Alendronate Decreases Hip Fracture Risk in Older Patients Using Oral Prednisolone

Patients age 65 years or older who use medium to high doses of prednisolone and receive treatment with alendronate experience significantly lower risk of hip fracture over a median of 1.32 years than patients on prednisolone who are not treated with alendronate. Kristian F. Axelsson, MD, MSc, from Skaraborg Hospital in Sweden, and colleagues published the results of their observational study in the July 11 issue of JAMA. Their findings support the use of alendronate in older patients taking prednisolone.¹

The researchers used a Swedish national database of 433,195 patients and compared patients on prednisolone to patients not on prednisolone. They found that the risk of hip fracture only increased among patients taking ≥5 mg prednisolone daily and, thus, focused their efforts on these patients. For their retrospective cohort study, researchers identified 1,802 patients who were prescribed alendronate after at least three months of oral prednisolone treatment. These patients had a mean age of 79.9 years and had been receiving alendronate for a median duration of 2.9 years. The majority of patients were women (70%). The investigators used propensity score matching to create a well-matched group of patients taking prednisolone who were not treated with alendronate. The standardized difference between the two groups was below 10% for all baseline characteristics—except for osteoporosis, which was 12.4%.

The investigators note that the number of hip fractures in their study was small: 27 in the alendronate-treated group and 73 in the no-alendronate group. This number corresponded to incidence rates of 9.5 (95% confidence interval [CI], 6.5–13.9) fractures per 1,000 person-years in the alendronate group and 27.2 (95% CI, 21.6–34.2) fractures per 1,000 person-years in the no-alendronate group. When researchers used an unadjusted Cox model, alendronate treatment was associated with a lower risk of hip fracture (hazard ratio [HR] 0.35; 95% CI, 0.23–0.55). Researchers then used a multivariable-adjusted Cox model, adjusting for anthropometric variables, clinical risk factors and comorbidity, and calculated that the use of alendronate was associated with a lower risk of hip fracture (HR 0.35; 95% CI, 0.22–0.54). When they included cumulative prednisolone dose as a covariate in the multivariable Cox model, the risk estimate for the association between alendronate use and risk of hip fracture did not change. They also performed extensive sensitivity analyses with several alendronate treatment variables to address possible sources of bias and were unable to identify any.

Additionally, the researchers documented 642 deaths (35.6%) among patients using alendronate and 698 deaths (38.7%) among those not using alendronate. When they used a Cox model adjusted for age, sex, height, weight and Charlson comorbidity index, they found that alendronate treatment in patients using prednisolone was associated with a lower risk of death (HR 0.88; 95% CI, 0.79–0.98) when compared with patients not treated with alendronate. Moreover, deaths for which hip fractures were listed as a possible cause did not differ significantly between the two groups. Incident fall injuries also did not differ significantly between alendronate-treated and untreated patients.

Finally, treatment with alendronate was not associated with increased risk of mild upper gastrointestinal tract symptoms or peptic ulcers. Researchers also saw no cases of incident drug-induced osteonecrosis and only one case of femoral shaft fracture in each group.

Lara C. Pullen, PhD, is a medical writer based in the Chicago area.

Reference

1. Axelsson KF, Nilsson AG, Wedel H, et al. Association between alendronate use and hip fracture risk in older patients using oral prednisolone. JAMA. 2017 Jul 11;318(2):146–155. doi: 10.1001/jama.2017.8040.