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Original Investigation
July 11, 2017

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

Author Affiliations
  • 1Department of Orthopaedic Surgery, Skaraborg Hospital, Skövde, Sweden
  • 2Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
  • 3Department of Endocrinology, Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 4Health Metrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  • 5School of Bioscience, University of Skövde, Skövde, Sweden
  • 6Geriatric Medicine, Sahlgrenska University Hospital, Mölndal, Sweden
JAMA. 2017;318(2):146-155. doi:10.1001/jama.2017.8040
Key Points

Question  Is alendronate associated with lower risk of hip fracture among older patients taking medium to high doses of oral glucocorticoids?

Findings  In this retrospective cohort study of 3604 patients using medium or high doses of prednisolone, the additional use of alendronate was associated with a significantly lower risk of hip fracture over a median 1.32 years of follow-up (9.5 vs 27.2 fractures per 1000 person-years).

Meaning  Among older patients using medium to high doses of prednisolone, alendronate use was associated with a lower risk of hip fracture.


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.