parathyroid hormone (iPTH) for hyperparathyroidism 2
  • Sex hormone levels:
    • Men: serum testosterone, SHBG, LH, FSH 2
    • Women: estradiol, LH, FSH 2

• Inflammatory markers:

  • Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) if inflammatory conditions are suspected 2

• Other tests:

  • 24-hour urine calcium (especially in men) 4
  • Liver function tests (GOT, GPT, gamma-GT) if liver disease is suspected 2
  • Serum and urine protein electrophoresis if multiple myeloma is suspected 5

Imaging Studies

• Dual-energy X-ray absorptiometry (DXA) of lumbar spine and femoral neck is the gold standard for diagnosis 2
• Lateral X-rays of thoracic and lumbar spine to identify vertebral fractures, which may be asymptomatic 2

Clinical Implications

• Secondary causes of osteoporosis are present in 44-90% of patients with low bone mineral density 1
• Older women and men with metabolic disorders associated with secondary osteoporosis have a 2-3 fold higher risk of hip and vertebral fractures 3, 1
• More than one secondary cause can be found in the same patient, even when they already have a known secondary cause 4

Management Approach

1. Identify and treat underlying secondary causes 3
2. For patients with osteopenia, calculate 10-year fracture risk using FRAX tool 3
3. Recommend calcium (1000-1500 mg) and vitamin D (800-1000 IU) daily for all patients with low BMD 3
4. Consider pharmacologic treatment for:
   • Postmenopausal women and men ≥50 years with T-score ≤ -2.5 3
   • Patients with history of fragility fracture 3
   • Patients with osteopenia and 10-year risk of all osteoporotic fracture ≥20% or hip fracture ≥3% 3

Important Caveats

• Laboratory abnormalities in severe vitamin D deficiency (osteomalacia) include low calcium and phosphorus levels, low 25(OH)D levels, and elevated alkaline phosphatase and parathyroid hormone levels 3
• In patients with primary hyperparathyroidism, hyperthyroidism, hypercortisolism, and multiple myeloma, both the secondary cause and its treatment have an impact on BMD and fractures 4
• When interpreting DXA results in premenopausal women and men under 50, z-scores (not t-scores) should be used, with z-scores of -2.0 or less considered below the expected age range 3