Nitrogen-containing bisphosphonates may lower risk of pneumonia in patients with hip fracture

A recent study led by researchers from the University of Hong Kong (HKU) shows that the use of nitrogen-containing bisphosphonates (N-BPs), particularly alendronate, is associated with reduced risks of pneumonia and pneumonia mortality compared with no anti-osteoporotic treatment and non-N-BP anti-osteoporotic treatment.

In the retrospective cohort study, data of 54,047 patients aged ≥50 years with an incident hip fracture who were admitted to hospital via an emergency room between 1 January 2005 and 31 December 2015, and who were diagnosed with or died of pneumonia, were retrieved from the Clinical Data Analysis and Reporting System (CDARS), a population-wide medical database managed by the Hospital Authority (HA). Patients were followed up until 31 December 2016. [J Bone Miner Res 2020, doi: 10.1002/jbmr.4030]

At baseline, 4,041 patients exposed to any N-BPs (ie, alendronate, ibandronate, risedronate and zoledronate) during the study period were matched with 11,802 patients who received no anti-osteoporotic treatment. More than 15 percent (15.8 percent) and 14.3 percent of patients with and without N-BP treatment, respectively, received seasonal influenza vaccine in the past year or pneumococcal vaccine on/before the index date.

Likewise, 1,284 patients with N-BP treatment were matched with 507 patients with non-N-BP anti-osteoporotic treatment, with strontium ranelate, salcatonin, denosumab, teriparatide and raloxifene used in 166, 161, 135, 38 and 7 patients, respectively.

In patients who received N-BPs vs no anti-osteoporotic treatment, the incidence of pneumonia and pneumonia mortality was 6.9 vs 9.0 per 100 person-years and 2.3 vs 3.5 per 100 person-years, respectively, during a median of 2.7 years of follow-up.

Patients treated with N-BPs had a 24 percent lower risk of incident pneumonia (hazard ratio [HR], 0.76; 95 percent confidence interval [Cl], 0.70 to 0.83; p<0.001) vs those with no anti-osteoporotic treatment, translating to an absolute risk difference (ARD) of 0.02 and number needed to treat (NNT) of 46.

A significant risk reduction in pneumonia mortality was also observed in patients who received N-BPs vs no anti-osteoporotic treatment (HR, 0.65; 95 percent CI, 0.56 to 0.75; p<0.001).

“The study included mainly alendronate-exposed patients [81.6 percent],” the researchers noted. Among these patients, similar risk reductions in incident pneumonia (HR, 0.74; 95 percent CI, 0.67 to 0.81; p<0.001) and pneumonia mortality (HR, 0.63; 95 percent CI, 0.54 to 0.74; p<0.001) were observed vs no anti-osteoporotic treatment.

Of note, reductions in risk of incident pneumonia and pneumonia mortality with N-BPs vs no anti-osteoporotic treatment remained significant regardless of gender and vaccination status (incident pneumonia: female, p<0.001; male, p=0.009; vaccination, p=0.007; no vaccination, p<0.001) (pneumonia mortality: female: p<0.001; male, p=0.025; vaccination, p=0.055; no vaccination, p<0.001).

In a secondary analysis, consistent reductions in risk of incident pneumonia and associated mortality were seen with N-BPs vs non-N-BP anti-osteoporotic treatment (incident pneumonia: HR, 0.68; 95 percent CI, 0.53 to 0.87; p=0.002) (pneumonia mortality: HR, 0.60; 95 percent CI, 0.41 to 0.89; p=0.01).

According to the researchers, the study’s results suggest that N-BPs could confer additional protection against pneumonia to compensate for the reported shortage and low acceptance of vaccine, as well as the high cost of large-scale vaccination programmes. “Drug repositioning of N-BPs as a pneumonia prevention drug, especially in high-risk groups [eg, patients with osteoporosis], may be of public health importance,” they suggested.  “Further randomized clinical trials may be warranted to further validate our findings.”