Dietary xylitol in the prevention of experimental osteoporosis. Beneficial effects on bone resorption, structure and biomechanics

Pauli Mattila

Institute of Dentistry, University of Oulu, FIN-90220 Oulu, Finland

Abstract

Dietary xylitol supplementation increases bone calcium and phosphorus concentrations in healthy rats, as well as protects against the decrease of bone minerals and bone density during experimental osteoporosis. This suggests that dietary xylitol might have a favorable effect on the prevention of osteoporosis. However, before any conclusions can be drawn about the usefulness of a compound, studies including structural evaluation and biomechanical testing of bones must first be performed.

Thus, the aim of the present study was to clarify whether dietary xylitol affects bone resorption, bone structure, and bone biomechanics in healthy rats, and whether dietary xylitol offers some preventive effects against the increased bone resorption, decreased bone trabeculation, and weakened bone biomechanical properties during experimental osteoporosis.

Dietary xylitol reduced bone resorption in 3-mo old healthy male rats, and protected significantly against the increase of bone resorption in 3-mo old ovariectomized rats, as measured by the urinary excretion of 3H following [3H];tetracycline-prelabeling. In addition, increased trabecular bone volume of proximal tibia in 4-mo old healthy male rats was detected after a 1-mo xylitol feeding period, and significant protection against the decrease of trabecular bone volume in 6-mo old ovariectomized rats was observed after a 3-mo xylitol feeding period. Furthermore, dietary xylitol increased the strength properties of long bones in 6-mo old healthy male rats after a 3-mo feeding period, without affecting the bone elastic properties as tested by three-point bending of tibia, torsion of femur, and loading of femoral neck. Accordingly, dietary xylitol protected significantly against the weakening of bone biomechanical properties in 6-mo old ovariectomized rats after a 3-mo feeding period.

In conclusion, the above results strongly support the hypothesis that oral administration of xylitol protects effectively against the progression of experimental osteoporosis. Dietary xylitol was effective both in increasing bone mass in healthy rats, and in preventing bone loss in ovariectomized rats, suggesting a favorable effect of xylitol on both main targets in the prevention of osteoporosis. As dietary xylitol was effective also in protecting against the experimental osteoporosis-caused changes in bone structure and weakening of bone biomechanical properties, oral xylitol administration seems to provide interesting possibilities when searching for new physiological choices for the prevention of osteoporosis.


Table of Contents
Acknowledgements
Abbreviations
List of original publications
1. Introduction
2. Review of the literature
2.1. Xylitol
2.2. Xylitol in mineral metabolism
2.3. Other sugar alcohols
2.4. Osteoporosis
2.4.1. Peak bone mass
2.4.2. Bone loss
2.4.3. Prevention and treatment of bone loss
2.5. Experimental osteoporosis
3. Aims of the study
4. Materials and methods
4.1. Animals
4.2. Experimental design
4.2.1. Dietary regimen
4.2.2. Ovariectomy
4.3. Analyses
4.3.1. Bone resorption rate
4.3.2. Analyses of bone inorganic fraction
4.3.3. Trabecular bone volume
4.3.4. Analyses of bone organic fraction
4.3.5. Bone biomechanical properties
4.4. Statistical analyses
5. Results
5.1. General findings
5.2. The effects of polyols on bone resorption
5.3. The effects of xylitol on bone composition and structure
5.3.1. The effects on bone inorganic fraction
5.3.2. The effects on bone collagen
5.3.3. The effects on bone trabeculation
5.4. The effects on bone biomechanical properties
6. Discussion
6.1. Methodological aspects
6.1.1. Measuring bone resorption
6.1.2. Measuring bone biomechanics
6.2. General and side effects
6.3. Bone resorption
6.4. Bone structure
6.5. Bone biomechanical properties
7. Summary and conclusions
References
List of Tables
4-1. Main background data of the animals and of the experimental design.
5-1. Tibial density and biochemical data of the inorganic fraction of humerus in ovariectomized rats (ovx), in ovariectomized rats fed a diet supplemented with 10% xylitol (ovx+xyl), and in sham-operated rats (sham)*
List of Figures
2-1. Structural formula of xylitol.
2-2. Structural formulas of sorbitol, D-mannitol and erythritol.
4-1. Schematic presentation of the mechanical tests of the bones. F is the applied force, T is the applied torque, and the arrows represent the direction of the loading.
5-1. Urinary 3H excretion in different xylitol supplementation groups compared with the control group. All values are means, n=10 in each group. The mean value of the control group is set to 100 in each time point (Study I, Fig. 2.).
5-2. Urinary 3H excretion of the rats fed different polyols (1 mol/kg dry diet) for 1 mo. Values are means, n=10 in each group (Study II, Fig. 2.).
5-3. Urinary 3H excretion of rats with sham-operatation, ovariectomy or ovariectomy followed by 10% dietary xylitol supplementation. The values are presented in proportion to the baseline levels (%), n=10 in each group (Study III, Fig. 1.).
5-4. Proximal tibia (representing average) of a control rat (A), and of a rat fed a diet supplemented with 5% (B), 10% (C), or 20% xylitol (D). Trabecular bone volumes (%, mean±SD) of different groups were 15.3±2,5, 18.4±4.1, 19.3±2.6 and 25.9±2.3, respectively (n=10 in each group) (Study IV, Fig. 2.).
5-5. Proximal tibia (representing average) of a sham-operated (A), of an ovariectomized (B), and of a 10% xylitol-fed ovariectomized rat (n=10 in each group) (Study III, Fig. 2.).
5-6. Biomechanical results of three-point bending of tibia, of torsion test of femur, and of loading test of femoral neck in controls, and in rats fed a diet supplemented with 5, 10, or 20% xylitol (n=10 in each group) (Study IV, Fig. 1.).
5-7. Biomechanical results of three-point bending of tibia, of torsion test of femur, and of loading test of femoral neck in sham-operated rats, in ovariectomized rats, and in 10% xylitol-fed ovariectomized rats (n=14 in each group).