Nitrogen-containing bisphosphonates reduce pneumonia risk, mortality after hip fracture
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Older adults prescribed nitrogen-containing bisphosphonate therapy after a hip fracture were less likely to develop pneumonia or die from the infection compared with similar adults who received no osteoporosis therapy, researchers report.
“Bisphosphonates are not only drugs for treating disorders of bone metabolism, but they may also have extra-skeletal effects,” Ching-Lung Cheung, PhD, assistant professor in the department of pharmacology and pharmacy at the University of Hong Kong, told Healio. “Using real-world clinical data, our team reported in 2018 that bisphosphonate use was associated with lower risk for cardiovascular events among individuals with hip fracture, possibly due to its lipid-lowering effects. In the latest study, we further demonstrated that use of bisphosphonates was associated with reduced risk for pneumonia and its associated death. In addition to the lipid-lowering effect, bisphosphonates also possess anti-inflammatory and immune-modulatory properties.”
Cheung and colleagues analyzed data from 54,047 adults aged at least 50 years who were admitted an emergency department with an incident hip fracture between 2005 and 2015, using data from the Clinical Data Analysis and Reporting System, and EMR database managed by the Hong Kong Hospital Authority. Researchers followed all patients for at least 1 year or until Dec. 31, 2016, for any pneumonia or pneumonia mortality (median follow-up, 2.7 years). Patients were classified as exposed to nitrogen-containing bisphosphonates if they had a prescription for alendronate, ibandronate, risedronate or zoledronate before the end of the study. For the primary analysis, researchers compared patients treated with nitrogen-containing bisphosphonates to those who did not receive any osteoporosis therapy.
In a secondary analysis, researchers compared patients treated with nitrogen-containing bisphosphonates to those treated with non-nitrogen containing bisphosphonates and osteoporosis medications with different mechanisms of action, including denosumab (Prolia, Amgen), raloxifene, salcatonin, strontium ranelate and teriparatide (Forteo, Eli Lilly; Bonsity, Alvogen).
Within the cohort, 6,467 patients (14.9%) were prescribed an osteoporosis medication by the end of the study. For the primary analysis, researchers matched 4,041 patients prescribed nitrogen-containing bisphosphonates with 11,802 patients not exposed to therapy using propensity score matching. For the secondary analysis, researchers matched 1,284 patients prescribed nitrogen-containing bisphosphonates with 507 patients prescribed non-nitrogen containing osteoporosis therapies, also using propensity score matching.
Researchers found that incidence of pneumonia was lower among patients prescribed nitrogen-containing bisphosphonates vs. those not exposed to any osteoporosis therapy (6.9 vs. 9 per 100 patient-years), for an HR of 0.76 (95% CI, 0.7-0.83) and an absolute risk difference of 0.02 (95% CI, 0.02-0.03). The number needed to treat to prevent one case of pneumonia was 46.
Similarly, pneumonia mortality was lower among patients prescribed nitrogen-containing bisphosphonate therapy vs. those not exposed to osteoporosis therapy (2.3 vs. 3.5 per 100 patient-years) for an HR of 0.65 (95% CI, 0.56-0.75). In subgroup analysis, results persisted independent of pneumonia vaccination status.
In analysis comparing nitrogen-containing bisphosphonate therapy with non-nitrogen containing bisphosphonate therapy, the associations with reduced pneumonia risk and pneumonia mortality remained significant, with HRs of 0.68 (95% CI, 0.53-0.87) and 0.6 (95% CI, 0.41-0.89), respectively.
“Based on these findings, we hope that clinicians would be encouraged to treat their hip fracture patients with bisphosphonates, which is not only beneficial for bone, but may also potentially prevent cardiovascular events and pneumonia,” Cheung said.
For more information:
Ching-Lung Cheung, PhD, can be reached at the University of Hong Kong, Department of Pharmacology and Pharmacy, 21 Sassoon Road, Pokfulam, Hong Kong; email: lung1212@hku.kh.c
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Jacqueline Center, MBBS, PhD
This is an excellent study with very interesting results. The study was well conducted with appropriate statistical analysis and quite rigorous adjustment for confounding with appropriate sensitivity analyses. There are some data to suggest that bisphosphonates may have an effect on decreasing pneumonia risk, and this group has demonstrated this effect in a high-risk hip fracture population. There have been several studies demonstrating a mortality benefit with bisphosphonates, and this study has suggested that post-hip fracture pneumonia-related mortality was also decreased.
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