Can bisphosphonates (e.g. alendronate or zoledronic acid) be started in an older adult patient with a history of fracture and osteoporosis, considering their medical history and risk factors?

Can You Start Bisphosphonate if Fracture?

Yes, bisphosphonates should be started immediately in patients with a history of osteoporotic fracture, as this defines them as high-risk and represents a strong indication for treatment. 1

High-Risk Patients with Prior Fracture: Strong Indication for Treatment

Patients with a history of osteoporotic fracture are explicitly defined as high-risk and have a strong indication for bisphosphonate therapy. 1 The American College of Physicians provides a strong recommendation for bisphosphonates in postmenopausal women with osteoporosis and prior fracture, based on high-certainty evidence. 1, 2

Fracture Risk Reduction Benefits

Bisphosphonates demonstrate robust fracture prevention in high-risk patients:

• Vertebral fractures reduced by 50% over 3 years in patients with prior fractures 1, 2
• Hip fractures reduced by 40-53% in postmenopausal women with osteoporosis 3
• Clinical vertebral fractures reduced by 47-56% in women with existing vertebral fractures 4
• Any clinical fractures reduced by 24 fewer events per 1000 patients at 36+ months 1

The evidence supporting bisphosphonates for fracture prevention is rated as high-certainty for patients with established osteoporosis and prior fractures. 1, 2

First-Line Treatment Selection

Oral bisphosphonates (alendronate or risedronate) should be prescribed as initial therapy for patients with prior osteoporotic fractures. 5

Specific Dosing Regimens

• Alendronate: 70 mg once weekly or 10 mg daily 5
• Risedronate: 35 mg once weekly, 5 mg daily, 75 mg on two consecutive days per month, or 150 mg monthly 5
• Zoledronic acid: 5 mg IV annually (if oral agents contraindicated or not tolerated) 5, 2

The preference for oral bisphosphonates is based on safety, cost-effectiveness, and proven antifracture efficacy. 1, 5

Critical Pre-Treatment Requirements

Before initiating bisphosphonate therapy in fracture patients, ensure:

• Vitamin D sufficiency (serum 25(OH)D >32 ng/mL) - vitamin D deficiency attenuates bisphosphonate efficacy and increases hypocalcemia risk 2
• Adequate calcium intake (1000-1200 mg daily) and vitamin D supplementation (800-1000 IU daily) throughout treatment 5, 2
• Complete necessary dental work before starting therapy to minimize osteonecrosis of the jaw risk (though this remains rare at <1 per 10,000 patient-years) 2

Never restart bisphosphonates without correcting vitamin D deficiency first, particularly with intravenous formulations. 2

Treatment Duration and Monitoring

Initial treatment duration should be 5 years for oral bisphosphonates or 3 years for intravenous zoledronic acid, after which fracture risk should be reassessed. 5, 6

For patients with prior fractures who remain at high risk:

• Continue treatment up to 10 years (oral) or 6 years (intravenous) with periodic evaluation 5, 6
• Do not implement drug holidays in high-risk patients with prior fractures - the vertebral fracture risk reduction outweighs rare adverse events 6
• Reassess fracture risk periodically during treatment rather than monitoring bone mineral density 7

Alternative Agents for Special Circumstances

If oral bisphosphonates are contraindicated or not tolerated in fracture patients:

• Intravenous zoledronic acid for adherence concerns or gastrointestinal intolerance 2
• Denosumab 60 mg subcutaneously every 6 months as second-line therapy (conditional recommendation, moderate-certainty evidence) 5, 2

Critical warning: Denosumab discontinuation causes rebound bone loss and multiple vertebral fractures - patients must transition to bisphosphonate therapy after stopping denosumab. 5

Very High-Risk Fracture Patients

For patients at very high risk (multiple prior fractures, recent fracture within 12 months, T-score ≤-3.0, or fractures despite ongoing bisphosphonate therapy):

• Consider anabolic agents (teriparatide or romosozumab) before or instead of antiresorptive therapy (conditional recommendation, low-certainty evidence) 5
• Mandatory sequential therapy: After completing anabolic therapy, transition to bisphosphonate or denosumab to maintain bone density gains and prevent rapid bone loss 5

Administration Instructions to Prevent Complications

For oral bisphosphonates, instruct patients to:

• Take with full glass of water on empty stomach 2
• Remain upright for 30 minutes after administration to prevent esophageal complications 2
• These specific instructions reduce the risk of upper GI adverse events 4

Safety Profile in Fracture Patients

Bisphosphonates demonstrate favorable safety in fracture patients:

• No differences in serious adverse events compared to placebo in RCTs at 12-36 months 1
• No differences in withdrawal due to adverse events (moderate certainty) 1
• Rare adverse events (osteonecrosis of the jaw, atypical femoral fractures) occur at very low rates and are outweighed by fracture prevention benefits in high-risk patients 1, 6