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.

     

Steroid injection for osteoarthritis of the hip: A randomized,double‐blind,placebo‐controlled trial

Objective

To determine the efficacy of fluoroscopically guided corticosteroid injection for hip osteoarthritis (OA) in a randomized, double‐blind, placebo‐controlled trial.

Methods

Fifty‐two patients with symptomatic hip OA were randomly allocated to receive placebo (10 mg bipuvicaine, 2 ml saline) (n = 21) or corticosteroid treatment (10 mg bipuvicaine, 40 mg triamcinolone hexacetonide) (n = 31). Patients were followed up for 1, 2, 3, and 6 months. The primary outcome measure was the pain improvement response, defined as a 20% decrease in the Western Ontario and McMaster Universities OA Index (WOMAC) pain score (on 5 100‐mm visual analog scales [VAS]) (WOMAC20) from baseline to 2 months postinjection. Secondary outcomes were a 50% decrease in the WOMAC pain score (WOMAC50), changes in other WOMAC subscale scores, patient's global assessment of health (on a 100‐mm VAS), and Short Form 36 (SF‐36) quality of life indices. Analyses were based on the intent‐to‐treat principle.

Results

The mean WOMAC pain score fell 49.2% (decreasing from 310.1 mm to 157.4 mm) at 2 months postinjection in patients receiving corticosteroid, compared with a decrease of 2.5% (from 314.3 mm to 306.5 mm) in the placebo group (P < 0.0001). The proportion of WOMAC20 responders at 2 months' followup was significantly higher in the corticosteroid group (67.7%) compared with the placebo group (23.8%) (P = 0.004); similar proportions of WOMAC50 responders were observed between groups (61.3% in the corticosteroid group versus 14.3% in the placebo group; P = 0.001). Response differences were maintained at 3 months' followup (58.1% responders in the corticosteroid group versus 9.5% responders in the placebo group; P = 0.004). Significant differences in the WOMAC stiffness and physical function scores (P < 0.0001), patient's global health scores (P = 0.005), and SF‐36 physical component scores (P = 0.04) were observed, with patients in the corticosteroid group showing greater improvements. There were no differences in the frequency of adverse events between groups.

Conclusion

This placebo‐controlled trial confirms that corticosteroid injection can be an effective treatment of pain in hip OA, with benefits lasting up to 3 months in many cases. Future studies should address questions related to the benefits of repeated steroid injection and the effects of this treatment on disease modification.

     

Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: A randomized,placebo‐controlled trial

Objective

Although common treatments for osteoarthritis (OA) pain, such as nonsteroidal antiinflammatory drugs (NSAIDs), simple analgesics, and weak opioids, provide relief in some cases, they fail to control pain or are poorly tolerated in many cases. Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies. Therefore, we tested the effects of transdermal fentanyl (TDF) in patients with moderate‐to‐severe OA pain, in a placebo‐controlled study.

Methods

The cohort comprised patients with radiologically confirmed OA of the hip or knee (meeting the American College of Rheumatology criteria) requiring joint replacement and with moderate‐to‐severe pain that had been inadequately controlled by weak opioids. The patients were randomized to receive TDF or placebo for 6 weeks after a 1‐week pretreatment run‐in phase. During study treatment, previously prescribed NSAIDs and simple analgesics were continued, but weak opioids were discontinued. All patients had access to paracetamol and metoclopramide. Pain was recorded on a visual analog scale (VAS), and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

Results

Data were available for 399 patients (202 receiving TDF, 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores −20 in the TDF group versus −14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group.

Conclusion

TDF can reduce pain and improve function in patients with knee or hip OA.

     

Comparing the efficacy of cyclooxygenase 2–specific inhibitors in treating osteoarthritis: Appropriate trial design considerations and results of a randomized,placebo‐controlled trial

Objective

To compare the efficacy of the cyclooxygenase 2 (COX‐2)–specific inhibitors celecoxib and rofecoxib in treating the signs and symptoms of osteoarthritis (OA).

Methods

In this randomized, placebo‐controlled, double‐blind, multicenter study, 475 patients with OA of the knee received either celecoxib 200 mg/day (n = 189), rofecoxib 25 mg/day (n = 190), or placebo (n = 96) for 6 weeks. Arthritis assessments were performed at baseline, week 3, and week 6 (or at the time of early termination).

Results

In primary measures of efficacy (OA pain score on a 100‐mm visual analog scale [VAS] and total domain score on the Western Ontario and McMaster Universities Osteoarthritis Index), celecoxib 200 mg/day and rofecoxib 25 mg/day demonstrated similar efficacy. At week 6, celecoxib was associated with a 34‐mm mean improvement on the VAS for OA pain, compared with 31.6 mm for rofecoxib and 21.2 mm for placebo. The difference between celecoxib and rofecoxib was −2.5 mm, with an upper limit of the 95% confidence interval of 2.7 mm and within the prespecified definition of noninferiority. Secondary measures of efficacy showed similar results. All differences in primary and secondary measures of efficacy between the 2 active treatments and placebo were statistically significant (P < 0.02), whereas all of the comparisons of efficacy between celecoxib and rofecoxib met the predefined criteria for noninferiority. All treatments were well tolerated throughout the study, with similar proportions of patients withdrawing due to adverse events.

Conclusion

Celecoxib 200 mg/day and rofecoxib 25 mg/day are equally efficacious in treating the signs and symptoms of OA.

     

Evaluation of the structure‐modifying effects of diacerein in hip osteoarthritis: ECHODIAH,a three‐year,placebo‐controlled trial

Objective

To evaluate the ability of diacerein, an interleukin‐1β inhibitor, to slow the progressive decrease in joint space width observed in patients with hip osteoarthritis (OA).

Methods

In this randomized, double‐blind, placebo‐controlled 3‐year study, 507 patients with primary OA of the hip (by the American College of Rheumatology criteria) received diacerein (50 mg twice a day) or placebo. The minimal hip joint space width was measured by a central reader on yearly pelvic radiographs, using a 0.1‐mm–graduated magnifying glass.

Results

Baseline characteristics were comparable in the 2 treatment groups (255 patients receiving diacerein, 252 receiving placebo); 238 patients (47%) discontinued the study, mainly because of adverse events in the diacerein group (25% versus 12% with placebo) and because of inefficacy in the placebo group (14% versus 7% with diacerein). The percentage of patients with radiographic progression, defined by a joint space loss of at least 0.5 mm, was significantly lower in patients receiving diacerein than in patients receiving placebo, both in the intent‐to‐treat analysis and in the completer analysis (50.7% versus 60.4% [P = 0.036] and 47.3% versus 62.3% [P = 0.007], respectively). In those patients who completed 3 years of treatment, the rate of joint space narrowing was significantly lower with diacerein (mean ± SD 0.18 ± 0.25 mm/year versus 0.23 ± 0.23 mm/year with placebo; P = 0.042). Diacerein had no evident effect on the symptoms of OA in this study. However, a post hoc covariate analysis that took into account the use of analgesics and antiinflammatory drugs showed an effect of diacerein on the Lequesne functional index. Diacerein was well tolerated during the 3‐year study. The most frequent adverse events were transient changes in bowel habits.

Conclusion

This study confirms previous clinical findings indicating that the demonstration of a structure‐modifying effect in hip OA is feasible, and shows, for the first time, that treatment with diacerein for 3 years has a significant structure‐modifying effect as compared with placebo, coupled with a good safety profile. The clinical relevance of these findings requires further investigation.

     

Very low prevalence of hip osteoarthritis among Chinese elderly in Beijing,China, compared with whites in the United States: The Beijing osteoarthritis study

Objective

To compare the prevalence of osteoarthritis (OA) of the hip among elderly persons in China and the US.

Methods

We recruited a population‐based sample of 1,506 persons (82% of those enumerated) ages ≥60 years living in Beijing, China. Subjects answered questions about joint symptoms and underwent radiography of the pelvis. Radiographs of the Beijing subjects were intermingled with hip radiographs of white women ages ≥65 years from the Study of Osteoporotic Fractures (SOF) and white men and women ages 60–74 years from the First National Health and Nutrition Examination Survey (NHANES‐I) and were then interpreted. Radiographic hip OA was defined as the presence of 1 of the following 3 findings in either hip: minimum joint space of ≤1.5 mm, definite osteophytes and joint space narrowing, or ≥3 radiographic features of OA. Symptomatic hip OA was defined as both radiographic OA and hip pain.

Results

The crude prevalence of radiographic hip OA in Chinese ages 60–89 years was 0.9% in women and 1.1% in men; it did not increase with age. Chinese women had a lower age‐standardized prevalence of radiographic hip OA compared with white women in the SOF (age‐standardized prevalence ratio 0.07) and the NHANES‐I (prevalence ratio 0.22). Chinese men had a lower prevalence of radiographic hip OA compared with white men of the same age in the NHANES‐I (prevalence ratio 0.19). There were no cases of symptomatic hip OA in the Chinese men and only 1 case in the Chinese women; 35 cases were expected in both sexes.

Conclusion

This is the first population‐based study of hip OA in China to use standardized radiographic methods and definitions. We found that hip OA was 80–90% less frequent than in white persons in the US. Identification of the genetic and environmental factors that underlie these differences may help elucidate the etiology and prevention of hip OA.

     

Comparative responsiveness of measures of pain and function after total hip replacement

Objective

To compare the responsiveness of the Functional Assessment System (FAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Medical Outcomes Study 36‐item Short Form (SF‐36) in patients with osteoarthritis (OA) scheduled for total hip replacement.

Method

Twenty patients with a mean age at surgery of 72.6 years, with primary OA of the hip, were investigated preoperatively and at 3, 6, and 12 months postoperatively with the FAS, WOMAC, and SF‐36. The responsiveness was calculated as standardized response mean, effect size, and relative efficiency.

Results

The pain and function scores of WOMAC and SF‐36 showed greater responsiveness than FAS at 3 months. These differences remained at 6 and 12 months postoperatively. The differences between these 3 outcome measures were found to be similar using several methods for calculating responsiveness.

Conclusion

Self‐administered questionnaires like WOMAC and SF‐36 are more responsive measures of pain and function than range of motion, performance tests, and observer‐administered questions (FAS) following total hip replacement.

     

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.

     

Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis: A randomized,double‐blind,placebo‐controlled clinical trial at a single center

Objective

To evaluate the symptomatic effects of highly purified chondroitin 4 and chondroitin 6 sulfate (CS) therapy in patients with osteoarthritis (OA) of the hand.

Methods

This investigator‐initiated, single‐center, randomized, double‐blind, placebo‐controlled clinical trial included 162 symptomatic patients with radiographic evidence of hand OA (American College of Rheumatology criteria). Inclusion criteria included patient's assessment of global spontaneous hand pain of at least 40 mm on a 0–100‐mm visual analog scale (VAS) and functional impairment of at least 6 (0–30 scale) on the Functional Index for Hand OA (FIHOA) in the most symptomatic hand. Patients received either 800 mg of CS (n = 80 patients) or placebo (n = 82 patients) once daily for 6 months and were analyzed in an intent‐to‐treat approach. The two primary outcomes were the change in the patient's assessment of global spontaneous hand pain and in hand function (by FIHOA score) from baseline to month 6. Secondary outcomes were improvement in grip strength, duration of morning stiffness, acetaminophen consumption, and the investigator's global impression of treatment efficacy.

Results

There was a significantly more pronounced decrease in the patient's global assessment of hand pain in the CS group than in the placebo group (difference VAS scores −8.7 mm; P = 0.016). Hand function improved significantly more in the CS group than in the placebo group (difference in FIHOA scores −2.14; P = 0.008). There was a statistically significant between‐group difference in favor of CS for the duration of morning stiffness and for the investigator's global impression of treatment efficacy. Changes in grip strength, acetaminophen consumption, and safety end points were not significantly different between the two groups.

Conclusion

This study demonstrates that CS improves hand pain and function in patients with symptomatic OA of the hand and shows a good safety profile.

     

The effectiveness of pulsed electrical stimulation in the management of osteoarthritis of the knee: Results of a double‐blind,randomized, placebo‐controlled,repeated‐measures trial

Objective

To determine the effectiveness of subsensory, pulsed electrical stimulation (PES) in the symptomatic management of osteoarthritis (OA) of the knee.

Methods

This was a double‐blind, randomized, placebo‐controlled, repeated‐measures trial in 70 participants with clinical and radiographically diagnosed OA of the knee who were randomized to either PES or placebo. The primary outcome was change in pain score over 26 weeks measured on a 100‐mm visual analog scale (VAS). Other measures included pain on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), function on the WOMAC, patient's global assessment of disease activity (on a 100‐mm VAS), joint stiffness on the WOMAC, quality of life on the Medical Outcomes Study Short‐Form 36 (SF‐36) health survey, physical activity (using the Human Activity Profile and an accelerometer), and global perceived effect (on an 11‐point scale).

Results

Thirty‐four participants were randomized to PES and 36 to placebo. Intent‐to‐treat analysis showed a statistically significant improvement in VAS pain score over 26 weeks in both groups, but no difference between groups (mean change difference 0.9 mm [95% confidence interval −11.7, 13.4]). Similarly, there were no differences between groups for changes in WOMAC pain, function, and stiffness scores (−5.6 [95% confidence interval −14.9, 3.6], −1.9 [95% confidence interval −9.7, 5.9], and 3.7 [95% confidence interval −6.0, 13.5], respectively), SF‐36 physical and mental component summary scores (1.7 [95% confidence interval −1.5, 4.8] and 1.2 [95% confidence interval −2.9, 5.4], respectively), patient's global assessment of disease activity (−2.8 [95% confidence interval −13.9, 8.4]), or activity measures. Fifty‐six percent of the PES‐treated group achieved a clinically relevant 20‐mm improvement in VAS pain score at 26 weeks compared with 44% of controls (12% [95% confidence interval −11%, 33%]).

Conclusion

In this sample of subjects with mild‐to‐moderate symptoms and moderate‐to‐severe radiographic OA of the knee, 26 weeks of PES was no more effective than placebo.

     

The effect of estrogen plus progestin on knee symptoms and related disability in postmenopausal women: The heart and estrogen/progestin replacement study,a randomized,double‐blind,placebo‐controlled trial

Objective

Most observational studies suggest that postmenopausal women taking hormone replacement therapy have a reduced risk of radiographic knee and hip osteoarthritis (OA). There are no randomized trial data on the association of hormone treatment with knee or hip OA, and no studies have been published regarding the relationship of hormone treatment to knee or hip symptoms. This study examined the association of hormone treatment with prevalent knee symptoms and disability related to knee pain as assessed at the final visit of the Heart and Estrogen/Progestin Replacement Study (HERS).

Methods

The HERS was a 4‐year randomized, double‐blind, placebo‐controlled trial of estrogen plus medroxy progesterone acetate for prevention of coronary heart disease in postmenopausal women with documented coronary disease. Participants in this substudy on knee pain were 969 postmenopausal women, with a mean age of 66 years and mean body mass index of 28.6 kg/m², attending the final visit at 9 clinical centers. Frequent knee symptoms were assessed by interview and the severity of knee pain and disability related to knee pain were determined using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Knee symptoms and disability were compared between women assigned to receive hormones and those assigned to receive placebo.

Results

Frequent knee pain was reported in 24.1% of women assigned to receive hormone therapy versus 26.1% of those assigned to the placebo group, a difference of −2.0% (95% confidence interval [95% CI] −7.4% to 3.5%). Among women with knee pain, there were no differences in the severity of pain (score difference −0.2, 95% CI −1.2 to 0.8) or disability (score difference −0.7, 95% CI −3.8 to 2.4) as assessed on the WOMAC. All results were similar for women whose body mass index was either above or below the median.

Conclusion

In a group of older, postmenopausal women with cardiac disease, we found no significant effect of 4 years of estrogen plus progestin therapy compared with placebo on knee pain and related disability. Our findings may not apply to other groups of women or to the effect of hormone therapy on the structural changes of knee OA.

     

Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty: A longitudinal voxel‐based morphometric study

Objective

Voxel‐based morphometry (VBM) is a method of assessing brain gray matter volume that has previously been applied to various chronic pain conditions. From this previous work, it appears that chronic pain is associated with altered brain morphology. The present study was undertaken to assess these potential alterations in patients with painful hip osteoarthritis (OA).

Methods

We studied 16 patients with unilateral right‐sided hip pain, before and 9 months after hip arthroplasty. This enabled comparison of gray matter volume in patients with chronic musculoskeletal pain versus healthy controls, as well as identification of any changes in volume following alleviation of pain (after surgery). Assessment involved self‐completion questionnaires to assess pain, function, and psychosocial variables, and magnetic resonance imaging scanning of the brain for VBM analysis.

Results

Significant differences in brain gray matter volume between healthy controls and patients with painful hip arthritis were seen. Specifically, areas of the thalamus in patients with chronic OA pain exhibited decreased gray matter volume. Furthermore, when these preoperative changes were compared with the brain morphology of the patients 9 months after surgery, the areas of reduced thalamic gray matter volume were found to have “reversed” to levels seen in healthy controls.

Conclusion

Our findings confirm that gray matter volume decreases within the left thalamus in the presence of chronic pain and disability in patients with hip OA. The results also show that these thalamic volume changes reverse after hip arthroplasty and are associated with decreased pain and increased function. These findings have potential implications with regard to optimizing the timing of orthopedic interventions such as arthroplasty.

     

A new marker for osteoarthritis: Cross‐sectional and longitudinal approach

Objective

To investigate the association between urinary concentrations of C‐telopeptide fragments of type II collagen (CTX‐II) and the prevalence and progression of radiographic osteoarthritis (OA) of the knee and hip.

Methods

The study population consisted of a sample of 1,235 men and women ages ≥55 years who were enrolled in the Rotterdam Study (a population‐based cohort study) and who were followed up for a mean of 6.6 years. Prevalent radiographic OA was defined as a Kellgren/Lawrence score ≥2; progression of radiographic OA was defined as a decrease in joint space width.

Results

Subjects with a CTX‐II level in the highest quartile had a 4.2‐fold increased risk of having radiographic OA of the knee (95% confidence interval [95% CI] 2.5–7.0) and of the hip (95% CI 2.2–7.8) compared with subjects with a CTX‐II level in the lowest quartile. We observed a substantially stronger association between CTX‐II levels and radiographic OA for subjects with hip pain (odds ratio [OR] 20.4, 95% CI 2.3–185.2) than for those without hip pain (OR 3.0, 95% CI 1.5–6.0). Subjects with a CTX‐II level in the highest quartile had a 6.0‐fold increased risk for progression of radiographic OA at the knee (95% CI 1.2–30.8) and an 8.4‐fold increased risk for progression of radiographic OA at the hip (95% CI 1.0–72.9). All of these associations were found to be independent of known risk factors for OA, such as age, sex, and body mass index.

Conclusion

This study shows that CTX‐II is associated with both the prevalence and the progression of radiographic OA at the knee and hip. Importantly, this association is independent of known clinical risk factors for OA and seems stronger in subjects with joint pain.

     

A large Icelandic family with early osteoarthritis of the hip associated with a susceptibility locus on chromosome 16p

Objective

To describe a large kinship with inherited hip osteoarthritis (OA) and its associated susceptibility locus.

Methods

Four generations of a kinship with familial hip OA were identified and characterized by family history and by clinical, radiographic, and histopathologic examination. In the genome‐wide search for a susceptibility locus, OA cases were defined as those who had undergone total hip replacement associated with a clinical and radiographic diagnosis of hip OA. A genome‐wide scan was performed using a framework set of microsatellite markers with an average spacing of 10 cM.

Results

The hip OA of this family was indistinguishable from that of idiopathic, nonfamilial hip OA. There was no apparent evidence of spondyloepiphyseal dysplasia or other dysplasias usually associated with mutations in collagen genes. The genome‐wide scan revealed a locus on chromosome 16p between 28 cM and 47 cM from the telomere, and this locus met the criteria for suggestive linkage (multipoint allele‐sharing logarithm of odds [LOD] score 2.58, P = 1.6 × 10⁻⁴). Two additional regions with LOD scores of >1.5 were obtained.

Conclusion

We have identified and described the largest kinship with familial hip OA reported to date. Evidence for linkage in this family suggests that a gene for susceptibility to hip OA exists on chromosome 16p. This represents an independent identification of a susceptibility locus previously reported for hip OA in this geographic region.

     

Normalization of Widespread Pressure Pain Hypersensitivity After Total Hip Replacement in Patients With Hip Osteoarthritis Is Associated With Clinical and Functional Improvements

Objective

To evaluate the relevance of ongoing nociceptive joint inputs to the maintenance of widespread pain hypersensitivity in patients with hip osteoarthritis (OA) and to determine whether a reversal in the widespread pressure hypersensitivity together with an improvement in pain and function occurs after total hip replacement in these patients.

Methods

Forty patients with hip OA participated. Twenty patients underwent total hip replacement, and the other 20 patients were assigned to a waiting list. Pressure–pain thresholds (PPTs) over the second metacarpal bone and the gluteus medius, vastus medialis, vastus lateralis, and tibialis anterior muscles were assessed bilaterally with a pressure algometer before and 3 months after total hip replacement surgery. Assessments of pain intensity (by visual analog scale [VAS]), physical function (by the Western Ontario and McMaster Universities Osteoarthritis Index), and health status (by the Short Form 12 health survey and the EuroQol 5‐domain index) were also performed.

Results

Patients who underwent total hip arthroplasty exhibited a reduction in widespread pressure pain hyperalgesia (increases in PPTs) over local and distant pain‐free areas, as compared with before surgery and as compared with the patients assigned to the waiting list. PPTs were related to hip pain intensity, and significant correlations were found between higher VAS scores and lower average PPTs over all points assessed (−0.409 < r < −0.306, P < 0.05). Patients who underwent total hip arthroplasty exhibited a greater decrease in pain intensity and greater increases in function and health status than did those who were on the waiting list. Changes in the intensity of hip pain were moderately associated with changes in pressure pain sensitivity in the hip arthroplasty group.

Conclusion

Normalization of widespread pressure pain hyperalgesia was found after successful hip joint replacement in patients with hip OA. Altered pain processing seems to be driven by ongoing peripheral joint pathology, which stresses the importance of reducing pain in OA.

     

Effects of doxycycline on progression of osteoarthritis: Results of a randomized,placebo‐controlled,double‐blind trial

Objective

To confirm preclinical data suggesting that doxycycline can slow the progression of osteoarthritis (OA). The primary outcome measure was joint space narrowing (JSN) in the medial tibiofemoral compartment.

Methods

In this placebo‐controlled trial, obese women (n = 431) ages 45–64 years with unilateral radiographic knee OA were randomly assigned to receive 30 months of treatment with 100 mg doxycycline or placebo twice a day. Tibiofemoral JSN was measured manually in fluoroscopically standardized radiographic examinations performed at baseline, 16 months, and 30 months. Severity of joint pain was recorded at 6‐month intervals.

Results

Seventy‐one percent of all randomized subjects completed the trial. Radiographs were obtained from 85% of all randomized subjects at 30 months. Adherence to the dosing regimen was 91.8% among subjects who completed the study per protocol. After 16 months of treatment, the mean ± SD loss of joint space width in the index knee in the doxycycline group was 40% less than that in the placebo group (0.15 ± 0.42 mm versus 0.24 ± 0.54 mm); after 30 months, it was 33% less (0.30 ± 0.60 mm versus 0.45 ± 0.70 mm). Doxycycline did not reduce the mean severity of joint pain, although pain scores in both treatment groups were low at baseline and remained low throughout the trial, suggesting the presence of a floor effect. However, the frequency of followup visits at which the subject reported a ≥20% increase in pain in the index knee, relative to the previous visit, was reduced among those receiving doxycycline. In contrast, doxycycline did not have an effect on either JSN or pain in the contralateral knee. In both treatment groups, subjects who reported a ≥20% increase in knee pain at the majority of their followup visits had more rapid JSN than those whose pain did not increase.

Conclusion

Doxycycline slowed the rate of JSN in knees with established OA. Its lack of effect on JSN in the contralateral knee suggests that pathogenetic mechanisms in that joint were different from those in the index knee.

     

Efficacy,safety, and effects on blood pressure of naproxcinod 750 mg twice daily compared with placebo and naproxen 500 mg twice daily in patients with osteoarthritis of the hip: A randomized,double‐blind,parallel‐group,multicenter study

Objective

To test the superiority of naproxcinod compared with placebo in relieving the signs and symptoms of hip osteoarthritis and to assess the safety of naproxcinod and its effects on blood pressure.

Methods

In a 13‐week, randomized, double‐blind, parallel‐group, multicenter study, 810 patients were randomized to receive either naproxcinod 750 mg twice daily, placebo, or naproxen 500 mg twice daily (2:2:1). Primary efficacy analyses compared naproxcinod and placebo using an analysis of covariance for 3 co‐primary end points (the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain and function subscales and patient's overall rating of disease status). Safety assessments included adverse events and in‐office blood pressure measurements.

Results

The least squares mean changes from baseline were significantly greater with naproxcinod than with placebo (P < 0.0001) and were similar to those with naproxen at week 13 for the WOMAC pain score (−25.81, −17.97, and −24.31 mm, respectively), the WOMAC function score (−22.24, −13.45, and −21.67 mm, respectively), and patient's rating of disease status (0.86, 0.51, and 0.82, respectively). Changes from baseline in systolic blood pressure were similar in the naproxcinod and placebo groups at weeks 2, 6, and 13 (differences between groups of 0.25, −0.45, and −0.11 mm Hg, respectively). Changes in the naproxen group were greater than those in the placebo group (differences of 3.11, 3.03, and 2.00 mm Hg, respectively). Systolic blood pressure increases ≥10 mm Hg from baseline to week 13 occurred in 13.3%, 15.0%, and 20.3% of patients receiving naproxcinod, placebo, and naproxen, respectively. Naproxcinod and naproxen had similar adverse event and general safety profiles.

Conclusion

The efficacy of naproxcinod for treating the signs and symptoms of hip osteoarthritis was statistically superior to that of placebo and similar to that of naproxen. Naproxcinod was well tolerated, with effects on systolic blood pressure similar to those of placebo.

     

Perceived self‐efficacy gained from,and health effects of,a rehabilitation program after hip joint replacement

Objective

To examine whether a routine multidisciplinary inpatient rehabilitation program can increase patient self‐efficacy, and to investigate the effects of high self‐efficacy at admission, and increases in self‐efficacy, on health changes in patients who undergo such rehabilitation after hip joint replacement.

Methods

Participants in this longitudinal study were 1,065 patients who underwent inpatient rehabilitation after hip joint replacement. Questionnaires were administered at admission, discharge, and 6‐month followup. The main outcome variables were disability, pain, depressive symptomatology, and self‐efficacy to cope with disability and pain.

Results

Significant improvements from admission to discharge from the inpatient rehabilitation program in disability, pain, depressive symptoms, and self‐efficacy were found. In addition, higher levels of self‐efficacy at admission and larger increases in self‐efficacy over the course of the program predicted larger health changes (i.e., greater decreases in disability, pain, and depressive symptoms). Results were generally similar for health changes from discharge to 6‐month followup.

Conclusion

A routine multidisciplinary inpatient rehabilitation program after hip joint replacement can result in enhanced self‐efficacy.

     

A randomized controlled trial to evaluate the slow‐acting symptom‐modifying effects of colchicine in osteoarthritis of the knee: A preliminary report

Objective

To determine if colchicine added to nimesulide may have a beneficial effect on osteoarthritis (OA) of the knee.

Methods

Colchicine 0.5 mg twice daily or placebo was added to nimesulide (a nonsteroidal antiinflammatory drug) in 36 patients with OA of the knee in a randomized, double‐blind, placebo‐controlled trial over a 5‐month period.

Results

The 30% improvement rate at 20 weeks was higher in the colchicine group than in the control group receiving placebo, as measured by total Western Ontario and McMaster University Osteoarthritis scores (57.9% versus 23.5%) and visual analog scale for index knee pain (52.6% versus 17.6%) (primary measures of response). The significance persisted on combined analysis by Mantel‐Haenszel test (P = 0.062). Comparison of means also showed significant improvement in the colchicine group versus the control group in a multivariate analysis performed using T² test (P = 0.0115).

Conclusion

Among patients with OA of the knee, the group receiving colchicine plus nimesulide exhibited significantly greater symptomatic benefit at 20 weeks than did the control group receiving nimesulide plus placebo.

     

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.”