F. Intema

A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models

BackgroundThis study evaluates changes in peri-articular bone in two canine models for osteoarthritis: the groove model and the anterior cruciate ligament transection (ACLT) model.MethodsEvaluation was performed at 10 and 20 weeks post-surgery and in addition a 3-weeks time point was studied for the groove model. Cartilage was analysed, and architecture of the subchondral plate and trabecular bone of epiphyses was quantified using micro-CT.ResultsAt 10 and 20 weeks cartilage histology and biochemistry demonstrated characteristic features of osteoarthritis in both models (very mild changes at 3 weeks). The groove model presented osteophytes only at 20 weeks, whereas the ACLT model showed osteophytes already at 10 weeks. Trabecular bone changes in the groove model were small and not consistent. This contrasts the ACLT model in which bone volume fraction was clearly reduced at 10 and 20 weeks (15–20%). However, changes in metaphyseal bone indicate unloading in the ACLT model, not in the groove model. For both models the subchondral plate thickness was strongly reduced (25–40%) and plate porosity was strongly increased (25–85%) at all time points studied.ConclusionThese findings show differential regulation of subchondral trabecular bone in the groove and ACLT model, with mild changes in the groove model and more severe changes in the ACLT model. In the ACLT model, part of these changes may be explained by unloading of the treated leg. In contrast, subchondral plate thinning and increased porosity were very consistent in both models, independent of loading conditions, indicating that this thinning is an early response in the osteoarthritis process.

In early OA, thinning of the subchondral plate is directly related to cartilage damage: results from a canine ACLT-meniscectomy model

OBJECTIVE The pathogenesis of osteoarthritis (OA) includes cartilage degeneration, synovial inflammation, and bone changes. Slowly, the sequence and inter-relationship of these features is becoming clearer. Early models of OA suggest thinning of the subchondral plate in addition to trabecular bone changes. In the present study subchondral bone changes were studied in the canine anterior cruciate ligament transection (ACLT)-meniscectomy model. This model is characterized by intra-joint variability with respect to cartilage damage (predominantly medial) and loading (lateral unloading due to a shifted axis). METHODS In 13 Labrador dogs, OA was induced by transection of the anterior cruciate ligament and removal of the medial meniscus. Twelve weeks later, cartilage integrity was evaluated histologically using the modified Mankin score (0-11), and proteoglycan content was determined by Alcian Blue assay. Bone architecture of the tibia was quantified by micro-CT. RESULTS Cartilage damage was severe in the medial compartment (Mankin score +3.5, glycosaminoglycan (GAG) content -28%) and mild in the lateral compartment (Mankin score +1.6, GAG content -15%). Thinning and porosity of the subchondral plate were only present on the medial side (-21%, +87%, respectively). Interestingly, changes in trabecular bone structure did almost not occur in the medial compartment (volume fraction -7%) but were clear in the lateral compartment (-20%). CONCLUSION Thinning of the subchondral plate is a localized phenomenon related to cartilage degeneration while trabecular bone changes are related to mechanical (un)loading. The different mechanisms responsible for bone changes in OA should be taken in account when designing and interpreting studies interfering with bone turnover in the treatment of OA.

Tissue structure modification in knee osteoarthritis by use of joint distraction: an open 1-year pilot study

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 to 1.9 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 45 to 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 studies on joint distraction are warranted.

Unloading joints to treat osteoarthritis, including joint distraction

Purpose of reviewPatients are increasingly becoming interested in nonpharmacologic 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 findingsMechanical 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. SummaryTo 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.

Similarities and discrepancies in subchondral bone structure in two differently induced canine models of osteoarthritis

In osteoarthritis (OA), cartilage degradation is accompanied by subchondral bone changes. The pathogenesis and physiology of bone changes in OA are still unclear. The changes in subchondral bone architecture and cartilage damage were compared in differently induced experimental models of OA. Experimental OA was induced bilaterally by anterior cruciate ligament transection (ACLT) or by cartilage trauma (Groove model); bilateral sham surgery served as control. Lysylpyridinoline (LP, bone resorption) and C‐telopeptide of type II collagen (CTX‐II, cartilage breakdown) were measured over time. At 20 weeks after surgery, the subchondral cortical plate and trabecular bone of the tibia were analyzed by micro–computed tomography (µCT) and cartilage degeneration was analyzed histologically and biochemically. In both models, cartilage degeneration and cortical subchondral plate thinning were present. CTX‐II levels were elevated over time in both models. Subchondral trabecular bone changes were observed only in the ACLT model, not in the Groove model. Correspondingly, LP levels were elevated over time in the ACLT model and not in the Groove model. Interestingly, the trabecular bone changes in the ACLT model were extended to the metaphyseal area. The early decrease in plate thickness, present in both models, as was cartilage damage, suggests that plate thinning is a phenomenon that is intrinsic to the process of OA independent of the cause/induction of OA. On the other hand, trabecular changes in subchondral and metaphyseal bone are not part of a common pathway of OA development and may be induced biomechanically in the destabilized and less loaded ACLT joint.

The canine bilateral groove model of osteoarthritis

In studies aimed at local treatment of experimental osteoarthritis (OA) it is optimal to have an internal (untreated) OA control. Such an approach excludes interanimal variation, and allows paired statistical evaluation of treatment efficacy. For this purpose, we developed and characterized a bilateral version of the canine Groove model. We hypothesized that the bilateral version of the canine Groove model would show consistent and clear development of features of OA similar to those found in the unilateral version. In six Beagle dogs, grooves were surgically made in the articular cartilage of the femoral condyles of both knee joints. Six additional dogs underwent bilateral sham surgery. The degree of OA was quantified 20 weeks after surgery and was compared in retrospect to 23 animals that undergone the same procedure in a single knee joint with the contralateral knee serving as a non‐OA control. Bilateral groove surgery resulted in OA. This was based on the observed ineffective repair response in which an increase in proteoglycan synthesis, a diminished retention of these newly formed proteoglycans, and an enhanced loss of resident proteoglycans resulted in a decreased cartilage proteoglycan content. These biochemical effects were corroborated by clear histological features of OA. All these effects were found in femor as well as in the (surgically untouched) tibia. Interestingly, features of OA were slightly more severe in the bilateral model than in the unilateral variant. The bilateral canine Groove model showed consistent and clear development of features of OA, comparable to the unilateral model.

Evidence of cartilage repair by joint distraction in a canine model of osteoarthritis

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.

Five-Year Follow-up of Knee Joint Distraction : Clinical Benefit and Cartilaginous Tissue Repair in an Open Uncontrolled Prospective Study

Objective In end-stage knee osteoarthritis, total knee arthroplasty (TKA) 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 5-year follow-up data of KJD. Design Patients (n = 20; age <60 years) with conservative therapy resistant tibiofemoral osteoarthritis considered for TKA were treated. Clinical evaluation was performed by questionnaires. Change in cartilage thickness was quantified on radiographs and magnetic resonance images (MRI). The 5-year changes after KJD were evaluated and compared with the natural progression of osteoarthritis using Osteoarthritis Initiative data. Results Five-years posttreatment, patients still reported clinical improvement from baseline: ΔWOMAC (Western Ontario and McMaster Universities Arthritis Index) +21.1 points (95% CI +8.9 to +33.3; P = 0.002), ΔVAS (visual analogue scale score) pain −27.6 mm (95%CI −13.3 to −42.0; P < 0.001), and minimum radiographic joint space width (JSW) of the most affected compartment (MAC) remained increased as well: Δ +0.43 mm (95% CI +0.02 to +0.84; P = 0.040). Improvement of mean JSW (x-ray) and mean cartilage thickness (MRI) of the MAC, were not statistically different from baseline anymore (Δ +0.26 mm; P = 0.370, and Δ +0.23 mm; P = 0.177). Multivariable linear regression analysis indicated that KJD treatment was associated with significantly less progression in mean and min JSW (x-ray) and mean cartilage thickness (MRI) compared with natural progression (all Ps <0.001). Conclusions 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. Level of evidence, II.

321 TISSUE STRUCTURE MODIFICATION IN END-STAGE KNEE OSTEOARTHRITIS BY USE OF JOINT DISTRACTION

to accomplish activities of daily living, to make the most of life (taking care of relatives, mainly grand-children, having a full social life), to be able to do what matters most. About personal integrity, patients expected a TKA that does not show, to forget having a TKA, a TKA that is not fragile and will last for a long time. Physicians had a quite realistic representation of what patients’ expectations usually are which does not mean that they fulfill these expectations especially those concerning care providers. Care providers had also expectations about patients which are classified in two main categories “the good patient” (cooperative, understanding, mature, as patients) and those potentially posing problems (over informed, asking for a personal relationship, who do not want to ear or understand, asking for surgery at once). Conclusions: Our results suggest that patients’ satisfaction about TKA could be increased by better analyzing and discussing patients’ expectations with them in order to make these expectations more realistic and individualized.

078 JOINT DISTRACTION IN TREATMENT OF CANINE EXPERIMENTALLY INDUCED OSTEOARTHRITIS LEADS TO CARTILAGE REPAIR ACCOMPANIED BY SUSTAINED RELIEVE OF PAIN

Purpose: Unlike for knee arthroplasties, there is no national register on high tibial osteotomies (HTO’s) performed in Sweden. Information on the outcome of HTO as a treatment for knee osteoarthritis (OA) is insufficient. The aim of this study was to evaluate the use and outcome, expressed by rate of revision to knee arthroplasty, of HTO’s performed in Sweden 1998-2007. Methods: Using the in-patient and out-patient care registers of the Swedish National Board of Health and Welfare during 1998-2007, patients 30 years or older, with the surgical code NGK 59 (angle, rotation or correction osteotomy in the knee or tibia) in combination with the ICD-10 code M17 (knee osteoarthritis), were identified. The number of surgeries per clinic and County, the genderand age distribution as well as changes over time were evaluated. Conversion of HTO to knee arthroplasty was identified using the Swedish Knee Arthroplasty Register (SKAR). 446/3,246 HTO’s had been converted but for 42 of these side of the the HTO was unknown and thus, if the subsequent arthroplasty had been on the same knee. In these cases we assumed a worst case scenario of the arthroplasty being a conversion. A 10-year survival analysis was performed using revision to an arthroplasty as the end point. Results: During 1998-2007 3246 HTO (2885 patients) were identified, or 325 per year on average. 8% were out-patient surgeries. During the period there was a 30% decrease in the number of HTO’s performed per year. Men had surgery more often (69%) and their mean age at surgery was 52 years (SD 8) as compared to 50 years (SD 7) in women. In 1998, 58% of the patients were younger than 55 years, compared to 65% in 2007, with similar trends for men and women. HTO’s were carried out in all Counties of Sweden. Five clinics (out of 75) performed 25% of all the HTO’s. As a percentage of all knee reconstructions, HTO decreased from 6% in 1998 to barely 3% in 2007. The cumulative revision rate (CRR) at 10 years, based on a worst case scenario, was 16% (95% CI 14-24). The risk of revision after adjusting for age was significantly higher in women than men (RR 1.45 (95% CI 1.14-1.83), p=0.002. Conclusions: In absolute numbers HTO has decreased by 30% during 19982007 and constituted less than 3% of the primary knee reconstructions in 2007. HTO was almost exclusively used for patients younger than 65 years. The majority of the HTOs was performed in clinics performing only few surgeries per year. With HTO becoming uncommon, a need to concentrate these surgeries to fewer and more experienced centers should be considered. The rate of conversion to knee arthroplasty was similar to what has been seen for unicompartmental knee arthroplasty.