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Bone Fractures at CROI 2010 - see slides below
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Reported by Jules Levin
In the summer of 2009 a research group from Boston including Steve Grinspoon published the first large study paper showing increased risk for fractures among HIV+. This was after I had been raising awareness and education for at least 1 year regarding the increased rates of low bone mineral density seen in HIV+ individuals: 50% osteopenia, 10% osteoporosis at the stunningly young age on average of about 45. I received push-back from severa HIV metabolic researchers telling me 'well, how do we kow this will translate into increased fracture rates'. This is typical for many HIV researchers as some said early on that increased lipids may not translate into increased CVD. In an oral session at CROI 3 reports were presented on fracture rates. As far as I’m concerned and I think several bone HIV thought leaders agree, that HIV+ individuals do face an increased risk for fractures as they age in addition to increased risk for frailty, and in studies in HIV-negative individuals fractures and frailty are associated with increased mortality. In addition at CROI there were numerous studies presented showing seriously low vitamin D levels in HIV+ individuals, there were a number of studies reporting low bone mineral density in HIV+ individuals, and there was ACTG 5202 which also found bone loss associated with tenofovir and HAART. And based o the studies presented at CROI, below. It appears that increased fracture rates in HIV+ are for fragility fractures, not non-fragility fractures, and fragility fractures are just the ones HIV+ individuals are more prone to be at risk for. The 2nd oral defined fragility fractures as mostly associated with low BMD, not associated with trauma, risk factors include: older age, low BMD, white race, glucocorticoid use, smoking and alcohol abuse; all associated with HIV+ patient populations.
Higher and Increasing Rates of Fracture among HIV-infected Persons in the HIV Outpatient Study Compared to the General US Population, 1994 to 2008
Christine Dao*1, B Young2,3, K Buchacz1, R Baker4, J Brooks1, and the HIV Outpatient Study Investigators
1CDC, Atlanta, GA, US; 2Denver Infectious Disease Consultants, CO, US; 3Hlth Connections Intl, Amsterdam, The Netherlands; and 4Cerner Corp, Vienna, VA, US
Background: Low bone mineral density is common among HIV-infected persons and has raised concerns for increased risk of fracture in this population. We sought to compare rates of fracture over time among HIV-infected persons to those in the general U.S. adult population and explore risk factors for fractures in contemporary HIV-infected patients.
Methods: We analyzed data from 8,456 HIV Outpatient Study (HOPS) participants followed at 10 HIV clinics in the US, who had at least 2 clinical encounters from 1994 to 2008. Only first fractures during the observation period were analyzed. We calculated age-standardized rates of fracture using the National Hospital Discharge Survey (NHDS) data from urgent care, emergency department and inpatient settings. We compared the magnitude and temporal trends in rates of fracture in the HOPS and NHDS using linear regression. Among HOPS patients observed during 2002 to 2008, we studied associations between fracture risk and demographic, clinical, and behavioral factors measured on 1 January 2002 or first HOPS visit, thereafter using multivariable Cox proportional hazards models.
Results: Of 8,456 HOPS patients included in the study (median age: 37 years; 80.5% male; 55.7% white), 276 patients had a fracture during a median follow-up of 4.8 years. Among HOPS patients, age-standardized fracture rates per 10,000 increased from 36.0 during 1994 to 165.3 during 2002 (P =0.03). Among persons 25 to 54 years of age, rates of fracture were higher among HOPS than NHDS patients; since 2002, rates have remained steady at a rate 4.3 times higher (see figure). Non-extremity fractures were more common in the HOPS than NHDS patients (40.4% vs 34.2%, respectively, figure). Among contemporary HOPS patients, nadir CD4 cell count < 200 cells/mm3 (adjusted hazard ratio (aHR) = 1.60, 95% confidence interval 1.11 to 2.31), hepatitis C infection (aHR = 1.61, 95%CI 1.13 to 2.29), diabetes (aHR = 1.62, 95%CI 1.00 to 2.64), and substance abuse (aHR = 1.52, 95%CI 1.00 to 2.32) were independently associated with increased fracture risk.
Conclusions: Rates of fracture among HIV-infected persons were higher than in the general U.S. population (as captured by NHDS), particularly among younger adults. Although rates of fracture in NHDS have decreased, rates among HIV-infected persons increased and then remained steady since 2002. The pathophysiology of bone disease in this population may reflect lifestyle, viral, or pharmacologic effects, and deserves attention in HIV care practice.
HIV-infection and Fragility Fracture Risk among Male Veterans
Julie Womack*1, J Goulet1, C Gibert2, C Brandt1,3, K Mattocks1,4, D Rimland5, M Rodriguez-Barradas6, J Tate1, M Yin7, J Amy1,4, and Veterans Aging Cohort Project Team
1VA Connecticut Hlthcare System, West Haven VAMC, US; 2George Washington Univ Sch of Med and Washington DC VAMC, US; 3Yale Ctr for Med Informatics, Yale Univ, New Haven, CT, US; 4Yale Sch of Med, New Haven, CT, US; 5Emory Univ Sch of Med and Atlanta VAMC, GA, US; 6Michael E De Bakey VAMC, Baylor Coll of Med, Houston, TX, US; and 7Columbia Univ, Coll of Physicians and Surgeons, New York, NY, US
Background: Decreased bone mineral density is more common in HIV-infected than uninfected individuals. Previous authors have documented increased wrist, hip, and vertebral fractures (fragility fractures) among HIV-infected as compared to uninfected individuals, however none has adjusted for body mass index (BMI), comorbidity, or alcohol abuse.
Methods: Our sample included 105,706 men (40,216 HIV-infected and 64,971 uninfected) enrolled in the Veterans Aging Cohort Study (VACS) virtual cohort, a prospective cohort study of HIV-infected and uninfected Veterans. Cox proportional hazard models were used to estimate the hazard ratio (HR) for fragility fractures in HIV-infected compared to uninfected Veterans. Adjusted models included age, HIV serostatus, race, body mass index, and comorbid medical and psychiatric conditions associated with fragility fracture risk. Because wrist fractures were more common among younger men regardless of HIV serostatus, we excluded them from the analysis.
Results: In this study, 952 (644 hip and 308 vertebral) fractures were observed during a median follow-up of 8 (4 to 11) years. Mean age at fracture was 55 (SD:11) years. Unadjusted incidence of vertebral and hip fractures was 16 for HIV-infected and 11 for uninfected Veterans/10,000 person-years of follow-up (P <0.0001) and increased substantially with age (P <0.0001). Compared to uninfected Veterans and after adjustment for white race (HR = 1.79, 95%CI 1.57 to 2.03), BMI <19 (HR = 2.50, 1.54 to 4.05), alcohol abuse (HR = 1.79, 1.47 to 2.18), pulmonary disease (HR = 1.38, 1.10 to 1.73), cerebrovascular disease (HR = 2.16, 1.54 to 3.02), and peripheral vascular disease (HR = 1.64, 1.10 to 2.44), HIV infection was not independently associated with fragility fracture (HR = 1.20, 0.99 to 1.45). However, HIV-infection in Veterans >50 years of age contributed additional, significant risk for fracture (HR = 1.37, 1.06 to 1.78).
Conclusions: Wrist fractures were associated with younger age in this sample of aging male Veterans. In contrast hip and vertebral fractures were strongly associated with age. After adjustment for established risk factors, HIV was associated with increased risk only among older Veterans.
Here is link to published study on WIHS and bone loss in Feb JAIDS:
Bone Loss in HIV+ Premenopausal Women & Fracture Risk
Short-Term Bone Loss in HIV-Infected Premenopausal Women ..... Personal history of fracture was obtained at the first WIHS metabolic study visit, ...
www.natap.org/2010/HIV/020410_03.htm
Fracture Rates Are Not Increased in Younger HIV+Women
Michael Yin*1, Q Shi2, D Hoover3, K Anastos4, A Sharma5, M Young6, A Levine7, M Cohen8, E Golub9, and P Tien10
1Columbia Univ Med Ctr, New York, NY, US; 2New York Med Coll, Valhalla, US; 3Rutgers Univ, Piscataway, NJ, US; 4Montefiore Med Ctr, Bronx, NY, US; 5State Univ of New York Downstate Med Ctr, Brooklyn, US; 6Georgetown Univ Sch of Med, Washington, DC, US; 7Univ of Southern California, Keck Sch of Med, Los Angeles, US;8Stroger Hosp and Rush Med Coll, Chicago, IL, US; 9Johns Hopkins Univ Bloomberg Sch of Publ Hlth, Baltimore, MD, US; and 10Univ of California, San Francisco, US
Background: Low bone mineral density (BMD) is common among HIV+ individuals, but its clinical significance is unclear. BMD is relatively stable in premenopausal women on established antiretroviral therapy (ART) and fracture data are limited.
Methods: We compared time to first fracture at any site (fragility and non-fragility) after a median follow-up of 5.4 years in 2391 (1728 HIV+, 663 HIV‑) women enrolled in the Women’s Interagency HIV Study (WIHS), and determined risk factors for incident fracture. Self-report of fracture was recorded at semiannual visits using a specific questionnaire. Cox Proportional Hazards Models were utilized to evaluate association of traditional risk factors for fracture and HIV disease characteristics measured at baseline with subsequent incident fracture.
Results: HIV+ individuals were older than HIV‑ individuals (40+/-8 vs 36+/-10 years, P <0.0001) and had lower body mass index (28+/-7 vs 30+/-8 kg/m2,P <0.0001); the proportion African American individuals was similar (56% vs 58%, P =0.30). HIV+ women were more often post-menopausal by self-report (20% vs 11%, P <0.0001), HCV-infected (25% vs 15%, P <0.0001), and taking vitamin D supplementation (42% vs 28%, P <0.0001), and less likely to be a current smoker (45% vs 51%, P =0.02) or use alcohol>2 drinks/day (2% vs 4%, P <0.0001). Personal history of previous fracture and serum creatinine levels did not differ by HIV status. Among HIV+, mean CD4 was 319+/-273 cells/μL; most were taking ART, with 30% on protease inhibitor-based and 30% on non-nucleoside reverse transcriptase inhibitor-based ART. Unadjusted fracture rates were similar between HIV+ and HIV‑ for any fracture (1.7 vs 1.4/100 person-years, P =0.18) and for fractures of the hip, spine or wrist (0.6/100 person-years in both groups, P =0.96). In multivariate analysis, white (vs African American) race, menopause, and higher serum creatinine were associated with increased fracture rate, but HIV status was not. Among HIV+ women, traditional risk factors for fracture (white race, previous fracture, and menopause) and history of AIDS defining illness were associated with increased fracture rate, while CD4 and cumulative exposure to ART were not.
Conclusions: After 5 years of follow up, fracture rates were not significantly increased in HIV+ women compared to HIV‑ women. Traditional risk factors were important predictors, while HIV status was not. Our data provide some reassurance that fracture risk is modest in predominantly premenopausal HIV+ women, but further research is necessary to define risk after menopause.
from Jules: Womack called the HIV causation for fractures as modest but look at the other risk factors, thee are all risk factors more prevalent among HIV+ compared to HIV-negs, so Womack tried to separate HIV from these established risk factors among HIV+, but this is a false separation. However, Womack did say the purpose of this study was to see if HIV was associated with fractures. Clearly, HIV by itself is unlikely to be the only risk factor a patient with HIV has so the indication to perform a dexa scan is more likely to occur!
all statistically significantly associated with fractures.
BMI was greater in HIV-negs in this study and greater BMI cis known to be protective.
no difference between groups in previous fracture.
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