Per Aspenberg

..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...

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

..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...

..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...

..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...

..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...

..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...

..In the present study we investigate if zoledronate, the most potent of the commercially available bisphosphonates, can be used to reduce the amount or speed of bone graft remodeling...

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

..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...

..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...

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

..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...

..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...

..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...

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

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

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

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

..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...

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

..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...

..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...

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

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

..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...

..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...

..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...

..The results suggest the possibility of targeting osteoclast recruitment via the RANKL system in patients with impending prosthetic loosening...

..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...

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

..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...

..Our findings suggest that the first bony response after meniscectomy occurs in the subchondral bone plate rather than in the trabecular bone...

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

..Our results indicate that a short episodes of early loading may improve the outcome of tendon healing. This could be of interest to clinical practice...

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

..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...

..A combination with perforation of the bone-cartilage junction appears to lead to reasonably quick removal of the cartilage matrix...

..Rats treated with topical alendronate had soft tissue areas reduced by half. Topical bisphosphonate treatment before cementing a joint implant could possibly reduce the risk of later loosening...

..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...

..A possible explanation for these discrepancies could be different definitions of atypical fractures. We aimed to identify specific radiographic fracture characteristics associated with bisphosphonate use...

..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...

..Bisphosphonates are used to reduce resorption of necrotic bone. We tested a systemic pretreatment before harvesting the graft in order to protect the bone and cartilage against collapse and secondary arthrosis...

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

..These results point to a new possibility in the treatment of fractures...

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..Although both are encouraging and appear to show acceleration of normal fracture healing, they have methodological shortcomings that preclude definitive conclusions...

..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...

..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...

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..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...

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

..The difference in the number of outliers also points in this direction, and may be more relevant than mean migration values...

..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...

..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...

..Therefore, fusion occurred not only in relation to the screws, but also between the screws and in the periphery of the patella. Our findings show that bony fusion can occur in a healthy joint without joint resection or debridement...

..This proposes a more complex expression pattern for Sost in response to unloading. Therapeutics that target Sclerostin during altered loading conditions may result in local bone mass changes that are difficult to predict...

..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...

..No difference was found between the treatment groups. The Harris hip scores were higher in the THR group, and pain was more common in the internal fixation group. In lucid patients, THR gives a better clinical result at the same cost...

..Instability-induced bone resorption therefore seems to be reduced by bisphosphonates, but higher doses are needed to obtain this effect than to reduce bone resorption associated with normal remodeling of untraumatized bone...

..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...

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..Local graft treatment with a bisphosphonate before insertion seems to be risk-free, and may prevent mechanical graft failure due to resorption in patients...

..Randomized efficacy trial comparing two types of noninstrumented posterolateral fusion between L5 and S1 in patients with L5 spondylolysis and vertebral slip less than 50%, as evaluated by radiostereometric analysis...

..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...

..To investigate this, we used a rat bone chamber model to subject a necrotic osteochondral graft to a large mechanical load during remodeling...

..This combination might be useful in various conditions in orthopedic reconstruction...

..The effect appears to be stronger on the new forming bone than on pre-existing bone. Based on these preclinical studies, we suggest that intermittent PTH treatment may also benefit fracture healing and implant fixation in patients...

..We now report the results of local peroperative treatment with another bisphosphonate, ibandronate, with the same prosthesis...

..However, we can not exclude that this might be due to a carrier problem, since the OP-1 was added as a solution directly to the dry graft...

..Although the problems associated with the use of OP-1 in impaction grafting may be solved by adding a bisphosphonate, some of the benefits of OP-1 can be lost...

..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...

..008) in the ROU compared to the BCC+ and the BOT, respectively. Similar results were found using muCT. The ROU model performed most similar to the BCC (gold standard) and is considered to be a promising new tool in biomaterials research...

..In conclusion, DRU-joint laxity was associated with impaired hand function, but no loss of strength in forearm rotation after distal radial fractures in non-osteoporotic patients...

..The guidelines should be harmonized between European and American regulatory authorities to ensure comparability of results of studies and to foster global harmonization of regulatory requirements...

..Early failures in impaction grafting, using mixes with OP-1, might be explained by the lack of fibrous tissue ingrowth and not by increased resorption and remodeling...

..The study design should be randomized, parallel, double-blind, and placebo-controlled, and all fracture subjects should receive a standardized method of fracture fixation, defined as Standard of Care...

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..06). In conclusion, subchondral hematomas in distal radial fractures can lead to early onset of mild OA and worse outcome after 1 year...

..None of them can be completely refuted, but the demonstration of living osteocytes within the lesion and the number of necessary assumptions speak against the theory of a primary, bisphosphonate-induced necrosis...