What is the first-line treatment for osteoporosis?

First-Line Treatment for Osteoporosis

Bisphosphonates are the recommended first-line pharmacologic treatment for osteoporosis due to their favorable balance of benefits, harms, patient values and preferences, and cost compared to other osteoporosis medications 1.

Treatment Algorithm Based on Fracture Risk

For Patients with Primary Osteoporosis:

1. First-line therapy: Oral bisphosphonates (alendronate, risedronate)

   • Strong recommendation with high-certainty evidence for postmenopausal women 1
   • Conditional recommendation with low-certainty evidence for men 1
   • Mechanism: Bisphosphonates inhibit osteoclast activity, reducing bone resorption without directly inhibiting bone formation 2

2. Second-line therapy: Denosumab (RANK ligand inhibitor)

   • For patients with contraindications to or who experience adverse effects from bisphosphonates 1
   • Conditional recommendation with moderate-certainty evidence for women 1
   • Conditional recommendation with low-certainty evidence for men 1

3. For very high fracture risk patients:

   • Consider anabolic agents (romosozumab or teriparatide) 1, 3
   • Very high risk defined as: prior osteoporotic fracture OR BMD T-score ≤-3.5 OR FRAX 10-year risk of major osteoporotic fracture ≥30% or hip ≥4.5% 3
   • After anabolic therapy, patients should transition to an antiresorptive agent to maintain bone mineral density gains 3

Efficacy of Bisphosphonates

• Bisphosphonates reduce the risk of vertebral fractures within the first year of treatment 4
• Alendronate and risedronate are the only agents shown in prospective trials to reduce the risk of hip fractures and other nonvertebral fractures 5
• Effects appear early (within 6-12 months) and are sustained 6
• Biochemical markers of bone turnover decrease as early as 1 month after initiation, reaching a plateau at 3-6 months 2, 4

Duration of Treatment

• Consider stopping bisphosphonate treatment after 5 years unless there is a strong indication for continued treatment 1
• Long-term data with alendronate indicate persistence of effects on bone mineral density and bone turnover markers for several years after stopping treatment 6
• The ACP recommends treating osteoporotic women with pharmacologic therapy for 5 years 1

Monitoring During Treatment

• The ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period 1
• Moderate-quality evidence showed that women treated with antiresorptive treatment benefited from reduced fractures even if there was no increase in BMD or if BMD decreased 1

Important Considerations and Potential Adverse Effects

• Bisphosphonates are associated with a higher risk for osteonecrosis of the jaw and atypical femoral fractures, with higher risk after longer treatment duration 1
• Oral bisphosphonates may cause mild gastrointestinal symptoms 1
• The incidence of endoscopically confirmed gastric ulcer is higher with alendronate (13.2%) than with risedronate (4.1%) 4

Supplementation and Lifestyle Modifications

• Calcium (1000-1200 mg daily) and vitamin D (800-1000 IU daily) supplementation should be provided alongside osteoporosis treatment 3
• Lifestyle modifications including regular weight-bearing exercise, smoking cessation, limiting alcohol intake, and maintaining adequate nutrition are recommended 3

Special Populations

• For glucocorticoid-induced osteoporosis: Bisphosphonates are indicated for men and women with osteoporosis associated with sustained systemic glucocorticoid therapy 7
• For patients transitioning from anabolic agents: An antiresorptive agent should be offered after discontinuation to preserve gains and prevent rebound bone loss 1

Bisphosphonates remain the cornerstone of osteoporosis treatment due to their proven efficacy, safety profile, and cost-effectiveness compared to other available options.