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3159 Bone Turnover Biomarkers May Discriminate Low Bone Mineral Density in HIV-Infected Adults
- Lauren Frances Collins, Anandi Sheth, Caitlin Moran, Laura Ward, Kehmia Titanji, Kirk Easley, Jeffrey Lennox, M. Neale Weitzmann, Igho Ofotokun
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, p. 36
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OBJECTIVES/SPECIFIC AIMS: Persons living with HIV (PLWH) are at increased risk for fragility bone disease. Current osteoporosis screening guidelines do not account for HIV status, and clinical risk assessment tools are not sensitive in PLWH. We examined the value of traditional osteoporosis risk factors, HIV-specific indices, and bone turnover biomarkers in predicting low bone mineral density (BMD) in PLWH. METHODS/STUDY POPULATION: Demographic and clinical characteristics, dual energy x-ray absorptiometry (DXA)-derived BMD, HIV indices (viral load, CD4 count, antiretroviral therapy [ART]), and biomarkers of bone turnover (C-terminal telopeptide of collagen [CTx], osteocalcin [OCN]) were evaluated in a cross-sectional analysis of PLWH (n=248) and HIV- controls (n=183). The primary outcome was low BMD, defined as osteopenia or osteoporosis by WHO criteria. Multivariable logistic and modified Poisson regression models were used to assess associations between low BMD and covariates of interest. RESULTS/ANTICIPATED RESULTS: Overall, median age was 44 years, 48% were male, 88% were black, median body mass index (BMI) was 28 kg/m2, 72% smoked cigarettes, and 53% used alcohol; characteristics did not differ by HIV status. PLWH had a mean CD4 of 408 cells/mm3, 55% were ART-naïve, and 45% had viral suppression on ART. Overall, 25% (109/431) had low BMD, including 31% of PLWH compared to 16% of HIV- controls. In multivariable models, HIV was significantly associated with low BMD (aOR 2.46, 95%CI 1.39-4.34; aRR 1.90, 95%CI 1.18-3.07). Adjusting for HIV, three traditional risks– age, race, and BMI– were independently associated with low BMD in the full cohort. However, bone turnover markers, CTx and OCN, were better able to discriminate low vs. normal BMD in PLWH compared to HIV- controls. In PLWH, mean serum CTx was 23% higher in low vs. normal BMD (mean CTx difference=0.06 ug/mL); in HIV- controls, no association with BMD was observed (mean CTx difference=0 ug/mL). In PLWH, mean serum OCN was 38% higher in those with low vs. normal BMD (mean OCN difference=2.48 ug/mL); in HIV- controls, mean serum OCN was only 16% higher in those with low vs. normal BMD (mean OCN difference=1.08 ug/mL). DISCUSSION/SIGNIFICANCE OF IMPACT: In PLWH as opposed to HIV- controls, serum biomarkers reflecting a high bone turnover state, may discriminate individuals with low versus normal BMD. Because changes in biomarkers precede changes in BMD, these markers should be explored further either alone or in combination with traditional risk assessment tools to improve early screening for osteoporosis in PLWH.
Body composition and grip strength are improved in transgenic sickle mice fed a high-protein diet
- Patrice L. Capers, Hyacinth I. Hyacinth, Shayla Cue, Prasanthi Chappa, Tatyana Vikulina, Susanne Roser-Page, M. Neale Weitzmann, David R. Archer, Gale W. Newman, Alexander Quarshie, Jonathan K. Stiles, Jacqueline M. Hibbert
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- Journal:
- Journal of Nutritional Science / Volume 4 / 2015
- Published online by Cambridge University Press:
- 27 February 2015, e6
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Key pathophysiology of sickle cell anaemia includes compensatory erythropoiesis, vascular injury and chronic inflammation, which divert amino acids from tissue deposition for growth/weight gain and muscle formation. We hypothesised that sickle mice maintained on an isoenergetic diet with a high percentage of energy derived from protein (35 %), as opposed to a standard diet with 20 % of energy derived from protein, would improve body composition, bone mass and grip strength. Male Berkeley transgenic sickle mice (S; n 8–12) were fed either 20 % (S20) or 35 % (S35) diets for 3 months. Grip strength (BIOSEB meter) and body composition (dual-energy X-ray absorptiometry scan) were measured. After 3 months, control mice had the highest bone mineral density (BMD) and bone mineral content (BMC) (P < 0·005). S35 mice had the largest increase in grip strength. A two-way ANOVA of change in grip strength (P = 0·043) attributed this difference to genotype (P = 0·025) and a trend in type of diet (P = 0·067). l-Arginine (l-Arg) supplementation of the 20 % diet was explored, as a possible mechanism for improvement obtained with the 35 % diet. Townes transgenic sickle mice (TS; n 6–9) received 0·8, 1·6, 3·2 or 6·4 % l-Arg based on the same protocol and outcome measures used for the S mice. TS mice fed 1·6 % l-Arg for 3 months (TS1.6) had the highest weight gain, BMD, BMC and lean body mass compared with other groups. TS3.2 mice showed significantly more improvement in grip strength than TS0·8 and TS1.6 mice (P < 0·05). In conclusion, the high-protein diet improved body composition and grip strength. Outcomes observed with TS1.6 and TS3.2 mice, respectively, confirm the hypothesis and reveal l-Arg as part of the mechanism.