title: Bone effects of rosiglitazone in HIV-infected patients with lipoatrophy.
abstract: OBJECTIVE
  Thiazoledinediones increase limb fat in HIV+ patients with lipoatrophy. However, their use in the general population has been associated with bone loss and fracture. We sought to determine the effects of rosiglitazone on bone metabolism in HIV-infected patients.
  
  
  METHODS
  HIV+ patients with lipoatrophy were randomized to rosiglitazone versus placebo for 48 weeks in a double-blind, placebo-controlled trial. Limb fat, bone mineral density (BMD), bone formation markers (procollagen type 1 amino-terminal propeptide [P1NP], osteocalcin [OC]) and bone resorption markers (C-terminal telopeptide of type I collagen [CTX]) were measured, along with receptor activator for nuclear factor kappa β ligand (RANKL), osteoprotegerin (OPG), and inflammatory cytokines.
  
  
  RESULTS
  Seventy-one subjects were randomized to rosiglitazone or placebo: 17% female and 51% white. Total BMD did not change significantly in either group. In the rosiglitazone group, P1NP showed statistically significant decreases at 24 and 48 weeks; however, changes compared to placebo were only significant at 24 weeks. OC decreased significantly in the rosiglitazone group at 24 weeks, but there were no between-group differences. CTX, RANKL, or OPG did not change for either group. Multivariable regression within the rosiglitazone arm showed P1NP changes were inversely associated with limb fat changes, protease inhibitors, and tenofovir use.
  
  
  CONCLUSIONS
  Rosiglitazone use was associated with decreased bone formation, but it did not alter bone resorption or total BMD. The increase in limb fat that accompanies rosiglitazone use appears to be associated with decreased osteoblast activity. Further studies are needed to determine the effect of thiazoledinediones on bone health in HIV-infected persons.
authors: Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia 30322, USA. across3@emory.edu
authors: Allison C
authors: AC
authors: Ross
authors: Corrilynn O
authors: CO
authors: Hileman
authors: Todd T
authors: TT
authors: Brown
authors: Neal
authors: N
authors: Fedarko
authors: Norma
authors: N
authors: Storer
authors: Danielle
authors: D
authors: Labbato
authors: Grace A
authors: GA
authors: McComsey
mesh_terms: D000328:Adult; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D024042:Collagen Type I / Q000097:blood; D003923:Diabetes Mellitus, Lipoatrophic / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000097:blood; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects*
chemical_list: D024042:Collagen Type I; D007004:Hypoglycemic Agents; D010455:Peptides; D045162:Thiazolidinediones; C052929:collagen type I trimeric cross-linked peptide; D000077154:Rosiglitazone; D015675:Osteocalcin