What are the recommended medications for treating osteoporosis?

Medication Recommendations for Osteoporosis

First-Line Treatment

Bisphosphonates are the recommended first-line pharmacologic treatment for osteoporosis, with alendronate, risedronate, and zoledronic acid being the preferred agents to reduce hip and vertebral fractures. 1

For Postmenopausal Women with Osteoporosis

• Oral bisphosphonates (alendronate or risedronate) or intravenous zoledronic acid should be prescribed as initial therapy to reduce the risk of hip, vertebral, and nonvertebral fractures (strong recommendation, high-certainty evidence). 1

• Alendronate dosing: 70 mg once weekly or 10 mg daily 1

• Risedronate dosing: 35 mg once weekly, 5 mg daily, 75 mg on two consecutive days per month, or 150 mg monthly 1

• Zoledronic acid dosing: 5 mg IV annually for treatment 1

• Treatment duration should be 5 years initially, after which reassessment of fracture risk determines whether to continue or take a drug holiday. 1

For Men with Primary Osteoporosis

• Bisphosphonates are recommended as first-line therapy to reduce vertebral fractures (conditional recommendation, low-certainty evidence). 1

• The same bisphosphonate agents used in women (alendronate, risedronate, zoledronic acid) are appropriate, though evidence is extrapolated primarily from female studies. 1

Second-Line Treatment

Denosumab

• Denosumab 60 mg subcutaneously every 6 months is recommended as second-line therapy for patients with contraindications to bisphosphonates or who experience adverse effects from bisphosphonates. 1

• For postmenopausal women: conditional recommendation with moderate-certainty evidence 1

• For men: conditional recommendation with low-certainty evidence 1

• Critical warning: Denosumab discontinuation causes rebound bone loss and multiple vertebral fractures—patients must transition to bisphosphonate therapy after stopping denosumab. 1

Very High-Risk Patients

Anabolic Agents (Teriparatide and Romosozumab)

For patients at very high risk for fracture, anabolic agents should be considered before or instead of antiresorptive therapy. 1

• Very high risk is defined as: age >74 years, recent fracture within 12 months, multiple prior osteoporotic fractures, T-score ≤-3.0, fractures despite ongoing bisphosphonate therapy, or high FRAX scores. 2

• Teriparatide 20 mcg subcutaneously daily for up to 24 months reduces vertebral fractures by 69 per 1000 patients and any clinical fractures by 27 per 1000 patients (high-certainty evidence). 2, 3

• Romosozumab is conditionally recommended for very high-risk postmenopausal women (limited to 12 monthly doses due to waning anabolic effect). 1

• Mandatory sequential therapy: After completing anabolic therapy, patients must transition to bisphosphonate or denosumab to maintain bone density gains and prevent rapid bone loss. 1, 2

Agents NOT Recommended

Do not use estrogen therapy, estrogen plus progestogen, or raloxifene for osteoporosis treatment (strong recommendation against, moderate-quality evidence). 1

• These agents carry unfavorable risk-benefit profiles including cardiovascular events, thromboembolic complications, and stroke. 1

Treatment Algorithm by Patient Category

Standard Osteoporosis (T-score ≤-2.5 or fragility fracture)

1. Start oral bisphosphonate (alendronate 70 mg weekly or risedronate 35 mg weekly) 1
2. If contraindicated or intolerant → denosumab 60 mg SC every 6 months 1
3. Treat for 5 years, then reassess fracture risk 1

Very High-Risk Osteoporosis

1. Consider teriparatide 20 mcg SC daily for up to 24 months 2, 3
2. Mandatory transition to bisphosphonate after completing teriparatide 2
3. Alternative: romosozumab for 12 months followed by bisphosphonate 1

Glucocorticoid-Induced Osteoporosis

1. Oral bisphosphonates strongly recommended for high or very high fracture risk 1
2. For very high risk: anabolic agents (teriparatide) conditionally recommended over antiresorptives 1

Osteopenia (Low Bone Mass, T-score -1.0 to -2.5)

• Take an individualized approach based on absolute fracture risk, patient preferences, and cost-benefit analysis (conditional recommendation, low-certainty evidence). 1
• Bisphosphonates may reduce fractures in high-risk osteopenic patients but evidence is limited. 1

Critical Safety Considerations

Bisphosphonate Administration Requirements

• Must be taken with at least 4 ounces of plain water on an empty stomach 4
• Patient must remain upright (sitting or standing) for at least 30 minutes after taking oral bisphosphonates 1, 4
• Wait 30 minutes before consuming food, beverages, or other medications 4

Rare but Serious Adverse Events

• Osteonecrosis of the jaw: Risk increases with longer treatment duration; dental examination recommended before starting therapy 1, 4
• Atypical femoral fractures: Higher risk after prolonged use (>5 years); consider drug holiday after 5 years in lower-risk patients 1
• Hypocalcemia: Must be corrected before starting bisphosphonates or denosumab; ensure adequate calcium and vitamin D supplementation 1, 4
• Esophageal adverse events: Contraindicated in patients with esophageal abnormalities or inability to remain upright 4

Drug Holiday Considerations

• After 5 years of bisphosphonate therapy, reassess fracture risk 1
• Patients at low fracture risk may discontinue for 1-2 years (drug holiday) 1
• Patients at persistently high risk should continue therapy beyond 5 years 1

Essential Adjunctive Measures

All patients should receive adequate calcium (1000-1200 mg daily) and vitamin D (800-1000 IU daily) supplementation throughout osteoporosis treatment. 1

Cost Considerations

Prescribe generic bisphosphonates whenever possible rather than brand-name medications, as they are significantly less expensive than other osteoporosis therapies while maintaining equivalent efficacy. 1