Mechanical loading and release of endogenous parathyroid hormone (PTH) during exercise facilitate the adaptation of bone. However, it remains unclear how exercise and PTH influence the composition of bone and how exercise and PTH-mediated compositional changes influence the mechanical properties of bone. Thus, the primary purpose of this study was to establish compositional changes within osteocytes’ perilacunar region of cortical bone following exercise, and evaluate the influence of endogenous PTH signaling on this perilacunar adaptation. Raman spectroscopy, Scanning electron microscopy (SEM), and Energy Dispersive X-ray Spectroscopy (EDS) were used to evaluate tissue composition surrounding individual lacuna within the tibia of 19 week old male mice exposed to treadmill running for 3 weeks. As a result of exercise, tissue within the perilacunar region (within 0–5 μm of the lacuna wall) had a lower Mineral-to-Matrix Ratio (MMR) compared to sedentary controls. In addition, exercise also increased the Carbonate-to-Phosphate Ratio (CPR) across both perilacunar and non-perilacunar regions (5–10 μm and 10–15 μm from the lacuna walls). Tibial post-yield work had a significant negative correlation with perilacunar MMR. Inhibition of PTH activity with PTH(7–34) demonstrated that perilacunar remodeling during exercise was dependent on the cellular response to endogenous PTH. The osteocytes’ response to endogenous PTH during exercise was characterized by a significant reduction in SOST expression and significant increase in FGF-23 expression. The potential reduction in phosphate levels due to FGF-23 expression may explain the increase in carbonate substitution. Overall, this is the first study to demonstrate that adaptation in tissue composition is localized around individual osteocytes, may contribute to the changes in whole bone mechanics during exercise, and that PTH signaling during exercise contributes to these adaptations.

The lacunar-canaliculi system is a network of channels that is created and maintained by osteocytes as they are embedded throughout cortical bone. As osteocytes modify their lacuna space, the local tissue composition and tissue strength are subject to change. Although continual exposure to parathyroid hormone (PTH) can induce adaptation at the lacunar wall, the impact of intermittent PTH treatment on perilacunar adaptation remains unclear. Therefore, the primary objective of this study was to establish how intermittent PTH(1–34) treatment influences perilacunar adaptation with respect to changes in tissue composition. We hypothesized that local changes in tissue composition following PTH(1–34) are associated with corresponding gains in tissue strength and resistance to microdamage at the whole bone level. Adult male C57BL/6J mice were treated daily with PTH(1–34) or vehicle for 3 weeks. In response to PTH(1–34), Raman spectroscopy revealed a significant decrease in the carbonate-to-phosphate ratio and crystallinity across the entire tissue, while the mineral-to-matrix ratio demonstrated a significant decrease in just the perilacunar region. The shift in perilacunar composition largely explained the corresponding increase in tissue strength, while the degree of new tissue added at the endosteum and periosteum did not produce any significant changes in cortical area or moment of inertia that would explain the increase in tissue strength. Furthermore, fatigue testing revealed a greater resistance to crack formation within the existing tissue following PTH(1–34) treatment. As a result, the shift in perilacunar composition presents a unique mechanism by which PTH(1–34) produces localized differences in tissue quality that allow more energy to be dissipated under loading, thereby increasing tissue strength and resistance to microdamage. In addition, our findings demonstrate the potential for PTH(1–34) to amplify osteocytes’ mechanotransduction by producing a more compliant tissue. Overall, the present study demonstrates that changes in tissue composition localized at the lacuna wall contribute to the strength and fatigue resistance of cortical bone gained in response to intermittent PTH(1–34) treatment.

Lower extremity weakness is a serious problem afflicting people all over the world. Until recently, the mobility options for people with this condition have been confining and limit the individual’s functionality. Walking assist devices are presently in development to restore hands-free walking to people with lower extremity weakness. These devices provide the necessary support and power to enable the individual to restore normal ambulation. The proposed design of exoleg, a single leg external walking assist device, addresses the demographic of people with lower extremity weakness. The design includes replication of the gait cycle utilizing mechanical links and user control interface with emphasis on safety. The design couples the actuation of the knee and hip through the use of linkages connected to a single motor. The actuation of the hip is controlled by a 4 bars crank-rocker linkage system while the knee is actuated by corresponding linkages (designed in WORKING MODEL 2D, a commercial simulation software) that generates the knee kinematic profile. The angular profiles of the knee and hip actuations are compared with the actual knee and hip angular trajectories. The frame of the device incorporates a passive ankle stabilization system to compensate for the effects of foot drop. The system utilizes feedback from trigger points from pressure sensors on the foot and goniometers at the hip and knee joints to measure the angulations in gait to keep the device in synchronization with natural ambulation. An on-board microprocessor receives the feedback from the trigger points and sends the actuation signal to the motor. A conceptual design of electrostatic actuator motor is also proposed to keep the device light weight and compact.