The effects of phytochemicals on bone turnover and validation of a novel method to assess bone turnover

Jennifer Mei Kuin Cheong, Purdue University


The effect of phytoestrogens on bone is inconclusive. Therefore, we undertook a blinded, randomized, crossover study to identify the effective dose of isoflavone-enriched soy protein isolate for suppressing bone resorption in postmenopausal women. Thirteen postmenopausal women consumed 0, 97.5, and 135.5 mg of total isoflavones in randomized order during sequential 50-day treatment periods. None of the isoflavone levels suppressed bone resorption as measured by urinary 41Ca and biochemical markers of bone turnover in postmenopausal women. Our ultimate goal is to develop use of urinary 41Ca appearance from bone to directly measure bone resorption in humans. To investigate 41Ca technology further, two animal studies were conducted using bone seeking labels 45Ca and 3H-tetracycline as a proxy for 41Ca. The first study aimed to compare the labeling pattern and efficiency of 3H-tetracycline and 45Ca at trabecular-rich versus cortical-rich bone, and to compare single and multiple 3H-tetracycline and 45Ca injections. Labeling efficiencies were significantly higher in trabecular-rich than cortical-rich bone. Rats receiving the multiple injections had significantly higher total skeletal 3H-tetracycline retention, but similar 45Ca retention, than rats receiving a single injection. Bone resorption rates determined from urinary 45Ca and 3H-tetracycline were not significantly different from each other. The second study aimed to understand timing of label incorporation and release when bone resorption was manipulated by ovariectomy stabilization and dietary calcium. At one month post dose, but not at later time points, a 0.5%, in comparison to a 0.2% calcium diet suppressed bone resorption by ∼17% in ovariectomized stabilized rats. In contrast, ovariectomized stabilized rats had ∼26% lower urinary 3H-tetracycline than recent ovariectomized rats up to 6 months post dose. In conclusion, urinary loss of label in bone when perturbed by dietary calcium, but not ovariectomized stabilization, appears to be an acute phenomenon. The rate of change in total skeletal 3H-tetracycline was positively related to the rate of change in urinary 3H-tetracycline. The animal studies suggested that monitoring urinary excretion of a pre-labeled skeleton with a single dose over 1 month is feasible to measure perturbations in bone turnover. Effects of calcium and ovariectomy, but not phytoestrogens, were detected using this approach.




Weaver, Purdue University.

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