What is the diagnostic approach for osteoporosis?

Diagnostic Approach for Osteoporosis

Dual-energy X-ray absorptiometry (DXA) of the hip and lumbar spine is the gold standard for diagnosing osteoporosis, with diagnosis based on WHO criteria: T-score ≤ -2.5 indicates osteoporosis, T-score between -1.0 and -2.4 indicates osteopenia, and T-score > -1.0 is normal. 1, 2

Who Should Be Screened

Women

• All women age 65 years and older 1
• Women younger than 65 years with risk factors including: estrogen deficiency, maternal hip fracture after age 50, low body weight (<127 lb or 57.6 kg), history of amenorrhea (>1 year before age 42), current smoking, or loss of height/thoracic kyphosis 1

Men

• Men age 70 years and older 1
• Men younger than 70 years with risk factors including: age >70 years, low BMI (<20-25 kg/m²), weight loss (>10%), physical inactivity, oral corticosteroid use, androgen deprivation therapy, or previous fragility fracture 1

Universal Indications (Any Age, Either Sex)

• Individuals with bone mass osteopenia or fragility fractures on imaging (radiographs, CT, or MRI) 1
• Anyone age 50+ who develops wrist, hip, spine, or proximal humerus fracture with minimal/no trauma 1
• Anyone with one or more insufficiency fractures 1
• Monitoring effectiveness of osteoporosis drug therapy 1

Diagnostic Testing Algorithm

Step 1: DXA Bone Densitometry

• Primary sites: Measure BMD at proximal femur (hip) and lumbar spine 1, 2
• Interpretation using T-scores (for postmenopausal women and men ≥50 years): 1
  • Normal: T-score > -1.0
  • Osteopenia: T-score -1.0 to -2.4
  • Osteoporosis: T-score ≤ -2.5
• Z-scores should be used for premenopausal women, men <50 years, and children 3
• DXA has 90-95% sensitivity for detecting osteoporosis 2

Step 2: Fracture Risk Assessment (for Osteopenia)

• For patients with T-scores between -1.0 and -2.4, use FRAX tool to calculate 10-year fracture probability 1, 4
• FRAX factors: hip BMD, age, gender, height, weight, family history of hip fracture, smoking, steroid use >3 months, rheumatoid arthritis, alcohol use 1
• Treatment thresholds: 10-year probability of hip fracture ≥3% OR 10-year probability of major osteoporotic fracture ≥20% 1

Step 3: Essential Laboratory Evaluation

All patients with suspected or confirmed osteoporosis require laboratory testing to exclude secondary causes (present in 32-85% of cases): 2

• Complete blood count (CBC) 2
• Serum calcium 2
• Serum phosphorus 2
• Serum creatinine 2
• Alkaline phosphatase 2
• 25-hydroxyvitamin D [25(OH)D] 2
• Thyroid-stimulating hormone (TSH) 2
• Parathyroid hormone (PTH) 2

This panel has 92% sensitivity for detecting secondary causes of osteoporosis. 2

Step 4: Sex-Specific Testing

• Men: Assess for hypogonadism (testosterone levels) 2
• Premenopausal women: Evaluate for clinical estrogen deficiency or primary ovarian failure 2

Step 5: Additional Testing Based on Clinical Suspicion

• Suspected multiple myeloma: Serum protein electrophoresis (80-90% sensitivity) 2
• Suspected malabsorption: Tissue transglutaminase antibodies for celiac disease (90-95% sensitivity) 2
• Suspected Cushing's syndrome: Cortisol testing (95-100% sensitivity) 2

Step 6: Vertebral Fracture Assessment

• Review previous imaging studies (spine radiographs, CT, MRI) to identify missed vertebral fractures (80-90% sensitivity) 2
• Consider plain radiographs of thoracic/lumbar spine or DXA with vertebral fracture assessment software in patients with osteopenia and height loss 2

Alternative Screening Tests (Limited Role)

Calcaneal Ultrasonography

• At T-score threshold of -1.0: 75% sensitivity, 66% specificity for DXA-determined osteoporosis 1
• Not sufficiently sensitive or specific to replace DXA for diagnosis 1
• May predict fractures independently but treatment trials have not established effectiveness of therapy based on ultrasonography diagnosis 1

Osteoporosis Self-Assessment Tool (OST)

• Formula: (weight in kg - age in years) × 0.2 1
• At risk score of -1: 81% sensitivity, 68% specificity for DXA-determined osteoporosis 1
• Not recommended as substitute for DXA 1

Quantitative CT (QCT)

• Provides volumetric BMD (vs. areal BMD from DXA) 1
• WHO T-scores do not apply to QCT 1
• ACR defines osteopenia as 80-120 mg/mL and osteoporosis as <80 mg/mL 1
• More expensive and less widely available than DXA 1

Follow-Up Testing Intervals

• If initial DXA does not warrant treatment: Repeat every 2-5 years depending on proximity to treatment thresholds 2
• Patients on bone loss-inducing medications or baseline BMD near treatment threshold: DXA every 2 years or more frequently if medically necessary 2

Critical Pitfalls to Avoid

• Don't miss secondary causes: Most common include hypogonadism and glucocorticoid exposure in men; estrogen deficiency and glucocorticoid exposure in premenopausal women 2
• Don't overlook vitamin D deficiency: Present in 32-85% of osteoporotic patients; causes osteomalacia with bone pain, muscle weakness, and stiffness 2
• Don't use T-scores in wrong populations: Use Z-scores for premenopausal women, men <50 years, and children 3
• Don't rely on alternative tests alone: Calcaneal ultrasonography and OST are not sufficiently accurate to replace DXA for diagnosis 1
• Don't forget vertebral fracture assessment: Up to 80% of vertebral fractures are clinically silent 5