title: The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone increases bone resorption in women with type 2 diabetes: a randomized, controlled trial.
abstract: In previous studies, with up to 16 weeks of exposure to rosiglitazone or pioglitazone, circulating markers of bone formation [procollagen I N-terminal propeptide (P1NP), osteocalcin, and bone-specific alkaline phosphatase] decreased but no change in bone resorption markers was found. We examined the effect of rosiglitazone on bone resorption and formation markers when used for 24 weeks. This post-hoc analysis of a double-blind, placebo-controlled, randomized trial evaluated the effects of 6 months of rosiglitazone use versus placebo on circulating markers of bone turnover in 111 patients with type 2 diabetes and cardiovascular disease or additional cardiac risk factors. The principal end points for analysis were changes in bone formation and resorption markers, measured by P1NP and carboxy-terminal cross-links (CTX), respectively. There were 111 subjects who completed the study and had baseline and 6-month data; mean age was 56, including 41% women and 67% nonwhite (50 black, 18 Hispanic, and six other), and subjects were evenly distributed between placebo and rosiglitazone groups. Women treated with rosiglitazone had higher CTX levels (0.43 ng/mL) than those who received placebo (0.23 ng/mL) (P = 0.007), with no significant differences in P1NP or OPG. Overall, in stratified analyses of men and in stratified analyses among different ethnicities, there were no statistically significant differences observed in CTX, P1NP, OPG, PTH, or 25-OHD between the treatment groups. Women taking rosiglitazone had higher circulating markers of bone resorption, which is contrary to prior studies of shorter duration, where the principal observation was a decrease in markers of bone formation.
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. ugis.gruntmanis@utsouthwestern.edu
authors.forename: Ugis
authors.initials: U
authors.lastname: Gruntmanis
authors.forename: Steve
authors.initials: S
authors.lastname: Fordan
authors.forename: Hans K
authors.initials: HK
authors.lastname: Ghayee
authors.forename: Shuaib M
authors.initials: SM
authors.lastname: Abdullah
authors.forename: Raphael
authors.initials: R
authors.lastname: See
authors.forename: Colby R
authors.initials: CR
authors.lastname: Ayers
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
mesh_terms: D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000097:blood / Q000139:chemically induced*; D024042:Collagen Type I; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000208:ethnology / Q000378:metabolism; D004311:Double-Blind Method; D005006:Ethnicity; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides; D017698:Postmenopause; D011347:Procollagen / Q000097:blood; D012016:Reference Values; D000077154:Rosiglitazone; D013781:Texas / Q000208:ethnology; D045162:Thiazolidinediones / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D045162:Thiazolidinediones; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D000077154:Rosiglitazone