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Bone Microarchitecture, Not Just BMD, Worse in Women With Than Without HIV
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from Jules - "deathly epidemic of aging is ignored.....once a fracture occurs in an older person particularly an HIV+ person the spiral downwards can be bad" – see below background on falls, fractures & death in WIHS women with HIV and all with HIV.
from Jules: following this background & links is report on presentation Sept 12 2016 by Anjali Sharma at the 18th International Workshop on Comorbidities and Adverse Drug Reactions in HIV in NYC at the World Trade Center. Current reports are older HIV+ are experienced increased falls due to frailty, cognitive impairment, walking & balance issues & then experiencing increased rates of fractures due to increased rates of osteoporosis - bone disease -. We predicted this would happen & it will get worse. In women the problem is likely to be worse but men will equally experience these problems. Aside from all the despair & increased death rates this will cause, the cost of healthcare will also increase due to aging-related conditions in older HIV+ - already 30% in USA are >50 years old, in NYC & SF 50% are >50-60 years old and soon 50% in the USA will be > 60 years old. Many clinicians do NOT perform the labs necessary to monitor patients & comorbidities, and many clinicians do not prescribe the correct medications to treat properly the comorbidities. When will the NIH, the White House & advocates wake up & pay attention to this problem. If you are not addressing this crucial issue you are part of the problem. PrEP & Cure advocates are part of the problem, they are ignoring this real-life epidemic of aging, the politics of HIV is killing older patients, it is an epidemic for patients with HIV and soon will be equally as bad globally.
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Our data suggest that fracture rates will increase over time in HIV-infected women as they age.....factors that influence fall risk such as muscle strength and balance can influence fracture rates independently of bone strength.....http://www.natap.org/2015/HIV/Increased_Fracture_Incidence_in_Middle_Aged.7.pdf
Low bone mineral density (BMD) occurs in 40%-90% of human immunodeficiency virus (HIV)-infected individuals [1]. The etiology of low BMD is multifactorial, with contributions from antiretroviral therapy (ART), HIV and its associated immune dysfunction, and traditional osteoporosis risk factors [2]. HIV-infected individuals have a 60% increased fracture risk as compared to uninfected individuals [3].....http://www.natap.org/2016/HIV/071316_05.htm.......In 2010 WIHS reported: premenopausal HIV+ women with ART exposure had slightly lower BMD than comparable HIV- women but experienced similar rates of short-term bone loss....http://www.natap.org/2010/HIV/020410_03.htm.....In Sept 2015 Sharma et al reported WIHS women : Middle-aged HIV-infected women had a higher adjusted fracture rate than HIV-uninfected women. Cocaine use and injection drug use were unadjusted incidence rates of any fracture were higher in HIV-infected than in HIV-uninfected women [2.19/100 person-years (py) vs. 1.54/100 py, P= 0.002]......
5-fold increased risk for frailty combines with & contributes to increased falls and fractures in older aging HIV+.....in a population of middle-aged HIV-infected individuals, predominantly with undetectable HIV viral load on cART, and similar HIV-uninfected controls.: "HIV-infected individuals were more likely to be frail (10.6 vs. 2.7%) and prefrail (50.7 vs. 36.3%) than HIV-uninfected individuals (Ptrend<0.001); this was true for all age-categories”...."This suggests that not only abdominal fat accumulation (of which high waist circumference is an accepted surrogate), but also peripheral lipoatrophy (which may result in a reduced hip-circumference) may contribute to the development of frailty in the context of treated HIV infection.”.....Depression, low BMI and higher WHR were strongly associated with a higher frailty category, but none of the investigated factors could fully explain the observed association between HIV infection, prefrailty, and frailty......Depression may be a consequence of as well as a contributor to frailty......Chronic HCV infection was independently associated with (pre)frailty....http://www.natap.org/2016/HIV/012716_08.htm
CROI/2015: Fracture incidence is increased in aging HIV-infected women (WIHS) by 30% vs HIV-- - (03/02/15).....Cocaine and injection drug use were also significant predictors of incident fracture" " of note age matters, every 10-year increase in age increased risk for fracture in HIV+ women by 25%...."Adjusted for age, race, prior fracture, and history of cocaine and injection drug use, HIV+ women had significantly higher incidence rate of any fracture compared with HIV- women - 30% higher risk -(aHR1.30; 95% CI 1.02-1.66). Among HIV+ women, older age, white race, prior fracture, smoking, and prior AIDS defining illness(aHR=1.56; 95% CI: 1.22-1.98) significantly predicted new fracture, while CD4+ count and antiretroviral exposure did not.”
in this SUN Study analysis at CROI 2015 in Seattle : In this healthy HIV adult cohort with predominantly controlled viremia, total hip BMD decline was associated with IL-6, replicative senescent T-cells, CCR5+ and tissue factor expressing monocytes. Memory CD4+ and CD8+ CD28+ T cells were associated with increases in BMD. Immunologic alterations that persist after virologic suppression may contribute to ongoing loss of BMD.
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18th International Workshop on Comorbidities and Adverse Drug Reactions in HIV, September 12-13, 2016, New York
Mark Mascolini
Bone microarchitecture assessed by trabecular bone score (TBS) proved worse in HIV-positive US women than in demographically similar HIV-negative women in the Women's Interagency HIV Study (WIHS) [1]. But change in lumbar spine microarchitecture over time did not differ significantly by HIV status.
Bone studies in people with HIV usually focus on bone mineral density (BMD) determined by DXA scans. But WIHS investigators who conducted this study noted that bone strength depends on both BMD and bone microstructure, which can be assessed retrospectively as TBS derived from existing DXA scans. They conducted this study to compare TBS-reckoned skeletal microarchitecture in women with versus without HIV.
The analysis involved HIV-positive and negative women younger than 65 who enrolled in the WIHS Metabolic Substudy. These women had DXA scans of the lumbar spine, total hip, and femoral neck at a baseline visit then 2 and 5 years later. The 149 women with HIV were significantly older than the 66 HIV-negative women (median 44 versus 38 years, P < 0.001) and had a marginally lower body mass index (median 28 versus 30 kg/m2, P = 0.06). A nonsignificantly lower proportion of HIV-positive women smoked (54% versus 67%, P = 0.09). About half of the women in both groups were African American and about one third Hispanic.
Lumbar spine BMD proved significantly lower in women with HIV (1.2 versus 1.3 g/cm2, P = 0.001), and mean spine TBS was significantly lower (worse) in women with HIV (1.3 versus 1.4, P < 0.001). Proportions of HIV-positive versus negative women with normal spine TBS (38% versus 65%), intermediate TBS (38% versus 24%), and degraded TBS (24% versus 11%) also differed significantly (P = 0.001).
An analysis adjusted for age, postmenopausal status, race/ethnicity, and body mass index independently linked HIV positivity to lower baseline TBS (estimate -0.061, P < 0.0001). In a similar analysis, women with HIV had a 62% lower chance of having normal TBS (adjusted odds ratio 0.38, 95% confidence interval 0.23 to 0.63, P = 0.0002).
Every year lumbar spine BMD fell 0.65% in the HIV group and 0.32% in the HIV-negative group, a nonsignificant trend (P = 0.07). Respective annual changes in TBS were -0.97% and -0.77%, P = 0.52). Annual change in TBS correlated with lumbar spine BMD in women with HIV (r = 0.37, P < 0.001) and women without HIV (r = 0.27, P = 0.01).
The researchers noted that this is the first study that demonstrates microstructural differences in bone (not just density differences) between women with and without HIV. Whether TBS-determine bone microarchitecture will improve fracture prediction remains unclear, the investigators added. They suggested that future research should explore adding TBS to BMD in the FRAX algorithm as a fracture predictor.
Reference
1. Sharma A, Ma Y, Tien PC, et al. Measurement of bone microarchitecture among HIV-infected and uninfected women using trabecular bone score. 18th International Workshop on Comorbidities and Adverse Drug Reactions in HIV, September 12-13, 2016, New York. Abstract 004.
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