Tetracycline and calcium kinetics are comparable for estimating bone resorption in rats.

(3)H-tetracycline ((3)H-TC) is thought to be superior to calcium (Ca) isotopic tracers for estimating bone resorption rates due to the less redeposition upon release in animal models. However, these 2 tracers have not been compared directly using complete kinetic studies with sampling of blood, urine, feces, and bone. Our goal was to compare the 2 isotopes for evaluating bone turnover. We firstly developed a model for (3)H-TC kinetics in 4-mo-old female rats (n = 3) by measuring the tracer in serum, urine, and feces over 4 d. Then, 9-mo-old ovariectomized (OVX) rats (n = 6) were given both (45)Ca and (3)H-TC subcutaneously. Urine was collected in 24-h pools and assayed for both tracers. Rats were killed 7 and 46 d after the dose and whole skeleton was harvested. We calculated bone resorption rates by modeling the (45)Ca and (3)H-TC data in urine and bone. (3)H-TC kinetics revealed that, like Ca, there are 2 exchangeable compartments between serum and bone. An additional pool was required to account for bone mass of Ca. Bone resorption rates determined from urinary (45)Ca and (3)H-TC did not differ significantly. The tracers (45)Ca and (3)H-TC can be used interchangeably to determine bone resorption rates in OVX rats. Thus, both labels can be used to screen dietary and other interventions for beneficial effects on bone.

Bone seeking labels as markers for bone turnover: effect of dosing schedule on labeling various bone sites in rats.

Urinary excretion of bone labels can be used to monitor bone resorption. Here we investigate the effects of dosing frequency on label incorporation of various sites when bone turnover was perturbed by ovariectomy. We compared tritiated tetracycline ((3)H-TC) and (45)Ca in two studies. Nine-month-old rats were given single or multiple injections of (3)H-TC and (45)Ca and sacrificed after 7 or 14 days. Six-month-old OVX rats were given (3)H-TC and (41)Ca tracers 1 or 3 months following ovariectomy (OVX + 1 mo or OVX + 3 mo, when bone turnover was higher or lower, respectively) and sacrificed 1 week, 1 month, 3 months, or 6 months postdose. Twenty-four-hour urine pools over 2-4 consecutive days as well as the proximal tibia, femur midshaft, lumbar vertebrae (L1-L4), and remaining skeleton were analyzed for (3)H, (45)Ca, and calcium content. Bone turnover as assessed by urinary (3)H-TC was greater in OVX + 1 mo compared to OVX + 3 mo rats up to 6 months postdose. (45)Ca labeling efficiency (% dose/g Ca) was significantly higher than for (3)H and labeling was higher in trabecular-rich than cortical-rich bone. This study affirms that a single administration of either (3)H-TC or (45)Ca is a useful approach to measuring bone turnover directly. The amount of label incorporation into bone was greater in bone sites that were more metabolically active and in all sites when closer vs farther from OVX.

Soy isoflavones and bone health: the relationship is still unclear.

Evidence of the effect of purified soy isoflavones and soy protein isolates containing isoflavones on bone health in rats and in humans is inconsistent. Differences may be because of synergies or antagonisms among the isoflavones, threshold or biphasic dose effects, life stage of animals or human subjects, estrogen status, and environment-genetic interactions, including the ability to produce metabolites upon ingestion of isoflavones. At this time, the benefits of soy protein and isoflavones on bone health are inconclusive. This overview will summarize these discrepancies and will suggest future studies to clarify the conditions under which these dietary substances can be helpful for bones.