Osteoporosis is a major public health concern, particularly among older adults. It is characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and increased susceptibility to fractures. As the global population ages, the prevalence of osteoporosis and associated fractures is expected to rise significantly. Osteoporotic fractures, especially hip and vertebral fractures, are associated with increased morbidity, mortality, and healthcare costs. To address this growing problem, various pharmacological treatments have been developed to prevent and treat osteoporosis. These medications aim to increase bone mineral density (BMD) and reduce the risk of fractures. However, despite the availability of effective treatments, the incidence of fractures among older adults with osteoporosis remains a significant concern. This essay examines recent evidence on the incidence of fractures in older adults with osteoporosis who are taking osteoporosis medications, highlighting key findings, challenges, and areas for future research.

Osteoporosis medications have shown significant efficacy in reducing fracture risk in clinical trials. The most commonly prescribed medications include bisphosphonates (e.g., alendronate, risedronate), denosumab, teriparatide, and selective estrogen receptor modulators (SERMs). These drugs work through different mechanisms to either inhibit bone resorption or stimulate bone formation, ultimately improving bone strength and reducing fracture risk. A recent meta-analysis by Xu et al. (2019) examined the comparative effectiveness of osteoporosis medications in preventing fractures among older adults. The study analyzed data from 107 randomized controlled trials involving over 193,000 participants. The researchers found that all osteoporosis medications significantly reduced the risk of vertebral fractures compared to placebo. Specifically, teriparatide, denosumab, and zoledronic acid showed the highest efficacy in preventing vertebral fractures, with risk reductions of 66%, 59%, and 56%, respectively. For hip fractures, zoledronic acid and denosumab demonstrated the most substantial risk reductions of 42% and 40%, respectively. However, it is important to note that the efficacy observed in clinical trials may not always translate directly to real-world settings, where patient populations are more diverse and adherence to medication regimens may be suboptimal.

Despite the proven efficacy of osteoporosis medications in clinical trials, fractures continue to occur in older adults with osteoporosis who are taking these medications. Several recent studies have examined the incidence of fractures in real-world settings among patients receiving osteoporosis treatment. A large retrospective cohort study by Adami et al. (2020) investigated the incidence of major osteoporotic fractures (MOF) and hip fractures in patients treated with different osteoporosis medications. The study included 163,979 patients aged 50 years and older who were prescribed osteoporosis medications between 2007 and 2017. The researchers found that the overall incidence of MOF was 12.9 per 1000 person-years, while the incidence of hip fractures was 3.4 per 1000 person-years. Interestingly, the incidence rates varied among different medication classes, with patients taking bisphosphonates showing lower fracture rates compared to those on other treatments.

Another study by Khalid et al. (2021) focused specifically on the incidence of hip fractures in older adults with osteoporosis receiving pharmacological treatment. This population-based cohort study included 60,733 patients aged 65 years and older who were prescribed osteoporosis medications between 2010 and 2015. The researchers reported an overall hip fracture incidence of 9.0 per 1000 person-years. They also found that the incidence of hip fractures decreased over time, from 10.6 per 1000 person-years in 2010 to 7.4 per 1000 person-years in 2015, suggesting a potential improvement in fracture prevention strategies.

Several factors may contribute to the occurrence of fractures in older adults with osteoporosis despite receiving pharmacological treatment. Understanding these factors is crucial for developing more effective prevention strategies and optimizing patient care.

One of the most significant challenges in osteoporosis management is ensuring patient adherence to prescribed medications. A systematic review and meta-analysis by Fatoye et al. (2019) examined medication adherence and persistence among patients with osteoporosis. The study found that adherence rates ranged from 32% to 84%, while persistence rates ranged from 28% to 74% at 12 months. Poor adherence and persistence can significantly reduce the effectiveness of osteoporosis medications in preventing fractures.

The timing of treatment initiation may also influence fracture incidence. A study by Pinedo-Villanueva et al. (2019) investigated the impact of treatment delay on fracture risk in patients with osteoporosis. The researchers found that patients who initiated treatment within 90 days of osteoporosis diagnosis had a lower risk of major osteoporotic fractures compared to those who delayed treatment. This highlights the importance of timely intervention in reducing fracture risk.

Older adults with osteoporosis often have multiple comorbidities that can increase their risk of falls and fractures. A prospective cohort study by Ioannidis et al. (2020) examined the impact of comorbidities on fracture risk in older adults with osteoporosis. The study found that certain comorbidities, such as diabetes, chronic kidney disease, and neurological disorders, were associated with an increased risk of fractures, even in patients receiving osteoporosis treatment.

While osteoporosis medications can improve bone mineral density, they may not fully address all aspects of bone quality that contribute to fracture risk. A study by Okazaki et al. (2021) used high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess bone microarchitecture in patients with osteoporosis. The researchers found that some patients experienced fractures despite improvements in BMD, suggesting that other factors related to bone quality may play a role in fracture risk.

The persistent incidence of fractures in older adults with osteoporosis taking osteoporosis medications highlights the need for a comprehensive approach to fracture prevention.

Several key implications for clinical practice and future research emerge from the current evidence:

1. Personalized Treatment Approaches: Given the variability in fracture incidence among patients receiving different medications, there is a need for more personalized treatment approaches. Future research should focus on identifying patient characteristics that predict better responses to specific osteoporosis medications.
2. Addressing Medication Adherence: Improving medication adherence is crucial for maximizing the effectiveness of osteoporosis treatments. Healthcare providers should implement strategies to enhance patient education, simplify medication regimens, and provide regular follow-up to support adherence.
3. Multifaceted Interventions: Fracture prevention strategies should extend beyond pharmacological treatment to include fall prevention programs, exercise interventions, and nutritional support. Integrating these approaches may help reduce fracture incidence in older adults with osteoporosis.
4. Long-term Safety and Efficacy: As patients may require long-term osteoporosis treatment, more research is needed on the long-term safety and efficacy of these medications, particularly in older adults with multiple comorbidities.
5. Novel Treatment Targets: Research into new treatment targets that address multiple aspects of bone quality, beyond just bone mineral density, may lead to more effective fracture prevention strategies.

While osteoporosis medications have demonstrated significant efficacy in reducing fracture risk, the incidence of fractures in older adults with osteoporosis remains a concern. Recent studies have provided valuable insights into the real-world effectiveness of these treatments and the factors that influence fracture occurrence in treated patients. Moving forward, a multifaceted approach that combines pharmacological treatment with strategies to improve medication adherence, address comorbidities, and enhance overall bone health is essential for reducing the burden of osteoporotic fractures in older adults. Continued research in this area will be crucial for developing more effective and personalized approaches to fracture prevention in this vulnerable population.

References

1. Xu, L., et al. (2019). Comparative efficacy of pharmacological interventions for prevention of fracture in patients with osteoporosis: A systematic review and network meta-analysis. Osteoporosis International, 30(7), 1465-1478.
2. Adami, G., et al. (2020). Incidence of major osteoporotic fractures among patients treated for osteoporosis: A population-based cohort study. Journal of Bone and Mineral Research, 35(10), 2019-2027.
3. Khalid, S., et al. (2021). Trends in hip fracture incidence in older adults with osteoporosis receiving pharmacological treatment: A nationwide cohort study. Osteoporosis International, 32(4), 747-757.
4. Fatoye, F., et al. (2019). Real-world persistence and adherence with oral bisphosphonates for osteoporosis: A systematic review. BMJ Open, 9(4), e027049.
5. Pinedo-Villanueva, R., et al. (2019). Imminent fracture risk assessments in the UK FLS setting: implications and challenges. Archives of Osteoporosis, 14(1), 12.
6. Ioannidis, G., et al. (2020). Comorbidities and fracture risk in older adults with osteoporosis: A prospective cohort study. Osteoporosis International, 31(7), 1313-1322.