Biomedical subjects

Hyun W Bae

Publications and source records attributed to Hyun W Bae.

10 recordsLinked to original sources

PubMed2006

Intervariability and intravariability of bone morphogenetic proteins in commercially available demineralized bone matrix products.

STUDY DESIGN: Enzyme-linked immunosorbent assay was used to detect bone morphogenetic proteins (BMPs) 2, 4, and 7 in 9 commercially available ("off the shelf") demineralized bone matrix (DBM) product formulations using 3 different manufacturer's production lots of each DBM formulation. OBJECTIVES: To evaluate and compare the quantity of BMPs among several different DBM formulations (inter-product variability), as well as examine the variability of these proteins in different production lots within the same DBM formulation (intra-product variability). SUMMARY OF BACKGROUND DATA: DBMs are commonly used to augment available bone graft in spinal fusion procedures. Surgeons are presented with an ever-increasing variety of commercially available human DBMs from which to choose. Yet, there is limited information on a specific DBM product's osteoinductive efficacy, potency, and constancy. METHODS: There were protein extracts from each DBM sample separately dialyzed 4 times against distilled water at 4 degrees C for 48 hours. The amount of BMP-2, BMP-4, and BMP-7 was determined using enzyme-linked immunosorbent assay. RESULTS.: The concentrations of detected BMP-2 and BMP-7 were low for all DBM formulations, only nanograms of BMP were extracted from each gram of DBM (20.2-120.6 ng BMP-2/g DBM product; 54.2-226.8 ng BMP-7/g DBM). The variability of BMP concentrations among different lots of the same DBM formulation, intra-product variability, was higher than the variability of concentrations among different DBM formulations, inter-product variability (coefficient of variation range BMP-2 [16.34% to 76.01%], P < 0.01; BMP-7 [3.71% to 82.08%], P < 0.001). BMP-4 was undetectable. CONCLUSIONS: The relative quantities of BMPs in DBMs are low, in the order of 1 x 10(-9) g of BMP/g of DBM. There is higher variability in concentration of BMPs among 3 different lots of the same DBM formulation than among different DBM formulations. This variability questions DBM products' reliability and, possibly, efficacy in providing consistent osteoinduction.

Biological Products↗

PubMed2006

Controlling bone morphogenetic protein diffusion and bone morphogenetic protein-stimulated bone growth using fibrin glue.

STUDY DESIGN: An in vitro and in vivo study. OBJECTIVE: To evaluate the ability of fibrin glue to limit diffusion of recombinant human bone morphogenetic protein (rhBMP)-2 and its ability to protect spinal nerves from rhBMP-2 stimulated bone growth. SUMMARY OF BACKGROUND DATA: Studies have shown bone morphogenetic protein (rhBMP-2) stimulated bone growth can encroach on the spinal canal and nerves, causing neural compression. More recently, rhBMP-2 use in the cervical spine has been associated with life-threatening swelling. Fibrin glue has been used as a biologic carrier but has not been evaluated for its ability to limit rhBMP-2. METHODS: In phase 1 of the study, rhBMP-2 soaked absorbable collagen sponges (ACS) were encapsulated in fibrin glue and immediately incubated in physiologic lactated ringers solution at 38 degrees C. Samples of solution were tested for rhBMP-2 concentration. In phase 2 of the study, rats were surgically treated with laminectomy and placement of rhBMP-2/ACS versus laminectomy and placement of fibrin glue before placement of rhBMP-2/ACS. After 8 weeks, animals were euthanized and imaged using micro-computerized tomography. RESULTS: The diffusion study showed a significant limitation in rhBMP-2 diffusion when encapsulated in fibrin glue. The laminectomy study revealed blockage of bone formation by fibrin glue and protection of the spinal canal. CONCLUSIONS: Fibrin glue can limit the diffusion of rhBMP-2, and, thus, it can be used to help protect the spinal canal and nerve roots from rhBMP-2 stimulated bone growth.

Animals↗

PubMed2006

Graft resorption with the use of bone morphogenetic protein: lessons from anterior lumbar interbody fusion using femoral ring allografts and recombinant human bone morphogenetic protein-2.

STUDY DESIGN: This is a prospective cohort study examining the results and radiographic characteristics of anterior lumbar interbody fusion (ALIF) using femoral ring allografts (FRAs) and recombinant human bone morphogenetic protein-2 (rhBMP-2). This was compared to a historical control ALIF using FRAs with autologous iliac crest bone graft (ICBG). OBJECTIVE: To determine whether the use of rhBMP-2 can enhance fusion ALIF with stand-alone FRAs. SUMMARY OF BACKGROUND DATA: ALIF is a well-accepted procedure in reconstructive spine surgery. Advances in spinal surgery have produced a multitude of anterior interbody implants. The rhBMP-2 has promoted fusion in patients undergoing ALIF with cages and threaded allograft dowels. The FRA still remains a traditional alternative for anterior support. However, as a stand-alone device, the FRA has fallen into disfavor because of high rates of pseudarthrosis. With the advent of rhBMP-2, the FRA may be more attractive because of its simplicity and remodeling potential. It is important to understand the implications when rhBMP-2 is used with such structural allografts. METHODS: A total of 36 consecutive patients who underwent ALIF with stand-alone FRAs by a single surgeon (E.G.D.) at 1 institute were included. A cohort of 9 consecutive patients who received FRAs filled with rhBMP-2 was followed prospectively. After noticing suboptimal results, the senior author terminated this method of lumbar fusion. A total of 27 prior consecutive patients who received FRAs filled with autogenous ICBG were used for comparison. Analyzing sequential radiographs, flexion-extension radiographs, and computerized tomography with multiplanar reconstructions determined nonunions. Minimum follow-up was 24 months. RESULTS: Pseudarthrosis was identified in 10 of 27 (36%) patients who underwent stand-alone ALIF with FRAs and ICBG. Nonunion rate was higher among patients who received FRAs with rhBMP-2 (i.e., 5 of 9 [56%]). Statistical significance was not established because of the early termination of the treatment group (P > 0.3). Of interest, radiographs and computerized tomography revealed early and aggressive resorption of the FRAs when used with rhBMP-2. This preceded graft fracture and even disintegration, resulting in instability and eventual nonunion. CONCLUSION: The use of rhBMP-2 did not enhance the fusion rate in stand-alone ALIF with FRAs. In fact, the trend was toward a higher nonunion rate with rhBMP-2, although this was not significant with the numbers available. This result appears to be caused by the aggressive resorptive phase of allograft incorporation, which occurs before the osteoinduction phase.

Adult↗

PubMed2006

Computed tomography assessment of the accuracy of in vivo placement of artificial discs in the lumbar spine including radiographic and clinical consequences.

STUDY DESIGN: Prospective cohort study of 52 patients who had undergone artificial lumbar disc replacement. OBJECTIVES: To evaluate the implantation accuracy of prosthesis positioning, subsequent facet joint changes and prosthesis migration, and the clinical consequences of implant position. SUMMARY OF BACKGROUND DATA: Accuracy of spinal prosthesis implantation has not been evaluated rigorously, especially with a mini-incision approach. It is unknown if the inexact placement of a mobile device in the spine has any biomechanical, radiographic, or clinical repercussions. METHODS: A total of 52 consecutive patients were treated using standard methods of disc implantation with an intervertebral prosthesis. Computed tomography scans were performed within 3 days and again at 6 to 24 months. An independent radiologist analyzed the images for prosthesis position, rotation, migration, and facet changes. Results were compared with clinical outcome, measured by the Visual Analog Scale and Oswestry Disability Index. RESULTS: Deviation of the prosthesis from the center position was under 1.2 mm, and rotation off of midline was under 12 degrees. Follow-up CT scans showed no migration or facet changes. Regression analysis showed no correlation of prosthesis position with clinical outcome. CONCLUSIONS: Current prosthetic disc implantation methods, with minimally invasive access techniques, are relatively accurate. Although there can be deviation of the prosthesis from ideal placement, no repercussions were attributable.

Adult↗

PubMed2006

Kyphoplasty reduction of osteoporotic vertebral compression fractures: correction of local kyphosis versus overall sagittal alignment.

STUDY DESIGN: A retrospective study of patients who underwent 1-3-level kyphoplasty procedures at a single institute. OBJECTIVE: To examine and compare the effects of single and multilevel kyphoplasty procedures on local versus overall sagittal alignment of the spine. SUMMARY OF BACKGROUND DATA: Cement augmentation has been a safe and effective method in the treatment of symptomatic vertebral compression fractures (VCFs). In addition to providing rapid pain relief, balloon tamp kyphoplasty has reduced acute fractures, allowed controlled cement placement under lower pressure, and resulted in improvement of deformity. The restoration of normal overall spinal sagittal alignment in the elderly patient with a VCF and kyphotic deformity has obvious benefits. Although significant correction of local kyphosis (fractured vertebra) has been reported in the literature, to our knowledge, there have been no reports on whether this leads to an improved overall sagittal alignment. METHODS: A total of 65 consecutive patients with symptomatic VCFs who underwent 1-3-level kyphoplasty procedures were included in the study. Preoperative and postoperative radiographs were analyzed to quantify local and overall spinal sagittal alignment correction. Preoperative and postoperative vertebral heights at the fractured levels were also measured and categorized into anterior, middle, or posterior vertebral heights. RESULTS: Measurements revealed that kyphoplasty reduced local kyphotic deformity at the fractured vertebra by an average of 7.3 degrees (63% of preoperative kyphosis). This result did not translate to similar correction in overall sagittal alignment. In fact, angular correction decreased to 2.4 degrees (20% of preoperative kyphosis at fractured level) when measured 1 level above and below. The angular correction further decreased to 1.5 degrees and 1.0 degrees (13% and 8% of preoperative kyphosis at fractured level), respectively, at spans of 2 and 3 levels above and below. Average height gain was highest in the middle of the vertebral body (39% increase) compared to the anterior or posterior edges (19% and 3% increases, respectively). With multilevel kyphoplasty procedures, higher angular gains were seen over more vertebrae compared to the 7.3 degrees for a single-level kyphoplasty: 7.8 degrees over 2 levels and 7.7 degrees over 3 levels for 2 and 3-level kyphoplasty procedures, respectively. Kyphoplasty was able to achieve higher angular reduction in thoracic versus lumbar fractures (8.5 vs. 6.4 degrees, P < 0.01). The angular correction was also better maintained over adjacent segments in the thoracic spine. CONCLUSION: The majority of kyphosis correction by kyphoplasty is limited to the vertebral body treated. The majority of height gained after kyphoplasty occurs in the midbody. Higher correction over longer spans of the spine can be achieved with multilevel kyphoplasty procedures, in proportion to the number of levels addressed. Notwithstanding its well-published clinical efficacy, it is unrealistic to expect a 1 or 2-level kyphoplasty to improve significantly the overall sagittal alignment after VCFs.

Aged↗

PubMed2005

Clinical results of ProDisc-II lumbar total disc replacement: report from the United States clinical trial.

The much-awaited clinical use of lumbar artificial discs has begun in the United States. The United States Investigational Device Exemption (US IDE) clinical trial of the ProDisc-II prosthetic disc (Synthes, Paoli, PA) was recently completed, with all indications that it meets or surpasses the test of equivalence against fusion controls. This is a review of the clinical performance of the ProDisc-II artificial disc and includes an interim report from the US IDE trial at one site.

Adult↗

PubMed2004

Accuracy and interobserver agreement for determinations of rabbit posterolateral spinal fusion.

STUDY DESIGN: The accuracy and interobserver agreement of fine detail radiography and computed tomography (CT) determination of spinal fusion were evaluated in an established animal spine fusion model. OBJECTIVE: To determine the accuracy and interobserver agreement of radiographic determinations of spinal fusion in rabbit posterolateral spine fusion. SUMMARY OF BACKGROUND DATA: The rabbit posterolateral intertransverse process spine fusion model is an established animal model for evaluating bone graft alternatives for spinal fusion. However, little is known regarding the accuracy and interobserver agreement of radiographic determinations of spondylodesis in this model. METHODS: Forty-two New Zealand White rabbits underwent posterolateral spinal fusion. The animals were killed at 9 weeks and the lumbar spine harvested. Manual manipulation, fine detail radiography, and CT images were used to assess spinal fusion. RESULTS: Using manual palpation testing as the standard by which to assess fusion, there was high sensitivity and negative predictive value for both radiographic methods. Positive predictive value, however, was poor (26% fine detail radiography, 61% CT scan). CT correlated better with manual palpation testing when compared with fine detail radiographs. There was substantial interobserver agreement of successful fusion using CT scan imaging (kappa = 0.63) and moderate interobserver agreement radiographs (kappa = 0.52). CONCLUSIONS: Both radiographic techniques used in the study recorded high sensitivity and negative predictive value. However, positive predictive value was poor, especially with fine detail radiographs. Nevertheless, CT with reformatted images did appear to be superior to fine detail radiographs in accurately identifying nonunions in this animal model.

Animals↗

PubMed2003

Augmentation of rabbit posterolateral spondylodesis using a novel demineralized bone matrix-hyaluronan putty.

STUDY DESIGN: Posterolateral spinal fusion with allogeneic demineralized bone graft-hyaluronan putty in addition to autogenous iliac crest bone graft in a rabbit model. OBJECTIVES: To determine the potential efficacy of demineralized bone graft-hyaluronan putty as a bone graft enhancer. SUMMARY OF BACKGROUND DATA: Autograft bone is the material of choice for posterolateral lumbar intertransverse process fusion. Bone graft alternatives such as demineralized bone matrices that can be used as graft extenders, enhancers, or substitutes continue to be developed. METHODS: One hundred New Zealand white rabbits underwent bilateral posterolateral spinal fusion with autogenous iliac crest bone graft or bone graft with allogeneic rabbit demineralized bone graft-hyaluronan putty. The rabbits were killed 9 weeks later, and the lumbar spines were removed. Manual manipulation and fine detail radiography were used to assess spinal fusion, and computed tomographic images were used to quantify the volume of the fusion mass. RESULTS: In comparison with autograft bone alone, the fusion rates were greater when demineralized bone graft-hyaluronan putty was used as an adjunct to autogenous bone. Furthermore, the radiographic fusion rate was greater when demineralized bone graft-hyaluronan putty was used in a 2:1 ratio to autograft bone in comparison with a 1:1 ratio (P = 0.001). The addition of demineralized bone graft-hyaluronan putty to autograft bone was found to increase mineralized bone volume in a ratio-dependent manner (P < 0.05). CONCLUSIONS: Allogeneic demineralized bone matrix-hyaluronan putty enhances rabbit posterolateral spine fusion when used as an adjunct to autogenous bone graft. This new formulation of demineralized bone matrix may facilitate greater bone formation and successful fusion.

Animals↗

PubMedDate not supplied

The use of simvastatin in rabbit posterolateral lumbar intertransverse process spine fusion.

BACKGROUND CONTEXT: There has been recent enthusiasm regarding the potential positive effects of statins on bone. Statins vary in their ability to influence bone activity. Simvastatin has been shown in experimental models to stimulate bone acting growth factors and enhance bone formation. PURPOSE: The potential efficacy of Simvastatin in enhancing spinal fusion was evaluated in a rabbit posterolateral intertransverse process fusion model. STUDY DESIGN/SETTING: Posterior lumbar intertransverse process spinal fusion performed on New Zealand White rabbits. PATIENT/STUDY SAMPLE: 44 New Zealand White rabbits. OUTCOME MEASURES: Spinal fusion as determined by manual palpation testing and fine detail radiography. Bone fusion mass volume and density as determined by CT scan imaging. METHODS: Forty-four New Zealand White rabbits underwent posterolateral intertransverse process spine fusion using autogenous iliac crest bone graft. Simvastatin was administered orally in 20 animals and the serum lipid profile quantified in test and control animals. The animals were euthanized 9 weeks following index surgery and the lumbar spine was harvested. Spinal fusion was determined by manual palpation testing and fine detail radiography. The volume and density of the bone fusion mass was quantified by computed tomography. RESULTS: Drug treatment for 9 weeks caused a reduction in serum lipid biochemical markers when compared with controls. The spinal fusion rate, as judged by manual palpation testing (13.0% control group, 16.6% Simvastatin group) and fine detail radiography, was not significantly different comparing treatment with control animals. Accordant with the assessment of spinal fusion, there was no statistically significant effect on the volume of the fusion mass (1,224.7+/-98.7 mm(3) in the control group and 1,075.9+/-66.3 mm(3) in the Simvastatin group), the density of bone in the lumbar spine or that in the formed fusion mass. CONCLUSIONS: Systemic use of Simvastatin caused a reduction in lipid biochemical parameters in treated animals. Successful spinal fusion as judged by manual palpation testing and fine detail radiography was not significantly different in treated versus untreated animals. The bone volume density of the formed fusion mass was not significantly different in treated versus untreated animals. There did not appear to be a significant advantage or disadvantage to the use of Simvastatin rabbit posterolateral spinal fusion. The potential positive effects of statins on bone require further study.

Animals↗

PubMedDate not supplied

An in vitro and in vivo analysis of fibrin glue use to control bone morphogenetic protein diffusion and bone morphogenetic protein-stimulated bone growth.

BACKGROUND CONTEXT: Recombinant human bone morphogenetic protein-2 (rh-BMP2) has become popular for augmenting spine fusion in the lumbar and cervical spine. Concerns exist, however, over bone morphogenetic protein (BMP)-stimulated soft-tissue swelling and bone growth stimulation in areas where bone is not desired, especially as the material "leaks" into such spaces. The most detrimental effects of such leakage might be airway compromise, while heterotopic bone formation into the spinal canal has been reported in animal and human studies. Fibrin glue has been used as a carrier of many osteoinductive materials; however, its efficacy at modulating the clinical effects of BMP are not known. The amorphous nature of fibrin glue makes it a candidate to control diffusion of BMP and possibly limit bone formation by limiting BMP diffusion to areas where such bone is not desired. PURPOSE: To evaluate the use of fibrin glue to limit BMP diffusion and BMP-stimulated bone growth. STUDY DESIGN/SETTING: This is an in vitro basic science study and an in vivo prospective randomized animal study. STUDY SAMPLE: Eighteen Lewis rats. OUTCOME MEASURES: In vitro study: Enzyme-linked immunosorbent assay measurement of rh-BMP2 concentration in saline. In vivo study: At day 60, rats were evaluated for neurologic deficits before sacrifice. Spines were harvested, and the following studies were performed: 1) manual testing for fusion and bone growth; 2) X-ray evaluation; 3) Micro-computed tomography (micro-CT) scans. METHODS: In vitro study: Collagen sponges soaked with BMP at two different concentrations were incubated in saline solution with and without encapsulation by fibrin glue. Saline BMP concentrations were measured at consecutive time points. In vivo study: A rat fusion model using rh-BMP2 for fusion has been developed and tested with resultant100% fusion in over 100 rats. Lewis rats were divided into two groups and treated as follows: I: Exposure of L4-L5 transverse processes, decortication, and placement of BMP sponge in the lateral intertransverse space. II: Exposure and decortication as above and placement of fibrin glue before BMP sponge placement. RESULTS: In vitro study: Peak rh-BMP2 concentrations in saline were 20% and 45% of the maximum possible for fibrin glue encapsulated sponges and controls, respectively, with a more gradual increase to peak concentration in samples encapsulated in fibrin glue. In vivo study: No rats exhibited any neurologic deficits. X-rays revealed at least partial bone formation in all rats. Manual testing of intertransverse fusion spines revealed 100% fusion in rats treated with BMP only, whereas rats treated with fibrin glue before placement of BMP sponges revealed only one possible fusion. Posterior-lateral bone formation was present on X-ray in both groups, and micro-CT imaging revealed bridging bone from transverse processes to the BMP-stimulated bone in the control groups. In spines treated with fibrin glue before rh-BMP2 placement, bone formation could still be seen within the soft tissues; however, bridging bone connecting to the transverse processes was either significantly decreased or not present. CONCLUSIONS: Fibrin glue can limit rh-BMP2 diffusion. Also, because it limited bone formation at the transverse processes, it can be inferred that fibrin glue can limit bone formation when used to separate areas of desired bone formation from areas where bone formation is not desired.

Animals↗