Per Aspenberg

..0) microg/ml. In conclusion, tendon healing can be affected by doxycycline at clinically relevant serum concentrations. This observation might be of relevance to further studies exploring effects of MMP-inhibitors on tendon tissue...

..This is seen around loose screws, for example, but may also contribute to prosthetic loosening. Previous animal studies have shown that such zones can be induced by fluctuations in fluid pressure or flow, caused by implant instability...

..Also, locally delivered, that is, surface immobilized alendronate showed a better fixation than systemically delivered. Using sol-gel derived TiO(2) as a platform, it is possible to administer controllable amounts of a variety of BPs...

..Sclerostin expression is upregulated in unloaded bone and is downregulated by loading. We wanted to determine whether an anti-sclerostin antibody would stimulate metaphyseal healing in unloaded bone in a rat model...

..No pronounced increase was seen around the pamidronate coated screws. Together, the results demonstrate the possibility of obtaining a significant local therapeutic effect with minute amounts of surface immobilized zoledronate...

..In the late phase of healing, tendon-specific genes (scleraxis and tenomodulin) were upregulated with loading, and the healing tissue might to some extent represent a regenerate rather than a scar...

..Loading strongly decreased the expression of follistatin, which could lead to increased signaling. The BMP system appears involved in tendon maintenance and healing, and may respond to mechanical loading...

..This is the first description of early tendon healing in sheep Achilles tendons...

..Strontium is known to improve bone density, but it appears that this effect is weak in conjunction with metaphyseal bone repair and early implant fixation...

..Several experimental studies show that MMP inhibitors administered systemically alleviate postoperative weakening of intestinal anastomoses. We hypothesised that local delivery of MMP inhibitors would achieve a similar effect...

..INTERPRETATION: We provide proof of a novel treatment principle. MMP inhibitor-coated sutures improve suture-holding capacity during early repair of collagenous tissues...

..This suggests that patients might be allowed early short loading episodes following, e.g., an Achilles tendon rupture for a better outcome...

..Animal studies have shown that local application of platelet-rich plasma (PRP) stimulates tendon repair. Preliminary results from a retrospective case series have shown faster return to sports...

..We therefore investigated whether blocking of TNF-α with etanercept influences the healing process in established rat models of injury of tendons and metaphyseal bone...

..Thus, we hypothesized that in contrast to the case in osteoporosis treatment, PTH and bisphosphonates have an additive effect in situations involving bone regeneration...

..It also seems that Dkk1 is up-regulated both after metaphyseal trauma and after unloading, and that Dkk1 is involved in mechano-transduction...

..However, no effect on further development towards connective tissue formation was found...

..Thus, as measured by the amount of bone and its mechanical resistance, the sclerostin antibody increased bone formation during metaphyseal repair but also in untraumatized bone...

..In a rat Achilles tendon transection model, 1 postoperative injection resulted in increased strength after 4 weeks. Considering the short half-lives of factors released by platelets, this very late effect calls for an explanation...

..We conclude that the fixation of titanium implants in bone can be improved by fibrinogen matrix-bound bisphosphonates...

..Upon tissue injury, platelets are activated by thrombin, which has many biological properties in common with growth factors. We wanted to differentiate the effect of platelets from that of thrombin...

..This suggests that the mechanical microenvironment might be favourable for the clinical use of growth factors or platelets for this indication. New methods to quantitate human Achilles tendon repair have been developed...

..We tested the hypothesis that primary osteocyte death is not necessary for the development of jaw osteonecrosis...

..Animal studies have also suggested that these drugs can accelerate fracture healing and implant fixation. This brief overview focuses on currently available information on the effects of manipulations of Wnt signaling on bone healing...

..As radiographic cortical continuity appears late in the healing process, perhaps too late for clinical relevance, we studied the qualitative appearance of the callus 5 weeks after fracture...

..Studies show conflicting results regarding the possible excess risk of atypical fractures of the femoral shaft associated with bisphosphonate use...

..This could tamper prosthesis fixation. We investigated whether celecoxib, a selective Cox-2 inhibitor, increases prosthesis migration in total knee replacement (TKR)...

..No effect of doxycycline was observed. The results suggest that in growing animals, the tendons continue to grow regardless of mechanical loading history, whereas maintenance of damping properties requires mechanical stimulation...

..We tested if Roentgen stereophotogrammetric analysis (RSA) can be used to follow the restoration of mechanical properties during healing of ruptured Achilles tendons, and if early measurements can predict clinical results...

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..The shortened time to healing for teriparatide 20 microg compared with placebo still may suggest that fracture repair can be accelerated by teriparatide, but this result should be interpreted with caution and warrants further study...

..In this study, simvastatin was administered either subcutaneously or directly to the fracture area, with the goal of stimulating fracture repair at acceptable doses...

..This stimulation appears to affect mainly tissue quality, whereas stronger stimulation also increases callus size...

..We measured the plasma levels of MMPs and their tissue inhibitors (TIMPs) in patients with rotator cuff tears and related changes in the pattern of MMP and TIMP levels to the extent of the rotator cuff tear...

..This indicates that these MMP inhibitors, if proven effective for any novel indication, may be quickly brought into clinical practice...

..Cox2 inhibitors decrease prostaglandin production and therefore influence bone healing especially in unstable long bone models. It is unclear to what extent implant fixation in stable metaphyseal bone is impaired...

..In conclusion, the fact that there were hardly any regulated genes 24 h after loading suggests that optimal stimulation of healing requires a mechanical loading stimulus every day...

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..CLINICAL RELEVANCE: The results suggest that cyclooxygenase-2 inhibitors should be used with care in the early period after tendon injury...

..Recent case reports have identified an association between long-term bisphosphonate treatment and stress fractures of the femoral shaft. The risk of such fractures in bisphosphonate users has not been determined...

..012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants...

..A bisphosphonate coating improves screw fixation 2 weeks after implantation in cancellous bone. This study on rats examined further development of fixation over time for screws inserted in cancellous and cortical bone...

..e., greater maturation of the tendon callus. This was confirmed by blinded histological scoring. INTERPRETATION: Platelet concentrate may prove useful for the treatment of Achilles tendon ruptures...

..We present an exploratory evaluation of such a dichotomy using a mixture distribution algorithm...

..Only the CDMP-2 group and the controls contained significantly less calcium than the OP-1 group.In conclusion, the three CDMPs appeared similar as regards improvement of tendon repair and osteogenicity in this setting...

..Clinical Relevance: 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...

..This study suggests that the response to CDMP-2 is dependent on the mechanical situation at the site where it is applied...

..INTERPRETATION: Suture anchors or devices with a pegged undersurface are better for soft tissue fixation to bone than devices with a flat surface, such as screws with washers or staples...

..Because of the reduction in cross-sectional area without an effect on failure load, the use of Cox-inhibitors may be beneficial in clinical situations where thickening of a healing tendon is a problem--e.g., in the hand or shoulder...