Association Between Alendronate Use and Hip Fracture Risk in Older Patients Using Oral Prednisolone

Abstract

Importance: Oral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids.

Objective: To investigate whether alendronate treatment in older patients using oral prednisolone is associated with decreased hip fracture risk and adverse effects.

Design, setting, and participants: Retrospective cohort study using a national database (N = 433 195) of patients aged 65 years or older undergoing a health evaluation (baseline) at Swedish health care facilities; 1802 patients who were prescribed alendronate after at least 3 months of oral prednisolone treatment (≥5 mg/d) were identified. Propensity score matching was used to select 1802 patients without alendronate use from 6076 patients taking prednisolone with the same dose and treatment time criteria. Follow-up occurred between January 2008 and December 2014.

Exposures: Alendronate vs no alendronate use; no patients had previously taken alendronate at the time of prednisolone initiation.

Main outcomes and measures: The primary outcome was incident hip fracture.

Results: Of the 3604 included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34 years), there were 27 hip fractures in the alendronate group and 73 in the no-alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and 27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate difference of -17.6 (95% CI, -24.8 to -10.4). The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3-18.0] per 1000 person-years; P = .40) or peptic ulcers (10.9 [95% CI, 7.7-15.5] vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years; P = .86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group.

Conclusions and relevance: Among older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group.

Figure 1.. Study Population

^aEach patient may be included in more than 1 exclusion group. ^bAccepted values after exclusion of top and bottom 0.1% of weight, height, and body mass index (BMI): weight, 30-176 kg; height, 114-197 cm; BMI, 12.23-73.05.

Figure 2.. Schematic Description of Study Design

The drug evaluation period was between 2005, when the Swedish Prescribed Drug Register started, and baseline. All patients (n = 3604) had daily average prednisolone doses of 5 mg or more, ongoing treatment at baseline, longer treatment than 3 months (dashed vertical line), and no record of another glucocorticoid than prednisolone. Patients with alendronate use (n = 1802) started treatment after prednisolone, alendronate treatment was ongoing at baseline for longer than 3 months (dashed vertical line), and there was no record of another osteoporosis medication than alendronate. Median time from prednisolone initiation to alendronate initiation in the alendronate group was 3.9 months (interquartile range, 0.5-20.0 months). The evaluation period for medical history data (prebaseline diseases, prevalent fall injuries, and fractures) was 1987 to baseline. Weight and height were retrieved at baseline from the Senior Alert Register. Evaluation of outcomes during the time at risk was performed from baseline to end of study (December 31, 2014; emigration; or death). The Cox model accounted for different time of follow-up, but the initial setup of covariates and alendronate use (yes/no) remained the same during follow-up. Solid vertical lines on the treatment exposure bars indicate median length of treatment exposure.

Figure 3.. Hip Fracture Risk With and Without Alendronate in Patients With Prednisolone Treatment

Cox regression model adjusted for age, sex, weight, height, known fracture-free time, previous fracture, number of previous fractures, previous hip fracture, previous vertebral fracture, previous fall injury, osteoporosis, secondary osteoporosis, Charlson comorbidity index, rheumatoid arthritis, previous calcium and vitamin D treatment, and alcohol-related diseases. The inset shows the same data on an enlarged y-axis. Median follow-up for alendronate use was 498 (interquartile range, 228-851) days; for no alendronate use, 468 (interquartile range, 187-855) days.