6.3. Bone resorption

Dietary xylitol supplementation (10 and 20 %) diminished bone resorption in healthy rats, measured as urinary excretion of ³H radioactivity of the [³H];tetracycline-prelabeled rats. Furthermore, 10% dietary xylitol supressed significantly the ovariectomy-induced increase of bone resorption. Accordingly, significantly more ³H radioactivity was preserved in the bones of the xylitol-fed rats as compared to the controls, and to the ovariectomized rats without xylitol at the end of the experimental period. This further confirms the retarded bone resorption, and also that the xylitol-induced effect can not be explained by any major disturbances in general metabolism or by failure in renal function of these animals. Dietary sorbitol, and to a lesser degree D-mannitol also retarded bone resorption in healthy rats, but the side effects associated with the use of these polyols were more harmful than those when using xylitol. Furthermore, no significant increase of presereved bone ³H radioactivity at the end of the experiment was detected in rats fed sorbitol or D-mannitol as compared to the controls.

Dietary supplementation with 1M sorbitol led to reduced weight gain and decreased weight of the bones as compared to the control rats. This suggests a slower growth rate of the sorbitol-fed rats, accompanied by slower bone metabolism. This, most likely, also partly explains the diminished bone resorption values during dietary sorbitol supplementation.

However, the effects of other polyols suggest that the diminished bone resorption is not a xylitol-specific phenomenon, but more likely, a polyol-associated effect, which is greatly dependent on the metabolic differences between the polyols.

The detailed chemical mechanism of decreased bone resorption caused by dietary polyols is obscure, but an overload of calcium is most likely involved. A parallel, rapidly expressing decrease in the urinary excretion of ³H was detected by Mühlbauer and Fleisch (1990) when dietary calcium supplementation was given to animals that were first fed a low-calcium diet. Increased calcium absorption (Hämäläinen et al. 1985) and increased bone calcium content (Knuuttila et al. 1989) has been observed during xylitol administration. Accordingly, increased calcium absorption has been detected during dietary administrations of sorbitol and D-mannitol (Vaughan & Filer 1960, Hämäläinen & Mäkinen 1986, Knuuttila et al. 1989), and increased bone calcium content during dietary administration of sorbitol, although to a lesser degree than with xylitol (Knuuttila et al. 1989).

The enhanced calcium absorption may be related to complex formation between calcium and the polyols. It has been suggested that the complexed calcium remains soluble in the gut lumen for prolonged periods of time promoting its absorption (Hämäläinen & Mäkinen 1989a). The metal cation must, however, be able to assimilate from the complex to prevent it from being excreted in urine or in feces. Thus, complexes with intermediate stability are the most effective promotors of calcium absorption. Briggs et al. (1981) have shown that the relative complexation coefficients (measuring relative stabilities of complexes) of xylitol, sorbitol, D-mannitol and erythritol with calcium are 0.30, 0.40, 0.20 and 0.19, respectively. Accordingly, the polyols, xylitol and sorbitol, that form stronger complexes, were also more effective in retarding bone resorption.

Another interesting metabolic point of view is that xylitol and sorbitol, which are mostly metabolized, seem to retard bone resorption more effectively than the poorly utilized D-mannitol and the unmetabolized erythritol. The first step of the metabolism of absorbed polyols is their oxidation by L-iditol dehydrogenase to the corresponding 2-ketoses with concomitant production of NADH. Ingested xylitol and sorbitol will thus increase the cellular NADH/NAD ratio, while the low oxidation rate of D-mannitol should not elevate the cellular NADH level significantly. The high cellular NADH/NAD ratio may lead to many metabolic reactions and hormonal effects that may affect bone metabolism. One of the possible targets is the citric acid cycle (Jakob et al. 1971). Increased urinary and bone citrate levels have been detected in xylitol-fed rats (Hämäläinen & Mäkinen 1986, Knuuttila et al. 1989). However, the actual significance of the increased NADH achieved during xylitol feeding and its possible mechanism affecting bone metabolism are not known.

Postmenopausal osteoporosis and ovariectomy are accompanied by reduced intestinal absorption of calcium, probably contributing to the accompanying bone loss (Heaney et al. 1978, Ash & Goldin 1988, Gallagher 1990). This estrogen deficiency-induced effect has been linked to decreased serum levels of 1,25-dihydroxyvitamin D₃ (Gallagher et al. 1980), or to intestinal resistance to the action of 1,25-dihydroxyvitamin D₃ (Gennari et al. 1990). It has also been suggested, that estrogen may play a physiological role in the regulation of intestinal calcium absorption, and that its deficiency in postmenopausal osteoporosis, and following ovariectomy, may result directly in calcium malabsorption (Arjmandi et al. 1993). Furthermore, increased intestinal secretion of calcium has been suggested to be essential in the impaired calcium balance in these situations (O"Loughlin & Morris 1994).

Dietary xylitol, on the other hand, is known to increase calcium absorption independently of vitamin D action (Hämäläinen et al. 1985). Thus, xylitol is able to fulfill its bone resorption inhibiting action despite the state of estrogen deficiency.