What is the diagnostic approach for a patient with osteoporosis, considering their medical history, physical examination, and laboratory tests?

Diagnostic Approach to Osteoporosis

The diagnostic workup for osteoporosis should begin with DXA scanning of the lumbar spine and hip as the primary diagnostic test, combined with a comprehensive clinical assessment for fracture risk factors and laboratory testing to exclude secondary causes. 1

Clinical Assessment

History Taking

Obtain a detailed history focusing on:

• Prior fragility fractures (the strongest predictor of future fractures, and diagnostic of osteoporosis regardless of BMD) 2, 1
• Glucocorticoid use (dose, duration, pattern) 2
• Falls and frailty assessment 2
• Specific risk factors: malnutrition, significant weight loss or low body weight, hypogonadism, secondary hyperparathyroidism, thyroid disease, family history of hip fracture, alcohol use (≥3 units/day), smoking 2
• Medications that contribute to bone loss 2

Physical Examination

Perform a focused examination including:

• Height and weight measurement (without shoes) to detect height loss 2
• Muscle strength testing 2
• Spinal examination for tenderness, deformity, and reduced space between lower ribs and upper pelvis (suggesting undiagnosed vertebral fractures) 2
• Kyphosis assessment 3

Imaging Studies

Primary Diagnostic Test

• DXA of lumbar spine (L1-L4) and hip (femoral neck and total hip) is the gold standard for diagnosis 2, 1
• T-score ≤ -2.5 at the femoral neck, total hip, or lumbar spine establishes the diagnosis of osteoporosis 2, 1
• T-score between -1 and -2.5 indicates osteopenia 2

Alternative Imaging Sites

• Distal one-third radius of the nondominant arm when advanced degenerative changes are present in the spine 1
• Quantitative CT (QCT) of lumbar spine and hip may be considered as an alternative when DXA is limited by degenerative changes 1

Vertebral Fracture Assessment

• Plain radiographs of thoracic and lumbar spine should be performed to detect vertebral fractures, particularly in patients with height loss 2, 1
• Vertebral fracture assessment (VFA) via DXA is recommended, as more than 65% of vertebral fractures are clinically silent 1
• A vertebral compression fracture with minimal or no trauma is diagnostic of osteoporosis regardless of T-score 1

Laboratory Testing for Secondary Causes

Secondary causes of osteoporosis are present in 44-90% of cases in postmenopausal women, premenopausal women, and men <50 years of age. 2

Essential Laboratory Tests

• Comprehensive metabolic panel: assess kidney function (creatinine, BUN) and liver function (ALT, AST, alkaline phosphatase) 1
• 25-hydroxyvitamin D levels: to detect vitamin D deficiency (be aware of seasonal variation and laboratory variability) 2, 4
• Serum calcium and phosphorus: low levels suggest osteomalacia 2
• Parathyroid hormone (PTH): if hyperparathyroidism or secondary hyperparathyroidism is suspected 2, 1
• Alkaline phosphatase: elevated in osteomalacia 2

Additional Tests Based on Clinical Suspicion

• Thyroid function tests: if thyroid disease is suspected 2
• Testosterone or estrogen levels: if hypogonadism is suspected 2
• These tests have 92% sensitivity for detecting secondary causes when no cause is apparent from history and physical examination 2

Fracture Risk Assessment

For Adults ≥40 Years

• Calculate 10-year fracture risk using FRAX (with BMD if available) 2, 5
• Adjust FRAX for glucocorticoid dose: multiply major osteoporotic fracture risk by 1.15 and hip fracture risk by 1.2 if prednisone dose >7.5 mg/day 2
• Treatment threshold: 10-year risk of major osteoporotic fracture ≥20% or hip fracture ≥3% 2

For Adults <40 Years

• BMD testing is indicated if history of previous osteoporotic fracture or other significant risk factors are present 2
• Use Z-scores (comparison to age-matched controls) rather than T-scores to detect secondary causes 1

Common Pitfalls to Avoid

• Do not rely solely on plain radiographs for diagnosis, as radiographic evidence of bone loss is not apparent until 30-40% of bone mass has been lost 1
• Do not overlook secondary causes, particularly in premenopausal women, men under 50, and patients with very low Z-scores 1
• Do not ignore degenerative changes that can falsely elevate BMD measurements in the spine 1
• Do not miss clinically silent vertebral fractures, which represent the majority of vertebral fractures and significantly increase future fracture risk 1
• Recognize that most fragility fractures occur in individuals with T-scores higher than -2.5, so clinical context and fracture history are critical 1

Follow-Up Assessment

• Repeat DXA every 2-3 years in patients with normal BMD or osteopenia not on treatment 2
• Repeat DXA every 1-3 years in high-risk patients (history of fracture, Z-score <-3, >10%/year bone loss, very high-dose glucocorticoids) 2
• Annual clinical fracture risk reassessment for all patients on long-term glucocorticoid therapy 2