What is the best treatment approach for an older adult or postmenopausal woman with osteopenia?

Treatment for Osteopenia

For postmenopausal women or older adults over age 65 with osteopenia, 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 they have high fracture risk—defined as prior fragility fracture, FRAX score ≥20% for major osteoporotic fracture or ≥3% for hip fracture, or T-score approaching -2.5. 1

Risk Stratification Is Mandatory Before Treatment Decisions

The American College of Physicians emphasizes that osteopenia diagnosis alone does not indicate treatment—fracture risk assessment determines management. 1

High-risk osteopenia requiring immediate pharmacologic therapy includes: 1, 2, 3

• Any history of minimal trauma fracture (this alone mandates treatment regardless of FRAX)
• T-score < -2.0 (severe osteopenia near osteoporosis threshold) in women ≥65 years
• FRAX 10-year risk ≥20% for major osteoporotic fracture OR ≥3% for hip fracture
• Long-term glucocorticoid therapy

Low-risk osteopenia NOT requiring pharmacologic therapy includes: 1

• Women <65 years with osteopenia and no risk factors
• Women ≥65 years with mild osteopenia (T-score -1.0 to -1.5) and no additional risk factors
• FRAX scores below treatment thresholds

The 2017 American College of Physicians guideline found that women with severe osteopenia (T-score < -2.0) who received risedronate had 73% lower fragility fracture risk compared to placebo, with effects similar to osteoporosis treatment. 1 The 2023 updated guideline reaffirmed this individualized approach with low-certainty evidence. 1

Universal Non-Pharmacologic Interventions for All Osteopenic Patients

Every osteopenic patient requires these interventions regardless of fracture risk: 2, 3, 4, 5

• Calcium supplementation 1,200 mg daily
• Vitamin D supplementation 800 IU daily (target serum level ≥20 ng/mL)
• Weight-bearing exercise and resistance training
• Smoking cessation
• Limit alcohol intake (≤2 drinks daily)
• Fall prevention strategies
• Maintain healthy body weight

These lifestyle modifications reduce fracture risk independent of pharmacologic therapy with high-certainty evidence. 2

First-Line Pharmacologic Treatment: Oral Bisphosphonates

For high-risk osteopenia, bisphosphonates are the mandatory first-line therapy based on the most favorable balance of efficacy, safety, and cost. 1, 2, 3

Specific bisphosphonate regimens: 1, 2, 3

• Alendronate 70 mg orally once weekly (preferred)
• Risedronate 35 mg orally once weekly
• Zoledronic acid 5 mg IV annually (for patients unable to tolerate oral formulations)

The 2023 American College of Physicians guideline provides high-certainty evidence that bisphosphonates reduce hip fractures by 50% and vertebral fractures by 47-56% over 3 years in postmenopausal women with osteoporosis, with similar benefits expected in high-risk osteopenia. 1, 2 A 2024 review confirmed that oral and intravenous bisphosphonates cost-effectively reduce fractures in older osteopenic women. 6

Critical administration instructions for oral bisphosphonates: 2, 3

• Take on empty stomach with full glass of water
• Remain upright for 30-60 minutes after administration
• Take at least 30 minutes before first food, beverage, or other medication

Treatment Duration and Monitoring Strategy

Initial treatment duration is 5 years with bisphosphonates, after which fracture risk should be reassessed to determine if continued therapy is warranted. 2, 3

Do not monitor bone mineral density during the initial 5-year treatment period—the American College of Physicians found no clinical benefit to routine BMD monitoring during active treatment, and bisphosphonates reduce fractures even without BMD increases. 2, 3

After 5 years, patients at low fracture risk should be considered for drug discontinuation with periodic fracture risk reevaluation. 1

Safety Profile and Adverse Effects

High-certainty evidence from randomized trials shows bisphosphonates cause no difference in serious adverse events compared to placebo at 2-3 years. 1, 2

Common adverse effects (not serious): 3

• Mild upper GI symptoms
• Influenza-like symptoms (especially with IV zoledronic acid)
• Myalgias and arthralgias
• Headaches

Rare but serious adverse effects (higher risk with prolonged use >5 years): 1, 2, 3

• Osteonecrosis of the jaw (risk increases with dental procedures)
• Atypical femoral fractures
• Esophageal irritation or ulceration (oral formulations)

The risk of severe adverse effects increases with prolonged bisphosphonate use, which is why treatment duration is limited and reassessment is required after 5 years. 1

Second-Line Pharmacologic Options

For patients with contraindications to or intolerance of bisphosphonates, denosumab 60 mg subcutaneously every 6 months is the recommended second-line therapy. 1, 3

Critical safety warning for denosumab: Never discontinue denosumab abruptly without transitioning to bisphosphonate therapy—abrupt discontinuation is associated with multiple vertebral fractures in some patients. 1, 2

Denosumab adverse effects include mild GI symptoms, rash/eczema, and increased infection risk. 3

Agents to Avoid in Osteopenia

The American College of Physicians strongly recommends against using menopausal estrogen therapy, estrogen plus progestogen therapy, or raloxifene for osteoporosis or osteopenia treatment due to unfavorable benefit-harm balance. 1, 3 Moderate-quality evidence showed these agents did not reduce fracture risk in postmenopausal women with established osteoporosis and are associated with serious harms including thromboembolism and stroke. 1

Teriparatide and romosozumab are reserved for very high-risk osteoporosis (not osteopenia) and should not be used as first-line therapy. 1 Teriparatide carries a black box warning for osteosarcoma risk based on rat studies. 7

Evaluation for Secondary Causes

All patients with osteopenia require workup for secondary causes of bone loss before initiating treatment: 3

• Vitamin D deficiency (25-OH vitamin D level)
• Hypogonadism (testosterone in men, estrogen status in women)
• Glucocorticoid exposure history
• Malabsorption disorders (celiac disease screening)
• Hyperparathyroidism (serum calcium, PTH)
• Hyperthyroidism (TSH)
• Alcohol abuse assessment

Common Pitfalls to Avoid

Do not treat osteopenia based on T-score alone—this leads to overtreatment of low-risk patients and undertreatment of high-risk patients. Always calculate fracture risk using clinical factors or FRAX. 1, 2

Do not prescribe bisphosphonates without ensuring adequate calcium and vitamin D supplementation—pharmacologic therapy is significantly less effective without adequate supplementation. 2, 3

Do not order routine BMD monitoring during the first 5 years of treatment—this provides no clinical benefit and increases costs unnecessarily. 2, 3

Do not continue bisphosphonates indefinitely without reassessing fracture risk—prolonged use beyond 5-10 years increases risk of rare but serious adverse effects. 1