What are the recommended biphosphonates (bisphosphonates) for treating osteoporosis?

Recommended Bisphosphonates for Treating Osteoporosis

Bisphosphonates are the first-line pharmacologic treatment for osteoporosis, with oral alendronate, risedronate, and intravenous zoledronic acid being the recommended agents due to their proven efficacy in reducing vertebral, nonvertebral, and hip fractures. 1

First-Line Treatment Options

For Postmenopausal Women with Osteoporosis:

• Oral bisphosphonates:
  • Alendronate: 5 mg daily or 35 mg once-weekly 2, 3
  • Risedronate: 5 mg daily, 35 mg once-weekly, 75 mg on two consecutive days monthly, or 150 mg once-monthly 2
  • Zoledronic acid: IV formulation

For Men with Osteoporosis:

• Oral bisphosphonates:
  • Risedronate: 35 mg once-weekly 2
  • Alendronate (for increasing bone mass)

Efficacy of Recommended Bisphosphonates

The American College of Physicians (ACP) strongly recommends bisphosphonates based on high-certainty evidence showing they effectively reduce fracture risk 1. These agents have demonstrated:

• Vertebral fracture reduction: All approved bisphosphonates reduce relative risk
• Hip fracture reduction: Alendronate, risedronate, and zoledronic acid specifically reduce hip fracture risk 1, 4
• Nonvertebral fracture reduction: Alendronate, risedronate, and zoledronic acid are effective 4

Risedronate has shown particularly rapid efficacy, with significant vertebral fracture risk reduction (62%) observed after just 6 months of treatment 5.

Second-Line Treatment Options

If bisphosphonates are contraindicated or not tolerated:

• Denosumab (RANK ligand inhibitor) is recommended as second-line therapy 1

For patients at very high risk of fracture:

• Romosozumab (sclerostin inhibitor) or teriparatide (recombinant PTH) should be considered 1

Administration Considerations

• Oral bisphosphonates must be taken:
  • With 6-8 ounces of plain water
  • At least 30 minutes before first food, beverage, or medication of the day
  • Patient must remain upright for 30 minutes after taking 2
  • Weekly dosing (e.g., 70 mg alendronate once weekly) offers improved convenience while maintaining therapeutic efficacy 6

Safety Considerations

Potential Adverse Effects:

• Mild gastrointestinal symptoms (common with oral formulations)
• Osteonecrosis of the jaw (rare, risk increases with longer treatment duration)
• Atypical femoral fractures (rare, risk increases with longer treatment duration)
• Zoledronic acid: hypocalcemia, influenza-like symptoms, arthralgia, headache 1

Important Precautions:

• Correct hypocalcemia before initiating therapy
• Ensure adequate calcium (1000-1200 mg) and vitamin D (600-800 IU) intake
• Consider drug discontinuation after 3-5 years in low-risk patients 2
• Monitor for thigh or groin pain (potential sign of atypical femur fracture)
• Avoid in patients with severe renal impairment (creatinine clearance <30-35 mL/min) 3

Treatment Duration

• Treatment should generally continue for 5 years 1
• After 5 years, consider a drug holiday based on individual fracture risk assessment
• Patients initially treated with anabolic agents should receive an antiresorptive agent after discontinuation to preserve bone gains 1

Special Populations

Glucocorticoid-Induced Osteoporosis:

• Oral bisphosphonates are first-line therapy
• Risedronate has shown 70% reduction in vertebral fracture risk in the first year of treatment for patients on long-term glucocorticoid therapy 5

Low Bone Mass (Osteopenia):

• Individualized approach based on fracture risk assessment
• Consider bisphosphonates for women over 65 with osteopenia and elevated fracture risk 1

Bisphosphonates remain the cornerstone of osteoporosis treatment due to their established efficacy, safety profile, and cost-effectiveness compared to newer agents. The choice between specific bisphosphonates should consider patient-specific factors including fracture history, comorbidities, and medication adherence capabilities.