Transient Local Bone Remodeling Effects of rhBMP-2 in an Ovine Interbody Spine Fusion Model

Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a powerful osteoinductive morphogen capable of stimulating the migration of mesenchymal stem cells (MSCs) to the site of implantation and inducing the proliferation and differentiation of these MSCs into osteoblasts. Vertebral end-plate and vertebral body resorption has been reported after interbody fusion with high doses of rhBMP-2. In this study, we investigated the effects of 2 rhBMP-2 doses on peri-implant bone resorption and bone remodeling at 7 time points in an end-plate-sparing ovine interbody fusion model. Methods: Twenty-one female sheep underwent an end-plate-sparing discectomy followed by interbody fusion at L2-L3 and L4-L5 using a custom polyetheretherketone (PEEK) interbody fusion device. The PEEK interbody device was filled with 1 of 2 different doses of rhBMP-2 on an absorbable collagen sponge (ACS): 0.13 mg (1·) or 0.90 mg (7·). Bone remodeling and interbody fusion were assessed via high-resolution radiography and histological analyses at 1, 2, 3, 4, 8, 12, and 20 weeks postoperatively. Results: Peri-implant bone resorption peaked between 3 and 8 weeks in both the 1· and the 7· rhBMP-2/ACS-dose group. Osteoclastic activity and corresponding peri-implant bone resorption was dose-dependent, with moderate-tomarked resorption at the 7·-dose level and less resorption at the 1·-dose level. Both dose (p \u3c 0.0007) and time (p \u3c 0.0025) affected bone resorption significantly. Transient bone-resorption areas were fully healed by 12 weeks. Osseous bridging was seen at all but 1 spinal level at 12 and at 20 weeks. Conclusions: In the ovine end-plate-sparing interbody fusion model, rhBMP-2 dose-dependent osteoclastic resorption is a transient phenomenon that peaks at 4 weeks postoperatively. Clinical Relevance: Using the U.S. Food and Drug Administration (FDA)-approved rhBMP-2 concentration and matching the volume of rhBMP-2/ACS with the volume of desired bone formation within the interbody construct may limit the occurrence of transient bone resorption

Dosimetric comparison study between intensity modulated radiation therapy and three-dimensional conformal proton therapy for pelvic bone marrow sparing in the treatment of cervical cancer.

The objective was to compare intensity-modulated radiation therapy (IMRT) with 3D conformal proton therapy (3DCPT) in the treatment of cervical cancer. In particular, each technique's ability to spare pelvic bone marrow (PBM) was of primary interest in this study. A total of six cervical cancer patients (3 postoperative and 3 intact) were planned and analyzed. All plans had uniform 1.0 cm CTV-PTV margin and satisfied the 95% PTV with 100% isodose (prescription dose = 45 Gy) coverage. Dose-volume histograms (DVH) were analyzed for comparison. The overall PTV and PBM volumes were 1035.9 ± 192.2 cc and 1151.4 ± 198.3 cc, respectively. In terms of PTV dose conformity index (DCI) and dose homogeneity index (DHI), 3DCPT was slightly superior to IMRT with 1.00 ± 0.001, 1.01 ± 0.02, and 1.10 ± 0.02, 1.13 ± 0.01, respectively. In addition, 3DCPT demonstrated superiority in reducing lower doses (i.e., V30 or less) to PBM, small bowel and bladder. Particularly in PBM, average V10 and V20 reductions of 10.8% and 7.4% (p = 0.001 and 0.04), respectively, were observed. However, in the higher dose range, IMRT provided better sparing (> V30). For example, in small bowel and PBM, average reductions in V45 of 4.9% and 10.0% (p = 0.048 and 0.008), respectively, were observed. Due to its physical characteristics such as low entrance dose, spread-out Bragg peak and finite particle range of protons, 3DCPT illustrated superior target coverage uniformity and sparing of the lower doses in PBM and other organs. Further studies are, however, needed to fully exploit the benefits of protons for general use in cervical cancer

Probabilistic dose distribution from interfractional motion in carbon ion radiation therapy for prostate cancer shows rectum sparing with moderate target coverage degradation

学位記番号：医博甲171