The outcome of total elbow arthroplasty in juvenile idiopathic arthritis (juvenile rheumatoid arthritis) patients.

BACKGROUND: Elbow prosthetic replacement in patients with juvenile idiopathic arthritis (JIA) can be complicated and technically challenging. Thus, we sought to evaluate the clinical benefit and the prosthetic longevity of primary semiconstrained linked total elbow arthroplasty (TEA) performed to treat these patients. METHODS: Between 1983 and 2005, 29 elbows in 24 patients (20 women and 4 men) had been replaced because of JIA. The mean age was 37 years (range, 24-68 years). Because of underlying deformity, the implant contour was modified for 9 elbows (31%) and a customized implant was inserted in 5 elbows (17%). The mean follow-up duration was 10.5 years (range, 4.6-20.1 years). RESULTS: During the follow-up period, 8 elbows underwent reoperation, including 6 (21%) that underwent implant revision. At most recent follow-up, 22 elbows (76%) subjectively had a satisfactory overall functional result. The mean Mayo Elbow Performance Score was 78 points (range, 50-100 points), with 18 elbows graded as having an excellent or good result. Compared with preoperative range of motion, the mean extension-flexion arc improved from 65° ± 44° to 89° ± 35° (P = .01), mean flexion improved from 113° ± 23° to 126° ± 26° (P = .02), and mean extension improved from 48° ± 25° to 37° ± 26° (P = .08). By use of the Kaplan-Meier survivorship method, the rate of TEA survival from any revision was 96.4% (95% confidence interval, 89.8%-100%) and 79.9% (95% confidence interval, 65.1%-97.5%) at 5 years and 10 years, respectively. CONCLUSION: Primary TEA for JIA patients is technically challenging and frequently requires implant modification or custom designs. These patients might have high complication and revision rates. However, most benefit from the intervention for a long term.

Anatomic shoulder arthroplasty for treatment of proximal humerus malunions.

BACKGROUND: Malunion of proximal humeral fractures complicated by damage to the glenohumeral cartilage and injury to the joint capsule and rotator cuff can include treatment requiring anatomic shoulder arthroplasty. This study defines results and complications of this procedure and identifies factors associated with success or failure. METHODS: From 1976 to 2007, 109 patients underwent shoulder arthroplasty for proximal humerus malunions. Ninety-five met the criteria for analysis with a mean follow-up period of 9.2 years. Fracture types according to the Neer classification were two part in 20, three part in 37, four part in 31, and head splitting in 2, with 16 fracture-dislocations. Hemiarthroplasty was performed in 45 patients, with 50 undergoing total arthroplasty. RESULTS: Pain scores improved from 7.8 to 3.1 (P < .001). The mean active elevation and external rotation improved from 69° to 109° and from 8° and 39°, respectively (P = .001). Of 31 patients with available radiographs, 20 had healed tuberosity osteotomies. Sixteen complications required 10 reoperations, including 6 of 9 patients with severe postoperative instability. There were 57 excellent or satisfactory results by use of the Neer rating. No patient, injury pattern, previous treatment, surgical, or radiologic variation was significantly associated with an increased risk of an unsatisfactory result, except for severe postoperative instability. Kaplan-Meier survivorship for reoperation, in 109 shoulders, was 94.8% (95% confidence interval, 90.5%-99.4%) at 5 years and 90.1% (95% confidence interval, 83.6%-97.1%) at 10 and 15 years. CONCLUSION: Anatomic shoulder arthroplasty improves pain and motion. Surgery is complex. Tuberosity osteotomies often heal. Postoperative instability is the most common complication leading to reoperation and is usually associated with rotator cuff and shoulder capsule injury.

Screw orientation and plate type (variable- vs. fixed-angle) effect strength of fixation for in vitro biomechanical testing of the Synthes CSLP.

BACKGROUND CONTEXT: Two common justifications for orienting cervical screws in an angled direction are to increase pullout strength and to allow use of longer screws. This concept is widely taught and has guided implant design. Fixed- versus variable-angle systems may offer strength advantages. Despite these teachings, there is a paucity of supporting biomechanical evidence. The purpose of our study is to test the influence of screw orientation and plate design on the maximum screw pullout force. PURPOSE: This study evaluates the effect of screw orientation and plate type (fixed- vs. variable-angle) on screw pullout strength. STUDY DESIGN: Anterior cervical plates of both a fixed- and variable-angle CSLP, were tested for peak pullout strength in a direct plate pullout model using polyurethane foam bone, which models osteoporotic bone. METHODS: Self-tapping, locking screws (4.0x14mm and 4.0x16mm) were used. Screws were oriented in the fixed-angle plate in the standard fashion. In the variable plate, screws were instrumented in three different orientations. Biomechanical testing was performed on an Instron DynaMight 8841 servohydraulic testing machine, measuring maximum pullout force under a displacement-controlled pullout rate of 1mm/min. Five samples were tested per group. RESULTS: When all screws were placed 90 degrees to the plate, there was a significantly increased peak pullout strength (412.8+/-22.2N) compared with when all screws were placed 12 degrees "up and in" (376.2+/-24.3N, p less than or equal to .03). When the 90 degrees construct was reproduced using 14-mm screws and compared with 16-mm screws oriented 12 degrees "all up and in," there was still significantly higher pullout strength with the all 90 degrees construct (434.2+/-28.7N vs. 376.2+/-24.3N, p less than or equal to .009). The fixed-angle plate had a significantly decreased peak pullout strength (288.2+/-15.7N) compared with the variable-angle plate (416.6+/-12.6N) (p less than .00001) when the screws were placed in the same orientation. Overall, the variable-angle plate, regardless of the orientation of screws, had a significantly greater pullout strength than the fixed-angle plate (p less than .001). CONCLUSIONS: In this system, a variable-angle plate has greater pullout strength than a fixed-angle plate, regardless of the orientation of screws. With the variable-angle plate, a construct of all screws 12 degrees "up and in" is the weakest configuration. We found that with the 90 degrees construct, both 16- and 14-mm screws performed significantly better than 16-mm convergent screws. These findings are remarkable because they contradict the current doctrine. This may be a function of plate-dependent factors and should not be applied universally to all plate systems. Further study of screw orientation in additional plating systems is warranted.

Unconstrained shoulder arthroplasty for treatment of proximal humeral nonunions.

BACKGROUND: Unconstrained shoulder arthroplasty is one of several methods for treatment of proximal humeral fracture nonunions. The goal of this study was to define the results and complications of this procedure. METHODS: From 1976 to 2007, sixty-seven patients underwent unconstrained shoulder arthroplasty for proximal humeral nonunion and were followed for more than two years. There were forty-nine women and eighteen men with a mean age of sixty-four years and a mean duration of follow-up of nine years (range, two to thirty years). The fracture type according to the Neer classification was two-part in thirty-six patients, three-part in sixteen, and four-part in fifteen. Hemiarthroplasty was performed in fifty-four patients and total shoulder arthroplasty was done in the remaining thirteen. RESULTS: There were thirty-three excellent or satisfactory results according to the modified Neer rating. Tuberosity healing about the prosthesis occurred in thirty-five shoulders. The mean pain score improved from 8.3 preoperatively to 4.1 at the time of follow-up (p < 0.001). The average active shoulder elevation and external rotation improved from 46° and 26° to 104° and 50° (p < 0.001). Shoulders with anatomic or nearly anatomic healing of the tuberosities had greater active elevation at the time of final follow-up (p = 0.02). There were fourteen complications in twelve patients, with twelve reoperations including five revisions. Kaplan-Meier survivorship with revision as the end point was 97% (95% confidence interval [CI]: 94.3, 100) at one year and 93% (95% CI: 88.0, 99.2) at five, ten, and twenty years. CONCLUSIONS: Shoulder arthroplasty decreases pain and improves function in patients with a proximal humeral nonunion. However, the overall results are satisfactory in less than half of the patients. Tuberosity healing is inconsistent and influences the functional outcome.

Bone marrow-derived matrix metalloproteinase-9 is associated with fibrous adhesion formation after murine flexor tendon injury.

The pathogenesis of adhesions following primary tendon repair is poorly understood, but is thought to involve dysregulation of matrix metalloproteinases (Mmps). We have previously demonstrated that Mmp9 gene expression is increased during the inflammatory phase following murine flexor digitorum (FDL) tendon repair in association with increased adhesions. To further investigate the role of Mmp9, the cellular, molecular, and biomechanical features of healing were examined in WT and Mmp9(-/-) mice using the FDL tendon repair model. Adhesions persisted in WT, but were reduced in Mmp9(-/-) mice by 21 days without any decrease in strength. Deletion of Mmp9 resulted in accelerated expression of neo-tendon associated genes, Gdf5 and Smad8, and delayed expression of collagen I and collagen III. Furthermore, WT bone marrow cells (GFP(+)) migrated specifically to the tendon repair site. Transplanting myeloablated Mmp9(-/-) mice with WT marrow cells resulted in greater adhesions than observed in Mmp9(-/-) mice and similar to those seen in WT mice. These studies show that Mmp9 is primarily derived from bone marrow cells that migrate to the repair site, and mediates adhesion formation in injured tendons. Mmp9 is a potential target to limit adhesion formation in tendon healing.

Teriparatide therapy and beta-tricalcium phosphate enhance scaffold reconstruction of mouse femoral defects.

To investigate the efficacy of endocrine parathyroid hormone treatment on tissue-engineered bone regeneration, massive femoral defects in C57Bl/6 mice were reconstructed with either 100:0 or 85:15 poly-lactic acid (PLA)/beta-tricalcium phosphate (ß-TCP) scaffolds (hereafter PLA or PLA/ßTCP, respectively), which were fabricated with low porosity (<30%) to improve their structural rigidity. Experimental mice were treated starting at 1 week postop with daily subcutaneous injections of 40 µg/kg teriparatide until sacrifice at 9 weeks, whereas control mice underwent the same procedure but were injected with sterile saline. Bone regeneration was assessed longitudinally using planar X-ray and quantitative microcomputed tomography, and the reconstructed femurs were evaluated at 9 weeks either histologically or biomechanically to determine their torsional strength and rigidity. Teriparatide treatment increased bone volume and bone mineral content significantly at 6 weeks and led to enhanced trabeculated bone callus formation that appeared to surround and integrate with the scaffold, thereby establishing union by bridging bone regeneration across the segmental defect in 30% of the reconstructed femurs, regardless of the scaffold type. However, the bone volume and mineral content in the PLA reconstructed femurs treated with teriparatide was reduced at 9 weeks to control levels, but remained significantly increased in the PLA/ßTCP scaffolds. Further, bridged teriparatide-treated femurs demonstrated a prototypical brittle bone torsion behavior, and were significantly stronger and stiffer than control specimens or treated specimens that failed to form bridging bone union. Taken together, these observations suggest that intermittent, systemic parathyroid hormone treatment can enhance bone regeneration in scaffold-reconstructed femoral defects, which can be further enhanced by mineralized (ßTCP) particles within the scaffold.

Evaluation of dense polylactic acid/beta-tricalcium phosphate scaffolds for bone tissue engineering.

Advances in biomaterial fabrication have introduced numerous innovations in designing scaffolds for bone tissue engineering. Often, the focus has been on fabricating scaffolds with high and interconnected porosity that would allow for cellular seeding and tissue ingrowth. However, such scaffolds typically lack the mechanical strength to sustain in vivo ambulatory stresses in models of load bearing cortical bone reconstruction. In this study, we investigated the microstructural and mechanical properties of dense PLA and PLA/beta-TCP (85:15) scaffolds fabricated using a rapid volume expansion phase separation technique, which embeds uncoated beta-TCP particles within the porous polymer. PLA scaffolds had a volumetric porosity in the range of 30 to 40%. With the embedding of beta-TCP mineral particles, the porosity of the scaffolds was reduced in half, whereas the ultimate compressive and torsional strength were significantly increased. We also investigated the properties of the scaffolds as delivery vehicles for growth factors in vitro and in vivo. The low-surface porosity resulted in sub optimal retention efficiency of the growth factors, and burst release kinetics reflecting surface coating rather than volumetric entrapment, regardless of the scaffold used. When loaded with BMP2 and VEGF and implanted in the quadriceps muscle, PLA/beta-TCP scaffolds did not induce ectopic mineralization but induced a significant 1.8-fold increase in neo vessel formation. In conclusion, dense PLA/beta-TCP scaffolds can be engineered with enhanced mechanical properties and potentially be exploited for localized therapeutic factor delivery.

Remodeling of murine intrasynovial tendon adhesions following injury: MMP and neotendon gene expression.

Tendon injury frequently results in the formation of adhesions that reduce joint range of motion. To study the cellular, molecular, and biomechanical events involved in intrasynovial tendon healing and adhesion formation, we developed a murine flexor tendon healing model in which the flexor digitorum longus (FDL) tendon of C57BL/6 mice was transected and repaired using suture. This model was used to test the hypothesis that murine flexor tendons heal with differential expression of matrix metalloproteases (MMPs), resulting in the formation of scar tissue as well as the subsequent remodeling of scar and adhesions. Healing tendons were evaluated by histology, gene expression via real-time RT-PCR, and in situ hybridization, as well as biomechanical testing to assess the metatarsophalangeal (MTP) joint flexion range of motion (ROM) and the tensile failure properties. Tendons healed with a highly disorganized fibroblastic tissue response that was progressively remodeled through day 35 resulting in a more organized pattern of collagen fibers. Initial repair involved elevated levels of Mmp-9 at day 7, which is associated with catabolism of damaged collagen fibers. High levels of Col3 are consistent with scar tissue, and gradually transition to the expression of Col1. Scleraxis expression peaked at day 7, but the expression was limited to the original tendon adjacent to the injury site, and no expression was present in granulation tissue involved in the repair response. The MTP joint ROM with standardized force on the tendon was decreased on days 14 and 21 compared to day 0, indicating the presence of adhesions. Peak expressions of Mmp-2 and Mmp-14 were observed at day 21, associated with tendon remodeling. At day 28, two genes associated with neotendon formation, Smad8 and Gdf-5, were elevated and an improvement in MTP ROM occurred. Tensile strength of the tendon progressively increased, but by 63 days the repaired tendons had not reached the tensile strength of normal tendon. The murine model of primary tendon repair, described here, provides a novel mechanism to study the tendon healing process, and further enhances the understanding of this process at the molecular, cellular, and biomechanical level.

Erythropoietin accelerates functional recovery after peripheral nerve injury.

BACKGROUND: Erythropoietin is a naturally occurring hormone with multiple effects on a number of different cell types. Recent data have suggested neuroprotective and perhaps even neurotrophic roles for erythropoietin. We hypothesized that these functional effects could be demonstrable in standard models of peripheral nerve injury. METHODS: Experiments were undertaken to evaluate the effect of erythropoietin on the previously reported standard course of healing of sciatic injuries in mice. The injury groups included mice that were subjected to (1) sham surgery, (2) a calibrated sciatic crush injury, (3) transection of the sciatic nerve followed by epineural repair, or (4) a transection followed by burial of the proximal stump in the adjacent muscle tissue (neurectomy). Either erythropoietin or saline solution was administered to the mice in each of these experimental groups twenty-four hours preinjury, immediately after surgical creation of the injury, twenty-four hours postinjury, or one week postinjury. All mice were evaluated on the basis of the published model for recovery of sciatic nerve motor function by measuring footprint parameters at specific times after the injury. Immunohistochemistry was also performed to assess the erythropoietin-receptor expression profile at the site of injury. RESULTS: In general, the mice treated with erythropoietin recovered sciatic nerve motor function significantly faster than did the untreated controls. This conclusion was based on a sciatic function index that was 60% better in the erythropoietin-treated mice at seven days postinjury (p < 0.05). Although the group that had been given the erythropoietin immediately postinjury showed the best enhancement of recovery, the timing of the administration of the drug was not critical. Histological analysis demonstrated enhanced erythropoietin-receptor positivity in the nerves that recovered fastest, suggesting that accelerated healing correlates with expression of the receptor in nerve tissue. CONCLUSIONS: Erythropoietin treatment of an acute sciatic nerve crush injury leads to an effect consistent with functional neuroprotection. This protective effect may have clinical relevance, especially since it was detectable even when erythropoietin had been administered up to one week after injury.

Adhesions in a murine flexor tendon graft model: autograft versus allograft reconstruction.

Reconstruction of flexor tendons often results in adhesions that compromise joint flexion. Little is known about the factors involved in the formation of flexor tendon graft adhesions. In this study, we developed and characterized a novel mouse model of flexor digitorum longus (FDL) tendon reconstruction with live autografts or reconstituted freeze-dried allografts. Grafted tendons were evaluated at multiple time points up to 84 days post-reconstruction. To assess the flexion range of the metatarsophalangeal joint, we developed a quantitative outcome measure proportional to the resistance to tendon gliding due to adhesions, which we termed the Gliding Coefficient. At 14 days post-grafting, the Gliding Coefficient was 29- and 26-fold greater than normal FDL tendon for both autografts and allografts, respectively (p < 0.001), and subsequently doubled for 28-day autografts. Interestingly, there were no significant differences in maximum tensile force or stiffness between live autograft and freeze-dried allograft repairs over time. Histologically, autograft healing was characterized by extensive remodeling and exuberant scarring around both the ends and the body of the graft, whereas allograft scarring was abundant only near the graft-host junctions. Gene expression of GDF-5 and VEGF were significantly increased in 28-day autografts compared to allografts and to normal tendons. These results suggest that the biomechanical advantages for tendon reconstruction using live autografts over devitalized allografts are minimal. This mouse model can be useful in elucidating the molecular mechanisms in tendon repair and can aid in preliminary screening of molecular treatments of flexor tendon adhesions.

Screw pull-out force is dependent on screw orientation in an anterior cervical plate construct.

Two common justifications for orienting cervical screws in an angled direction is to increase pull-out strength and to allow use of longer screws. This concept is widely taught and has guided implant design. Fixed versus variable angle systems may offer strength advantages. The purpose of our study is to test the influence of screw orientation and plate design on the maximum screw pull-out load. Variable and fixed angle 4.0 x 15 mm and 4.0 x 13 mm self-tapping screws were used to affix a Medtronic Atlantis cervical plate to polyurethane foam bone samples (density 0.160/cm). This synthetic product is a model of osteoporotic cancellous bone. The fixed angle screws can only be placed at 12 degrees convergent to the midline and 12 degrees in the cephalad/caudal ("12 degrees up and in") direction. Three groups were tested: (1) all fixed angle screws, (2) variable angle, all screws 12 degrees up and in, (3) variable angle, all screws 90 degrees to the plate. Plate constructs were pulled off with an Instron DynaMight 8841 servohydrolic machine measuring for maximum screw pull-out force. There was no difference between group 1, fixed angle (288.4 +/- 37.7 N) (mean +/- SD) and 2, variable angle group (297.7 +/- 41.31 N P< or =0.73). There was a significant increase in maximum pull-out force to failure for the construct with all screws at 90 degrees (415.2+/-17.4 N) compared with all screws 12 degrees "up and in" (297.4 +/- 41.3 N, P< or =0.0016). Group 3 done with 13 mm screws, showed a trend toward better pull-out strength, compared to group 2 w/15 mm screws (345.2 +/- 20.5 vs. 297.4 +/- 41.3, P< or =0.06). In this plate pull-out model, screw orientation influences maximum force to failure. When all 4 screws are 90 degrees to the plate the construct has the greatest ability to resist pullout. Fixed angle designs show no advantage over variable angle. These findings are contrary to current teaching.

Biomechanical analysis of in situ single versus double screw fixation in a nonreduced slipped capital femoral epiphysis model.

Slipped capital femoral epiphyses (SCFE) were created in 24 pairs of immature bovine femurs. In 17 pairs of femurs, the slip was left nonreduced (one-third diameter of physis), and in 7 pairs, the slip was reduced. Stabilization of the slips was with either 1 or 2 threaded 6.5-mm screws in a compression mode. The specimens were subjected to shear or torsional loading forces to failure, with the goal of trying to reproduce clinical conditions of in situ screw fixation for acute or unstable SCFE. In the nonreduced model, double-screw fixation was 312% stiffer than single-screw fixation under torsional loading. In the reduced model, double-screw fixation was 137% stiffer than single-screw fixation under torsional loading. The increased rotational stability of double-screw fixation under torsional loading conditions may justify its use in in situ stabilization of acute or unstable SCFE.