Mechanical loading disrupts osteocyte plasma membranes which initiates mechanosensation events in bone.

Osteocytes sense loading in bone, but their mechanosensation mechanisms remain poorly understood. Plasma membrane disruptions (PMD) develop with loading under physiological conditions in many cell types (e.g., myocytes, endothelial cells). These PMD foster molecular flux across cell membranes that promotes tissue adaptation, but this mechanosensation mechanism had not been explored in osteocytes. Our goal was to investigate whether PMD occur and initiate consequent mechanotransduction in osteocytes during physiological loading. We found that osteocytes experience PMD during in vitro (fluid flow) and in vivo (treadmill exercise) mechanical loading, in proportion to the level of stress experienced. In fluid flow studies, osteocyte PMD preferentially formed with rapid as compared to gradual application of loading. In treadmill studies, osteocyte PMD increased with loading in weight bearing locations (tibia), but this trend was not seen in non-weight bearing locations (skull). PMD initiated osteocyte mechanotransduction including calcium signaling and expression of c-fos, and repair rates of these PMD could be enhanced or inhibited pharmacologically to alter downstream mechanotransduction and osteocyte survival. PMD may represent a novel mechanosensation pathway in bone and a target for modifying skeletal adaptation signaling in osteocytes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:653-662, 2018.

Effect of intervening tissues on ultrasonic backscatter measurements of bone: An in vitro study.

Ultrasonic backscatter techniques are being developed to diagnose osteoporosis. Tissues that lie between the transducer and the ultrasonically interrogated region of bone may produce errors in backscatter measurements. The goal of this study is to investigate the effects of intervening tissues on ultrasonic backscatter measurements of bone. Measurements were performed on 24 cube shaped specimens of human cancellous bone using a 5 MHz transducer. Measurements were repeated after adding a 1 mm thick plate of cortical bone to simulate the bone cortex and a 3 cm thick phantom to simulate soft tissue at the hip. Signals were analyzed to determine three apparent backscatter parameters (apparent integrated backscatter, frequency slope of apparent backscatter, and frequency intercept of apparent backscatter) and three backscatter difference parameters [normalized mean backscatter difference (nMBD), normalized slope of the backscatter difference, and normalized intercept of the backscatter difference]. The apparent backscatter parameters were impacted significantly by the presence of intervening tissues. In contrast, the backscatter difference parameters were not affected by intervening tissues. However, only one backscatter difference parameter, nMBD, demonstrated a strong correlation with bone mineral density. Thus, among the six parameters tested, nMBD may be the best choice for in vivo backscatter measurements of bone when intervening tissues are present.