Microdamage accumulation changes according to animal mass: an intraspecies investigation.

The fatigue life of a structure is also influenced by its size. Statistically, a bone from a large animal is expected to bear a higher risk of stress fracture if compared to the same bone from a small animal of the same species. This is not documented in the dog, where individuals can have a 40 times difference in body mass. We investigated the effect of body size on cortical bone microdamage accumulation, cortical microstructural organization (porosity, osteon area, and osteocyte lacunar density), and turnover in dogs with a wide body mass range. The aim was to understand and mathematically model how the bone tissue copes with the microdamage accumulation linked to body mass increase. Calcified transverse cortical sections of 18 canine radii of remarkably different size were examined by means of a standard bulk-staining technique and histomorphometric standard algorithms. Relationships between the investigated histomorphometric variables age, sex and mass were analyzed by general linear multivariate models and exponential equations. Type and location of microdamage and bone turnover were not influenced by body mass. Gender did not influence any parameter. Age influenced bone turnover and activation frequency. Microcrack density was influenced by bone mass. Bones had a similar microstructural organization within the same species regardless of the subject's dimension. Microdamage accumulation is inversely related to bone mass, whereas bone turnover is mass-invariant. We theorize a mass-related change in the bone fracture toughness targeted to reach an optimal unique dimensionless curve for fatigue life.

Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis.

Compelling evidences suggest that increased production of osteoclastogenic cytokines by activated T cells plays a relevant role in the bone loss induced by estrogen deficiency in the mouse. However, little information is available on the role of T cells in post-menopausal bone loss in humans. To investigate this issue we have assessed the production of cytokines involved in osteoclastogenesis (RANKL, TNFalpha and OPG), in vitro osteoclast (OC) formation in pre and post-menopausal women, the latter with or without osteoporosis. We evaluated also OC precursors in peripheral blood and the ability of peripheral blood mononuclear cells to produce TNFalpha in both basal and stimulated condition by flow cytometry in these subjects. Our data demonstrate that estrogen deficiency enhances the production of the pro-osteoclastogenetic cytokines TNFalpha and RANKL and increases the number of circulating OC precursors. Furthermore, we show that T cells and monocytes from women with osteoporosis exhibit a higher production of TNFalpha than those from the other two groups. Our findings suggest that estrogen deficiency stimulates OC formation both by increasing the production of TNFalpha and RANKL and increasing the number of OC precursors. Women with post-menopausal osteoporosis have a higher T cell activity than healthy post-menopausal subjects; T cells thus contribute to the bone loss induced by estrogen deficiency in humans as they do in the mouse.

Risedronate reduces osteoclast precursors and cytokine production in postmenopausal osteoporotic women.

UNLABELLED: This paper studies the effect of oral risedronate on osteoclast precursors, osteoclast formation, and cytokine production in 25 osteoporotic women. Risedronate is effective in reducing the number of osteoclast precursors, their formation, vitality, and activity and the level of RANKL and TNF-alpha in cultures. INTRODUCTION: Bisphosphonates inhibit bone resorption by acting against osteoclasts. Some in vitro studies suggest that they induce osteoclast apoptosis; others suggest that they exert an effect on the production of pro-osteoclastogenic cytokines. The effect of risedronate on osteoclastogenesis by peripheral blood mononuclear cells (PBMCs) in postmenopausal osteoporosis has not been previously studied. This paper examined the influence of risedronate on the formation of osteoclast precursors and cytokine production within the compass of osteoclastogenesis in osteoporosis. MATERIALS AND METHODS: This study was conducted on 38 osteoporotic women; 25 patients were treated with risedronate 5 mg/d, whereas 13 were treated with calcium 1 g/d and vitamin D 800 UI/d. The following parameters were assessed: changes in bone turnover, circulating osteoclast precursors, formation of osteoclasts in PBMC cultures, their activity and vitality, and variations in the production of pro-osteoclastogenic cytokines before and after therapy. RESULTS: After 3 mo of risedronate, there was a significant reduction in the number and degree of differentiation of osteoclast precursors, osteoclast formation, vitality and activity, and in the level of RANKL and TNF in cultures and of TNF and osteoprotegerin (OPG) in serum, whereas in the group treated with calcium and vitamin D, there were no significant changes. CONCLUSIONS: Our data show that risedronate is effective in lowering the number of circulating osteoclast precursors, their formation, vitality, and activity in cultures, and in reducing the level of pro-osteoclastogenic cytokines in culture supernatants and in serum.

Allometric scaling and biomechanical behavior of the bone tissue: an experimental intraspecific investigation.

INTRODUCTION: Adaptation of bone to different loads has received much attention. This paper examines the consequences of differences in size on bones from the same animal species. METHODS: The study was conducted on 32 canine radii. Their geometry, densitometry and mechanical properties were determined and one-way ANOVA was used to analyze their distribution by sex. Bending failure was observed during the mechanical test. The bones were then likened to thin beams and the mechanical parameters of interest were appraised via beam theory. A multiple linear regression model with stepwise analyses was employed to determine which parameters rule the mechanical characteristics. The relationships between the bone mass and the parameters investigated were analyzed by means of a model II regression in order to state how the scaling of the bone characteristics act on its mechanical behavior. RESULTS: The linear regression model demonstrated that an animal's mass, its sex and the mineral content and the geometrical properties of its bones almost entirely predict their mechanical behavior. A close fit was found between the experimentally determined and the theoretical slopes of the log regressed allometric equations. The work to failure was found to scale almost linearly with the animal and bone mass and the macroscopical bone material properties were found to be mass invariant. The allometric equations showed that as the animal mass increases, employing proportionally the same amount of tissue, bones get proportionally shorter and proportionally distribute their tissue further from the cross-sectional centroid. CONCLUSIONS: Our results suggest that dimensional analysis on the assumption of geometrical self-similarity and mechanical testing according to classic elastic solutions are reasonable in bones tested in accordance to our set up. The bone geometry is the parameter able to curb the energy effects of an animal mass increase. The allometric scaling of the bone length and the cross-sectional layout, without an increase in the amount of material proportionally employed, preserves linear with the animal mass the amount of energy necessary to fracture a bone and restrain the rise of stresses and strains in the cross-section.

Cross-sectional geometrical properties of distal radius and ulna in large, medium and toy breed dogs.

Fractures of the distal radius and the ulna are the third most common fractures in dogs. Toy and miniature breeds have a propensity to develop antebrachial fractures after falling or jumping. Most affect the distal third of both bones involving between 15% and 37% of the radial length. Larger dogs, instead, typically sustain hyperextension injuries to the carpus. The causative mechanisms for this fracture prevalence in toy dogs are unknown. Breed-related changes in bone geometry and/or mineral density have been suggested as possible etiologic factors. In a multifactorial study, the main etiological factors potentially responsible for determining susceptibility to fractures in toy breeds are considered. The aim of this first study is to evaluate the geometric bone features in different dog sizes. The cortical bone cross-sectional properties along the length of the right radius and the ulna of 28 dogs from three different size categories have been quantified by computerized tomographic scanning. Geometrical cross-sectional parameters were measured and normalized to radial length to allow intergroup comparisons. Discriminant analysis was used to classify the observations into different groups. Through statistical analysis of the normalized values, significant differences in cross-sectional properties of different bone sizes were found. The results suggest that, when proportionally loaded, the antibrachii of toy breed dogs are more susceptible to fracture than those of large breed dogs due to morphological differences.