Statin therapy and risk of fracture results from the jupiter randomized clinical trial

Jessica M. Pena, Sara Aspberg, Jean MacFadyen, Robert J. Glynn, Daniel H. Solomon, Paul M. Ridker

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE Osteoporosis and cardiovascular disease may share common biological pathways, with inflammation playing a role in the development of both. Although observational studies have suggested that statin use is associated with a lower risk of fractures, randomized trial data addressing this issue are scant. OBJECTIVE To determine whether statin therapy reduces the risk of fracture and, in a secondary analysis, whether baseline levels of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) are associated with the risk of fracture. DESIGN, SETTING, AND PARTICIPANTS The JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial was an international, randomized, double-blind, placebo-controlled study enrolling 17 802 men older than 50 years and women older than 60 years with hs-CRP level of at least 2mg/L. Participants were screened from 2003 to 2006 and observed prospectively for up to 5 years (median follow-up, 1.9 years). INTERVENTION Rosuvastatin calcium, 20mg daily, or placebo. MAIN OUTCOMES AND MEASURES Incident fracturewas a prespecified secondary end point of JUPITER. Fractures were confirmed by radiographs, computed tomography, bone scan, or other methods. Cox proportional hazards models were used to calculate hazard ratios (HRs) and associated 95%confidence intervals for the risk of fracture according to randomized treatment assignment, as well as increasing tertiles of hs-CRP, controlling for potential confounders. RESULTS During the study, 431 incident fractures were reported and confirmed. Among participants allocated to rosuvastatin, 221 fractures were confirmed, compared with 210 among those allocated to placebo, such that the incidence of fracture in the rosuvastatin and placebo groups was 1.20 and 1.14 per 100 person-years, respectively (adjusted HR, 1.06 [95% CI, 0.88-1.28]; P = .53). Overall, increasing baseline hs-CRP level was not associated with an increased risk of fractures (adjusted HR for each unit increase in hs-CRP tertile, 1.06 [95%CI, 0.94-1.20]; P for trend, .34). CONCLUSIONS AND RELEVANCE Among men and women with elevated hs-CRP level enrolled in a large trial of rosuvastatin therapy for cardiovascular disease, statin therapy did not reduce the risk of fracture. Higher baseline hs-CRP level was not associated with an increased risk of incident fracture. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00239681.

Original languageEnglish (US)
Pages (from-to)171-177
Number of pages7
JournalJAMA Internal Medicine
Volume175
Issue number2
DOIs
StatePublished - Feb 1 2015

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
C-Reactive Protein
Randomized Controlled Trials
Placebos
Therapeutics
Cardiovascular Diseases
Proportional Hazards Models
Osteoporosis
Observational Studies
Rosuvastatin Calcium
Biomarkers
Tomography
Confidence Intervals
Inflammation
Bone and Bones
Incidence

ASJC Scopus subject areas

  • Internal Medicine
  • Medicine(all)

Cite this

Pena, J. M., Aspberg, S., MacFadyen, J., Glynn, R. J., Solomon, D. H., & Ridker, P. M. (2015). Statin therapy and risk of fracture results from the jupiter randomized clinical trial. JAMA Internal Medicine, 175(2), 171-177. https://doi.org/10.1001/jamainternmed.2014.6388

Statin therapy and risk of fracture results from the jupiter randomized clinical trial. / Pena, Jessica M.; Aspberg, Sara; MacFadyen, Jean; Glynn, Robert J.; Solomon, Daniel H.; Ridker, Paul M.

In: JAMA Internal Medicine, Vol. 175, No. 2, 01.02.2015, p. 171-177.

Research output: Contribution to journalArticle

Pena, JM, Aspberg, S, MacFadyen, J, Glynn, RJ, Solomon, DH & Ridker, PM 2015, 'Statin therapy and risk of fracture results from the jupiter randomized clinical trial', JAMA Internal Medicine, vol. 175, no. 2, pp. 171-177. https://doi.org/10.1001/jamainternmed.2014.6388
Pena, Jessica M. ; Aspberg, Sara ; MacFadyen, Jean ; Glynn, Robert J. ; Solomon, Daniel H. ; Ridker, Paul M. / Statin therapy and risk of fracture results from the jupiter randomized clinical trial. In: JAMA Internal Medicine. 2015 ; Vol. 175, No. 2. pp. 171-177.
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abstract = "IMPORTANCE Osteoporosis and cardiovascular disease may share common biological pathways, with inflammation playing a role in the development of both. Although observational studies have suggested that statin use is associated with a lower risk of fractures, randomized trial data addressing this issue are scant. OBJECTIVE To determine whether statin therapy reduces the risk of fracture and, in a secondary analysis, whether baseline levels of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) are associated with the risk of fracture. DESIGN, SETTING, AND PARTICIPANTS The JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial was an international, randomized, double-blind, placebo-controlled study enrolling 17 802 men older than 50 years and women older than 60 years with hs-CRP level of at least 2mg/L. Participants were screened from 2003 to 2006 and observed prospectively for up to 5 years (median follow-up, 1.9 years). INTERVENTION Rosuvastatin calcium, 20mg daily, or placebo. MAIN OUTCOMES AND MEASURES Incident fracturewas a prespecified secondary end point of JUPITER. Fractures were confirmed by radiographs, computed tomography, bone scan, or other methods. Cox proportional hazards models were used to calculate hazard ratios (HRs) and associated 95{\%}confidence intervals for the risk of fracture according to randomized treatment assignment, as well as increasing tertiles of hs-CRP, controlling for potential confounders. RESULTS During the study, 431 incident fractures were reported and confirmed. Among participants allocated to rosuvastatin, 221 fractures were confirmed, compared with 210 among those allocated to placebo, such that the incidence of fracture in the rosuvastatin and placebo groups was 1.20 and 1.14 per 100 person-years, respectively (adjusted HR, 1.06 [95{\%} CI, 0.88-1.28]; P = .53). Overall, increasing baseline hs-CRP level was not associated with an increased risk of fractures (adjusted HR for each unit increase in hs-CRP tertile, 1.06 [95{\%}CI, 0.94-1.20]; P for trend, .34). CONCLUSIONS AND RELEVANCE Among men and women with elevated hs-CRP level enrolled in a large trial of rosuvastatin therapy for cardiovascular disease, statin therapy did not reduce the risk of fracture. Higher baseline hs-CRP level was not associated with an increased risk of incident fracture. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00239681.",
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AU - Ridker, Paul M.

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N2 - IMPORTANCE Osteoporosis and cardiovascular disease may share common biological pathways, with inflammation playing a role in the development of both. Although observational studies have suggested that statin use is associated with a lower risk of fractures, randomized trial data addressing this issue are scant. OBJECTIVE To determine whether statin therapy reduces the risk of fracture and, in a secondary analysis, whether baseline levels of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) are associated with the risk of fracture. DESIGN, SETTING, AND PARTICIPANTS The JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial was an international, randomized, double-blind, placebo-controlled study enrolling 17 802 men older than 50 years and women older than 60 years with hs-CRP level of at least 2mg/L. Participants were screened from 2003 to 2006 and observed prospectively for up to 5 years (median follow-up, 1.9 years). INTERVENTION Rosuvastatin calcium, 20mg daily, or placebo. MAIN OUTCOMES AND MEASURES Incident fracturewas a prespecified secondary end point of JUPITER. Fractures were confirmed by radiographs, computed tomography, bone scan, or other methods. Cox proportional hazards models were used to calculate hazard ratios (HRs) and associated 95%confidence intervals for the risk of fracture according to randomized treatment assignment, as well as increasing tertiles of hs-CRP, controlling for potential confounders. RESULTS During the study, 431 incident fractures were reported and confirmed. Among participants allocated to rosuvastatin, 221 fractures were confirmed, compared with 210 among those allocated to placebo, such that the incidence of fracture in the rosuvastatin and placebo groups was 1.20 and 1.14 per 100 person-years, respectively (adjusted HR, 1.06 [95% CI, 0.88-1.28]; P = .53). Overall, increasing baseline hs-CRP level was not associated with an increased risk of fractures (adjusted HR for each unit increase in hs-CRP tertile, 1.06 [95%CI, 0.94-1.20]; P for trend, .34). CONCLUSIONS AND RELEVANCE Among men and women with elevated hs-CRP level enrolled in a large trial of rosuvastatin therapy for cardiovascular disease, statin therapy did not reduce the risk of fracture. Higher baseline hs-CRP level was not associated with an increased risk of incident fracture. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00239681.

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