AGN1 implant material to treat bone loss: Resorbable implant forms normal bone with and without alendronate in a canine critical size humeral defect model.

BACKGROUND: Fractures secondary to osteoporosis, particularly those of the hip and spine, are a major public health concern with high social and economic costs. The Local Osteo-Enhancement Procedure (LOEP) is an approach intended to strengthen skeletal areas that are at the highest risk for fracture due to osteoporosis. LOEP involves the implantation of AGN1, a triphasic, calcium-based, osteoconductive material which is then resorbed and replaced by bone. Since alendronate is the most prescribed osteoporotic treatment, the purpose of this canine study is to determine if the newly formed bone has the same properties as normal bone and whether alendronate treatment impacts AGN1 resorption and replacement with bone. METHODS: Sixty skeletally mature male hounds (24-38 kg) were evenly divided between alendronate (0.2 mg/kg/day) and non-alendronate treatment groups. A critical-size core bone defect created in one proximal humerus was implanted with AGN1 while the contralateral non-operated humerus served as a paired control in each animal. Animals were sacrificed 13, 26, and 52 weeks post-operatively (10 per treatment per timepoint). The control and treatment site bone specimens from each animal were examined using radiographic, histomorphometric, and biomechanical techniques. Results between alendronate-treated and non-alendronate-treated animals were compared as groups. RESULTS: AGN1 implant material was consistently resorbed and replaced by bone in all animals. At 52 weeks, only minimal residual implant material could be detected (0.9 ± 2.3% non-alendronate group; 2.2 ± 3.1% alendronate group), and new bone filled the defects in both the non-alendronate and alendronate groups. At 13 and 26 weeks, microCT revealed the newly formed bone in the defects had significantly higher trabecular bone volume and number connectivity than control bone in both groups. Mechanical testing demonstrated that the new bone had ultimate compressive strength and modulus equivalent to control bone as early as 13 weeks post-surgery which was maintained to 52 weeks in both groups. CONCLUSIONS: In this canine critical-sized humeral core defect model, AGN1 was progressively replaced by normal bone as evaluated by all outcome measures. Concurrent alendronate therapy did not significantly impact AGN1 resorption or new bone formation. These results demonstrate that AGN1 can be used in conjunction with alendronate in non-osteoporotic animals. CLINICAL RELEVANCE: This study suggests that the AGN1 implant material demonstrates potential for local restoration of bone in critical-size core defects, and that the material is compatible with alendronate drug therapy. Further studies will be required to determine if these results apply to other osteoporosis medications.

Clinical Outcomes After Microfracture of the Knee: Midterm Follow-up.

BACKGROUND: Microfracture is a single-stage arthroscopic procedure used to treat small- and medium-sized cartilage defects, the clinical results of which have been mixed to date. PURPOSE: To retrospectively evaluate prospectively collected patient-reported outcomes (PROs) after microfracture as well as to determine patient-related and defect-related factors associated with clinical outcomes and which factors predict the need for additional surgery. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: All patients between the ages of 10 and 70 years who underwent microfracture by the senior author for a focal chondral defect of the knee between January 1, 2005, and March 1, 2010, were eligible for study enrollment. Patients were excluded if they underwent concomitant procedures that violated the subchondral bone. Functional outcomes were determined using preoperative and final follow-up PROs, including the Lysholm, International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short Form-12 (SF-12), and overall satisfaction scores. Patient-related factors (sex, age, body mass index [BMI]) and defect-related factors (lesion size, location, concomitant procedures, prior procedures) were analyzed for correlations with outcome scores. All patient-related and defect-related factors were also analyzed as predictors for subsequent surgery. RESULTS: Overall, 101 patients (102 knees; 55 male, 46 female; mean age, 35.87 ± 12.52 years; mean BMI, 26.3 ± 5.5 kg/m2; mean defect size, 2.635 ± 1.805 cm2) were included. Lesion location included 44.90% at the medial femoral condyle, 21.43% at the trochlea, 11.22% at the lateral femoral condyle, 10.20% at multiple sites, 8.16% at the patella, and 4.08% at the tibial plateau. Microfracture was performed alone in 72 of 102 (71%) knees. At a mean follow-up of 5.66 ± 2.54 years (range, 2-11 years), clinically meaningful and statistically significant improvements were seen in all PROs (P < .05) except the SF-12 mental component score. Patients who had an isolated tibial plateau defect or multiple defects demonstrated reduced improvements in the symptom rate (P = .0237). Patients with a BMI >30 kg/m2 had lower postoperative scores on the KOOS activities of daily living subscale (P = .0261) and poorer WOMAC function and WOMAC pain scores (P = .029 and .0307, respectively). Patient BMI, age, sex, defect location, concomitant procedures, and operative side were not significant predictors for additional surgery. Larger defect size (>3.6 cm2) and prior knee surgery were independent risk factors for additional knee surgery after microfracture. CONCLUSION: After microfracture, all PROs demonstrated clinically and statistically significant improvements at 5.7 years. Functionally, male patients benefited more from microfracture than female patients. Microfracture of tibial lesions and multisite microfracture provided less benefit than microfracture of isolated femoral defects. Larger lesion size (>3.6 cm2) and prior knee surgery predicted the need for additional knee surgery after microfracture.

Can Competitive Athletes Return to High-Level Play After Osteochondral Allograft Transplantation of the Knee?

PURPOSE: To investigate functional outcomes among competitive athletes undergoing osteochondral allograft (OCA) transplantation of the knee, including rates of return to play (RTP), and factors preventing RTP. METHODS: A retrospective review identified all competitive athletes (high school, intercollegiate, professional) undergoing isolated femoral condyle OCA from 2004 to 2013. Patient-reported outcome (PRO) questionnaires (Lysholm, International Knee Documentation Committee [IKDC], Knee Injury and Osteoarthritis Outcome Score [KOOS], Western Ontario and McMasters Universities Arthritis Index [WOMAC], 12-Item Short Form Health Survey [SF-12], Tegner, and Marx) and custom RTP surveys were administered. All subsequent reoperations were documented. RESULTS: Thirteen athletes (4 intercollegiate, 9 high-school) were identified with an average follow-up of 5.9 ± 2.5 years. Seven athletes (54%) returned to competitive sport at an average of 7.9 ± 3.5 months, 5 of whom returned to preinjury functional levels. Of the 8 athletes who either did not return to competitive sport or failed to sustain their high level of play, the most common reasons cited were graduation from high school or college (4 patients, 50%) or fear of reinjury (3 patients, 38%). All 4 patients citing graduation as the primary factor preventing return to preinjury level of competitive sport resumed recreational sport without limitations, yielding an adjusted RTP rate of 10 patients (77%) who either returned to competitive play or believed they could return if they had not graduated. At final follow-up, athletes reported significant improvements in all PRO scores except for KOOS-Sport, WOMAC-Stiffness, and SF-12 Mental subscales. There were 3 reoperations at an average of 3.8 ± 3.3 years after the index OCA. There were no instances of graft failure. CONCLUSIONS: OCAs provide an adjusted RTP rate of 77% for high-level adolescent athletes. Social factors may be more likely than persistent pain to prevent return to sport. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Flexion Posteroanterior Radiographs Affect Both Enrollment for and Outcomes After Injection Therapy for Knee Osteoarthritis.

BACKGROUND: Knee injection therapy is less effective for severe osteoarthritis (OA), specifically Kellgren-Lawrence (KL) grade 4. Patient selection for knee injection trials has historically been based on extension anteroposterior (AP) radiographic evaluation; however, emerging evidence suggests that KL grading using a flexion posteroanterior (PA) radiograph more accurately and reproducibly predicts disease severity. The impact of radiographic view on patient selection and outcome after knee injection therapy remains unknown. HYPOTHESIS: A 45° flexion PA radiograph will reveal more advanced knee OA in certain patients. These patients will report worse pre- and postinjection outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Four raters independently graded extension AP and flexion PA radiographs from 91 patients previously enrolled in a knee injection trial. Patients determined to have KL grade 4 OA by any rater on extension AP radiographs were excluded. Among included patients, those upgraded to KL grade 4 on flexion PA radiographs by at least 2 raters constituted group 2, while all remaining patients constituted group 1. Demographic data and patient-reported outcome scores before injection and at 6 weeks, 3 months, 6 months, and 12 months postinjection were compared between groups. RESULTS: Overall, 64 patients met the inclusion criteria, of which 19 patients (30%) constituted group 2. Compared with group 1, patients in group 2 were older (58.7 vs 52.3 years, P = .02), had worse visual analog scale pain scores before (6.6 vs 5.3, P = .03) and 6 months after injection (5.3 vs 3.5, P = .01), had less improvement in both Lysholm (8.5 vs 20.5, P = .02) and Short Form-12 physical component (-2.2 vs 1.7, P = .03) scores from preinjection to 6 months postinjection, and had less improvement in both Lysholm (1.6 vs 13.1, P = .03) and Knee injury and Osteoarthritis Outcome Score sport subscale (-2.1 vs 16, P = .01) scores from preinjection to 12 months postinjection. CONCLUSION: One in 3 patients considered to have mild to moderate knee OA on extension AP radiography is upgraded to severe knee OA (KL grade 4) on flexion PA radiography. These patients report worse preinjection outcomes, worse pain scores at short-term follow-up, and decreased improvement in knee function scores between 6 months and 1 year postinjection.

Autologous Chondrocyte Implantation Improves Knee-Specific Functional Outcomes and Health-Related Quality of Life in Adolescent Patients.

BACKGROUND: Existing studies of autologous chondrocyte implantation (ACI) in adolescent patients have primarily reported outcomes that have not been validated for cartilage repair and have failed to include measures of general health or health-related quality of life. PURPOSE: This study assesses validated knee-specific functional outcomes and health-related quality of life after ACI in adolescent patients. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients younger than 18 years who underwent ACI between 1999 and 2011 with a minimum 2-year clinical follow-up were identified from a prospectively collected database. A total of 37 patients were included in the analysis. Patient demographic data and pre- and postoperative functional outcomes scores were collected and chondral lesion characteristics were assessed. Primary outcome measures were the International Knee Documentation Committee (IKDC) subjective score and the Knee Injury and Osteoarthritis Outcome Score-Quality of Life (KOOS-QOL) subscore; secondary outcome measures were Short Form-12 (SF-12) and other KOOS subscores. In subgroup analyses, we assessed whether primary outcome results differed based on lesion location, concurrent meniscal allograft transplantation (MAT), and subsequent surgery after ACI. RESULTS: Study patients had a mean 4.6 ± 2.4 years of follow-up, a mean age of 16.7 ± 1.5 years, and a mean lesion size of 4.0 ± 2.2 cm2. The IKDC subjective score improved from 34.9 preoperatively to 64.6 postoperatively (mean improvement, 29.7 points [95% CI, 20.7 to 38.7 points]; P < .001) and the KOOS-QOL subscore improved from 24.3 to 55.3 (mean improvement, 31.0 points [95% CI, 21.3 to 40.7 points]; P < .001) at final follow-up. All other KOOS subscales and the SF-12 physical component score also showed significant improvements ( P < .008 in all cases), whereas the SF-12 mental component score showed no improvement ( P = .464). There was a 37.8% rate of subsequent surgery after ACI (most commonly, chondral debridement [54%], meniscectomy [11%], microfracture [9%], and loose body removal [9%]). Subgroup analysis showed no effect of lesion location, concurrent MAT, or subsequent surgery on improvement in IKDC subjective scores and KOOS-QOL subscores ( P > .05 in all cases). CONCLUSION: ACI is an effective treatment for adolescent patients with symptomatic, large chondral lesions, resulting in significant improvements in knee-specific functional outcome scores and health-related quality of life scores. Although patients must be cautioned on the relatively high reoperation rate (37.8%) and limitations in knee function even after ACI, all patients in this study exhibited improvements over preoperative knee function at the most recent follow-up regardless of ACI location, concurrent MAT, or subsequent surgery.

Meniscal Allograft Transplantation in the Adolescent Population.

PURPOSE: To report the results of meniscal allograft transplantation (MAT) with minimum 2-year follow-up in an active adolescent population. METHODS: After institutional review board approval, all patients aged 16 years or younger who underwent MAT and had more than 2 years' clinical follow-up were identified from a prospectively collected database. Demographic data were collected and summary statistics calculated. Functional outcome scores were collected preoperatively and at 6 months, 1 year, 2 years, and final follow-up. Differences between scores at each time point were calculated using a mixed-model repeated-measures analysis of variance. All prior procedures and reoperations were documented. RESULTS: Thirty-seven MAT procedures were performed in 36 children (84% lateral and 16% medial). For 32 of these procedures (86%), the patients met the inclusion criteria with minimum 2-year follow-up. The mean age was 15.4 ± 1.04 years (range, 13 to 16 years). All patients had undergone prior knee surgery. Of the 32 patients, 23 (72%) were girls and 9 (28%) were boys. Eleven patients had open physes. Forty-eight percent of patients underwent concomitant procedures, mainly for chondral defects. The mean length of clinical follow-up was 7.2 ± 3.2 years (range, 2 to 15 years). MAT resulted in significant improvements in the Knee Injury and Osteoarthritis Outcome Score, Lysholm score, International Knee Documentation Committee subjective score, Western Ontario and McMaster Universities Osteoarthritis Index pain score, Western Ontario and McMaster Universities Osteoarthritis Index function score, and Short Form 12 physical score. After MAT, 7 patients (22%) underwent 8 surgical procedures, most of which were for chondral disease. The meniscal reoperation rate was 6%. No revision MAT procedures were required. No angular deformities or limb-length inequalities were reported. CONCLUSIONS: MAT resulted in predictable improvements in functional outcomes in the adolescent population. The meniscal reoperation rate was low (6%), no revision MAT procedures were required, and no growth complications were reported. Chondral disease remains the primary reason for reoperation after MAT. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

DeNovo NT Particulated Juvenile Cartilage Implant.

Biological repair of focal chondral defects represents a significant clinical challenge as cartilage lacks intrinsic healing ability. Although it can be difficult to measure the objective success of cartilage repair techniques, the primary objective is symptom relief leading to less pain and improved function for the patient. Likely, the most important key to success is proper clinical indications. Second to this, the type of cartilage treatment utilized should be based on lesion location, size, depth, and other patient factors. One such treatment is DeNovo Natural Tissue. This method relies on the ability of juvenile chondrocytes to migrate from cartilage explants after being secured in a cartilage defect. Although approximately 8700 cases have been performed since 2007, long-term clinical outcomes are not yet available. However, basic science and early clinical data are promising.