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Comparative anti-fracture effectiveness of different oral anti-osteoporosis therapies based on “real-world” data: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database

Authors Khalid S, Calderon-Larrañaga S, Hawley S, Ali MS, Judge A, Arden N, van Staa T, Cooper C, Javaid MK, Prieto-Alhambra D

Received 30 January 2018

Accepted for publication 20 April 2018

Published 9 October 2018 Volume 2018:10 Pages 1417—1431


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 5

Editor who approved publication: Professor Henrik Toft Sørensen

Sara Khalid,1,2 Sara Calderon-Larrañaga,3 Samuel Hawley,2 M Sanni Ali1,2,4 Andrew Judge,1,2,5 Nigel Arden,6 Tjeerd van Staa,7,8 Cyrus Cooper,2,9,10 Muhammad Kassim Javaid,2 Daniel Prieto-Alhambra2,11

1Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, 2Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom; 3Family and Community Medicine Teaching Unit of Granada. Cartuja University Health Centre. Andalusian Health Service (SAS), Granada, Spain; 4London School of Hygiene and Tropical Medicine, London, United Kingdom; 5Bristol NIHR Biomedical Research Centre, Musculoskeletal Research Unit, Southmead Hospital, University of Bristol, Bristol, United Kingdom; 6Arthritis Research UK Centre for Sport, Exercise, and Osteoarthritis, University of Oxford, Oxford, United Kingdom; 7Farr Institute, University of Manchester, Manchester, United Kingdom; 8Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; 9Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom; 10NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; 11GREMPAL (Grup de Recerca en Malalties Prevalents de l’Aparell Locomotor) Research Group, Idiap Jordi Gol Primary Care Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain

Purpose: This paper aims to compare the clinical effectiveness of oral anti-osteoporosis drugs based on the observed risk of fracture while on treatment in primary care actual practice.
Materials and methods: We investigated two primary care records databases covering UK National Health Service (Clinical Practice Research Datalink, CPRD) and Catalan healthcare (Information System for Research in Primary Care, SIDIAP) patients during 1995–2014 and 2006–2014, respectivey. Treatment-naive incident users of anti-osteoporosis drugs were included and followed until treatment cessation, switching, death, transfer out, or study completion. We considered hip fracture while on treatment as main outcome and major osteoporotic fractures (hip, clinical spine, wrist, and proximal humerus) as secondary outcome. Users of alendronate (reference group) were compared to those of (1) OBP, (2) strontium ranelate (SR), and (3) selective estrogen receptor modulators (SERMs), after matching on baseline characteristics using propensity scores. Multiple imputation was used to handle missing data on confounders and competing risk modelling for the calculation of relative risk according to therapy. Country-specific data were analyzed separately and meta-analyzed.
Results: A total of 163,950 UK and 145,236 Catalan patients were identified. Hip (sub-hazard ratio [SHR] [95% CI] 1.04 [0.77–1.40]) and major osteoporotic (SHR [95% CI] 1 [0.78–1.27]) fracture risks were similar among OBP compared to alendronate users. Both hip (SHR [95% CI] 1.26 [1.14–1.39]) and major osteoporotic (SHR [95% CI] 1.06 [1.02–1.12]) fracture risk were higher in SR compared to alendronate users. SERM users had a reduced hip (SHR [95% CI] 0.75 [0.60–0.94]) and major osteoporotic (SHR [95% CI] 0.77 [0.72–0.83]) fracture risk compared to alendronate users.
Conclusion: We found a 26% excess hip fracture risk among SR compared to matched alendronate users, in line with placebo-controlled RCT findings. Conversely, in a lower risk population, SERM users had a 25% reduced hip fracture risk compared to alendronate users. Head-to-head RCTs are needed to confirm these findings.

Keywords: pharmaco-epidemiology, anti-osteoporosis medication, osteoporosis, fracture risk, electronic health records

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