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

Treatment of Osteopenia in Older Postmenopausal Women

Treatment Decision Based on Fracture Risk Assessment

The decision to treat osteopenia with pharmacologic therapy depends entirely on fracture risk, not the osteopenia diagnosis itself—treatment is indicated for women ≥65 years with 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, 2

Risk Stratification Algorithm

• Any history of fragility fracture automatically triggers pharmacologic treatment, regardless of FRAX calculations, because this represents high fracture risk that warrants immediate intervention. 2

• For osteopenic patients without prior fracture, calculate 10-year fracture risk using the WHO FRAX tool and initiate pharmacologic therapy if FRAX shows ≥20% risk of major osteoporotic fracture OR ≥3% risk of hip fracture. 2

• Women with severe osteopenia (T-score < -2.0) benefit most from treatment, with 73% lower fragility fracture risk compared to placebo when treated with bisphosphonates—similar to fracture reductions seen in osteoporosis treatment. 1, 2

• Women with mild osteopenia (T-score between -1.0 and -1.5) benefit less and treatment should be reserved for those with additional high-risk factors including lower body weight, smoking, weight loss, family history of fractures, decreased physical activity, or alcohol/caffeine use. 1

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, with the most favorable balance of efficacy, safety, and cost. 2, 3

Specific Bisphosphonate Regimens

• Alendronate 70 mg once weekly is the preferred first-line option. 2, 4, 3

• Risedronate 35 mg once weekly is an equivalent alternative to alendronate. 2, 4, 3

• Zoledronic acid 5 mg IV annually is reserved for patients unable to tolerate oral formulations. 2, 3

Critical Administration Instructions

• Take oral bisphosphonates 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. 4

Essential Supplementation (Non-Negotiable)

All patients must receive calcium 1,200 mg daily and vitamin D 800 IU daily, as pharmacologic therapy is significantly less effective without adequate supplementation. 2, 4, 3

• Target serum vitamin D level ≥20 ng/mL to ensure adequate bone mineralization. 2

• Dosages should be carefully monitored because excess calcium supplementation has been associated with hypercalcemia and increased kidney stones. 1

Mandatory Lifestyle Modifications

• Weight-bearing exercise and resistance training reduce fall and fracture risk in all osteopenic patients. 2, 4, 3

• Smoking cessation and limiting alcohol intake are essential interventions to reduce fracture risk. 2, 4, 3

• Fall prevention strategies including home safety assessment and balance training should be implemented. 2

• Maintain healthy body weight as low body weight increases fracture risk. 1, 2

Evaluate 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

• Patients with long-term glucocorticoid therapy require treatment at higher bone density thresholds because they fracture at higher BMD levels than other patients. 4

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, 4, 3

• Do not monitor bone density during the initial 5-year treatment period as routine BMD monitoring provides no clinical benefit during active treatment. 2, 3

• 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. 2

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. 2, 3

• Common adverse effects include mild upper GI symptoms, influenza-like symptoms, myalgias, arthralgias, and headaches. 1, 2

• Rare but serious adverse effects include osteonecrosis of the jaw (<1 per 100,000 person-years) and atypical femoral fractures (3.0-9.8 per 100,000 patient-years), with risk increasing with longer treatment duration. 2, 4, 3

Second-Line Pharmacologic Options

• Denosumab 60 mg subcutaneously every 6 months is the recommended second-line therapy for patients with contraindications to or intolerance of bisphosphonates. 2, 3

• Never discontinue denosumab abruptly without transitioning to bisphosphonate therapy—abrupt discontinuation is associated with multiple vertebral fractures in some patients. 2

• Denosumab adverse effects include mild GI symptoms, rash/eczema, and increased infection risk. 1, 2

Agents to Avoid

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 including increased risk for cerebrovascular accidents, venous thromboembolic events, and breast cancer. 1, 2

• Teriparatide and romosozumab are reserved for very high-risk osteoporosis (not osteopenia) and should not be used as first-line therapy in osteopenic patients. 2

Common Pitfalls to Avoid

• Do not treat based on osteopenia diagnosis alone—fracture risk assessment determines management, not the T-score in isolation. 2, 5

• Do not prescribe expensive brand-name medications or newer agents when generic bisphosphonates are available, as they are significantly more cost-effective while maintaining equivalent efficacy. 3

• Do not forget calcium and vitamin D supplementation—pharmacologic therapy effectiveness is substantially reduced without adequate supplementation. 2, 4, 3

• Do not continue bisphosphonates indefinitely without reassessment—evaluate fracture risk after 5 years to determine if continued therapy is warranted. 2, 4, 3