No abstract

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

Cartilage-derived morphogenetic proteins (CDMPs), belonging to the bone morphogenetic protein (BMP) family, are known to be cartilage and bone inducers as well as to induce tendon and ligament-like tissue. In this study we investigated the influence of CDMP-I, -2 or -3 a t four different doses (0, 0.4, 2 and 10 pg) on tendon healing in a rat model, as well as differences in osteogenesis between the different CDMPs and doses.In 1 10 rats, a 3 mm segment of the Achilles tendon was removed via a 2 mm skin incision. CDMP-1, -2 or -3 was injected into the defect 6 h postoperative. The rats were killed 8 days after operation. The tendon regenerates were tested biornechanically. There was a significant dose-related increase in strength and stiffness with all three CDMPs, but no difference between the CDMPs was found.Another 50 rats were used to compare the highest dose of the CDMPs with controls and osteogenic protein 1 (OP-I), as regards cartilage or bone formation after 4 weeks. Cartilage occurred in all groups, including the controls. Some specimens in all groups contained bone, except the controls. N o difference between the CDMPs could be demonstrated. The CDMP-1, CDMP-3 and OP-1 groups contained significantly more calcium than controls. Only the CDMP-2 group and the controls contained significantly less calcium than the OP-l group.In conclusion, the three CDMPs appeared similar as regards improvement of tendon repair and osteogenicity in this setting.

No abstract

One single injection CDMP-2 can augment tendon repair. Mechanical stimulation is of great importance for tissue differentiation and tendon repair. The tendons in our model were mechanically loaded during healing and this might explain why CDMP-2 injections induced a strong tendon-like tissue instead of bone or cartilage in this model.

Similar results from a larger animal model would suggest a possible future use of cartilage-derived morphogenetic protein-2 in the treatment of human Achilles tendon ruptures.

No abstract

Cartilage derived morphogenetic proteins (CDMPs, also known as growth and ditkrentiation factors, GDFs) are a subgroup of the bone morphogenetic protein (BMP) gene family. As most BMPs, they are known to induce cartilage or bone formation when implanted subcutaneously or intramuscularly on an appropriate carrier. However, similar implantation experiments with CDMPs have also reported the formation of a tendon-like tissue, without any cartilage or bone. A solution to this apparent contradiction might be offered by the mechanical tissue differentiation theory, suggesting that tissue differentiation depends on the mechanical environment. This study analyzes the response to CDMP-9 implants at different sites and under different loading conditions in the rat. Collagen sponges carrying CDMP-2 were implanted subcutaneously, intramuscularly or inside a freshly created defect in the achilles tendon. Large amounts of bone were induced subcutaneously, smaller amounts intramuscularly, and in the tendons, only small amounts of bone or cartilage were seen in few animals. Thus, the amount of bone appeared inversely related to the degree of mechanical stimulus. To confirm this, CDMP was also injected into tendon defects that were either loaded or partially unloaded. All the unloaded tendons showed bone induction after one CDMP-2 injection, whereas only 4 of 10 loaded ones showed any cartilage or bone (p = 0.0005). Single injections of a similar dose of CDMP-2 have previously been shown to augment tendon repair by increasing the size of the tendon callus. This study suggests that the response to CDMP-3 is dependent on the mechanical situation at the site where it is applied.