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Recent reports, from The Netherlands1 and the UK,2 suggest that statins have a modifying role in osteoarthritis (OA) using different outcome definitions, specifically radiographic OA in the Rotterdam cohort and general practitioner diagnosis from a national database in the UK study. On the other hand, a large longitudinal study from the USA found that statin use was not associated with improvements in knee pain, function or structural progression over a 4-year period.3 A separate US longitudinal study in elderly women found that statin use may be associated with an increased risk of developing incident radiographic hip OA.4 The discrepancies between published studies on statins and OA may be due to methodological factors as has been discussed elsewhere.5
Studies of generalised OA suggest the potential role of systemic processes in disease pathogenesis.6 It has been hypothesised, based on evidence from in vitro studies, that a dysfunction in lipid metabolism may play a role in the pathogenesis of OA.7
It is therefore possible that lipid dysregulation may be involved more in generalised polyarticular OA than in single large joint OA. Generalised OA (GOA) refers to the involvement of at least three joints, or a group of joints, for example, the interphalangeal (IP) joints. The nodal type of GOA, characterised by Heberden's and Bouchard's nodes predominates in women and associates with underlying radiographic IP OA.8 There is no agreed consensus definition for generalised OA, but the presence of IP nodes has been shown to result in a different profile of risk factors for both hip and knee OA.9
In order to test if statin use is associated with generalised nodal OA, we used data from the Genetics of OA and Lifestyle (GOAL) study, a large case-control study involving clinically severe OA cases, with full radiographic assessment, recruited from secondary care. 8 We focused on the following eight outcomes: (1) nodal OA defined as Heberden's or Bouchard's nodes affecting two or more rays of both hands; (2) knee OA defined as a Kellgren–Lawrence (K/L) score ≥2 at the tibiofemoral compartment of either knee excluding hip OA; (3) radiographic hip OA defined as a K/L ≥2 at either hip excluding knee OA; (4) hip and knee OA pelvis K/L ≥2 at either hip and tibiofemoral ≥2 at either knee; (5) generalised knee OA defined as knee OA in addition to nodal status excluding hip OA; (6) generalised hip OA defined as hip OA in addition to nodal status excluding knee OA; (7) generalised hip and knee OA; (8) any GOA (the sum of 5, 6 and 7 above). Details on X-rays and patient recruitment have been reported elsewhere.9 The descriptive characteristics of study participants are shown in table 1.
After adjustment for confounders we find no evidence for an association between nodal OA, hip OA or knee OA and use of statins (table 2). However, use of statins is associated with a lower prevalence of the GOA phenotype. This association remains statistically significant after further adjustment for a diagnosis of various comorbidities (table 2).
The present study has a number of limitations: its cross-sectional nature, a hospital-based case control design, and the lack of statin dose information. Nonetheless, our data provide further evidence supporting that statin use may affect OA although in our case only a specific OA phenotype (ie, generalised nodal OA). Given the lack of structure-modifying drugs,10 it would be much welcome news if statins were proved to reduce OA risk or progression even if this was only on a subset of patients. Further studies primarily designed to address this question are warranted.
Contributors All authors contributed to the study design, data interpretation and the final manuscript. AMV analysed and interpreted the data and prepared the manuscript.
Funding Supported by a EULAR project grant to AMV (grant 108239), AstraZeneca UK funded the GOAL study sample and data collection.
Competing interests None.
Ethics approval The Nottingham City Hospital and North Nottinghamshire Research Ethics Committees.
Provenance and peer review Not commissioned; externally peer reviewed.