Bones meet competing demands both structurally and metabolically with an ability to “functionally adapt” to the surrounding environment. Diets high in saturated fat and sucrose (HFS) can adversely affect bone by limiting calcium availability. Conversely, applying a mechanical stimulus, appropriate in magnitude, frequency, and rate has been shown to be osteogenic. Thus, we hypothesized that groups subject to a mechanical loading would incur skeletal benefits, whereas exposure to a HFS diet would adversely affect structural integrity. We also proposed that despite the osteogenic potential of loading stimuli, the calcium-limiting effects of a HFS diet would result in a net decrease in bone structural properties, when considered in combination. Female mice underwent non-invasive exogenous cantilever bending of the right tibia with a 1Hz trapezoidal waveform for 60s, five days per week, for thee weeks. Loading was calibrated to induce peak strain magnitudes of 1000 microstrain. Mice were randomly assigned to one of two dietary cohorts: high-fat-sucrose (HFS, n=36) or adjusted starch diets (n=36). Mice were further subdivided into groups based on loading status: control, sham, or loaded. Upon sacrifice, tibiae were dissected; morphometrical and mechanical properties were assessed and compared. Control mice fed a HFS diet had significantly reduced cross-sectional area, cortical thickness, maximal load, and energy to failure when compared to control mice fed the starch diet. No changes in material properties were seen. Mice eating a HFS diet as well as experiencing mechanical loading had significantly greater cross-sectional area, energy to failure, and maximal load when compared to control mice fed a HFS diet, but had reduced structural properties when compared with loaded mice within the starch cohort. To date, bone structural properties, and not material properties were adversely affected as a result of ingesting a HFS diet. A diet effect was observed, between control mice fed a HFS diet and control mice fed a starch diet, with the former group experiencing the negative affects previously associated with HFS diets in rodents. Presently, a load effect was only observed within the HFS cohort.
Altered joint mechanics produced by periarticular bone remodelling may precede the cartilage changes of osteoarthritis (OA). Recently, receptor activator of nuclear factor kappa beta (RANK), along with its soluble ligand (RANK-L), have been shown to induce both maturation and activation of bone-degrading osteoclasts. Activation of RANK on osteoclast cells by RANK-L is opposed by another soluble factor, osteoprotegerin (OPG). Thus RANK/OPG balance is important in regulating bone turnover. Here, we compared periarticular bone from patients with end-stage OA undergoing total knee arthroplasty (TKA) with those of cadaveric controls. We assessed bony, histological and molecular changes that are important in the pathogenesis of OA. Using in-situ hybridization, we found increased staining of digoxygenase (DIG)-labelled OPG in osteoblasts of TKA bone. A corresponding increase in subchondral and insertional bone was seen on micro-CT (μCT) sections from TKA bone in comparison with cadaveric controls. Those changes were accompanied by marked articular cartilage degeneration on histology. This study is the first of which we are aware that directly assessed the role of OPG in inducing the bony changes seen in human end-stage OA. We used μCT to compare corresponding samples qualitatively from TKA and cadaveric bone. Adjacent sections underwent hybridization of digoxygenase (DIG)-labelled OPG riboprobes to assess gene expression in situ. Finally, samples were stained and analysed for histology. Bony hypertrophy may be a result of overexpression of OPG that occurs as an important feature of OA pathophysiology. Funding: This work was supported by a grant from the Hip Hip Hooray Fund of the Canadian Orthopaedic Research Foundation (CORF) and the Wood Professorship in Joint Injury Research. There was no commercial funding for this research project.
