Can nitrogen-containing bisphosphonates protect against pneumonia?

Patients taking nitrogen-containing bisphosphonates have a lower risk of developing and dying from pneumonia after hip fracture than patients taking other types of osteoporosis drugs or no osteoporosis drugs, a study published in Journal of Bone and Mineral Research he found.

Nitrogen-containing bisphosphonates (N-BPs), particularly alendronate, are widely used to treat osteoporosis, and some studies have suggested that alendronate may have beneficial effects on the lung, prompting researchers to question whether nitrogen-containing bisphosphonates could protect against pneumonia.

From a population-wide database, researchers identified 54,047 patients who suffered their first hip fracture between 2005 and 2015 and were followed up through the end of 2016.

A total of 4041 patients taking nitrogen-containing bisphosphonates had a propensity score corresponding to 11,802 patients not taking any anti-osteoporosis drugs.

Use of nitrogen-containing bisphosphonates was found to be associated with a significantly lower risk of pneumonia than with no treatment (6.9 vs 9.0 per 100 person-years; [HR] 0.76; 95% CI, 0.70 to 0.83). The absolute risk difference (ARD) was 0.02 and the number of patients who needed to be treated to prevent one case of pneumonia was 46.

It was also found that patients taking nitrogen-containing bisphosphonates have a reduced risk of death from pneumonia (HR 0.65; 95% CI, 0.56-0.75).

In a further analysis, 1,284 patients taking nitrogen-containing bisphosphates had a propensity score corresponding to 507 patients taking other osteoporosis treatments. The results showed that the association of the lower risk of pneumonia and pneumonia mortality with nitrogen-containing bisphosphonates remained significant.

“Bisphosphonate has long been used to treat bone diseases, our study provides evidence on the novel role of nitrogen-containing bisphosphonate (N-BP) in non-skeletal disease,” said Dr. Ching-Lung Cheung, assistant professor, Department of Pharmacology and Pharmacy at the University of Hong Kong, Hong Kong, China.

“Our study was the first to report the protective effect of N-BP against pneumonia,” he said, but more studies, preferably randomized controlled trials, were needed to confirm this.

Meanwhile, he hoped the results would encourage more optimal use of nitrogen-containing bisphosphonates. “There is a crisis in the treatment of osteoporosis, mainly due to patients being aware of rare but serious adverse side effects,” he said.

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“Rheumatologists can discuss with osteoporotic patients the risk and benefits of using anti-osteoporosis drugs, particularly nitrogen-containing bisphosphonates, and hopefully this will lead to a better risk-benefit profile.”

The researchers conducted the study because they hypothesized that nitrogen-containing bisphosphonates could impact pneumonia by having a similar inhibitory effect on alveolar macrophages as osteoclasts do. Alveolar macrophages play an important role in defending against pneumonia through early phagocytosis of pathogens and subsequent induction of apoptosis to minimize inflammation.

“This drug targets the drug pathway that is important for macrophage survival, which is related to the pathogenesis of pneumonia,” explained Dr. Cheung. “Furthermore, a pharmacokinetic study showed that N-BPs have the highest concentration in the trachea among all the non-bone tissues studied. Together with its immunomodulatory and anti-inflammatory effect, it is believed that N-BP may have this effect on the basis of these mechanisms and / or other unknown mechanisms. “

Nitrogen-containing bisphosphonates target the same pathway as statins and have similar anti-inflammatory and immunomodulatory effects. A recent study found that statins improved neutrophil function and hospital-free survival in pneumonia.[i]



Sing CW, Kiel DP, Hubbard RB, Lau WC, Li GH, Kung AW, Wong IC, Cheung CL. Nitrogen-containing bisphosphonates are associated with a reduced risk of pneumonia in patients with hip fractures. J Bone Miner Res. 2020 September; 35 (9): 1676-1684. doi: 10.1002 / jbmr.4030. Epub 2020 Jun 2. PMID: 32488902.

[i] Sapey E, Patel JM, Greenwood H, et al. Simvastatin improves neutrophil function and clinical outcomes in pneumonia. A randomized controlled pilot study. I’m J Respir Crit Care Med. 2019; 200 (10): 1282–93.


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