Nomaan Ashraf

Radiation therapy for heterotopic ossification prophylaxis acutely after elbow trauma: a prospective randomized study.

BACKGROUND Heterotopic ossification around the elbow can result in pain, loss of motion, and impaired function. We hypothesized that a single dose of radiation therapy could be administered safely and acutely after elbow trauma, could decrease the number of elbows that would require surgical excision of heterotopic ossification, and might improve clinical results. METHODS A prospective randomized study was conducted at three medical centers. Patients with an intra-articular distal humeral fracture or a fracture-dislocation of the elbow with proximal radial and/or ulnar fractures were enrolled. Patients were randomized to receive either single-fraction radiation therapy of 700 cGy immediately postoperatively (within seventy-two hours) or nothing (the control group). Clinical and radiographic assessment was performed at six weeks, three months, and six months postoperatively. All adverse events and complications were documented prospectively. RESULTS This study was terminated prior to completion because of an unacceptably high number of adverse events reported in the treatment group. Data were available on forty-five of the forty-eight patients enrolled in this study. When the rate of complications was investigated, a significant difference was detected in the frequency of nonunion between the groups. Of the nine patients who had a nonunion, eight were in the treatment group. The nonunion rate was 38% (eight) of twenty-one patients in the treatment group, which was significantly different from the rate of 4% (one) of twenty-four patients in the control group (p = 0.007). There were no significant differences between the groups with regard to the prevalence of heterotopic ossification, postoperative range of motion, or Mayo Elbow Performance Score noted at the time of study termination. CONCLUSIONS This study demonstrated that postoperative single-fraction radiation therapy, when used acutely after elbow trauma for prophylaxis against heterotopic ossification, may play a role in increasing the rate of nonunion at the site of the fracture or an olecranon osteotomy. The clinical efficacy of radiation therapy could not be determined on the basis of the sample size. Further research is needed to determine the role of limited-field radiation for prophylaxis against heterotopic ossification after elbow trauma.

Evidence for overgrowth after midfemoral fracture via increased RNA for mitosis

Middiaphyseal femoral fractures in children and young rats stimulate linear femoral growth, a phenomenon commonly attributed to increased vascularity. To test for changes in mRNA expression of genes related to blood vessels, nerve fibers, cartilage, bone, and cell metabolism, we measured mRNA gene expression for all known rat genes in the physis at various times after diaphyseal fracture. Female Sprague-Dawley rats, 4 weeks of age at surgery, were subjected to a unilateral, simple, transverse, middiaphyseal femoral fracture stabilized with an intramedullary rod. At 0 (intact), 0.1, 0.4, 1, 2, 3, 4, and 6 weeks after fracture, the femoral head with the proximal physis was collected from fractured and intact femora. The RNA was extracted, processed to biotinlabeled cRNA, and hybridized to Affymetrix Rat 230 2.0 GeneChip microarrays. Transcripts from fracture-induced lengthening of the injured femora were compared to those of the intact contralateral femur. In the proximal physis, transcripts related to blood vessels and cartilage formation were down-regulated by fracture. Transcripts related to bone remodeling, nerve axon elongation, cell division, and protein synthesis were up-regulated by fracture. The data support increased mitotic activity in the physis after a midshaft fracture and not increased vascularity.

Transient Soft-tissue Edema Associated with Implantation of Increasing Doses of rhbmp-2 on an Absorbable Collagen Sponge in an Ectopic Rat Model

BACKGROUND Recombinant human bone morphogenetic protein-2 (rhBMP-2) is an osteoinductive protein. However, soft-tissue edema adjacent to the site of rhBMP-2 implantation has been reported. This animal study was designed to examine soft-tissue edema associated with increasing rhBMP-2 doses with implantation on an absorbable collagen sponge (ACS) and with injection directly into muscle. METHODS Thirty-six Lewis rats received intramuscular implantation of rhBMP-2 on an ACS (Part I) or intramuscular injection of rhBMP-2 solution (Part II). Part-I sites received rhBMP-2/ACS at doses of 0 μg, 30 μg (normal), 129 μg (mid), or 450 μg (high). Part-II sites received rhBMP-2/ACS or rhBMP-2 intramuscular injection at doses of 10 μg (normal) or 150 μg (mid). A previous rat model showed 10 μg to be 100% effective at inducing osseous spinal fusion. In our study, T2-weighted magnetic resonance imaging (MRI) was performed at two and seven days to assess edema volume, and statistical comparisons were carried out with analysis of variance (ANOVA). Cellular response, vascularity, and ossification were examined histologically. RESULTS Quantitative MRI demonstrated similar peri-implant edema volumes in the control (buffer on an ACS) and normal-dose rhBMP-2 groups. Higher doses resulted in increased edema volume. Edema decreased significantly from two to seven days. Similar capillary densities were observed in all rhBMP-2 groups at two days, and there was dose-dependent increased ossification at seven days. Compared with the rhBMP-2 injection, implantation of the rhBMP-2/ACS resulted in increased edema. This edematous response was transient in all groups. Minimal or no ossification occurred after the rhBMP-2 injections. CONCLUSIONS Transient peri-implant soft-tissue edema occurred in a dose-dependent manner following implantation of rhBMP-2/ACS in this rat model. The normal dose of rhBMP-2/ACS produced edema similar to that in the controls. Finally, rhBMP-2 solutions injected directly into muscle resulted in minimal soft-tissue edema.