What is the recommended workup and management for a postmenopausal woman or older adult with osteopenia?

Osteopenia Workup and Management

For postmenopausal women and older adults with osteopenia, the workup should include DXA bone density measurement, FRAX score calculation to assess 10-year fracture risk, and laboratory evaluation for secondary causes of bone loss, with treatment decisions based primarily on fracture risk rather than bone density alone. 1, 2

Initial Diagnostic Workup

Bone Density Assessment

• Obtain DXA scan of the lumbar spine, total hip, and femoral neck as the gold standard for diagnosing osteopenia (T-score between -1.0 and -2.5) 1
• DXA provides the most accurate prediction of fracture risk and has been validated for absolute, relative, and lifetime fracture risk at multiple sites 1
• Peripheral bone density testing may identify higher-risk patients but requires confirmation with central DXA 1

Laboratory Evaluation for Secondary Causes

• Screen all osteopenic patients for secondary causes of bone loss including vitamin D deficiency, hypogonadism, hyperthyroidism, hyperparathyroidism, and malabsorption syndromes 2
• Measure serum 25-hydroxyvitamin D levels, with a target of ≥20 ng/mL 2
• Consider additional testing based on clinical suspicion (TSH, calcium, phosphate, alkaline phosphatase, complete blood count, creatinine) 2

Fracture Risk Assessment

• Calculate 10-year fracture risk using the FRAX tool, which incorporates age, sex, BMD, body weight, prior fracture history, parental hip fracture, smoking, glucocorticoid use, rheumatoid arthritis, and alcohol consumption 1, 2
• The FRAX algorithm is country-specific and intended for previously untreated postmenopausal women and men aged 40-90 years 1
• Document history of fragility fractures (fractures from standing height or less), as this significantly increases future fracture risk independent of BMD 1, 3

Risk Stratification and Treatment Thresholds

High-Risk Osteopenia Requiring Treatment

Initiate pharmacologic treatment when any of the following criteria are met:

• 10-year probability of major osteoporotic fracture ≥20% on FRAX 1, 2
• 10-year probability of hip fracture ≥3% on FRAX 1, 2
• History of low-trauma/fragility fracture, regardless of FRAX score or BMD 2
• T-score approaching -2.5 (severe osteopenia with T-score <-2.0) in women ≥65 years 1

The evidence supporting treatment in high-risk osteopenia comes from post-hoc analyses showing that women with advanced osteopenia (T-scores near -2.5) who received bisphosphonates had 73% lower fracture risk compared to placebo, similar to reductions seen in osteoporotic women 1. Most fractures in the population occur in osteopenic women rather than those with osteoporosis, making this a critical target for intervention 3.

Lower-Risk Osteopenia

• Women <65 years with mild osteopenia (T-score between -1.0 and -1.5) without additional risk factors generally do not require pharmacologic treatment 1
• Focus on non-pharmacologic interventions and reassess periodically 1, 2

Universal Non-Pharmacologic Management

All osteopenic patients should receive the following interventions:

• Calcium supplementation: 1000-1200 mg/day (dietary plus supplemental) 1, 2, 4
• Vitamin D supplementation: 600-800 IU/day, with higher doses for those at increased risk of deficiency (age >70, nursing home residents, chronically ill, malabsorption) 1, 2, 4
• Weight-bearing exercise and resistance training to improve bone density and reduce fall risk 2, 5
• Smoking cessation 1, 2
• Limit alcohol consumption to ≤2 drinks per day 1, 2

Pharmacologic Treatment for High-Risk Patients

First-Line Therapy

Oral bisphosphonates are the recommended first-line treatment for postmenopausal women and men ≥50 years meeting treatment thresholds 1, 2:

• Alendronate 70 mg once weekly 4
• Risedronate (alternative oral bisphosphonate) 1

The evidence for bisphosphonates in osteopenia is strongest for reducing vertebral fractures, with zoledronate showing reduction in clinical vertebral fractures in high-risk osteopenic women 1. Generic bisphosphonates are cost-effective in this population when fracture risk is elevated 6.

Administration Instructions for Oral Bisphosphonates

• Take at least 30 minutes before first food, beverage, or medication of the day with plain water only 4
• Swallow with full glass of water (6-8 oz) 4
• Remain upright (do not lie down) for at least 30 minutes after taking medication 4
• Do not take at bedtime 4

Alternative Therapies

For patients intolerant or with contraindications to oral bisphosphonates, consider 1, 2:

• Intravenous bisphosphonates (zoledronic acid)
• Denosumab
• Raloxifene (though associated with increased thromboembolism risk) 1

Avoid menopausal estrogen therapy or estrogen plus progestogen therapy for osteoporosis treatment due to lack of fracture reduction benefit in established osteoporosis and serious harms 1

Treatment Duration and Monitoring

Duration of Therapy

• Treat for 5 years initially with bisphosphonates 1
• After 3-5 years, reassess fracture risk and consider drug discontinuation in patients at low risk for fracture 1, 4
• Patients who discontinue therapy should have fracture risk reevaluated periodically 1, 4

Monitoring During Treatment

• Do not routinely monitor BMD during the initial 5 years of treatment, as fracture reduction occurs even without BMD increases 1
• For untreated low-risk osteopenic patients, repeat DXA every 2-3 years 2
• For patients on treatment or at higher risk, consider DXA every 1-2 years 2

Important Clinical Considerations

Race and Ethnicity

• African-American women have higher average BMD than White women at any given age and lower fracture incidence, making them less likely to benefit from screening at younger ages 1
• Asian women may have lower BMD than White women but paradoxically lower fracture risk, suggesting BMD alone doesn't fully capture fracture risk across populations 1

Common Pitfalls

• Avoid treating osteopenia based on T-score alone without considering overall fracture risk—osteopenia is not a disease but a risk factor 7, 6
• The label "osteopenia" encompasses a wide range of fracture risks and can cause unnecessary anxiety 7
• Over half of all fragility fractures occur in women with osteopenia rather than osteoporosis, making risk stratification critical 3
• Women with osteopenia plus a prevalent fracture have the same fracture risk as women with osteoporosis alone 3

Bisphosphonate Safety

• Bisphosphonates are associated with rare but serious adverse events including atypical subtrochanteric fractures and osteonecrosis of the jaw, particularly with prolonged use 1
• Zoledronic acid carries additional risks of hypocalcemia, influenza-like symptoms, and uveitis 1
• Denosumab discontinuation is associated with multiple vertebral fractures in some patients 1