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BACKGROUND: Radiotherapy for tumor treatment in or near bones often causes osteopenia and/or osteoporosis, and the resulting increased bone fragility can lead to pathologic fractures. Bone mineral density (BMD) is often used to screen for fracture risk, but no conclusive relationship has been established between BMD and the microstructural/ biomechanical changes in irradiated bone. Understanding the effects of radiation dosing regimen on the bone structure-strength relationship would improve the ability to reduce fracture-related complications resulting from cancer treatment. METHODS: Thirty-two C57B6J mice aged 10 – 12 weeks old were randomized to single dose (1 x 25 Gy) and fractionated dose (5 x 5 Gy) irradiation groups. Right hindlimbs were irradiated while the contralateral hindlimbs served as the non-irradiated control. Twelve weeks after irradiation, BMD and bone microstructure were assessed with micro-computed tomography, and mechanical strength/stiffness was assessed with a torsion test. The effects of radiation dosing regimen on bone microstructure and strength were assessed using ANOVA, and bone strength-structure relationships were investigated through correlation analysis of microstructural and mechanical parameters. RESULTS: Fractionated irradiation induced significantly greater losses in BMD in the femur (23% - male mice, p=0.016; 19% - female mice) and the tibia (18% - male mice; 6% - female mice) than the single-dose radiation. The associated reductions in trabecular bone volume (-38%) and trabecular number (-34% to -42%), and the increase in trabecular separation (23% to 29%) were only significant in the male mice with fractionated dosing. There was a significant reduction in fracture torque in the femurs of male (p=0.021) and female (p=0.0017) mice within the fractionated radiation group, but not in the single dose radiation groups. There was moderate correlation between bone microstructure and mechanical strength in the single-dose radiation group (r = 0.54 to 0.73), but no correlation in the fractionated dosing group (r=0.02 to 0.03). CONCLUSION: Our data indicate more detrimental changes in bone microstructure and mechanical parameters in the fractionated irradiation group compared to the single dose group. This may suggest the potential for protecting bone if a needed therapeutic radiation dose can be delivered in a single session rather than administered in fractions.

BACKGROUND: This study compares effectiveness of two commercially available signals, Pulsed Electromagnetic Field (PEMF) and Combined Magnetic Field (CMF) clinical signals, to stimulate bone healing in rabbit tibial osteotomies. METHODS: One millimeter osteotomies in New Zealand White rabbits, stabilized with external fixators, were exposed daily to either signal for 30 minutes, three or six hours. Osteotomized sham controls received no signal exposure. Analyses of torsional strength, periosteal callus area and fracture healing stage demonstrated dose responses to increasing daily exposures to both signals. RESULTS: By 14 days torsional strength increased over shams in the three and six hour-treated groups, significant only for the six hour groups (p

Two categories of joint overloading cause post-traumatic osteoarthritis (PTOA): single acute traumatic loads/impactions and repetitive overloading due to incongruity/instability. We developed and refined three classes of complementary models to define relationships between joint overloading and progressive cartilage loss across the spectrum of acute injuries and chronic joint abnormalities: explant and whole joint models that allow probing of cellular responses to mechanical injury and contact stresses, animal models that enable study of PTOA pathways in living joints and pre-clinical testing of treatments, and patient-specific computational models that define the overloading that causes OA in humans. We coordinated methodologies across models so that results from each informed the others, maximizing the benefit of this complementary approach. We are incorporating results from these investigations into biomathematical models to provide predictions of PTOA risk and guide treatment. Each approach has limitations, but each provides opportunities to elucidate PTOA pathogenesis. Taken together, they help define levels of joint overloading that cause cartilage destruction, show that both forms of overloading can act through the same biologic pathways, and create a framework for initiating clinical interventions that decrease PTOA risk. Considered collectively, studies extending from explants to humans show that thresholds of joint overloading that cause cartilage loss can be defined, that to at least some extent both forms of joint overloading act through the same biologic pathways, and interventions that interrupt these pathways prevent cartilage damage. These observations suggest that treatments that decrease the risk of all forms of OA progression can be discovered. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:515-523, 2017.

Laminectomy has been regarded as a standard treatment for multi-level cervical stenosis. Concern for complications such as kyphosis has limited the indication of multi-level laminectomy; hence it is often augmented with an instrumented fusion. Laminoplasty has emerged as a motion preserving alternative. The purpose of this study was to compare the multidirectional flexibility of the cervical spine in response to a plate-only open door laminoplasty, double door laminoplasty, and laminectomy using a computational model. A validated three-dimensional finite element model of a specimen-specific intact cervical spine (C2-T1) was modified to simulate each surgical procedure at levels C3-C6. An additional goal of this work was to compare the instrumented computational model to our multi-specimen experimental findings to ensure similar trends in response to the surgical procedures. Model predictions indicate that mobility was retained following open and double door laminoplasty with a 5.4% and 20% increase in flexion, respectively, compared to the intact state. Laminectomy resulted in 57% increase in flexion as compared to the intact state, creating a concern for eventual kyphosis - a known risk/complication of multi-level laminectomy in the absence of fusion. Increased disc stresses were observed at the altered and adjacent segments post-laminectomy in flexion.