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

      research-article
      , MD, MSc 1 , 2 , , MD, PhD 2 , 3 , , PhD 4 , , PhD 5 , , MD, PhD 2 , 6 ,
      JAMA
      American Medical Association

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          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.

          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.

          Abstract

          This Swedish cohort study investigates whether treatment with alendronate is associated with reduced risk of hip fracture among older patients using oral glucocorticoids.

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          Author and article information

          Journal
          JAMA
          JAMA
          JAMA
          JAMA
          American Medical Association
          0098-7484
          1538-3598
          11 July 2017
          11 July 2017
          11 January 2018
          : 318
          : 2
          : 146-155
          Affiliations
          [1 ]Department of Orthopaedic Surgery, Skaraborg Hospital, Skövde, Sweden
          [2 ]Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
          [3 ]Department of Endocrinology, Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
          [4 ]Health Metrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
          [5 ]School of Bioscience, University of Skövde, Skövde, Sweden
          [6 ]Geriatric Medicine, Sahlgrenska University Hospital, Mölndal, Sweden
          Author notes
          Article Information
          Corresponding Author: Mattias Lorentzon, MD, PhD, Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy, Bldg K, Sixth Floor, Sahlgrenska University Hospital, Mölndal, 431 80 Mölndal, Sweden ( mattias.lorentzon@ 123456medic.gu.se ).
          Accepted for Publication: June 13, 2017.
          Author Contributions: Drs Axelsson and Lorentzon had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
          Study concept and design: Axelsson, Nilsson, Lorentzon.
          Acquisition, analysis, or interpretation of data: All authors.
          Drafting of the manuscript: Axelsson, Nilsson, Lorentzon.
          Critical revision of the manuscript for important intellectual content: All authors.
          Statistical analysis: All authors.
          Obtained funding: Axelsson, Lorentzon.
          Administrative, technical, or material support: Axelsson, Lorentzon.
          Study supervision: Lorentzon.
          Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Axelsson has received lecture fees from Lilly and Meda. Dr Nilsson has received lecture fees from Shire and Pfizer. Dr Lorentzon has received lecture fees from Amgen, Lilly, Meda, Renapharma, and UCB and consulting fees from Radius Health and Consilient Health. No other disclosures were reported.
          Funding/Support: This study was funded by the Research Fund at Skaraborg Hospital Skövde, the Skaraborg Institute, the Swedish Research Council, the ALF/LUA grant from the Sahlgrenska University Hospital, and King Gustaf V’s and Queen Victoria’s Freemason Foundation.
          Role of the Funders/Sponsors: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
          Additional Contributions: Aldina Pivodic, MSc (Statistiska Konsultgruppen, Gothenburg, Sweden) contributed specific analyses regarding verification of the Cox model proportionality assumption and confidence intervals for incidence rates per 1000 person-years, for which she was financially compensated.
          Article
          PMC5817469 PMC5817469 5817469 joi170071
          10.1001/jama.2017.8040
          5817469
          28697254
          ddc83b87-f521-4bad-94ad-217fb7de8b2a
          Copyright 2017 American Medical Association. All Rights Reserved.
          History
          : 2 March 2017
          : 5 June 2017
          : 13 June 2017
          Funding
          Funded by: Skaraborg Hospital Skövde
          Funded by: Skaraborg Institute
          Funded by: Swedish Research Council
          Funded by: Sahlgrenska University Hospital
          Funded by: King Gustaf V’s and Queen Victoria’s Freemason Foundation
          Categories
          Research
          Research
          Original Investigation

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