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Knee OA (knee + oa)

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Medical Sciences	88%

Selected Abstracts

Impact of Chronic Musculoskeletal Pathology on Older Adults: A Study of Differences between Knee OA and Low Back Pain

PAIN MEDICINE, Issue 4 2009
Natalia E. Morone MD
ABSTRACT Objectives., The study aimed to compare the psychological and physical characteristics of older adults with knee osteoarthritis (OA) vs those of adults with chronic low back pain (CLBP) and to identify psychological and physical predictors of function as measured by gait speed. Design., Secondary data analysis. Method and Patients., Eighty-eight older adults with advanced knee OA and 200 with CLBP who had participated in separate randomized controlled trials were selected for this study. Measures., Inclusion criteria for both trials included age ,65 and pain of at least moderate intensity that occurred daily or almost every day for at least the previous 3 months. Psychological constructs (catastrophizing, fear avoidance, self-efficacy, depression, affective distress) and physical measures (comorbid medical conditions, pain duration, pain severity, pain related interference, self-rated health) were obtained. Results., Subjects with CLBP had slower gait (0.88 m/s vs 0.96 m/s, P = 0.002) and more comorbid conditions than subjects with knee pain (mean 3.36 vs 1.97, P < 0.001). All the psychological measures were significantly worse in the CLBP group except the Multidimensional Pain Inventory,Affective Distress score. Self-efficacy, pain severity, and medical comorbidity burden were associated with slower gait regardless of the location of the pain. Conclusions., Older adults with chronic pain may have distinct psychological and physical profiles that differentially impact gait speed. These findings suggest that not all pain conditions are the same in their psychological and physical characteristics and may need to be taken into consideration when developing treatment plans. [source]

Glucosamine sulphate in the treatment of knee osteoarthritis: cost-effectiveness comparison with paracetamol

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2010
S. Scholtissen
Summary Introduction:, The aim of this study was to explore the cost-effectiveness of glucosamine sulphate (GS) compared with paracetamol and placebo (PBO) in the treatment of knee osteoarthritis. For this purpose, a 6-month time horizon and a health care perspective was used. Material and methods:, The cost and effectiveness data were derived from Western Ontario and McMaster Universities Osteoarthritis Index data of the Glucosamine Unum In Die (once-a-day) Efficacy trial study by Herrero-Beaumont et al. Clinical effectiveness was converted into utility scores to allow for the computation of cost per quality-adjusted life year (QALY) For the three treatment arms Incremental Cost-Effectiveness Ratio were calculated and statistical uncertainty was explored using a bootstrap simulation. Results:, In terms of mean utility score at baseline, 3 and 6 months, no statistically significant difference was observed between the three groups. When considering the mean utility score changes from baseline to 3 and 6 months, no difference was observed in the first case but there was a statistically significant difference from baseline to 6 months with a p-value of 0.047. When comparing GS with paracetamol, the mean baseline incremental cost-effectiveness ratio (ICER) was dominant and the mean ICER after bootstrapping was ,1376 ,/QALY indicating dominance (with 79% probability). When comparing GS with PBO, the mean baseline and after bootstrapping ICER were 3617.47 and 4285 ,/QALY, respectively. Conclusion:, The results of the present cost-effectiveness analysis suggested that GS is a highly cost-effective therapy alternative compared with paracetamol and PBO to treat patients diagnosed with primary knee OA. [source]

Predictors of disability among Filipinos with knee osteoarthritis

INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2008
Ester G. Penserga
Abstract Aims: This study aims to describe the level of disability of Filipino patients with knee osteoarthritis (OA) in relation to common risk factors. Methodology: This is a cross-sectional analytic study. Patients with knee osteoarthritis diagnosed using the American College of Rheumatology criteria for the classification of knee OA, seen at East Avenue Medical Center, using the Quezon City, Philippines, were entered by convenient sampling. The Western Ontario and McMaster Universities (WOMAC (va) 3.1 Tagalog Version) osteoarthritis index was used. Self-reported disability was measured by the function subscale of the WOMAC OA index and used as the dependent variable. Independent variables assessed as possible risk factors affecting disability were age, sex, weight, height, body mass index (BMI), education (in years), number of comorbidities present, smoking status (pack years), duration of knee OA, pain and stiffness. Categories of disability were identified as high, moderate and low. Analyses of the data were performed using Statistical Package for the Social Sciences (SPSS) version 13. Results: Eighty-five subjects were included in the study. The mean disability score was 674.1 ± 318.81 (moderate disability). Chi-square tests showed that the categories or levels of disability are not significantly dependent on the categorical variables. Significant direct correlations were seen between mean disability and weight (r = 0.260, P = 0.016), pain (r = 0.574, P = 0.000), and stiffness (r = 0.616, P = 0.000). Conclusion: This is the first study analysing the relationship between disability and specific risk factors among Filipino patients with knee OA. Self-reported disability of knee OA in the population studied was strongly related to pain scores, weight and joint stiffness scores. [source]

Change in serum COMP concentration due to ambulatory load is not related to knee OA Status

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2009
Annegret Mündermann
Abstract The aim of this study was to test the hypothesis that a change in serum cartilage oligomeric matrix protein (COMP) concentration is related to joint load during a 30-min walking exercise in patients with medial compartment knee osteoarthritis (OA) and in age-matched control subjects. Blood samples were drawn from 42 patients with medial compartment knee OA and from 41 healthy age-matched control subjects immediately before, immediately after, and 0.5, 1.5, 3.5, and 5.5 h after a 30-min walking exercise on a level outdoor walking track at self-selected normal speed. Serum COMP concentrations were determined using a commercial ELISA. Basic time,distance gait variables were recorded using an activity monitor. Joint loads were measured using gait analysis. Serum COMP concentrations increased immediately after the walking exercise (+6.3% and +5.6%; p,<,0.001) and decreased over 5.5 h after the exercise (,11.1% and ,14.6%; p,<,0.040 and p,=,0.001) in patients and control subjects, respectively. The magnitude of increase in COMP concentration did not differ between groups (p,=,0.902) and did not correlate with any variables describing ambulatory loads at the joints of the lower extremity. These results, taken together with a previous study of a younger healthy population, suggest the possibility that the influence of ambulatory loads on cartilage turnover is dependent on age. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1408,1413, 2009 [source]

Lower extremity walking mechanics of young individuals with asymptomatic varus knee alignment

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2009
Joaquin A. Barrios
Abstract Varus knee alignment is associated with an increased risk for developing medial knee osteoarthritis (OA). Medial knee OA is commonly associated with altered walking mechanics in the frontal and sagittal planes, as well as altered ground reaction forces. It is unknown whether these mechanics are present in young, asymptomatic individuals with varus knees. We expected that varus-aligned individuals would generally present with frontal plane mechanics that were similar to those reported for individuals with medial knee OA. The gait mechanics of 17 asymptomatic individuals with varus knees and 17 healthy, normally aligned controls were recorded. Gait parameters associated with medial knee OA were compared between groups. The individuals with varus knees exhibited greater knee external adduction moments, knee adduction, eversion, and lateral ground reaction force than the normally aligned individuals. In addition, those with varus knees also demonstrated increased knee flexion and external knee flexor moments during midstance. These results suggest that individuals with varus knees exhibit some, but not all, of the altered mechanics seen in medial knee OA. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1414,1419, 2009 [source]

Assessment of the efficacy of joint lavage in rabbits with osteoarthritis of the Knee,

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2009
Xin Fu
Abstract We investigated the efficacy of joint lavage to alter the progression of the disease process in a rabbit model of knee OA in varying stages of the disease. Thirty-three white rabbits were operated to induce OA, and then the rabbits were divided into three groups (10 in each) randomly. In group 1, on week 1 after the operation, joint lavage was performed on both knees in five rabbits as treatment group, and the other five rabbits were used as control group received no intervention. By the end of week 2 after operation, the rabbits were sacrificed. In group 2, five received joint lavage on week 2, and all were sacrificed on week 3. In group3, five received joint lavage on week 3, and all were sacrificed on week 4. In each group, histological evaluation showed that both the breakdown of articular cartilage and the inflammation of synovium were less in the knees treated with joint lavage than that in the control knees. The enzyme-linked immunosorbent assay revealed that the expression of IL-1, and TNF-, in synovial fluid decreased significantly in the treatment group. Our findings suggested that joint lavage was beneficial for OA at different phases of OA in rabbit models. Joint lavage may be a beneficial method for the treatment of OA clinically. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:91,96, 2009 [source]

Muscle stabilization strategies in people with medial knee osteoarthritis: The effect of instability

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2008
Laura C. Schmitt
Abstract The sensation of knee instability (shifting, buckling. and giving way) is common in people with medial knee osteoarthritis (OA). Its influence on knee stabilization strategies is unknown. This study investigated the influence of knee instability on muscle activation during walking when knee stability was challenged. Twenty people with medial knee OA participated and were grouped as OA Stable (OAS) (n,=,10) and OA Unstable (OAU) (n,=,10) based on self-reported knee instability during daily activities. Quadriceps strength, passive knee laxity, and varus alignment were assessed and related to knee instability and muscle cocontraction during walking when the support surface translated laterally. Few differences in knee joint kinematics between the groups were seen; however, there were pronounced differences in muscle activation. The OAU group used greater medial muscle cocontraction before, during, and following the lateral translation. Self-reported knee instability predicted medial muscle cocontraction, but medial laxity and limb alignment did not. The higher muscle cocontraction used by the OAU subjects appears to be an ineffective strategy to stabilize the knee. Instability and high cocontraction can be detrimental to joint integrity, and should be the focus of future research. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1180,1185, 2008 [source]

The knee adduction moment during gait in subjects with knee osteoarthritis is more closely correlated with static alignment than radiographic disease severity, toe out angle and pain

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2002
D. E. Hurwitz
This study tested whether the peak external knee adduction moments during walking in subjects with knee osteoarthritis (OA) were correlated with the mechanical axis of the leg, radiographic measures of OA severity, toe out angle or clinical assessments of pain, stiffness or function. Gait analysis was performed on 62 subjects with knee OA and 49 asymptomatic control subjects (normal subjects). The subjects with OA walked with a greater than normal peak adduction moment during early stance (p = 0.027). In the OA group, the mechanical axis was the best single predictor of the peak adduction moment during both early and late stance (R = 0.74, p < 0.001). The radiographic measures of OA severity in the medial compartment were also predictive of both peak adduction moments (R = 0.43 to 0.48, p < 0.001) along with the sum of the WOMAC subscales (R = ,0.33 to ,0.31, p < 0.017). The toe out angle was predictive of the peak adduction moment only during late stance (R = ,0.45, p < 0.001). Once mechanical axis was accounted for, other factors only increased the ability to predict the peak knee adduction moments by 10,18%. While the mechanical axis was indicative of the peak adduction moments, it only accounted for about 50% of its variation, emphasizing the need for a dynamic evaluation of the knee joint loading environment. Understanding which clinical measures of OA are most closely associated with the dynamic knee joint loads may ultimately result in a better understanding of the disease process and the development of therapeutic interventions. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]

Evidence based guidelines and current practice for physiotherapy management of knee osteoarthritis

MUSCULOSKELETAL CARE, Issue 1 2009
Nicola E. Walsh MSc MCSP
Abstract Objectives:,To document physiotherapy provision for patients with knee osteoarthritis (OA) in relation to the United Kingdom (UK) recently published National Institute of health and Clinical Excellence (NICE) guidelines for osteoarthritis. Design:,Questionnaire survey of chartered physiotherapists. Method:,300 postal questionnaires were distributed to Physiotherapy Departments requesting information regarding source of referrals, treatment aims, preferred methods of treatment and service delivery. Results:,Responses were received from 83 physiotherapists (28 %), predominantly working in the UK National Health Service. Approximately equal numbers of referrals came from primary and secondary care. Aims of physiotherapy management were to; encourage self-management; increase strength and range of movement; reduce pain; and improve function. To achieve these, exercise was utilised by 100% of practitioners, often supplemented with electrotherapeutic modalities (66%), manual therapy (64%) and acupuncture (60%). The majority of patients received individual treatment for a total contact time of 1,2 hours, whilst most group interventions lasted 5,6 hours. Approximately half (54%) of respondents reported using outcome measures to determine treatment efficacy. Conclusions:,Although knee OA is usually managed in primary care, the similar number of referrals from primary and secondary care may suggest a deviation from evidence-based management guidelines. The guidelines' recommendations of exercise, patient education and self-management are observed by physiotherapists, but other modalities are often used despite poor or no research evidence supporting their efficacy. Whether any of these interventions are clinically beneficial is speculative as treatment outcomes were frequently under-evaluated. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Impact of Chronic Musculoskeletal Pathology on Older Adults: A Study of Differences between Knee OA and Low Back Pain

Necessary and Discretionary Activities in Knee Osteoarthritis: Do They Mediate the Pain,Depression Relationship?

PAIN MEDICINE, Issue 5 2007
Patricia A. Parmelee PhD
ABSTRACT Objective., This study examined direct vs indirect associations of pain and physical function with depression in 369 older adults with osteoarthritis (OA) of the knee. A key focus was the distinction of functional disability in necessary tasks (basic and instrumental activities of daily living) from discretionary, leisure activities. Design., A naturalistic longitudinal study examined effects of demographic variables, indicators of arthritis status, general health, pain, and several measures of functional disability upon depressive symptoms at baseline and 1 year later. Setting and Patients., Participants with diagnosed knee OA were recruited from rheumatological and general geriatric outpatient clinics, as well as public service announcements. Outcome Measure., Depressive symptoms, measured with the Center for Epidemiologic Studies Depression scale. Results., At baseline, the relationships of depression with functional disability and activity limitation were wholly mediated by pain. In contrast, activity participation was independently linked with depression, even controlling health and demographic variables. A 1-year follow-up revealed that depressive symptoms increased with increasing health problems, and with reduction in activity participation over time. Having and retaining favorite pastimes were also associated with reduced depressive symptomatology at baseline and follow-up, respectively. Conclusions., These data highlight the disease-specific nature of paths among depression, pain, and disability, and the importance of considering discretionary as well as necessary activities in evaluating effects of pain upon quality of life. [source]

Choice of treatment modalities was not influenced by pain, severity or co-morbidity in patients with knee osteoarthritis

PHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 1 2010
Gro Jamtvedt
Abstract Background and Purpose.,Patients with knee osteoarthritis (OA) are commonly treated by physiotherapists in primary care. The physiotherapists use different treatment modalities. In a previous study, we identified variation in the use of transcutaneous electrical nerve stimulation (TENS), low level laser or acupuncture, massage and weight reduction advice for patients with knee OA. The purpose of this study was to examine factors that might explain variation in treatment modalities for patients with knee OA.,Methods.,Practising physiotherapists prospectively collected data for one patient with knee osteoarthritis each through 12 treatment sessions. We chose to examine factors that might explain variation in the choice of treatment modalities supported by high or moderate quality evidence, and modalities which were frequently used but which were not supported by evidence from systematic reviews. Experienced clinicians proposed factors that they thought might explain the variation in the choice of these specific treatments. We used these factors in explanatory analyses.,Results.,Using TENS, low level laser or acupuncture was significantly associated with having searched databases to help answer clinical questions in the last six months (odds ratio [OR] = 1.93, 95% confidence interval [CI] = 1.08,3.42). Not having Internet access at work and using more than four treatment modalities were significant determinants for giving massage (OR = 0.36, 95% CI = 0.19,0.68 and OR = 8.92, 95% CI = 4.37,18.21, respectively). Being a female therapist significantly increased the odds for providing weight reduction advice (OR = 3.60, 95% CI = 1.12,11.57). No patient characteristics, such as age, pain or co-morbidity, were significantly associated with variation in practice.,Conclusions.,Factors related to patient characteristics, such as pain severity and co-morbidity, did not seem to explain variation in treatment modalities for patients with knee OA. Variation was associated with the following factors: physiotherapists having Internet access at work, physiotherapists having searched databases for the last six months and the gender of the therapist. There is a need for more studies of determinants for physiotherapy practice. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Impact of an exercise and walking protocol on quality of life for elderly people with OA of the knee

PHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 3 2003
Rosângela Corrêa Dias
Abstract Background and Purpose The knee is the weight-bearing joint most commonly affected by osteoarthritis (OA). The symptoms of pain, morning stiffness of short duration and physical dysfunction in the activities of daily living (ADL) can have an effect on many aspects of health, affecting quality of life. Regular and moderate physical activity adapted to individuals' life-styles and education, and joint protection strategies have been advocated as conservative management. The purpose of the present study was to assess the impact of an exercise and walking protocol on the quality of life of elderly people with knee OA. Method The study design was a randomized controlled clinical trial. The subjects comprised 50 elderly people, aged 65 or more, with knee OA who had been referred to the geriatric outpatient unit for rehabilitation. Changes in severity of pain and quality of life were compared between a control group (CG) and an experimental group (EG). Both groups participated in an educational session and the EG also received a 12-week exercise and walking protocol. Both groups were assessed at baseline and after three and six months by an independent observer. The Lequesne Index of Knee OA Severity (LI), the Health Assessment Questionnaire (HAQ) and the Medical Outcomes Short-Form Health Survey (SF-36) were used as measurement instruments. Results In the CG, the measures of quality of life (SF-36), the HAQ and the LI between subjects did not yield statistically significant differences over the three measurement points. For the EG, there was a significant improvement in function, measured by HAQ, and decreasing OA symptom severity, measured by LI. For the SF-36 there were significant improvements in physical function, functional role limitation and pain. Comparisons between the groups showed statistically significant differences after three and six months for all measures, except for the SF-36 emotional domains. Conclusion The exercise protocol and walking programme had a positive effect on the quality of life of elderly individuals with knee OA. Copyright © 2003 Whurr Publishers Ltd. [source]

Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain model

ARTHRITIS & RHEUMATISM, Issue 10 2010
Hee-Jeong Im
Objective To verify the biologic links between progressive cellular and structural alterations within knee joint components and development of symptomatic chronic pain that are characteristic of osteoarthritis (OA), and to investigate the molecular basis of alterations in nociceptive pathways caused by OA-induced pain. Methods An animal model of knee joint OA pain was generated by intraarticular injection of mono-iodoacetate (MIA) in Sprague-Dawley rats, and symptomatic pain behavior tests were performed. Relationships between development of OA with accompanying pain responses and gradual alterations in cellular and structural knee joint components (i.e., cartilage, synovium, meniscus, subchondral bone) were examined by histologic and immunohistologic analysis, microscopic examination, and microfocal computed tomography. Progressive changes in the dynamic interrelationships between peripheral knee joint tissue and central components of nociceptive pathways caused by OA-induced pain were examined by investigating cytokine production and expression in sensory neurons of the dorsal root ganglion and spinal cord. Results We observed that structural changes in components of the peripheral knee joint correlate with alterations in the central compartments (dorsal root ganglia and the spinal cord) and symptomatic pain assessed by behavioral hyperalgesia. Our comparative gene expression studies revealed that the pain pathways in MIA-induced knee OA may overlap, at least in part, with neuropathic pain mechanisms. Similar results were also observed upon destabilization of the knee joint in the anterior cruciate ligament transection and destabilization of the medial meniscus models of OA. Conclusion Our results indicate that MIA-induced joint degeneration in rats generates an animal model that is suitable for mechanistic and pharmacologic studies on nociceptive pain pathways caused by OA, and provide key in vivo evidence that OA pain is caused by central sensitization through communication between peripheral OA nociceptors and the central sensory system. Furthermore, our data suggest a mechanistic overlap between OA-induced pain and neuropathic pain. [source]

Genetic variation in the SMAD3 gene is associated with hip and knee osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 8 2010
Ana M. Valdes
Objective Smad3 (or, MADH3) is a key intracellular messenger in the transforming growth factor , signaling pathway. In mice, Smad3 deficiency accelerates growth plate chondrocyte maturation and leads to an osteoarthritis (OA),like disease. We undertook this study to investigate the role of genetic variation in SMAD3 in the risk of large-joint OA in humans. Methods Ten tag single-nucleotide polymorphisms (SNPs) in the SMAD3 gene region were tested in a discovery set: 313 patients who had undergone total knee replacement, 214 patients who had undergone total hip replacement, and 520 controls from the UK. The SNP associated with both hip and knee OA was subsequently genotyped in 1,221 controls and 1,074 cases from 2 cohorts of patients with hip OA and 2,537 controls and 1,575 cases from 4 cohorts of patients with knee OA. Results A SNP (rs12901499) mapping to intron 1 of SMAD3 was associated with both knee and hip OA (P < 0.0022 and P < 0.021, respectively) in the discovery set. In all study cohorts, the major allele (G) was increased among OA patients relative to controls. A meta-analysis for knee OA yielded an odds ratio (OR) of 1.22 (95% confidence interval [95% CI] 1.12,1.34), P < 7.5 × 10,6. For hip OA, the OR was 1.22 (95% CI 1.09,1.36), P < 4.0 × 10,4. No evidence for heterogeneity was found (I2 = 0%). Conclusion Our data indicate that genetic variation in the SMAD3 gene is involved in the risk of both hip OA and knee OA in European populations, confirming the results from animal models on the potential importance of this molecule in the pathogenesis of OA. [source]

Frequency of varus and valgus thrust and factors associated with thrust presence in persons with or at higher risk of developing knee osteoarthritis,,

ARTHRITIS & RHEUMATISM, Issue 5 2010
Alison Chang
Objective Varus thrust observed during gait has been shown to be associated with a 4-fold increase in the risk of medial knee osteoarthritis (OA) progression. Valgus thrust is believed to be less common than varus thrust; the prevalence of each is uncertain. Racial differences in risk factors may help explain variations in the natural history of knee OA. We undertook this study to determine the frequency of varus and valgus thrust in African Americans and Caucasians and to identify factors associated with thrust presence. Methods The Osteoarthritis Initiative cohort includes men and women who have knee OA or are at increased risk of developing it. Trained examiners assessed thrust presence by gait observation. Logistic regression with generalized estimating equations was used to identify factors associated with thrust presence, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results Compared with Caucasians, African Americans had lower odds of varus thrust, controlling for age, sex, body mass index (BMI), injury, surgery, disease severity, strength, pain, and alignment in persons without knee OA (adjusted OR 0.50 [95% CI 0.36, 0.72]) and in those with knee OA (adjusted OR 0.46 [95% CI 0.34, 0.61]). Also independently associated with varus thrust were age, sex, BMI, disease severity, strength, and alignment. The odds of valgus thrust were greater for African Americans than for Caucasians in persons without knee OA (adjusted OR 1.69 [95% CI 1.02, 2.80]) and in those with knee OA (adjusted OR 1.98 [95% CI 1.35, 2.91]). Also independently associated with valgus thrust were disease severity and malalignment. Conclusion Compared with Caucasians, African Americans had lower odds of varus thrust and greater odds of valgus thrust. These findings may help explain the difference between these groups in the pattern of OA involvement at the knee. [source]

Sex differences of chondrogenic progenitor cells in late stages of osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 4 2010
Sebastian Koelling
Objective Osteoarthritis (OA), a mainly degenerative disease, is known to be multifactorial in origin. Gene expression patterns vary between populations and sexes. Sex hormone receptors have been described in the cartilage tissue of animals and humans. We undertook this study to determine whether the regenerative potential of chondrogenic progenitor cells (CPCs) present in the arthritic tissue during the late stages of human OA might also be subject to sex-specific differences and influenced by sex steroids. Methods We analyzed sex-specific differences in the regenerative potential of CPCs and the involvement of sex hormones in vitro in cartilage samples from patients with late-stage knee OA, using electrochemiluminescence immunoassay, microarray analysis, real-time reverse transcription,polymerase chain reaction, immunohistochemistry, Western blot analysis, fluorescence-activated cell sorting, and cell culture. Results We detected expression of estrogen and testosterone in the OA synovial fluid as well as CPCs positive for estrogen receptor , (ER,), ER,, and androgen receptor. Both hormones influenced the expression of all 3 receptor genes as well as the chondrogenic potential of CPCs by regulating gene expression of Sox9, Runx2, type II collagen, and type I collagen. We found regulatory effects on the collagens via Sox9 and Runx2 as well as regulatory effects independent of these transcription factors. These effects were sex-specific and relied on hormone concentrations. Conclusion Physiologic concentrations of testosterone in men and premenopausal concentrations of estrogen in women have a positive effect on the chondrogenic potential of CPCs in vitro. Therefore, strategies of hormone replacement in the synovial fluid of women and men might have beneficial effects on the regenerative potential of arthritic cartilage tissue in late stages of human OA. [source]

Nonsteroidal antiinflammatory drugs and prostaglandin E2 modulate the synthesis of osteoprotegerin and RANKL in the cartilage of patients with severe knee osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 2 2010
Juan Moreno-Rubio
Objective Although the osteoprotegerin (OPG)/RANK/RANKL system is the main modulator of bone remodeling, it remains unclear whether it is regulated in cartilage during osteoarthritis (OA). The aim of this study was to examine whether nonsteroidal antiinflammatory drug (NSAID) treatment modulates the synthesis of OPG and RANKL in the cartilage of patients with OA, and to investigate whether prostaglandin E2 (PGE2) modifies this system in human OA chondrocytes in culture. Methods A 3-month clinical trial was carried out in 20 patients with severe knee OA, all of whom were scheduled to undergo knee replacement surgery. Ten of these patients were treated with celecoxib, and the other 10 patients, who did not want to be treated, served as the control group. After surgery, cartilage was processed for molecular biology studies. We also used human OA chondrocytes to examine the effects of PGE2 on OPG/RANKL synthesis, examining which surface receptors were affected by PGE2. Results In patients with OA, celecoxib decreased RANKL synthesis in the cartilage, thereby increasing the OPG:RANKL ratio. In human OA chondrocytes in culture, PGE2 elicited a dose- and time-dependent increase in the synthesis of RANKL, the extent of which was greater than that of OPG. Confocal microscopy revealed that PGE2 induced RANKL transport to the cell membrane. Only EP2/EP4 agonists reproduced the effects of PGE2 on OPG and RANKL induction. Conclusion Long-term NSAID treatment inhibited the resorptive signal synthesized by chondrocytes. In vitro, PGE2 regulated the expression and release of these key mediators of bone metabolism by articular chondrocytes. The role of OPG/RANK/RANKL in OA cartilage metabolism is still unknown, although the synthesis of these proteins would enable the cartilage to control the activity of subchondral bone cells. [source]

Denuded subchondral bone and knee pain in persons with knee osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 12 2009
Kirsten Moisio
Objective It is unclear how articular cartilage loss contributes to pain in patients with knee osteoarthritis (OA). Full-thickness cartilage defects expose the subchondral bone plate. The relationship between denuded bone and pain has not been examined. The aim of this study was to investigate whether the percent of denuded bone is associated with moderate-to-severe knee pain or frequent knee pain and longitudinally with frequent knee pain 2 years after the baseline evaluation. Methods We studied 182 persons with knee OA (305 knees). Applying specialized magnetic resonance imaging techniques, manual segmentation was used to compute cartilage-covered and denuded bone areas for each surface. Moderate-to-severe knee pain was defined as a score of ,40 mm on a knee-specific 100-mm visual analog scale, and frequent knee pain was defined as pain on most days during the past month. Logistic regression and generalized estimating equations were used in analyses, adjusting for age, sex, body mass index, and bone marrow lesions. Results Cross-sectional analyses revealed that moderate-to-severe knee pain was associated with percent denuded bone in the medial compartment (adjusted odds ratio [OR] 3.90, 95% confidence interval [95% CI] 1.33,11.47), in the medial and patellar surfaces together, and in the lateral and patellar surfaces. Frequent knee pain was associated with percent denuded bone in the patellar surface (adjusted OR 3.11, 95% CI 1.24,7.81), in the medial and patellar surfaces, and in the lateral and patellar surfaces. Longitudinal analyses (in 168 knees without frequent knee pain at baseline) revealed that percent denuded bone in the medial and patellar surfaces was associated with frequent incident knee pain (adjusted OR 4.19, 95% CI 1.56,11.22). Conclusion These results support a relationship between subchondral bone plate exposure and prevalent and incident knee pain in patients with knee OA. [source]

The infrapatellar fat pad in knee osteoarthritis: An important source of interleukin-6 and its soluble receptor

ARTHRITIS & RHEUMATISM, Issue 11 2009
Emilie Distel
Objective Obesity is a potent risk factor in knee osteoarthritis (OA). It has been suggested that adipokines, secreted by adipose tissue (AT) and largely found in the synovial fluid of OA patients, derive in part from the infrapatellar fat pad (IFP), also known as Hoffa's fat pad. The goal of this study was to characterize IFP tissue in obese OA patients and to compare its features with thigh subcutaneous AT to determine whether the IFP contributes to local inflammation in knee OA via production of specific cytokines. Methods IFP and subcutaneous AT samples were obtained from 11 obese women (body mass index ,30 kg/m2) with knee femorotibial OA. Gene expression was measured by real-time quantitative polymerase chain reaction. Cytokine concentrations in plasma and in conditioned media of cultured AT explants were determined by enzyme-linked immunosorbent assay or by Luminex xMAP technology. Results In IFP tissue versus subcutaneous AT, there was a decrease in the expression of genes for key enzymes implicated in adipocyte lipid metabolism, whereas the expression levels of genes for AT markers remained similar. A 2-fold increase in the expression of the gene for interleukin-6 (IL-6), a 2-fold increase in the release of IL-6, and a 3.6-fold increase in the release of soluble IL-6 receptor (sIL-6R) were observed in IFP samples, compared with subcutaneous AT, but the rates of secretion of other cytokines in IFP samples were similar to the rates in subcutaneous AT. In addition, leptin secretion was decreased by 40%, whereas adiponectin secretion was increased by 70%, in IFP samples versus subcutaneous AT. Conclusion Our results indicate that the IFP cytokine profile typically found in OA patients could play a role in paracrine inflammation via the local production of IL-6/sIL-6R and that such a profile might contribute to damage in adjacent cartilage. [source]

Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 10 2009
Timothy M. Griffin
Objective To test the hypothesis that obesity resulting from deletion of the leptin gene or the leptin receptor gene results in increased knee osteoarthritis (OA), systemic inflammation, and altered subchondral bone morphology. Methods Leptin-deficient (ob/ob) and leptin receptor,deficient (db/db) female mice compared with wild-type mice were studied, to document knee OA via histopathology. The levels of serum proinflammatory and antiinflammatory cytokines were measured using a multiplex bead immunoassay. Cortical and trabecular subchondral bone changes were documented by microfocal computed tomography, and body composition was quantified by dual x-ray absorptiometry. Results Adiposity was increased by ,10-fold in ob/ob and db/db mice compared with controls, but it was not associated with an increased incidence of knee OA. Serum cytokine levels were unchanged in ob/ob and db/db mice relative to controls, except for the level of cytokine-induced neutrophil chemoattractant (keratinocyte chemoattractant; murine analog of interleukin-8), which was elevated. Leptin impairment was associated with reduced subchondral bone thickness and increased relative trabecular bone volume in the tibial epiphysis. Conclusion Extreme obesity due to impaired leptin signaling induced alterations in subchondral bone morphology without increasing the incidence of knee OA. Systemic inflammatory cytokine levels remained largely unchanged in ob/ob and db/db mice. These findings suggest that body fat, in and of itself, may not be a risk factor for joint degeneration, because adiposity in the absence of leptin signaling is insufficient to induce systemic inflammation and knee OA in female C57BL/6J mice. These results imply a pleiotropic role of leptin in the development of OA by regulating both the skeletal and immune systems. [source]

Vascular cell adhesion molecule 1 as a predictor of severe osteoarthritis of the hip and knee joints

ARTHRITIS & RHEUMATISM, Issue 8 2009
Georg Schett
Objective Osteoarthritis (OA) is a leading cause of pain and physical disability in middle-aged and older individuals. We undertook this study to determine predictors of the development of severe OA, apart from age and overweight. Methods Joint replacement surgery due to severe hip or knee OA was recorded over a 15-year period in the prospective Bruneck cohort study. Demographic characteristics and lifestyle and biochemical variables, including the level of soluble vascular cell adhesion molecule 1 (VCAM-1), were assessed at the 1990 baseline visit and tested as predictors of joint replacement surgery. Results Between 1990 and 2005, hip or knee joint replacement due to OA was performed in 60 subjects. VCAM-1 level emerged as a highly significant predictor of the risk of joint replacement surgery. Intervention rates were 1.9, 4.2, and 10.1 per 1,000 person-years in the first, second, and third tertiles, of the VCAM-1 level, respectively. In multivariable logistic regression analysis, the adjusted relative risk of joint replacement surgery in the highest versus the lowest tertile group of VCAM-1 level was 3.9 (95% confidence interval 1.7,8.7) (P < 0.001). Findings were robust in various sensitivity analyses and were consistent in subgroups. Addition of the VCAM-1 level to a risk model already including age, sex, and body mass index resulted in significant gains in model discrimination (C statistic) and calibration and in more accurate risk classification of individual participants. Conclusion The level of soluble VCAM-1 emerged as a strong and independent predictor of the risk of hip and knee joint replacement due to severe OA. If our findings can be reproduced in other epidemiologic cohorts, they will assist in routine risk classification and will contribute to a better understanding of the etiology of OA. [source]

Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: The Chingford study

ARTHRITIS & RHEUMATISM, Issue 7 2009
Gregory Livshits
Objective There is a great need for identification of biomarkers that could improve the prediction of early osteoarthritis (OA). We undertook this study to determine whether circulating levels of interleukin-6 (IL-6), tumor necrosis factor , (TNF,), and C-reactive protein (CRP) can serve as useful markers of radiographic knee OA (RKOA) in a normal human population. Methods RKOA data were obtained from the cohort of the Chingford Study, a prospective population-based study of healthy, middle-aged British women. The RKOA-affected status of the subjects was assessed using the Kellgren/Lawrence (K/L) grade as determined on radiographs obtained at baseline (n = 908) and at 10 years and 15 years thereafter. Serum levels of CRP, IL-6, and TNF, were assayed at 5, 8, and 15 years, using high-sensitivity commercial assays. A K/L grade of ,2 in either knee was used as the outcome measure. Statistical analyses included analysis of variance for repeated measurements and logistic regression models, together with longitudinal modeling of dichotomous responses. Results During 15 years of followup, the prevalence of RKOA (K/L grade ,2) increased from 14.7% to 48.7% (P < 0.00001 versus baseline). The body mass index (BMI) and circulating levels of CRP and IL-6 were consistently and significantly higher in subjects diagnosed as having RKOA. When multiple logistic regression was applied to the data, the variables of older age (P = 3.93 × 10,5), higher BMI at baseline (P = 0.0003), and increased levels of IL-6 at year 5 (P = 0.0129) were determined to be independent predictors of the appearance of RKOA at year 10. The results were fully confirmed using longitudinal modeling of repeated measurements of the data obtained at 3 visits. The odds ratio for RKOA in subjects whose IL-6 levels were in the fourth quartile of increasing levels (versus the first quartile) was 2.74 (95% confidence interval 1.94,3.87). Conclusion This followup study showed that individuals were more likely to be diagnosed as having RKOA if they had a higher BMI and increased circulating levels of IL-6. These results should stimulate more work on IL-6 as a potential therapeutic target. [source]

Variation at the ANP32A gene is associated with risk of hip osteoarthritis in women

ARTHRITIS & RHEUMATISM, Issue 7 2009
Ana M. Valdes
Objective The ANP32A gene encodes a tumor suppressor molecule that plays a regulatory role in apoptosis and interferes with canonical Wnt signaling in vitro. We undertook this study to test whether genetic variation at ANP32A was associated with osteoarthritis (OA) in women. Methods Single-nucleotide polymorphisms (SNPs) in the ANP32A gene were genotyped in 438 control women, 425 women with total knee replacements (TKRs), and 537 women with total hip replacements (THRs) from the Nottingham case,control study as well as in 820 women from the population-based Chingford Study cohort for whom hip and knee radiographs were available. The most highly associated SNP was further tested in women from the Rotterdam Study (131 with THRs, 633 with knee OA, and 1,567 controls) and the TwinsUK Study cohort (67 with THRs, 43 with TKRs, and 358 controls), for a total of 2,170 patients with OA and 2,849 controls. Results The ANP32A transcript was abundantly expressed in normal and OA articular cartilage. Three SNPs in the ANP32A gene were significantly associated in Nottingham patients with hip OA, but not knee OA. One of these (rs7164503) was associated with hip and knee OA in the Chingford Study cohort and with THR in the TwinsUK Study cohort, but the association was not statistically significant in the Rotterdam Study. When we combined hip data from all 4 cohorts, we found that the minor allele of rs7164503 was associated with a significantly lower risk of hip OA (Mantel-Haenszel odds ratio 0.67 [95% confidence interval 0.53,0.84], P < 3.8 × 10,4) and that a similar trend was observed for knee OA (Mantel-Haenszel odds ratio 0.87 [95% confidence interval 0.73,1.01], P < 0.055). Conclusion Our results provide evidence suggesting that ANP32A is involved in the pathogenesis of OA of the hip. [source]

Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand

ARTHRITIS & RHEUMATISM, Issue 6 2009
Evangelos Evangelou
Objective GDF5 and FRZB have been proposed as genetic loci conferring susceptibility to osteoarthritis (OA); however, the results of several studies investigating the association of OA with the rs143383 polymorphism of the GDF5 gene or the rs7775 and rs288326 polymorphisms of the FRZB gene have been conflicting or inconclusive. To examine these associations, we performed a large-scale meta-analysis of individual-level data. Methods Fourteen teams contributed data on polymorphisms and knee, hip, and hand OA. For rs143383, the total number of cases and controls, respectively, was 5,789 and 7,850 for hip OA, 5,085 and 8,135 for knee OA, and 4,040 and 4,792 for hand OA. For rs7775, the respective sample sizes were 4,352 and 10,843 for hip OA, 3,545 and 6,085 for knee OA, and 4,010 and 5,151 for hand OA, and for rs288326, they were 4,346 and 8,034 for hip OA, 3,595 and 6,106 for knee OA, and 3,982 and 5,152 for hand OA. For each individual study, sex-specific odds ratios (ORs) were calculated for each OA phenotype that had been investigated. The ORs for each phenotype were synthesized using both fixed-effects and random-effects models for allele-based effects, and also for haplotype effects for FRZB. Results A significant random-effects summary OR for knee OA was demonstrated for rs143383 (1.15 [95% confidence interval 1.09,1.22]) (P = 9.4 × 10,7), with no significant between-study heterogeneity. Estimates of effect sizes for hip and hand OA were similar, but a large between-study heterogeneity was observed, and statistical significance was borderline (for OA of the hip [P = 0.016]) or absent (for OA of the hand [P = 0.19]). Analyses for FRZB polymorphisms and haplotypes did not reveal any statistically significant signals, except for a borderline association of rs288326 with hip OA (P = 0.019). Conclusion Evidence of an association between the GDF5 rs143383 polymorphism and OA is substantially strong, but the genetic effects are consistent across different populations only for knee OA. Findings of this collaborative analysis do not support the notion that FRZB rs7775 or rs288326 has any sizable genetic effect on OA phenotypes. [source]

Serum levels of vitamin D, sunlight exposure, and knee cartilage loss in older adults: The Tasmanian older adult cohort study

ARTHRITIS & RHEUMATISM, Issue 5 2009
Changhai Ding
Objective To determine the associations between serum levels of vitamin D, sunlight exposure, and knee cartilage loss cross-sectionally and longitudinally in older adults. Methods A total of 880 randomly selected subjects (mean age 61 years [range 51,79 years], 50% women) were studied at baseline, and 353 of these subjects were studied 2.9 years later. Serum levels of 25-hydroxyvitamin D (25[OH]D) were assessed by radioimmunoassay, and sunlight exposure was assessed by questionnaire. T1-weighted fat-suppressed magnetic resonance imaging (MRI) of the right knee was performed to determine knee cartilage volume and defects. Knee radiographic osteoarthritis (OA) and knee pain were also assessed. Results The mean 25(OH)D serum level was 52.8 nmoles/liter at baseline (range 13,119 nmoles/liter). Winter sunlight exposure and serum 25(OH)D level were both positively associated with medial and lateral tibial cartilage volume, and a serum 25(OH)D level <50 nmoles/liter was associated with increased medial tibiofemoral joint space narrowing (all P < 0.05). Longitudinally, baseline serum 25(OH)D level predicted change in both medial and lateral tibial cartilage volume (, = +0.04% per annum per nmole/liter for both; P < 0.05), and change in serum 25(OH)D level was positively associated with change in medial tibial cartilage volume. These associations were consistent in subjects with radiographic OA and knee pain and/or in women, but not in men or in subjects without radiographic OA or knee pain. Conclusion Sunlight exposure and serum 25(OH)D levels are both associated with decreased knee cartilage loss (assessed by radiograph or MRI). This is best observed using the whole range of 25(OH)D levels rather than predefined cut points and implies that achieving vitamin D sufficiency may prevent and/or retard cartilage loss in knee OA. [source]

Meniscal tear in knees without surgery and the development of radiographic osteoarthritis among middle-aged and elderly persons: The multicenter osteoarthritis study,

ARTHRITIS & RHEUMATISM, Issue 3 2009
Martin Englund
Objective Although partial meniscectomy is a risk factor for the development of knee osteoarthritis (OA), there is a lack of evidence that meniscal damage that is not treated with surgery would also lead to OA, suggesting that surgery itself may cause joint damage. Furthermore, meniscal damage is common. The aim of this study was to evaluate the association between meniscal damage in knees without surgery and the development of radiographic tibiofemoral OA. Methods We conducted a prospective case,control study nested within the observational Multicenter Osteoarthritis Study, which included a sample of men and women ages 50,79 years at high risk of knee OA who were recruited from the community. Patients who had no baseline radiographic knee OA but in whom tibiofemoral OA developed during the 30-month followup period were cases (n = 121). Control subjects (n = 294) were drawn randomly from the same source population as cases but had no knee OA after 30 months of followup. Individuals whose knees had previously undergone surgery were excluded. Meniscal damage was defined as the presence of any medial or lateral meniscal tearing, maceration, or destruction. Results Meniscal damage at baseline was more common in case knees than in control knees (54% versus 18%; P < 0.001). The model comparing any meniscal damage with no meniscal damage (adjusted for baseline age, sex, body mass index, physical activity, and mechanical knee alignment) yielded an odds ratio of 5.7 (95% confidence interval 3.4,9.4). Conclusion In knees without surgery, meniscal damage is a potent risk factor for the development of radiographic OA. These results highlight the need for better understanding, prevention, and treatment of meniscal damage. [source]

Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: The study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo-controlled trial

ARTHRITIS & RHEUMATISM, Issue 2 2009
André Kahan
Objective To assess the long-term effects of chondroitins 4 and 6 sulfate (CS) on the radiographic progression of, and symptom changes associated with, knee osteoarthritis (OA). Methods We performed an international, randomized, double-blind, placebo-controlled trial in which 622 patients with knee OA were randomly assigned to receive either 800 mg CS (n = 309 patients) or placebo (n = 313 patients) once daily for 2 years. Radiographs of the target knee, using the Lyon schuss view, were obtained at the time of enrollment and at 12, 18, and 24 months. The minimum joint space width (JSW) of the medial compartment of the tibiofemoral joint was assessed by digital image analysis. The primary outcome was the loss in minimum JSW over 2 years. Results The intent-to-treat analysis demonstrated a significant reduction (P < 0.0001) in minimum JSW loss in the CS group (mean ± SEM ,0.07 ± 0.03 mm) as compared with the placebo group (,0.31 ± 0.04 mm). The percentage of patients with radiographic progression ,0.25 mm was significantly reduced in the CS group compared with the placebo group (28% versus 41% [P < 0.0005]; relative risk reduction 33% [95% confidence interval 16,46%]). The number of patients needed to treat was 8 (95% confidence interval 5,17). Pain improved significantly faster in the CS group than in the placebo group (P < 0.01). There were no differences in safety between groups. Conclusion The long-term combined structure-modifying and symptom-modifying effects of CS suggest that it could be a disease-modifying agent in patients with knee OA. [source]

Quadriceps strength and the risk of cartilage loss and symptom progression in knee osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 1 2009
Shreyasee Amin
Objective To determine the effect of quadriceps strength in individuals with knee osteoarthritis (OA) on loss of cartilage at the tibiofemoral and patellofemoral joints (assessed by magnetic resonance imaging [MRI]) and on knee pain and function. Methods We studied 265 subjects (154 men and 111 women, mean ± SD age 67 ± 9 years) who met the American College of Rheumatology criteria for symptomatic knee OA and who were participating in a prospective, 30-month natural history study of knee OA. Quadriceps strength was measured at baseline, isokinetically, during concentric knee extension. MRI of the knee at baseline and at 15 and 30 months was used to assess cartilage loss at the tibiofemoral and patellofemoral joints, with medial and lateral compartments assessed separately. At baseline and at followup visits, knee pain was assessed using a visual analog scale, and physical function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index. Results There was no association between quadriceps strength and cartilage loss at the tibiofemoral joint. Results were similar in malaligned knees. However, greater quadriceps strength was protective against cartilage loss at the lateral compartment of the patellofemoral joint (for highest versus lowest tertile of strength, odds ratio 0.4 [95% confidence interval 0.2, 0.9]). Those with greater quadriceps strength had less knee pain and better physical function over followup (P < 0.001). Conclusion Greater quadriceps strength had no influence on cartilage loss at the tibiofemoral joint, including in malaligned knees. We report for the first time that greater quadriceps strength protected against cartilage loss at the lateral compartment of the patellofemoral joint, a finding that requires confirmation. Subjects with greater quadriceps strength also had less knee pain and better physical function over followup. [source]

Tibial subchondral trabecular volumetric bone density in medial knee joint osteoarthritis using peripheral quantitative computed tomography technology

ARTHRITIS & RHEUMATISM, Issue 9 2008
Kim L. Bennell
Objective Knee osteoarthritis (OA) is an organ-level failure of the joint involving pathologic changes in articular cartilage and bone. This cross-sectional study compared apparent volumetric bone mineral density (vBMD) of proximal tibial subchondral trabecular bone in people with and without knee OA, using peripheral quantitative computed tomography (pQCT). Methods Seventy-five individuals with mild or moderate medial compartment knee OA and 41 asymptomatic controls were recruited. Peripheral QCT was used to measure vBMD of trabecular bone beneath medial and lateral tibiofemoral compartments at levels of 2% and 4% of tibial length, distal to the tibial plateau. Results There was no significant difference in vBMD beneath the overall medial and lateral compartments between the 3 groups. However, in the affected medial compartment of those with moderate OA, lower vBMD was seen in the 2 posterior subregions compared with controls and those with mild knee OA, while higher vBMD was seen in the anteromedial subregion. Beneath the unaffected or lesser affected lateral compartment, significantly lower vBMD was seen at the 2% level in the anterior and lateral subregions of those with moderate disease. Volumetric BMD ratios showed relatively higher vBMD in the medial compartment compared with the lateral compartment, but these ratios were not influenced by disease status. Conclusion Subregional vBMD changes were evident beneath the medial and lateral compartments of those with moderate medial knee OA. Of import, the posterior subchondral trabecular regions of the medial tibial plateau have markedly lower vBMD. [source]