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Incident fractures in HIV-infected individuals: a systematic review and meta-analysis
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"While at present the overall increase in risk of fracture is modest, this can be expected to increase in the future as the HIV-infected population continues to age, and studies of risk reduction interventions are warranted."
from Jules: although the overall fracture risk was what they call modest, very relevant is how many risk factors one has & this might controbute to greater fracture risk, of course the only way to get a bone fracture, other than a fragility fracture perhaps, is to fall, so low BMD & risk for fracture is different. Of note at CROI was I think the first study ever on falls in HIV+ & the NATAP report on frailty is of great relevance, see links below.
Update from 20th CROI: Bones, Vitamin D, Frailty - Todd T. Brown, MD, PhD Association Professor of Medicine and Epidemiology Division of Endocrinology and Metabolism Johns Hopkins University - (04/01/13)
CROI: Fall Frequency and Associated Factors among Men and Women with or at Risk for HIV Infection - (04/01/13)
Shiau, Stephanie; Broun, Emily C.; Arpadi, Stephen M.; Yin, Michael T.
"This systematic review and meta-analysis suggests that HIV infection and/or ART are associated with modest increases in fracture risk with a pooled IRR of 1.58 (95% CI: 1.25, 2.00) for all fracture. Our results show the importance of including fracture outcomes in prospective studies that provide individual patient level data in order to establish the attributable risk of HIV infection and/or ART on fracture, as well as the contribution of other risk factors, including age, sex, race, weight and smoking. Validation of fracture prediction algorithms, such as FRAX [32], for HIV-infected individuals remains an important area of research. While at present the overall increase in risk of fracture is modest, this can be expected to increase in the future as the HIV-infected population continues to age, and studies of risk reduction interventions are warranted."
"Predictors of fracture......
.......A summary of significant predictors of all fractures and fragility fractures in multivariable or adjusted analyses for HIV-infected individuals is presented in Table 3. Though predictors varied, several traditional risk factors remained consistent across studies, including older age [11,13-16], white race [11,13,15,16,23], low weight or BMI [13,14,16], smoking [11,13,15,16,24], and alcohol or substance abuse [13,14,18], particularly for fragility fractures.
Diabetes, liver disease and a co-morbidity index were also been reported as significant predictors of fracture [11,13-15]. Although not a traditional risk factor, HCV was found to be a significant predictor of fracture in many studies [11,14,15,18,21,22]. Use of glucocorticoids was also found to be a significant predictor of fracture in three studies [13,17,24], while only one study found proton pump inhibitors to be associated with fractures [13]. As for HIV-specific variables, two studies found an association between low CD4 count and fracture risk [14,17]. Few studies reported an independent effect of ART types or exposure on fractures. Bedimo et al. found that tenofovir and ritonavir-boosted protease inhibitors (PIs) were associated with an increased risk of osteoporotic fractures, adjusted for traditional risk factors among those who entered the cohort in the HAARTera (1996-2009) [16]......HCV was consistently identified as an independent risk factor for both fragility and non-fragility incident fractures [11,14-16,18,21,22]. The increased risk of fracture is approximately 1.5-2 times greater in HIV/HCV co-infected than HIV mono-infected individuals [15,16,21,22]......Low body weight may not only increase risk of fracture by leading to decreased BMD, but may also be associated with increased prevalence of the frailty phenotype at earlier ages and predisposition to falls. While early frailty has been previously documented in HIV-infected men, current data on fall rates in HIV-infected individuals is limited [27,28] and is an important area for future research.......
The role of HIV-specific factors in bone loss and fracture also remains unclear. Lower CD4 counts before ART initiation has been reported to be a predictor of both bone loss after ART initiation and increases in bone turnover [29]. Low current CD4 count (<200cells/ml) in studies by Yong et al. [17] and Hasse et al. [25] were associated with increased fragility fracture incidence in multivariate analyses. Similarly, nadir CD4 count <200 cells/ml in Young et al. was associated with increased all fracture incidence in multivariate analysis [14]. However, pretreatment CD4 count was not associated with fracture incidence in the longitudinal follow-up of participants enrolled in randomized clinical trials of ART initiation [24], and nadir or current CD4 count was not predictive of fractures in other studies [13,15,25]"
Objective(s): Some but not all studies indicate that individuals with HIV infection are at increased risk of fracture. We systematically reviewed the literature to investigate whether incidence of fracture (both overall and fragility) differs between individuals with and without HIV.
Design: Systematic review and meta-analysis.
Methods: Medline, Scopus, and the Cochrane Library databasesfor all studies ever published up to September 28, 2012and electronically available conference abstracts from CROI, ASBMR, IAS, and AIDS were searched. All studies reporting incidence of all fracture and fragility fracture in HIV-infected adults were included. A random effects model was used to calculate pooled estimates of incidence rate ratios (IRR) for studies that presented data for HIV-infected and controls. For all studies, incidence rates of fracture and predictors of fracture among HIV-infected individuals were summarized.
Results: Thirteen eligible studies were analyzed, of which seven included controls. Nine studies reported all incident fractures and tenpresented incident fragility fractures. The pooled IRR was 1.58 (95% CI: 1.25, 2.00) for all fracture and 1.35 (95% CI: 1.10, 1.65) for fragility fracture. Smoking, white race, and older age were consistent predictors for fragility fractures.
Conclusions: Our results indicate that HIV-infection is associated with a modest increase in incident fracture. Future research should focus on clarifying risk factors, designing appropriate interventions, and the long-term implications of this increased risk for an aging HIV-infected population.

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