How should I evaluate and manage osteopenia in a post‑menopausal woman with risk factors such as low body weight, smoking, alcohol use, and glucocorticoid therapy, using DXA, FRAX, laboratory testing, lifestyle measures, calcium/vitamin D supplementation, and appropriate pharmacologic therapy?

Management of Osteopenia in Post-Menopausal Women with Risk Factors

Initiate oral bisphosphonates (alendronate 70 mg weekly or risedronate 35 mg weekly) combined with calcium 1,200 mg daily and vitamin D 800 IU daily if this patient meets high fracture-risk criteria: prior fragility fracture, FRAX ≥20% for major osteoporotic fracture or ≥3% for hip fracture, or chronic glucocorticoid use ≥7.5 mg prednisone daily for ≥3 months. 1

Initial Evaluation and Risk Stratification

Obtain DXA Scan and Calculate FRAX Score

• Perform dual-energy x-ray absorptiometry (DXA) of the lumbar spine, total hip, and femoral neck to establish baseline bone mineral density and confirm osteopenia (T-score between -1.0 and -2.5). 2
• Calculate 10-year fracture risk using the WHO FRAX tool, which incorporates age, sex, body weight, prior fracture history, parental hip fracture, current smoking, glucocorticoid use, and alcohol consumption (≥3 units/day). 2, 1
• Any history of fragility fracture (minimal-trauma fracture from standing height or lower) mandates immediate pharmacologic therapy regardless of FRAX score or T-score, because prior fracture represents very high risk independent of bone density. 1, 3

Screen for Vertebral Fractures

• If the patient reports height loss >4 cm (>1.5 inches) or self-reported prior vertebral fracture, obtain DXA vertebral fracture assessment (VFA) or thoracic/lumbar spine radiographs to detect silent vertebral compression fractures. 2, 1
• The presence of vertebral fractures mandates pharmacologic treatment irrespective of FRAX score, as two-thirds of vertebral fractures are clinically silent but predict future fractures at all sites. 2

Laboratory Testing for Secondary Causes

• Order serum calcium, phosphorus, 25-hydroxyvitamin D, alkaline phosphatase, parathyroid hormone, serum creatinine, and complete blood count to detect secondary causes of bone loss (this panel has 92% sensitivity). 1
• Specifically evaluate for: vitamin D deficiency (<20 ng/mL), hyperparathyroidism, hyperthyroidism, hypogonadism/premature menopause, malabsorption disorders, chronic kidney disease, and alcohol abuse. 2, 1
• Document glucocorticoid exposure history: doses ≥5 mg prednisone daily for ≥3 months significantly increase fracture risk and lower treatment thresholds. 2, 1

Treatment Decision Algorithm

High-Risk Criteria Requiring Pharmacologic Therapy

Initiate bisphosphonates if ANY of the following are present:

• Prior fragility fracture (hip, spine, wrist, shoulder, proximal humerus, pelvis, or distal forearm from minimal trauma). 1, 3
• FRAX 10-year risk ≥20% for major osteoporotic fracture OR ≥3% for hip fracture. 2, 1
• Chronic glucocorticoid therapy ≥7.5 mg prednisone daily for ≥3 months (this mandates immediate treatment even with osteopenia). 1
• Severe osteopenia (T-score <-2.0) plus additional risk factors such as low body weight (<127 lb or BMI <19 kg/m²), parental hip fracture, current smoking, or alcohol ≥3 units/day. 1, 4

Low-Risk Criteria: Defer Pharmacologic Therapy

• If FRAX <20% for major osteoporotic fracture AND <3% for hip fracture, AND no prior fragility fracture, AND T-score >-2.0, defer pharmacologic therapy. 2, 1
• Repeat DXA in 2 years (or 1 year if additional risk factors develop or glucocorticoid therapy is initiated). 2, 5

Universal Non-Pharmacologic Management (All Patients)

Calcium and Vitamin D Supplementation

• Prescribe calcium 1,200 mg daily (combined from diet and supplements) for all osteopenic patients. 2, 1, 6
• Prescribe vitamin D 800 IU daily, targeting serum 25-hydroxyvitamin D ≥20 ng/mL. 2, 1, 6
• For documented vitamin D deficiency (<20 ng/mL), use high-dose repletion: vitamin D₂ 50,000 IU weekly for 8–12 weeks followed by monthly dosing, or vitamin D₃ 2,000 IU daily for 12 weeks then 1,000–2,000 IU daily for maintenance. 1
• Pharmacologic therapy is significantly less effective without adequate calcium and vitamin D supplementation—this is mandatory, not optional. 1, 6

Lifestyle Modifications

• Smoking cessation is mandatory because tobacco accelerates bone loss and increases fracture risk by approximately two-fold. 2, 1
• Limit alcohol to ≤1–2 standard drinks per day (≤3 units/day); excessive alcohol consumption is a modifiable risk factor for fractures. 2, 1
• Weight-bearing aerobic exercise (walking, jogging) for ≥30 minutes on ≥3 days per week improves bone mineral density. 1, 6
• Resistance and muscle-strengthening exercises reduce fall risk by 23% and support bone health. 1, 6
• Balance-training programs further diminish fall likelihood, especially in older adults. 1
• Maintain healthy body weight (BMI ≥19 kg/m²); low body weight is an independent fracture risk factor. 2, 1

Pharmacologic Therapy for High-Risk Patients

First-Line Treatment: Oral Bisphosphonates

• Oral bisphosphonates are the mandatory first-line therapy based on high-certainty evidence showing 50% reduction in hip fractures and 47–56% reduction in vertebral fractures over 3 years, with the most favorable balance of efficacy, safety, and cost. 1, 5, 6
• Alendronate 70 mg once weekly is the preferred regimen. 2, 1
• Risedronate 35 mg once weekly is an alternative option; in patients with severe osteopenia (T-score <-2.0), risedronate reduced fragility fractures by 73% versus placebo. 1, 4
• Administration instructions: Take on an empty stomach with 8 oz plain water, 30–60 minutes before food or other medications; remain upright for 30 minutes after dosing; separate from calcium supplements by at least 2 hours (calcium inactivates bisphosphonates). 1

Second-Line Treatment: IV Bisphosphonate or Denosumab

• Zoledronic acid 5 mg IV once yearly is recommended for patients unable to tolerate oral bisphosphonates (esophageal disorders, inability to remain upright). 2, 1
• Denosumab 60 mg subcutaneously every 6 months is indicated for patients with contraindications to bisphosphonates or severe renal impairment (eGFR <35 mL/min). 2, 1, 6
• Critical warning: Never discontinue denosumab abruptly without transitioning to bisphosphonate therapy—abrupt discontinuation causes rebound bone loss and multiple vertebral fractures in some patients. 1

Treatment Duration and Monitoring

• Initial bisphosphonate treatment duration is 5 years. 2, 1, 5
• Do not monitor bone density during the initial 5-year treatment period—bisphosphonates reduce fractures even when BMD does not increase or actually decreases, and routine monitoring provides no clinical benefit. 1, 5
• After 5 years, reassess individual fracture risk using FRAX to determine whether to continue, pause, or switch therapy. 1, 5
• Bone density assessment should not be conducted more frequently than annually. 2, 6

Adverse Effects to Monitor

• Common, non-serious effects: Mild upper GI irritation (dyspepsia, esophagitis), influenza-like symptoms after IV zoledronic acid, myalgias, arthralgias, headache. 1
• Rare but serious effects: Osteonecrosis of the jaw (risk <1 in 10,000 patient-years) and atypical subtrochanteric femoral fractures (risk <1 in 1,000 patient-years with prolonged use >5 years). 1, 6
• Denosumab-specific: Rash/eczema, increased infection risk (particularly skin and urinary tract infections). 1

Agents Strongly Contraindicated

The American College of Physicians strongly recommends AGAINST the following agents due to unfavorable benefit-harm balance:

• Menopausal estrogen therapy—increases risk of stroke, venous thromboembolism, and breast cancer. 1, 5
• Estrogen plus progestogen therapy—higher incidence of invasive breast cancer and breast-cancer mortality. 1, 5
• Raloxifene—elevated risk of thromboembolic events, pulmonary embolism, cerebrovascular death, and hot flashes. 1, 5
• Teriparatide and romosozumab are reserved for very high-risk osteoporosis (T-score ≤-2.5 with multiple fractures or recent vertebral/hip fracture) and should not be used as first-line therapy for osteopenia. 1

Special Considerations for This Patient's Risk Factors

Glucocorticoid Exposure

• If this patient is taking ≥5 mg prednisone daily for ≥3 months, she meets criteria for immediate bisphosphonate therapy regardless of FRAX score or T-score. 2, 1
• Glucocorticoid-induced osteoporosis causes rapid bone loss and fractures occur at higher T-scores than postmenopausal osteoporosis. 2

Smoking and Alcohol

• Current smoking and alcohol ≥3 units/day are both incorporated into FRAX calculations and significantly increase fracture risk independent of BMD. 2, 1
• These modifiable risk factors must be addressed through counseling and cessation programs as part of comprehensive management. 2, 1

Low Body Weight

• Body weight <127 lb (58 kg) or BMI <19 kg/m² is an independent risk factor that increases FRAX scores and may lower treatment thresholds even with moderate osteopenia. 2, 1

Common Pitfalls to Avoid

• Do not treat based on T-score alone—osteopenia (T-score -1.0 to -2.5) without high fracture risk does not warrant pharmacologic therapy, as the number needed to treat exceeds 100. 4
• Do not start bisphosphonates without ensuring adequate calcium and vitamin D—supplementation is mandatory for drug efficacy. 1, 6
• Do not monitor BMD annually during treatment—this provides no clinical benefit and may lead to inappropriate treatment changes. 1, 5
• Do not combine two osteoporosis medications simultaneously—there is no fracture reduction data supporting combination therapy, and it increases cost and adverse effects. 6
• Do not use anabolic agents (teriparatide, romosozumab) for osteopenia—these are reserved for very high-risk osteoporosis only. 1