This article is more than 5 years old. Information may no longer be current.
Fracture healing abilities of EP-2 receptor agonist debated by orthopedic surgeons, radiologists
While one group observed a significant improvement, the other said one could not be found.
Click Here to Manage Email Alerts
NEW ORLEANS – Prostaglandin EP-2 receptor agonist CP-533,536 demonstrated accelerated healing in patients with acute tibial fractures evaluated by an orthopedic panel but not a panel of radiologists, according to a study presented here.
Mohit Bhandari, MD, PhD, FRSC, presented the study at the annual meeting of the Orthopaedic Research Society.
He said the identification of novel therapeutics to accelerate acute fracture healing is a critical aspect of medicine that requires more attention. CP-533,536 has reportedly demonstrated acceleration of fracture healing in preclinical models.
Two separate panels
The research team performed a phase II randomized, blinded, placebo-controlled trial wherein the efficacy of a local injection of three doses of CP-533,536 was compared to both placebo and a standard of care arm in patients with closed tibial shaft fractures that had been treated with reamed, inter-locked intramedullary nails.
Patients were followed at 2-week intervals up to 6 months, with a final evaluation at 1-year. Fracture healing was assessed by a panel of radiologists and a panel of orthopedic surgeons.
Radiologists find no difference
Bhandari reported that, in all, 99 patients were enrolled with comparable baseline characteristics.
When investigated by the panel of radiologists, there were no reported statistically significant differences in median healing time between any of the CP-533,536 treatment groups and the placebo groups. Significant differences were, however, demonstrated by the orthopedic panel.
At time points, 8, 10, 12, 14 and 16 weeks, a higher percentage of subjects in the CP-533,536 groups were considered healed by the orthopedic panel’s assessment. Moreover, Bhandari added, the CP-533,536 group showed a statistically higher mean radiographic healing score than placebo-treated groups at 8, 14, 16, 18 and 24 weeks.
More trials are needed
EP-2 has promise in acceleration of fracture healing. However, Bhandari said that confirmatory trials are required to assure the validity of the observed treatment effects, noting that the diversity in findings between panels brings to light another important question that needs answering.
“CP-533,536 did not demonstrate accelerated healing in patients with acute tibial fractures evaluated by a panel of radiologists,” he said. “This is contrary to the results determined by the orthopedic panel. Clearly the determinations are conflicting.”
“In the absence of a gold standard, we are left with a question: Who should be evaluating outcomes?” he added.
Bhandari told Orthopedics Today that he believes orthopedic surgeons should be more involved in outcomes adjudication in fracture healing trials given that most drugs will be administered by surgeons in the clinical setting. – by Robert Press
Reference:
- Bhandari M, Thompson DD, Kaplan IV, et al. The efficacy of a locally injectable prostaglandin EP-2 receptor agonist on fracture healing. Paper #130. Presented at the 2010 Annual Meeting of the Orthopaedic Research Society. March 6-9, 2010. New Orleans.
Mohit Bhandari, MD, PhD, FRSC, can be reached at bhandam@mcmaster.ca.