From the Guidelines
Bisphosphonates are the recommended first-line treatment for preventing fractures in patients with primary osteoporosis, due to their favorable balance of benefits, harms, and cost, as evidenced by high-certainty evidence 1. The most commonly prescribed bisphosphonates include alendronate (Fosamax) 70mg weekly, risedronate (Actonel) 35mg weekly, and zoledronic acid (Reclast) 5mg IV yearly. These medications work by inhibiting bone resorption by osteoclasts, thereby increasing bone mineral density and reducing fracture risk. For optimal effectiveness, bisphosphonates should be taken with a full glass of water on an empty stomach, followed by remaining upright for 30-60 minutes to prevent esophageal irritation (except for IV zoledronic acid). Key points to consider when prescribing bisphosphonates include:
- Calcium (1000-1200mg daily) and vitamin D (800-1000 IU daily) supplementation should accompany bisphosphonate therapy.
- Treatment duration typically ranges from 3-5 years, after which a "drug holiday" may be considered for lower-risk patients to minimize potential long-term adverse effects like atypical femur fractures and osteonecrosis of the jaw.
- Higher-risk patients may benefit from longer treatment or switching to alternative osteoporosis medications.
- Bisphosphonates reduce vertebral fracture risk by 40-70%, hip fracture risk by 40-50%, and non-vertebral fracture risk by 20-35%, with benefits beginning within 6-12 months of treatment initiation, as supported by previous guidelines 1 and more recent living clinical guidelines 1.
From the FDA Drug Label
Zoledronic acid injection is a bisphosphonate indicated for the treatment of: Patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. Atypical subtrochanteric and diaphyseal femoral fractures have been reported in patients receiving bisphosphonate therapy.
Atypical, low-energy, or low trauma fractures of the femoral shaft have been reported in bisphosphonate-treated patients.
The FDA drug label does not directly answer the question of fracture prevention with bisphosphonates. However, it does mention that atypical subtrochanteric and diaphyseal femoral fractures have been reported in patients receiving bisphosphonate therapy, which suggests a potential increased risk of fractures.
- Key points:
- Bisphosphonates, such as zoledronic acid and alendronate, are associated with a risk of atypical femur fractures.
- The labels do not provide direct evidence for fracture prevention.
- Patients with a history of bisphosphonate exposure who present with thigh or groin pain should be suspected of having an atypical fracture and evaluated to rule out an incomplete femur fracture 2 3.
From the Research
Bisphosphonates and Fracture Prevention
- Bisphosphonates reduce the risk of fracture by suppressing bone resorption and increasing bone strength, and they have been widely used for the prevention and treatment of osteoporosis 4.
- The amino-bisphosphonates are first-line therapy for the treatment of most patients with osteoporosis, with proven efficacy to reduce fracture risk at the spine, hip, and other nonvertebral skeletal sites 5.
- Bisphosphonates have been associated with a significant decrease in morbidity and increase in survival 5.
Benefits and Risks of Bisphosphonate Therapy
- Benefits on bone mineral density (BMD) and fracture prevention appear to be sustained for 7-10 years 6.
- However, the use of bisphosphonates for the management of osteoporosis remains a clinical challenge, with considerations including appropriate patient selection, pretreatment evaluation, potential adverse effects, patient preferences, and adherence 4.
- Potential side effects of bisphosphonates appear to be rare and may not be causally related, but may include osteonecrosis of the jaw, atypical femur fractures, atrial fibrillation, and esophageal cancer 5.
Duration of Bisphosphonate Therapy
- The concept of a drug holiday has emerged, whereby the risk of adverse effects might be decreased while the patient still benefits from antifracture efficacy 5, 6.
- Data suggest that bisphosphonates have a residual therapeutic effect after being stopped and that fracture benefit appears to be sustained 2-5 years after discontinuation 6.
- For most patients with osteoporosis, the benefits of treatment outweigh the risks, but consideration could be given to stopping therapy for 2-5 years in lower risk patients 6, 7.
Time to Benefit of Bisphosphonate Therapy
- A meta-analysis found that 12.4 months were needed to avoid 1 nonvertebral fracture per 100 postmenopausal women receiving bisphosphonate therapy at an absolute risk reduction of 0.010 8.
- To prevent 1 hip fracture, 200 postmenopausal women with osteoporosis would need to receive bisphosphonate therapy for 20.3 months at an absolute risk reduction of 0.005 8.
- These results suggest that bisphosphonate therapy is most likely to benefit postmenopausal women with osteoporosis who have a life expectancy greater than 12.4 months 8.