| |
HIV & Bone Loss/Osteopenia & Osteoporosis & Fractures
|
| |
| |
Jules Levin, NATAP
The understanding of bone loss in HIV+ & HIV-negs is multifactorial with numerous studies having been conducted over the revet few years. Most studies, listed immediately below, found HIV independently associated with bone loss after, with several of these studies collectively finding this outcome after adjusting for traditional risk factors including smoking & weight loss or having a skinny body both of which are traditional risk factors. Studies have found a dysregulated immune system interacting with nine markers as associated as well with bone loss,and studies have also found an association with tenofovir use. A study just published today in JID (full text below) conducted in The Netherlands found the opposite, that HIV was not associated with bone loss in HIV+, that it was due to smoking & low weight & that tenofovir was not associated with bone loss. Of note in this JID study twice as many HIV+ study participate were taking a stain (14% vs 7%), this year at CROI study reported statin protective affects against bone loss: Rosuvastatin Improves Hip Bone Mineral Density but Worsens Insulin Resistance: http://www.natap.org/2014/CROI/croi_44.htm
There have been more studies that I have not linked to finding HIV associated with bone loss but that might be information overload, you can go to the NATAP website & use the Search Engine & insert whatever terms you want: HIV & Bone, osteoporosis & HIV, fracture & HIV etc. The cause of increased bone loss & fracture rates in HIV+ vs HIV-negs is very complicated & as I said multifactorial including that HIV appears to dysregulate the immune system & this appears to affect bone markers.
Is bone loss linked to chronic inflammation in antiretroviral-naive HIV-infected adults? A 48-week matched cohort study.......http://www.natap.org/2014/HIV/060114_01.htm......after adjustment for traditional osteoporosis risk factors, the ART-naive HIV-infected adults were more likely to have bone loss at the trochanter site than controls, and this risk appeared to be associated with heightened inflammation. Also, progression from normal bone to osteopenia or from osteopenia to osteoporosis was independently associated with higher baseline IL-6 levels in the HIV-infected group........BMD at the total hip and trochanter sites decreased in the HIV-infected, ART-naive adults, but not controls, over this 48-week study. Higher serum interleukin-6 concentrations were associated with progression to osteopenia or osteoporosis status in the HIV-infected group.....In the HIV-infected group, total hip and trochanter, but not spine, BMD decreased over 48 weeks [hip -0.005 (-0.026-0.008) g/cm2, P = 0.02 within group; trochanter -0.013 (-0.03-0.003), P < 0.01]. BMD did not change at any site within controls. The HIV-infected group was more likely to have bone loss at the trochanter (P = 0.03). This risk persisted after adjustment for age, sex, race, BMI, smoking, and hepatitis C (odds ratio 4, 95% confidence interval 1.2-15.8).
Mechanism of Bone Disease in HIV and HCV:
Impact of Tenofovir Exposure and Severity of Liver Disease (CROI/2014) [HIV & HCV associated with bone loss].......http://www.natap.org/2014/CROI/croi_162.htm ........HIV and HCV independently predict lower femoral neck BMD, controlling for age, race and BMI (model 1).......The effect of HIV on BMD is likely mediated through increased bone turnover: HIV patients had higher levels of CTX (p<0.005) and OC (p<0.001).....The impact of HIV on BMD appears to be explained (at least in large part) by TDF exposure and higher bone turnover. HCV association with BMD is independent of the severity of liver disease, as measured by APRI score.
[HIV remained independently associated bone loss after adjustment for fat & lean mass] [Lower fat & lean mass are independently associated with bone loss] [Greater fat mass correlated with higher BMD at all three sites] Lean Mass Inches Out Fat Mass as Predictor of Low Bone Density With HIV......http://www.natap.org/2013/EACS/EACS_38.htm
HIV[ART] and HCV infections independently contribute to lower bone mineral density but have different effects on bone turnover markers (IAS/2013)......http://www.natap.org/2013/IAS/IAS_33.htm
HIV is an Independent Predictor of Lower Bone Mineral Density in HIV-positive Subjects Compared to HIV-negative Subjects (CROI/2013).......http://www.natap.org/2013/CROI/croi_200.htm
HIV infection was independently associated with a 0.068g/cm2 lower FN BMD after adjustment for gender, ethnicity, age, smoking status, education and body mass index (BMI). After further adjustment for ALP, HIV remained independently associated with reduced BMD with a reduced effect size, 0.047 g/cm2 (table 1), suggesting that some, but not all, of the effect of HIV is mediated through ALP. Similar effects on BMD were determined at TH and LS.
Low Bone Mineral Density is Associated with Increased Risk of Incident Fracture in HIV-infected Adults "highlighting the potential value of DEXA screening in this population"......median age 42[35-48]....36% osteopenia/2.9% osteoporosis (CROI/2014) .......http://www.natap.org/2014/CROI/croi_58.htm
----------------------
Low bone mineral density in patients with well-suppressed HIV infection is largely explained by body weight, smoking and prior advanced HIV disease
Journal of Infectious Diseases Advance Access published September 1, 2014
"We compared lumbar spine, total hip and femoral neck BMD by dual-energy X-ray absorptiometry in 581 HIV-positive (94.7% on cART) and 520 HIV-negative participants of the AGEhIV Cohort Study, aged ≥45 years. Independent associations between HIV, HIV-disease characteristics, (c)ART and BMD were investigated using multivariable linear regression..............The study population largely consisted of men having sex with men (MSM). Osteoporosis was significantly more prevalent in those with HIV (13.3 vs. 6.7%, p<0.001). After adjusting for body weight and smoking, being HIV-positive as such was no longer independently associated with BMD. Low body weight was more strongly negatively associated with BMD in HIV-positive persons with a history of a CDC-B or CDC-C event. Interestingly, regardless of HIV-status, younger MSM had significantly lower BMD than older MSM, heterosexual males and females......Having experienced symptomatic HIV disease, often associated with weight loss, was an additional risk factor. The low BMD, observed in younger MSM, remains unexplained and needs further study. [from Jules: if you look in Table 1, baseline characteristics 14.5% in the HIV+ group were black vs 8.1% in the HIV-neg group; 3.4% were past IDUs in HIV+ group vs 1% in the HIV-neg group. The HIV-neg group exercised more often in the 5-7 day a week category: 38.8% vs 32.5% and the HIV+ group more often did not exercise; HIV-negs exercised more often. Of note HIV+ group used statins more 14% vs 3.7%, statins may have a protective affect. The HIV+ group took less vit D and had higher inflammation markers."
"The observed lower BMD in those individuals who had experienced loss of body weight associated with advanced HIV-disease, supports the need for earlier identification and treatment of individuals with HIV. Furthermore, clinicians should be aware of the high prevalence of low BMD, particularly in the (relatively) young MSM population. Such individuals may be particularly prone to develop osteoporosis/osteopenia as a result of the BMD decline generally observed following cART initiation (5). Avoidance of regimens associated with greater BMD loss, supportive treatment with vitamin D and calcium (39), and BMD monitoring, especially in the presence of additional risk factors for low BMD, may each be worth considering in such men"
This published study was reported originally at EACS 2013 & its informative to read the original report, data & slides herein this link:
Reduced bone mineral density is largely explained by lower body weight in HIV-positive individuals and more pronounced in younger men having sex with men, regardless of HIV-status. 14th European AIDS Conference......http://www.natap.org/2013/EACS/EACS_35.htm..............This large comparative study confirms a higher prevalence of osteopenia and osteoporosis in middle-aged to older people with HIV than in a comparable HIV-negative group. But statistical analysis accounting for other risk factors did not identify HIV infection as an independent risk factor for lower BMD at any of three sites. Instead, traditional risk factors (weight, smoking, ethnicity, and older age-in cohort members who were not MSM) were associated with BMD. Among HIV-positive people, treatment with tenofovir or protease inhibitors did not significantly affect BMD.
.......Traditional risk factors, including low weight, did raise chances of lower BMD, but older men who have sex with men (MSM) had better chances of higher BMD.......Two other factors were independently associated with lower BMD in this analysis of HIV-positive and negative cohort members: being an MSM (-0.263 g/cm(2), P = 0.002 for lumbar spine; -0.248 g/cm(2), P < 0.001 for total hip) and every additional 10 pack-years of smoking (-0.006 g/cm(2), P = 0.006 for lumbar spine; -0.007 g/cm(2), P < 0.001 for total hip).......Analyzing the HIV-1-positive cohort separately, independent associations were observed between a longer duration of a CD4 count below 200 and lower BMD in the total hip (-0.008 g/cm2/yr, p=0.02) and between HCV-RNA positivity and lower BMD in total hip (-0.084 g/cm2, p=0.004) and femoral neck (-0.075 g/cm2, p=0.006). No independent association was found between known duration of HIV-1 infection, current or past use of TDF or protease inhibitors and reduced BMD in any of the three locations.......older men who have sex with men (MSM) had better chances of higher BMD......Every 10 years in age among HIV-positive and negative MSM were associated with significantly higher lumbar spine BMD (0.033 g/cm(2), P < 0.001) and nonsignificantly higher total hip BMD (0.004 g/cm(2), P = 0.5). In contrast, every 10 years of age in non-MSM were associated with significantly lower total hip BMD (-0.042 g/cm(2), P < 0.001) and nonsignificantly lower lumbar spine BMD (-0.012 g/cm(2), P = 0.4). The counterintuitive association between older age and higher BMD in MSM, the researchers suggested, "may be the result of unmeasured lifestyle and behavioral factors."
--------------------
Low bone mineral density in patients with well-suppressed HIV infection is largely explained by body weight, smoking and prior advanced HIV disease
Journal of Infectious Diseases Advance Access published September 1, 2014
Download the PDF here
Katherine W. Kooij1, Ferdinand W.N.M. Wit1,2, Peter H. Bisschop3, Judith Schouten1,4, Ineke G. Stolte2,5, Maria
Prins2,5, Marc van der Valk2, Jan M. Prins2, Berthe L.F. van Eck-Smit6, Paul Lips7, Peter Reiss1,2,8, on behalf of the
AGEhIV Cohort Study group
1Academic Medical Center and Amsterdam Institute for Global Health and Development, Department of Global Health, Amsterdam, the Netherlands
2Academic Medical Center, Division of Infectious Diseases and Center for Infection and Immunity Amsterdam (CINIMA), Amsterdam, the Netherlands
3Academic Medical Center, Department of Endocrinology and Metabolism, Amsterdam, the Netherlands
4Academic Medical Center, Department of Neurology, Amsterdam, the Netherlands
5Public Health Service Amsterdam, Infectious Diseases Research, Amsterdam, the Netherlands
6Academic Medical Center, Department of Nuclear Medicine, Amsterdam, the Netherlands
7VU University Medical Center, Department of Internal Medicine/Endocrinology, Amsterdam, the Netherlands
8Stichting HIV Monitoring, Amsterdam, the Netherlands
Abstract
Background. HIV and combination antiretroviral therapy (cART) may both contribute to the higher prevalence of osteoporosis and osteopenia in HIV-infected individuals.
Methods. We compared lumbar spine, total hip and femoral neck BMD by dual-energy X-ray absorptiometry in 581 HIV-positive (94.7% on cART) and 520 HIV-negative participants of the AGEhIV Cohort Study, aged ≥45 years. Independent associations between HIV, HIV-disease characteristics, (c)ART and BMD were investigated using multivariable linear regression.
Results. The study population largely consisted of men having sex with men (MSM). Osteoporosis was significantly more prevalent in those with HIV (13.3 vs. 6.7%, p<0.001). After adjusting for body weight and smoking, being HIV-positive as such was no longer independently associated with BMD.Low body weight was more strongly negatively associated with BMD in HIV-positive persons with a history of a CDC-B or CDC-C event. Interestingly, regardless of HIV-status, younger MSM had significantly lower BMD than older MSM, heterosexual males and females.
Conclusion.The observed lower BMD in treated HIV-positive individuals was largely explained by both lower body weight and more smoking. Having experienced symptomatic HIV disease, often associated with weight loss, was an additional risk factor. The low BMD, observed in younger MSM, remains unexplained and needs further study.
INTRODUCTION
A high prevalence of low bone mineral density (BMD) has been observed in HIV-infected populations. A meta-analysis reported the prevalence of osteoporosis and osteopenia in HIV-positive individuals to be as high as 15% and 30%, respectively, corresponding to an odds ratio of 3.7 for osteoporosis and 6.4 for reduced BMD as compared to -uninfected individuals (1). There are also several reports of a higher (lifetime) incidence of fragility fractures in those with HIV, possibly as a consequence of more osteoporosis (2-4). Randomized clinical trials showed a BMD decline within 12 months after starting any type of combination antiretroviral therapy (cART) in treatment-naive patients (5). Use of tenofovir disoproxil fumarate (TDF) and, to a lesser extent, protease inhibitors (PIs) is associated with an accelerated decline of BMD in antiretroviral-naive subjects (6-8). The same is seen in treatment-experienced patients who switch to a combination of TDF with emtricitabine (9-11), but not in those who switch to a different (non-TDF-containing) antiretroviral regimen (12,13). While the rate of BMD decline observed after starting cART generally stabilizes with time (14,15), there are indications that the prolonged use of TDF may be associated with a persistent increase in the rate of BMD decline (16).
The pathogenesis of the increased prevalence of reduced BMD is likely multifactorial. It might be partially explained by a lower average body weight of HIV-infected individuals (17) and other traditional risk factors, such as hypogonadism, smoking, alcohol or opiate use and vitamin D deficiency which are more prevalent in HIV-positive populations (18). It remains unclear whether and how HIV per se may be independently associated with a reduced BMD. The objective of this study was to further elucidate the relationship between BMD and HIV-1, use of cART and traditional risk factors for low BMD in a cohort of HIV-1-infected individuals, predominantly on cART, and HIV-uninfected controls with a comparable background, all aged 45 years and older.
|
|
| |
| |
|
|
|
