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

Osteopenia Treatment

Treatment Decision Algorithm

For postmenopausal women or older adults 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 any of the following high-risk criteria are met: prior fragility fracture, FRAX score ≥20% for major osteoporotic fracture OR ≥3% for hip fracture, or severe osteopenia with T-score <-2.0 in patients age ≥65 years. 1, 2

Risk Stratification Determines Treatment Threshold

• Any history of fragility fracture triggers immediate pharmacologic therapy, even with osteopenia, because this represents high fracture risk that warrants treatment independent of FRAX calculations. 1

• For osteopenia 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. 1

• Women with severe osteopenia (T-score <-2.0) who are age 65 or older should receive bisphosphonate therapy, as this population had 73% lower fragility fracture risk compared to placebo in clinical trials. 2

• Women with mild osteopenia (T-score -1.0 to -1.5) should focus on lifestyle modifications and supplementation only, as the balance of benefits and harms from bisphosphonates is less favorable in this population. 2

• The 2023 American College of Physicians guideline recommends an individualized approach for females over age 65 with low bone mass, balancing benefits with harms and costs based on baseline fracture risk (conditional recommendation, low-certainty evidence). 3

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. 1, 4

• Specific bisphosphonate options include alendronate 70 mg once weekly, risedronate 35 mg once weekly, and zoledronic acid 5 mg IV annually for patients unable to tolerate oral formulations. 1, 2

• Evidence from trials shows that oral and intravenous bisphosphonates cost-effectively reduce fractures in older osteopenic women, with major osteoporotic fracture risks of 10-15% being acceptable indications for treatment with generic bisphosphonates in patients older than 65 years. 5

• 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. 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. 1, 2, 4

• Target serum vitamin D level ≥20 ng/mL, with higher doses of vitamin D (up to 2,000 IU daily) potentially needed in certain populations. 1, 2

Mandatory Lifestyle Modifications

• Implement weight-bearing exercise and progressive resistance training exercises, as combination exercise programs are most effective for improving bone mineral density at the spine. 1, 2

• Smoking cessation, limit alcohol intake to avoid excessive consumption, fall prevention strategies, and maintain healthy body weight for all patients. 1, 4

Evaluate Secondary Causes of Bone Loss

• 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. 1

Treatment Duration and Monitoring Strategy

• Initial treatment duration is 5 years with bisphosphonates, and do not monitor bone density during the initial 5-year treatment period as no clinical benefit has been demonstrated. 1, 2, 4

• After 5 years, reassess fracture risk to determine if continued therapy is warranted; patients at low risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. 1, 4

• Women not on pharmacologic therapy should have their bone density monitored every 2 years, and should be considered for bisphosphonate therapy if their T-score declines to ≤-2.5 (osteoporosis). 2

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, 4

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

• Rare serious adverse effects include osteonecrosis of the jaw and atypical femoral fractures, with risk increasing with prolonged bisphosphonate use beyond 5 years. 1, 4

• Bisphosphonates probably resulted in no differences in withdrawal due to adverse events or risk for atrial fibrillation in RCTs assessing harms at 12-36 months (moderate to low certainty evidence). 3

Second-Line Pharmacologic Option

• Denosumab 60 mg subcutaneously every 6 months is the recommended alternative for patients with contraindications to or intolerance of bisphosphonates. 1, 4

• Critical warning: Never discontinue denosumab abruptly without transitioning to bisphosphonate therapy—abrupt discontinuation is associated with multiple vertebral fractures in some patients. 3, 4

• Adverse effects of denosumab include mild GI symptoms, rash/eczema, and increased infection risk. 1

Agents to Avoid in Osteopenia

• Strongly avoid using menopausal estrogen therapy, estrogen plus progestogen therapy, or raloxifene for osteoporosis or osteopenia treatment due to unfavorable benefit-harm balance. 1

• Teriparatide and romosozumab are reserved for very high-risk osteoporosis (not osteopenia) and should not be used as first-line therapy. 1

Common Pitfalls to Avoid

• Do not treat osteopenia diagnosis alone—fracture risk assessment determines management, as most fractures occur in osteopenic individuals despite their lower individual risk compared to osteoporosis. 5

• Do not routinely monitor BMD during active treatment, as bisphosphonates reduce fractures even without BMD increases. 1

• Do not continue bisphosphonates indefinitely without reassessment—reevaluate fracture risk after 5 years and consider drug holiday in low-risk patients. 4