Jacobs, David R.

Abstract Context: Most association studies of bone-related biomarkers (BBMs) with bone mineral density (BMD) have been conducted in postmenopausal women. Objective: We tested whether the following BBMs were cross-sectionally associated with BMD among young adults: serum 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25OHD), PTH, osteocalcin, bone-specific alkaline phosphatase (BAP), and urinary pyridinoline/urinary creatinine. Setting and Participants: We studied 319 individuals (134 women, 149 black, 24–36 years) recruited during 1992 through 1993 in Oakland, California. BMD was assessed with dual-energy x-ray absorptiometry. Linear regression models estimated the association between BMD and each BBM. Results: 1,25(OH)2D was inversely associated with all BMDs. 25OHD was positively, and PTH inversely, associated with lumbar spine, total hip, and whole-body BMD. BAP was inversely associated with left arm, right arm, and whole-body BMD but not with spine or hip BMD. Neither osteocalcin nor urinary pyridinoline/urinary creatinine was associated with BMD. When we placed all BBMs (including 1,25(OH)2D) in one model, the pattern and magnitude of association was similar except for PTH, which was attenuated. The association of BMD and BBMs did not differ significantly by race or sex. Conclusions: In this cross-sectional study of healthy young men and women who had PTH levels considered normal in clinical practice, higher PTH was associated with lower BMD, particularly in weight-bearing sites (ie, spine and hip). The inverse association of 1,25(OH)2D, together with the attenuation of PTH, suggests that the observed association of PTH is mediated by 1,25(OH)2D. BAP was inversely associated with arm BMD. BBMs can be important markers of skeletal activity in young adults, but their clinical role on bone health among this population is yet to be fully determined.

AbstractBACKGROUNDSoluble intercellular adhesion molecule 1 (sICAM-1) is associated with endothelial dysfunction and clinical cardiovascular disease. We investigated the relationship of subclinical atherosclerosis with sICAM-1 concentration.METHODSsICAM-1 concentration was assayed at year 15 of the Coronary Artery Risk Development in Young Adults (CARDIA) Study (black and white men and women, average age 40 years). We assessed progression of coronary artery calcification (CAC) through year 20 (n = 2378), and both carotid artery stenosis (n = 2432) and intima-media thickness (IMT) at year 20 (n = 2240).RESULTSMedian sICAM-1 was 145.9 μg/L. Among a subgroup with advanced atherosclerotic plaque (either CAC or stenosis), IMT was 0.010 (95% CI 0.003–0.017 mm) higher per SD of sICAM-1 (44 μg/L) in a model adjusted for age, race, sex, clinic, smoking, exercise, body size, education, blood pressure, antihypertensive medication, plasma lipids, and cholesterol-lowering medication. With the same adjustment, the odds ratio (OR) for the presence of year-20 carotid artery stenosis per SD of sICAM-1 was 1.12 (95% CI 1.01–1.25, P < 0.04), whereas for occurrence of CAC progression the OR was 1.16 (1.04–1.31, P < 0.01). The associations with CAC and carotid stenosis were strongest in the top 20th of the sICAM-1 distribution.CONCLUSIONSsICAM-1 concentration may be an early biomarker that indicates changes in the artery wall that accompany atherosclerosis, as well as the presence of advanced plaque in the coronary and carotid arteries. This finding holds in people with low total burden of atherosclerosis, decades before the development of clinical CVD.