Experimental Spinal Fusion With Recombinant Human Bone Morphogenetic Protein-2 Without Decortication of Osseous Elements

Study Design. L4-L5 intertransverse process fusions were produced with 58 μg, 230 μg, or 920 μg of recombinant human bone morphogenetic protein-2 in 20 dogs. Eleven had traditional decortication of posterior elements before insertion of the implant. Nine were left undecorticated. All animals were evaluated 3 months after surgery. Objectives. To determine whether decortication is a prerequisite for successful fusion in the presence of osteoinductive proteins such as bone morphogenetic protein-2. Summary of Background Data. Recombinant osteoinductive proteins can induce de novo bone in ectopic soft-tissue sites in the absence of bone marrow elements. Traditional methods for achieving spinal fusion rely on exposure of bone marrow through decortication to facilitate osteogenesis. It is hypothesized that the presence of an implanted osteoinductive protein obviates the need for exposure and release of host inductive factors. Methods. Recombinant human bone morphogenetic protein-2-induced intertransverse process fusions were performed with and without decortication. Fusion sites were evaluated by computed tomography imaging, high-resolution radiography, manual testing, mechanical testing, and histologic analysis. Results. One hundred percent of decorticated spines and 89% of undecorticated spines were clinically fused by 3 months. Ninety-one percent of decorticated spines and 78% of undecorticated specimens exhibited bilateral transverse process osseous bridging. The only spines that failed to achieve solid bilateral arthrodesis were in the lowest dose group. With the higher two doses, there was histologic evidence of osseous continuity between the fusion mass and undecorticated transverse processes. Conclusions. There were no statistical differences in clinical and radiographic fusion rates between decorticated and undecorticated sites. With higher doses of recombinant human bone morphogenetic protein-2, there was little histologic distinction between fusions in decorticated versus undecorticated spines

Histologic Evaluation of the Efficacy of rhBMP-2 Compared With Autograft Bone in Sheep Spinal Anterior Interbody Fusion

Study Design. The sheep anterior lumbar spinal fusion model was used to study the efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2)–collagen composite in comparison with autograft to enhance spinal interbody fusion. Comparisons were drawn from temporal radiographic and end-point biomechanical and histologic data. Objective. To analyze histologically the ability of rhBMP-2 to achieve complete arthrodesis between vertebral bodies. Summary of Background Data. Studies using rhBMP for enhancement of anterior interbody fusion have used numerous endpoints. However, systematic histologic evaluation of the fusion has not been conducted. Methods. Twelve sheep underwent single-level anterior lumbar interbody fusion performed with a cylindrical fenestrated titanium interbody fusion device (INTER FIX, Medtronic Sofamor Danek, Inc., Memphis, TN). The device was filled either with rhBMP-2–collagen (n = 6) or autogenous iliac crest bone graft (n = 6). Radiologic evaluation was carried out at 2-month intervals, and all sheep were killed 6 months after surgery. Nondestructive biomechanical testing for stiffness to flexion, extension, and lateral bending moments, un-decalcified histology, and qualitative and quantitative histologic evaluation were performed. Results. Radiographs revealed a bony bridge anterior to the cage in five of six rhBMP-2-treated animals, whereas it was present only in one of five in the autogenous bone graft group. Segments treated with rhBMP-2 were 20% stiffer in flexion than autograft-treated segments at 6 months. Six of six in the rhBMP-2 group and two of six in the autograft group showed complete fusion. There was a significantly higher rate of bony continuity observed at the fenestrations of the rhBMP-2 group. Three times more number of cage fenestrations in the rhBMP-2 group demonstrated “all-bone” when compared with the autograft group (P \u3c 0.001). Further, the scar tissue in and around the autograft-treated cages was 16-fold more (P \u3c 0.01) than that seen for rhBMP-2-treated cages. Conclusions. The study demonstrates that rhBMP-2 can lead to earlier radiologic fusion and a more consistent increased stiffness of the segments when compared with autograft in sheep anterior lumbar interbody fusion. Furthermore, a three times higher histologic fusion rate is attainable with significantly reduced fibrous tissue around the implant when rhBMP-2 is used

Effective Doses of Recombinant Human Bone Morphogenetic Protein-2 in Experimental Spinal Fusion

Study Design Nineteen dogs underwent L4-L5 intertransverse process fusions with either 58 μg, 115 μg, 230 μg, 460 μg, or 920 μg of recombinant human bone morphogenetic protein-2 carried by a polylactic acid polymer. A previous study (12 dogs) compared 2300 μg of recombinant human bone morphogenetic protein-2, autogenous iliac bone, and carrier alone in this model. All fusions subsequently were compared. Objectives To characterize the dose-response relationship of recombinant human bone morphogenetic protein-2 in a spinal fusion model. Summary of Background Data Recombinant osteoinductive morphogens, such as recombinant human bone morphogenetic protein-2, are effective in vertebrate diaphyseal defect and spinal fusion models. It is hypothesized that the quality of spinal fusion produced with recombinant human bone morphogenetic protein-2, above a threshold dose, does not change with increasing amounts of inductive protein. Methods After decortication of the posterior elements, the designated implants were placed along the intertransverse process space bilaterally. The fusion sites were evaluated after 3 months by computed tomography imaging, high-resolution radiography, manual testing, mechanical testing, and histologic analysis. Results As in the study using 2300 μg of recombinant human bone morphogenetic protein-2, implantation of 58–920 μg of recombinant human bone morphogenetic protein-2 successfully resulted in intertransverse process fusion in the dog by 3 months. This had not occurred in animals containing autograft or carrier alone. The cross-sectional area of the fusion mass and mechanical stiffness of the L4-L5 intersegment were not dose-dependent. Histologic findings varied but were not related to rhBMP-2 dose. Inflammatory reaction to the composite implant was proportional inversely to the volume of the fusion mass. Conclusions No mechanical, radiographic, or histologic differences in the quality of intertransverse process fusion resulted from a 40-fold variation in dose of recombinant human bone morphogenetic protein-2

How Long Do Endoprosthetic Reconstructions for Proximal Femoral Tumors Last?

As the life expectancy of patients with musculoskeletal tumors improves, long-term studies of endoprosthetic reconstructions are necessary to establish realistic expectations for the implants and compare them to other reconstruction approaches. (1) What is the long-term survival of cemented bipolar proximal femoral replacements? (2) How does prosthesis survival compare to patient survival among patients with Stage I, II, and III disease? (3) Do modular implants outperform custom-built prostheses? (4) Do some proximal femoral replacements require conversion to THA? We retrospectively reviewed all 86 proximal femoral replacements used for tumor reconstruction from 1982 to 2008. Primary diagnoses were 43 high-grade tumors (IIA/IIB), 20 low-grade tumors (IA/IB or benign), and 23 with metastatic disease. We reviewed prosthesis survival, patient survival, complication rates, functional outcomes, and rates of conversion to THA. Five of 86 patients (5.8%) required revision of the femoral component. Five-, 10-and 20-year implant survivorships were 93%, 84%, and 56%, respectively. All patients with low-grade disease survived; the 5-year survival rate for patients with metastatic disease was 16%; the 5-, 10-, and 20-year survival for IIA/IIB patients was 54%, 50%, and 44%, respectively. Five of 86 patients (5.8%) underwent conversion to THA for groin pain. Cemented bipolar proximal femoral replacements after tumor resection proved a durable reconstruction technique. The implants outlived patients with metastatic disease and high-grade localized disease while patients with low-grade disease outlived their implants. The survival of modular prostheses was comparable to that of older, one-piece custom designs. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence

Cemented Endoprosthetic Reconstruction of the Proximal Tibia: How Long Do They Last?

The few available studies documenting the long-term survival of cemented proximal tibial endoprostheses for musculoskeletal tumors do not differentiate between stem designs or patient diagnosis. There is wide variation in survival rates reported, possibly a result of this heterogeneity in patient population and implant design. We therefore asked: (1) How long do proximal tibial endoprostheses last? (2) What is the typical long-term functional result after proximal tibial replacement? And (3) what are the short- and long-term complications associated with endoprosthetic reconstruction of the proximal tibia, particularly with respect to the soft tissue reconstruction? We retrospectively reviewed 52 patients with 52 proximal tibial endoprosthetic reconstructions for a tumor-related diagnosis. Kaplan-Meier survivorship analysis was performed using revision of the stemmed components for any reason as an endpoint for implants, and death due to disease progression for patients. Function was assessed using the MSTS scoring system. The minimum followup was 1 month (mean, 96 months: range, 1–284 months; median, 69 months). Using revision of the stemmed components for any reason as an end point, overall prosthesis survival at 5, 10, 15, and 20 years was 94%, 86%, 66%, and 37%, respectively. The 29 modular implants demonstrated a trend toward improved survival compared to the 23 custom-designed components, with a 15-year survivorship of 88% versus 63%. The mean postoperative Musculoskeletal Tumor Society score at most recent followup was 82% of normal function (mean raw score, 24.6; range, 4–29). Cemented endoprosthetic reconstruction of the proximal tibia provides a reliable method of reconstruction following tumor resection. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence

Validation of a 3D CT method for measurement of linear wear of acetabular cups: A hip simulator study

Background We evaluated the accuracy and repeatability of a 3D method for polyethylene acetabular cup wear measurements using computed tomography (CT). We propose that the method be used for clinical in vivo assessment of wear in acetabular cups. Material and methods Ultra-high molecular weight polyethylene cups with a titanium mesh molded on the outside were subjected to wear using a hip simulator. Before and after wear, they were (1) imaged with a CT scanner using a phantom model device, (2) measured using a coordinate measurement machine (CMM), and (3) weighed. CMM was used as the reference method for measurement of femoral head penetration into the cup and for comparison with CT, and gravimetric measurements were used as a reference for both CT and CMM. Femoral head penetration and wear vector angle were studied. The head diameters were also measured with both CMM and CT. The repeatability of the method proposed was evaluated with two repeated measurements using different positions of the phantom in the CT scanner. Results The accuracy of the 3D CT method for evaluation of linear wear was 0.51 mm and the repeatability was 0.39 mm. Repeatability for wear vector angle was 17?. Interpretation This study of metal-meshed hip-simulated acetabular cups shows that CT has the capacity for reliable measurement of linear wear of acetabular cups at a clinically relevant level of accuracy

Cemented Distal Femoral Endoprostheses for Musculoskeletal Tumor: Improved Survival of Modular versus Custom Implants

Advocates of newer implant designs cite high rates of aseptic loosening and failure as reasons to abandon traditional cemented endoprosthetic reconstruction of the distal femur. We asked whether newer, modular distal femoral components had improved survivorship compared with older, custom-casted designs. We retrospectively reviewed 254 patients who underwent distal femoral endoprosthetic reconstruction. We excluded two patients with cementless implants, 27 with expandable prostheses, and 39 who had a nontumor diagnosis. This left 186 patients: 101 with older custom implants and 85 with contemporary modular implants. The minimum followup was 1 month (mean, 96.0 months; range, 1–336 months). The tumor was classified as Stage IIA/IIB in 122 patients, Stage IA/IB or benign in 43, and Stage III or metastatic in 21. Kaplan-Meier analysis revealed overall 10-, 20-, and 25-year implant survival rates of 77%, 58%, and 50%, respectively, using revision of the stemmed components as an end point. The 85 modular components had a greater 15-year survivorship than the 101 custom-designed implants: 93.7% versus 51.7%, respectively. Thirty-five stemmed components (18.8%) were revised for aseptic loosening in 22 patients, implant fatigue fracture in 10, infection in two, and local recurrence in one. Cemented modular rotating-hinge distal femoral endoprostheses demonstrated improved survivorship compared with custom-casted implants during this three-decade experience. Patients with low-grade disease and long-term survivors of high-grade localized disease should expect at least one or more revision procedures in their lifetime. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence