Preclinical and clinical evaluation of osteogenic protein-1 (BMP-7) in bony sites.

Osteogenic proteins (OPs), also referred to as bone morphogenetic proteins (BMPs), are a family of bone-matrix polypeptides isolated from a variety of mammalian species. Implantation of osteogenic proteins induces a sequence of cellular events that leads to the formation of new bone. In preclinical studies, the implantation of recombinantly produced human osteogenic protein-1 (OP-1, also referred to as BMP-7) into surgically created, critical-size diaphyseal segmental defects resulted in the regeneration of new bone that was fully functional biologically and biomechanically. Injection of an OP-1 solution into a fresh fracture model accelerated the bone repair process compared with control fracture healing. This was the result of greater and earlier new bone formation. Further study has demonstrated that OP-1 can be used as a bone graft substitute to promote spinal fusion, aid in the incorporation of metal implants, and improve the performance of autograft and allograft bone. Clinical study of OP-1 implanted in conjunction with a bovine bone-derived type 1 collagen carrier for the treatment of tibial nonunion fractures has shown healing characteristics similar to that obtained with autogenous iliac crest bone graft. Advantages of OP-1 included no donor site complications, less blood loss, and a shorter operative time.     

Extrakorporale Stoßwellentherapie

Extracorporeal shock wave therapy (ESWT) has been established as a unique treatment option for soft tissue and bone pathologies. Typical indications include plantar fasciitis, tendinosis calcarea, and tennis elbow, as well as bone pathologies such as nonunions. Regarding the efficacy of ESWT in acute fractures, the literature is herein reviewed. Significant and effective acceleration of fracture and osteotomy healing as well as improvement of biomechanical bone properties by ESWT has been demonstrated in most of the relevant published animal studies. Thus, variable and noncomparable treatment parameters have been applied, and an optimized treatment protocol still must be established. Clinical data are limited to one prospective randomized trial, which demonstrated significant stimulation of healing of long bone fractures after ESWT was applied to the fracture site immediately after open reduction and internal fixation. Additional studies are required to corroborate the effectiveness of ESWT in acute fractures. Although the effectiveness of ESWT has been postulated in a myriad of trials investigating nonunions, published data are not sufficient to allow the recommendation of shock wave treatment for acute fractures also.     

Recombinant bone morphogenetic protein-7 as an intracorporal bone growth stimulator in unstable thoracolumbar burst fractures in humans: preliminary results

The study presented here is a pilot study in five patients with unstable thoracolumbar spine fractures treated with transpedicular OP-1 transplantation, short segment instrumentation and posterolateral fusion. Recombinant bone morphogenetic protein-7 in combination with a collagen carrier, also referred to as OP-1, has demonstrated ability to induce healing in long-bone segmental defects in dogs, rabbits and monkeys and to induce successful posterolateral spinal fusion in dogs without need for autogenous bone graft. Furthermore OP-1 has been demonstrated to be effective as a bone graft substitute when performing the PLIF maneuver in a sheep model. Five patients with single-level unstable burst fracture and no neurological impairment were treated with intracorporal OP-1 transplantation, posterior fixation (USS) and posterolateral fusion. One patient with osteomalacia and an L2 burst fracture had an additional intracorporal transplantation performed proximal to the instrumented segment, i.e. OP-1 into T 12 and autogenous bone into T 11. Follow-up time was 12–18 months. On serial radiographs, Cobb and kyphotic angles, as well as anterior, middle and posterior column heights, were measured. Serial CT scans were performed to determine the bone mineral density at fracture level. In one case, radiographic and CT evaluation after 3 and 6 months showed severe resorption at the site of transplantation, but after 12 months, new bone had started to fill in at the area of resorption. In all cases there was loss of correction with regard to anterior and middle column height and sagittal balance at the latest follow-up. These preliminary results regarding OP-1 as a bone graft substitute and stimulator of new bone formation have been disappointing, as the OP-1 device in this study was not capable of inducing an early sufficient structural bone support. There are indications to suggest that OP-1 application to a fracture site in humans might result in detrimental enhanced bone resorption as a primary event. Received: 13 February 1999 Revised: 4 August 1999 Accepted: 18 August 1999     

Cement spacers with antibiotics for the treatment of posttraumatic infected nonunions and bone defects of the upper extremity

Treatment of patients with posttraumatic infected nonunions or highly contaminated open fractures with segmental bone loss of the long bones of the upper extremity is demanding. The use of a 2-stage reconstruction technique, being the first stage characterized by thorough debridement, copious lavage, soft tissue coverage, and placement of a cement spacer with antibiotics at the infected site, and the second stage by cement spacer removal, internal fixation, and placement of bone graft with local antibiotics, is presented. We carried out this technique in 20 cases, in 12 cases the cement was molded to fit the defect and placed as a solid interposition mass, in 3 cases it was placed lateral to the affected bone, and in the remaining 5 cases a Rush nail covered with a cement mantle was used. Follow-up averaged 18 months. All nonunions and fractures healed after an average of 5 months. Disabilities of the arm, shoulder, and hand (DASH) score at last follow-up in nonunions averaged 14 points and 21 points in bone losses. Although generally 2 surgical procedures are needed, 1 to cure or prevent infection and another to achieve bony union, this approach for complex open fractures with segmental bone loss and for infected nonunions of the long bones of the upper extremity represents a valid treatment alternative.     

The effect of osteogenic protein-1 in instrumented and noninstrumented posterolateral fusion in rabbits.

BACKGROUND CONTEXT: The use of rigid instrumentation combined with bone graft makes intuitive sense given the requirements for vascular ingrowth, bone formation and a stable environment for the cellular events of healing to develop. However, with the advances of potent osteoinductive growth factors, the role of internal fixation may come into question. Whether bone morphogenic proteins (BMPs) would benefit from a more "stable" spinal segment for bone production and modeling remains unknown. In addition, it is unknown whether BMP and rigid fixation may have an additive effect on fusion healing. PURPOSE: This study is proposed to test the hypothesis that rigid fixation in the lumbar spine would be advantageous to achieve fusion for autogenous bone grafting, but fusion would occur regardless of fixation with the use of osteogenic protein (OP)-1. STUDY DESIGN/SETTING: A histologic and radiographic analysis of BMP in a rabbit lumbar fusion model. METHODS: Thirty-two rabbits were randomized into four groups: 1) control animals: in situ posterolateral L5-L6 arthrodesis using autogenous iliac crest bone graft; 2) fixation group: posterolateral arthrodesis L5-L6 with autogenous bone graft and interspinous fixation; 3) OP-1 group: in situ posterolateral L5-L6 arthrodesis using OP-1 and 4) combined OP-1 and fixation group. Radiographic fusion analysis was performed with computed tomography scans at 3 and 12 weeks after surgery. Decalcified histology was performed to assess tissue morphology and cellularity. RESULTS: Minimal evidence of fusion was noted at 3 weeks with autograft or OP-1. By 12 weeks, all OP-1-treated animals had solid fusion, whereas no fusion was noted in autograft animals. The addition of fixation slightly increased radiographic fusion at 3 weeks in autograft and OP-1 groups but did not affect OP-1 animals at 12 weeks where all were fused. Decalcified histologic results confirmed the proliferative bone formation noted with OP-1 and the variable cellular response with autograft. CONCLUSIONS: The results of the present study suggest that the osteoinductive effect of OP-1 may be only minimally enhanced early in the bone healing process but does not appear to be affected in the long term by spinal fixation in the rabbit intertransverse fusion model. Fixation appeared to enhance early fusion in the autograft group.     

The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study.

BACKGROUND CONTEXT: Although autogenous bone is still considered to be the gold standard graft material for promoting spinal fusion, other bone graft substitutes have been developed in an attempt to improve arthrodesis rates and avoid the complications associated with the procurement of autograft. The bone morphogenetic proteins (BMPs) represent a family of osteoinductive growth factors that are known to stimulate the osteoblastic differentiation of stem cells. Osteogenic protein-1 (OP-1) Putty is a commercially available BMP preparation that is already approved for use in humans. Previous clinical studies involving patients with degenerative spondylolisthesis have reported that the efficacy and safety of OP-1 Putty is comparable to that of autograft at both 1- and 2-year follow-up. PURPOSE: The purpose of this study was to evaluate the intermediate-term efficacy and safety of OP-1 Putty as an alternative to autogenous bone by comparing the 4-year radiographic, clinical, and safety data of these same patients who underwent decompression and uninstrumented fusion with either OP-1 Putty or iliac crest autograft. STUDY DESIGN/SETTING: A prospective, randomized, controlled, multicenter clinical pilot study. PATIENT SAMPLE: Thirty-six patients undergoing decompressive laminectomy and single-level uninstrumented fusion for degenerative spondylolisthesis and symptomatic spinal stenosis were randomized in a 2:1 fashion to receive either OP-1 Putty (24 patients) or autogenous iliac crest bone graft (12 patients). OUTCOME MEASURES: Patient-reported outcome measures consisting of Oswestry Disability Index and Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) scores were used to evaluate clinical efficacy. Perioperative data including operative time, estimated blood loss, and duration of hospital stay were also recorded for each surgery. Postoperatively, a neurological examination and an assessment of donor-site pain (if applicable) were performed at every follow-up visit. Radiographic fusion success was defined as the presence of continuous bridging bone formation between the transverse processes at the level of the spondylolisthesis with minimal motion evident on dynamic lateral x-ray films. The primary efficacy endpoint was the overall success rate, a composite measure derived from both radiographic and clinical parameters. The safety of OP-1 Putty was confirmed by comparing the nature and frequency of all adverse events and complications that were prospectively observed in either of the groups. METHODS: Thirty-six patients with degenerative spondylolisthesis and symptoms of neurogenic claudication underwent decompressive laminectomy and single-level uninstrumented fusion with either OP-1 Putty or autograft. All patients were evaluated at 6 weeks and 3, 6, 9, 12, and 24 months, after which time they were instructed to return on a yearly basis. Multiple neuroradiologists blinded to the assigned treatment reviewed static and dynamic X-ray films with digital calipers to assess fusion status according to the presence of continuous bridging bone across the transverse processes as well as the amount of residual motion evident at the level of interest. Oswestry Disability Index surveys and SF-36 questionnaires were used to assess clinical outcomes. RESULTS: At the 48-month time point, complete radiographic and clinical data were available for 22 of 36 patients (16 OP-1 Putty and 6 autograft) and 25 of 36 patients (18 OP-1 Putty and 7 autograft), respectively. Radiographic evidence of a solid arthrodesis was present in 11 of 16 OP-1 Putty patients (68.8%) and 3 of 6 autograft patients (50%). Clinically successful outcomes defined as at least a 20% improvement in preoperative Oswestry scores were experienced by 14 of 19 OP-1 Putty patients (73.7%) and 4 of 7 autograft patients (57.1%); these clinical findings were corroborated by similar increases in SF-36 scores. The respective overall success rates of the OP-1 Putty and autograft group were 62.5% and 33.3%. In this study, there were no incidents of local or systemic toxicity, ectopic bone production, or other adverse events directly related to the use of OP-1 Putty. CONCLUSION: Despite the challenges associated with obtaining a solid uninstrumented fusion in patients with degenerative spondylolisthesis, the rates of radiographic fusion, clinical improvement, and overall success associated with the use of OP-1 Putty were at least comparable to that of the autograft controls for at least 48 months after surgery. These results appear to validate the short-term results previously reported for OP-1 Putty and suggest that this material may potentially represent a viable bone graft substitute for certain fusion applications.     

Anterior lumbar interbody fusion with osteoinductive growth factors

Anterior intervertebral fusion increasingly is used as a treatment for discogenic or intersegmental pathologic diseases of the lumbar spine. This is in part attributable to the evolution and refinement of laparoscopic and minimally invasive surgical techniques that now can be used to access the anterior spinal column. It also is attributable to the availability of newer generation intervertebral fixation devices such as the threaded titanium cages or threaded allograft bone dowels, both of which are technically simpler to implant. Recently, limited clinical studies of intervertebral lumbar fusion have examined the use of these devices combined with osteoinductive growth factors as substitutes for autogenous bone graft. Early clinical results of lumbar fusion using threaded intervertebral implants filled with recombinant human bone morphogenetic protein-2 have been favorable. Higher fusion rates, shorter operative times, and shorter hospital stays have been reported in the initial series. Clinical trials involving larger cohorts with various spinal applications for osteoinductive molecules currently are in progress.     

Clinical evaluation of recombinant human bone morphogenetic protein-2

Recombinant human bone morphogenetic protein-2 is an osteoinductive protein that plays a pivotal role in bone growth and regeneration. Several hundred studies were conducted in the past 7 years in numerous animal models to establish unequivocally the efficacy, safety, mechanism of action, pharmacokinetics, and surgical handling properties of recombinant human bone morphogenetic protein-2, building a solid foundation for clinical development programs. Pilot clinical trials have shown the feasibility and safety of recombinant human bone morphogenetic protein-2 treatment, and defined the effective dose for its use in open long bone fractures and for augmentation or preservation of the alveolar bone in the dental ridge. Prospective observational clinical studies helped define clinical efficacy end points, identify significant variables, and estimate appropriate population sample size for pivotal clinical trials. Pivotal clinical trials of recombinant human bone morphogenetic protein-2 are underway in patients with open tibial shaft fractures and in patients with a deficiency of the alveolar ridge.     

Bone morphogenetic proteins in clinical applications

The role of bone morphogenetic proteins (BMPs) in bone healing has been shown in numerous animal models. To date, at least 20 BMPs have been identified, some of which have been shown in vitro to stimulate the process of stem cell differentiation into osteoblasts in human and animal models. Having realized the osteoinductive properties of BMPs and having identified their genetic sequences, recombinant gene technology has been used to produce BMPs for clinical application - most commonly, as alternatives or adjuncts in the treatment of cases in which fracture healing is compromised. BMP-2 and BMP-7 are approved for clinical use in open fractures of long bones, non-unions and spinal fusion. However, despite significant evidence of their potential benefit to bone repair and regeneration in animal and preclinical studies, there is, to date, a dearth of convincing clinical trials. The purpose of this paper is to give a brief overview of BMPs and to critically review the clinical data currently available on the use of BMP-2 and BMP-7 in fracture healing.     

Recent advances toward the clinical application of bone morphogenetic proteins in bone and cartilage repair

Inefficient healing of bony and cartilaginous defects is a common situation encountered by orthopedic surgeons. Enhancing the regenerative potential of bone and articular cartilage has the potential for profound applications in treatment of nonunions, large segmental bone and cartilage defects, and arthritis. The bone morphogenetic proteins (BMPs) encode a highly conserved class of signaling factors that possess the ability to induce ectopic cartilage and bone formation in vivo. Bone morphogenetic protein family members are expressed during limb development, endochondral ossification, and early fracture and cartilage repair. Loss-of-function and gain-of-function studies have demonstrated the necessity and sufficiency of these genes, respectively, in regulating both cartilage and bone development. Several recent animal studies have demonstrated the potential of BMPs to enhance spinal fusion, repair critical-size defects, accelerate union, and heal articular cartilage lesions. A limited number of clinical trials using BMPs in human beings have been reported, and these agents are currently available for clinical use within and outside the United States. Current challenges to be met are the development of efficient delivery systems to present BMP proteins or genes to target sites and to enhance their duration and function at these locations.     

Effect of recombinant human osteogenic protein-1 on the healing of a freshly closed diaphyseal fracture

Osteogenic protein-1 (OP-1), or bone morphogenetic protein-7, is an osteoinductive morphogen that is involved in embryonic skeletogenesis and in bone repair. In bone defect models without spontaneous healing, local administration of recombinant human OP-1 (rhOP-1) induces complete healing. To investigate the ability of rhOP-1 to accelerate normal physiologic fracture healing, an experimental study was performed. In 40 adult female goats a closed tibial fracture was made, stabilized with an external fixator, and treated as follows: (1) no injection; (2) injection of 1 mg rhOP-1 dissolved in aqueous buffer; (3) injection of collagen matrix; and (4) injection of 1 mg rhOP-1 bound to collagen matrix. The test substances were injected in the fracture gap under fluoroscopic control. At 2 and 4 weeks, fracture healing was evaluated with radiographs, three-dimensional computed tomography (CT), dual-energy X-ray absorptiometry, biomechanical tests, and histology. At 2 weeks, callus diameter, callus volume, and bone mineral content at the fracture site were significantly increased in both rhOP-1 groups compared with the no-injection group. As signs of accelerated callus maturation, bending and torsional stiffness were higher and bony bridging of the fracture gap was observed more often in the group with rhOP-1 dissolved in aqueous buffer than in uninjected fractures. Treatment with rhOP-1 plus collagen matrix did not result in improved biomechanical properties or bony bridging of the fracture gap at 2 weeks. At 4 weeks there were no differences between groups, except for a larger callus volume in the rhOP-1 plus collagen matrix group compared with the control groups. All fractures showed an advanced stage of healing at 4 weeks. In conclusion, the healing of a closed fracture in a goat model can be accelerated by a single local administration of rhOP-1. The use of a carrier material does not seem to be crucial in this application of rhOP-1.     

Role of locking plates in treatment of difficult ununited fractures: a clinical study

Objective:To present our experience in treatment of difficult ununited long bone fractures with locking plate.Methods:Retrospective evaluation of locking plate fixation in 10 difficult nonunions of lon...     

A pilot safety and efficacy study of OP-1 putty (rhBMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions

The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to an increasing interest in the potential for their use in fusion surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety of one such BMP—osteogenic protein 1, in the form of OP-1 putty—combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements followed by intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and radiographically using static and dynamic radiographs to assess their fusion status. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. In addition to bridging bone, less than or equal to 5° of angular motion and less than or equal to 2 mm of translation were required to classify the patients as successfully fused, as per the definition of successful fusion provided by the FDA for use in clinical trials involving investigational devices to attain spinal fusion. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed 9 of the 12 patients (75%) obtained at least a 20% improvement in their preoperative Oswestry score, while 6 of 11 patients (55%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in 10 of the 11 patients (91%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was approximately 45%. The lack of adverse events related to the OP-1 putty implant in this study is in agreement with other studies supporting the safety of bone morphogenetic proteins in spinal surgery.     

A 2-year follow-up pilot study evaluating the safety and efficacy of op-1 putty (rhbmp-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions

The ability of bone morphogenetic proteins (BMPs) to induce bone formation has led to a multitude of investigations into their use as bone graft substitutes in spinal surgery. The purpose of this multi-center clinical pilot study was to evaluate the safety and efficacy of BMP-7 (osteogenic protein 1, OP-1), in the form of a putty, combined with autograft for intertransverse process fusion of the lumbar spine in patients with symptomatic spinal stenosis and degenerative spondylolisthesis following spinal decompression. Twelve patients with spinal stenosis and degenerative lumbar spondylolisthesis underwent a laminectomy and partial or complete medial facetectomy as required for decompression of the neural elements, followed by an intertransverse process fusion by placing iliac crest autograft and OP-1 putty between the decorticated transverse processes. No instrumentation was used. Patients were followed clinically using the Oswestry scale and SF-36 outcome forms, and radiographically using static and dynamic radiographs to assess their fusion status over a 2-year period. Independent and blinded radiologists assessed the films for the presence of bridging bone between the transverse processes and measured translation and angulation on dynamic films using digital calipers. Radiographic outcome was compared to a historical control (autograft alone fusion without instrumentation for the treatment of degenerative spondylolisthesis). All adverse events were recorded prospectively. The results showed eight of the nine evaluable patients (89%) obtained at least a 20% improvement in their preoperative Oswestry score, while five of ten patients (50%) with radiographic follow-up achieved a solid fusion by the criteria used in this study. Bridging bone on the anteroposterior film was observed in seven of the ten patients (70%). No systemic toxicity, ectopic bone formation, recurrent stenosis or other adverse events related to the OP-1 putty implant were observed. A successful fusion was observed in slightly over half the patients in this study, using stringent criteria without adjunctive spinal instrumentation. This study did not demonstrate the statistical superiority of OP-1 combined with autograft over an autograft alone historical control, in which the fusion rate was 45%. There were no adverse events related to the OP-1 putty implant in this study, which supports findings in other studies suggesting the safety of bone morphogenetic proteins in spinal surgery.     

OP-1/BMP-7 in cartilage repair

Three years ago we published a book chapter on the role of bone morphogenetic proteins (BMPs) in cartilage repair. Since that time our understanding of the function of osteogenic protein-1 (OP-1) or BMP-7 in cartilage homeostasis and repair has substantially improved and therefore we decided to devote a current review solely to this BMP. Here we summarise the information accumulated on OP-1 from in vitro and ex vivo studies with cartilage cells and tissues as well as from in vivo studies of cartilage repair in various animal models. The primary focus is on articular chondrocytes and cartilage, but data will also be presented on nonarticular cartilage, particularly from the intervertebral disc. The data show that OP-1 is a unique growth factor which, unlike other members of the same BMP family, exhibits in addition to its strong pro-anabolic activity very prominent anti-catabolic properties. Animal studies have demonstrated that OP-1 has the ability to repair cartilage in vivo in various models of articular cartilage degradation, including focal osteochondral and chondral defects and osteoarthritis, as well as models of degeneration in intervertebral disc cartilage. Together our findings indicate a significant promise for OP-1 as therapeutic in cartilage repair.     

Development of nonunions in the rat fibula after removal of periosteal neural mechanoreceptors

Periosteal proprioceptive nerve receptors may act as mechanoreceptors of long bones during adaptive remodeling after fracture. They may also contribute to the mechanisms of coordinated functional activity of fractured limbs and thus inhibit harmful overloading of fracture callus. The area of proprioceptive nerve receptors around the distal part of the rat fibula was stripped surgically, and a standard fracture of the fibular shaft was produced. Animals failed to unite their fractures and developed mainly atrophic nonunions. Atrophy of ununited fragments was due to osteoclastic bone resorption. Atrophy of the bone fragments was aggravated if the legs were also subjected to sciatic denervation. Sciatic denervation alone, without removal of receptors, did not interfere with the union of fractures. The results indicate that the area of proprioceptive receptors in the rat tibiofibular bone is critical for the healing of fibular fractures. Because the effect on bone healing of receptor removal was not inhibited by sciatic denervation, the effect was not transmitted through spinal pathways of the sciatic nerve. The development of nonunions could not be explained by the surgical trauma alone. Aggravation of fibular atrophy by sectioning of the sciatic nerve suggests that some neural elements are associated with the phenomenon, either directly or indirectly through neuromuscular function.     

Osteogenic protein-1 (bone morphogenic protein-7) combined with various adjuncts in the treatment of humeral diaphyseal nonunions

A prospective study was conducted to determine the efficacy of using recombinant BMP-7 (rhOP-1) as an adjuvant in the treatment of diaphyseal humeral nonunions. Twenty-three consecutive patients with atrophic humeral diaphyseal nonunions were treated at seven separate institutions. All nonunions were fixed with either a compression plate or an intramedullary nail in conjunction with various bone grafting techniques. Recombinant OP-1 was delivered to the fracture site in a Type I collagen carrier at the time of fixation. All fractures went on to eventual union. There were no serious complications and no adverse reactions to the rhOP-I implant. Our study suggests that rhOP-1 may be a safe and effective adjuvant for the treatment of humeral diaphyseal nonunions.     

The role of human bone morphogenetic proteins in spinal fusion

The attainment of a stable arthrodesis is critical to the successful management of some types of spinal disorders. Autologous iliac-crest bone graft has been the most commonly utilized substance associated with predictable healing in spinal fusion applications. Although alternative graft substances exist, these have not been shown to be as uniformly effective in achieving spinal fusion. Because of the morbidity associated with bone autograft harvest, there is increasing interest in alternative graft substances and especially in the osteoinductive abilities of bone morphogenetic proteins (BMPs). Several animal models have demonstrated that BMP-containing allograft or synthetic carrier medium is as effective as or superior to autograft bone in promoting spinal fusion. Furthermore, the limited number of human trials utilizing BMPs to treat nonunions in the appendicular skeleton indicate that the results found in animal models will be reproducible in the clinical setting.     

The role of electromagnetic stimulation in the management of established non-union of long bone fractures: what is the evidence?

BACKGROUND: Non-union following long bone fractures is a cause of significant morbidity to the patient. The management of this condition has proved difficult for the orthopaedic surgeon. Much research has been carried out on the use of electromagnetic stimulation in the healing of non-union. OBJECTIVES: The objective of this review is to determine what evidence exists to support electromagnetic stimulation in the management of established non-union of long bone fractures. METHODS: A systematic search was carried out of the peer-reviewed English language literature to identify all studies investigating electromagnetic stimulation in the treatment of non-union of fractures of long bones. RESULTS: Three of the articles reviewed were randomised clinical trials. Forty-six other studies were also included in the review. CONCLUSIONS: There is a consensus that electromagnetic stimulation is an effective adjunct to conventional therapy when used in the management of non-union of long bone fractures.