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Clin Epidemiol. 2018 Oct 9;10:1417-1431. doi: 10.2147/CLEP.S164112. eCollection 2018.

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.

Author information

Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences.
Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom,
Family and Community Medicine Teaching Unit of Granada. Cartuja University Health Centre. Andalusian Health Service (SAS), Granada, Spain.
London School of Hygiene and Tropical Medicine, London, United Kingdom.
Bristol NIHR Biomedical Research Centre, Musculoskeletal Research Unit, Southmead Hospital, University of Bristol, Bristol, United Kingdom.
Arthritis Research UK Centre for Sport, Exercise, and Osteoarthritis, University of Oxford, Oxford, United Kingdom.
Farr Institute, University of Manchester, Manchester, United Kingdom.
Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom.
NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
GREMPAL (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,



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.


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.


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.


anti-osteoporosis medication; electronic health records; fracture risk; osteoporosis; pharmaco-epidemiology

Conflict of interest statement

Disclosure All authors have completed the ICMJE uniform disclosure form and declare: financial support for the submitted work from the National Osteoporosis Society (UK) DPA’s research group has received a Project Grant from the National Osteoporosis Society (United Kingdom), research grants and speaker fees from Amgen, consultancy fees and research grant from UCB; and research grants from Servier Laboratoires; DPA receives funding from the National Institute of Health Research (NIHR) in the form of a Clinician Scientist award (CS-2013-13-012); AJ has received consultancy, lecture fees and honoraria from Servier, UK Renal Registry, Oxford Craniofacial Unit, Idiap Jordi Gol, Freshfields Bruckhaus Deringer, has held advisory board positions (which involved receipt of fees) from Anthera Pharmaceuticals, Inc., and received research sponsorship from ROCHE; CC has received personal fees from Alliance for Better Bone Health, Amgen, Elli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda, and UCB; all other authors have no conflicts of interest to declare. Part of the work on this paper was presented as an oral communication in Rheumatology 2017 (Birmingham, 25–27 April 2017).

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