The results suggest that cyclooxygenase-2 inhibitors should be used with care in the early period after tendon injury.
Recently, several articles have been published dealing with the anabolic effects on bone by statins. Mundy and associates discovered that several statins were able to activate the promotor of bone morphogenetic protein (BMP) 2. Additionally, oral simvastatin and lovastatin increased the cancellous bone volume in rats, presumably an effect of the increase of BMP-2. Other studies have followed, with conflicting results; some have found a positive bone metabolic effect of statins and others have not. Studies published so far have focused on osteoporosis. In this study, femur fractures were produced in 81 mature male BALB/c mice and stabilized with marrow-nailing. Forty-one mice were given a diet prepared with simvastatin, so that each mouse received an approximate dose of 120 mg/kg of body weight per day. The remaining mice received the same diet with the exception of the simvastatin. Bilateral femurs were harvested at 8, 14, and 21 days postoperatively (po), the marrow-nail was extracted, and diameters were measured. Biomechanical tests were performed on 42 mice, by way of three-point bending. Histological specimens were prepared using standard techniques. For statistical analysis, ANOVA with Scheffé's post hoc test was used. At 8 days, the fracture callus was too soft for meaningful biomechanical testing. At 14 days, the callus of the simvastatin-treated mice had a 53% larger transverse area than controls (p ؍ 0.001), the force required to break the bone was 63% greater (p ؍ 0.001), and the energy uptake was increased by 150% (p ؍ 0.0008). Stiffness and modulus of elasticity were not significantly affected. At 21 days, the fractures were histologically healed and the mechanical differences had disappeared. The contralateral unbroken bone showed a slight increase in transverse area because of the simvastatin treatment, but there was no significant effect on the force required to break the bone or on energy uptake. These results point to a new possibility in the treatment of fractures. (J Bone Miner Res
The trauma involved with inserting implants into bone leads to an activation of the inflammatory response and an activation of osteoclasts. In addition, apoptosis of osteocytes in the surrounding area has been implicated in further activation of osteoclasts. If the balance between resorption and bone formation shortly after implantation favours resorption, an impairment of early fixation might ensue.Because bisphosphonates inhibit resorption, this study analyses whether they can improve early fixation. Stainless steel screws (M 1.7) were inserted into the tibiae of 76 male Sprague-Dawley rats. Daily subcutaneous injections of ibandronate (3 pg) or saline were given to 20 rats. The remaining rats received ibandronate or saline directly applied into the drill hole before the screw was inserted. Tibiae were harvested at 14 days. Mechanical tests were performed on 50 tibiae. Systemically treated tibiae were tested for pull-out strength alone. Locally treated tibiae were tested for either pull-out or torque resistance. The remaining 18 tibiae were prepared for histology.Systemic ibandronate increased the pull-out force at failure by 30% (p = 0.04). Local treatment increased the force at failure by 15% (p = 0.02) and stiffness by 28% (p = 0.01). In the removal torque measurements, local ibandronate increased the torquemoment at failure by 60% (p = 0.04), and the maximum friction moment by 51% (p = 0.04). Energy for turning the screw 1/4 revolution was increased by 68% (p = 0.02).These results demonstrate that early remodeling events plays an important role in screw fixation, and that systemic or local bisphosphonate treatment could be an effective pharmacological path to improve early implant fixation.
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