Association between bisphosphonate use and implant survival after primary total arthroplasty of the knee or hip: population based retrospective cohort study

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Abstract

Objectives To test whether bisphosphonate use is related to improved implant survival after total arthroplasty of the knee or hip.

Design Population based retrospective cohort study.

Setting Primary care data from the United Kingdom.

Participants All patients undergoing primary total arthroplasty of the knee (n=18 726) or hip (n=23 269) in 1986-2006 within the United Kingdom’s General Practice Research Database. We excluded patients with a history of hip fracture before surgery or rheumatoid arthritis, and individuals younger than 40 years at surgery.

Intervention Bisphosphonate users were classified as patients with at least six prescriptions of bisphosphonates or at least six months of prescribed bisphosphonate treatment with more than 80% adherence before revision surgery.

Outcome measures Revision arthroplasties occurring after surgery, identified by READ and OXMIS codes. Parametric survival models were used to determine effects on implant survival with propensity score adjustment to account for confounding by indication.

Results Of 41 995 patients undergoing primary hip or knee arthroplasty, we identified 1912 bisphosphonate users, who had a lower rate of revision at five years than non-users (0.93% (95% confidence interval 0.52% to 1.68%) v 1.96% (1.80% to 2.14%)). Implant survival was significantly longer in bisphosphonate users than in non-users in propensity adjusted models (hazard ratio 0.54 (0.29 to 0.99); P=0.047) and had an almost twofold increase in time to revision after hip or knee arthroplasty (time ratio 1.96 (1.01 to 3.82)). Assuming 2% failure over five years, we estimated that the number to treat to avoid one revision was 107 for oral bisphosphonates.

Conclusions In patients undergoing lower limb arthroplasty, bisphosphonate use was associated with an almost twofold increase in implant survival time. These findings require replication and testing in experimental studies for confirmation.

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Most cited references 23

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Bisphosphonate use and atypical fractures of the femoral shaft.

Karl Michaëlsson, Per Aspenberg, Jörg Schilcher (2011)

Studies show conflicting results regarding the possible excess risk of atypical fractures of the femoral shaft associated with bisphosphonate use. In Sweden, 12,777 women 55 years of age or older sustained a fracture of the femur in 2008. We reviewed radiographs of 1234 of the 1271 women who had a subtrochanteric or shaft fracture and identified 59 patients with atypical fractures. Data on medications and coexisting conditions were obtained from national registries. The relative and absolute risk of atypical fractures associated with bisphosphonate use was estimated by means of a nationwide cohort analysis. The 59 case patients were also compared with 263 control patients who had ordinary subtrochanteric or shaft fractures. The age-adjusted relative risk of atypical fracture was 47.3 (95% confidence interval [CI], 25.6 to 87.3) in the cohort analysis. The increase in absolute risk was 5 cases per 10,000 patient-years (95% CI, 4 to 7). A total of 78% of the case patients and 10% of the controls had received bisphosphonates, corresponding to a multivariable-adjusted odds ratio of 33.3 (95% CI, 14.3 to 77.8). The risk was independent of coexisting conditions and of concurrent use of other drugs with known effects on bone. The duration of use influenced the risk (odds ratio per 100 daily doses, 1.3; 95% CI, 1.1 to 1.6). After drug withdrawal, the risk diminished by 70% per year since the last use (odds ratio, 0.28; 95% CI, 0.21 to 0.38). These population-based nationwide analyses may be reassuring for patients who receive bisphosphonates. Although there was a high prevalence of current bisphosphonate use among patients with atypical fractures, the absolute risk was small. (Funded by the Swedish Research Council.).

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One in four people may develop symptomatic hip osteoarthritis in his or her lifetime.

Andrea Murphy, Derrick Renner, Gary G. Koch … (2010)

To estimate the lifetime risk of symptomatic hip osteoarthritis (OA). We analyzed data from the Johnston County Osteoarthritis Project [a longitudinal population-based study of OA in North Carolina, United States (n=3068)]. The weighted baseline sample comprised 18% blacks and 54% women, and the mean age was 63 years (range=45-93). Symptomatic hip OA was defined as a Kellgren-Lawrence (K-L) radiographic score of ≥ 2 (anterior-posterior pelvis X-rays) and pain, aching or stiffness on most days, or groin pain, in the same hip. Lifetime risk, defined as the proportion who developed symptomatic hip OA in at least one hip by age 85, among people who live to age 85, was modeled using logistic regression with repeated measures (through generalized estimating equations). Lifetime risk of symptomatic hip OA was 25.3% [95% confidence interval (CI)=21.3-29.3]. Lifetime risk was similar by sex, race, highest educational attainment, and hip injury history. We studied lifetime risk by body mass index (BMI) in three forms: at age 18; at baseline and follow-up; and at age 18, baseline and follow-up and found no differences in estimates. The burden of symptomatic hip OA is substantial with one in four people developing this condition by age 85. The similar race-specific estimates suggest that racial disparities in total hip replacements are not attributable to differences in disease occurrence. Despite increasing evidence that obesity predicts an increased risk of both hip OA and joint replacement, we found no association between BMI and lifetime risk. Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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Parametric survival analysis and taxonomy of hazard functions for the generalized gamma distribution.

Haitao Chu, F. Schneider, Alvaro Muñoz-Noval … (2007)

The widely used Cox proportional hazards regression model for the analysis of censored survival data has limited utility when either hazard functions themselves are of primary interest, or when relative times instead of relative hazards are the relevant measures of association. Parametric regression models are an attractive option in situations such as this, although the choice of a particular model from the available families of distributions can be problematic. The generalized gamma (GG) distribution is an extensive family that contains nearly all of the most commonly used distributions, including the exponential, Weibull, log normal and gamma. More importantly, the GG family includes all four of the most common types of hazard function: monotonically increasing and decreasing, as well as bathtub and arc-shaped hazards. We present here a taxonomy of the hazard functions of the GG family, which includes various special distributions and allows depiction of effects of exposures on hazard functions. We applied the proposed taxonomy to study survival after a diagnosis of clinical AIDS during different eras of HIV therapy, where proportionality of hazard functions was clearly not fulfilled and flexibility in estimating hazards with very different shapes was needed. Comparisons of survival after AIDS in different eras of therapy are presented in terms of both relative times and relative hazards. Standard errors for these and other derived quantities are computed using the delta method and checked using the bootstrap. Description of standard statistical software (Stata, SAS and S-Plus) for the computations is included and available at http://statepi.jhsph.edu/software.

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Author and article information

Contributors

: Role: postdoctoral research fellow

: Role: lecturer in metabolic bone disease

: Role: senior statistician

: Role: professor of orthopaedics

: Role: professor of rheumatology

: Role: professor in rheumatic diseases and consultant rheumatologist

Journal

Journal ID (nlm-ta): BMJ

Journal ID (publisher-id): bmj

Title: BMJ : British Medical Journal

Publisher: BMJ Publishing Group Ltd.

ISSN (Print): 0959-8138

ISSN (Electronic): 1468-5833

Publication date Collection: 2011

Publication date (Print): 2011

Publication date (Electronic): 06 December 2011

Volume: 343

Electronic Location Identifier: d7222

Affiliations

[1 ]Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK

[2 ]Institut Català de la Salut, Barcelona, Spain

[3 ]Unitat de Recerca en Fisiopatologia Òssia i Articular (URFOA), Institut Municipal d’Investigació Mèdica (IMIM), Barcelona

[4 ]Department of Medicine, Universitat Autonoma de Barcelona, Barcelona

[5 ]Primary Care Research Institute, IDIAP (Institut D’Investigació en Atenció Primària) Jordi Gol, Barcelona

[6 ]MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK

Author notes

Correspondence to: N Arden nigel.arden@ 123456ndorms.ox.ac.uk

Article

Publisher ID: prid887786

DOI: 10.1136/bmj.d7222

PMC ID: 3232250

PubMed ID: 22147909

SO-VID: 056adf50-601c-41dd-9f6a-1ddcb979aeea

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

Association between bisphosphonate use and implant survival after primary total arthroplasty of the knee or hip: population based retrospective cohort study

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SICOT-J (Orthopedic surgery and traumatology)

Most cited references 23

Bisphosphonate use and atypical fractures of the femoral shaft.

One in four people may develop symptomatic hip osteoarthritis in his or her lifetime.

Parametric survival analysis and taxonomy of hazard functions for the generalized gamma distribution.

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