No abstract

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.

Background: HMG-CoA reductase inhibitors, statins, are widely prescribed to lower cholesterol. High doses of orally administered simvastatin has previously been shown to improve fracture healing in a mouse femur fracture model. In this study, simvastatin was administered either subcutaneously or directly to the fracture area, with the goal of stimulating fracture repair at acceptable doses.

Wear particles commonly used for experiments may carry adherent endotoxin on their surfaces, which may be responsible for the observed effects. In this study, we attached titanium plates to the tibiae of 20 rats. After osseointegration, endotoxin-contaminated or uncontaminated high-density-polyethylene (HDPE) particles were applied. Contaminated specimens showed a dramatic resorption of bone after seven days but new bone filled the site again at 21 days. Uncontaminated specimens showed no resorption. In 18 rats we implanted intramuscularly discs of ultra-high-molecular-weight polyethylene (UHMWPE) with baseline or excess contamination of endotoxin. Excess endotoxin disappeared within 24 hours and the amount of endotoxin remained at baseline level (contamination from production). Uncontaminated titanium discs did not adsorb endotoxin in vivo. The endotoxin was measured by analytical chemistry. Locally-applied endotoxin stimulated bone resorption similarly to that in experiments with wear particles. Endotoxin on the surface of implants and particles appeared to be inactivated in situ. A clean implant surface did not adsorb endotoxin. Our results suggest that endotoxin adhering to orthopaedic implants is not a major cause for concern.

Amongst the wear debris particles implicated in the particle hypothesis for prosthetic loosening are polymethylmethacrylate (PMMA), and particularly PMMA with barium sulphate contrast agent. Another suggested cause for loosening is hydrostatic pressure. PMMA particles were combined with hydrostatic pressure in a study to investigate whether there could be a synergistic or additive effect between these two factors. Titanium plates were fastened onto tibiae of 59 rats. After osseointegration, PMMA particles with barium sulphate were administered to the bone-implant interface. Further, PMMA particles were introduced into a previously published model for hydrostatic pressure induced osteolysis. There was measurable resorption in response to the PMMA particles but no additive or synergistic effect from introducing particles to the pressure model, and the effect of pressure was far greater than that of particles. These results suggest that, whereas particles can be shown to elicit an osteolytic response, the much less studied osteolytic effects of pressure could be far more important.

This study examines the hypothesis that cartilage-derived morphogenic protein-2 (CDMP-2) can improve tendon healing after surgical repair. We have previously found improved tendon healing by applying CDMP-2 in models for conservative treatment with mechanically loaded Achilles tendon defects in rats and rabbits. In this study, the patellar tendon was unloaded by patello- tibial cerclage and cut transversely in 40 rabbits. Two hours post-operative, the rabbits received a dose of 20 microg of CDMP-2 or vehicle injected into the hematoma. Specimens were harvested after 14 and 28 days and evaluated by biomechanical testing, radiography and histology. At 14 days, CDMP-2 caused a 65% increase in force at failure, a 50% increase in ultimate stress and a 57% increase in stiffness, as compared with controls. There was no effect on callus size. At 28 days, no differences between the treatment groups could be demonstrated. No bone or cartilage was found in any tendon or regenerated tissue at any time point. Thus, early tendon repair can be stimulated by CDMP-2 in an unloaded model. These results suggest that CDMP-2 might be of interest for clinical use as a complement to surgical treatment of tendon ruptures.