rhBMP-2 enhancement of posterolateral spinal fusion in a rabbit model in the presence of concurrently administered doxorubicin.

BACKGROUND CONTEXT: Spinal fusions can be necessary in patients undergoing chemotherapy with doxorubicin. In a previous study, doxorubicin was shown to decrease spinal fusion rates in a rabbit model of lumbar intertransverse process spinal fusion with autograft iliac crest bone. In the current study, we determine whether spinal fusion with recombinant human bone morphogenetic protein-2 (rhBMP-2) can overcome the inhibitory effect of doxorubicin in spinal fusion. PURPOSE: To determine if rhBMP-2 can overcome the inhibitory effects of doxorubicin (adriamycin) in an animal model of posterolateral spinal fusion. STUDY DESIGN/SETTING: Prospective, controlled, rabbit model of posterolateral lumbar fusion. OUTCOME MEASURES: Spine fusion was assessed by manual palpation (by observers blinded to the treatment group) at the level of arthrodesis. Fusion was graded according to a five-tiered classification (0-4). Posteroanterior radiographs of the excised spines were also graded in a blinded fashion using a six-point scoring system (0-5) devised to describe the amount of bone observed between the L5-L6 transverse processes. METHODS: Thirty-two New Zealand White rabbits underwent posterolateral fusion at L5-L6 with either autograft (iliac crest autograft bone) or rhBMP-2 (rhBMP-2/absorbable collagen sponge (0.86 mg/level). All animals received a dose of doxorubicin (2.5 mg/kg) known to inhibit spine fusion via the central vein of the ear immediately postoperatively. Five weeks postoperatively the rabbits were euthanized. Spine fusion was assessed by manual palpation, and graft quality was assessed with posteroanterior radiographs. RESULTS: Four of the 16 spines (25%) in the autograft group and 16 of the 16 spines (100%) in the rhBMP-2 group fused in the presence of doxorubicin administration (p<.05). There was significantly increased bone formation in the rhBMP-2 group (p<.05). One unilateral, subclinical wound infection was observed in each group at the time of euthanization (autograft [n=1, 6%] and rhBMP-2 [n=1, 6%]). CONCLUSIONS: We confirm that when autograft is used, doxorubicin decreases spinal fusion rate (25%) compared with historical controls (60-75%). More importantly, using rhBMP-2 overcomes the inhibitory effect of doxorubicin, resulting in 100% fusion in our animal model. This study suggests that rhBMP-2 has the potential to improve fusion rates in human patients undergoing chemotherapy with doxorubicin.

Comparison of the vastus-splitting and median parapatellar approaches for primary total knee arthroplasty: a prospective, randomized study. Surgical technique.

BACKGROUND: A vastus-splitting approach for total knee arthroplasty has been advocated to preserve function of the extensor mechanism and to decrease the prevalence of lateral release. Critics have claimed that there is greater blood loss and compromised exposure in large patients who are managed with this approach. The purpose of the present study was to compare vastus-splitting and median parapatellar approaches for primary total knee arthroplasty. METHODS: Forty-two consecutive patients (fifty-one knees) undergoing primary total knee arthroplasty were randomized to treatment with a median parapatellar or vastus-splitting approach. The interval of the vastus muscle split was marked with radiopaque vascular clips. Surgical data, functional parameters, and preoperative and postoperative electromyograms were assessed. RESULTS: Early (six-month) and intermediateterm (five-year) follow-up showed no differences in functional parameters, tourniquet time, or the frequency of patellar resurfacing. Significantly more lateral releases (p < 0.01) and greater blood loss (p = 0.03) occurred in the median parapatellar group. Nine (43%) of twenty-one knees in the vastus-splitting group had abnormal electromyographic findings at six months postoperatively, whereas all patients in the median parapatellar group had normal findings. Seven knees with abnormal electromyographic findings at six months had normal findings when restudied at five years; in each of these knees, the vastus split had been developed bluntly. The other two knees with abnormal findings at six months had had sharp dissection for the muscle split. Both of these knees had chronic changes, one with changes indicative of reinnervation and the other with ongoing denervation, but neither demonstrated functional compromise. CONCLUSIONS: The vastus-splitting approach offers a viable alternative to the median parapatellar approach for primary total knee arthroplasty that reduces the need for lateral retinacular release without impairment of quadriceps function. Electromyographic abnormalities in the quadriceps muscle have no functional consequence and most likely represent reversible neurapraxic injury that may be avoided by blunt dissection in the vastus medialis muscle.

Comparison of the vastus-splitting and median parapatellar approaches for primary total knee arthroplasty: a prospective, randomized study.

BACKGROUND: A vastus-splitting approach for total knee arthroplasty has been advocated to preserve function of the extensor mechanism and to decrease the prevalence of lateral release. Critics have claimed that there is greater blood loss and compromised exposure in large patients who are managed with this approach. The purpose of the present study was to compare vastus-splitting and median parapatellar approaches for primary total knee arthroplasty. METHODS: Forty-two consecutive patients (fifty-one knees) undergoing primary total knee arthroplasty were randomized to treatment with a median parapatellar or vastus-splitting approach. The interval of the vastus muscle split was marked with radiopaque vascular clips. Surgical data, functional parameters, and preoperative and postoperative electromyograms were assessed. RESULTS: Early (six-month) and intermediate-term (five-year) follow-up showed no differences in functional parameters, tourniquet time, or the frequency of patellar resurfacing. Significantly more lateral releases (p < 0.01) and greater blood loss (p = 0.03) occurred in the median parapatellar group. Nine (43%) of twenty-one knees in the vastus-splitting group had abnormal electromyographic findings at six months postoperatively, whereas all patients in the median parapatellar group had normal findings. Seven knees with abnormal electromyographic findings at six months had normal findings when restudied at five years; in each of these knees, the vastus split had been developed bluntly. The other two knees with abnormal findings at six months had had sharp dissection for the muscle split. Both of these knees had chronic changes, one with changes indicative of reinnervation and the other with ongoing denervation, but neither demonstrated functional compromise. CONCLUSIONS: The vastus-splitting approach offers a viable alternative to the median parapatellar approach for primary total knee arthroplasty that reduces the need for lateral retinacular release without impairment of quadriceps function. Electromyographic abnormalities in the quadriceps muscle have no functional consequence and most likely represent reversible neurapraxic injury that may be avoided by blunt dissection in the vastus medialis muscle.

Optimal timing of preoperative radiation for prophylaxis against heterotopic ossification. A rabbit hip model.

BACKGROUND: In a previous study, we developed a rabbit model of heterotopic ossification and demonstrated that 800 or 1200 cGy of radiation before an operation on the hip significantly decreased postoperative ectopic bone formation compared with that seen after the operation on the non-irradiated, contralateral hip. The purpose of this study was to determine the optimal preoperative timing of radiation prophylaxis against heterotopic ossification following hip surgery in this same experimental model. METHODS: Seventy-two hips in thirty-six New Zealand White rabbits were divided into four treatment groups corresponding to four preoperative points in time (four hours, twenty-four hours, seventy-two hours, and three weeks). The hips were irradiated with 1200 cGy at the different preoperative time points (eighteen hips at each time) to investigate the efficacy of the four preoperative radiation protocols. The rabbits then underwent bilateral hip surgery. They were killed and radiographs were made four months postoperatively. Heterotopic ossification was graded according to a modification of the scale of Brooker et al. The mean grade, the interobserver and intraobserver reliability, and the significance (p < 0.05) of the differences between the groups were evaluated. RESULTS: Radiation delivered at twenty-four hours preoperatively was significantly more effective for prophylaxis against heterotopic ossification than was radiation delivered at four hours or seventy-two hours preoperatively (p < 0.05), and the difference between the twenty-four-hour and three-week groups approached significance (p = 0.088). Furthermore, the twenty-four-hour group had a significantly lower percentage of hips with high-grade heterotopic ossification than did the four-hour (p = 0.02), seventy-two-hour (p = 0.002), and three-week (p = 0.03) groups. CONCLUSIONS: Preoperative irradiation to prevent heterotopic ossification optimally should be administered twenty-four hours before the operation. This latency period probably allows expression of radiation-induced sublethal mutations in the genetic code of pluripotential stem cells and precludes differentiation to osteoblastic cell lines.

The origin of osteoprogenitor cells responsible for heterotopic ossification following hip surgery: an animal model in the rabbit.

PURPOSE: To investigate the source of osteoprogenitor cells responsible for heterotopic ossification (HO) following total hip arthroplasty in an animal model. METHODS: New Zealand White (NZW) rabbits (n = 20) received a radiation treatment 24 h preoperatively to the hip joint of one hindquarter and to the femoral shaft of the contralateral side. Subjects underwent bilateral hip surgery 24 h after treatment. Subjects were euthanized and radiographed 4 months postoperatively. Heterotopic ossification was graded according to a modified Brooker scale. Mean grade, intra-observer reliability, and statistical significance (p < 0.05) were evaluated to compare the severity of heterotopic ossification between hindquarters treated with hip irradiation versus those treated with femoral shaft irradiation. RESULTS: The Fleiss Weighted Kappa Statistic indicated "almost perfect" (0.872) intra-rater reliability of radiographic heterotopic ossification grading. The average heterotopic ossification grade for the group receiving radiation to the hip was significantly greater than that for the group receiving radiation to the femoral shaft (2.575 versus 2.0, p < 0.02). CONCLUSION: Although both have some beneficial effect, our results demonstrate that irradiation of the femoral canal is significantly more effective than irradiation of the hip joint and abductor musculature for heterotopic ossification prophylaxis. This suggests that osteoprogenitor cells responsible for heterotopic ossification originate from both the hip abductors and the femoral canal, but the data provide indirect evidence that the femoral canal may be a more dominant source of these cells in the rabbit model.