In osteoporosis treatment, current interventions, including pharmaceutical treatments and exercise protocols, suffer from challenges of guaranteed efficacy for patients and poor patient compliance. Moreover, bone loss continues to be a complicating factor for conditions such as spinal cord injury, prescribed bed-rest, and space flight. A low-cost treatment modality could improve patient compliance. Electrical stimulation has been shown to improve bone mass in animal models of disuse, but there have been no studies of the effects of electrical stimulation on bone in the context of bone loss under hormone deficiency such as in post-menopausal osteoporosis. The purpose of this study was to explore the effects of electrical stimulation on changes in bone mass in the ovariectomized rat model of post-menopausal osteoporosis. All animal protocols were approved by the institutional Animal Research Ethics Board. We developed a custom electrical stimulation device capable of delivering a constant current, 15 Hz sinusoidal signal. We used 30 female Sprague Dawley rats (12–13 weeks old). Half (n=15) were ovariectomized (OVX), and half (n=15) underwent sham OVX surgery (SHAM). Three of each OVX and SHAM animals were sacrificed at baseline. The remaining 24 rats were separated into four equal groups (n=6 per group): OVX electrical stimulation (OVX-stim), OVX no stimulation (OVX-no stim), SHAM electrical stimulation (SHAM-stim), and SHAM no stimulation (SHAM-no stim). While anaesthetized, stimulation groups received transdermal electrical stimulation to the right knee through bilateral skin-mounted electrodes (10 × 10 mm) with electrode gel. The left knee served as a non-stimulated contralateral control. The no-stimulation groups had electrodes placed on the right knee, but not connected. Rats underwent the stim/no-stim procedure for one hour per day for six weeks. Rats were sacrificed (CO2) after six weeks. Femurs and tibias were scanned by microCT focussed on the proximal tibia and distal femur. MicroCT data were analyzed for trabecular bone measures of bone volume fraction (BV/TV), thickness (Tb.Th), and anisotropy, and cortical bone cross-sectional area and second moment of area. Femurs and tibias from OVX rats had significantly less trabecular bone than SHAM (femur BV/TV = −74.1%, tibia BV/TV = −77.6%). In the distal femur of OVX-stim rats, BV/TV was significantly greater in the stimulated right (11.4%, p < 0 .05) than the non-stimulated contralateral (left). BV/TV in the OVX-stim right femur also tended to be greater than that in the OVX-no-stim right femur, but the difference was not significant (17.7%, p=0.22). There were no differences between stim and no-stim groups for tibial trabecular measures, or cortical bone measures in either the femur or the tibia. This study presents novel findings that electrical stimulation can partially mitigate bone loss in the OVX rat femur, a model of human post-menopausal bone loss. Further work is needed to explore why there was a differential response of the tibial and femoral bone, and to better understand how bone cells respond to electrical stimulation. The long-term goal of this work is to determine if electrical stimulation could be used as a complementary modality for preventing post-menopausal bone loss.
Osteochondral allografts (frozen uncontrolled, or cryo-protected with dimethyl sulfoxide) were transplanted into medial femoral condyles of eighteen sheep. Cores from the ipsilateral graft site served as autografts for the contralateral limb. Analysis of graft and host cancellous bone microarchitecture by μCT at three months post transplant demonstrated no significant differences among the treatment groups. Dramatic bone resorption at the graft–host interface, however, occurred in up to 1/3 of condyles from all treatment groups, including fresh autografts suggesting that factors other than donor source or tissue storage played an important role in the bone incorporation of osteochondral grafts. The purpose of this study was to study the effect of different freezing protocols on periarticular cancellous bone architecture after osteochondral allograft transplantation. There were no significant differences in graft or host cancellous bone architecture among the groups (autografts, frozen allografts, cryopreserved allografts). Dramatic resorption of graft bone in condyles from all treatment groups suggested that factors other than donor source or tissue storage played important roles during incorporation of osteochondral grafts. Graft positioning, graft orientation, and recipient bed necrosis may play significant roles during incorporation of osteochondral graft bone. Osteochondral allografts (10 mm diameter) were transplanted into medial femoral condyles of eighteen skeletally mature Suffolk ewes. Allografts were frozen (–80°C) without cryoprotectant (FROZ) or treated with dimethyl sulfoxide (cryoprotectant) and frozen (–80°C at 1°C · min−1) (CRYO). Osteochondral cores removed from ipsilateral graft sites served as fresh autografts (AUTO) for the contralateral medial femoral condyles. Condyles were harvested at three months and scanned (micro computed tomography –μCT). Three dimensional μCT data of graft and host cancellous bone regions were analyzed for bone volume fraction, trabecular thickness, bone surface–volume ratio, and trabecular anisotropy. No morphological differences were found among treatment groups. Excessive bone resorption of graft and interface precluded analysis of some samples from each group (ALLO — 2/9, CRYO — 3/9, AUTO — 6/18). Dramatic bone loss did not correlate with poor graft orientation, placement, infection, or recipient–bed necrosis, but a combination of these factors may contribute to excessive cancellous bone resorption in osteochondral grafts.
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