Purpose of review: Patients are increasingly becoming interested in non-pharmacologic approaches to manage their osteoarthritis. This review examines the recent literature on the potential beneficial effects of unloading joints in the treatment of osteoarthritis, with a focus on joint distraction.

Recent findings: Mechanical factors are involved in the development and progression of osteoarthritis. If ‘loading’ is a major cause in development and progression of osteoarthritis, then ‘unloading’ may be able to prevent progression. There is evidence that unloading may be effective in reducing pain and slowing down structural damage. This review describes unloading by footwear and bracing (nonsurgical), unloading by osteotomy (surgical), and has a focus on unloading by joint distraction. Excellent reviews in all these three fields have been published over the past few years. Recent studies argue for the usefulness of a biomechanical approach to improve function and possibly reduce disease progression in osteoarthritis.

Summary: To improve patient function and possibly reduce disease progression, a biomechanical approach should be considered in treating patients with osteoarthritis. Further research (appropriate high-quality clinical trials) and analysis (clinical as well as preclinical and fundamental) are still necessary, however, to understand, validate, and refine the different approaches of unloading to treat osteoarthritis.

In this Review we describe three approaches for cartilage tissue repair at the rheumatology–orthopaedics interface: disease-modifying osteoarthritis (OA) drug (DMOAD) treatment; cell-based therapies, and intrinsic cartilage repair by joint distraction. DMOADs can slow the progression of joint damage. Cell-based therapies have evolved to do the same, through selection of the most potent cell types (and combinations thereof), as well as identification of permissive boundary conditions for indications. Joint distraction techniques, meanwhile, have now demonstrated the capacity to stimulate actual intrinsic tissue repair. Although this progress is promising, true biological joint reconstruction remains distant on the developmental pathway of ‘regenerative medicine’. Prolonged functional repair—that is, cure of diseases such as OA—remains an unmet medical need and scientific challenge, for which comparative and constructive interaction between these physical, chemical and cellular approaches will be required. Careful selections of patients and combinations of approaches will need to be made and tested to demonstrate their cost-effectiveness. Only with such rational and integrated assessment of outcomes will the promising results of these approaches be consolidated in clinical practice.

In 1994, the first article on quantitative magnetic resonance imaging (qMRI) of articular cartilage was published, and tremendous progress in image acquisition, image analysis, and applications has since been made. The objective of this personal perspective is to highlight milestones in the field of qMRI of cartilage and other articular tissues over these past 20 years.
Based on a Pubmed search of original articles, the authors selected 30 articles which they deemed to be among the first to provide an important technological step forward in qMRI of cartilage, provided a first application in a particular context, or provided mechanistic insight into articular cartilage physiology, pathology, or treatment.
This personal perspective summarizes results from these 30 articles. Further, the authors provide examples of how qMRI of cartilage has translated to quantitative analysis approaches of other articular tissues, including bone, meniscus, and synovium/edema. Eventually, the report provides a summary of how the lessons learned might be applied to future clinical trials and clinical practice.
Over the past 20 years, quantitative imaging of articular tissues has emerged from a method to a dynamic field of research by its own. Continuing the qMRI biomarker qualification process will be crucial in convincing regulatory agencies to accept these as primary outcomes in phase 3 intervention trials. Once successful structural intervention will actually become available in OA, qMRI biomarkers may play an essential role in monitoring response to therapy in the clinic, and in stratifying disease phenotypes that respond differently to treatment

“In the same year, however, a first treatment study was published that demonstrated that an increase in cartilage thickness could be achieved by a ‘mechanical’ intervention, in the compartment affected by radiographic OA [36]. This ‘anabolic’ response was achieved by 2-month joint distraction with an external fixation frame in patients with late stage disease (mostly KLG = 3 and 4) aged <60 (48 ± 7) years. qMRI revealed an 25% increase in cartilage thickness and a significant reduction in denuded bone areas 1 year later, accompanied by an increase in weight-bearing radiographic JSW. This study thus Provides an important ‘proof-of-concept’ that reversal of cartilage loss is attainable. The patients treated by distraction also generally improved clinically, with the WOMAC increasing from 45 to 77 points, and the VAS decreasing from 73 to 31 mm over 1 year.”

BACKGROUND: Total joint replacements for end-stage osteoarthritis of the hip and knee are cost-effective and demonstrate significant clinical improvement. However, robust population based lifetime-risk data for implant revision are not available to aid patient decision making, which is a particular problem in young patient groups deciding on best-timing for surgery.

METHODS: We did implant survival analysis on all patients within the Clinical Practice Research Datalink who had undergone total hip replacement or total knee replacement. These data were adjusted for all-cause mortality with data from the Office for National Statistics and used to generate lifetime risks of revision surgery based on increasing age at the time of primary surgery.

FINDINGS: We identified 63 158 patients who had undergone total hip replacement and 54 276 who had total knee replacement between Jan 1, 1991, and Aug 10, 2011, and followed up these patients to a maximum of 20 years. For total hip replacement, 10-year implant survival rate was 95·6% (95% CI 95·3-95·9) and 20-year rate was 85·0% (83·2-86·6). For total knee replacement, 10-year implant survival rate was 96·1% (95·8-96·4), and 20-year implant survival rate was 89·7% (87·5-91·5). The lifetime risk of requiring revision surgery in patients who had total hip replacement or total knee replacement over the age of 70 years was about 5% with no difference between sexes. For those who had surgery younger than 70 years, however, the lifetime risk of revision increased for younger patients, up to 35% (95% CI 30·9-39·1) for men in their early 50s, with large differences seen between male and female patients (15% lower for women in same age group). The median time to revision for patients who had surgery younger than age 60 was 4·4 years.

INTERPRETATION: Our study used novel methodology to investigate and offer new insight into the importance of young age and risk of revision after total hip or knee replacement. Our evidence challenges the increasing trend for more total hip replacements and total knee replacements to be done in the younger patient group, and these data should be offered to patients as part of the shared decision making process.

Purpose: Joint distraction has been used to treat osteoarthritis and was found to delay the need for arthrodesis or joint replacement. However, there has been little basic research on articulated joint distraction for the repair of osteochondral defects. We investigated the effects of joint distraction with motion after drilling on a fresh osteochondral defect in the weight bearing area of the rabbit knee joint.

Methods: A full thickness osteochondral defect was created in the weight bearing area of both medial femoral condyles of an adult Japanese white rabbit. After drilling of the defect, the experimental knee joint was distracted for 1.5 mm using a pair of external fixators to decrease compression force. The contralateral knee joint was used as a control with no apparatus. Gross findings and histological evaluation were assessed to study morphology of the repaired cartilage.

Results: A partial repair with cartilage-like tissue was observed in the joints of the experimental group at 4 weeks. While cartilage-like tissue stained with Safranin 0 was found in the experimental group at 8 and 12 weeks, destructive changes were observed in the control joints. Morphological changes were evaluated using the histological grading scale. There was no significant difference between experimental and control groups at 4 weeks (mean 11.2 and 13.8 points, respectively). However, the mean scores of the experimental groups at 8 and 12 weeks (mean 6.8 and 7.5, respectively) were significantly better than those of the control groups at the same time points (mean 14 points each). Between the experimental groups, the scores at 8 and 12 weeks were both significantly better than those at 4 weeks.

Conclusion: A combination of subchondral drilling, joint motion and distraction by an articulated external fixator promoted repair of a fresh osteochondral defect in the weight bearing area. Although distraction for 4 weeks was not a long enough period to repair the defect, distraction for 8 and 12 weeks resulted in a good outcome.

Objective: From a clinical point of view, joint distraction as a treatment for osteoarthritis (OA) of hip and ankle has been demonstrated to be very promising. Pain, joint mobility and functional ability, the most important factors for a patient with severe OA, all improved. Although radiographic joint space enlargement in a significant number of patients suggested cartilage repair, actual cartilage repair remains difficult to evaluate. Therefore the present study was initiated to evaluate the actual effects of joint distraction on cartilage.

Methods: For this purpose a canine model for OA, anterior cruciate ligament transection (ACLT) was used. Sixteen weeks after ACLT articulating Ilizarov joint distraction of the knee was carried out. Absence of mechanical contact between articular surfaces and presence of intra-articular intermittent fluid pressure, characteristics of Ilizarov joint distraction, were confirmed. Twenty-five weeks after ACLT joint tissue of the dogs was analyzed.

Results: Biochemical analysis showed that after joint distraction the abnormal cartilage proteoglycan (PG) metabolism, characteristic for OA, had changed to a level found in control joints. Moreover, a mild degree of inflammation, present after ACLT, was reduced upon joint distraction. PG-content and histological cartilage degeneration had not (yet) improved within the time of treatment.

Discussion: Results suggest that the promising clinical results of Ilizarov joint distraction in patients with OA are accompanied by changes in cartilage metabolism. A change in proteoglycan turnover, indicating normalization of overall chondrocyte function, might in the long term, with normal joint use, lead to actual repair of cartilage.

Objective: Knee osteoarthritis (OA) is a degenerative joint disorder characterized by cartilage, bone, and synovial tissue changes that lead to pain and functional impairment. Joint distraction is a treatment that provides long-term improvement in pain and function accompanied by cartilage repair, as evaluated indirectly by imaging studies and measurement of biochemical markers. The purpose of this study was to evaluate cartilage tissue repair directly by histologic and biochemical assessments after joint distraction treatment.

Methods: In 27 dogs, OA was induced in the right knee joint (groove model; surgical damage to the femoral cartilage). After 10 weeks of OA development, the animals were randomized to 1 of 3 groups. Two groups were fitted with an external fixator, which they wore for a subsequent 10 weeks (one group with and one withoutjoint distraction), and the third group had no external fixation (OA control group). Pain/function was studied by force plate analysis. Cartilage integrity and chondrocyteactivity of the surgically untouched tibial plateaus were analyzed 25 weeks after removal of the fixator.

Results: Changes in force plate analysis values between the different treatment groups were not conclusive. Features of OA were present in the OA control group, in contrast to the generally less severe damage after joint distraction. Those treated with joint distraction had lower macroscopic and histologic damage scores, higher proteoglycan content, better retention of newly formed proteoglycans, and less collagen damage. In the fixator group without distraction, similarly diminished joint damage was found, although it was less pronounced.

Conclusion: Joint distraction as a treatment of experimentally induced OA results in cartilage repair activity, which corroborates the structural observations of cartilage repair indicated by surrogate markers in humans.

Purpose: The aim of this study was to evaluate the clinical results of a new distraction arthroplasty device when used in conjunction with a bone marrow–stimulating technique for the treatment of osteoarthritis of the knee.

Methods: We developed a new distraction arthroplasty device that allows continuous joint movement. We compared preoperative and postoperative findings for 6 knees (6 patients; age range, 42 to 58 years). The fixation period for the distraction device ranged from 7 to 13 weeks, and the follow-up period ranged from 1 to 3.5 years.

Results: The Japanese Orthopaedic Association knee score, range of motion, and joint space values were significantly improved in all cases at the latest follow-up (P < .05). Scores on a visual analogue pain scale were also significantly improved (P < .05).

Conclusions: We conclude that treatment using this new arthroplasty device in combination with a bone marrow–stimulating method was effective for osteoarthritic knees in middle-aged patients. Level of Evidence: Level IV, therapeutic case series.

Osteoarthritic disease is the result of mechanical and biological events that destabilize the normal processes of degradation and synthesis of articular cartilage chondrocytes, extracellular matrix, and subchondral bone. Osteoarthritis of the knee can cause symptoms ranging from mild to disabling. Initial management of most patients should be nonoperative, but because of the progressive nature of the disease, many patients with osteoarthritis of the knee eventually benefi t from operative treatment.

Various procedures have been described for treatment of the osteoarthritic knee, ranging from arthroscopic lavage and debridement to total knee arthroplasty. The aim of this study was to evaluate the clinical results of distraction arthroplasty combined with arthroscopic lavage and drilling of cartilage defects for treatment of osteoarthritis of the knee.

Nineteen patients (15 women and 4 men; age range, 39-65 years) were operated on. Pre- and postoperative fi ndings were compared. A control group comprising 42 patients treated with only arthroscopic procedures was evaluated for comparison. Follow- up ranged from 3 to 5 years.

Results were evaluated both clinically and radiologically postoperatively and throughout the follow-up period. Clinically, pain and walking capacity improved in most patients. Radiologically, joint space widening and improvement of the tibiofemoral angle was noted in nearly all patients.

Background: Modification of joint tissue damage is challenging in late-stage osteoarthritis (OA). Few options are available for treating end-stage knee OA other than joint replacement. Objectives To examine whether joint distraction can effectively modify knee joint tissue damage and has the potential to delay prosthesis surgery.

Methods: 20 patients (<60 years) with tibiofemoral OA were treated surgically using joint distraction. Distraction (~5 mm) was applied for 2 months using an external fixation frame. Tissue structure modification at 1 year of follow-up was evaluated radiographically (joint space width (JSW)), by MRI (segmentation of cartilage morphology) and by biochemical markers of collagen type II turnover, with operators blinded to time points. Clinical improvement was evaluated by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analogue Scale (VAS) pain score.

Results: Radiography demonstrated an increase in mean and minimum JSW (2.7 to 3.6 mm and 1.0 to1.9 mm; p<0.05 and <0.01). MRI revealed an increase in cartilage thickness (2.4 to 3.0 mm; p<0.001) and a decrease of denuded bone areas (22% to 5%; p<0.001). Collagen type II levels showed a trend towards increased synthesis (+103%; p<0.06) and decreased breakdown (−11%; p<0.08). The WOMAC index increased from 45to 77 points, and VAS pain decreased from 73 to 31 mm (both p<0.001).

Conclusions: Joint distraction can induce tissue structure modification in knee OA and could result in clinical benefit. No current treatment is able to induce such changes. Larger, longer and randomised studieson joint distraction are warranted.

Background: Treatment of severe osteoarthritis (OA) in relatively young patients is challenging. Although successful, total knee prosthesis has a limited lifespan, with the risk of revision surgery, especially in active young patients. Knee joint distraction (KJD) provides clinical benefit and tissue structure modification at 1-year follow-up. The present study evaluates whether this benefit is preserved during the second year of follow-up.

Methods: Patients included in this study presented with end-stage knee OA and an indication for total knee replacement (TKR); they were less than 60 years old with a VAS pain >60 mm (n = 20). KJD was applied for 2 months (range 54-64 days) and clinical parameters assessed using the WOMAC questionnaire and VAS pain score. Changes in cartilage structure were measured using quantitative MRI, radiography, and biochemical analyses of collagen type II turnover (ELISA).

Results: Average follow-up was 24 (range 23-25) months. Clinical improvement compared with baseline (BL) was observed at 2-year follow-up: WOMAC improved by 74% (P < 0.001) and VAS pain decreased by 61% (P < 0.001). Cartilage thickness observed by MRI (2.35 mm (95%CI, 2.06-2.65) at BL) was significantly greater at 2-year follow-up (2.78 mm (2.50-3.09); P < 0.03). Radiographic minimum joint space width(JSW) (1.1 mm (0.5 -1.7) at BL) was significantly increased at 2-year follow-up as well (1.7 mm (1.1-2.3); P < 0.03). The denuded area of subchondral bone visualized by MRI (22% (95%CI, 12.5-31.5) at BL) was significantly decreased at 2-year follow-up (8% (3.6-12.2); P < 0.004). The ratio of collagen type II synthesis over breakdown was increased at 2-year follow-up (P < 0.07).

Conclusion: Clinical improvement by KJD treatment is sustained for at least 2 years. Cartilage repair is still present after 2 years (MRI) and the newly formed tissue continues to be mechanically resilient as shown by an increased JSW under weight-bearing conditions.

Introduction: Osteoarthritis (OA) often affects the tibio-femoral joint, resulting in persistent pain, progressive cartilage damage, and impaired function. Although a total knee prosthesis (TKP) may finally become inevitable, at a relatively young age this comes with the risk of future revision surgery. Therefore, in these cases, joint preserving surgery such as knee joint distraction (KJD) is preferred. Here we present five-year follow-up data of KJD.

Methods: Patients (n=20; <60yrs) with conservative therapy resistant tibio-femoral OA were treated. Clinical evaluation was performed by WOMAC and VAS-pain scores. Changes in cartilage thickness were quantified by radiographs and MRI. The five-year changes after KJD were evaluated and compared with the natural progression of OA in OsteoArthritis-Initiative participants with similar baseline characteristics.

Results: Two patients withdrew informed consent and three other patients were treated with TKP (after three and four years). In these cases the last measures werecarried forward. Five years after treatment patients reported clinical improvementfrom baseline: Δ WOMAC +21,1 points (95%CI +8,9-+33,3; p=0.002), Δ VAS pain -27,6mm (95%CI -13,3–42,0; p<0.001). Minimum radiographic joint-space-width(JSW) was increased at five years as compared to pre-treatment values: Δ+0,43mm(95%CI +0,02-+0,84; p=0.040). Mean JSW on radiographs and mean cartilagethickness on MRI, of the most affected compartment (medial/lateral: 18/2), were after their initial statistically significant increase not statistically different frombaseline anymore (Δ+0,26mm; p=0.370, and Δ+0,23mm; p=0.177, respectively). Taking natural loss of cartilage thickness into account, this change was significantlydifferent from the changes as a result of estimated natural progression (Δ-0,39mmand Δ-0,18mm, respectively) resulting at five years in a difference of +0,65mm (95%CI +0,07-+1,23; p=0.031) and of +0,41mm (95%CI +0,07-+0,74; p=0.020) forradiographic mean JSW and average cartilage thickness on MRI, respectively.

Conclusion: KJD treatment results in prolonged clinical benefit, potentially explained by an initial boost of cartilaginous tissue repair that provides a long-term tissue structure benefit as compared to natural progression of tissue loss. KJD therefore represents a promising therapeutic option for young patients.

Objective: Knee joint distraction (KJD), a joint-preserving surgery for severe osteoarthritis (OA), provides clinical and structural improvement and postpones the need for total knee arthroplasty (TKA). This study evaluates 9-year treatment outcome and identifies characteristics predicting long-term treatment success.

Design: Patients with severe tibiofemoral OA (n = 20; age<60 years) indicated for TKA were treated with KJD. Questionnaires, radiographs, and magnetic resonance imaging (MRI) were used for evaluation. Survival after treatment was analyzed, where ‘failure’ was defined by TKA over time.

Results: 9-year survival was 48%, and 72% for men (compared to 14% for women; P = 0.035) and 73% for those with a first-year minimum joint space width (JSW) increase of >0.5 mm (compared to 0% for <0.05 mm; P = 0.002). Survivors still reported clinical improvement compared to baseline (ΔWOMAC +29.9 points (95%CI 16.9-42.9; P = 0.001), ΔVAS -46.8 mm (-31.6-61.9; P < 0.001)). Surprisingly, patients getting TKA years after KJD still reported clinical improvement although less pronounced (ΔWOMAC +20.5 points (-1.8-42.8; P = 0.067), ΔVAS -25.4 mm (-3.2-47.7; P = 0.030)). Survivors showed long-lasting minimum JSW increase (baseline 0.3 mm (IQR 1.9), follow-up 1.3 mm (2.5); P = 0.017) while ‘failures’ did not (baseline 0.4 mm (1.8), follow-up 0.2 mm (1.5); P = 0.161). First-year minimum JSW on radiographs and cartilage thickness increase on MRI predict 9-year survival (HR 0.05 and 0.12, respectively; both P < 0.026). Male gender was associated with survival (HR 0.24; P = 0.050).

Conclusion: KJD shows long-lasting clinical and structural improvement. In addition to a greater survival rate for males (>two out of three), the initial cartilage repair activity appears to be important for long-term clinical success.

Aim: In case of refractory knee osteoarthritis at a relatively young age causing persisting pain, treatment options are limited. In case of medial degeneration high tibial osteotomy (HTO) may be considered, or in case of more generalized OA, a total knee prosthesis (TKP). However, these young and active patients have a major risk of revision surgery. Knee joint distraction (KJD) could be an alternative treatment; prolonged clinical benefit and cartilage tissue repair have been demonstrated. Therefore, two RCTs were designed, evaluating clinical efficacy and for HTO additionally comparing cartilage tissue repair.

Materials and methods: Patients<65 years of age considered in regular clinical practice for TKP or HTO were included. TKP and HTO were performed according to usual standard of care. KJD was performed for six continuous weeks by use of an external fixator bridging the joint, fixed at each side to two bone pins.

Results: Inclusion rate was stable over time and took 42 and 22 months for TKP vs KJD and HTO vs KJD, respectively. At baseline, patient characteristics differed: age was 55.2±0.9 and 50.0±0.7 p<0.000, KOOS-score was 36.6±1.4 and 42.2±1.6 p=0.012, and VAS-pain was 68.7±2.1 and 61.4±2.4 p=0.028, in the KJD-TKP cohort and KJD-HTO cohort, respectively.

Conclusion: For implementation of KJD a comparison with available surgical alternatives is needed. TKP and HTO were chosen as the most relevant comparators. Inclusion is closed, and all treatments are completed. Data have to be awaited to determine the position of KJD in surgical treatment of refractory knee OA.A new articulated distraction arthroplasty device for treatment of the osteoarthritic knee joint: a preliminary report.

Purpose: Both, knee joint distraction as a relatively new approach and valgus-producing opening-wedge high tibial osteotomy (HTO), are knee-preserving treatments for knee osteoarthritis (OA). The efficacy of knee joint distraction compared to HTO has not been reported.

Methods: Sixty-nine patients with medial knee joint OA with a varus axis deviation of <10° were randomized to either knee joint distraction (n = 23) or HTO (n = 46). Questionnaires were assessed at baseline and 3, 6, and 12 months. Joint space width (JSW) as a surrogate measure for cartilage thickness was determined on standardized semi-flexed radiographs at baseline and 1-year follow-up.

Results: All patient-reported outcome measures (PROMS) improved significantly over 1 year (at 1 year p < 0.02) in both groups. At 1 year, the HTO group showed slightly greater improvement in 4 of the 16PROMS (p < 0.05). The minimum medial compartment JSW increased 0.8 ± 1.0 mm in the knee joint distraction group (p = 0.001) and 0.4 ± 0.5 mm in the HTO group (p < 0.001), with minimum JSW improvement in favour of knee joint distraction (p = 0.05). The lateral compartment showed a small increase in the knee joint distraction group and a small decrease in the HTO group, leading to a significant increase in mean JSW for knee joint distraction only(p < 0.02).

Conclusion: Cartilaginous repair activity, as indicated by JSW, and clinical outcome improvement occurred with both, knee joint distraction and HTO. These findings suggest that knee joint distraction may be an alternative therapy for medial compartmental OA with a limited mechanical leg malalignment. Level of evidence Randomized controlled trial, Level I.

Aims: Knee joint distraction (KJD) is a relatively new, knee-joint preserving procedure with the goal to postpone a first total knee arthroplasty (TKA) in specifically young and middle-aged patients, to decrease the chance for revision surgery later in life. However, the clinical efficacy of KJD has never been compared to TKA.

Patients and Methods: Sixty patients ≤ 65 years with end-stage knee osteoarthritis were randomized to either KJD (n=20) or TKA (n=40). Questionnaires were assessed at baseline, three, six, nine, and twelve months. In the KJD-group, radiographic joint space width (JSW), representing cartilage thickness, was determined as well.

Results:  Fifty-six patients received the allocated intervention (TKA=36, KJD=20). All patient reported outcome measures improved significantly over one year (at one year p<0.02) in both groups. At one year, the TKA-group showed a greater improvement in only 1 out of the 16 PROMS assessed (p<0.05). OARSI-OMERACT clinical response was 83% after TKA and 80% after KJD. Twelve patients (60%) in the KJD-group suffered from pin tract infections. In the KJD-group both minimum (+0.9±1.1mm,) and mean JSW (+1.2±1.1mm) increased significantly (p<0.01).

Conclusions: In relatively young patients with end-stage knee osteoarthritis treatment with KJD did not demonstrate relevant inferiority in efficacy compared to TKA.Arthrodiatasis for management of knee osteoarthritis.

Objective: Both, knee joint distraction (KJD) and high tibial osteotomy (HTO) are joint-preserving surgeries that postpone total knee arthroplasty (TKA) in younger osteoarthritis (OA) patients. Here we evaluate the 2-year follow-up of KJD versus TKA and KJD versus HTO in 2 noninferiority studies.

Design: Knee OA patients indicated for TKA were randomized to KJD ( n = 20; KJDTKA) or TKA ( n = 40). Medial compartmental knee OA patients considered for HTO were randomized to KJD ( n = 23; KJDHTO) or HTO ( n = 46). Patient-reported outcome measures were assessed over 2 years of follow-up. The radiographic joint space width (JSW) was measured yearly. In the KJD groups, serum-PIIANP and urinary-CTXII levels were measured as collagen type-II synthesis and breakdown markers. It was hypothesized that there was no clinically important difference in the primary outcome, the total WOMAC, when comparing KJD with HTO and with TKA.

Results: Both trials were completed, with 114 patients (19 KJDTKA; 34 TKA; 20 KJDHTO; 41 HTO) available for 2-year analyses. At 2 years, the total WOMAC score (KJDTKA: +38.9 [95%CI 28.8-48.9] points; TKA: +42.1 [34.5-49.7]; KJDHTO: +26.8 [17.1-36.6]; HTO: +34.4 [28.0-40.7]; all: P < 0.05) and radiographic minimum JSW (KJDTKA: +0.9 [0.2-1.6] mm; KJDHTO: +0.9 [0.5-1.4]; HTO: +0.6 [0.3-0.9]; all: P < 0.05) were still increased for all groups. The net collagen type-II synthesis 2 years after KJD was increased ( P < 0.05). Half of KJD patients experienced pin tract infections, successfully treated with oral antibiotics.

Conclusions: Sustained improvement of clinical benefit and (hyaline) cartilage thickness increase after KJD is demonstrated. KJD was clinically noninferior to HTO and TKA in the primary outcome.

Background and purpose: During knee joint distraction (KJD) treatment, using an external fixation-frame, pin-tract infections frequently occur. These local skin infections, although treated successfully with oral antibiotics, might lead to latent infections. This raises concern about subsequent placement of a total knee prosthesis (TKP). This study evaluates the first five cases in which patients had to be treated with TKO after KJD failure.

Patients and methods: An overall survival analysis of the first 26 patients treated with KJD revealed five failures, because of declining efficacy over time. These patients were treated with TKP. Complications of these TKPs are described and all cases were compared with age and gender matched primary-TKP-controls. WOMAC and VAS pain scores were assessed before and after TKP treatment.

Results: The mean survival time of the five KJD before TKP was 61 ± 15 months (range 45-84 months). No peri-operative complications were registered and none of the patients suffered from an infection post-TKP. There were no differences between baseline characteristics of patients with primary TKP compared to those with TKP after KJD except for a higher VAS pain score (p<0.02) for primary TKP. Mean follow-up after TKP was 21 ± 12 months (range 9-39 months). Efficacy after TKP was similar for patients with primary TKP compared to those with TKP after KJD.

Conclusion: Based on the first five cases it appears safe to treat patients several years after KJD with a TKP. There is no indication these patients have a higher infection risk and post-operative outcome is comparable with primary TKP.

Background: Knee joint distraction (KJD) is a surgical joint-preserving treatment in which the knee joint is temporarily distracted by an external frame. It is associated with joint tissue repair and clinical improvement. Initially, patients were submitted to an eight-week distraction period, and currently patients are submitted to a six-week distraction period. This study evaluates whether a shorter distraction period influences the outcome.

Methods: Both groups consisted of 20 patients. Clinical outcome was assessed by WOMAC questionnaires and VAS-pain. Cartilaginous tissue repair was assessed by radiographic joint space width (JSW) and MRI-observed cartilage thickness.

Results: Baseline data between both groups were comparable. Both groups showed an increase in total WOMAC score; 24 ± 4 in the six-week group and 32 ± 5 in the eight-week group (both p < 0.001). Mean JSW increased 0.9 ± 0.3 mm in the six-week group and 1.1 ± 0.3 mm in the eight-week group (p = 0.729 between groups). The increase in mean cartilage thickness on MRI was 0.6 ± 0.2 mm in the eight-week group and 0.4 ± 0.1 mm in the six-week group (p = 0.277).

Conclusions: A shorter distraction period does not influence short-term clinical and structural outcomes statistically significantly, although effect sizes tend to be smaller in six week KJD as compared to eight week KJDKnee joint distraction compared with high tibial osteotomy: a randomized controlled trial.

Objective: High tibial osteotomy (HTO) and knee joint distraction (KJD) are treatments to unload the osteoarthritic (OA) joint with proven success in postponing a total knee arthroplasty (TKA). While both treatments demonstrate joint repair, there is limited information about the quality of the regenerated tissue. Therefore, the change in quality of the repaired cartilaginous tissue after KJD and HTO was studied using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC).

Design: Forty patients (20 KJD and 20 HTO), treated for medial tibiofemoral OA, were included in this study. Radiographic outcomes, clinical characteristics, and cartilage quality were evaluated at baseline, and at 1- and 2-year follow-up.

Results: Two years after KJD treatment, clear clinical improvement was observed. Moreover, a statistically significant increased medial (Δ 0.99 mm), minimal (Δ 1.04 mm), and mean (Δ 0.68 mm) radiographic joint space width (JSW) was demonstrated. Likewise, medial (Δ 1.03 mm), minimal (Δ 0.72 mm), and mean (Δ 0.46 mm) JSW were statistically significantly increased on radiographs after HTO. There was on average no statistically significant change in dGEMRIC indices over two years and no difference between treatments. Yet there seemed to be a clinically relevant, positive relation between increase in cartilage quality and patients’ experienced clinical benefit.

Conclusions: Treatment of knee OA by either HTO or KJD leads to clinical benefit, and an increase in cartilage thickness on weightbearing radiographs for over 2 years posttreatment. This cartilaginous tissue was on average not different from baseline, as determined by dGEMRIC, whereas changes in quality at the individual level correlated with clinical benefit.

Objective: Knee joint distraction (KJD) is a novel, but poorly understood, treatment for osteoarthritis (OA) associated with remarkable ‘spontaneous’ cartilage repair in which resident synovial fluid (SF) multipotential mesenchymal stromal cells (MSCs) may play a role. We hypothesised that SF hyaluronic acid (HA) inhibited the initial interaction between MSCs and cartilage, a key first step to integration, and postulate that KJD environment favoured MSC/cartilage interactions.

Methods: Attachment of dual-labelled SF-MSCs were assessed in a novel in vitro human cartilage model using OA and rheumatoid arthritic (RA) SF. SF was digested with hyaluronidase (hyase) and its effect on adhesion was observed using confocal microscopy. MRI and microscopy were used to image autologous dual-labelled MSCs in an in vivo canine model of KJD. SF-HA was investigated using gel electrophoresis and densitometry.

Results: Osteoarthritic-synovial fluid (OA-SF) and purified high molecular weight (MW) HA inhibited SF-MSC adhesion to plastic, while hyase treatment of OA-SF but not RA-SF significantly increased MSC adhesion to cartilage (3.7-fold, p<0.05) These differences were linked to the SF mediated HA-coat which was larger in OA-SF than in RA-SF. OA-SF contained >9 MDa HA and this correlated with increases in adhesion (r=0.880). In the canine KJD model, MSC adhesion to cartilage was evident and also dependent on HA MW.

Conclusions: These findings highlight an unappreciated role of SF-HA on MSC interactions and provide proof of concept that endogenous SF-MSCs are capable of adhering to cartilage in a favourable biochemical and biomechanical environment in OA distracted joints, offering novel one-stage strategies towards joint repair.

Objective: In end-stage knee osteoarthritis the treatment of choice is total knee arthroplasty (TKA). An alternative treatment is knee joint distraction (KJD), suggested to postpone TKA. Several studies reported significant and prolonged clinical improvement of KJD. To make an appropriate decision regarding the position of this treatment, a cost-effectiveness and cost-utility analysis from healthcare perspective for different age and gender categories was performed.

Methods: A treatment strategy starting with TKA and a strategy starting with KJD for patients of different age and gender was simulated. To extrapolate outcomes to long-term health and economic outcomes a Markov (Health state) model was used. The number of surgeries, QALYs, and treatment costs per strategy were calculated. Costs-effectiveness is expressed using the cost-effectiveness plane and cost-effectiveness acceptability curves.

Results: Starting with KJD the number of knee replacing procedures could be reduced, most clearly in the younger age categories; especially revision surgery. This resulted in the KJD strategy being dominant (more effective with cost-savings) in about 80% of simulations (with only inferiority in about 1%) in these age categories when compared to TKA. At a willingness to pay of 20.000 Euro per QALY gained, the probability of starting with KJD to be cost-effective compared to starting with a TKA was already found to be over 75% for all age categories and over 90-95% for the younger age categories.

Conclusion: A treatment strategy starting with knee joint distraction for knee osteoarthritis has a large potential for being a cost-effective intervention, especially for the relatively young patient.