Eirik Solheim

Autologous Chondrocyte Implantation Compared with Microfracture in the Knee: A Randomized Trial

BACKGROUND New methods have been used, with promising results, to treat full-thickness cartilage defects. The objective of the present study was to compare autologous chondrocyte implantation with microfracture in a randomized trial. We are not aware of any previous randomized studies comparing these methods. METHODS Eighty patients without general osteoarthritis who had a single symptomatic cartilage defect on the femoral condyle in a stable knee were treated with autologous chondrocyte implantation or microfracture (forty in each group). We used the International Cartilage Repair Society, Lysholm, Short Form-36 (SF-36), and Tegner forms to collect data. An independent observer performed a follow-up examination at twelve and twenty-four months. Two years postoperatively, arthroscopy with biopsy for histological evaluation was carried out. The histological evaluation was done by a pathologist and a clinical scientist, both of whom were blinded to each patients treatment. RESULTS In general, there were small differences between the two treatment groups. At two years, both groups had significant clinical improvement. According to the SF-36 physical component score at two years postoperatively, the improvement in the microfracture group was significantly better than that in the autologous chondrocyte implantation group (p = 0.004). Younger and more active patients did better in both groups. There were two failures in the autologous chondrocyte implantation group and one in the microfracture group. No serious complications were reported. Biopsy specimens were obtained from 84% of the patients, and histological evaluation of repair tissues showed no significant differences between the two groups. We did not find any association between the histological quality of the tissue and the clinical outcome according to the scores on the Lysholm or SF-36 form or the visual analog scale. CONCLUSIONS Both methods had acceptable short-term clinical results. There was no significant difference in macroscopic or histological results between the two treatment groups and no association between the histological findings and the clinical outcome at the two-year time-point. LEVEL OF EVIDENCE Therapeutic study, Level I-1a (randomized controlled trial [significant difference]). See Instructions to Authors for a complete description of levels of evidence.

A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years.

BACKGROUND The optimal treatment for cartilage lesions has not yet been established. The objective of this randomized trial was to compare autologous chondrocyte implantation with microfracture. This paper represents an update, with presentation of the clinical results at five years. METHODS Eighty patients who had a single chronic symptomatic cartilage defect on the femoral condyle in a stable knee without general osteoarthritis were included in the study. Forty patients were treated with autologous chondrocyte implantation, and forty were treated with microfracture. We used the International Cartilage Repair Society, Lysholm, Short Form-36, and Tegner forms to collect clinical data, and radiographs were evaluated with use of the Kellgren and Lawrence grading system. RESULTS At two and five years, both groups had significant clinical improvement compared with the preoperative status. At the five-year follow-up interval, there were nine failures (23%) in both groups compared with two failures of the autologous chondrocyte implantation and one failure of the microfracture treatment at two years. Younger patients did better in both groups. We did not find a correlation between histological quality and clinical outcome. However, none of the patients with the best-quality cartilage (predominantly hyaline) at the two-year mark had a later failure. One-third of the patients in both groups had radiographic evidence of early osteoarthritis at five years. CONCLUSIONS Both methods provided satisfactory results in 77% of the patients at five years. There was no significant difference in the clinical and radiographic results between the two treatment groups and no correlation between the histological findings and the clinical outcome. One-third of the patients had early radiographic signs of osteoarthritis five years after the surgery. Further long-term follow-up is needed to determine if one method is better than the other and to study the progression of osteoarthritis.

Registration of cruciate ligament injuries in Norwegian top level team handball. A prospective study covering two seasons

All cruciate ligament injuries in the three upper divisions for men and women (3392 players) in Norwegian team handball in the 1989‐90 and 1990–91 seasons were registered. A questionnaire was mailed to all injured players. Ninety‐three cruciate ligament injuries were registered; 87 in the anterior cruciate ligament (ACL), and six in the posterior cruciate ligament (PCL). Among women, 1.8% were injured compared with 1.0% of the men. In the first division, the risk of being injured was considerably higher: 4.5% of the players had a cruciate ligament injury. There were 0.97 cruciate ligament injuries per 1000 playing hours in the three divisions taken together. Seventy‐five per cent of the injuries occurred during games. Ninety‐five per cent involved no contact between players. Activities in which the friction between shoe and floor was significant caused 55% of the injuries. Injuries caused by running into another player contributed to only 5% of the injuries. No significant differences were observed in injury incidence during matches between different types of floors (parquet, Pulastic and other synthetic sufaces).

Growth factors in bone

Summary.Bone contains several growth factors, including bone morphogenetic proteins (BMPs), transforming growth factor beta (TGF-β), insulin-like growth factors I and II (IGF-I and IGF-II), platelet derived growth factor (PDGF) and basic and acidic fibroblast growth factor (bFGF and aFGF). Spatial and temporal variations in the expression and secretion of the various growth factors have been demonstrated in osteoblastic cultures and in various experimental and clinical in vivo models, including fracture healing in humans. Local application of various growth factors influences proliferation, differentiation and protein synthesis in osteoblastic cultures and bone formation in different animal models, including experimental fractures and skeletal defects. The BMPs are the only growth factors known to provoke bone formation heterotopically by making undifferentiated mesenchymal cells differentiate into osteoblasts (osteoinduction). BMPs and other growth factors, soon to become commercially available for clinical use, need a delivery system for their sustained release, as the factors are otherwise rapidly absorbed. Some existing systems inhibit bone formation by inducing chronic inflammation or physically by unresorbed carrier obstructing bone formation. New delivery systems are being investigated.Résumé.L’os contient plusieurs facteurs de croissance notamment: la protéine morphogénétique osseuse (BMPs), le facteur de croissance bêta (TGF-B), les facteurs de croissance insuline-like I et II (IGF-I et IGF-II), le facteur de croissance plaquettaire (PDGF) et les facteurs de croissance fibroblastique basique et acide (bFGF et aFGF). Des variations spatiales et temporelles de la secrétion des différents facteurs de croissance ont été démontrées dans les cultures ostéoblastiques et dans différent modèle expérimental et clinique notamment, la consolidation de fracture chez l’homme. L’application locale des différents facteurs de croissance influence la prolifération, la différenciation et la synthèse protéique dans les cultures d’ostéoblastes ainsi que la formation osseuse dans les différents modèles animaux avec notamment fracture expérimentale et perte de substance squelettique. Les BMPs sont les seuls facteurs de croissance connus pour provoquer une formation d’os hétérotopique par différenciation en ostéoblastes des cellules mésenchymateuses indifférenciées (ostéoinduction). Les BMPs et les autres facteurs de croissance seront bientôt commercialement disponibles pour l’usage clinique ce qui nècessitera des systèmes de distribution particuliers pour leur préservation. Il existe déjà des systèmes inhibant la formation osseuse de façon physique ou en induisant une inflammation chronique.

Open reduction and internal fixation of displaced intraarticular fractures of the distal radius: 31 patients followed for 3-7 years

We have used open reduction and internal fixation with a T-plate in 31 displaced, intraarticular fractures of the distal radius which were judged irreducible or in which closed reduction failed. The mean follow-up time was 4 (3-7) years. The dorsal angulation, the radial length, the articular step-off and the intraarticular gap between fragments were substantially improved after surgery. 30 patients had excellent or good extraarticular alignment, and only 1 patient had a postoperative intraarticular step-off of 2 mm. The function was excellent or good in 26 patients at follow-up. Complications occurred in 6 patients: 1 compartment syndrome, 1 postoperative wound infection, 2 ruptures of the extensor pollicis longus tendon, and 2 patients had median nerve paresthesias.

Prediction of secondary displacement in Colles' fracture

In a prospective study, 645 consecutive Colles’ fractures treated conservatively were followed until union. The fractures subsequently lost some of their manipulated position during the immobilization period. However, the anatomical end result was significantly improved compared with the initial deformity. The mean shortening of the radius during plaster-cast treatment was 3 mm, and the mean increase of dorsal angulation was 7°. Multiple regression analyses showed that initial dorsal angulation, age, and Older type were important predictor variables for the end result of dorsal angulation. Initial radial length, age and initial dorsal angulation were of importance for the end result of radial length. The strongest linear relationship was found between the end result of radial length and the initial radial length (r = 0.67). This may indicate that the patients who will malunite with radial shortening are those with significant radial axial shortening at the initial presentation. Thus, these patients should be treated with a more stable fixation device.

Results at 10 to 14 years after osteochondral autografting (mosaicplasty) in articular cartilage defects in the knee

PURPOSE The aim of this study was to evaluate the medium-term (5-9 years) and long-term (10-14 years) outcomes of mosaicplasty in the knee and identify possible risk factors for poor outcome. METHODS We included patients 60 years or younger with symptomatic focal full-thickness chondral lesions. Seventy-three patients (87%) with median age of 34 years were available for analyses. Clinical outcome was evaluated by Lysholm score and VAS of pain. RESULTS Both the mean Lysholm score and mean VAS pain score improved significantly from baseline, 49 (SD 17) and 58 (SD 23), respectively, to both the mid-term follow-up, 72 (SD18, p<0.001) and 27 (SD 20, p<0.001), respectively, and the long-term follow-up, 72 (SD 21, p<0.001) and 33 (SD 23, p<0.001), respectively. A poor outcome at the long-term follow-up - defined as a Lysholm score of 64 or less or having had a knee replacement - was found in 40%. A poor outcome was more frequent in patients 40 years or older (59%), in women (61%) and in defects with an area of 3 cm(2) or more (57%). Conversely, in a subgroup of male individuals younger than 40 years with defect size less than 3 cm(2) the failure rate was 12.5% and the mean Lysholm score was 82 (SD 16). CONCLUSION We conclude that the long-term clinical outcome after mosaicplasty varies greatly depending on age, gender and the size of the lesion. LEVEL OF EVIDENCE IV-Retrospective Case Series.

Biocompatibility and effect on osteogenesis of poly(ortho ester) compared to poly(DL-lactic acid)

Implantation of demineralized bone induces new bone formation by the action of contained growth factors, of which bone morphogenetic proteins are of prime importance. A biodegradable polymer may be used as a carrier for demineralized bone particles or recombinant bone growth factors to prevent displacement of the implant, preserve its volume and shape, and assure sustained release of the incorporated active components. A polymer for this use should be biocompatible and completely absorbed without interfering with the osteogenesis. We investigated the host-tissue response and effect on demineralized bone-induced bone formation by two biodegradable polymers, a poly(ortho ester) and an amorphous low-molecular poly(DL-lactic acid). Both polymers had a plastic consistency, could easily be molded, and adhered well to the demineralized bone particles. Demineralized bone particles were implanted alone and in combination with each of the polymers in the abdominal muscles of 45 male Wistar rats. Four weeks after the operation the implants were recovered and subjected to (85)Sr uptake analysis to quantify bone formation and histologic examination. The poly(ortho ester) provoked little inflammation; it was largely absorbed by 4 weeks, and no qualitative or quantitative effect on bone formation was found. The poly(DL-lactic acid) provoked a chronic inflammation with multinuclear giant cells, macrophages with engulfed material, and proliferating fibroblasts; part of the material was still present, and the bone formation was inhibited.

Osteochondral autografting (mosaicplasty) in articular cartilage defects in the knee: Results at 5 to 9 years

We evaluated short- and medium-term results of the treatment of articular cartilage defects of the knee with autogenous cylindrical osteochondral grafts (mosaicplasty) in 69 patients (median age 33 years) with symptomatic articular cartilage defects. Data of Lysholm score and visual analogue scale (VAS) of pain (0=no pain; 100=worst possible pain) were collected before the surgery, at 12 months postoperatively and 5 to 9 (median 7) years after the surgery. At the last follow-up the patients were also asked to state their degree of satisfaction with the outcome on a VAS (0=not at all satisfied; 100=completely satisfied), and to answer if they would have undergone the surgery again if necessary (yes or no). The mean Lysholm score and VAS of pain improved from 48 and 62, respectively, at the time of surgery to 81 and 24, respectively, at the 12-months follow-up (p<0.001 for both comparisons). From 12 months postoperatively, the Lysholm score and VAS of pain deteriorated to 68 and 32, respectively at the 5- to 9-year follow-up (p<0.001 and p=0.018, respectively). The mean degree of satisfaction with the outcome was 70 (SD 28), and 61 patients (88%) stated that they would have undergone the surgery again. In conclusion, the mosaicplasty leads to improvement of symptoms and function at short- and medium-term follow-up. A deterioration of the results is observed from 12 months postoperatively to 5-9 years postoperatively.

A Randomized Multicenter Trial Comparing Autologous Chondrocyte Implantation with Microfracture: Long-term Follow-up at 14 to 15 Years.

BACKGROUND The management of cartilage and osteochondral lesions in the knee remains problematic and controversial. Our group reported the 2-year and 5-year results of a randomized controlled trial comparing autologous chondrocyte implantation (ACI) and microfracture in patients with focal femoral cartilage injuries. The objective of the present study was to report the long-term results. METHODS Eighty patients with a single symptomatic chronic cartilage defect on the femoral condyle without general osteoarthritis were included in the study at the time of the index operation (January 1999 to February 2000). We used the International Cartilage Repair Society (ICRS), Lysholm, Short Form-36 (SF-36), and Tegner forms to collect data at the time of inclusion and at follow-up evaluations. Standing weight-bearing radiographs were evaluated for evidence of osteoarthritis according to the method described by Kellgren and Lawrence. For the long-term follow-up in 2014, we used the Synaflexer frame to standardize the radiographs. The operation was considered to have failed if a reoperation was performed because of symptoms from a lack of healing of the treated defect. RESULTS At the long-term follow-up evaluation, no significant differences between the treatment groups were detected with respect to the results on the clinical scoring systems. At the 15-year evaluation, there were 17 failures in the ACI group compared with 13 in the microfracture group. We observed that more total knee replacements were needed in the ACI group than in the microfracture group (6 compared with 3). The surviving patients in both groups, i.e., those who had not had a failure, had significant improvement in the clinical scores compared with baseline. Fifty-seven percent of the surviving patients in the ACI group and 48% of such patients in the microfracture group had radiographic evidence of early osteoarthritis (a Kellgren and Lawrence grade of ≥2); the difference was not significant. CONCLUSIONS The survivors in both groups improved their clinical scores in the short, medium, and long-term evaluations, and no significant difference between the groups was found at the long-term follow-up. The risk of treatment failure and the frequency of radiographic osteoarthritis are problematic. Our findings raise serious concerns regarding the efficacy of these procedures in delaying osteoarthritis and preventing further surgery. Continued basic and clinical research is needed in this field. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.