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HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures Among HIV Patients. Roger Bedimo, MD; Henning Drechsler, MD; Song Zhang, PhD; Andrew Westfall, MS; Naim Maalouf, MD. Osteoporotic Fractures among HIV-Infected Patients: Incidence.
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HCV Co-infection is Associated with a High Risk of Osteoporotic Fractures Among HIV Patients Roger Bedimo, MD; Henning Drechsler, MD; Song Zhang, PhD; Andrew Westfall, MS; Naim Maalouf, MD
Osteoporotic Fractures among HIV-Infected Patients: Incidence • Decreased bone mineral density is increasingly reported in the aging HIV-positive population. • Interaction b/w low BMD and bone turnover in predicting fracture risk1 • 15-30% of HIV-infected patients are co-infected with hepatitis C, which by itself is associated with osteoporosis and bone turnover2 • The aging of the HIV population suggests that fracture risk will increase in HAART vs. pre-HAART era. 1Gamero. J Bone Miner Res 1996,11:1531-1538; 2Gastroenterology 2003,125:937-940
Osteoporotic Fractures among HIV-Infected Patients: Mortality • Fracture prevalence is increased in HIV-infected compared with non-HIV-infected patients.1 • The HIV population in the US is predominantly male. • Although the overall prevalence of fragility fractures is higher in women, men generally have higher rates of fracture-related mortality. 2,3 • The overall mortality is about 20% in the first 12 months after hip fracture and is higher in men than women • 2Center JR, et al. Lancet 1999; 353:878; 3Hasserius R, et al.. Osteoporos Int 2003;14:61. 1Triant V, et al., JCEM 2008;93: 3499–3504;
Factors Likely Associated with Decreased Bone Health in HIV HCV HIV HAART Hypogonadism • OSTEOPOROSIS and • FRACTURE RISK Malnutrition, low BMI Tobacco, Alcohol Glucocorticoids Inflammatory Cytokines Vitamin D deficiency Chronic kidney disease • Aims: • To evaluate the impact of HCV co-infection on the risk of osteoporotic fractures among HIV-infected patients. • To evaluate the impact of osteoporotic fractures on all-cause mortality
Methods: Data Source, Predictors and Outcome Measures • Data Source: Veterans Affairs’ Clinical Case Registry; HIV patients in pre-HAART (’88-’95) and HAART eras (’96-’09). • Predictors: • HCV co-infection: ICD-9 codes for HCV or HCV antibody + • Chronic kidney disease: Estimated GFR<60 by MDRD • BMI, Age, Race, Antiretroviral exposure, Smoking • Outcomes: • Osteoporotic fractures: Vertebral fractures (ICD-9 codes 805.2 through 805.7), Hip fractures (820.0 through 820.9), and Wrist fractures (814.0, 814.1, 813.4 and 813.5) • All-cause mortality: Cox survival model
Results: Study Population, Treatment Exposure and Events • Patients: 56,660 included in the analysis; 98.1% male; 17,281 (31.2%) HCV+; Mean age at entry: 45.0 (SD:10.4) • Follow-up: 305,237 patient-years; mean: 5.4 yrs/patient (range: 0 – 23.8 years) • ARV exposure: 64.2% of patients exposed for ≥ 30 days. Mean Rx duration: 4.08 years (range: 0 – 18.7; SD: 3.92). • Osteoporotic fractures during period of observation: • 951 individual patients sustained at least one osteoporotic fracture (106 vertebral, 451 wrist and 308 hip). • Rate/1000 patient-years for HIV and HIV/HCV patients were 2.54 and 3.25 respectively.
Risk Factors among Patients with and without Osteoporotic Fracture
Age-adjusted Rates of Osteoporotic Fractures (Entire Cohort) 8 7 6 Vertebral 5 Hip Fracture Rate (per 1,000 patient-years) Wrist 4 Total 3 General population1 2 1Data from Triant V, et al., JCEM 2008;93: 3499–3504 1 0 18-29 30-39 40-49 50-59 60-69 ≥70 Age at Diagnosis (Years)
Rates of Osteoporotic Fractures by Year of Diagnosis and HCV Status
Fracture Rates in HIV and HIV/HCV Patients Fracture Rate (per 1,000 patient-years)
Discussion - I • HCV co-infection is associated with a higher risk of osteoporotic fractures among HIV-infected patients. • Risk of osteoporotic fractures appears to be increasing in the HAART era among HIV/HCV patients. • Exposure to antiretroviral therapy appears to be protective of osteoporotic fractures. • Higher overall mortality in the pre-HAART era might not have allowed time to develop osteoporotic fractures • It is possible that HAART is not protective, but a surrogate measure of patients with better care
Discussion - II • Patients with HIV have a higher incidence of fractures than the general population, in spite of HAART therapy which may reduce fracture risk • Other factors associated with increased risk of osteoporotic fractures include White race, advancing age and smoking. • CKD and diabetes were not associated with osteoporotic fracture • Osteoporotic fracture is an independent predictor of all-cause mortality.
Strengths and Limitations • Our study is a retrospective cohort study. • Large sample size (more than 56,000 patients; more than 900 with fracture events) • Uniform data collection on exposures and outcomes across VA system, including pre-HAART and HAART eras. • Osteoporotic fracture events not ascertained (only ICD-9 code used – validated in other VA studies) • Bone mineral density is not evaluated. Fractures cannot be proven to be osteoporotic in nature. • Impact of type (HAART and non-HAART) and duration of antiretroviral exposure not completed (in progress)
Acknowledgements • VA Center for Quality Management for access to CCR data and material support • Dr. Pablo Tebas for great insight, critical review and comments • IAS for giving us the opportunity to share our work