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Determinants (HIV, Cytokines) of Low Bone Density in Postmenopausal HIV+ Women
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"Bone mineral density is significantly lower and prevalence of low bone mineral density higher in postmenopausal HIV+ than HIV- women. HIV status remains an independent predictor of bone mineral density after adjustment for traditional factors, and modeling suggests that reduced bone mineral density is partially mediated by up-regulation of pro-resorptive cytokines. Longitudinal evaluation is necessary to determine whether higher levels of bone turnover markers associated with ART results in increased bone loss or fracture."
Reported by Jules Levin-
CROI Feb 2009 Montreal--
Michael Yin*1, D Ferris2, D McMahon1, J Laurence3, H Eisenberg1, S Cremers1, and E Shane1
1Columbia Univ, New York, NY, US; 2Bronx Lebanon Hosp Ctr, NY, US; and 3Weill Med Coll of Cornell Univ, New York, NY, US
Background: Low bone mineral density is associated with HIV infection and/or its therapy. Although postmenopausal HIV+ women may be at higher risk of fracture than younger HIV+ women and men, little is known about their skeletal status.
Methods: Bone mineral density was measured by DEXA in 99 HIV+ and 102 HIV- postmenopausal women from New York City. Serum levels of cytokines associated with bone resorption (tumor necrosis factor-alpha [TNF--], interleukin-6 [IL-6], receptor activator for NFkB ligand [RANKL]), markers of bone formation (osteocalcin, bone alkaline phosphatase) and resorption (N-telopeptide [NTX], C-telopeptide [CTX]), vitamin D metabolites, parathyroid hormone, and estrone were also measured.
Results: --HIV+ women were younger (56±6 vs 60±6 years, p <0.0001) and had lower body mass index (27±6 vs 30±5 kg/m2, p = 0.001) but had similar race/ethnicity (66% Hispanic, 34% African American) as HIV-. Mean CD4 count was 479±309 cells/mm3 and 78% were on ART. --T scores were lower in HIV+ than HIV- women at the lumbar spine (-1.8±0.1 vs -1.30±0.1, p = 0.0003), total hip (-0.9±0.1 vs -0.5±0.1, p = 0.03), and femoral neck (-1.2±0.1 vs -0.9±0.1, p = 0.03). --Prevalence of low bone mineral density (T scores <-1.0) was greater in HIV+ women at the lumbar spine (78% vs 61%, p = 0.01), total hip (44% vs 28%, p = 0.02), and femoral neck (64% vs 46%, p = 0.01) but prevalence of osteoporosis (T score <-2.5) and self-reported fracture were similar between groups. --HIV+ status remained negatively associated with lumbar spine T score (partial correlations r = 0.13, p = 0.05) after adjustment for age, body mass index, and other known predictors. --Serum TNF-- (44±3 vs 31±2 pg/mL, p <0.001), NTX (19±1 vs 16±1 nmol/BCE/L, p = 0.02), and CTX (0.7±0.1 vs 0.5±0.02 ng/mL, p = 0.02) levels were higher, while parathyroid hormone and estrone were lower in HIV+ women than controls. Cytokine levels were not associated with bone mineral density, but statistically controlling for TNF-- reduced HIV+ vs HIV- group differences at lumbar spine and femoral neck. Bone alkaline phosphatase and NTX were higher among women on ART; but bone mineral density was not associated with cumulative exposure to ART by class.
Conclusions: Bone mineral density is significantly lower and prevalence of low bone mineral density higher in postmenopausal HIV+ than HIV- women. HIV status remains an independent predictor of bone mineral density after adjustment for traditional factors, and modeling suggests that reduced bone mineral density is partially mediated by up-regulation of pro-resorptive cytokines. Longitudinal evaluation is necessary to determine whether higher levels of bone turnover markers associated with ART results in increased bone loss or fracture.
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