Purpose: Identification of novel therapeutics to accelerate acute fracture healing remains critical. A prostaglandin EP-2 receptor agonist (CP-533,536) has demonstrated acceleration of fracture healing in preclinical models.

Method: In a phase II randomized, blinded, placebo-controlled trial the efficacy of a single local injection of three doses of CP-533,536 (0.5mg, 1.5mg and 15mg) was compared to both placebo and a standard of care arm in patients with closed tibial shaft fractures treated with reamed inter-locked intramedullary nails. Patients were followed at two week intervals to six months with a final evaluation at one year. Fracture healing was independently adjudicated by a radiologist panel and an orthopedic surgeon panel.

Results: Ninety-nine patients were enrolled ranging in age from 17–76 years. Baseline characteristics were comparable across treatment groups. No statistically significant differences in median healing time between any of the CP-533,536 treatment groups and placebo were observed based on radiology panel assessment, however significant differences were demonstrated by an orthopedic panel. At weeks eight, 10, 12, 14 and 16 a higher percentage of subjects in the CP-533,536 1.5 and 0.5 mg groups were considered healed compared to the placebo and the 15 mg groups by the orthopedic panel assessment. Moreover, the CP-533,536 – 0.5 mg group showed a statistically higher (p≤0.05) mean radiographic healing score than placebo treated group at weeks eight, 14, 16, 18, and 24.

Conclusion: CP-533,536 demonstrated accelerated healing in patients with acute tibia fractures by an orthopedic panel. Confirmatory trials are required to assure validity of the observed treatment effects.

Background: Bone morphogenetic proteins (BMPs) induce new bone in patients with bone defects and at extraskeletal sites in animals. Standard treatment for symptomatic scaphoid non-unions is bone graft with or without internal fixation by a screw or wires. We tested the ability of human recombinant osteogenic protein-1 (OP-1, BMP-7) with compressed autologous or allogeneic bone graft to accelerate the healing of scaphoid non-union.

Study Design: Randomized and controlled pilot study in 17 patients with a scaphoid nonunion.

Methods: Patients were randomly assigned to one of three groups: (1) Autologous iliac graft (n=6), (2) Autologous iliac graft + OP-1 (n=6) and (3) Allogeneic iliac graft + OP-1 (n=5). Radiographic, scintigraphic and clinical outcomes were assessed throughout the follow-up period of 24 months.

Results: OP-1 improved the performance of both autologous and allogeneic bone implants. Three dimensional helical CT scans and scintigraphy showed that the pre-existing sclerotic bone within proximal scaphoid poles was mainly replaced in OP-1 treated patients with well vascularized new bone. Addition of OP-1 to allogeneic bone implant equalized the clinical outcome with the autologous graft procedure and enabled circumventing the second donor graft harvest procedure resulting in less blood loss, shorter anesthesia and no pain at the donor side.

Conclusion: This is the first evidence that a recombinant human BMP accelerates scaphoid bone non-union repair and resorption of sclerotic bone in this specific microenvironment.

Clinical Relevance: OP-1 might be successfully used in healing of scaphoid non-union.