Selection of knee radiographs for trials of structure‐modifying drugs in patients with knee osteoarthritis: A prospective,longitudinal study of lyon schuss knee radiographs with the definition of adequate alignment of the medial tibial plateau

Objective

The quality of medial tibial plateau (MTP) alignment, which is assessed by measuring the distance between the anterior and posterior margins (intermargin distance [IMD]) of the tibial plateau, and the reproducibility of alignment in serial radiographs are suggested to be key elements in determining the accuracy and sensitivity to change in knee radiographs in patients with tibiofemoral osteoarthritis (OA). We evaluated the influence of both MTP alignment and radiograph superimposition on the sensitivity to change in radiographic joint space narrowing (JSN) in knee OA.

Methods

The study group comprised 106 patients with knee pain (73 with OA). Lyon schuss radiographic images of the knee were obtained twice (at baseline [month 0] and 12 months later), using a standardized radiographic procedure. Computerized measurement of the IMD for the assessment of MTP alignment was compared with the grading of MTP alignment by 2 observers using a 5‐point scale (excellent, good, fair, poor, bad). To obtain the rate of JSN, computerized measurement of the joint space width was performed at month 0 and month 12. The sensitivity of the joint space width to change over 1 year was evaluated by the standardized response mean (SRM).

Results

The mean (±SD) IMD was 1.2 ± 0.9 mm. The correlation between scoring and computer measurement of MTP alignment was highly significant. The cutoff value for satisfactory alignment (excellent or good) was an IMD of ≤1.2 mm. In OA knees, the mean (±SD) annual rate of JSN and the SRM were statistically higher in knees with an IMD of ≤1.2 mm at both month 0 and month 12 (0.34 ± 0.50 mm and 0.68, respectively) than in knees with an IMD of >1.2 mm at month 0 and/or month 12.

Conclusion

The quality of MTP alignment at both baseline and the end point highly influences the sensitivity to change in radiographic JSN in knee OA. To obtain relevant data, only radiographs showing an IMD of ≤1.2 mm at both baseline and the end point would have to be analyzed in studies of structure‐modifying OA drugs.

     

Effect of alignment of the medial tibial plateau and X‐ray beam on apparent progression of osteoarthritis in the standing anteroposterior knee radiograph

Objective

Previous studies of knee osteoarthritis (OA) have yielded variable estimates of the rate of joint space narrowing (JSN) in the standing anteroposterior (AP) radiograph, due largely to longitudinal changes in the alignment of the medial tibial plateau (MTP) and x‐ray beam. To characterize this bias, we examined serial radiographs of subjects with knee OA in population‐based and clinical OA cohorts from 3 locations in the United States and the United Kingdom.

Methods

Radiographic features of knee OA (e.g., osteophytosis, JSN) and MTP alignment in 428 OA knees were evaluated by consensus of 2 readers. Alignment was considered satisfactory if the anterior and posterior margins of the MTP were superimposed within 1 mm. Readers were blinded to subject identity, and films were read in random order. The minimum medial joint space width was also measured manually (standard error of repeated measurements 0.20 mm) in serial knee images.

Results

Only 14% of serial radiographs exhibited alignment of the MTP in both images. In OA knees with satisfactory alignment in both images, the mean rate of JSN over 2–3 years (0.26 mm/year) was significantly larger (P = 0.004) than that in OA knees with misalignment in 1 or both radiographs and was 86% more rapid than the mean JSN in all OA knees. Moreover, the within‐group standard deviation of JSN was significantly smaller among knees with reproduced alignment of the MTP than in knees in which misalignment occurred in 1 or both images (P = 0.006).

Conclusion

Poor standardization of knee positioning in serial standing AP radiographs in previous studies of OA progression has obscured the rate and variability of articular cartilage loss in subjects with knee OA. True JSN (i.e., JSN that is not attributable to longitudinal changes in the alignment of the MTP with the x‐ray beam in serial radiographic examinations) may occur more rapidly, and with less between‐subject variability, than that previously thought to be characteristic of knee OA.

     

Independent association of joint space narrowing and osteophyte formation at the knee with health‐related quality of life in Japan: A cross‐sectional study

Objective

To clarify the individual associations of joint space narrowing (JSN) and osteophytosis at the knee with quality of life (QOL) in Japanese men and women using a large‐scale population‐based cohort from the Research on Osteoarthritis Against Disability (ROAD) study.

Methods

The associations of minimum joint space width (JSW) and osteophyte area in the medial compartment of the knee with QOL parameters, such as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), were examined. Minimum JSW and osteophyte area in the medial compartment of the knee were measured using a computer‐aided system for the diagnosis of knee osteoarthritis.

Results

Of the 3,040 participants in the ROAD study, the present study included 2,039 participants age 40 years or older who completed the questionnaires (741 men and 1,298 women with a mean ± SD age of 68.6 ± 10.9 years). Multiple regression analysis after adjustment for age and body mass index showed that minimum JSW was significantly associated with scores on the pain domains of the WOMAC in men and women, while osteophyte area was significantly associated with scores on the physical function domains of the WOMAC in men and women.

Conclusion

The findings of this cross‐sectional study using a large‐scale population from the ROAD study indicate that JSN and osteophytosis are independently associated with QOL.

     

Longitudinal performance evaluation and validation of fixed‐flexion radiography of the knee for detection of joint space loss

Objective

The ability of nonfluoroscopically guided radiography of the knee to assess joint space loss is an important issue in studies of progression and treatment of knee osteoarthritis (OA), given the practical limitations of protocols involving fluoroscopically guided radiography of the knee. We evaluated the ability of the nonfluoroscopically guided fixed‐flexion radiography protocol to detect knee joint space loss over 3 years.

Methods

We assessed the same‐day test–retest precision for measuring minimum joint space width (JSW), the sensitivity for detection of joint space loss using serial films obtained a median of 37 months (range 23–47 months) apart, and the relationship of joint space loss to radiographic and magnetic resonance imaging (MRI) measures of knee OA. Participants were men and women (ages 70–79 years) with knee pain who were participating in the Health, Aging, and Body Composition Study. We assessed baseline radiographic OA and measured JSW using a computerized algorithm. Serial knee MRIs obtained over the same interval were evaluated for cartilage lesions.

Results

A total of 153 knees were studied, 35% of which had radiographic OA at baseline. The mean ± SD joint space loss for all knees over 3 years was 0.24 ± 0.59 mm (P < 0.001 for change). In knees with OA at baseline, the mean ± SD joint space loss over 3 years was 0.43 ± 0.66 mm (P < 0.001), and in knees with joint space narrowing at baseline, joint space loss was 0.50 ± 0.67 mm (P < 0.001). Joint space loss and its standardized response mean increased with the severity of baseline joint space narrowing and with the presence of cartilage lesions at baseline and worsening during followup.

Conclusion

Radiography of the knee in the fixed‐flexion view provides a sensitive and valid measure of joint space loss in multiyear longitudinal studies of knee OA, without the use of fluoroscopy to aid knee positioning.

     

One‐year change in radiographic joint space width in patients with unilateral joint space narrowing: Data from the osteoarthritis initiative

Objective

To examine the rate of joint space width (JSW) loss in both knees of patients with unilateral medial joint space narrowing (JSN) at baseline.

Methods

Cases were selected from a pool of 2,678 subjects enrolled in the Osteoarthritis Initiative cohort. Inclusion criteria for the present study were unilateral medial JSN, bilateral frequent knee pain, and body mass index (BMI) ≥25 kg/m². Baseline and 1‐year fixed flexion radiographs of both knees were read (blinded to time point) using an automated algorithm for minimum JSW and JSW at 4 fixed locations in the medial compartment.

Results

Sixty‐seven participants met the inclusion criteria: 43 women and 24 men, with mean ± SD age 60 ± 9 years and mean ± SD BMI 31 ± 4 kg/m². Thirty‐seven subjects (55%) had ≥1 definite tibiofemoral osteophyte. The average progression in no‐JSN knees was comparable with that in JSN knees (approximately ?0.2 mm/year). However, JSW change was more variable in no‐JSN knees, resulting in standardized response means (SRMs; the mean/SD) of approximately ?0.24 in no‐JSN knees versus approximately ?0.41 in JSN knees on average at the 4 fixed locations, and SRMs of ?0.24 and ?0.35, respectively, for minimum JSW. Young age and high BMI were associated with increased progression, especially in JSN knees.

Conclusion

JSN and no‐JSN knees progressed at a comparable rate, but a wider distribution of JSW change in no‐JSN knees resulted in a poorer sensitivity to change in these knees.

     

Efficacy and safety of four doses of lumiracoxib versus diclofenac in patients with knee or hip primary osteoarthritis: A phase II,four‐week,multicenter, randomized,double‐blind,placebo‐controlled trial

Objective

To compare the efficacy and tolerability of the novel cyclooxygenase 2‐selective inhibitor lumiracoxib with placebo and diclofenac in osteoarthritis (OA).

Methods

Adults (n = 583) with knee or hip OA were randomized to receive for 4 weeks lumiracoxib 50, 100, or 200 mg twice daily or 400 mg once daily; placebo; or diclofenac 75 mg twice daily. Efficacy assessments included overall joint pain intensity and Western Ontario and McMaster Universities Osteoarthritis Index subscales; tolerability was evaluated by adverse event and physician reporting.

Results

All lumiracoxib doses were superior to placebo in relieving pain, improving stiffness, and improving physical function after 4 weeks. At study endpoint, pain relief was comparable among all lumiracoxib dosages and similar to diclofenac. Lumiracoxib tolerability was superior to diclofenac and comparable to placebo.

Conclusion

Lumiracoxib provides predictable and sustained relief from pain, stiffness, and impaired physical function in OA. Lumiracoxib shows clinically comparable efficacy and superior tolerability to diclofenac.

     

Trabecular morphometry by fractal signature analysis is a novel marker of osteoarthritis progression

Objective

To evaluate the effectiveness of using subchondral bone texture observed on a radiograph taken at baseline to predict progression of knee osteoarthritis (OA) over a 3‐year period.

Methods

A total of 138 participants in the Prediction of Osteoarthritis Progression study were evaluated at baseline and after 3 years. Fractal signature analysis (FSA) of the medial subchondral tibial plateau was performed on fixed flexion radiographs of 248 nonreplaced knees, using a commercially available software tool. OA progression was defined as a change in joint space narrowing (JSN) or osteophyte formation of 1 grade according to a standardized knee atlas. Statistical analysis of fractal signatures was performed using a new model based on correlating the overall shape of a fractal dimension curve with radius.

Results

Fractal signature of the medial tibial plateau at baseline was predictive of medial knee JSN progression (area under the curve [AUC] 0.75, of a receiver operating characteristic curve) but was not predictive of osteophyte formation or progression of JSN in the lateral compartment. Traditional covariates (age, sex, body mass index, knee pain), general bone mineral content, and joint space width at baseline were no more effective than random variables for predicting OA progression (AUC 0.52–0.58). The predictive model with maximum effectiveness combined fractal signature at baseline, knee alignment, traditional covariates, and bone mineral content (AUC 0.79).

Conclusion

We identified a prognostic marker of OA that is readily extracted from a plain radiograph using FSA. Although the method needs to be validated in a second cohort, our results indicate that the global shape approach to analyzing these data is a potentially efficient means of identifying individuals at risk of knee OA progression.

     

Safety and efficacy of long‐term intraarticular steroid injections in osteoarthritis of the knee: A randomized,double‐blind,placebo‐controlled trial

Objective

To evaluate the safety and efficacy of long‐term intraarticular (IA) steroid injections for knee pain related to osteoarthritis (OA).

Methods

In a randomized, double‐blind trial, 68 patients with OA of the knee received IA injections of triamcinolone acetonide 40 mg (34 patients) or saline (34 patients) into the study knee every 3 months for up to 2 years. The primary outcome variable was radiologic progression of joint space narrowing of the injected knee after 2 years. Measurements of minimum joint space width were performed by an automated computerized method on standardized fluoroscopically guided radiographs taken with the patient standing and with the knee in a semiflexed position. The clinical efficacy measure of primary interest was the pain subscale from the Western Ontario and McMaster Universities OA Index (WOMAC). Efficacy measures of secondary interest were the total score on the WOMAC, physician's global assessment, patient's global assessment, patient's assessment of pain, range of motion (ROM) of the affected knee, and 50‐foot walking time. Clinical symptoms were assessed just before each injection.

Results

At the 1‐year and 2‐year followup evaluations, no difference was noted between the two treatment groups with respect to loss of joint space over time. The steroid‐injected knees showed a trend toward greater symptom improvement, especially at 1 year, for the WOMAC pain subscale, night pain, and ROM values (P = 0.05) compared with the saline‐injected knees. Using area under the curve analyses, knee pain and stiffness were significantly improved throughout the 2‐year study by repeated injections of triamcinolone acetonide, but not saline (P < 0.05).

Conclusion

Our findings support the long‐term safety of IA steroid injections for patients with symptomatic knee OA. No deleterious effects of the long‐term administration of IA steroids on the anatomical structure of the knee were noted. Moreover, long‐term treatment of knee OA with repeated steroid injections appears to be clinically effective for the relief of symptoms of the disease.

     

Change in joint space width: Hyaline articular cartilage loss or alteration in meniscus?

Objective

To explore the relative contribution of hyaline cartilage morphologic features and the meniscus to the radiographic joint space.

Methods

The Boston Osteoarthritis of the Knee Study is a natural history study of symptomatic knee osteoarthritis (OA). Baseline and 30‐month followup assessments included knee magnetic resonance imaging (MRI) and fluoroscopically positioned weight‐bearing knee radiographs. Cartilage and meniscal degeneration were scored on MRI in the medial and lateral tibiofemoral joints using a semiquantitative grading system. Meniscal position was measured to the nearest millimeter. The dependent variable was joint space narrowing (JSN) on the plain radiograph (possible range 0–3). The predictor variables were MRI cartilage score, meniscal degeneration, and meniscal position measures. We first conducted a cross‐sectional analysis using multivariate regression to determine the relative contribution of meniscal factors and cartilage morphologic features to JSN, adjusting for body mass index (BMI), age, and sex. The same approach was used for change in JSN and change in predictor variables.

Results

We evaluated 264 study participants with knee OA (mean age 66.7 years, 59% men, mean BMI 31.4 kg/m²). The results from the models demonstrated that meniscal position and meniscal degeneration each contributed to prediction of JSN, in addition to the contribution by cartilage morphologic features. For change in medial joint space, both change in meniscal position and change in articular cartilage score contributed substantially to narrowing of the joint space.

Conclusion

The meniscus (both its position and degeneration) accounts for a substantial proportion of the variance explained in JSN, and the change in meniscal position accounts for a substantial proportion of change in JSN.

     

Tidal irrigation as treatment for knee osteoarthritis: A sham‐controlled,randomized, double‐blinded evaluation

Objective

To evaluate the effectiveness of tidal irrigation (TI) in comparison with a well‐matched sham irrigation (SI) procedure as a treatment for knee osteoarthritis (OA).

Methods

One hundred eighty subjects with knee OA were randomized to receive TI or SI, with clinical followup over the ensuing 12 months. The primary outcomes of interest were change in pain and function, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Subjects and the nurse assessor were blinded, and success of blinding was assessed.

Results

Although the study groups were otherwise comparable, the baseline WOMAC pain and physical functioning scores were higher (worse) in the SI group. After adjustment for baseline, there were no differences between the effects of SI and TI. Blinding was successful, with ∼90% of SI and TI subjects stating that they had received the TI procedure.

Conclusion

Most, if not all, of the effect of TI appears to be attributable to a “placebo response.”

     

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

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.

     

Discordance between pain and radiographic severity in knee osteoarthritis: Findings from quantitative sensory testing of central sensitization

Objective

Radiographic measures of the pathologic changes of knee osteoarthritis (OA) have shown modest associations with clinical pain. We sought to evaluate possible differences in quantitative sensory testing (QST) results and psychosocial distress profiles between knee OA patients with discordant versus congruent clinical pain reports relative to radiographic severity measures.

Methods

A total of 113 participants (66.7% women; mean ± SD age 61.05 ± 8.93 years) with knee OA participated in the study. Radiographic evidence of joint pathology was graded according to the Kellgren/Lawrence scale. Central sensitization was indexed through quantitative sensory testing, including heat and pressure–pain thresholds, tonic suprathreshold pain (cold pressor test), and repeated phasic suprathreshold mechanical and thermal pain. Subgroups were constructed by dichotomizing clinical knee pain scores (median split) and knee OA grade scores (grades 1–2 versus 3–4), resulting in 4 groups: low pain/low knee OA grade (n = 24), high pain/high knee OA grade (n = 32), low pain/high knee OA grade (n = 27), and high pain/low knee OA grade (n = 30).

Results

Multivariate analyses revealed significantly heightened pain sensitivity in the high pain/low knee OA grade group, while the low pain/high knee OA grade group was less pain‐sensitive. Group differences remained significant after adjusting for differences on psychosocial measures, as well as age, sex, and race.

Conclusion

The results suggest that central sensitization in knee OA is especially apparent among patients with reports of high levels of clinical pain in the absence of moderate‐to‐severe radiographic evidence of pathologic changes of knee OA.

     

Normalization of widespread hyperesthesia and facilitated spatial summation of deep‐tissue pain in knee osteoarthritis patients after knee replacement

Objective

The modest association between radiographic joint damage and pain in osteoarthritis (OA) has led to the suggestion of facilitated central pain processing. This study evaluated the importance of ongoing tissue pathology in the maintenance of enhanced central pain processing.

Methods

Pain assessment was performed on 48 patients with symptomatic knee OA and 21 sex‐ and age‐matched pain‐free healthy control subjects. Twenty of the OA patients subsequently underwent total knee replacement surgery and were reassessed. Pressure–pain thresholds (PPTs) were recorded using a pressure algometer (both over and distant from the knee) and a double‐chamber inflatable cuff mounted around the calf. Spatial summation was assessed by relating PPTs using the dual‐ and single‐chamber cuff. Conditioned pain modulation (CPM) was assessed by recording the increase in PPT in response to experimental arm pain.

Results

PPTs at the knee and at sites away from the knee were reduced in OA patients as compared with healthy pain‐free control subjects (P < 0.0001). Cuff PPTs were decreased in OA patients as compared with the healthy controls (P < 0.05), who also exhibited a greater degree of spatial summation (P < 0.05). Whereas an elevation of PPTs was noted in the healthy controls in response to experimental arm pain (P < 0.0001), no such CPM was observed in the OA patients. Following joint replacement in the OA patients, there was a reduction in the widespread mechanical hyperesthesia, along with normalization of spatial summation ratios and restoration of CPM.

Conclusion

The widespread hyperesthesia and enhanced spatial summation observed in OA patients imply sensitized central pain mechanisms together with the loss of CPM. Normalization of the results following joint replacement implies that these central pain processes are maintained by peripheral input.

     

Biomarkers of incident radiographic knee osteoarthritis: Do they vary by chronic knee symptoms?

Objective

To explore the ability of osteoarthritis (OA)–related biomarkers to predict incident radiographic knee OA in a large sample of African American and Caucasian men and women.

Methods

Baseline levels of serum cartilage oligomeric matrix protein (COMP), hyaluronan (HA), high‐sensitivity C‐reactive protein (hsCRP), and keratan sulfate (KS) and baseline and followup radiographs were available for 353 knees without baseline osteophyte formation and for 446 knees without baseline joint space narrowing (JSN). Cox models estimated the hazard ratio (HR) and 95% confidence interval (95% CI) for incident knee OA for a 1‐unit increase in the ln of each biomarker, with adjustment for age, race, sex, body mass index, and knee OA of the contralateral limb. Report of chronic knee symptoms was explored as a modifier of the association.

Results

The hazard of incident knee osteophytes (HR 2.16 [95% CI 1.39–3.37]) and incident JSN (HR 1.82 [95% CI 1.15–2.89]) increased with higher baseline ln(COMP) levels. The hazard of incident knee JSN increased with higher ln(HA) levels (HR 1.46 [95% CI 1.14–1.87]). Baseline ln(hsCRP) and ln(KS) did not predict incident knee outcomes. HRs per unit increase in ln(COMP), ln(HA), and ln(KS) were higher among knees with chronic symptoms than among those without symptoms.

Conclusion

Higher baseline ln(COMP) and ln(HA) levels were associated with incident knee OA over an average followup period of 6.3 years. These results represent detection of a molecular stage of OA prior to radiographic manifestations. Further exploration is needed to determine how chronic knee symptoms modify the biomarker–incident knee OA association.

     

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

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.

     

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

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.

     

Increase in vastus medialis cross‐sectional area is associated with reduced pain,cartilage loss,and joint replacement risk in knee osteoarthritis

Objective

Although there is evidence for a beneficial effect of increased quadriceps strength on knee symptoms, the effect on knee structure is unclear. We undertook this study to examine the relationship between change in vastus medialis cross‐sectional area (CSA) and knee pain, tibial cartilage volume, and risk of knee replacement in subjects with symptomatic knee osteoarthritis (OA).

Methods

One hundred seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of the knee at baseline and at 2 and 4.5 years. Vastus medialis CSA was measured at baseline and at 2 years. Tibial cartilage volume was measured at baseline and at 2 and 4.5 years. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index at baseline and at 2 years. The frequency of knee joint replacement over 4 years was determined. Regression coefficients (B) and odds ratios were determined along with 95% confidence intervals (95% CIs).

Results

After adjusting for confounders, baseline vastus medialis CSA was inversely associated with current knee pain (r = −0.16, P = 0.04) and with medial tibial cartilage volume loss from baseline to 2 years (B coefficient −10.9 [95% CI −19.5, −2.3]), but not with baseline tibial cartilage volume. In addition, an increase in vastus medialis CSA from baseline to 2 years was associated with reduced knee pain over the same time period (r = 0.24, P = 0.007), reduced medial tibial cartilage loss from 2 to 4.5 years (B coefficient −16.8 [95% CI −28.9, −4.6]), and reduced risk of knee replacement over 4 years (odds ratio 0.61 [95% CI 0.40, 0.94]).

Conclusion

In a population of patients with symptomatic knee OA, increased vastus medialis size was associated with reduced knee pain and beneficial structural changes at the knee, suggesting that management of knee pain and optimizing vastus medialis size are important in reducing OA progression and subsequent knee replacement.

     

Cannabinoid‐mediated antinociception is enhanced in rat osteoarthritic knees

Objective

To determine whether local administration of the cannabinoid 1 (CB₁) receptor agonist arachidonyl‐2‐chloroethylamide (ACEA) can modulate joint nociception in control rat knee joints and in experimental osteoarthritis (OA).

Methods

OA was induced in male Wistar rats by intraarticular injection of 3 mg of sodium mono‐iodoacetate, with a recovery period of 14 days. Electrophysiologic recordings were made of knee joint primary afferent nerve fibers in response to normal rotation and noxious hyperrotation of the joint both before and after close intraarterial injection of different doses of ACEA.

Results

Local application of the CB₁ agonist significantly reduced the firing rate of afferent nerve fibers by up to 50% in control knee joints (n = 19) and up to 62% in OA knee joints (n = 29; P < 0.01). Coadministration of the CB₁ receptor antagonist AM251 or the transient receptor potential vanilloid 1 (TRPV‐1) ion channel antagonist SB366791 significantly reduced the desensitizing effect of ACEA. The CB₁ receptor antagonist AM251 by itself had no effect in the control joint but significantly increased the firing rate of afferent nerve fibers in the OA joint.

Conclusion

These findings indicate that activation of peripheral CB₁ receptors reduces the mechanosensitivity of afferent nerve fibers in control and OA knee joints. Blockade of either the CB₁ receptor or the TRPV‐1 channel significantly reduced the efficacy of ACEA, which suggests that both receptors are involved in cannabinoid‐mediated antinociception. The increased nerve activity observed following CB₁ receptor antagonism suggests a tonic release of endocannabinoids during OA. As such, peripheral CB₁ receptors may be important targets in controlling OA pain.

     

Pilot study of the effects of a heat‐retaining knee sleeve on joint pain,stiffness, and function in patients with knee osteoarthritis

Objective

To identify changes in joint pain, stiffness, and functional ability in patients with knee osteoarthritis (OA) after use of a knee sleeve that prevents loss of body heat by the joint.

Methods

Subjects with symptomatic knee OA (n = 52) were randomized to 2 treatment groups: verum sleeve (specially fabricated to retain body heat) or placebo sleeve (standard cotton/elastane sleeve). Subjects wore the sleeve over the more painful OA knee for at least 12 hours daily for 4 weeks. Pain, stiffness, and functional impairment (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) in the index knee were measured at baseline and after 4 weeks of wear, after which sleeve use was discontinued. Telephone followup interviews were conducted 2 and 4 weeks later.

Results

After 4 weeks of sleeve wear, subjects in the active treatment group reported a 16% decrease in mean WOMAC pain score relative to baseline (P = 0.001). Those who wore the placebo sleeve reported a 9.7% decrease from baseline (P = 0.002). The difference between treatment groups was not statistically significant (P = 0.12). However, it was found that the 12 subjects who believed correctly that they had received the verum sleeve reported a highly significant decrease in WOMAC pain score (?27.5% relative to baseline, P = 0.0001). In comparison, subjects who received the verum sleeve but believed they had received the placebo sleeve exhibited only a marginally significant improvement in pain (?13.0% relative to baseline, P = 0.07). In the placebo group, the modest improvement in pain scores appeared unrelated to the subject's impression of the type of sleeve worn.

Conclusion

This pilot study was insufficiently powered to be a definitive trial of the heat‐retaining sleeve. Given the magnitude of changes in knee pain in the active treatment group, heat retention merits further scientific investigation as a treatment modality for patients with knee OA.

     

Femorotibial subchondral bone area and regional cartilage thickness: A cross‐sectional description in healthy reference cases and various radiographic stages of osteoarthritis in 1,003 knees from the Osteoarthritis Initiative

Objective

To identify structural differences in total subchondral bone area (tAB) and cartilage thickness between healthy reference knees and knees with radiographic osteoarthritis (OA).

Methods

Baseline magnetic resonance images from 1 knee of 1,003 Osteoarthritis Initiative participants were studied: 112 healthy reference knees without radiographic OA, symptoms, or risk factors; 70 preradiographic OA knees (calculated Kellgren/Lawrence [K/L] grade 0/1); and 821 radiographic OA knees (calculated K/L grade ≥2). Means and standard (Z) scores (SD unit differences compared with normal subjects) of the tAB and regional cartilage thickness were assessed in the weight‐bearing femorotibial joint and compared between groups.

Results

In men, tAB was 8.2% larger in preradiographic OA knees and 6.6%, 8.1%, and 8.5% larger in calculated K/L grade 2, 3, and 4 radiographic OA knees, respectively, than in reference knees. In women, the differences were +6.8%, +7.3%, +9.9%, and +8.1%, respectively. The external medial tibia showed the greatest reduction in cartilage thickness (Z scores ?5.1/?5.6 in men/women) with Osteoarthritis Research Society International medial joint space narrowing (JSN) grade 3, and the external lateral tibia (Z scores ?6.0 for both sexes) showed the greatest reduction with lateral JSN grade 3. In all subregions of end‐stage radiographic OA knees, ≥25% of the average normal cartilage thickness was maintained. An overall trend toward thicker cartilage was found in preradiographic OA and calculated K/L grade 2 knees, especially in the external central medial femur.

Conclusion

tABs were larger in preradiographic OA and radiographic OA knees than in healthy reference knees, and the difference did not become larger with higher calculated K/L grades. Specific subregions with substantial cartilage thickening or thinning were identified in pre‐, early, and late radiographic OA.