title: Evaluation of Quantitative Computed Tomography Cortical Hip Quadrant in a Clinical Trial With Rosiglitazone: A Potential New Study Endpoint.
abstract: Quantitative computed tomography (QCT) measurements have been used extensively to ascertain information about bone quality and density due to the 3-dimensional information provided and the ability to segment out trabecular and cortical bones. QCT imaging helps to improve our understanding of the role that each bone compartment plays in the pathogenesis and prognosis of fracture. This study was conducted to explore longitudinal changes in femoral neck (FN) cortical bone structure using both volumetric bone mineral density (vBMD) and cortical shell thickness assessments via QCT in a double-blind, randomized, multicenter clinical trial in postmenopausal women with type 2 diabetes mellitus. This study also examined whether treatment-associated changes in the cortical bone vBMD and thickness in femoral neck quadrants could be evaluated. Subjects were randomized to rosiglitazone (RSG) or metformin (MET) for 52 wk followed by 24 wk of open-label MET. A subset of 87 subjects underwent QCT scans of the hip at baseline, after 52 wk of double-blind treatment, and after 24 wk of treatment with MET using standard full-body computed tomography scanners. All scans were evaluated and analyzed centrally. Cortical vBMD at the FN was precisely segmented from trabecular bone and used to assess a possible therapeutic effect on this bone compartment. QCT analysis showed reductions in adjusted mean percentage change in vBMD and in absolute cortical thickness occurred with RSG treatment from baseline to week 52, whereas changes with MET were generally minimal. The reductions observed during RSG treatment for 1 yr appeared to partially reverse during the open-label MET phase from weeks 52 to 76. The femoral neck quadrant may provide utility as a potential endpoint in clinical trials for the understanding of the therapeutic effect of new entities on cortical bone vs trabecular bone; however, further clinical validation is needed.
  
  
  
  The protocol (GSK study number AVD111179) was registered on ClinicalTrials.gov as NCT00679939.
authors.affiliation: Medical Affairs, BioClinica Inc., Princeton, NJ, USA.
authors.forename: Colin G
authors.initials: CG
authors.lastname: Miller
authors.affiliation: Instituto Investigaciones Metabolicas, Buenos Aires, Argentina.
authors.forename: Cesar C
authors.initials: CC
authors.lastname: Bogado
authors.affiliation: Research and Development, GlaxoSmithKline, King of Prussia, PA, USA. Electronic address: Antonio.J.nino@gsk.com.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Nino
authors.affiliation: Research and Development, GlaxoSmithKline, Durham, NC, USA.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Northcutt
authors.affiliation: Medical Affairs, BioClinica Inc., Princeton, NJ, USA.
authors.forename: Hui Jing
authors.initials: HJ
authors.lastname: Yu
authors.affiliation: New Mexico Clinical Research & Osteoporosis Center, University of New Mexico School of Medicine, Albuquerque, NM, USA.
authors.forename: E Michael
authors.initials: EM
authors.lastname: Lewiecki
authors.affiliation: Research and Development, GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Paul
authors.affiliation: Research and Development, GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Cobitz
authors.affiliation: Research and Development, GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wooddell
authors.affiliation: College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Bilezikian
authors.affiliation: Research and Development, GlaxoSmithKline, King of Prussia, PA, USA.
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: Fitzpatrick
mesh_terms: D000071538:Cortical Bone / Q000000981:diagnostic imaging* / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging* / Q000187:drug effects; D050723:Fractures, Bone / Q000175:diagnosis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008137:Longitudinal Studies; D017698:Postmenopause; D012307:Risk Factors; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone
keywords: Bone QCT; DXA; clinical trials; other therapeutics