Osteoporosis Treatment
Bisphosphonates (oral alendronate, risedronate, or IV zoledronic acid) are the first-line treatment for osteoporosis in both postmenopausal women and men, with proven efficacy in reducing hip, vertebral, and nonvertebral fractures. 1, 2
First-Line Treatment: Bisphosphonates
For most patients with osteoporosis, start with oral bisphosphonates or IV zoledronic acid as initial therapy. 1, 2
- Alendronate: 70 mg once weekly or 10 mg daily 2, 3
- Risedronate: 35 mg once weekly, 5 mg daily, 75 mg on two consecutive days per month, or 150 mg monthly 2
- Zoledronic acid: 5 mg IV annually 2
Prescribe generic formulations whenever possible—they cost significantly less with equivalent efficacy. 1, 2
Treat for 5 years initially, then reassess fracture risk to determine whether to continue or take a drug holiday. 1, 2 This recommendation is based on the fact that bisphosphonates remain in bone for extended periods and continue to suppress resorption even after discontinuation. 3
Mechanism and Efficacy
Bisphosphonates bind to bone hydroxyapatite and specifically inhibit osteoclast activity without directly affecting bone formation, though formation eventually decreases as remodeling couples together. 3 They reduce bone resorption markers by 50-70% within 1-6 months and maintain this suppression throughout treatment. 3 Alendronate and risedronate are the best-studied agents, with proven reduction in vertebral, hip, and nonvertebral fractures. 4, 5
Second-Line Treatment: Denosumab
Use denosumab 60 mg subcutaneously every 6 months only for patients with contraindications to bisphosphonates or who experience adverse effects from bisphosphonates. 1, 2
Critical Warning About Denosumab
Never stop denosumab abruptly—discontinuation causes rebound bone loss and multiple vertebral fractures. 1, 2 Patients must transition to bisphosphonate therapy after stopping denosumab. 1, 6 This is high-certainty evidence and represents a major safety concern. 1
Very High-Risk Patients: Anabolic Agents First
For patients at very high risk for fracture, initiate anabolic agents (teriparatide or romosozumab) before bisphosphonates, followed by mandatory transition to bisphosphonates or denosumab. 1, 7
Defining Very High Risk
Very high risk includes patients with: 1, 7, 2
- 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 Agent Options
Teriparatide: 20 mcg subcutaneously daily for up to 24 months 2, 8
- Reduces vertebral fractures by 69 per 1000 patients and clinical fractures by 27 per 1000 patients 1, 7, 2
- FDA-approved for postmenopausal women, men with primary or hypogonadal osteoporosis, and glucocorticoid-induced osteoporosis 8
Romosozumab: Limited to 12 monthly doses due to waning anabolic effect 1, 2
- Conditionally recommended for very high-risk postmenopausal women with moderate-certainty evidence 1, 7
Mandatory Sequential Therapy
After completing anabolic therapy, patients must transition to bisphosphonate or denosumab to maintain bone density gains and prevent rapid bone loss. 7, 2 This is non-negotiable—anabolic gains are lost without subsequent antiresorptive therapy. 2
Essential Adjunctive Measures for ALL Patients
Every patient requires the following regardless of pharmacologic treatment: 1, 7, 2
- Calcium: 1000-1200 mg daily
- Vitamin D: 800-1000 IU daily (target serum level ≥20 ng/mL) 1
- Weight-bearing and muscle resistance exercises
- Balance exercises and fall prevention counseling
- Smoking cessation
- Alcohol reduction
These measures have high-certainty evidence and are mandatory adjuncts to pharmacologic therapy. 1, 2
Treatment Indications
Treat patients with: 1
- T-score ≤-2.5
- T-score between -1.0 and -2.5 with 10-year FRAX risk of major osteoporotic fracture ≥20% or hip fracture ≥3%
- Low-trauma fracture, even if DEXA does not indicate osteoporosis
Monitoring Strategy
Do not perform bone density monitoring during the 5-year pharmacologic treatment period. 1 This recommendation is based on weak evidence but reflects the understanding that bisphosphonates work slowly and continuously. 3
Reassess fracture risk at 5 years to determine continuation versus drug holiday. 1, 2
Agents NOT Recommended
Do not use estrogen therapy, estrogen plus progestogen, or raloxifene for osteoporosis treatment. 2 These agents carry unfavorable risk-benefit profiles including cardiovascular events, thromboembolic complications, and stroke. 2
Common Pitfalls and Caveats
Upper GI adverse events with bisphosphonates: While generally well tolerated, bisphosphonates can cause esophageal irritation. 3, 6, 5 Instruct patients to take with a full glass of water, remain upright for 30 minutes, and take on an empty stomach at least 30 minutes before food or other medications. 3, 9
Rare but serious bisphosphonate complications: Osteonecrosis of the jaw and atypical femur fractures can occur with long-term use. 6 Examine patients' mouths before starting treatment and ensure good dental hygiene. 6
Denosumab rebound: This is the most critical safety issue—never discontinue denosumab without transitioning to bisphosphonates. 1, 2, 6
Infection risk with denosumab: Denosumab may impair immune function and increase risk of serious infections including skin infections, endocarditis, and others. 6