Nuclear factor erythroid 2-related factor 2 (Nrf2) deficiency causes age-dependent progression of female osteoporosis.

BACKGROUND: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial transcription factor for cellular redox homeostasis. The association of Nrf2 with elderly female osteoporotic has yet to be fully described. The aim was to elucidate a potential age-dependent Nrf2 contribution to female osteoporosis in mice. METHODS: Eighteen female wild type (WT) and 16 Nrf2-knockout (KO) mice were sacrificed at different ages (12 weeks = young mature adult and 90 weeks = old) to analyze their femurs. The morphological properties (trabecular and cortical) were evaluated by micro-computed tomography (µCT) and compared to gold standard histochemistry analysis. The quasi-static compression tests were performed to calculate the mechanical properties of bones. Additionally, the population of bone resorbing cells and aromatase expression by osteocytes was immunohistochemically evaluated and empty osteocyte lacunae was counted in cortical bone. RESULTS: Old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density (BMD), cortical thickness, cortical area, and bone fraction compared to old WT mice, regardless of no significant difference in skeletally mature young adult mice between WT and KO. Specifically, while all old WT mice showed thin metaphyseal trabeculae, trabecular bone was completely absent in 60% of old KO mice. Additionally, old KO mice showed significantly more osteoclast-like cells and fewer aromatase-positive osteocytes than WT mice, whereas the occurrence of empty osteocyte lacunae did not differ between both groups. Nrf2-KO mice further showed an age-dependently reduced fracture resilience compared to age-matched WT mice. CONCLUSION: Our results suggest that chronic Nrf2 loss can lead to age-dependent progression of female osteoporosis.

Design of an Affordable, Modular Implant Device for Soft Tissue Tension Assessment and Range of Motion Tracking During Total Hip Arthroplasty.

Background: In hip arthroplasties, surgeons rely on their experience to assess the stability and balance of hip tissues when fitting the implant to their patients. During the operation, surgeons use a modular, temporary set of implants to feel the tension in the surrounding soft tissues and adjust the implant configuration. This process is naturally subjective and therefore depends on the operator. Inexperienced surgeons undertaking hip arthroplasties are twice as likely to experience errors than their experienced colleagues, leading to dislocations, pain and discomfort for the patients. Methods: To address this issue, a new, 3DOF force measurement system was developed and integrated into the modular, trial implants that can quantify forces and movements intraoperatively in 3D. The prototypes were evaluated in three post-mortem human specimens (PMHSs), to provide surgeons with objective data to help determine the optimal implant fit and configuration. The devices comprise a deformable polymer material providing strain-based displacements measured with electromagnetic-based sensors and an inertial measurement unit (IMU) for motion data. Results: Device results show a relative accuracy of approx. 2% and a sensitivity of approx. 1%. PMHS results indicated that soft tissue forces on the hip joint peak in the order of ~100 N and trend with positions of the leg during range of motion (ROM) tests, although force patterns differ between each PMHS. Conclusion: By monitoring forces and force patterns of hip soft tissues, in combination with standardised ROM tests, the force patterns could shed a light on potential anomalies that can be addressed during surgery. Clinical and Translational Impact Statement: The development of an instrumented hip implant device for use during surgery knowledge will eventually allow us to develop a predictive model for soft tissue balancing, that can be used for pre- and intra-operative planning for each patient on a tailored and personalised basis. Ultimately, we hope that with this device, patients will benefit from a faster recovery, from a more-precisely fitted hip, and an improved quality of life.