Premature Spinal Bone Loss in Women Living with HIV is Associated with Shorter Leukocyte Telomere Length

Abstract

With advances in combination antiretroviral therapy (cART), people living with HIV are now surviving to experience aging. Evidence suggests that individuals living with HIV are at greater risk for low bone mineral density (BMD), osteoporosis, and fractures. Better understanding of the pathophysiology of bone health in women living with HIV (WLWH) is important for treatment strategies. The goal of this study was to explore new biological factors linked to low BMD in WLWH. Standardized BMD measures of WLWH were compared to reference values from an unselected population of women from the same geographical region of the same age range. Linear regression analysis was used to assess relationships among health-related characteristics, cellular aging (measured by leukocyte telomere length; LTL), cART, and BMD of WLWH. WLWH (n = 73; mean age 43 ± 9 years) had lower BMD Z-scores at the lumbar spine (LS) (mean difference = −0.39, p < 0.001) and total hip (TH) (−0.29, p = 0.012) relative to controls (n = 290). WLWH between 50 and 60 years (n = 17) had lower Z-scores at the LS (p = 0.008) and TH (p = 0.027) compared to controls (n = 167). Among WLWH, LS BMD was significantly associated with LTL (R2 = 0.09, p = 0.009) and BMI (R2 = 0.06, p = 0.042). Spinal BMD was adversely affected in WLWH. Reduction of LTL was strongly associated with lower BMD and may relate to its pathophysiology and premature aging in WLWH.

Can telomere length predict bone health? A review of current evidence

“…Women living with HIV aged ≥50 years also had lower BMD T-scores at lumbar spine (mean difference = -0.74; 95% CI: -1.34, -0.15) and total hip (mean difference = -0.52; 95% CI: -1.01, -0.02). Among women living with HIV, lumbar spine BMD was associated with leukocyte telomere length (R 2 = 0.09; p = 0.009), indicating that leukocyte telomere length was strongly associated with lower BMD in women living with HIV [22]. Tao et al (2019) conducted a study among elderly Chinese men (n = 433; aged 68.7 ± 6.3 years) and women (n = 584; aged 66.4 ± 5.7 years) to examine the association between leukocyte telomere length, BMD, and osteoporosis.…”

“…In a cross-sectional study involving women living with human immunodeficiency virus [HIV] (n = 73; aged 43 ± 9 years) and reference controls (n = 280; aged 50 ± 8 years), Kalyan et al (2018) identified that women living with HIV had the greatest deficit in BMD Z-score at the lumbar spine The deterioration of trabecular and cortical bone microarchitectures, lower level for polar and second moment of inertia in SAMP6 mice Telomere length was shortened in SAMP6 mice [17] Wild type and Wrn -/-Terc -/double mutant mice…”

“…Telomere length was positively correlated with BMD at spine and forearm Longer telomere was associated with a lower risk of clinical osteoporosis at two or more sites Among women aged 50 years and above, shorter telomere length (117 bp = 5.2 years of telomeric aging) was associated with clinical osteoporosis [21] Women living with HIV (n=73; aged 43±9 years) Women living with HIV had lower BMD Z-score and T-scores at the lumbar spine and total hip as compared to the controls Leukocyte telomere length was the independent predictor variable for lumbar spine BMD [22] Chinese elderly men and women (n=1017; aged ≥60 years)…”

“…Women living with HIV aged ≥50 years also had lower BMD T-scores at lumbar spine (mean difference = -0.74; 95% CI: -1.34, -0.15) and total hip (mean difference = -0.52; 95% CI: -1.01, -0.02). Among women living with HIV, lumbar spine BMD was associated with leukocyte telomere length (R 2 = 0.09; p = 0.009), indicating that leukocyte telomere length was strongly associated with lower BMD in women living with HIV [ 22 ].…”

Innovations in Women’s Bone Health—Appreciating Important “Bone Variables” Besides Estrogen

“…This Issue included work from scientists in five countries and presented an incredible array of perspectives/topics. These bone-relevant variables included shorter leukocyte telomere lengths related to lower BMD in women living with HIV [ 6 ], insulin resistance related to reduced bone strength in menopausal Chinese women without diabetes [ 7 ] and altered polar lipid metabolomics associated with lower femoral neck BMD [ 8 ].…”