What are the first line treatments for osteoporosis?

First-Line Treatment for Osteoporosis

Bisphosphonates are the first-line pharmacologic treatment for osteoporosis in both postmenopausal women and men, with oral alendronate or risedronate preferred due to strong fracture reduction evidence and low cost. 1, 2, 3

Standard Risk Osteoporosis Treatment Algorithm

Initial Pharmacologic Therapy

• Prescribe oral bisphosphonates (alendronate or risedronate) as first-line treatment for postmenopausal women (strong recommendation, high-certainty evidence) and men (conditional recommendation, low-certainty evidence). 1, 3
• Generic formulations should be prescribed whenever possible due to significantly lower cost with equivalent efficacy. 2, 3
• Zoledronic acid (intravenous) is an alternative bisphosphonate option for patients who cannot tolerate oral formulations. 2, 3
• Do not use ibandronate as first-line therapy because evidence does not demonstrate hip fracture reduction. 1

Bisphosphonate Efficacy

High-certainty evidence demonstrates bisphosphonates reduce:

• Hip fractures by 6 fewer events per 1,000 patients 1
• Clinical vertebral fractures by 18 fewer events per 1,000 patients 1
• Any clinical fracture by 24 fewer events per 1,000 patients 1
• Radiographic vertebral fractures by 56 fewer events per 1,000 patients 1

Treatment Duration and Monitoring

• Treat for 5 years initially, then reassess fracture risk to determine whether to continue or take a drug holiday (strong recommendation, moderate-certainty evidence). 3
• Do not perform bone density monitoring during the 5-year treatment period (weak recommendation, low-quality evidence). 3

Very High-Risk Patients: Modified Algorithm

Defining Very High Risk

Very high-risk criteria include patients with: 4, 3

• Age >74 years
• Recent fracture within 12 months
• Multiple prior osteoporotic fractures
• T-score ≤-3.0
• Fractures despite ongoing bisphosphonate therapy
• High FRAX scores (≥20% for major osteoporotic fracture or ≥3% for hip fracture)

Anabolic-First Strategy for Very High Risk

• Initiate treatment with anabolic agents (teriparatide or romosozumab) before bisphosphonates for very high-risk patients (strong recommendation, high-certainty evidence). 4, 3
• Teriparatide reduces vertebral fractures by 69 per 1,000 patients and any clinical fractures by 27 per 1,000 patients. 4, 3
• Romosozumab is conditionally recommended for very high-risk postmenopausal women, limited to 12 monthly doses due to waning anabolic effect (conditional recommendation, moderate-certainty evidence). 3
• Mandatory transition to bisphosphonates or denosumab after completing anabolic therapy to maintain bone gains. 4, 3

Second-Line Treatment

Denosumab Indications

• Use denosumab 60 mg subcutaneously every 6 months as second-line therapy for patients with contraindications to bisphosphonates or who experience adverse effects (conditional recommendation, moderate-certainty evidence for women, low-certainty evidence for men). 1, 2, 3

Critical Denosumab Warning

• Denosumab discontinuation causes rebound bone loss and multiple vertebral fractures—patients must transition to bisphosphonate therapy after stopping denosumab (high-certainty evidence). 3
• This rebound effect makes denosumab less desirable than bisphosphonates for initial therapy despite similar efficacy. 1

Essential Adjunctive Measures for ALL Patients

Every patient with osteoporosis requires non-pharmacologic interventions: 4, 2, 3

• Calcium 1,000-1,200 mg daily
• Vitamin D 800-1,000 IU daily (targeting serum level ≥20 ng/mL)
• Weight-bearing and muscle resistance exercises
• Balance exercises and fall prevention counseling
• Smoking cessation
• Alcohol reduction to moderate levels

Important Safety Considerations

Bisphosphonate Adverse Effects

• High-certainty evidence shows no difference in serious adverse events or withdrawals compared to placebo in randomized trials. 1
• However, observational studies show increased risk of rare complications (low-certainty evidence): 1
  • Osteonecrosis of the jaw (0.01% to 0.3% incidence, adjusted risk ratio 3.4)
  • Atypical femoral fractures
• These rare events typically occur after 2-3 years of treatment. 1

Administration Requirements

• Oral bisphosphonates must be taken in the fasting state with water at least 30 minutes before consuming food or beverages to ensure adequate absorption. 5
• Once-weekly dosing (alendronate 70 mg, risedronate 35 mg) is therapeutically equivalent to daily dosing and reduces gastrointestinal adverse effects. 6, 5