What are the recommended prescription medications for osteoporosis treatment?

Recommended Prescription Medications for Osteoporosis

Oral bisphosphonates—specifically alendronate or risedronate—are the first-line pharmacologic treatment for osteoporosis in both postmenopausal women and men, with strong evidence for reducing hip, vertebral, and nonvertebral fractures. 1, 2

First-Line Treatment: Oral Bisphosphonates

For patients with osteoporosis at high fracture risk, prescribe oral bisphosphonates as initial therapy:

• Alendronate: 70 mg once weekly or 10 mg daily 2
• Risedronate: 35 mg once weekly, 5 mg daily, 75 mg on two consecutive days monthly, or 150 mg monthly 1, 2, 3

These agents reduce vertebral fractures by approximately 52 per 1000 person-years and hip fractures by 6 per 1000 person-years 4. The American College of Physicians provides a strong recommendation with high-certainty evidence for this approach in postmenopausal women 1, 2. For men with osteoporosis, oral bisphosphonates also carry a strong recommendation as first-line therapy 1.

Critical administration requirements to prevent esophageal complications:

• Take immediately after breakfast (not on an empty stomach) with at least 4 ounces of plain water 3
• Swallow tablets whole—do not chew, cut, or crush 3
• Remain upright (sitting, standing, or walking) for at least 30 minutes after taking the medication 3
• Wait 30 minutes before taking other medications, calcium supplements, antacids, or food 3

Treatment duration: Continue bisphosphonates for 5 years initially, then reassess fracture risk to determine whether to continue or take a drug holiday 1, 2. Evidence suggests that extending beyond 5 years reduces vertebral fractures but not other fractures, while increasing risk for long-term harms 1.

Second-Line Treatment: Intravenous Zoledronic Acid or Denosumab

When oral bisphosphonates are contraindicated or not tolerated:

• Zoledronic acid: 5 mg IV annually 1, 2
• Denosumab: 60 mg subcutaneously every 6 months 1, 2

Denosumab carries a conditional recommendation with moderate-certainty evidence for postmenopausal women and low-certainty evidence for men 1, 2. Zoledronic acid is recommended as second-line therapy for men at high fracture risk 1.

CRITICAL WARNING for denosumab: Discontinuation causes rebound bone loss and multiple vertebral fractures—patients MUST transition to bisphosphonate therapy after stopping denosumab 1, 2. This is not optional; failure to provide sequential antiresorptive therapy results in rapid, severe bone loss 1.

Very High-Risk Patients: Anabolic Agents First

For patients at very high risk for fracture, start with anabolic agents before antiresorptive therapy:

Very high risk is defined as: 2

• Age >74 years
• Recent fracture within 12 months
• Multiple prior osteoporotic fractures
• T-score ≤-3.0
• Fractures despite ongoing bisphosphonate therapy
• High FRAX scores

Anabolic agent options:

• Teriparatide: 20 mcg subcutaneously daily for up to 24 months 2, 5
  • Reduces vertebral fractures by 69 per 1000 patients and any clinical fractures by 27 per 1000 patients 5
• Romosozumab: Limited to 12 monthly doses due to waning anabolic effect (conditional recommendation for very high-risk postmenopausal women) 2
• Abaloparatide: Considered appropriate first-line treatment for men with osteoporosis at very high risk (weak recommendation based on BMD data) 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, 5. This is high-certainty evidence and non-negotiable 2.

Agents NOT Recommended

The American College of Physicians strongly recommends AGAINST:

• Estrogen therapy 1, 2
• Estrogen plus progestogen 1, 2
• Raloxifene 1, 2

These agents carry unfavorable risk-benefit profiles including cardiovascular events, thromboembolic complications, and stroke 2.

Essential Adjunctive Measures

All patients must receive adequate supplementation throughout treatment:

• Calcium: 1000-1200 mg daily 1, 2, 4
• Vitamin D: 600-1000 IU daily 1, 2, 4

This carries a strong recommendation with high-certainty evidence 2. Vitamin D and calcium repletion should be ensured in all men above age 65 years 1.

Take calcium supplements, antacids, magnesium-based supplements, iron preparations, and laxatives at a different time of day, as they interfere with bisphosphonate absorption 3.

Cost Considerations

Prescribe generic bisphosphonates whenever possible rather than brand-name medications—they are significantly less expensive than other osteoporosis therapies while maintaining equivalent efficacy 1, 2.

Common Pitfalls to Avoid

• Do NOT prescribe alendronate to patients with GFR <35 mL/min/1.73m² 6
• Do NOT discontinue denosumab without follow-up bisphosphonate therapy—this causes rebound bone loss and multiple vertebral fractures 1, 6, 2
• Do NOT allow patients to lie down within 30 minutes of taking oral bisphosphonates—this increases risk of esophageal irritation 6, 3
• Do NOT prescribe oral bisphosphonates to patients with esophageal problems or inability to remain upright for 30 minutes 3
• Do NOT use combination therapy—it is not recommended 6
• Do NOT stop anabolic therapy without transitioning to antiresorptive therapy—this results in rapid bone loss and increased fracture risk 1, 2, 5