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

Treatment of Osteopenia in Older Adults and Postmenopausal Women

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 for all postmenopausal women or older adults with osteopenia who meet high fracture risk criteria. 1

Risk Stratification Determines Who Gets Treated

Treatment decisions depend entirely on fracture risk assessment, not the osteopenia diagnosis itself. 1, 2

Immediate pharmacologic therapy is mandatory if:

• Any history of fragility fracture exists, regardless of FRAX score—this alone defines high fracture risk requiring treatment 1
• FRAX 10-year risk shows ≥20% for major osteoporotic fracture OR ≥3% for hip fracture 1
• Age ≥65 years with severe osteopenia (T-score < -2.0) 2, 3

For mild osteopenia (T-score -1.0 to -1.5) without additional risk factors:

• Focus on lifestyle modifications and supplementation only 2
• Monitor bone density every 2 years 2

First-Line Pharmacologic Treatment

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. 1 They have the most favorable balance of efficacy, safety, and cost. 1, 3

Specific bisphosphonate options:

• Alendronate 70 mg once weekly (oral) 1, 3
• Risedronate 35 mg once weekly (oral) 1, 3
• Zoledronic acid 5 mg IV annually for patients unable to tolerate oral formulations 1, 3

Women with severe osteopenia (T-score < -2.0) who received risedronate had 73% lower fragility fracture risk compared to placebo. 1

Essential Concurrent Supplementation

All patients must receive calcium 1,200 mg daily and vitamin D 800 IU daily—pharmacologic therapy is significantly less effective without adequate supplementation. 1, 2, 3 Target serum vitamin D level ≥20 ng/mL. 1

Mandatory Lifestyle Modifications

Implement the following for all patients regardless of pharmacologic treatment status: 1

• Weight-bearing exercise and resistance training 1, 2
• Smoking cessation 1
• Limit alcohol intake 1
• Fall prevention strategies 1
• Maintain healthy body weight 1

Evaluate Secondary Causes of Bone Loss

All patients with osteopenia require workup for: 1

• Vitamin D deficiency
• Hypogonadism
• Glucocorticoid exposure
• Malabsorption disorders
• Hyperparathyroidism
• Hyperthyroidism
• Alcohol abuse

Treatment Duration and Monitoring

Initial treatment duration is 5 years with bisphosphonates. 1, 2, 3

Do not monitor bone density during the initial 5-year treatment period—fracture reduction occurs even without BMD increases, and routine monitoring provides no clinical benefit. 1, 2, 3

After 5 years, reassess fracture risk to determine if continued therapy is warranted. 1, 2, 3

Safety Profile

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

Common adverse effects include: 1

• Mild upper GI symptoms
• Influenza-like symptoms
• Myalgias, arthralgias, headaches

Rare but serious adverse effects: 1

• Osteonecrosis of the jaw
• Atypical femoral fractures (risk increases with prolonged use beyond 5 years)

Second-Line Pharmacologic Options

Denosumab 60 mg subcutaneously every 6 months is the recommended alternative for patients with contraindications to or intolerance of bisphosphonates. 1, 3

Critical warning: Never discontinue denosumab abruptly without transitioning to bisphosphonate therapy—abrupt discontinuation is associated with multiple vertebral fractures. 3

Agents to Avoid in Osteopenia

Strongly avoid the following due to unfavorable benefit-harm balance: 1, 3

• Menopausal estrogen therapy
• Estrogen plus progestogen therapy
• Raloxifene (increases venous thromboembolism, pulmonary embolism, and fatal stroke risk)

Teriparatide and romosozumab are reserved for very high-risk osteoporosis (not osteopenia) and should not be used as first-line therapy. 1 These anabolic agents are appropriate only for severe osteoporosis with very high fracture risk. 4

Common Pitfalls to Avoid

• Do not treat based on osteopenia diagnosis alone—always calculate fracture risk first 1, 2
• Do not use calcium or vitamin D as monotherapy—they are insufficient alone for fracture prevention 3
• Do not order routine BMD monitoring during active treatment—it adds no clinical value 1, 2, 3
• Do not continue bisphosphonates indefinitely without reassessing at 5 years—rare adverse effects increase with prolonged use 1, 3