The osteoporosis drug alendronate has been linked with a reduced risk of cardiovascular death, heart attack, and stroke in a study of patients with hip fractures. The association was seen for up to 10 years after fracture. In the study, patients newly diagnosed with hip fracture from 2005 through 2013 were followed until late 2016. Among 34,991 patients, 4602 (13%) received osteoporosis treatment during follow-up.
Alendronate was associated with 67% and 45% lower risks of one-year cardiovascular death and heart attack, respectively. It was associated with an 18% reduced risk of stroke within five years and a 17% reduced risk of stroke within 10 years. Protective effects were not evident for other classes of osteoporosis treatments.
"It is well established that there is a world-wide crisis in the treatment of osteoporosis, due to patients' awareness of the extremely rare side effects," said senior author Dr Ching-Lung Cheung, of the University of Hong Kong. "Our findings show that alendronate is potentially cardio-protective in hip fracture patients.
Therefore, physicians should consider prescribing alendronate or other nitrogen-containing bisphosphonates to hip fracture patients soon after their fracture, and patients should also have good compliance with alendronate treatment, as this is not only good for your bones, but also your heart."
In addition to clinical management, the study also has important implications in clinical trial design of anti-osteoporosis medications.
The US Food and Drug Administration recently requested more data before reaching a decision on whether to approve the osteoporosis drug romosozumab, due to excess cardiovascular adverse events in the romosozumab arm compared with the alendronate arm. "In light of these important deliberations, our results suggest that such differences in cardiovascular adverse events could be potentially related to a protective association of alendronate, rather than an increase in cardiovascular adverse events related to romosozumab use, said Cheung."
Abstract
The risk of cardiovascular events (CVEs) with alendronate use in real‐world hip fracture patients is unknown. This study aimed to investigate the risk of CVE with and without use of alendronate in patients with hip fracture. We conducted a retrospective cohort study using a population‐wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with hip fracture from 2005 through 2013 were followed until November 6, 2016. Alendronate and other antiosteoporosis medications use during the study period were examined. We matched treated and nontreated patients based on time‐dependent propensity score. The risks of cardiovascular mortality, myocardial infarction, and stroke between treatment groups were evaluated using conditional Cox regression stratified by match pairs. To examine the associations over time, outcomes were assessed at 1 year, 3 years, 5 years, and 10 years. Among 34,991 patients with newly diagnosed hip fracture, 4602 (13.2%) received antiosteoporosis treatment during follow‐up. Physical functioning or survival prospect was not significantly different between treated and nontreated patients. A total of 4594 treated patients were matched with 13,568 nontreated patients. Results of Cox regression analysis revealed that alendronate was associated with a significantly lower risk of 1‐year cardiovascular mortality (HR 0.33; 95% CI, 0.17 to 0.65) and incident myocardial infarction (HR 0.55; 95% CI, 0.34 to 0.89), whereas marginally significant reduction in risk of stroke was observed at 5 years and 10 years (HR at 5 years: 0.82; 95% CI, 0.67 to 1.00; p = 0.049; HR at 10 years: 0.83; 95% CI, 0.69 to 1.01; p = 0.065). The strength of the association declined over time but remained significant. Similar results were observed when all nitrogen‐containing bisphosphonates (N‐BPs) were analyzed together. These findings were robust in multiple sensitivity analyses. Additional studies in other population samples and randomized clinical trials may be warranted to further understand the relationship between use of various antiosteoporosis medication and risk of CVE in patients with hip fracture. © 2018 American Society for Bone and Mineral Research.
Authors
Chor-Wing Sing, Angel YS Wong, Douglas P Kiel, Elaine YN Cheung, Joanne KY Lam, Tommy T Cheung, Esther W Chan, Annie WC Kung, Ian CK Wong, Ching-Lung Cheung
[link url="https://www.sciencedaily.com/releases/2018/05/180511123233.htm"]Wiley material[/link]
[link url="https://onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.3448"]Journal of Bone and Mineral Research abstract[/link]