How should osteopenia be diagnosed and managed in an at‑risk adult, such as a post‑menopausal woman or older man?

Osteopenia: Diagnosis and Management

Diagnosis

Osteopenia is diagnosed when dual-energy X-ray absorptiometry (DXA) of the lumbar spine, femoral neck, or total hip yields a T-score between -1.0 and -2.5. 1, 2

Who Should Be Screened

• All women ≥65 years should undergo DXA screening at the hip and lumbar spine, regardless of risk factors 1, 2
• Women aged 50-64 years require screening if they have any of the following risk factors 1, 3:
  • Low body weight (<127 lb or 57.6 kg / BMI <20-25 kg/m²) 1, 3
  • Maternal hip fracture after age 50 1
  • Current cigarette smoking 1
  • Prolonged amenorrhea (>1 year before age 42) 1
  • Loss of height or thoracic kyphosis 1
  • Chronic glucocorticoid use (≥5 mg prednisone daily for ≥3 months) 2, 3
• Men ≥70 years should be screened universally 1
• Any individual ≥50 years with a fragility fracture (wrist, hip, spine, proximal humerus, pelvis, distal forearm) requires immediate DXA and treatment consideration, regardless of age 1, 2

Technical Considerations

• DXA must measure both the lumbar spine (L1-L4) and both hips (femoral neck and total hip) 1, 2
• Use the lowest T-score from any measured site to classify bone density status 2
• Do not use T-scores in premenopausal women or men <50 years; instead use Z-scores, with ≤-2.0 considered abnormal 2, 4
• Exclude up to 2 vertebral levels from lumbar spine analysis if falsely elevated by fracture, facet arthritis, or spondylosis; if >2 levels require exclusion, substitute the contralateral hip or distal one-third radius 1

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Management Strategy

The diagnosis of osteopenia alone is NOT an automatic indication for pharmacologic treatment—it requires fracture risk stratification using FRAX. 2, 5

Step 1: Calculate 10-Year Fracture Risk

Use the WHO FRAX tool to calculate 10-year probabilities by entering 2:

• Age, sex, BMI
• Femoral neck BMD (g/cm²)
• Prior fragility fracture (yes/no)
• Parental hip fracture (yes/no)
• Current smoking (yes/no)
• Glucocorticoid use ≥3 months at ≥5 mg prednisone daily (yes/no)
• Rheumatoid arthritis (yes/no)
• Secondary osteoporosis causes (yes/no)
• Alcohol ≥3 drinks/day (yes/no)

Step 2: Determine Treatment Threshold

Initiate pharmacologic therapy for osteopenia when FRAX shows 2:

• 10-year hip fracture risk ≥3%, OR
• 10-year major osteoporotic fracture risk ≥20%

Also treat immediately if the patient has 2, 6:

• Any prior fragility fracture of the hip, vertebra, proximal humerus, pelvis, or distal forearm (this establishes an osteoporosis diagnosis regardless of T-score)

Step 3: First-Line Pharmacologic Treatment

Oral bisphosphonates are first-line therapy 2:

• Alendronate 70 mg orally once weekly, OR
• Risedronate 35 mg orally once weekly or 150 mg once monthly 2

Administration instructions 2:

• Take on an empty stomach with 8 oz plain water
• Remain upright for 30-60 minutes
• Wait ≥30 minutes before eating or taking other medications

Step 4: Alternative Agents

Denosumab 60 mg subcutaneously every 6 months is indicated when 2:

• Severe renal impairment (eGFR <30-35 mL/min) contraindicates bisphosphonates
• Esophageal disorders (stricture, achalasia, Barrett's) preclude oral bisphosphonates
• Patient cannot tolerate bisphosphonates

Critical warning: Upon discontinuation of denosumab, immediately transition to a bisphosphonate to prevent rebound vertebral fractures from rapid bone loss 2

Step 5: Agents to Avoid

Do NOT use for osteopenia or osteoporosis treatment 2:

• Menopausal estrogen therapy
• Estrogen + progestogen
• Raloxifene (selective estrogen receptor modulator)

These agents have inferior benefit-to-harm ratios compared to bisphosphonates 2

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Universal Non-Pharmacologic Interventions

All patients with osteopenia require 2:

• Calcium 1,000-1,200 mg daily (dietary plus supplement)
• Vitamin D 800-1,000 IU daily
• Weight-bearing exercise ≥30 minutes most days (walking, stair climbing, resistance training)
• Fall prevention: home safety assessment, balance training, vision correction
• Mandatory smoking cessation counseling
• Limit alcohol to <3 drinks per day

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Evaluation for Secondary Causes

Before initiating treatment, obtain laboratory studies to identify reversible causes 2:

• Serum 25-hydroxyvitamin D
• Calcium
• Phosphorus
• Parathyroid hormone (PTH)
• Thyroid-stimulating hormone (TSH)
• Complete blood count
• Comprehensive metabolic panel (creatinine, liver enzymes)

Secondary causes are identified in 44-90% of cases, most commonly 2, 3:

• Vitamin D deficiency
• Primary hyperparathyroidism
• Hyperthyroidism (including iatrogenic levothyroxine excess)
• Chronic glucocorticoid use
• Gastrointestinal malabsorption

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Monitoring Strategy

Do NOT perform routine BMD testing during the first 5 years of pharmacologic therapy—evidence does not show outcome benefit 2

If BMD monitoring is clinically indicated (suspected non-adherence, new secondary cause) 2:

• Repeat DXA in 1-2 years using the same scanner and protocol
• Compare absolute BMD values (g/cm²), not T- or Z-scores
• Consider changes significant only if they exceed the facility's least significant change (typically 3-5%)

Perform baseline vertebral fracture assessment (VFA) imaging at initial DXA, as asymptomatic vertebral fractures are the strongest predictor of future fractures 2

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Critical Pitfalls to Avoid

• Do not treat osteopenia based on T-score alone—most fractures occur in the osteopenic range, but treatment requires FRAX-based risk stratification 2, 5
• Do not use lumbar spine BMD in patients with vertebral fractures, severe osteoarthritis, or aortic calcification, as these falsely elevate values 2
• Do not stop denosumab without transitioning to a bisphosphonate—abrupt discontinuation causes rapid bone loss and rebound vertebral fractures 2
• Do not screen women <50 years or men <50 years with T-scores—use Z-scores instead 2, 4
• Do not rely on peripheral DXA, quantitative ultrasound, or quantitative CT for diagnosis—only central DXA of hip and spine is acceptable 2