Challenges and Controversies of Foot and Ankle Trauma.

Traumatic injury to the foot and ankle can result in long-term disability, which may have substantial negative implications on a patient's functional outcomes and quality of life. The diagnosis and appropriate management of these challenging injuries are not always agreed on or straightforward. In particular, the appropriate diagnosis and management of distal tibiofibular syndesmotic injuries as well as the surgical approach and role of primary subtalar arthrodesis for intra-articular calcaneal fractures are controversial.

Achilles Tendon Rupture in Elite Athletes.

The management of acute Achilles tendon rupture in elite athletes is a current area of clinical controversy. Recent studies have reported near-equivocal outcomes in patients who undergo either nonsurgical or surgical treatment of Achilles tendon rupture; however, similar functional outcomes may not be observed in elite athletes who are at the highest levels of athletic performance and undergo nonsurgical or surgical treatment of Achilles tendon rupture. Surgeons should understand the risks and benefits of nonsurgical and surgical management of acute Achilles tendon rupture. Surgeons also should understand the accelerated rehabilitation protocols; functional nonsurgical and postoperative rehabilitation protocols; as well as the standard open, percutaneous, and minimally invasive surgical techniques for the management of Achilles tendon rupture from the perspective of a sports medicine foot and ankle specialist.

Lisfranc Injuries in the Elite Athlete.

The management of sports-related Lisfranc injuries is optimized by a detailed understanding of the relevant anatomy, mechanisms of injury, clinical diagnostic maneuvers, imaging, and treatment options for patients with this disabling injury. A lower energy ligamentous variant Lisfranc injury, which was first observed in professional football players, has recently been described. The treatment options for patients with a Lisfranc injury include nonsurgical management, open reduction and internal fixation, suture-button fixation techniques, and arthrodesis.

High-Risk Stress Fractures in Elite Athletes.

Surgeons should understand common factors that predispose high-level athletes to stress injuries as well as the importance of vitamin D and specifics related to vascular supply, location of injury, biomechanics, and susceptibility factors in high-level athletes who have stress injuries. Surgeons should be aware of diagnostic- and management-based recommendations for and the outcomes of anterior tibia, medial malleolus, tarsal navicular, and proximal fifth metatarsal stress fractures in professional athletes.

Management of Osteochondral Lesions of the Talus.

Management strategies for symptomatic osteochondral lesions of the talus are primarily surgical. Treatment options for symptomatic osteochondral lesions of the talus most commonly include bone marrow stimulation techniques, osteochondral autograft transplantation, osteochondral allograft transplantation, autologous chondrocyte implantation, matrix-induced autologous chondrocyte implantation, and particulated juvenile articular cartilage. The selection of the most appropriate treatment option should be based on the specifics of a talar lesion, in particular, lesion size.

Lateral Ankle Instability and Peroneal Tendon Pathology.

Surgeons should understand the anatomic, vascular, biomechanical, and predisposing factors related to lateral ankle instability and peroneal tendon injuries, including peroneal tendinitis and tenosynovitis, peroneal tendon tears and ruptures, as well as peroneal tendon subluxation and dislocation. Surgeons should understand the treatment options and recommendations for patients who have lateral ankle instability and peroneal tendon injuries from the perspective of a sports medicine foot and ankle specialist. In addition, surgeons should be aware of arthroscopic approaches and an algorithm for the treatment of patients who have lateral ankle instability and peroneal tendon injuries.

Use of autogenous bone graft compared with RhBMP in high-risk patients: a comparison of fusion rates and time to fusion.

STUDY DESIGN: A retrospective study. OBJECTIVE: To evaluate whether recombinant human bone morphogenetic protein (rhBMP-2) can improve fusion rates and time to fusion in high-risk patients when compared with autograft in lumbar posterolateral fusion. SUMMARY OF BACKGROUND DATA: The use of rhBMP-2 in the general population for posterolateral fusion has resulted in relatively good reported outcomes; however, it is currently considered "off-label" use. Few studies, however, have determined the outcomes of rhBMP-2 when used in patients with numerous risk factors for a pseudarthrosis. METHODS: One hundred ninety-five patients were divided into 4 groups depending on fusion material and the presence/absence of fusion-related risk factors for nonunions; group A was defined as rhBMP-2 used in the presence of high-risk factors (FRRF), group B was defined as rhBMP-2 used in the absence of FRRF, group C was defined as autograft used in the presence of FRRF, and group D was defined as autograft used in the absence of FRRF. The time to fusion, fusion rate were compared between each group. RESULTS: The time to fusion was significantly faster in group B than in group D in patients with no history of smoking (P<0.05), hypertension (P<0.01), or other significant comorbidity (P<0.05). The time to complete fusion was also significantly faster in group B than in group D in patients under the age of 65 (P<0.05), patients undergoing primary surgery (P<0.05), single-level surgery (P<0.01), no smoking history (P<0.05), no diabetes mellitus (P<0.01), no hypertension (P=0.001), no osteoporosis (P<0.01), and no significant comorbidity (P<0.01). Although the fusion rate was higher in group B than in group D, with the exception of sex and single-level surgery, there were no significant differences between groups B and D. Although initial fusion mass and time to solid fusion was faster in group A than in group C, there were no significant differences between groups A and C. In addition, fusion rates were higher in group C than in group A, looking at all factors except revision surgery, but the differences were not statistically significant. CONCLUSIONS: With relative low dosage of rhBMP-2 compared with the dose used in Food and Drug Administration trial, in patients without fusion-related risk factors, rhBMP-2 may lead to acceptable fusion rates and faster fusion time when compared with autograft. Therefore, rhBMP-2 may serve as an acceptable alternative to autogenous bone graft in patients without fusion-related risk factors undergoing instrumented posterolateral lumbar fusions. When compared with patients with fusion-related risk factors, the use of rhBMP-2 was comparable with autograft but was not sufficient to overcome all aspects of the weakened osteoinductive capacity encountered in patients with these risk factors.

BMP induced inflammation: a comparison of rhBMP-7 and rhBMP-2.

Concern has been raised because of reports of inflammatory swelling following the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human bone morphogenetic protein-7 (rhBMP-7). The purpose of this study is to compare the inflammatory action of rhBMP-7 with those of rhBMP-2. ELISA assays (IL-6, TNF-α) were used to measure the cytokine response to different concentrations of rhBMP-7 and -2. Recombinant human BMP-7 was absorbed into absorbable collagen sponges and different amounts were implanted either subcutaneously (SC) or intramuscularly (IM) into the backs of rats. Using MRI and MIPAV software, we measured the degree of soft tissue edema at 3 h and at 2, 4, and 7 days postoperatively. After sacrificing rats on day 7 the inflammatory zone and mass were measured and the tissue examined histologically. Soft tissue edema after rhBMP-7 and rhBMP-2 implantation was dose-dependent and peaked at 3 h for the subcutaneous implants and at 2 days for the intramuscular implants. RhBMP-7 was associated with a significantly smaller soft tissue edema volume than was rhBMP-2 only at the highest dose (20 µg/ml). Both rhBMP-2 and rhBMP-7 triggered dose-dependent inflammatory reactions. Compared to rhBMP-2, rhBMP-7 is associated with somewhat smaller soft tissue edema volumes. Although rhBMP-7 is associated with an inflammatory reaction leading to soft tissue edema, at high doses this response is significantly less than that seen with rhBMP-2. Our animal model can be used to test materials that could ameliorate this reaction.

Radiological changes in anterior cervical discectomy and fusion with cage and plate construct: the significance of the anterior spur formation sign.

STUDY DESIGN: Retrospective review. OBJECTIVE: To analyze the changes of fusion process and radiological parameters during the postoperative period after anterior cervical discectomy and fusion with cage and plate construct (ACDF-CPC). SUMMARY OF BACKGROUND DATA: Because of its well-reported efficacy, plate augmentation has been performed to avoid the various complications associated with the cage-alone procedure. The radiological changes at the fusion site after ACDF-CPC have yet to be fully explored. METHODS: Seventy-eight patients (122 fusion sites) who underwent ACDF-CPC were observed at 6 weeks and at 3, 6, 12, and 24 months postoperatively. Fusion status was classified into 3 categories: Type I (pseudoarthrosis), Type II (borderline), and Type III (fusion). Changes at the fusion site were described through radiological parameters at each follow-up time point. In addition, the ability of the radiological parameters to predict fusion rates was analyzed. RESULTS: The fusion process after ACDF-CPC progresses slower when compared with the standard procedure utilizing autograft. Fusion between bone graft chips begins at 6 weeks post surgery. At 3 months, initial bone bridging between graft and host bones begins to form. Anterior spur formation occurs at 3 to 6 months, and "kissing" lesions form at 6 to 12 months. Bony incorporation is achieved at 1 to 2 years. Persistent or newly developed Type I at the 1-year follow-up exhibited significantly higher pseudoarthrosis rates in comparison with rates determined at the 3- and 6-month time points. Among 29 subsidence cases, 9 of the 16 (56.3%) cases that exhibited anterior spur formation eventually achieved fusion, whereas 2 of the 13 (15.4%) cases that did not exhibit anterior spur formation eventually achieved fusion. In cases that demonstrated anterior spur formation, the fusion rate was significantly higher than in cases without it (P = 0.016). CONCLUSION: The fusion process after ACDF-CPC progresses slower than the standard procedure utilizing autograft. Cage subsidence of greater than 2 mm, a radiolucent defect, or a halo sign are poor prognostic signs indicating a high probability for pseudoarthrosis when detected radiographically after 1 year postoperatively. The anterior spur formation sign and "kissing" lesion, on the contrary, represent signs for eventual successful fusion.

Bone morphogenetic protein-binding peptide reduces the inflammatory response to recombinant human bone morphogenetic protein-2 and recombinant human bone morphogenetic protein-7 in a rodent model of soft-tissue inflammation.

BACKGROUND CONTEXT: Bone morphogenetic protein (BMP)-2 and BMP-7 are used to enhance bone formation in spine surgery, but the use of these materials is associated with side effects including inflammation, especially in the soft tissues of the neck. Bone morphogenetic protein-binding peptide (BBP) binds BMP-2 and BMP-7 and imparts a "slow-release" property to collagen carrier. PURPOSE: To test the hypothesis that the addition of BBP will reduce the soft-tissue inflammation induced by the implantation of BMP-2 and BMP-7 on a collagen sponge. STUDY DESIGN/SETTING: Prospective in vivo rodent model of inflammation. METHODS: We implanted six different materials absorbed onto collagen sponges: absorbable collagen sponge (ACS) alone; BBP alone; recombinant human bone morphogenetic protein (rhBMP)-2 alone; rhBMP-2 plus BBP; rhBMP-7 alone; and rhBMP-7 plus BBP. Sponges were implanted bilaterally (subcutaneously [SC] and intramuscularly [IM]) into the backs of rats. Using magnetic resonance imaging, inflammation was assessed in terms of soft-tissue edema volume at 3 hours and at 2, 4, and 7 days. The animal subjects were killed on Day 7, and the dimensions of the inflammatory mass were measured manually in the case of SC tissue and those of the inflammatory zone were determined subsequently by microscopic examination in the case of muscle. RESULTS: Both the SC and the IM soft-tissue edema volumes in the rhBMP-2 plus BBP and the rhBMP-7 plus BBP groups were significantly lower than those observed in the rhBMP-2 alone and rhBMP-7 alone groups. The edema volume associated with BBP alone was greater than that associated with ACS alone but less than that associated with the other treatment groups. The measurements of inflammatory masses and zone yielded similar results. CONCLUSIONS: Bone morphogenetic protein-binding peptide may reduce the inflammatory response associated with the use of rhBMP-2 and rhBMP-7 in a rodent model of inflammation and in a form that has previously been shown to enhance the activity of BMPs. These preliminary studies suggest that BBP may have the potential to be used in the future to improve healing and reduce soft-tissue swelling in surgical applications of BMPs.

Organotypic human spinal cord slice culture as an alternative to direct transplantation of human bone marrow precursor cells for treating spinal cord injury.

OBJECTIVE: To determine the possibility of differentiation of human bone marrow-derived mesenchymal precursor cells (BMDMPCs) into neuronal lineage cells using a human spinal cord organotypic slice coculture technique as an alternative to an in vivo human study. METHODS: Human BMDMPCs were stained with PKH-26 dye before transplantation into 12 human spinal cord slices. In the control group, BMDMPCs were embedded into one spinal cord-free six-well plate containing media. The morphologic differentiation of the transplanted BMDMPCs were observed at 0, 3, 7, and 14 days. Neuroglial differentiation was identified with immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Spherical cells were seen in both groups at day 0. On days 7 and 14, cells developed one or two thick, short processes and typical spindle-shaped cells in the control group and three to five thin, long processes and neuron-like cells in the experimental group. Immunohistochemistry showed double-stained cells with PKH-26 dye (positive) and vimentin (positive), PKH-26 (positive) and neuronal nuclei (NeuN) (positive), and PKH-26 (positive) and glial fibrillary acidic protein (GFAP) (positive) in the experimental group only. RT-PCR showed weak expression of tyrosine kinase A, NeuN, ß-tubulin III, and GFAP in the experimental group. CONCLUSIONS: Organotypic human spinal cord slice culture may be a useful method to verify the neuroglial differentiation of human BMDMPCs as an alternative to a direct human study.

Effects of the bone morphogenetic protein binding protein spp24 (secreted phosphoprotein 24 kD) on the growth of human lung cancer cells.

Bone morphogenetic proteins (BMPs) and transforming growth factor-beta (TGF-ß) contribute to the growth of some skeletal metastases through autocrine stimulation. Secreted phosphoprotein 24 kDa (spp24) has been shown to bind to both BMP-2 and TGF-ß and to markedly inhibit the osteogenic properties of rhBMP-2. We hypothesized that the addition of spp24 would sequester autocrine growth factors (especially BMP-2) and reduce tumor growth in a system (A549 human non-small cell lung cancer cell line) where autocrine stimulation by BMP-2 is known to be important. A549 cells were injected into two sites (subcutaneous and intraosseus) in SCID mice with and without the co-injection of BMP-2 and spp24. Tumor growth after 8 weeks was assessed through gross examination, radiological imaging, and histological analysis. Spp24 attenuated the tumor growth enhancing effects of rhBMP-2 and reduced the tumor growth when added to tumor cells that were not treated with BMP-2. We conclude that spp24 can reduce A549 cell tumor growth in both soft tissue and intraosseus environments. We hypothesize that the mechanism for this inhibition is interruption of autocrine stimulation through the sequestration of BMP-2. Spp24 can be developed into a therapeutic agent that can be employed in clinical situations where the inhibitions of BMPs and related proteins is advantageous.

Effect of sagittal alignment on kinematic changes and degree of disc degeneration in the lumbar spine: an analysis using positional MRI.

STUDY DESIGN: Retrospective analysis using positional MRI. OBJECTIVE: To determine the effects of total sagittal lordosis on spinal kinematics and degree of disc degeneration in the lumbar spine. SUMMARY OF BACKGROUND DATA: Changes in sagittal lordosis alter the load on the spine and may affect spinal mobility. There is increasing recognition of the clinical impact that sagittal alignment has on back pain, especially its possible role in accelerating adjacent segment degeneration after spinal fusion. However, its relationship to segmental mobility and degeneration of the lumbar spine has yet to be determined. METHODS: Four hundred and thirty patients who had low back pain with or without leg pain (241 males and 189 females) with a mean age of 42.98 years (range, 16-85 years) were included. Total sagittal lordosis (T12-S1) was divided into three groups; Group A: Straight or Kyphosis (<20°, n = 84), Group B: Normal lordosis (20-50°, n = 294), and Group C: Hyperlordosis (>50°, n = 52). The degree of disc degeneration was graded using midsagittal T2-weighted MR images. Segmental mobility, including translational motion and angular variation, was measured using positional MRI. Their relationship with total segmental lordosis was identified. RESULTS: When compared with group B, the segmental motion in group C tended to be lower at the border of lordosis and higher at the apex of lordosis, with a significant difference in angular motion at L2-L3. The contrary finding was identified in group A, which had a higher segmental motion at border segments and lower motion at apical segments of lordosis, with significant difference of translational motion at L3-L4 and angular motion at L1-L2. Apical segments contributed more, whereas border segments contributed less to the total angular mobility in more lordotic spines. The opposite was seen in more kyphotic spines. Disc degeneration tended to be greater at all levels in group C, and at L1-L2 and L5-S1 in group A. CONCLUSION: Changes in sagittal alignment may lead to kinematic changes in the lumbar spine. This may subsequently influence load bearing and the distribution of disc degeneration at each level. Sagittal alignment, disc degeneration, and segmental mobility likely have a reciprocal influence on one another.

Inflammatory characteristics of rhBMP-2 in vitro and in an in vivo rodent model.

STUDY DESIGN: In vivo and in vitro model. OBJECTIVE: Investigate soft-tissue inflammation caused by rhBMP-2. SUMMARY OF BACKGROUND DATA: Although rhBMP-2 produces excellent rates of fusion in the spine, dysphagia and respiratory compromise have occurred when used in the neck. The mechanism of the swelling and inflammatory response has yet to be fully elucidated. METHODS: ELISA kits (IL-6, IL-10, TNF-α) were used to measure cytokine levels at different concentrations of rhBMP-2. Absorbable collagen sponges were implanted with or without different concentrations of rhBMP-2 into the backs of rats subcutaneously (SC) and intramuscularly (IM). Magnetic resonance imaging was used to measure inflammation at 3 hours and 2, 4, and 7 days. The inflammatory volumes were measured and compared using MIPAV software. Rats were killed after 7 days and studied. RESULTS: IL-6, IL-10, and TNF-α release was dose-dependent. Soft-tissue edema after rhBMP-2 implantation was also dose-dependent, peaking at 3 hours SC, after SC and IM implantations, and on day 2 IM after IM implantation. All formed a granuloma-type mass after SC insertion. The mass was much larger in the 10 and 20 µg/10 µL (high-concentration) groups. The inflammatory response did not diffuse across physiologic barriers (subcutaneous fascia). Both high-dose groups were associated with encapsulated hematomas and a significant increase in the inflammatory zone. CONCLUSION: Swelling and inflammation after rhBMP-2 use are dose-dependent. Swelling may be due to direct contact as well as spread in the plane of access. The causes are a robust inflammatory reaction as well as sterile seroma and encapsulated hematoma formation.

The relationship between degree of facet tropism and amount of dynamic disc bulge in lumbar spine of patients symptomatic for low back pain.

Facet tropism has been investigated as a predisposing factor for degenerative changes in the lumbar spine; however, no prior study has evaluated the relationship between disc bulge and facet tropism. In this study, we used kinetic magnetic resonance imaging (kMRI) to investigate the association between degree of facet tropism and amount of disc bulge in the lumbar spine in relation to age. kMRIs in the flexion, neutral, and extension positions were performed on 410 consecutive patients with low back pain. T2-weighted midsagittal and axial mid-disc cuts were analyzed to measure disc bulge and facet angle. Facet asymmetry was calculated and classified as: no facet tropism, <6°; mild facet tropism, 6-11°; or severe facet tropism, ≥11°. Maximal static bulge (MSB), maximal dynamic bulge (MDB), and age in the facet tropism groups were compared by age subpopulations and MDB categories, defined by the positions between which the largest change in disc bulge occurs. We found the severe facet tropism group to be associated with a nearly significant increase in MSB and MDB over the no facet tropism group in the older subpopulation at the L4-L5 level only, and a larger MDB in the L4-L5 MDB category [E-N], where the greatest change in disc bulge occurs between neutral and extension positions (p = 0.013). Our findings suggest that severe facet tropism is associated with increased disc bulge at L4-L5 in only a subset of older age patients, but may in large part be due to biomechanical factors that define the [E-N] category.

Kinematic Evaluation of Association between Disc Bulge Migration, Lumbar Segmental Mobility, and Disc Degeneration in the Lumbar Spine Using Positional Magnetic Resonance Imaging.

Degenerative disc disease and disc bulge in the lumbar spine are common sources of lower back pain. Little is known regarding disc bulge migration and lumbar segmental mobility as the lumbar spine moves from flexion to extension. In this study, 329 symptomatic (low back pain with or without neurological symptoms) patients with an average age of 43.5 years with varying degrees of disc degeneration were examined to characterize the kinematics of the lumbar intervertebral discs through flexion, neutral, and extension weight-bearing positions. In this population, disc bulge migration associated with dynamic motion of the lumbar spine significantly increased with increased grade of disk degeneration. Although no obvious trends relating the migration of disc bulge and angular segmental mobility were seen, translational segmental mobility tended to increase with disc bulge migration in all of the degenerative disc states. It appears that many factors, both static (intervertebral disc degeneration or disc height) and dynamic (lumbar segmental mobility), affect the mechanisms of lumbar disc bulge migration.

The effect of needle size inducing degeneration in the rat caudal disc: evaluation using radiograph, magnetic resonance imaging, histology, and immunohistochemistry.

BACKGROUND CONTEXT: The rat caudal disc has been increasingly used in studying of disc degeneration because of its simplicity, low cost, and efficiency. However, the reproducibility and standardization are essential to facilitate the investigations of biologic therapeutics at different stages of degeneration. PURPOSE: To identify the effect of different needle gauges to the degenerative response in rat caudal discs and to examine its pathogenesis by looking at the cellular and matrix changes. STUDY DESIGN: In vivo study of injury-induced rat caudal disc degeneration using needle puncture. PATIENT SAMPLE: Thirty-six Lewis rats aged 12-14 weeks. OUTCOME MEASURES: The induced degenerative discs were analyzed by plain radiograph, magnetic resonance imaging (MRI) and histological examination. Proteoglycan content was assessed by alcian blue stain. Immunohistochemistry using aggrecan, collagen II, and Sox-9 was also evaluated to investigate cell differentiation and matrix changes. METHODS: All rats were divided into three groups according to different needle gauges (18G, 20G, and 22G). Caudal discs were punctured percutaneously under image guidance. Radiographs and MRI were obtained at 2 weeks interval until 8 weeks. At each time point, three rats from each group were sacrificed for histological analysis and immunohistochemistry. RESULTS: Larger needle gauges, especially 18G, produced more deterioration of the disc when compared with smaller sizes, particularly with time. Significant differences were identified in almost all parameters compared between 18G and 22G at the 8-week time point. For the effect of time in the same needle size, the differences occurred between 2- or 4-week and 8-week time point in the 18G and 20G groups. The proteoglycan and aggrecan stain gradually decreased over time. Chondrogenic differentiation was identified within the degenerative disc by detecting Sox-9 positive cells and collagen II accumulation increased as degeneration progressed. CONCLUSIONS: The puncture-induced degenerative changes in rat caudal discs can imitate the human degenerative cascade as observed in plain radiograph, MRI, histology, and immunohistochemistry. We suggest that needle size affects the occurrence of progression of degeneration; thus, the large needle size was required to accelerate the deterioration. The size of needle and time point after injury should be considered when investigating the effect of therapeutic materials to retard degeneration or regenerate the intervertebral disc.

MRI classification of interspinous ligament degeneration of the lumbar spine: intraobserver and interobserver reliability and the frequency of disagreement.

Posterior spinal ligament pathology is becoming increasingly recognized as a significant cause of low back pain. Despite the growing clinical importance of interspinous ligament degeneration in low back pain patients, formal reliability studies for the magnetic resonance imaging (MRI) evaluation of interspinous ligaments have not been performed. We proposed an MRI classification system for interspinous ligament degeneration and conducted a comprehensive reliability and reproducibility assessment. Fifty patients who had low back pain with or without leg discomfort (26 males and 24 females) with a mean age of 48.8 years (range 23-85 years) were studied. The classification for lumbar interspinous ligament degeneration was developed on the basis of the literature using mid-sagittal T1- and T2-weighted images. Three spine surgeons independently graded a total of 200 interspinous ligament levels. Intraobserver and interobserver reliability were assessed by kappa statistics. The frequency of disagreement was also identified. The intraobserver agreement was excellent in all readers (kappa range 0.840-0.901). The interobserver agreement was lower as expected, and was substantial to excellent (kappa range 0.726-0.818). Overall complete agreement was obtained in 87.8% of all interspinous ligament levels. A difference of 1, 2, and 3 grades occurred in 8.1, 3.0, and 1.1% of readings, respectively. This proposed MRI classification of interspinous ligament degeneration was simple, reliable, and reproducible. Its use as a standardized nomenclature in clinical and radiographic research may be recommended.

Magnetic resonance imaging grading of interspinous ligament degeneration of the lumbar spine and its relation to aging, spinal degeneration, and segmental motion.

OBJECT: Degenerative changes of the interspinous ligaments (ISLs) have generally been ignored in previous studies. Factor-related causes, the effects that these changes have on other structures within the spinal functional unit, and their relation to kinematic changes in the spine are lacking. In this study, the authors evaluated the reliability of a proposed MR imaging grading system of ISL degeneration (ISLD). They also investigated the relationship between ISLD and aging, disc/facet joint degeneration, and lumbar segmental motion. METHODS: The authors studied 256 lumbar motion segments from L-2 to S-1 in 64 patients (35 men and 29 women) with a mean age of 46.08 years (range 23­85 years). An MR imaging­based grading system for ISLD was developed and ranged from Grade A (mild) to Grade D (severe). The reliability was tested, and the correlation of the grade with the severity of the disc and facet joint degeneration was examined. The segmental motion of each functional unit was measured using flexion/extension MR imaging, and their relationships with ISL grades were identified. RESULTS: Grade A was observed in 115 levels (44.9%), Grade B in 105 (41.0%), Grade C in 15 (5.9%), and Grade D in 21 levels (8.2%). The kappa coefficients for intraobserver and interobserver agreements were substantial to excellent (intraobserver [0.871] and interobserver [0.721­0.807]). Grade D was observed primarily in elderly patients. Segmental motion tended to decrease in the most severe grade, with a significant difference in angular mobility. As the severity of ISLD increased, the severity of disc/facet joint degeneration increased (p < 0.001 and p < 0.05, respectively). CONCLUSIONS: The authors proposed a reliable and reproducible grading system that may be used to investigate spinal kinematics in association with ISLD. The authors' findings illustrated the distribution of ISLD grades. The most severe grade occurred primarily in elderly patients. Mobility decreased in the most severe grade; therefore, the stage of ISLD should be taken into consideration when evaluating spinal stability.

Bone morphogenetic protein binding peptide mechanism and enhancement of osteogenic protein-1 induced bone healing.

STUDY DESIGN: In vitro and in vivo evaluation of BBP interactions with BMP. OBJECTIVE: To explore bone morphogenetic protein-binding peptide (BBP)'s mechanism of action, investigate an extended repertoire for BBP applications, and evaluate the usefulness of BBP as a surgical adjuvant when used with recombinant human osteogenic protein-1 (rhOP-1). SUMMARY OF BACKGROUND DATA: Bone morphogenetic proteins (BMPs) are osteoinductive proteins that provide a potential alternative to autograft. Their utility is limited by cost, and potential dose-dependent risks, such as local inflammatory reactions and ectopic bone formation. BBP, a cyclized synthetic peptide, avidly binds recombinant human BMP-2(rhBMP-2) and has been shown to accelerate and enhance its osteogenic qualities. METHODS: BBP binding with 4 growth factors from the transforming growth factor -beta family were assessed using surface plasmon resonance. The in vivo retention of rhBMP-2 was quantified by comparing the percentage of retained [¹²5I]-labeled rhBMP-2 in absorbable collagen sponge implants with or without BBP at 1, 3, and 7 days postimplantation. The adjunctive effect of BBP with rhOP-1-induced bone growth was evaluated by comparing time to fusion and fusion rates in a rodent posterolateral fusion model with 2 different doses of rhOP-1 with or without BBP. RESULTS: BBP bound all 4 growth factors with an intermediate affinity. The in vivo retention of rhBMP-2 alone ranged from about 40% on day 1 to about 30% on day 7, whereas, the retention of rhBMP-2 in the presence of BBP was about 85% on day 1 and about 55% on day 7. The addition of BBP to rhOP-1 resulted in significantly earlier and greater fusion rates than achieved with rhOP-1 alone. CONCLUSION: The mechanism of the BBP enhanced osteoinductive properties of BMPs involves the binding and retention of the growth factor, resulting in a prolonged exposure of BMP to the desired fusion site. The use of BBP in conjunction with BMPs may prove to provide satisfactory fusion outcomes, while reducing the costs and side effects associated with BMP use.