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

Treatment of Osteopenia in Older Postmenopausal Women

For an older postmenopausal woman 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 she meets high fracture risk criteria: prior fragility fracture, FRAX score ≥20% for major osteoporotic fracture, or ≥3% for hip fracture. 1

Risk Stratification Determines Who Gets Treatment

The diagnosis of osteopenia alone does not trigger treatment—fracture risk assessment is mandatory. 1 This is a critical distinction that prevents both overtreatment and undertreatment.

Immediate treatment indications (regardless of FRAX score):

• Any history of fragility fracture (minimal trauma fracture) automatically qualifies for pharmacologic therapy, even with osteopenia, because this represents high fracture risk independent of bone density measurements 1, 2

Treatment thresholds for osteopenia without prior fracture:

• Calculate 10-year fracture risk using the WHO FRAX tool 1, 2, 3
• Initiate bisphosphonates if FRAX shows ≥20% risk of major osteoporotic fracture OR ≥3% risk of hip fracture 1, 2, 3
• Women with severe osteopenia (T-score < -2.0) who received bisphosphonates had 73% lower fragility fracture risk compared to placebo 1

The evidence supporting treatment in high-risk osteopenia is compelling: most fractures actually occur in osteopenic individuals rather than those with osteoporosis, simply because osteopenia is far more prevalent. 4

First-Line Pharmacologic Treatment

Oral bisphosphonates are 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

Specific bisphosphonate options:

• Alendronate 70 mg once weekly (preferred first-line agent) 1, 2, 6
• Risedronate 35 mg once weekly (equally effective alternative) 1, 2
• Zoledronic acid 5 mg IV annually for patients unable to tolerate oral formulations 1

The FDA has approved alendronate for treatment of osteoporosis in postmenopausal women, with demonstrated increases in bone mass and reduction in fractures including hip and spine. 6

Essential Supplementation (Non-Negotiable)

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

Critical implementation details:

• Correct vitamin D deficiency before starting bisphosphonates to prevent bisphosphonate-related hypocalcemia 2
• Target serum 25-hydroxyvitamin D level ≥20 ng/mL 1, 2
• These supplements are not optional adjuncts but essential components of fracture prevention 1

Mandatory Lifestyle Modifications

Weight-bearing and resistance training exercises:

• 30 minutes at least 3 times weekly (walking, jogging, resistance training) 1, 2, 3
• Improves bone density and reduces fall risk 3

Risk factor modification:

• Smoking cessation (accelerates bone loss) 1, 2, 3
• Limit alcohol intake to ≤2 drinks per day 1, 3
• Fall prevention strategies 1
• Maintain healthy body weight 1

Evaluate Secondary Causes of Bone Loss

All patients with osteopenia require workup for secondary causes, including vitamin D deficiency, hypogonadism, glucocorticoid exposure, malabsorption disorders, hyperparathyroidism, hyperthyroidism, and alcohol abuse. 1 Treating these underlying conditions is essential for treatment success.

Treatment Duration and Monitoring Strategy

Initial treatment duration: 5 years with bisphosphonates 1, 3, 6

Do not monitor bone 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. 1 This is an important cost-saving measure that contradicts common practice patterns.

After 5 years:

• Reassess fracture risk to determine if continued therapy is warranted 1, 3
• Patients at low risk for fracture should be considered for drug discontinuation after 3-5 years of use 6
• Patients who discontinue therapy should have their risk for fracture re-evaluated periodically 6

The optimal duration of bisphosphonate use has not been definitively determined, but limiting duration reduces the risk of rare severe adverse effects that increase with prolonged use. 1, 6

Safety Profile and Adverse Effects

Common adverse effects:

• Mild upper GI symptoms, influenza-like symptoms, myalgias, arthralgias, and headaches 1

Rare but serious adverse effects:

• Osteonecrosis of the jaw 1
• Atypical femoral fractures 1

High-certainty evidence from randomized trials shows bisphosphonates cause no difference in serious adverse events compared to placebo at 2-3 years. 1 The risk-benefit ratio strongly favors treatment in high-risk patients.

Second-Line Options for Bisphosphonate Intolerance

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 in some patients. 1 This rebound effect makes denosumab a less desirable first-line option.

Agents to Avoid in Osteopenia

The American College of Physicians strongly recommends against:

• Menopausal estrogen therapy 1
• Estrogen plus progestogen therapy 1
• Raloxifene 1

These agents have an unfavorable benefit-harm balance for osteoporosis treatment. 1

Anabolic agents (teriparatide, romosozumab) are reserved for very high-risk osteoporosis, not osteopenia, and should not be used as first-line therapy. 1 While these agents may be superior to bisphosphonates in severe osteoporosis with vertebral fractures 5, they are not indicated for osteopenia management.

Common Pitfalls to Avoid

• Do not treat based on osteopenia diagnosis alone—always calculate FRAX score first 1
• Do not skip calcium and vitamin D supplementation—bisphosphonates are significantly less effective without them 1
• Do not monitor BMD during the first 5 years of treatment—it provides no clinical benefit and wastes resources 1
• Do not continue bisphosphonates indefinitely without reassessing fracture risk at 5 years 1, 6
• Do not use hormone therapy or raloxifene for osteopenia treatment 1