title: Mechanisms of bone disease in HIV and hepatitis C virus: impact of bone turnover, tenofovir exposure, sex steroids and severity of liver disease.
abstract: OBJECTIVE
  Both HIV and hepatitis C virus (HCV) infections are associated with higher osteoporotic fracture risk. Increased bone turnover, liver fibrosis, tenofovir (TDF) use or hormonal imbalances are possible underlying mechanisms.
  
  
  METHODS
  This prospective, cross-sectional study assessed 298 male volunteers with either virologically suppressed HIV or untreated HCV mono-infections, HIV/HCV co-infection and noninfected controls.
  
  
  METHODS
  Study participants underwent bone mineral density (BMD) by dual-energy x-ray absorptiometry and measurement of bone turnover markers [BTM: C-telopeptide (CTX) and osteocalcin (OC)], insulin-like growth factor-1 (IGF-1), the sex steroids testosterone (T) and estradiol (E2), and the aspartate aminotransferase-to-platelet ratio index (APRI). Impact of HIV and HCV status on BMD was evaluated in multivariate models adjusting for APRI score, BTM, TDF exposure, IGF-1, and sex steroids.
  
  
  RESULTS
  HIV and HCV status independently predicted lower BMD, controlling for age, race, BMI, and smoking (P = 0.017 and P = 0.010, respectively), whereas APRI did not (P = 0.84). HIV was associated with increased bone resorption (CTX: P < 0.001) and formation (OC: P = 0.014), whereas HCV infection was not associated with CTX (P = 0.30) or OC (P = 0.36). TDF exposure was associated with lower BMD (P < 0.01). IGF-1 was significantly decreased in HCV and increased in HIV. Tumor necrosis factor-α (P = 0.98), IGF-1 (P = 0.80), bioavailable T (P = 0.45) and E2 (P = 0.27) were not associated with BMD and did not attenuate the impact of HIV or HCV on BMD.
  
  
  CONCLUSIONS
  HIV and TDF exposure decrease BMD through increased bone turnover, although the lower BMD in HCV is not explained by a high turnover state. Neither virus' effect on BMD is likely mediated through increased inflammation, liver fibrosis, IGF-1, or sex steroids.
authors.affiliation: aVA North Texas Health Care System bUniversity of Texas Southwestern Medical Center, Dallas, Texas cUniversity of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Bedimo
authors.forename: James
authors.initials: J
authors.lastname: Cutrell
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.forename: Henning
authors.initials: H
authors.lastname: Drechsler
authors.forename: Ang
authors.initials: A
authors.lastname: Gao
authors.forename: Geri
authors.initials: G
authors.lastname: Brown
authors.forename: Irfan
authors.initials: I
authors.lastname: Farukhi
authors.forename: Rosinda
authors.initials: R
authors.lastname: Castanon
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Naim M
authors.initials: NM
authors.lastname: Maalouf
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D015519:Bone Density; D001847:Bone Diseases / Q000473:pathology*; D016723:Bone Remodeling; D003430:Cross-Sectional Studies; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068698:Tenofovir / Q000494:pharmacology*
chemical_list: D044966:Anti-Retroviral Agents; D012739:Gonadal Steroid Hormones; D000068698:Tenofovir