From the Guidelines
Denosumab (Prolia) and zoledronic acid (Reclast) are the most effective treatments for preventing non-vertebral fractures in osteoporosis, with denosumab reducing non-vertebral fracture risk by approximately 20% and zoledronic acid by about 25%. These medications work by different mechanisms, with denosumab being a RANK ligand inhibitor that blocks osteoclast formation, and zoledronic acid being a bisphosphonate that inhibits osteoclast activity 1.
Key Considerations
- The choice between denosumab and zoledronic acid should consider individual patient factors, including renal function, compliance concerns, and specific fracture risk profile 1.
- For patients with very high fracture risk, teriparatide (Forteo) or abaloparatide (Tymlos) may be more effective as they actually build new bone rather than just preventing bone loss 1.
- All patients should also take calcium (1000-1200mg daily) and vitamin D (800-1000 IU daily) supplements as adjunctive therapy, and engage in weight-bearing exercise to maximize treatment effectiveness 1.
- Adherence to treatment is crucial, and monitoring of bone turnover markers can help identify patients who are not responding to therapy 1.
Treatment Options
- Denosumab: 60mg subcutaneous injection every 6 months
- Zoledronic acid: 5mg intravenous infusion once yearly
- Teriparatide: daily subcutaneous injections for up to 2 years
- Abaloparatide: daily subcutaneous injections for up to 2 years
Supporting Evidence
The American College of Physicians recommends offering pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women with known osteoporosis 1. A 2024 study published in Nature Reviews Rheumatology found that denosumab and zoledronic acid are effective in improving bone mineral density and reducing fracture risk in men with osteoporosis 1. A 2023 living clinical guideline from the American College of Physicians recommends the same first- and second-line treatments for both males and females with primary osteoporosis or low bone mass 1.
From the FDA Drug Label
In postmenopausal women with osteoporosis, teriparatide injection reduces the risk of vertebral and nonvertebral fractures. In postmenopausal women with osteoporosis, Prolia reduces the incidence of vertebral, nonvertebral, and hip fractures
Both teriparatide and denosumab have been shown to reduce the risk of nonvertebral fractures in postmenopausal women with osteoporosis. However, the most effective treatment cannot be directly determined from the provided drug labels, as they do not include a direct comparison of the two treatments.
- Teriparatide 2 and denosumab 3 are both effective in reducing nonvertebral fractures, but the labels do not provide a comparison of their effectiveness.
From the Research
Osteoporosis Treatment Options
The most effective osteoporosis treatment for preventing non-vertebral fractures includes:
- Antiresorptive drugs, such as bisphosphonates and the RANKL inhibitor denosumab, which increase bone mineral density (BMD) and reduce the risk of nonvertebral fractures by 25-40% 4
- Bisphosphonates, such as alendronate and risedronate, which have been shown to provide non-vertebral anti-fracture efficacy in intention-to-treat populations 5
- Zoledronic acid, which has been found to be the most effective in preventing vertebral fracture, nonvertebral fracture, and any fracture 6
Comparison of Treatment Options
A comparison of the efficacy of different bisphosphonates in preventing nonvertebral fractures found that:
- Zoledronic acid was the most effective in preventing nonvertebral fracture 6
- Alendronate and risedronate also provided significant reductions in the relative risk of nonvertebral fracture 5
- Denosumab achieves greater suppression of bone turnover and greater increases of bone mineral density (BMD) at all skeletal sites, but no superiority on fracture risk reduction has been documented so far 7
Treatment Considerations
When considering treatment options, it is important to note that:
- Bisphosphonates have a plateau in BMD response after 2-3 years, while denosumab continues to increase BMD as long as it is administered 7
- Denosumab discontinuation fully and rapidly reverses its effects on bone markers and BMD, and increases the risk for fractures 7
- Combination of teriparatide with denosumab or zoledronic acid provides increased BMD gains at all sites 7