Course Of Knee Osteoarthritis Research Articles

Identifying common trajectories of joint space narrowing over two years in knee osteoarthritis

Little is known about the natural history of knee osteoarthritis (OA). We sought to identify common patterns of joint space narrowing (JSN) in well-characterized knee OA patients in the placebo arm of a 2-year international study. We performed secondary data analyses of 622 adults ages 39-80 years in North America (n = 310) and Europe (n = 312) with symptomatic knee OA. Fluoroscopically positioned semiflexed anteroposterior radiographs were obtained at 0, 12, and 24 months. Group-based trajectory modeling was used to identify distinctive groups of individuals with similar trajectories of JSN, taking into account sex, age, and body mass index. Seven groups were identified. Four exhibited joint space width (JSW) stability over 2 years representing the most common trajectory (71%), which was unrelated to initial JSW. Atypical courses included slow, rapid, and moderate progressors; most had significant JSN at study entry. Slow progressors (20%) had a mean JSN of 0.2 mm over 2 years. Only 2% of the sample demonstrated rapid JSN (2.1 mm), while 7% had JSN of 0.7 mm. Rapid progressors tended to be men, while slow and moderate progressors were older and heavier. Most (70%) people with OA demonstrated no significant JSN over 2 years; 20% showed slow progression, 7% had moderate, and 2% had rapid JSN. Progressors tended to have less JSW at study entry and were older and heavier; rapid progressors were more likely to be men. Understanding common patterns of the course of knee OA may offer new opportunities to target those at greatest risk of disability.

Potential Influence of Interleukin-1 Receptor Antagonist Gene Polymorphism on Knee Osteoarthritis Risk

Objectives:Genes encoding for cytokines have been associated with susceptibility for joint osteoarthritis (OA) and interleukin (IL)-1 gene is supposed to be involved in the cartilage destruction process. In this regard, interleukin-1 receptor antagonist (IL-1RA) competing with IL-1 for binding to its receptor may act as an inhibitor of cartilage breakdown. We assessed the association of primary knee OA with IL-1RA region as a putative factor of susceptibility to knee OA in Egyptian patients.Design and methods:Eighty patients with primary knee OA and 40 aged-matched healthy controls were included into the study. DNA samples were used to study genotypes of IL-1RN gene by polymerase chain reaction (PCR) in both groups.Results:An increased frequency of the IL-1RN*1 and IL-1RN*2 alleles was found in OA patients relative to controls (60.5% vs. 39.5%,P= 0.039, 85.4% vs. 14.6%,P= 0.002, respectively) however, only the carriage rate of IL-1RN*2 allele was found to be significant when OA patients were compared to the controls. Significant higher frequencies of IL-1RN*1/*2 and IL-1RN*2/*2 genotypes in OA patients were observed as compared with controls. Both visual analogue scale (VAS) and radiographic score revealed significant correlation with both the allelic frequency and the carriage rate of IL-1RN*2 allele. Moreover, absolute frequency of IL-1RN*1/*2 genotype OA patients revealed severe VAS and high radiographic score.Conclusion:These results suggest that IL-1RN*2 allele represent a significant factor influencing the severity and course of knee OA; thereby supporting the potential role of IL-1 in the pathogenesis of this disease.

Potential influence of interleukin-1 receptor antagonist gene polymorphism on knee osteoarthritis risk.

Objectives: Genes encoding for cytokines have been associated with susceptibility for joint osteoarthritis (OA) and interleukin (IL)-1 gene is supposed to be involved in the cartilage destruction process. In this regard, interleukin-1 receptor antagonist (IL-1RA) competing with IL-1 for binding to its receptor may act as an inhibitor of cartilage breakdown. We assessed the association of primary knee OA with IL-1RA region as a putative factor of susceptibility to knee OA in Egyptian patients. Design and methods: Eighty patients with primary knee OA and 40 aged-matched healthy controls were included into the study. DNA samples were used to study genotypes of IL-1RN gene by polymerase chain reaction (PCR) in both groups. Results: An increased frequency of the IL-1RN*1 and IL-1RN*2 alleles was found in OA patients relative to controls (60.5% vs. 39.5%, P = 0.039, 85.4% vs. 14.6%, P = 0.002, respectively) however, only the carriage rate of IL-1RN*2 allele was found to be significant when OA patients were compared to the controls. Significant higher frequencies of IL-1RN*1/*2 and IL-1RN*2/*2 genotypes in OA patients were observed as compared with controls. Both visual analogue scale (VAS) and radiographic score revealed significant correlation with both the allelic frequency and the carriage rate of IL-1RN*2 allele. Moreover, absolute frequency of IL-1RN*1/*2 genotype OA patients revealed severe VAS and high radiographic score. Conclusion: These results suggest that IL-1RN*2 allele represent a significant factor influencing the severity and course of knee OA; thereby supporting the potential role of IL-1 in the pathogenesis of this disease.

ADAMTS-5 deficient mice do not develop mechanical allodynia associated with osteoarthritis following medial meniscal destabilization

To characterize pain-related behavior during the course of knee osteoarthritis (OA) induced by destabilization of the medial meniscus (DMM) in wild type (WT) and in ADAMTS-5 null mice. DMM surgery was performed in the right knee of CD-1 mice. At regular intervals up to 8 weeks after surgery, mice were assessed for the following parameters: mechanical allodynia (via withdrawal thresholds to von Frey filaments applied to the plantar surface of both hind paws or to the tail), thermal hyperalgesia, locomotor activity and gait analysis. In addition, mechanical allodynia was tested in C57BL/6 WT or ADAMTS-5 null mice following DMM surgery. In CD-1 mice, a robust and progressive decrease in withdrawal threshold was observed in both hind paws after DMM but not sham surgery. Allodynia was apparent as early as 14 days postoperatively. Both sexes developed OA changes after surgery with concurrent mechanical allodynia. No other pain-related behavioral changes were detected up to 8 weeks post-surgery. In C57BL/6 mice, a genetic background in which only males develop OA changes after DMM, males but not females developed allodynia in the ipsilateral hind paw. In contrast, C57BL/6 ADAMTS-5 null mice did not develop OA changes or mechanical allodynia up to 8 weeks post-surgery. Joint pathology following DMM surgery in mice is associated with progressive mechanical allodynia. ADAMTS-5 null mice are resistant to DMM-induced OA-like lesions and to the associated mechanical allodynia.

Natural course of knee osteoarthritis in middle-aged subjects with knee pain: 12-year follow-up using clinical and radiographic criteria

Objective:To explore the natural course of knee osteoarthritis (OA) in a middle-aged population with chronic knee pain.Methods:A population-based sample of 143 subjects (mean age 45 (range 35–54), 44% women) with...

Clinical outcomes from a physiotherapist‐led intra‐articular hyaluronic acid injection clinic

To describe the clinical course of knee osteoarthritis following a single course of intra-articular hyaluronic acid (HA) injection clinic, and specifically to explore treatment withdrawal. Prospective consecutive case series with follow-up, set in an innovative physiotherapist-led clinic, based in a hospital orthopaedic surgery department. A total of 100 patients with knee osteoarthritis referred to the clinic received a single course of five injections of Hyalgan. Patients were followed up in clinic at five, 13, 26 and 52 weeks. The primary outcome measures were Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) Likert 3.0 pain (0-20) and physical function (0-68) scores. In addition, at 13 and 26 weeks, patients were reviewed independently by an orthopaedic surgeon, with the option of withdrawing for alternative management those patients who had not responded. Ninety (90%) patients were successfully followed to study endpoint. Improvements were seen at five weeks and, to a lesser extent, at 13 weeks (mean reduction in WOMAC pain at 13 weeks = 1.3; 95% confidence interval [CI] 0.5, 2.0; mean reduction in WOMAC Physical Function at 13 weeks = 5.6; 95% CI 3.0, 8.1). Of 34 treatment withdrawals, most had returned to baseline levels by 13 weeks. The remaining 56 patients maintained improvements up to 52 weeks, although the pattern of outcome was highly variable between individuals. Withdrawals and non-responders had higher initial pain severity. Physiotherapist-led intra-articular HA clinics are feasible. Clinical outcomes for individual patients are highly heterogeneous up to one year after injections. Patients with initially high levels of pain may be less likely to benefit.

Progression of osteoarthritis of the knee after unilateral total hip arthroplasty: minimum 10-year follow-up study

Patients undergoing total hip arthroplasty (THA) exhibit changes in the alignment of lower extremities following the procedure, and these changes may exert effects on other joints over the long-term. Therefore, we investigated the course of knee osteoarthritis in patients undergoing long-term follow up after THA, in addition to the relationship between the course of knee osteoarthritis and alignment of lower extremities. We retrospectively performed radiographic evaluation of the course of knee osteoarthritis (OA) after THA. Thirty patients undergoing successful unilateral THA were followed for a minimum of 10 years. Eleven (33%) subjects showed progression of medial tibiofemoral OA on the non-THA side, while only three (10%) showed progression on the THA side, and this difference was significant (P = 0.033). In addition, the mechanical axes on the THA side passed through more lateral regions of the tibial plateau than those on the non-THA side (P = 0.044). Medial tibiofemoral OA on the THA side was less likely to deteriorate than on the non-THA side. The reduced vulnerability to OA progression on the THA side may be due to the lower offset and resultant lateral shift in mechanical axes.

Genetic Factors May Dictate Course of Knee Osteoarthritis

Genetic Factors May Dictate Course of Knee Osteoarthritis

Bone marrow edema and its relation to progression of knee osteoarthritis.

While factors affecting the course of knee osteoarthritis are mostly unknown, lesions on bone scan and mechanical malalignment increase risk for radiographic deterioration. Bone marrow edema lesions on magnetic resonance imaging correspond to bone scan lesions. To determine whether edema lesions in the subarticular bone in patients with knee osteoarthritis identify knees at high risk for radiographic progression and whether these lesions are associated with limb malalignment. Natural history study. A Veterans Administration hospital in Boston, Massachusetts. Persons 45 years of age and older with symptomatic knee osteoarthritis. Baseline assessments included magnetic resonance imaging of the knee and fluoroscopically positioned radiography. During follow-up at 15 and 30 months, patients underwent repeated radiography; at 15 months, long-limb films were obtained to assess mechanical alignment. Progression was defined as an increase over follow-up in medial or lateral joint space narrowing, based on a semi-quantitative grading. Generalized estimating equations were used to evaluate the relation of medial bone marrow edema lesions to medial progression and lateral lesions to lateral progression, before and after adjustment for limb alignment. Of 256 patients, 223 (87.1%) participated in at least one follow-up examination. Medial bone marrow lesions were seen mostly in patients with varus limbs, and lateral lesions were seen mostly in those with valgus limbs. Twenty-seven of 75 knees with medial lesions (36.0%) showed medial progression versus 12 of 148 knees without lesions (8.1%) (odds ratio for progression, 6.5 [95% CI, 3.0 to 14.0]). Approximately 69% of knees that progressed medially had medial lesions, and lateral lesions conferred a marked risk for lateral progression. These increased risks were attenuated by 37% to 53% after adjustment for limb alignment. Bone marrow edema is a potent risk factor for structural deterioration in knee osteoarthritis, and its relation to progression is explained in part by its association with limb alignment.

Magnetic resonance imaging of the knee in chronic knee pain. A 2-year follow-up

Objective The aim of the study was to evaluate the change over time of cartilage defects, subchondral lesions and meniscal abnormalities of the knee using magnetic resonance (MR) imaging with a 2-year interval in patients with chronic knee pain.Design In the format of a prospective study of early osteoarthritis (OA), the signal knee (most painful at the inclusion in the study 1990) in 47 individuals, 25 women and 22 men (aged 41–57 years, median 50), with chronic knee pain, with or without radiographically determined knee OA, were examined using MR imaging on a 1.0T imager with a 2-year interval (median 25 months, range 21–30). Cartilage defects, subchondral lesions and meniscal abnormalities were recorded and compared in blind between the examinations.Results Five new cartilage defects and eight subchondral lesions appeared during the 2-year interval. Seven defects and seven subchondral lesions disappeared during the same time. Thirty-two out of 93 cartilage defects (34%) and 19 out of 32 subchondral lesions (59%) displayed an increase or a decrease in size over time. A meniscal abnormality appeared in three locations, and disappeared in none. In 14 out of 54 locations (26%) with a meniscal abnormality an increase or a decrease of the abnormality was recorded over time and no abnormality decreased.Conclusions After the 2 years of observation it was possible to register, using MR imaging, the appearance, increase, decrease and disappearance of cartilage defects, subchondral lesions and meniscal abnormalities in middle-aged people with chronic knee pain. This has to be considered in studies of the natural course of knee OA as well as in studies of the intraarticular effect of pharmacological treatment aiming at cartilage repair or protection.