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HIV-Infected Postmenopausal Women at High Risk for Bone Fractures
- pdf publication attached
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Download the PDF here
from Jules: this finding that postmenopausal HIV+ women are at greater risk for bone loss & fractures compared to HIV- postmenopsusal women is not surprising and would be expected! Bone loss in older age can be associated with greater frailty. Experiencing a fracture in older age is associated with mortality. As well, frailty in older age can lead to increased risk for a fracture. Low vitamin D levels were found equally in both the HIV+ and HIV- women in this study. Vitamin D levels in HIV+ may be reduced by the p450 interaction of NNRTIs and PIs and as well the effect of tenofovir is of interest. Do integrase inhibitors or CCR5 antagonists have a more beneficial effect on bone? We don't know. If a patient with bone loss switched to an integrase or CCR5-antagonist regimen would this benefit BMD? We don't know. Studies have found bone loss in naives starting HAART but would the same loss be found if using integrase or CCR5 inhibitors? We don't know, perhaps these would be interesting studies. The best way to address the concern about bone loss and fractures is by prevention, eliminate risk factors - alcohol, smoking, exercise, good diet, measure vitamin D levels, see a bone specialist for an evaluation, an endocrinologist who specializes in bone.
Low Bone Mass and High Bone Turnover in Postmenopausal Human Immunodeficiency Virus-Infected Women - pdf of publication attached
Journal of Clinical Endocrinology & Metabolism Feb 2010 advance pub
Michael T. Yin*, Don J. McMahon, David C. Ferris, Chiyuan A. Zhang, Aimee Shu, Ronald Staron, Ivelisse Colon, Jeffrey Laurence, Jay F. Dobkin, Scott M. Hammer, and Elizabeth Shane. Columbia University Medical Center (M.T.Y., D.J.M., C.A.Z., A.S., R.S., I.C., J.F.D., S.M.H., E.S.), New York, New York 10032; Bronx-Lebanon Hospital Center (D.C.F.), Bronx, New York 10456; and Weill Cornell Medical College (J.L.), New York, New York 10065
ABSTRACT
Context: Low bone mineral density (BMD) is commonly reported in young men and women with HIV infection, and fracture rates may be higher. With effective antiretroviral therapy (ART), the HIV population is aging. However, little is known about the skeletal status of postmenopausal women.
Objective: We aimed to assess the effects of HIV infection and ART on BMD and bone turnover in postmenopausal minority women.
Design, Setting, and Patients: A prospective cohort study was performed in 92 HIV+ and 95 HIV- postmenopausal Hispanic and African-American women.
Main Outcome Measures: We measured BMD by dual-energy x-ray absorptiometry, fracture prevalence, serum levels of inflammatory cytokines (TNF{alpha}, IL-6), bone turnover markers, calciotropic hormones, and estrone.
Results: HIV+ women were younger (56 ± 1 vs. 60 ± 1 yr; P < 0.01) and had lower BMI (28 ± 1 vs. 30 ± 1 kg/m2; P < 0.01) and estrone levels. Prevalence of T scores below -1.0 was greater in HIV+ women at the spine (78 vs. 64%; P < 0.05), total hip (45 vs. 29%; P < 0.05), and femoral neck (64 vs. 46%; P < 0.05), and Z scores adjusted for BMI were lower in HIV+ women at the same sites. Serum TNF{alpha}, N-telopeptide, and C-telopeptide were significantly higher in HIV+ than HIV- women, particularly those receiving ART. HIV+ status was independently and negatively associated with spine and hip BMD after adjustment for age, ethnicity, BMI, and alcohol.
Conclusion: The lower BMD, higher prevalence of low BMD, and higher levels of bone turnover markers detected in HIV+ postmenopausal minority women could place them at high risk for future fractures.
"As HIV-infected individuals live longer with potent antiretroviral therapy (ART), metabolic complications such as low bone density and osteoporosis are increasingly recognized," said Michael Yin, MD of Columbia University Medical Center in New York and lead author of the study. "Although numbers of HIV-infected postmenopausal women are increasing and postmenopausal women are at highest risk for osteoporotic fractures, few studies have evaluated skeletal status in this group. We hypothesized that postmenopausal women might be particularly vulnerable to the adverse effects of HIV infection or ART on the skeleton and our results indicate that this may indeed be the case."
To test their hypothesis, Yin and his colleagues initiated a longitudinal study to assess bone health in 92 HIV-positive and 95 HIV-negative postmenopausal women. Bone mineral density of the lumbar spine, femoral neck and hip as well as body composition were measured by dual x-ray absorptiometry (DXA). Researchers found that HIV-positive postmenopausal women had lower bone mineral density at both the spine and hip than HIV-negative postmenopausal women.
"HIV infection was independently associated with lower bone mineral density after adjusting for body mass index (BMI) and traditional osteoporosis risk factors," said Yin. "While the reason for HIV-associated bone loss remains unclear, it may be related to increased levels of cytokines (proteins produced by cells that aid communication between cells), direct effects of antiretrovirals on bone cells or hormonal/nutritional deficiencies that are common in HIV."
"Estrogen protects against the effect of cytokines on bone resorption," said Yin. "Therefore, as HIV-positive women become estrogen deficient during menopause, they may be at higher risk for accelerated bone loss and fracture."
"In conclusion, low BMD was more common in postmenopausal HIV+ than HIV- minority women. HIV infection was independently associated with lower BMD after adjusting for BMI and traditional osteoporosis risk factors. BTMs (bone turnover markers) and TNFa were higher in HIV+ ART+ women, and multivariate modeling suggested that they may mediate the effect of HIV on BMD. Completion of the ongoing longitudinal study should permit assessment of whether increased bone turnover associated with ART translates into accelerated bone loss and increased fracture rates in aging postmenopausal women."
"The higher prevalence of low BMD in our subjects may reflect older age and postmenopausal status......our data suggest that whereas the effects of HIV or ART on BMD are modest, they are in part independent of weight.....Lower body weight is a powerful determinant of BMD.......Importantly, low body weight is a powerful risk factor for osteoporotic fracture. Thus, the fact that BMD is lower in HIV+ individuals is of clinical relevance, whether or not the mechanism by which it is lower is attributable directly to HIV or is mediated indirectly by effects of HIV on weight or other parameters......The 5.9% unadjusted difference in TH BMD between our HIV+and HIV- postmenopausal women is slightly greater than the 3% difference between HIV+ and HIV- men of median age 55 reported elsewhere....In the multivariate model, addition of BTMs (bone turnover markers) attenuated the effect of HIV on BMD in a model that included age, ethnicity, BMI, and alcohol use. This observation suggests that the association between HIV and low BMD is mediated by increased bone turnover."
"Hypothesizing that postmenopausal women might be particularly vulnerable to any adverse effects of HIV infection or ART on the skeleton, we initiated a longitudinal study to assess the prevalence of osteoporosis/osteopenia, determinants and etiology of low BMD, and rates of bone loss in HIV+ postmenopausal Hispanic and African-American women, who constitute the majority of new infections in women in the United States (22). Here,wesummarize cross-sectional analyses of the baseline visit of the study.....BMD of the lumbar spine (LS; L1-L4), femoral neck (FN), total hip (TH), non-dominant 1/3 radius, and body composition were measured by dual-energy x-ray absorptiometry (DXA) on a QDR4500 bone densitometer.
Unadjusted BMD (grams per square centimeter) was 5.9% lower in HIV+ compared with the HIV- women at the TH (Table 2), but did not differ significantly at the spine, FN, or forearm. We performed analysis of covariance to address HIV group differences in age, race/ethnicity, and BMI, important predictors of BMD. After adjustment for these parameters, BMD became lower (by 4.5%) in HIV+ women at the LS, and there was a trend toward lower BMD (by 3-4%) at the non-dominant 1/3 radius and TH (Fig. 1A). Mean T scores were 0.4 SD lower in HIV+ women (Fig. 1B) at the LS and TH. The prevalence of T scores below -1.0 was significantly higher in HIV+ women (Fig. 1C): 78 vs. 64% at the LS, 45 vs. 29% at the TH, and 64 vs. 46% at the FN. Prevalence of osteoporosis, however, did not differ between HIV+_ and HIV- groups. Osteoporosis and osteopenia were defined by World Health Organization criteria for postmenopausal Caucasian women: T scores of -2.5 or less represent osteoporosis; T scores between -1.0 and -2.49 represent osteopenia. We also evaluated Z scores, which compare BMD to age- and race/ethnicity-matched normal populations, after
adjustment for the lower BMI in HIV+ women. Adjusted Z scores were within the expected range for age (-2.0 to +2.0) in both groups but were significantly lower in HIV+ women at the spine (-0.56 +/- 0.1 vs. -0.01 +/- 0.1; P <0.05),
TH (-0.10 +/- 0.1 vs. +0.31 +/- 0.1; P <0.01), and FN (-0.17 +/- 0.1 vs. +0.14 +/- 0.1; P <0.05), but not the forearm (Fig. 1D). Z scores were similarly lower in HIV+ than HIV- Hispanics and in HIV+ than HIV- African-Americans (data not shown)."
"FRACTURES: The proportion of women with a history of fracture did not differ between HIV+ and HIV- wome nat the spine (0 vs. 1%), hip (1 vs. 0%), or forearm (3 vs. 3%). However, HIV+ women reported more fractures at other sites (ribs, ankles, shoulders, pelvis; 7 vs. 0%; P <0.05). Radiographs revealed mild thoracic vertebral fractures in 4.1% of HIV+ and 6.5% of HIV-women (P=0.72), with one severe fracture per group."
'Resorption markers, NTx and CTx, were significantly higher in HIV+ women. Serum BAP, OC, and CTx were significantly higher in HIV+ ART+ than HIV+ ART- women. Serum TNFa was higher in HIV+ than HIV- women, whereas IL-6 levels were similar. OC and CTx differences by ART status remained significant after adjusting for CD4 count or cytokine levels or weight."
"Formation markers, BAP, andOC were slightly but not significantly higher in HIV+ women (Table 2 and Fig. 2)."
"Bone formation and resorption markers correlated moderately in HIV- women (r=0.36 to 0.56; P<0.001) and HIV+ women on ART (r =0.56 to 0.69;
P <0.001) (Fig. 3). In contrast, formation and resorption markers were not correlated in HIV+ART- women, suggesting uncoupling of remodeling."
FIG. 2. BTM levels in HIV- women (open) and HIV+ women (shaded) by current status of ART. Background shaded areas represent the range of
normal serum levels of BAP, OC, NTx, and CTx in premenopausal women.
"Low bone mineral density (BMD) has been reported in many cross-sectional studies of younger HIV+ individuals (4 -10), but relatively few studies of middle-aged and older. Lower BMD measurements are strongly related to the generally lower body weight of HIV+ individuals (5, 14-16). In addition, some studies suggest that HIV infection and ART affect the skeleton directly. BMD declines by 2-6% within the first 2 yr of initiating various ART regimens (17-19) but is relatively stable in patients on established ART (16, 20). Of concern, a recent study suggests that fractures occur more commonly in HIV+ men and women, especially in older individuals (21). Hypothesizing that postmenopausal women might be particularly vulnerable to any adverse effects of HIV infection or ART on the skeleton, we initiated a longitudinal study to assess the prevalence of osteoporosis/osteopenia, determinants and etiology of low BMD, and rates of bone loss in HIV+ postmenopausal Hispanic and African-American women, who constitute the majority of new infections in women in the United States (22). Here, we summarize cross sectional analyses of the baseline visit of the study."
"Between 2002 and 2007, we screened 108 HIV- and 110 HIV+ postmenopausal women from Columbia University Medical Center (CUMC) and Bronx-Lebanon Hospital Center (BLHC) in New York City. HIV- controls were volunteers who were attending the General Internal Medicine Clinics of CUMC."
"BMD of the lumbar spine (LS; L1-L4), femoral neck (FN), total hip (TH), non-dominant 1/3 radius, and body composition were measured by dual-energy x-ray absorptiometry (DXA) on a QDR4500 bone densitometer (Hologic, Inc., Bedford, MA) at CUMC. Short-term in vivo reproducibility is 0.68% for the LS, 1.36% for the TH, and 0.70% for the radius. T scores, which compare subjects to young individuals of the same sex and race, were derived from the National Health and Nutrition Examination Survey (NHANESIII). Osteoporosis and osteopenia were defined by World Health Organization criteria for postmenopausal Caucasian women: T scores of -2.5 or less represent osteoporosis; T scores between -1.0 and -2.49 represent osteopenia (24). Z scores, comparing BMD to an age-, sex-, and ethnicity-matched reference population, were also calculated (12). Height and weight were measured by Harpenden stadiometer and balance beam scale, respectively."
"Spine radiographs were performed atCUMCaccording to the Study of Osteoporotic Fractures protocol (25). The semiquantitative method, which uses visual inspection and characterizes vertebrae as having no, mild, moderate, or severe deformity, was employed to diagnose vertebral fractures. The validity of this method compares favorably with morphometric assessment (25)."
"The primary outcome was BMD at four sites between HIV+ and HIV- groups without adjustment for testing multiple outcomes."
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