From the Guidelines
For a postmenopausal patient with ASCVD and decreasing BMD, denosumab (Prolia) is a preferred alternative to bisphosphonates, administered as a 60mg subcutaneous injection every 6 months, due to its excellent efficacy in reducing fracture risk and lack of accumulation in bone, as supported by the most recent guideline from the American College of Physicians 1.
Alternatives to Bisphosphonates
Several alternatives to bisphosphonates exist for postmenopausal patients with ASCVD and decreasing BMD. These include:
- Denosumab (Prolia), which is often a first-line alternative, administered as a 60mg subcutaneous injection every 6 months with excellent efficacy in reducing fracture risk, and does not accumulate in bone, making it a preferred option for patients with renal impairment 1.
- Teriparatide (Forteo) or abaloparatide (Tymlos), which are anabolic agents given as daily subcutaneous injections (20mcg for teriparatide, 80mcg for abaloparatide) for up to 24 months, stimulating new bone formation rather than just preventing resorption, making them valuable for patients at high fracture risk, though they require daily injections and are more expensive 1.
- Romosozumab (Evenity), another anabolic agent, administered monthly (210mg subcutaneously) for 12 months, but requires caution in ASCVD patients due to potential cardiovascular concerns 1.
- Selective estrogen receptor modulators (SERMs) like raloxifene (60mg daily) may benefit both bone health and cardiovascular risk in some women 1.
- For patients who cannot take oral medications but wish to avoid frequent injections, annual zoledronic acid infusion (5mg IV) provides a convenient bisphosphonate option with excellent compliance, although zoledronic acid may not be the best option due to its potential for atrial fibrillation and other adverse events, as noted in the 2017 guideline 1.
Treatment Selection
Treatment selection should consider the patient's fracture risk, comorbidities, medication adherence history, and preferences regarding administration route and frequency, as emphasized in the 2023 guideline from the American College of Physicians 1.
Key Considerations
- The decision to treat or not with pharmacological therapies does not depend on BMD Z-scores alone, but also on additional risk factors such as fracture history, genetics, cumulative Triad risk factors, which have been associated with an increased risk for low BMD and bone stress injury, and rate of bone loss with non-pharmacological management, as noted in the 2014 consensus statement 1.
- Clinicians should prescribe generic medications if possible rather than more expensive brand-name medications, as recommended in the 2023 guideline 1.
- Adequate calcium and vitamin intake should be part of fracture prevention in all postmenopausal females with low bone mass or osteoporosis, as emphasized in the 2023 guideline 1.
From the FDA Drug Label
Zoledronic acid injection is indicated for treatment of osteoporosis in postmenopausal women. In postmenopausal women with osteoporosis, diagnosed by bone mineral density (BMD) or prevalent vertebral fracture, zoledronic acid injection reduces the incidence of fractures (hip, vertebral and non-vertebral osteoporosis-related fractures) Teriparatide, when taken with calcium and vitamin D and compared with calcium and vitamin D alone, reduced the risk of 1 or more new vertebral fractures from 14.3% of women in the placebo group to 5. 0% in the teriparatide group
Alternatives to Bisphosphonates:
- Forteo (Teriparatide): Teriparatide is effective in reducing the risk of vertebral fractures and increasing bone mineral density (BMD) in postmenopausal women with osteoporosis.
- Zoledronic Acid: Zoledronic acid reduces the incidence of fractures (hip, vertebral, and non-vertebral osteoporosis-related fractures) in postmenopausal women with osteoporosis.
Key Considerations:
- Both teriparatide and zoledronic acid are alternatives to bisphosphonates for postmenopausal patients with decreasing BMD.
- Patients with a history of Atherosclerotic Cardiovascular Disease (ASCVD) should be evaluated on a case-by-case basis to determine the best treatment option.
- The choice between teriparatide and zoledronic acid depends on individual patient factors, such as the severity of osteoporosis, medical history, and potential side effects 2, 3.
From the Research
Alternatives to Bisphosphonates for Postmenopausal Patients with ASCVD and Decreasing BMD
- Forteo (teriparatide) and zoldronic acid are alternatives to bisphosphonates for postmenopausal patients with a history of Atherosclerotic Cardiovascular Disease (ASCVD) and decreasing Bone Mineral Density (BMD) 4, 5.
- Teriparatide is an anabolic agent that stimulates bone formation and has been shown to increase BMD in postmenopausal women with osteoporosis 6, 7.
- Zoldronic acid is a bisphosphonate that can be used as an alternative to oral bisphosphonates, but it has been shown to have a slower increase in BMD compared to teriparatide and denosumab 5, 8.
Efficacy of Teriparatide and Zoldronic Acid
- Teriparatide has been shown to increase lumbar spine BMD by 6.58% after 6 months of treatment, which is significantly higher than the increase seen with zoldronic acid 7.
- Combination therapy with teriparatide and zoldronic acid has been shown to provide the largest and most rapid increments in BMD at both spine and hip sites 5.
- Zoldronic acid has been shown to increase BMD, but the increase is slower and less pronounced compared to teriparatide and denosumab 5, 8.
Safety and Tolerability
- Teriparatide has been shown to be well-tolerated and safe, with no significant differences in adverse events compared to control groups 7.
- Zoldronic acid has been associated with a higher risk of adverse events, including atypical femoral fractures, compared to teriparatide and denosumab 8.
- The safety and efficacy of teriparatide and zoldronic acid in postmenopausal patients with ASCVD and decreasing BMD should be carefully evaluated, taking into account the individual patient's risk factors and medical history 4, 6.