Skip to main content
Top
Published in: Journal of General Internal Medicine 7/2013

Open Access 01-07-2013 | Original Research

Statin Use and Clinical Osteoarthritis in the General Population: A Longitudinal Study

Authors: U. T. Kadam, PhD, M. Blagojevic, PhD, J. Belcher, PhD

Published in: Journal of General Internal Medicine | Issue 7/2013

Login to get access

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.
Literature
1.
go back to reference Brandt KD, Doherty M, Lohmander LS. Osteoarthritis. 2nd ed. Oxford: OUP; 2003. Brandt KD, Doherty M, Lohmander LS. Osteoarthritis. 2nd ed. Oxford: OUP; 2003.
2.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
3.
go back to reference Kellgren JH, Moore R. Generalized osteoarthritis and Heberden’s nodes. Br Med J. 1952;1(4751):181–187.PubMedCrossRef Kellgren JH, Moore R. Generalized osteoarthritis and Heberden’s nodes. Br Med J. 1952;1(4751):181–187.PubMedCrossRef
4.
go back to reference 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.PubMed 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.PubMed
5.
go back to reference Aspden RM, Scheven BA, Hutchison JD. Osteoarthritis as a systemic disorder including stromal cell differentiation and lipid metabolism. Lancet. 2001;357(9262):1118–1120.PubMedCrossRef Aspden RM, Scheven BA, Hutchison JD. Osteoarthritis as a systemic disorder including stromal cell differentiation and lipid metabolism. Lancet. 2001;357(9262):1118–1120.PubMedCrossRef
6.
go back to reference Conaghan PG, Vanharanta H, Dieppe PA. Is progressive osteoarthritis an atheromatous vascular disease? Ann Rheum Dis. 2005;64(11):1539–1541.PubMedCrossRef Conaghan PG, Vanharanta H, Dieppe PA. Is progressive osteoarthritis an atheromatous vascular disease? Ann Rheum Dis. 2005;64(11):1539–1541.PubMedCrossRef
7.
go back to reference Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–147.PubMedCrossRef Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–147.PubMedCrossRef
8.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
9.
go back to reference Dumond H, Presle N, Terlain B, et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 2003;48(11):3118–3129.PubMedCrossRef Dumond H, Presle N, Terlain B, et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 2003;48(11):3118–3129.PubMedCrossRef
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
12.
go back to reference 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.PubMed 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.PubMed
13.
go back to reference 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.PubMed 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.PubMed
15.
go back to reference Baker JF, Walsh P, Mulhall KJ. Statins: a potential role in the management of osteoarthritis? Joint Bone Spine. 2011;78(1):31–34.PubMedCrossRef Baker JF, Walsh P, Mulhall KJ. Statins: a potential role in the management of osteoarthritis? Joint Bone Spine. 2011;78(1):31–34.PubMedCrossRef
16.
go back to reference 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.CrossRef 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.CrossRef
17.
go back to reference 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.PubMed 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.PubMed
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference Harding A, Stuart-Buttle C. The development and role of the Read Codes. J AHIMA. 1998;69(5):34–38.PubMed Harding A, Stuart-Buttle C. The development and role of the Read Codes. J AHIMA. 1998;69(5):34–38.PubMed
23.
go back to reference 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. 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.
24.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
25.
go back to reference 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.PubMed 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.PubMed
26.
go back to reference Kopec JA, Rahman MM, Berthelot JM, et al. Descriptive epidemiology of osteoarthritis in British Columbia, Canada. J Rheumatol. 2007;34(2):386–93.PubMed Kopec JA, Rahman MM, Berthelot JM, et al. Descriptive epidemiology of osteoarthritis in British Columbia, Canada. J Rheumatol. 2007;34(2):386–93.PubMed
27.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
28.
go back to reference Creamer P, Hochberg MC. Why does osteoarthritis of the knee hurt–sometimes? Br J Rheumatol. 1997;36(7):726–728.PubMedCrossRef Creamer P, Hochberg MC. Why does osteoarthritis of the knee hurt–sometimes? Br J Rheumatol. 1997;36(7):726–728.PubMedCrossRef
30.
31.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
33.
go back to reference Lakhan SE, Bagchi S, Hofer M. Statins and clinical outcome of acute ischemic stroke: a systematic review. Int Arch Med. 2010;3:22.PubMedCrossRef Lakhan SE, Bagchi S, Hofer M. Statins and clinical outcome of acute ischemic stroke: a systematic review. Int Arch Med. 2010;3:22.PubMedCrossRef
34.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
35.
go back to reference 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.PubMed 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.PubMed
36.
go back to reference 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.CrossRef 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.CrossRef
37.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
38.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
39.
go back to reference 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. 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.
40.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
41.
go back to reference Goldring SR, Goldring MB. The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res. 2004;427:S27–S36.PubMedCrossRef Goldring SR, Goldring MB. The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res. 2004;427:S27–S36.PubMedCrossRef
42.
go back to reference Burrage PS, Brinckerhoff CE. Molecular targets in osteoarthritis: metalloproteinases and their inhibitors. Curr Drug Targets. 2007;8(2):293–303.PubMedCrossRef Burrage PS, Brinckerhoff CE. Molecular targets in osteoarthritis: metalloproteinases and their inhibitors. Curr Drug Targets. 2007;8(2):293–303.PubMedCrossRef
43.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
Metadata
Title
Statin Use and Clinical Osteoarthritis in the General Population: A Longitudinal Study
Authors
U. T. Kadam, PhD
M. Blagojevic, PhD
J. Belcher, PhD
Publication date
01-07-2013
Publisher
Springer-Verlag
Published in
Journal of General Internal Medicine / Issue 7/2013
Print ISSN: 0884-8734
Electronic ISSN: 1525-1497
DOI
https://doi.org/10.1007/s11606-013-2382-8

Other articles of this Issue 7/2013

Journal of General Internal Medicine 7/2013 Go to the issue

Innovation and Improvement: Interval Examination

Interval Examination: Moving Toward Open Notes

Clinical Practice: Clinical Images

Nonmalignant Superior Vena Cava Syndrome

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.