For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
17
views
10
references
 Top references
cited by
1
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      747
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Mechanism of action study to evaluate the effect of rosiglitazone on bone in postmenopausal women with type 2 diabetes mellitus: rationale, study design and baseline characteristics

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objectives

          Post-hoc analyses have shown an increase incidence of fractures among type 2 diabetes (T2DM) patients treated with thiazolidinediones (TZDs). The mechanisms by which TZDs may be associated with increased fracture risk is not well understood.

          This article describes the study design and baseline characteristics for a prospective, randomized, double-blind, active-controlled trial to evaluate the effects of rosiglitazone on changes in measures of skeletal structure, surrogates of bone strength and metabolism.

          Methods

          Postmenopausal women without osteoporosis and diagnosed with T2DM were randomized in a double-blind design to either rosiglitazone or metformin for 52 weeks, then all subjects received open-label metformin for 24 weeks. Study endpoints included changes in bone mineral density (BMD), quantitative computed tomography (QCT), digitized hip radiography (HXR) and high resolution magnetic resonance imaging (hrMRI). Serum markers of bone metabolism and indices of glycemic control were assessed within and between treatment groups.

          Results

          A total of 226 subjects were randomized. Baseline characteristics included: age 63.8 ± 6.5 years; years postmenopausal 16.9 ± 8.4; duration of diabetes 3.5 (1.8–7.8) years; body mass index (BMI) 31.4 ± 5.9 kg/m 2; and glycated hemoglobin (HbA1c) 6.4 ± 0.65%. At baseline, mean T-scores were −0.95 ± 0.91 at the femoral neck, −0.02 ± 0.97 at the total hip and −0.55 ± 1.25 at the total spine.

          Since there are no well recognized techniques to determine bone mass and structure at the distal limbs (cortical bone sites where fractures were reported in RSG subjects), using the femoral neck as a surrogate for these areas may be a potential limitation of the study.

          Conclusion

          This is the first randomized trial utilizing multiple techniques to evaluate bone mass, structure, serum markers of bone remodeling, and potential reversibility of changes after discontinuation of rosiglitazone. This study will provide information about RSG bone effects in a population of postmenopausal women at risk for bone loss and subsequent fracture.

          ClinicalTrials.gov number

          NCT00679939

          Related collections

          Most cited references10

          • Record: found
          • Abstract: found
          • Article: not found

          Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture.

          Mohsen Janghorbani, Rob Van Dam, Walter C. Willett … (2007)
          The authors conducted a systematic review of published data on the association between diabetes mellitus and fracture. The authors searched MEDLINE through June 2006 and examined the reference lists of pertinent articles (limited to studies in humans). Summary relative risks and 95% confidence intervals were calculated with a random-effects model. The 16 eligible studies (two case-control studies and 14 cohort studies) included 836,941 participants and 139,531 incident cases of fracture. Type 2 diabetes was associated with an increased risk of hip fracture in both men (summary relative risk (RR) = 2.8, 95% confidence interval (CI): 1.2, 6.6) and women (summary RR = 2.1, 95% CI: 1.6, 2.7). Results were consistent between studies of men and women and between studies conducted in the United States and Europe. The association between type of diabetes and hip fracture incidence was stronger for type 1 diabetes (summary RR = 6.3, 95% CI: 2.6, 15.1) than for type 2 diabetes (summary RR = 1.7, 95% CI: 1.3, 2.2). Type 2 diabetes was weakly associated with fractures at other sites, and most effect estimates were not statistically significant. These findings strongly support an association between both type 1 and type 2 diabetes and increased risk of hip fracture in men and women.
          Article 0 comments Cited 383 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT).

            Steven E. Kahn, Bernard Zinman, John M. Lachin … (2008)
            The purpose of this study was to examine possible factors associated with the increased risk of fractures observed with rosiglitazone in A Diabetes Outcome Progression Trial (ADOPT). Data from the 1,840 women and 2,511 men randomly assigned in ADOPT to rosiglitazone, metformin, or glyburide for a median of 4.0 years were examined with respect to time to first fracture, rates of occurrence, and sites of fractures. In men, fracture rates did not differ between treatment groups. In women, at least one fracture was reported with rosiglitazone in 60 patients (9.3% of patients, 2.74 per 100 patient-years), metformin in 30 patients (5.1%, 1.54 per 100 patient-years), and glyburide in 21 patients (3.5%, 1.29 per 100 patient-years). The cumulative incidence (95% CI) of fractures in women at 5 years was 15.1% (11.2-19.1) with rosiglitazone, 7.3% (4.4-10.1) with metformin, and 7.7% (3.7-11.7) with glyburide, representing hazard ratios (95% CI) of 1.81 (1.17-2.80) and 2.13 (1.30-3.51) for rosiglitazone compared with metformin and glyburide, respectively. The increase in fractures with rosiglitazone occurred in pre- and postmenopausal women, and fractures were seen predominantly in the lower and upper limbs. No particular risk factor underlying the increased fractures in female patients who received rosiglitazone therapy was identified. Further investigation into the risk factors and underlying pathophysiology for the increased fracture rate in women taking rosiglitazone is required to relate them to preclinical data and better understand the clinical implications of and possible interventions for these findings.
            Article 0 comments Cited 118 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women.

              K Nicodemus, A Folsom, (2001)
              To examine whether postmenopausal women with diabetes experienced a higher incidence of hip fracture than women without diabetes. A prospective cohort of 32,089 postmenopausal women residing in Iowa were surveyed by mail in 1986 and followed for 11 years. Diabetes status and other potential risk factors were assessed by questionnaires at baseline; incidence of hip fracture was ascertained by follow-up questionnaires. A total of 490 hip fractures were reported over 306,900 person-years of follow-up. After adjustment for age, smoking status, estrogen use, BMI, and waist-to-hip ratio, women with type 1 diabetes (n = 47) were 12.25 times (95% CI 5.05-29.73) more likely to report an incident hip fracture than women without diabetes. Women with type 2 diabetes had a 1.70-fold higher risk (1.21-2.38) of incident hip fracture than women without diabetes. Longer duration of type 2 diabetes was associated with higher incidence, as was use of insulin or oral diabetes medications in women with type 2 diabetes. Furthermore, women who were initially free of diabetes but in whom diabetes developed had a relative risk of hip fracture of 1.60 (1.14-2.25) compared with women who never had diabetes. Postmenopausal women who have diabetes or in whom diabetes develops are at higher risk for hip fracture than nondiabetic postmenopausal women. Strategies to prevent osteoporosis and/or falling may be especially warranted in women with diabetes.
              Article 0 comments Cited 99 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): J Drug Assess
                Journal ID (iso-abbrev): J Drug Assess
                Journal ID (publisher-id): IJDA
                Title: Journal of Drug Assessment
                Publisher: Taylor & Francis
                ISSN (Electronic): 2155-6660
                Publication date Collection: 2012
                Publication date (Electronic): 16 December 2011
                Volume: 1
                Issue: 1
                Pages: 11-19
                Affiliations
                [1 ]GlaxoSmithKline Research and Development, 709 Swedeland Road, King of Prussia, PA 19406USA
                [2 ]College of Physicians and Surgeons, Columbia University, New York, NY, USA. Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, New York, NY 10032USA
                [3 ]GlaxoSmithKline Research and Development, 2301 Renaissance Boulevard, King of Prussia, PA 19406USA
                [4 ]BioClinica Inc., 826 Newtown-Yardley Road, Newtown, PA 18940USA
                [5 ]Instituto de Investigaciones, Metabolicas, Libertad 836 C1012AAR Buenos AiresArgentina
                [6 ]Imaging Therapeutics, 24301 Southland Drive, Suite 623, Hayward, CA 94545USA
                Author notes

                *M.J. Wooddell, Kyowa Hakko Kirin Pharma, 212 Carnegie Center, Princeton, NJ 08540, USA.

                †N.S. Kolatkar, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.

                Corresponding author: Lorraine A. Fitzpatrick, GlaxoSmithKline Research and Development,709 Swedeland Road, UW2291, King of Prussia, PA 19406, USA. Tel.: 610-270-5444; Fax: 610-270-5444 lorraine.a.fitzpatrick@ 123456gsk.com ;
                Article
                Publisher ID: ijda-1-11
                DOI: 10.3109/21556660.2011.641703
                PMC ID: 4980730
                SO-VID: 1e8a93b8-2645-4c92-b297-c64ce5803f4a
                Copyright © © 2012 The Author(s). Published by Taylor & Francis
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                Date accepted : Accepted on November 14, 2011
                Categories
                Subject: Original Articles

                Keywords: rosiglitazone,metformin,type 2 diabetes mellitus,mechanism of action,bone mineral density,dxa
                Data availability:
                Keywords: rosiglitazone, metformin, type 2 diabetes mellitus, mechanism of action, bone mineral density, dxa

                Comments

                Comment on this article

                scite_

                Similar content747

                See all similar

                Cited by1

                See all cited by

                Most referenced authors389

                See all reference authors