TY - JOUR
T1 - Mechanisms of bone disease in HIV and hepatitis C virus
T2 - Impact of bone turnover, tenofovir exposure, sex steroids and severity of liver disease
AU - Bedimo, Roger
AU - Cutrell, James
AU - Zhang, Song
AU - Drechsler, Henning
AU - Gao, Ang
AU - Brown, Geri
AU - Farukhi, Irfan
AU - Castanon, Rosinda
AU - Tebas, Pablo
AU - Maalouf, Naim M.
N1 - Publisher Copyright:
© 2016 Wolters Kluwer Health, Inc.
PY - 2016/2/20
Y1 - 2016/2/20
N2 - 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. Design: 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. Methodology: 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. Conclusion: 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.
AB - 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. Design: 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. Methodology: 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. Conclusion: 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.
KW - bone mineral density
KW - bone turnover markers
KW - estradiol
KW - hepatitis C
KW - insulin-like growth factor-1
KW - tenofovir
KW - testosterone
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U2 - 10.1097/QAD.0000000000000952
DO - 10.1097/QAD.0000000000000952
M3 - Article
C2 - 26558726
AN - SCOPUS:84957442209
SN - 0269-9370
VL - 30
SP - 601
EP - 608
JO - AIDS
JF - AIDS
IS - 4
ER -