Pharmacological Interventions to Reduce Fracture Risk

First-Line Treatment: Oral Bisphosphonates

The American College of Physicians recommends bisphosphonates as first-line treatment for reducing fracture risk in elderly patients with osteoporosis or previous fractures, due to their superior fracture reduction across all sites, cost-effectiveness, and extensive safety data 1, 2, 4
Bisphosphonates should be prescribed as initial therapy for 3-5 years in patients with osteoporosis or prior fractures, reducing vertebral fractures by 47-48%, non-vertebral fractures by 26-53%, and hip fractures by 51% 1, 2
Bisphosphonates demonstrate a 40% relative risk reduction in hip fractures 3
Bisphosphonates demonstrate a 20% relative risk reduction in nonvertebral fractures 3

Zoledronic acid or denosumab should be considered when oral bisphosphonates are not tolerated due to gastrointestinal issues, malabsorption, or non-compliance 1

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
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

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, 4

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 1, 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
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 and osteonecrosis 2, 3

Alendronate, risedronate, and teriparatide all reduce fracture risk in patients taking glucocorticoids 3, 5
Bisphosphonates are recommended as first-line therapy for men with primary osteoporosis, with the same treatment approach as postmenopausal women 6
For postmenopausal women over 65 with low bone mass but not osteoporosis, take an individualized approach to starting bisphosphonates based on fracture risk assessment 6

Do not use calcium or vitamin D alone without bisphosphonates in patients with established osteoporosis or prior fractures, as calcium or vitamin D monotherapy has uncertain effect on fracture risk 3, 4
Do not discontinue anabolic agents without immediately starting antiresorptive therapy, as this creates serious risk for rebound vertebral fractures 2
Do not continue bisphosphonates indefinitely without periodic reassessment, as atypical fracture risk increases substantially after 8 years 2, 3
Do not delay osteoporosis treatment in patients with confirmed fractures 4

Medication selection should prioritize cost, route preference, and individual contraindications rather than perceived superiority of one agent over another within the same class 2