Evaluation Of Recombinant Human Osteogenic Protein-1 (Rhop-1) In The Treatment Of Tibial Nonunions: A Randomized Clinical Trial Comparing Clinical And Radiographic Outcomes With Autograft

Abstract

Using a number of animal models, it has been established that a set of bone morphogenetic proteins (BMPs) is involved in bone repair. They encompassed such BMP as recombinant human osteogenic protein-1 (rhOP-1 or BMP- 7) which were produced and trialed in a Food and Drug Administration graduate of Investigational Device Exemption clinical trial, to determine the safety and efficacy of this BMP in the healing of tibial nonunions. Comparison of the clinical and radiographic outcome of the same osteogenic agent to those ones that were achieved through the use of fresh autogenous bones was also in the study.  There were 24- months of follow-up of the clinical trial which ran as multi-center, controlled prospective, randomized and somewhat blinded that involved 122 patients (124 tibial nonunions) between February 1992 and 8 August 1996. The treatment of the two patients was similar in the use of intramedullary rod, rhOP-1 in a type I carrier of collagen or fresh autograph carrier. The criteria were introduced at the level of the pain at the site of the fracture itself, on the possibility of supporting of the entire weight during movement, the necessity to re-interfere with the fracture and eliminate the nonunion, surgically treated during the study, and even on the rating of physicians in the readiness about the satisfactory nature of the clinical course. Secondly all the outpatients between visits were measured with antibodies to OP-1 and type-I collagen as well as adverse events noted. At the nine months follow up of the post surgery (the main final point of the research), eighty one percent of the OP-1 treated nonunions (n=63) and eighty five percent of the autogenous (n=61) were regarded as clinically successful (p=0,524). The percentage of healed fractures in the radiography was 75 percent amongst the OP-1 treated group and 84 percent amongst the patients that received autograft (p = 0.218). These clinical scales were similar to a randomized control group at the period of follow up which is 2 years and did not reveal the existence of a significant difference between the end-point scores in the two groups of treatment (p = 0.939). All the patients experienced adverse events, and of the 44 percent patients in the two groups, none of the patients was associated with bone grafts. More than 20 percent of the patients who had autograft treatment had chronic donor site pain that occurred after procedure. Application of rhOP-1 (BMP-7) on nonunion of the tibia through a collagen type I carrier was not only safe, but also effective treatment options. It produced similar clinical and radiographic results in comparison to bone autograft but there was no donor site morbidity.