What is the first line treatment for osteoporosis?

First-Line Treatment for Osteoporosis

Oral bisphosphonates, specifically alendronate, risedronate, or zoledronic acid, are strongly recommended as first-line therapy for osteoporosis to reduce the risk of hip and vertebral fractures. 1

Treatment Selection Based on Fracture Risk

Treatment decisions should be guided by fracture risk assessment:

Fracture Risk Categories:

• Low Risk: BMD T-score >-2.5 and FRAX 10-year risk of major osteoporotic fracture <10% and hip fracture ≤1%
• Moderate Risk: FRAX 10-year risk of major osteoporotic fracture 10-19% or hip fracture >1% and <3%
• High Risk: BMD T-score ≤-2.5 but >-3.5 OR FRAX 10-year risk of major osteoporotic fracture ≥20% but <30% or hip fracture ≥3% but <4.5%
• Very High Risk: Prior osteoporotic fracture OR BMD T-score ≤-3.5 OR FRAX 10-year risk of major osteoporotic fracture ≥30% or hip ≥4.5% 1

Treatment Algorithm:

1. High Fracture Risk: Oral bisphosphonates (alendronate 70mg weekly or risedronate 35mg weekly) 1, 2
2. Contraindication to Oral Bisphosphonates: IV bisphosphonate (zoledronic acid) or denosumab 1
3. Very High Fracture Risk: Consider anabolic agents (teriparatide, abaloparatide, romosozumab) followed by an antiresorptive agent 1, 3

Efficacy of First-Line Treatments

Bisphosphonates have demonstrated significant efficacy in multiple high-quality studies:

• Fracture Reduction: Alendronate and risedronate reduce the risk of vertebral fractures by 47-56% in postmenopausal women 4
• Hip Fracture Prevention: Only alendronate and risedronate have been shown in prospective trials to reduce the risk of hip fractures 5
• BMD Improvement: Zoledronic acid increases lumbar spine BMD by 6.1% and total hip BMD by 3.8% 1

Duration of Treatment

Treatment with bisphosphonates is generally recommended for 5 years (weak recommendation; low-quality evidence) 1. After this period, reassessment of fracture risk should guide decisions about continuing therapy or taking a drug holiday.

Adjunctive Treatments

All patients with osteoporosis should receive:

• Calcium supplementation: 1,000-1,200 mg daily 1
• Vitamin D supplementation: 800-1,000 IU daily 1
• Weight-bearing exercise: 30 minutes at least 3 days per week 1
• Lifestyle modifications: Smoking cessation and limiting alcohol intake (1-2 drinks per day) 1

Common Pitfalls and Considerations

1. Poor Adherence: 30-50% of patients do not take their medication correctly, which significantly reduces efficacy 1

   • Consider once-weekly formulations (alendronate 70mg, risedronate 35mg) to improve adherence 2

2. Upper GI Side Effects: Bisphosphonates can cause GI adverse events, particularly when not taken as directed 4

   • Patients must take oral bisphosphonates with a full glass of water and remain upright for 30-60 minutes after administration
   • For patients who cannot tolerate oral formulations, IV options should be considered

3. Cost Considerations: Generic medications should be prescribed when possible to improve adherence and reduce cost 1

4. Special Populations: Patients on glucocorticoids require adjustment of FRAX scores (multiply 10-year risk of major osteoporotic fracture by 1.15 and hip fracture by 1.2 for doses >7.5 mg/day) 1

The most recent evidence from the American College of Physicians and American College of Rheumatology strongly supports oral bisphosphonates as the first-line therapy for osteoporosis, with clear benefits for reducing fracture risk and improving bone mineral density 1, 3.