Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures a prospective, controlled, randomized study of four hundred and fifty patients

Date
2002
Authors
Govender S.
Csimma C.
Genant H.K.
Valentin-Opran A.
Amit Y.
Arbel R.
Aro H.
Atar D.
Bishay M.
Borner M.G.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Background: The treatment of open fractures of the tibial shaft is often complicated by delayed union and non-union. The objective of this study was to evaluate the safety and efficacy of the use of recombinant human bone morphogenetic protein-2 (rhBMP-2; dibotermin alfa) to accelerate healing of open tibial shaft fractures and to reduce the need for secondary intervention. Methods: In a prospective, randomized, controlled, single-blind study, 450 patients with an open tibial fracture were randomized to receive either the standard of care (intramedullary nail fixation and routine soft-tissue management [the control group]), the standard of care and an implant containing 0.75 mg/mL of rhBMP-2 (total dose of 6 mg), or the standard of care and an implant containing 1.50 mg/mL of rhBMP-2 (total dose of 12 mg). The rhBMP-2 implant (rhBMP-2 applied to an absorbable collagen sponge) was placed over the fracture at the time of definitive wound closure. Randomization was stratified by the severity of the open wound. The primary outcome measure was the proportion of patients requiring secondary intervention because of delayed union or nonunion within twelve months postoperatively. Results: Four hundred and twenty-one (94%) of the patients were available for the twelve-month follow-up. The 1.50-mg/mL rhBMP-2 group had a 44% reduction in the risk of failure (i.e., secondary intervention because of delayed union; relative risk = 0.56; 95% confidence interval = 0.40 to 0.78; pairwise p = 0.0005), significantly fewer invasive interventions (e.g., bone-grafting and nail exchange; p = 0.0264), and significantly faster fracture-healing (p = 0.0022) than did the control patients. Significantly more patients treated with 1.50 mg/mL of rhBMP-2 had healing of the fracture at the postoperative visits from ten weeks through twelve months (p = 0.0008). Compared with the control patients, those treated with 1.50 mg/mL of rhBMP-2 also had significantly fewer hardware failures (p = 0.0174), fewer infections (in association with Gustilo-Anderson type-III injuries; p = 0.0219), and faster wound-healing (83% compared with 65% had wound-healing at six weeks; p =0.0010). Conclusions: The rhBMP-2 implant was safe and, when 1.50 mg/mL was used, significantly superior to the standard of care in reducing the frequency of secondary interventions and the overall invasiveness of the procedures, accelerating fracture and wound-healing, and reducing the infection rate in patients with an open fracture of the tibia.
Description
Keywords
bone morphogenetic protein 2, recombinant bone morphogenetic protein 2, adolescent, adult, aged, ankle pain, article, bone radiography, bone transplantation, clinical trial, controlled clinical trial, controlled study, debridement, disease severity, drug efficacy, drug safety, edema, female, fracture fixation, fracture healing, fracture nonunion, human, implant, infection, intramedullary nailing, knee pain, leg pain, major clinical study, male, multicenter study, open fracture, outcomes research, priority journal, prosthesis failure, randomized controlled trial, single blind procedure, soft tissue injury, tibia, tibia fracture, treatment failure, treatment outcome, wound closure, wound healing, wound irrigation, Adolescent, Adult, Aged, Aged, 80 and over, Bone Morphogenetic Proteins, Female, Fractures, Open, Humans, Male, Middle Aged, Prospective Studies, Recombinant Proteins, Single-Blind Method, Tibial Fractures, Transforming Growth Factor beta
Citation
Journal of Bone and Joint Surgery - Series A
84
12