Scientists widely agree that peak bone mass relates directly to the likelihood of osteoporotic fractures later in life. A strong skeleton early in life should, then, help to prevent fragility fractures in future decades. Although full adult height is reached by age 18, skeletal consolidation can continue for several years, and a longitudinal, observational study from our laboratory recently confirmed that bone gain not stop until about age 30. In that study, the rate of gain in bone mass among healthy young women was directly related to the ratio of calcium-to- protein in their diets (protein increases loss of calcium in urine). (Whereas intakes at the 1989 RDAs would yield a dietary calcium-to-protein ratio of 26 mg/g, prevailing intakes among female subjects in their 20s average only about 12 mg/g.) Through calcium supplementation, the decade before age 30 may well represent a unique opportunity to offset earlier, self-imposed restriction of dietary calcium. The proposed study has been designed to examine that opportunity in a follow-up to our earlier observational study. We propose a three-year, double-blind, placebo-controlled randomized clinical trial of calcium (1500 mg/d as carbonate, in divided doses with meals) or an identical appearing placebo. The subjects will be non-smoking young women, aged 19 to 24 at entry and in good general health, whose dietary calcium-to-protein ratio (as assessed by 7-day food diary) does not exceed 12 mg/g. The purpose is to increase specificity by excluding subjects more likely to be calcium- replete. Before randomization to treatment, the sample will be stratified according to baseline total-body bone mineral content (above and below a TBBM of 1500 g/m height). 238 subjects will be enrolled to assure that at least 160 finish. Rates of change in TBBM and in regional bone mass (spine, hip, and forearm) will be determined for each subject over the period from 12 to 36 months (to avoid the influence of the remodeling transient, a potentially misleading early treatment effect). The proposed study will be the first controlled trial of calcium effects on bone designed to (i) avoid the remodeling transient, (ii) consider the importance of protein intake, (iii) test the influence of baseline bone mass, (iv) use an objective measure of compliance (fecal calcium density), and (v) examine calcium supplementation in this important age group.
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| Stains, Joseph P; Civitelli, Roberto (2003) Genomic approaches to identifying transcriptional regulators of osteoblast differentiation. Genome Biol 4:222 |
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