Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003090 (arthrodesis)
 8,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Periodontal ligament width is precisely maintained throughout the lifetime of adult mammals but the biological mechanisms that inhibit ingrowth of bone into this soft connective tissue are unknown. As bone morphogenic proteins strongly stimulate osteogenesis and can induce ectopic bone formation in vivo, we tested the hypothesis that topical application of this powerful osteogenic agent will overwhelm the osteogenic inhibitory mechanisms of periodontal ligament cells and induce ankylosis. Wounds through the alveolar bone and periodontal ligament were created in 45 male Wistar rats. Defects were filled with either a collagen implant or collagen plus bone morphogenic protein (BMP-7), or were left unfilled (controls). Three animals per time period were killed on days 2, 5, 10, 21 and 60 after surgery for each wound type. Cellular proliferation and clonal growth in periodontal tissues were assessed by 3H-thymidine labeling 1 h before death, followed by radioautography. Cellular differentiation of soft and mineralizing connective tissue cell populations was determined by immunohistochemical staining of alpha-smooth muscle actin, osteopontin and bone sialoprotein. In regenerating periodontium, BMP-7 induced abundant bone formation by 21 days (2.5-fold greater than controls or collagen implant only; P<0.001), but by day 60 the volume of the newly formed bone had returned to baseline levels and was similar for all groups. Independent of the type of treatment, periodontal ligament width was unchanged throughout the experimental period (P>0.05). Animals treated with BMP-7 implants showed greatly increased cellular proliferation in the periodontal ligament adjacent to the wound site and in the regenerating alveolar bone at days 5 and 10 after wounding compared to the other treatment groups (P<0.005). Animals in the BMP-7 group exhibited similar spatial and temporal staining patterns for alpha-smooth muscle actin, osteopontin and bone sialoprotein as controls. Collectively, these data show that BMP-7 promoted the proliferation of precursor cells in the periodontal ligament but did not induce osteogenic differentiation in this compartment. Consequently a powerful osteogenic stimulus like BMP-7 cannot significantly perturb the mechanisms that regulate periodontal ligament width and maintain periodontal homeostasis.
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PMID:Osteogenic inhibition by rat periodontal ligament cells: modulation of bone morphogenic protein-7 activity in vivo. 979 65

The use of autologous bone grafting is an essential component in spine fusion because it is the key factor in achieving long-term stable arthrodesis between spinal motion segments. However, harvesting autologous iliac crest bone graft can be associated with significant morbidity and its supply is limited. Although no current substitute for autologous graft is available, multiple studies have already established the success of bone morphogenetic proteins (BMPs) in augmenting spinal fusion in models using larger animals. The purpose of our study was to evaluate the ability of BMP to augment a posterolateral intertransverse process single-level fusion in a rat. To our knowledge, this model has not been used to evaluate the effects of recombinant BMPs. A posterolateral intertransverse process fusion was attempted in white male Sprague-Dawley rats. The following are the four study groups: insoluble collagen bone matrix (ICBM) alone, 3 microg BMP-7 + 25 mg ICBM, 10 microg BMP-7 + 25 mg ICBM, and a sham group with no implanted material. The animals were killed on postoperative day 21 and were evaluated for signs of clinical and/or radiographic fusion. All of the rats in the 10 microg BMP-7 + 25 mg ICBM group demonstrated clinical fusion and had solid bilateral fusion masses on radiographs. None of the rats in the sham group, ICBM group, or 3 microg BMP-7 + 25 mg ICBM group fused clinically; however, the rats in the 3 microg BMP-7 + 25 mg ICBM group did show evidence of new bone formation. Our study demonstrates that a rat posterolateral intertransverse process fusion model is inexpensive and efficient and produces consistent results. It also shows that BMP can augment fusion in a rat and that dosing plays a role in successful fusion. This is consistent with results that have been studied in larger animal models.
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PMID:The effects of BMP-7 in a rat posterolateral intertransverse process fusion model. 1257 90

Treatment of fracture non-union is a challenging situation in skeletal surgery. Since the discovery of bone morphogenetic proteins (BMPs) by Urist preclinical research as well as clinical trials has shown the efficacy of these molecules in bone healing enhancement. Recombinant bone morphogenetic protein became available in UK during August 2001. We evaluated the type of indications and the efficacy of BMP-7 in a variety of clinical conditions including persistent fracture non-unions, augmentation of periprosthetic fracture treatment and osteotomies, enhancement of fracture healing following acetalular reconstruction, distraction osteogenesis, free fibular graft and arthrodesis of joints. Out of 653 cases, the overall success rate was 82% (535 cases). No local or systemic adverse effects were encountered. The role of BMP's as a bone stimulating agent is safe, well established and could be considered as a power adjunct in the surgeon's armamentarium for the treatment of these challenging clinical conditions.
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PMID:Clinical applications of BMP-7: the UK perspective. 1618 50

The potentially revolutionary effect that bone morphogenic proteins (BMPs) could have on orthopaedic surgery has fueled an exhaustive research effort that continues today. Upwards of 1.5 million bone-grafting operations take place in the US annually, with the anterior and posterior iliac crest being the most common donor site for autologous bone graft. Harvesting autologous bone graft, however, is not benign. It is postulated that a synthetic bone graft containing BMPs would possess the characteristics of autologous bone that allow new bone formation: osteogenesis, osteoinduction, and osteoconduction, without the negative repercussions related to bone harvesting. As a result of the ensuing research following their discovery some 40 years ago by Marshall Urist, the basic science behind BMPs has been largely uncovered. New information on BMPs now comes from clinical trials regarding their utility and efficacy in surgical applications. To date, BMPs have been studied in skeletal bone surgery throughout the body, and have been found to be particularly useful in surgical applications such as spinal arthrodesis. Osteogenic protein-1 (OP-1), or recombinant human BMP-7, is one subtype of BMPs that has shown particular potential in clinical trials. Pre-clinical and clinical studies have, thus far, garnered OP-1 a Humanitarian Device Exemption approval for spinal applications in the US. As clinical trials with larger patient numbers and longer clinical follow-up are completed, the usefulness of OP-1 as a bone graft substitute will be better elucidated.
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PMID:Osteogenic protein-1 : a review of its utility in spinal applications. 1683 Oct 23

Bone grafting is not routinely required in primary arthrodesis in the absence of infection, avascular necrosis, bone defect or previous non-union; when any of the above factors is present, autograft is the gold-standard method. However, donor site morbidity and the quantitative and qualitative limitations of autograft have led to the development of alternatives. This study documents the use of the bone morphogenetic protein BMP-7 in a total of 19 joint fusions (ankle, subtalar, talonavicular, pubic and sacroiliac). Healing rates of 90% and satisfactory subjective functional outcome in 70% of cases were recorded over a minimum follow-up of 15 months. These data should provide a sound foundation for future clinical trials evaluating the application of BMP-7 in the fusion of joints.
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PMID:Use of bone morphogenetic proteins in arthrodesis: clinical results. 2008 94

The advent of recombinant DNA technology has substantially increased the intra-operative utilization of biologic augmentation in spine surgery over the past several years after the Food and Drug Administration approval of the bone morphogenetic protein (BMP) class of molecules for indications in the lumbar spine. Much less is known about the potential benefits and risks of the "off-label" use of BMP in the cervical spine. The history and relevant literature pertaining to the use of the "off-label" implantation of the BMP class of molecules in the anterior or posterior cervical spine are reviewed and discussed. Early prospective studies of BMP-2 implantation in anterior cervical spine constructs showed encouraging results. Later retrospective studies reported potentially "life threatening complications" resulting in a 2007 public health advisory by the FDA. Limited data regarding BMP-7 in anterior cervical surgery was available with one group reporting a 2.4% early (< 30 d) complication rate (brachialgia and dysphagia). BMP use in the decompressed posterior cervical spine may result in neurologic or wound compromise according to several retrospective reports, however, controlled use has been reported to increase fusion rates in select complex and pediatric patients. There were no cases of de novo neoplasia related to BMP implantation in the cervical spine. BMP-2 use in anterior cervical spine surgery has been associated with a high early complication rate. Definitive recommendations for BMP-7 use in anterior cervical spine surgery cannot be made with current clinical data. According to limited reports, select complex patients who are considered "high risk" for pseudoarthrosis undergoing posterior cervical or occipitocervical arthrodesis or children with congenital or traumatic conditions may be candidates for "off-label" use of BMP in the context of appropriate informed decision making. At the present time, there are no high-level clinical studies on the outcomes and complication rates of BMP implantation in the cervical spine.
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PMID:Bone morphogenetic protein in complex cervical spine surgery: A safe biologic adjunct? 2361 Jul 51