Statin use and clinical osteoarthritis in the general population: a longitudinal study

U T Kadam, M Blagojevic, J Belcher, U T Kadam, M Blagojevic, J Belcher

Abstract

Background: One hypothesis has posited whether abnormal lipid metabolism might be a causal factor in the pathogenesis of osteoarthritis (OA). Routine statin use in clinical practice provides the basis for a natural experiment in testing this hypothesis.

Objective: To test the hypothesis that statins reduce the long-term occurrence of clinically defined OA.

Design: Cohort design with a 10-year follow-up.

Participants: 16,609 adults cardiovascular disease cohorts aged 40 years and over from the UK General Practice Research Database with data available to 31 December 2006.

Intervention: Statins were summarised as annual mean daily dose and dose change over two-year time periods.

Main measures: Incident episode of clinically defined osteoarthritis was assessed within 2 years, and at 4-year and 10-year follow-up time periods, using Cox and discrete time survival analysis. Covariates included age, gender, deprivation, body mass index, cholesterol level, pain-modifying drug co-therapies, and duration and severity of cardiovascular disease.

Key results: Higher therapeutic dose of statin, with a treatment duration of at least 2 years was associated with a significant reduction in clinical OA compared to non-statin users in the follow-up time period. The estimated adjusted rate ratios were as follows: lowest statin dose quartile 1: 2.5 (95 % CI 2.3, 2.9); quartile 2: 1.3 (1.1, 1.5); quartile 3: 0.8 (0.7, 0.95); and highest statin dose quartile 4: 0.4 (0.3, 0.5). The largest statin dose increments were associated with significant reductions estimated at 18 % in OA outcome within 2 years and 40 % after 4 years, compared to non-statin users.

Conclusions: This longitudinal study from a national clinical practice setting provides evidence that higher statin dose and larger statin dose increments were associated with a reduction in clinically defined OA outcome.

Conflict of interest statement

The authors declare that they do not have a conflict of interest.

Figures

Figure 1.
Figure 1.
Statin dose increments over the 10-year follow-up period.
Figure 2.
Figure 2.
Cumulative Kaplan-Meier plots for statin dose quartile groups and osteoarthritis (OA) outcome over 10-year follow-up.

References

    1. Brandt KD, Doherty M, Lohmander LS. Osteoarthritis. 2. Oxford: OUP; 2003.
    1. Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence. Osteoarthritis Cartilage. 2007;15(9):981–1000. doi: 10.1016/j.joca.2007.06.014.
    1. Kellgren JH, Moore R. Generalized osteoarthritis and Heberden’s nodes. Br Med J. 1952;1(4751):181–187. doi: 10.1136/bmj.1.4751.181.
    1. Cooper C, Egger P, Coggon D, et al. Generalized osteoarthritis in women: pattern of joint involvement and approaches to definition for epidemiological studies. J Rheumatol. 1996;23(11):1938–1942.
    1. Aspden RM, Scheven BA, Hutchison JD. Osteoarthritis as a systemic disorder including stromal cell differentiation and lipid metabolism. Lancet. 2001;357(9262):1118–1120. doi: 10.1016/S0140-6736(00)04264-1.
    1. Conaghan PG, Vanharanta H, Dieppe PA. Is progressive osteoarthritis an atheromatous vascular disease? Ann Rheum Dis. 2005;64(11):1539–1541. doi: 10.1136/ard.2005.039263.
    1. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–147. doi: 10.1126/science.284.5411.143.
    1. Diascro DD, Jr, Vogel RL, Johnson TE, et al. High fatty acid content in rabbit serum is responsible for the differentiation of osteoblasts into adipocyte-like cells. J Bone Miner Res. 1998;13(1):96–106. doi: 10.1359/jbmr.1998.13.1.96.
    1. Dumond H, Presle N, Terlain B, et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 2003;48(11):3118–3129. doi: 10.1002/art.11303.
    1. Lippiello L, Walsh T, Fienhold M. The association of lipid abnormalities with tissue pathology in human osteoarthritic articular cartilage. Metabolism. 1991;40(6):571–576. doi: 10.1016/0026-0495(91)90046-Y.
    1. Kadam UT, Jordan K, Croft PR. Clinical comorbidity in patients with osteoarthritis: a case–control study of general practice consulters in England and Wales. Ann Rheum Dis. 2004;63(4):408–414. doi: 10.1136/ard.2003.007526.
    1. Singh G, Miller JD, Lee FH, Pettitt D, Russell MW. Prevalence of cardiovascular disease risk factors among US adults with self-reported osteoarthritis: data from the Third National Health and Nutrition Examination Survey. Am J Manag Care. 2002;8(15 Suppl):S383–S391.
    1. Sturmer T, Sun Y, Sauerland S, et al. Serum cholesterol and osteoarthritis. The baseline examination of the Ulm Osteoarthritis Study. J Rheumatol. 1998;25(9):1827–1832.
    1. Nuesch E, Dieppe P, Reichenbach S, Williams S, Iff S, Juni P. All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study. BMJ. 2011;342:d1165. doi: 10.1136/bmj.d1165.
    1. Baker JF, Walsh P, Mulhall KJ. Statins: a potential role in the management of osteoarthritis? Joint Bone Spine. 2011;78(1):31–34. doi: 10.1016/j.jbspin.2010.02.035.
    1. Kadam UT, Holmberg A, Blagojevic M, Nilsson PM, Åkesson K. Risk factors for cardiovascular disease and future osteoarthritis-related arthroplasty: a population-based cohort study in men and women from Malmö, Sweden. Scan J Rheum. 2011;40(6):478–85. doi: 10.3109/03009742.2011.585619.
    1. Beattie MS, Lane NE, Hung YY, Nevitt MC. Association of statin use and development and progression of hip osteoarthritis in elderly women. J Rheumatol. 2005;32(1):106–110.
    1. Clockaerts S, Van Osch GJ, Bastiaansen-Jenniskens Y, et al. Statin use is associated with reduced incidence and progression of knee osteoarthritis in the Rotterdam study. Ann Rheum Dis. 2012;71(5):642–7. doi: 10.1136/annrheumdis-2011-200092.
    1. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110(2):227–39. doi: 10.1161/01.CIR.0000133317.49796.0E.
    1. Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med. 2004;351(25):2611–2618. doi: 10.1056/NEJMoa041747.
    1. van Staa TP, Wegman S, de Vries F, Leufkens B, Cooper C. Use of statins and risk of fractures. JAMA. 2001;285(14):1850–1855. doi: 10.1001/jama.285.14.1850.
    1. Harding A, Stuart-Buttle C. The development and role of the Read Codes. J AHIMA. 1998;69(5):34–38.
    1. British Medical Association and the Royal Pharmaceutical Society of Great Britain. British National Formulary, No. 58 September 2009. London: BMJ Group and Pharm Press; 2009.
    1. Weng TC, Yang YH, Lin SJ, Tai SH. A systematic review and meta-analysis on the therapeutic equivalence of statins. J Clin Pharm Ther. 2010;35(2):139–51. doi: 10.1111/j.1365-2710.2009.01085.x.
    1. Kadam UT, Croft PR. Clinical comorbidity in osteoarthritis: associations with physical function in older patients in family practice. J Rheumatol. 2007;34(9):1899–1904.
    1. Kopec JA, Rahman MM, Berthelot JM, et al. Descriptive epidemiology of osteoarthritis in British Columbia, Canada. J Rheumatol. 2007;34(2):386–93.
    1. Pereira D, Peleteiro B, Araújo J, Branco J, Santos RA, Ramos E. The effect of osteoarthritis definition on prevalence and incidence estimates: a systematic review. Osteoarthritis Cartilage. 2011;19(11):1270–85. doi: 10.1016/j.joca.2011.08.009.
    1. Creamer P, Hochberg MC. Why does osteoarthritis of the knee hurt–sometimes? Br J Rheumatol. 1997;36(7):726–728. doi: 10.1093/rheumatology/36.7.726.
    1. Neogi T, Felson D, Niu J, et al. Association between radiographic features of knee osteoarthritis and pain: results from two cohort studies. BMJ. 2009;339:b2844. doi: 10.1136/bmj.b2844.
    1. Suissa S. Immortal time bias in pharmaco-epidemiology. Am J Epidemiol. 2008;167(4):492–9. doi: 10.1093/aje/kwm324.
    1. Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2008;16(2):137–162. doi: 10.1016/j.joca.2007.12.013.
    1. Office of the Deputy Prime Minister. The English Indices of deprivation 2004—summary (revised). 2004; Link: .
    1. Lakhan SE, Bagchi S, Hofer M. Statins and clinical outcome of acute ischemic stroke: a systematic review. Int Arch Med. 2010;3:22. doi: 10.1186/1755-7682-3-22.
    1. Bavry AA, Mood GR, Kumbhani DJ, Borek PP, Askari AT, Bhatt DL. Long-term benefit of statin therapy initiated during hospitalization for an acute coronary syndrome: a systematic review of randomized trials. Am J Cardiovasc Drugs. 2007;7(2):135–141. doi: 10.2165/00129784-200707020-00005.
    1. Hart DJ, Doyle DV, Spector TD. Association between metabolic factors and knee osteoarthritis in women: the Chingford Study. J Rheumatol. 1995;22(6):1118–1123.
    1. Lago F, Gomez R, Conde J, Scotece M, Gomez-Reino JJ, Gualillo O. Cardiometabolic comorbidities and rheumatic diseases: Focus on the role of fat mass and adipokines. Arthritis Care Res (Hoboken) 2011;63(8):1083–90. doi: 10.1002/acr.20488.
    1. Jonsson H, Helgadottir GP, Aspelund T, et al. Hand osteoarthritis in older women is associated with carotid and coronary atherosclerosis: the AGES Reykjavik study. Ann Rheum Dis. 2009;68(11):1696–1700. doi: 10.1136/ard.2008.096289.
    1. Haara MM, Manninen P, Kroger H, et al. Osteoarthritis of finger joints in Finns aged 30 or over: prevalence, determinants, and association with mortality. Ann Rheum Dis. 2003;62(2):151–158. doi: 10.1136/ard.62.2.151.
    1. Schett G, Kleyer A, Perricone C, et al. Diabetes is an independent predictor for severe osteoarthritis: results from a longitudinal cohort study. Diabetes Care. 2013;36(2):403–409.
    1. Attur MG, Dave M, Akamatsu M, Katoh M, Amin AR. Osteoarthritis or osteoarthrosis: the definition of inflammation becomes a semantic issue in the genomic era of molecular medicine. Osteoarthritis Cartilage. 2002;10(1):1–4. doi: 10.1053/joca.2001.0488.
    1. Goldring SR, Goldring MB. The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res. 2004;427:S27–S36. doi: 10.1097/01.blo.0000144854.66565.8f.
    1. Burrage PS, Brinckerhoff CE. Molecular targets in osteoarthritis: metalloproteinases and their inhibitors. Curr Drug Targets. 2007;8(2):293–303. doi: 10.2174/138945007779940098.
    1. Herrett E, Thomas SL, Schoonen WM, Smeeth L, Hall AJ. Validation and validity of diagnoses in the General Practice Research Database: a systematic review. Br J Clin Pharmacol. 2010;69(1):4–14. doi: 10.1111/j.1365-2125.2009.03537.x.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅