Severity Of Joint Degeneration Research Articles

Hybrid single-photon emission computed tomography bone imaging for the evaluation of non-specific lower back pain

BackgroundThis is a single-center retrospective study designed to assess the correlation between the location of “hots spots” on single-photon emission computed tomography (SPECT) and the severity of joint degeneration on computed tomography (CT), in addition to understanding whether these hot spots correlate with the pain generating sites causing the non-specific lower back pain. MethodsAll patients who had undergone hybrid SPECT-CT imaging of the lower back over a one-year period at our institution were identified. Twenty joints were assessed from each patient. Joints for assessment were chosen from the intervertebral discs, facet (zygapophysial) and sacroiliac joints. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) curves and quantified using the area under the receiver operating characteristic curve (AUROC). ResultsOver a one-year period, 111 patients were identified, with the primary indication being non-specific lower back pain in 73 (66%). Hot spots were observed on SPECT in 79% of patients, with 86% having some degree of degeneration in at least one joint on CT. Degeneration was found to be significantly associated with the presence of hot spots for the majority of joints, with the strongest association seen in the L3/L4 intervertebral joint, for which the rates of hot spots were 1% for grade 0, 26% for grade 1 and 78% for grades 2–3 (AUROC: 0.91, p<0.001). Neither the presence of hot spots nor degeneration were found to be significantly predictive of non-specific lower back pain for any of the joints considered. ConclusionsHot spots identified on SPECT are correlated with the presence of degeneration on CT but have limited diagnostic ability to identify potential causes of non-specific lower back pain.

Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1

Osteoarthritis (OA) is a prevalent joint disease with no effective treatment strategies. Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis. Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies, the epigenetic control of OA remains unclear. Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes, including cell differentiation, proliferation, autophagy, and apoptosis. However, the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown. In this work, we confirmed the upregulation of JMJD3 in aberrant force-induced cartilage injury in vitro and in vivo. Functionally, inhibition of JMJD3 by its inhibitor, GSK-J4, or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury. Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression. Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis, cartilage degeneration, extracellular matrix degradation, and inflammatory responses. In vivo, anterior cruciate ligament transection (ACLT) was performed to construct an OA model, and the therapeutic effect of GSK-J4 was validated. More importantly, we adopted a peptide-siRNA nanoplatform to deliver si-JMJD3 into articular cartilage, and the severity of joint degeneration was remarkably mitigated. Taken together, our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression. Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-siRNA nanocomplexes.

Groove model of tibia-femoral osteoarthritis in the rat.

ABSTRACTSeveral experimental models of osteoarthritis in rats are used to study the pathophysiology of osteoarthritis. Many mechanically induced models have the limitation that permanent joint instability is induced by, for example, ligament transection or meniscal damage. This permanent instability will counteract the potential beneficial effects of therapy. The groove model of osteoarthritis uses a one‐time trigger, surgically induced cartilage damage on the femoral condyles, and has been validated for the canine tibia‐femoral compartment. The present study evaluates this model for the rat knee joint. The articular cartilage of the weight bearing surface of both femoral condyles and trochlea were damaged (grooved) without damaging the underlying subchondral bone. Severity of joint degeneration was histologically assessed, in addition to patella cartilage damage, and subchondral bone characteristics by means of (contrast‐enhanced) micro‐CT. Mild histological degeneration of the surgically untouched tibial plateau cartilage was observed in addition to damage of the femoral condyles, without clear synovial tissue inflammation. Contrast enhanced micro‐CT demonstrated proteoglycan loss of the surgically untouched patella cartilage. Besides, a more sclerotic structure of the subchondral bone was observed. The tibia‐femoral groove model in a rat results in mild knee joint degeneration, without permanent joint instability and joint inflammation. This makes the rat groove model a useful model to study the onset and progression of post‐traumatic non‐inflammatory osteoarthritis, creating a relatively sensitive model to study disease modifying osteoarthritic drugs. © 2016 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 35:496–505, 2017.

Arthroscopic Partial Meniscectomy: MR Imaging for Prediction of Outcome in Middle-Aged and Elderly Patients

To determine whether preoperative magnetic resonance (MR) imaging could help identify factors associated with poor clinical outcome after arthroscopic partial meniscectomy (APM) in middle-aged and elderly patients with meniscal tears. The prospective, institutional review board-approved, HIPAA-compliant study was performed with informed consent in 53 men and 47 women (average ages, 54.5 and 56.6 years, respectively). Patients underwent knee MR imaging before APM; clinical symptoms were evaluated preoperatively and 1 year postoperatively with International Knee Documentation Committee (IKDC) questionnaire. Overall severity of knee joint degeneration and severity of each feature of joint degeneration were assessed with Boston Leads Osteoarthritis Knee (BLOK) scoring system. Tear length was measured, and type of meniscal tear was classified. Spearman correlation coefficients and relative risks showed the relationship between clinical outcome after APM (difference between preoperative and postoperative IKDC scores) and severity of joint degeneration. Seventy-four patients with isolated medial APM had a significant (P < .05) inverse correlation between clinical outcome and severity of cartilage loss and bone marrow edema in the medial femoral condyle and medial tibial plateau. Fifteen patients with isolated lateral APM had a significant (P < .05) inverse correlation between clinical outcome and severity of cartilage loss in the lateral femoral condyle and lateral tibial plateau and bone marrow edema in the lateral femoral condyle. One hundred patients with APM had a significant (P < .05) inverse correlation between clinical outcome and severity of meniscal extrusion, total BLOK score, and meniscal tear length. A significantly (P < .05) increased relative risk that a patient would not definitely improve after APM was observed if a meniscal root tear was present. Poorer clinical outcome after APM was associated with greater severity of cartilage loss and bone marrow edema in the same compartment as the meniscal tear, greater severity of meniscal extrusion, greater overall severity of joint degeneration, a meniscal root tear, and a longer meniscal tear at preoperative MR imaging.

Unravelling the relationship between age, nociception and joint destruction in naturally occurring osteoarthritis of Dunkin Hartley guinea pigs

Osteoarthritis (OA) is a debilitating and painful disease, the incidence of which increases with advancing age. One of the confounding aspects of OA is that there is a disconnect between the severity of joint degeneration and the intensity of pain reported. This study examined the relationship between age, joint nociception, and joint pathology in an animal model of naturally occurring OA. Dunkin Hartley guinea pigs were grouped according to age: young (2–5 months) and senescent (17–37 months). Joint nociception was objectively measured in these animals by recording electrophysiologically from knee joint primary afferents in response to non-noxious and noxious movements of the knee. Joint pathology in the same knees was then determined by histomorphology and micro-computerized tomography (micro-CT). A principal components analysis was carried out on the data to determine if any correlation exists between each of the measured variables. In aged guinea pigs, 33% of joint mechanosensory nerves were spontaneously active, whereas young animals showed no such neural activity at rest. The frequency of afferent firing evoked by noxious movements was greater in old guinea pigs. Micro-CT and histopathological determination of OA positively correlated with age; however, there was no significant correlation between the severity of joint degeneration and nociception. In the Dunkin Hartley model of inveterate OA, the level of joint pathology correlates well with increasing age. This study also provides the first objective evidence that there is no correlation between joint nociception and articular damage, thereby corroborating the clinical observation that pain is a poor predictor of OA severity.

Biomarkers of Cartilage and Bone Damage as a Measure of Joint Damage in Haemophilia.

Purpose Biomarkers of bone and cartilage turnover have frequently been evaluated for joint diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). Results have thus fare not been very conclusive. Some biomarkers such as urinary CTXII and serum COMP appear to correlate with severity of joint degeneration, whereas other are less distinctive. Hemophilic arthropathy (HA) is a very progressive joint degeneration as a result of frequent joint bleeds. From clinical practice it is concluded that the rate of degeneration exceeds that of OA and RA joints. This degeneration has characteristics of both inflammation mediated (as seen in RA) and degenerative (as seen in OA) joint disease. Furthermore, the joint damage is largely restricted to 3 major joints (ankle, knees, and elbows). Therefore, it might be that this rapidly progressive, localized joint degeneration can be used for the evaluation and validation of biomarkers of cartilage and bone turnover. In the present study we therefore investigated whether commercially available biomarkers of cartilage and bone in blood and/or urine are associated with severity of joint damage in patients with haemophilic arthropathy.Methods Blood and urine were collected from 36 patients suffering from haemophilia. Urine samples were assessed for the amount of CTX-I and CTX-II. Serum samples were assessed for the amount of CTX-I, CTX-II, COMP, C1,2C, C2C, and CS846. Radiographs of ankles, knees and elbows were scored according to Pettersson, a radiographic joint score specific for haemophilic arthropathy based on cartilage and bone changes.Results U-CTX-II (R=0.39; p=0.01), C1,2C (R=0.31; p=0.04) and CS846 (R=0.31; p=0.03) showed (marginal) correlations with the Pettersson score. Slightly better correlations were obtained when only narrowing of joint space width (JSW) as one of the items in the Pettersson score was used. The other biomarkers showed no correlation with the Pettersson score. Also the bone biomarkers did not correlate with specific bone changes. Interestingly, combined indexes of different markers, based on linear stepwise regression analysis, increased the correlation significantly up to R=0.65; p≤0.001) for the combination of U-CTX-II, COMP and CS846.Conclusions The present results show that even despite this rapidly progressive degeneration of 6 large joints, from the individual biomarkers determined only U-CTX-II, C1,2C and CS846 show correlation with the severity of arthropathy. Importantly, a relation improved when the markers were related to the process they are supposed to describe (cartilage degeneration markers with JSW narrowing). Most important, combination of markers, significantly improve the relation with the radiographically determined joint degeneration. In general however, it may be concluded that these markers alone seem not of sufficient value for evaluation of joint damage yet.

Arthroscopic Synovectomy of the Wrist in Rheumatoid Arthritis

Purpose : We evaluated the therapeutic effectiveness of arthroscopic synovectomy in patients with rheumatoid wrists. Materials and Methods : Nineteen wrists in 18 patients (4 males and 14 females, average age 49.2 years) who had not responded to anti-rheumatic medications, were treated with arthroscopic synovectomy. Patients’subjective symptoms were evaluated using a visual analogue scale for pain and satisfaction. Standard posteroanterior radiographs taken preoperatively and at the final follow up were analyzed using the modified Larsen/Rau score system (normal, 0; total destruction, 40). The average follow up period was 29.5 months. Results : The mean preoperative pain score was 8.6 and this decreased to 3.6 one year after the operation, but increased to 4.4 at the final follow-up, suggesting a tendency of pain aggravation with time. The average satisfaction score at the final follow up was 6.3. The mean modified Larsen/Rau score was 6.1 preoperatively and this increased to 8.4 at the final radiographs, demonstrating the slow progression of degenerative changes. The severity of joint degeneration showed no correlation with the postoperative results. Conclusion : Arthroscopic synovectomy of rheumatoid wrists results in an effective reduction of pain and high satisfaction. Prolonged benefit should be observed by long term follow-up.