What investigations are suggested for the work-up of osteoporosis?

Osteoporosis Work-Up Investigations

All patients with suspected or confirmed osteoporosis should undergo laboratory testing to exclude secondary causes, which are present in 32-85% of previously undiagnosed cases. 1

Essential Laboratory Tests

The following laboratory investigations have 92% sensitivity for detecting secondary causes of osteoporosis and should be obtained in all patients: 1

• Complete blood count (CBC) - to screen for hematologic disorders and malignancy 1
• Serum calcium - to identify hypercalcemia or hypocalcemia 1
• Serum phosphorus - to detect phosphate wasting and osteomalacia 1
• Serum creatinine - to assess renal function and chronic kidney disease 1
• Alkaline phosphatase - elevated in osteomalacia and Paget's disease 1
• 25-hydroxyvitamin D [25(OH)D] - vitamin D deficiency is extremely prevalent globally and a major contributor to bone loss 1
• Thyroid-stimulating hormone (TSH) - to exclude hyperthyroidism 1
• Parathyroid hormone (PTH) - elevated in primary hyperparathyroidism and vitamin D deficiency 1

Sex-Specific Testing

For Men

• Serum total or free testosterone - hypogonadism accounts for a substantial proportion of osteoporosis in men and should be assessed in all men undergoing osteoporosis evaluation 1

For Premenopausal Women

• Luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol - to identify clinical estrogen deficiency or primary ovarian failure in the presence of oligomenorrhea or amenorrhea 1

Additional Testing Based on Clinical Suspicion

When specific secondary causes are suspected based on history and physical examination, consider: 1

• Serum protein electrophoresis - if multiple myeloma is suspected
• Tissue transglutaminase antibodies - for celiac disease screening in malabsorption
• 24-hour urinary calcium - to identify idiopathic hypercalciuria
• Cortisol testing - if Cushing's syndrome is suspected
• Liver function tests - for hepatic disorders affecting bone metabolism

Bone Mineral Density Testing

Dual-energy X-ray absorptiometry (DXA) of the hip and lumbar spine is the gold standard for osteoporosis diagnosis and should be obtained in all patients being evaluated for osteoporosis. 2

• DXA should be performed at the proximal femur (hip) and lumbar spine as the recommended diagnostic sites 1
• In settings where DXA is unavailable, alternative methods include quantitative ultrasound (QUS) or calcaneal DXA, though these have lower accuracy (AUC 0.69-0.90 for calcaneal QUS) 1

Vertebral Fracture Assessment

• Review of previous imaging studies (spine radiographs, CT scans, or MRI) should be requested to identify missed vertebral fractures, as clinically silent vertebral fractures are common and would trigger pharmacologic therapy regardless of BMD or FRAX score 1
• Plain radiographs of thoracic and lumbar spine or DXA with vertebral fracture assessment software may be useful in patients with osteopenia and height loss 1

Common Pitfalls to Avoid

The most common secondary causes vary by population: 1

• In men: hypogonadism, alcoholism, and glucocorticoid exposure account for 40-60% of cases
• In premenopausal women: estrogen deficiency and glucocorticoid exposure account for 35-40% of cases
• In HIV-infected patients: low body weight is most frequently linked to low BMD, followed by testosterone/estrogen deficiency and glucocorticoid use

Vitamin D deficiency deserves special attention - when pronounced, it causes osteomalacia with bone pain, muscle weakness, and stiffness, distinguished from asymptomatic osteoporosis by clinical symptoms and biochemical abnormalities (low calcium, low phosphorus, elevated alkaline phosphatase and PTH). 1

Testing Frequency

• If initial DXA does not warrant treatment, repeat testing every 2-5 years depending on proximity to treatment thresholds 1
• Patients on bone loss-inducing medications or with baseline BMD near treatment threshold should have DXA every 2 years or more frequently if medically necessary, but generally not more than annually 1