Pharmacological Interventions to Reduce Fracture Risk
Bisphosphonates (alendronate or risedronate) are the first-line pharmacological treatment for reducing fracture risk in elderly patients with osteoporosis or previous fractures, reducing vertebral fractures by 47-48%, non-vertebral fractures by 26-53%, and hip fractures by 51%. 1
First-Line Treatment: Oral Bisphosphonates
Alendronate and risedronate should be prescribed as initial therapy for 3-5 years in patients with osteoporosis or prior fractures. 2, 1 These agents demonstrate:
- 68% relative risk reduction in new vertebral fractures at 3 years 2
- 40% relative risk reduction in hip fractures 2
- 20% relative risk reduction in nonvertebral fractures 2
- Efficacy maintained regardless of age, with bisphosphonates being at least as effective in older patients as younger patients 2
The American College of Physicians specifically recommends bisphosphonates over other agents due to their superior fracture reduction across all sites, cost-effectiveness as generics, and extensive safety data 2, 1, 3.
Second-Line Options
Zoledronic acid (intravenous bisphosphonate) or denosumab should be considered when oral bisphosphonates are not tolerated due to gastrointestinal issues, malabsorption, or non-compliance. 1
Denosumab demonstrated in FDA trials:
- 68% reduction in new vertebral fractures over 3 years 4
- 40% reduction in hip fractures 4
- 20% reduction in nonvertebral fractures 4
Anabolic Agents for Very High-Risk Patients
Teriparatide, abaloparatide, or romosozumab should be first-line treatment for patients at very high fracture risk, defined as recent vertebral fractures, hip fracture with T-score ≤-2.5, or multiple prior fractures. 2, 5, 6
Critical consideration: Patients initially treated with anabolic agents must transition to an antiresorptive agent (bisphosphonate or denosumab) after completion to preserve gains and prevent serious rebound vertebral fractures. 2
Post hoc analysis showed postmenopausal women with prevalent vertebral fractures benefited more from teriparatide than those without prevalent fractures 2.
Essential Adjunctive Therapy
All patients receiving osteoporosis treatment require calcium 1000-1200 mg daily plus vitamin D 800 IU daily, which reduces non-vertebral fractures by 15-20% and falls by 20%. 1, 3, 6
Avoid high-pulse dosages of vitamin D as they increase fall risk 3.
Treatment Duration and Drug Holidays
Bisphosphonates should be continued for 3-5 years initially, with reassessment for drug holiday after 5 years unless the patient remains at high fracture risk. 2, 1
Evidence shows that extending bisphosphonate therapy beyond 3-5 years reduces new vertebral fractures but not other fractures, while increasing risk for long-term harms including atypical subtrochanteric fractures (rate increases from 1.78 per 100,000 at <2 years to >100 per 100,000 at ≥8 years) and osteonecrosis 2.
The decision for temporary bisphosphonate discontinuation should be individualized based on baseline fracture risk, medication type and bone half-life, and balance of benefits versus harms. 2
Special Populations
Glucocorticoid-Induced Osteoporosis
Alendronate, risedronate, and teriparatide all reduce fracture risk in patients taking glucocorticoids. 2, 5
Men with Primary Osteoporosis
Bisphosphonates are recommended as first-line therapy for men with primary osteoporosis, with the same treatment approach as postmenopausal women. 2 Bisphosphonates reduced radiographic vertebral fractures by 140 fewer per 1000 treated patients in men 2.
Patients with Low Bone Mass (Osteopenia)
For postmenopausal women over 65 with low bone mass but not osteoporosis, take an individualized approach to starting bisphosphonates based on fracture risk assessment. 2 Low-certainty evidence suggests zoledronate may reduce clinical vertebral fractures in this population, but benefits must be balanced against harms and costs 2.
Critical Pitfalls to Avoid
- Do not use calcium or vitamin D alone without bisphosphonates in patients with established osteoporosis or prior fractures - calcium or vitamin D monotherapy has uncertain effect on fracture risk 2, 3
- Do not discontinue anabolic agents without immediately starting antiresorptive therapy - this creates serious risk for rebound vertebral fractures 2
- Do not continue bisphosphonates indefinitely without periodic reassessment - atypical fracture risk increases substantially after 8 years 2
- Do not delay osteoporosis treatment in patients with confirmed fractures 3
Comparative Effectiveness
Network meta-analyses show no statistically significant differences among various bisphosphonates, denosumab, or other therapies for fracture prevention 2. Therefore, medication selection should prioritize cost (generic oral bisphosphonates), route preference, and individual contraindications rather than perceived superiority of one agent over another within the same class. 2