What is the plan of care for a postmenopausal woman or older adult with osteopenia and a history of low bone density?

Plan of Care for Osteopenia

For postmenopausal women and older adults with osteopenia, the decision to initiate pharmacologic treatment depends entirely on fracture risk assessment—if FRAX shows ≥20% risk of major osteoporotic fracture OR ≥3% risk of hip fracture, or if there is any history of fragility fracture, start oral bisphosphonates immediately; otherwise, focus on calcium, vitamin D, and lifestyle modifications alone. 1, 2

Risk Stratification Determines Treatment Threshold

The critical first step is calculating 10-year fracture risk using the WHO FRAX tool, which combines bone mineral density with clinical risk factors 2. This calculation determines whether pharmacologic therapy is warranted:

• Any history of fragility fracture automatically triggers immediate pharmacologic therapy, even with osteopenia, because this represents high fracture risk independent of FRAX calculations 2
• For osteopenia without prior fracture: Initiate bisphosphonates if FRAX shows ≥20% risk of major osteoporotic fracture OR ≥3% risk of hip fracture 2
• For lower-risk osteopenia: Treatment decisions should be based on discussion of patient preferences, fracture risk profile, and medication benefits/harms/costs 1

Special populations requiring lower treatment thresholds include patients with long-term glucocorticoid therapy, who fracture at higher bone density thresholds and should receive bisphosphonates even with osteopenia 3.

First-Line Pharmacologic Treatment When Indicated

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 1, 2, 4. They have the most favorable balance of efficacy, safety, and cost compared to all alternatives 1, 4.

Specific bisphosphonate options include:

• Alendronate 70 mg once weekly (preferred due to generic availability) 1, 3, 4
• Risedronate 35 mg once weekly 1, 3, 4
• Zoledronic acid 5 mg IV annually for patients unable to tolerate oral formulations 1, 4

Critical administration instructions for oral bisphosphonates: Take with a full glass of water immediately upon rising, remain upright for at least 30 minutes after administration, and take on an empty stomach to minimize esophageal irritation 3, 5.

Essential Supportive Measures for All Osteopenic Patients

Regardless of whether pharmacologic treatment is initiated, all osteopenic patients must receive:

Supplementation

• Calcium 1,200 mg daily 1, 3, 2, 4
• Vitamin D 800 IU daily 1, 3, 2, 4
• Target serum vitamin D level ≥20 ng/mL 2
• Pharmacologic therapy is significantly less effective without adequate supplementation 2, 4

Lifestyle Modifications

• Weight-bearing exercise and resistance training to reduce fall and fracture risk 3, 2, 6, 7
• Smoking cessation 3, 6, 8
• Limit alcohol intake (avoid ≥3 drinks daily) 1, 3, 6
• Fall prevention strategies and home safety evaluation 1, 2
• Maintain healthy body weight (low body weight increases fracture risk) 1, 6

Evaluate and Treat Secondary Causes

All patients with osteopenia require workup for secondary causes of bone loss, including vitamin D deficiency, hypogonadism, glucocorticoid exposure, malabsorption disorders, hyperparathyroidism, hyperthyroidism, and alcohol abuse 2. Addressing these underlying conditions is essential before or concurrent with osteopenia treatment.

Treatment Duration and Monitoring

For patients started on bisphosphonates:

• Initial treatment duration is 5 years 1, 3, 2, 4
• Do not monitor bone density during the initial 5-year treatment period, as this provides no clinical benefit 1, 4
• After 5 years, reassess fracture risk to determine if continued therapy is warranted 1, 3, 2, 4
• Increasing bisphosphonate duration beyond 5 years probably reduces vertebral fractures but not other fractures, at the expense of increased long-term harms 1

Safety Profile and Adverse Effects

High-certainty evidence shows no difference in serious adverse events between bisphosphonates and placebo in randomized controlled trials at 3+ years 1, 2, 4. However, rare but serious adverse effects include:

• Osteonecrosis of the jaw: <1 per 100,000 person-years, with higher risk after longer treatment duration 1, 3, 4
• Atypical femoral fractures: 3.0-9.8 per 100,000 patient-years, with risk increasing with longer treatment duration 1, 3, 4

Second-Line Treatment Options

Denosumab 60 mg subcutaneously every 6 months is reserved as second-line therapy for patients with contraindications to or adverse effects from bisphosphonates 1, 9. However, denosumab is significantly more expensive than generic bisphosphonates and should not be used as first-line therapy 1, 4.

Critical warning: Patients with advanced chronic kidney disease (eGFR <30 mL/min/1.73 m²) are at greater risk of severe hypocalcemia with denosumab and require specialized management 9.

Medications to Avoid

Do not use menopausal estrogen therapy, menopausal estrogen plus progestogen therapy, or raloxifene for osteopenia or osteoporosis treatment, based on strong recommendation with moderate-quality evidence 1.

Cost Considerations

Prescribe generic bisphosphonates whenever possible rather than expensive brand-name medications or newer agents, as they are significantly more cost-effective while maintaining equivalent efficacy 1, 4.