Cartilage Injuries in the Knee : Natural History and Surgical Repair

Leddbrusk er et høyspesialisert vev utviklet for fordeling av belastning og friksjonsfri bevegelse. Skader i leddbrusken i kneet kan oppstå i forbindelse med idrett eller som en følge av sykdom i beinet under brusken. Slike skader rammer ofte unge mennesker og kan hindre fysisk aktivitet og føre til arbeidsuførhet i ung alder. Ortopedisk kirurg Sverre Bertrand Løken har i sitt doktorgradsarbeid vist at ved å transplantere bruskceller dyrket fra pasienten selv til en bruskskade i kneet, kan dette gi reparasjon av skaden. Bruskcelletransplanterte pasienter fikk bedret funksjon, men leddbrusken ble ikke normal og pasientene klarte ikke å gjenvinne normal muskelstyrke.. I avhandlingen ble det funnet at reparasjonsvevet etter bruskcelletransplantasjon lignet mer på arrvev enn på normal leddbrusk. I en studie av nesten 1000 pasienter som ble operert med kikkhullsteknikk (artroskopi) ble skader i leddbrusken påvist i ca 2/3 av knærne, mens dype leddbruskskader over 2 cm² ble funnet hos ca 6 %. Da pasientene med leddbruskskade ble undersøkt pånytt etter 6-7 år var knefunksjonen bedre både hos dem som var operert for bruskskaden og hos dem som ikke var operert. Knefunksjonen var likevel ikke normal i noen av pasientgruppene. Stamceller er ”moderceller” som kan videreutvikle seg til mer spesialiserte celler. Mesenchymale stamceller kan utvikle seg til blant annet bruskceller hvis de stimuleres i slik retning. I en delstudie i avhandlingen ble leddbruskskader hos kaniner behandlet ved at skaden ble fylt med et biomateriale (hyaluronan scaffold) som inneholdt stamceller dyrket fra kaninens beinmarg. Stamceller ga ikke vesentlig bedre reparasjon enn det man så i skadene som ikke fikk stamceller. Videre forskning er nødvendig for å se om man kan stimulere stamceller slik at de kan gi en bedre reparasjon av leddbruskskader enn det man har klart å oppnå med dagens metoder

The Long-Term Risk of Knee Arthroplasty in Patients with Arthroscopically Verified Focal Cartilage Lesions: A Linkage Study with the Norwegian Arthroplasty Register, 1999 to 2020

Background: Focal cartilage lesions are common in the knee. The risk of later ipsilateral knee arthroplasty remains unknown. The purposes of the present study were to evaluate the long-term cumulative risk of knee arthroplasty after arthroscopic identification of focal cartilage lesions in the knee, to investigate the risk factors for subsequent knee arthroplasty, and to estimate the subsequent cumulative risk of knee arthroplasty compared with that in the general population. Methods: Patients who had undergone surgical treatment of focal cartilage lesions at 6 major Norwegian hospitals between 1999 and 2012 were identified. The inclusion criteria were an arthroscopically classified focal cartilage lesion in the knee, an age of ≥18 years at the time of surgery, and available preoperative patient-reported outcomes (PROMs). The exclusion criteria were osteoarthritis or “kissing lesions” at the time of surgery. Demographic data, later knee surgery, and PROMs were collected with use of a questionnaire. A Cox regression model was used to adjust for and investigate the impact of risk factors, and Kaplan-Meier analysis was performed to estimate cumulative risk. The risk of knee arthroplasty in the present cohort was compared with that in the age-matched general Norwegian population. Results: Of the 516 patients who were eligible, 322 patients (328 knees) consented to participate. The mean age at the time of the index procedure was 36.8 years, and the mean duration of follow-up was 19.8 years. The 20-year cumulative risk of knee arthroplasty in the cartilage cohort was 19.1% (95% CI, 14.6% to 23.6%). Variables that had an impact on the risk of knee arthroplasty included an ICRS grade of 3 to 4 (hazard ratio [HR], 3.1; 95% CI, 1.1 to 8.7), an age of ≥40 years at time of cartilage surgery (HR, 3.7; 95% CI, 1.8 to 7.7), a BMI of 25 to 29 kg/m2 (HR, 3.9; 95% CI, 1.7 to 9.0), a BMI of ≥30 kg/m2 (HR, 5.9; 95% CI, 2.4 to 14.3) at the time of follow-up, autologous chondrocyte implantation (ACI) at the time of the index procedure (HR, 3.4; 95% CI, 1.0 to 11.4), >1 focal cartilage lesion (HR, 2.1; 95% CI, 1.1 to 3.7), and a high preoperative visual analog scale (VAS) score for pain at the time of the index procedure (HR, 1.1; 95% CI, 1.0 to 1.1). The risk ratio of later knee arthroplasty in the cartilage cohort as compared with the age-matched general Norwegian population was 415.7 (95% CI, 168.8 to 1,023.5) in the 30 to 39-year age group. Conclusions: In the present study, we found that the 20-year cumulative risk of knee arthroplasty after a focal cartilage lesion in the knee was 19%. Deep lesions, higher age at the time of cartilage surgery, high BMI at the time of follow-up, ACI, and >1 cartilage lesion were associated with a higher risk of knee arthroplasty.publishedVersio

Intraarticular location predicts cartilage filling and subchondral bone changes in a chondral defect: A randomized, blind, long-term follow-up trial involving 82 rabbit knees

Open Access - This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the source is credited.Background and purpose: The natural history of, and predictive factors for outcome of cartilage restoration in chondral defects are poorly understood. We investigated the natural history of cartilage filling subchondral bone changes, comparing defects at two locations in the rabbit knee. Animals and methods: In New Zealand rabbits aged 22 weeks, a 4-mm pure chondral defect (ICRS grade 3b) was created in the patella of one knee and in the medial femoral condyle of the other. A stereo microscope was used to optimize the preparation of the defects. The animals were killed 12, 24, and 36 weeks after surgery. Defect filling and the density of subchondral mineralized tissue was estimated using Analysis Pro software on micrographed histological sections. Results: The mean filling of the patellar defects was more than twice that of the medial femoral condylar defects at 24 and 36 weeks of follow-up. There was a statistically significant increase in filling from 24 to 36 weeks after surgery at both locations. The density of subchondral mineralized tissue beneath the defects subsided with time in the patellas, in contrast to the density in the medial femoral condyles, which remained unchanged. Interpretation: The intraarticular location is a predictive factor for spontaneous filling and subchondral bone changes of chondral defects corresponding to ICRS grade 3b. Disregarding location, the spontaneous filling increased with long-term follow-up. This should be considered when evaluating aspects of cartilage restoration

Focal cartilage defects in the knee –a randomized controlled trial comparing autologous chondrocyte implantation with arthroscopic debridement

Background Focal cartilage injuries in the knee might have devastating effect due to the predisposition of early onset osteoarthritis. Various surgical treatment options are available, however no statistically significant differences have been found between the different surgical treatments. This supports the suggestion that the improvement might be a result of the post-operative rehabilitation rather than the surgery itself. Autologous chondrocyte implantation (ACI) has become a recognized treatment option for larger cartilage lesions in the knee. Although ACI has been compared to other surgical treatment such as microfracture and mosaicplasty, it has never been directly compared to simple arthroscopic debridement and rehabilitation alone. In this study we want to increase clinical and economic knowledge about autologous chondrocyte implantation compared to arthroscopic debridement and physical rehabilitation in the short and long run. Methods/Design We will conduct a randomized controlled trial to compare ACI with simple arthroscopic debridement (AD) and physiotherapy for the treatment of cartilage lesions in the knee. The study will include a total of 82 patients, both men and non-pregnant women, with a full thickness cartilage defect in the weight bearing area of the femoral condyles or trochlea larger than 2 cm2. The lesion must be symptomatic, with a Lysholm score less than 75. The two treatment groups will receive identical rehabilitation protocol according to a modification of Wondrasch et al., which is an active rehabilitation and education program divided into 3 phases: accommodation, rehabilitation and return to activity. The patients will be followed for 24 months, with additional late follow-ups at 5 and 10 years to monitor the potential onset of osteoarthtitis. The primary outcome measure will be the difference in the KOOS knee-related quality of life (QoL) subscore in the ACI group compared to the AD group at 2 years. A combination of self-explanatory questionnaires, clinical parameters, clinical hop tests and radiographs and Magnetic Resonance Imaging (MRI) will be used as secondary endpoints. Discussion This is the first study with a high level of evidence to compare ACI with simple debridement and physiotherapy for the treatment of isolated symptomatic full thickness lesions of the knee. Trial registration ClinicalTrial NCT02636881 (21 December 2015

No degeneration found in focal cartilage defects evaluated with dGEMRIC at 12-year follow-up

Background and purpose — The natural history of focal cartilage defects (FCDs) is still unresolved, as is the long-term cartilage quality after cartilage surgery. It has been suggested that delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a biomarker of early OA. We aimed to quantitatively evaluate the articular cartilage in knees with FCDs, 12 years after arthroscopic diagnosis. Patients and methods — We included 21 patients from a cohort of patients with knee pain who underwent arthroscopy in 1999. Patients with a full-thickness cartilage defect, stable knees, and at least 50% of both their menisci intact at baseline were eligible. 10 patients had cartilage repair performed at baseline (microfracture or autologous chondrocyte implantation), whereas 11 patients had either no additional surgery or simple debridement performed. Mean follow-up time was 12 (10–13) years. The morphology and biochemical features were evaluated with dGEMRIC and T2 mapping. Standing radiographs for Kellgren and Lawrence (K&L) classification of osteoarthritis (OA) were obtained. Knee function was assessed with VAS, Tegner, Lysholm, and KOOS. Results — The dGEMRIC showed varying results but, overall, no increased degeneration of the injured knees. Degenerative changes (K&L above 0) were, however, evident in 13 of the 21 knees. Interpretation — The natural history of untreated FCDs shows large dGEMRIC variations, as does the knee articular cartilage of surgically treated patients. In this study, radiographic OA changes did not correlate with cartilage quality, as assessed with dGEMRIC

6-year follow-up of 84 patients with cartilage defects in the knee : knee scores improved but recovery was incomplete

Background and purpose: The natural history of focal cartilage injury is largely unknown. In this study we investigated 6-year outcomes in patients with arthroscopically verified, focal, fullthickness cartilage injuries of the knee. Methods: In a previous report (baseline study) of 993 knee arthroscopies, 98 patients were less than 50 years old at baseline and showed grade 3–4 focal cartilage injury, as assessed with the International Cartilage Repair Society (ICRS) scale. In the present study, 84 of the 98 patients completed follow-ups at median 6.1 (5.3–7.8) years after baseline assessments. At baseline, the patients had undergone different types of cartilage repair (n = 34) or had no treatment or only debridement (n = 64) for their cartilage injury. The follow-up included evaluations with the ICRS knee evaluation form, the Lysholm score, and other knee evaluation tests. 68 patients underwent radiographic assessments with weight bearing. Results: Improvements compared to baseline were noted in the average ICRS functional score, visual analog scale (VAS) pain score, and the patients’ rating of the function in the affected knee compared to the contra-lateral knee. However, the average ICRS activity level had decreased from baseline. The average Lysholm score was 76 (SD 21). 19 patients had Kellgren-Lawrence grades 2–3 in the affected knee and 6 patients had grades 2–3 in the contralateral knee. There was a statistically significant difference between affected and contralateral knees. Interpretation: Patients with arthroscopically diagnosed ICRS grade 3–4 cartilage injuries in the knee may show improvement in knee function over the following 5–8 years, with or without cartilage repair. However, knee function remains substantially affected. Further studies are needed to determine whether cartilage surgery can yield better functional outcomes than non-surgical or less invasive surgical treatments

6-year follow-up of 84 patients with cartilage defects in the knee : knee scores improved but recovery was incomplete

Open Access - This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the source is credited.Background and purpose: The natural history of focal cartilage injury is largely unknown. In this study we investigated 6-year outcomes in patients with arthroscopically verified, focal, fullthickness cartilage injuries of the knee. Methods: In a previous report (baseline study) of 993 knee arthroscopies, 98 patients were less than 50 years old at baseline and showed grade 3–4 focal cartilage injury, as assessed with the International Cartilage Repair Society (ICRS) scale. In the present study, 84 of the 98 patients completed follow-ups at median 6.1 (5.3–7.8) years after baseline assessments. At baseline, the patients had undergone different types of cartilage repair (n = 34) or had no treatment or only debridement (n = 64) for their cartilage injury. The follow-up included evaluations with the ICRS knee evaluation form, the Lysholm score, and other knee evaluation tests. 68 patients underwent radiographic assessments with weight bearing. Results: Improvements compared to baseline were noted in the average ICRS functional score, visual analog scale (VAS) pain score, and the patients’ rating of the function in the affected knee compared to the contra-lateral knee. However, the average ICRS activity level had decreased from baseline. The average Lysholm score was 76 (SD 21). 19 patients had Kellgren-Lawrence grades 2–3 in the affected knee and 6 patients had grades 2–3 in the contralateral knee. There was a statistically significant difference between affected and contralateral knees. Interpretation: Patients with arthroscopically diagnosed ICRS grade 3–4 cartilage injuries in the knee may show improvement in knee function over the following 5–8 years, with or without cartilage repair. However, knee function remains substantially affected. Further studies are needed to determine whether cartilage surgery can yield better functional outcomes than non-surgical or less invasive surgical treatments

Autologous chondrocyte implantation to repair knee cartilage injury : ultrastructural evaluation at 2 years and long term follow up including muscle strength measurements

Autologous chondrocyte implantation (ACI) usually results in improvement in clinical scores. However, long-term isokinetic muscle strength measurements have not been reported. Biopsies from the repair tissue have shown variable proportions of hyaline-like cartilage. In this study, 21 consecutive patients were treated with autologous cartilage implantations in the knee. Mean size of the lesions was 5.5 cm2. Follow-up arthroscopy with biopsy was performed at 2 years in 19 patients. The biopsies were examined with both light microscopy and transmission electron microscopy (TEM) techniques including immunogold analysis of collagen type 1. Patient function was evaluated with modified 10-point scales of the Cincinnati knee rating system obtained preoperatively and at 1 and 8.1 years. Isokinetic quadriceps and hamstrings muscle strength testing was performed at 1, 2 and 7.4 years. Light microscopy and TEM both showed predominately fibrous cartilage. The immunogold analysis showed a high percentage of collagen type I. At 7.4 years, the total work deficits when compared with the contra-lateral leg for isokinetic extension were 19.1 and 11.4%, and for isokinetic flexion 11.8 and 8.5% for 60 and 2408/s, respectively. Mean pain score improved from 4.3 preoperatively to 6.3 at 1 year (p = 0.031) and 6.6 at 8.1 years (p = 0.013). Overall health condition score improved from 4.1 preoperatively to 6.1 at 1 year (p = 0.004) and 6.5 at 8.1 years (p = 0.008). Three patients later went through revision surgery with other resurfacing techniques and are considered failures. In summary, the formation of fibrous cartilage following ACI was confirmed by TEM with immunogold histochemistry. Although the functional scores were generally good, strength measurements demonstrated that the surgically treated leg remained significantly weaker