What is the first-line treatment for a postmenopausal woman or older adult with osteoporosis?

Treatment for Osteoporosis

Bisphosphonates (alendronate, risedronate, or zoledronic acid) are the first-line pharmacologic treatment for osteoporosis in postmenopausal women and older adults, based on high-certainty evidence showing they reduce hip fractures by 50% and vertebral fractures by 47-56%. 1, 2

First-Line Treatment: Bisphosphonates

The American College of Physicians strongly recommends bisphosphonates as initial therapy for both postmenopausal women and men with primary osteoporosis. 1 This recommendation is based on:

• Superior efficacy: Bisphosphonates reduce hip fractures by approximately 50% and vertebral fractures by 47-56% over 3 years. 2
• Favorable safety profile: High-certainty evidence shows no difference in serious adverse events compared to placebo in randomized controlled trials. 1, 2
• Cost-effectiveness: Generic formulations are significantly cheaper than alternatives like denosumab, teriparatide, or romosozumab. 1, 2

Specific Bisphosphonate Dosing Options

Choose one of the following regimens 2:

• Alendronate 70 mg once weekly (oral)
• Risedronate 35 mg once weekly (oral)
• Zoledronic acid 5 mg annually (IV infusion)

Essential Supplementation

All patients must receive calcium 1,200 mg daily and vitamin D 800 IU daily, as pharmacologic therapy is less effective without adequate supplementation. 2, 3 This is non-negotiable for treatment success. 1

Treatment Duration and Monitoring

• Initial treatment duration is 5 years, after which fracture risk should be reassessed to determine if continued therapy is warranted. 2, 3
• Do not monitor bone density during the initial 5-year treatment period, as this provides no clinical benefit. 2, 3
• After 5 years of alendronate or 3 years of zoledronic acid, consider a drug holiday for patients at lower risk for fracture, as benefits are retained after discontinuation. 4

Second-Line Treatment: Denosumab

Denosumab is reserved as second-line therapy for patients who have contraindications to or experience adverse effects from bisphosphonates. 1

Key considerations for denosumab:

• Reduces vertebral fractures by 68% and non-vertebral fractures by 19%. 5
• Administered as 60 mg subcutaneous injection every 6 months. 6
• Critical warning: Discontinuation of denosumab leads to rebound bone turnover and increased risk of multiple vertebral fractures; must transition to a bisphosphonate if stopping denosumab. 3, 6

High-Risk Patients: Anabolic Agents First

For patients at very high risk of fracture (history of multiple fractures, very low bone density, or fracture on therapy), consider starting with anabolic agents (teriparatide, abaloparatide, or romosozumab) instead of bisphosphonates. 2, 7

• After completing anabolic therapy, patients must transition to an antiresorptive agent (bisphosphonate or denosumab) to preserve gains and prevent rebound vertebral fractures. 1, 2
• Teriparatide reduces vertebral fractures by 65% and non-vertebral fractures by 53%. 5

Safety Profile and Rare Adverse Effects

Bisphosphonates have an excellent safety profile, but clinicians should be aware of rare complications:

• Osteonecrosis of the jaw: 0.01% to 0.3% incidence, risk increases with longer treatment duration. 2
• Atypical femoral fractures: Rare, associated with longer treatment duration beyond 5 years. 1, 2
• These risks must be balanced against the substantial fracture reduction benefits. 4

Lifestyle Modifications

All patients should receive counseling on 1, 2:

• Weight-bearing and resistance training exercise
• Smoking cessation
• Limiting alcohol intake to 1-2 drinks per day
• Fall prevention strategies and evaluation

Treatment Algorithm for Males

The same approach applies to men with primary osteoporosis 1:

1. First-line: Bisphosphonates
2. Second-line: Denosumab (for contraindications or adverse effects from bisphosphonates)

Special Consideration: Glucocorticoid-Induced Osteoporosis

For patients on chronic glucocorticoid therapy (≥7.5 mg/day prednisone for ≥6 months), oral bisphosphonates remain first-line treatment. 1 For very high-dose glucocorticoids (≥30 mg/day prednisone with cumulative dose >5 gm/year), still use oral bisphosphonates as first-line over other agents. 1

Cost Considerations

Always prescribe generic bisphosphonates when possible rather than expensive brand-name medications or newer agents, as they are significantly more cost-effective while maintaining equivalent efficacy. 1, 2 This is particularly important given the chronic nature of osteoporosis treatment.