A mathematical model of cortical bone remodeling at cellular level under mechanical stimulus

A bone cell population dynamics model for cor- tical bone remodeling under mechanical stimulus is devel- oped in this paper. The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model. Not only can the model compare reasonably well with these ex- perimental results such as the increase percentage of final values of bone mineral content （BMC） and bone fracture en- ergy （BFE） among different loading schemes （which proves the validity of the model）, but also predict the realtime devel- opment pattern of BMC and BFE, as well as the dynamics of osteoblasts （OBA）, osteoclasts （OCA）, nitric oxide （NO） and prostaglandin E2 （PGE2） for each loading scheme, which can hardly be monitored through experiment. In conclusion, the model is the first of its kind that is able to provide an in- sight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechan- ical stimulus in order to start resorption/formation of bone mass. More importantly, this model has laid a solid foun- dation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimu- lus can be investigated. The to-be identified control mecha- nism will help to develop effective drugs and combined non- pharmacological therapies to combat bone loss pathologies. Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.

Bone disorders in experimentally induced liver disease in growing rats

AIM： To investigate the change of bone parameters in a new model of experimentally induced liver cirrhosis and hepatocellular carcinoma （HCC） in growing rats. METHODS： Fischer-344 rats （n = 55） were used. Carbon tetrachloride （CCh）, phenobarbital （PB）, and a single diethylnitrosamine （DEN） injection were used. Animals were killed at wk 8 and 16. Bone mineral content, femoral length, cortical index （quotient of cortical thickness and whole diameter） and ultimate bending load （Fmax） of the femora were determined. The results in animals treated with DEN＋PB＋CCh （DPC, n = 21） were com- pared to those in untreated animals （UNT, n = 14） and in control group treated only with DEN＋PB （DP, n = 20）. RESULTS： Fatty liver and cirrhosis developed in each DPC-treated rat at wk 8 and HCC was presented at wk 16. No skeletal changes were found in this group at wk 8, but each parameter was lower （P〈0.05 for each） at wk 16 in comparison to the control group. Neither fatty liver nor cirrhosis was observed in DP-treated animals at any time point. Femoral length and Fmax values were higher （P〈0.05 for both） in DP-treated animals at wk 8 compared to the UNT controls. However, no difference was found at wk 16. CONCLUSION： Experimental liver cirrhosis and HCC are accompanied with inhibited skeletal growth, reduced bone mass, and decreased mechanical resistance in growing rats. Our results are in concordance withthe data of other studies using different animal models. A novel finding is the transiently accelerated skeletal growth and bone strength after a 8-wk long phenobarbital treatment following diethylnitrosamine injection.

Subclinical Indication of Linkage Between Markers of Skeletal and Cardiovascular Properties

Little is known about early coincidental changes in bone and vascular properties, particularly in the context of skeletal anabolism （puberty） versus relative equilibrium （young adulthood）. We aimed to determine if subclinical markers of vascular function were associated with bone mineral content （BMC） and to evaluate the contribution of systemic factors in healthy females ages 14-42 years. Endothelial function was assessed by flow mediated dilatation （FMD）, arterial stiffness by pulse wave velocity （PWV） and augmentation index （AIx）, blood pressure （BP） by sphygmomanometer, BMC by DXA, and systemic factors by fasting blood draw. General linear models controlled for age, race and height indicated a positive association between systolic BP （SBP） and BMC independent of systemic factors. When stratified by age using 19 years as a cut-point, there was an inverse relationship between AIx75 in adolescents with insulin （P〈0.10） or inflammatory markers （P〈0.10） in statistical models. Conversely, there was a positive relationship between BMC and both PWV and AIx75 in young adults （P〈0.05）. The link between bone and the vasculature may be life stage-dependent. In the context of a less dynamic microenvironment in young adult females, metabolic factors appear to moderate less of an effect of hemodynamic properties on the skeleton relative to adolescents.