Continuous occurrence of both insufficient neovascularization and elevated vascular permeability in rabbit proximal femur during inadequate repair of steroid‐associated osteonecrotic lesions

Objective

To examine the features of the intraosseous vasculature, the size of the marrow stem cell pool (MSCP), and expression of vascular endothelial growth factor A (VEGF) during inadequate repair of steroid‐associated osteonecrotic lesions in rabbits.

Methods

Steroid‐associated osteonecrosis was induced in male rabbits. At 0, 1, 2, 4, and 6 weeks postinduction, vascularization and permeability indices were quantified by dynamic magnetic resonance imaging (MRI). In addition, the size of the MSCP in the hematopoietic and mesenchymal compartments was determined, and marrow mononuclear cells expressing specific surface markers for endothelial progenitor cells or periendothelial mural precursor cells were counted. At various time points after the rabbits were killed, the proximal femora were dissected to examine the intraosseous vasculature by angiography, histomorphometry, and ultramorphology. In addition, osteonecrotic lesion repair and marrow VEGF expression were evaluated.

Results

Lesion formation without repair was observed at 2 weeks after induction of steroid‐associated osteonecrosis. Rabbits displaying destructive repair (DR+) and those displaying reparative osteogenesis (DR−) from 4 weeks to 6 weeks postinduction were identified. From week 2 to week 6, the vascularization index was significantly lower in DR+ rabbits compared with DR− rabbits, whereas the permeability index was significantly higher in DR+ rabbits compared with DR− rabbits. The features of the intraosseous vasculature determined by angiography, histomorphometry, and ultramorphology were consistent with those determined by dynamic MRI. The MSCP size and number of marrow mononuclear cells expressing specific surface markers were all significantly lower in DR+ rabbits than in DR− rabbits from week 1 to week 6. The increased VEGF expression at 2 weeks was maintained through week 6 in DR+ rabbits, whereas VEGF expression decreased in DR− rabbits from week 2 to week 6.

Conclusion

Continuous occurrence of both insufficient neovascularization and elevated vascular permeability is accompanied by a continuously low‐ level MSCP and uncontrolled VEGF expression during inadequate repair of steroid‐associated osteonecrotic lesions.

     

A tumor necrosis factor receptor loop peptide mimic inhibits bone destruction to the same extent as anti–tumor necrosis factor monoclonal antibody in murine collagen‐induced arthritis

Objective

The cyclic peptide WP9QY (YCWSQYLCY) was designed to mimic the most critical tumor necrosis factor α (TNFα) recognition loop on TNF receptor I, and it prevents interactions of TNFα with its receptor. We undertook this study to compare the effects of the WP9QY peptide on collagen‐induced arthritis (CIA) in mice with those of anti‐TNFα monoclonal antibody.

Methods

CIA was induced by primary and secondary immunizations. Osmotic minipumps were implanted in the backs of all mice on the day of the booster injection (day 21), and vehicle, anti‐TNF antibody (4 mg/kg/day), or WP9QY peptide (2 mg/kg/day or 4 mg/kg/day) was continuously infused until the mice were killed (day 40). Thereafter, clinical, radiographic, and histologic assessments were performed.

Results

WP9QY treatment inhibited CIA‐induced increases in the arthritis score, but onset of disease was not delayed by the peptide. The inhibitory effect of WP9QY on inflammation was definitely weaker than that of anti‐TNF antibody. Microfocal computed tomography analyses, however, revealed that WP9QY blocked CIA‐induced bone destruction at the knee joints to the same extent as did anti‐TNF antibody. In addition, WP9QY inhibited synovial pannus infiltration and reduced osteoclast number. Furthermore, inhibition of CIA‐induced systemic bone loss by WP9QY was more apparent than that by anti‐TNF antibody.

Conclusion

The TNFα antagonist WP9QY would be a useful template for the development of small molecular inhibitors to prevent both inflammatory bone destruction and systemic bone loss in rheumatoid arthritis.

     

Anti‐20S proteasome autoantibodies inhibit proteasome stimulation by proteasome activator PA28

Objective

The ubiquitin‐proteasome system plays a central role in cellular homeostasis as well as in regulation of the inflammatory and stress responses. However, the occurrence of autoantibodies against 20S proteasome has, to date, been considered to be a nonspecific epiphenomenon in patients with autoimmune disorders. This study was undertaken to analyze the properties of antiproteasome antibodies by investigating their influence on the proteolytic activity of the proteasome complex.

Methods

The 20S proteasome, with or without addition of the proteasome activator (PA28), was preincubated with affinity‐purified human antiproteasome antibodies. Proteolytic activity was estimated using fluorogenic peptides as substrate.

Results

The baseline proteolytic properties of the 20S proteasome core complex were not influenced by the autoantibodies in vitro. In contrast, all human antiproteasome antibodies analyzed efficiently blocked the enhanced proteasomal substrate cleavage provided by PA28. A similar influence of proteasome activation was observed upon preincubation with affinity‐purified sheep polyclonal or mouse monoclonal antiproteasome antibody, whereas human immunoglobulin controls exhibited no effect.

Conclusion

Autoantibodies against 20S proteasomes are able to block proteasome activation by PA28, binding to their native antigen in vitro. Antibody targeting of the interaction between 20S proteasome and PA28 represents a novel mechanism of proteasome inhibition.

     

Microbubble‐enhanced ultrasound exposure promotes uptake of methotrexate into synovial cells and enhanced antiinflammatory effects in the knees of rabbits with antigen‐induced arthritis

Objective

To evaluate whether microbubble‐enhanced ultrasound (US) treatment promotes the delivery of methotrexate (MTX) into synovial cells and the enhanced antiinflammatory effects of intraarticular MTX therapy in a rabbit arthritis model.

Methods

Arthritis was induced in both knees of 53 rabbits by immunization with ovalbumin. MTX including a microbubble agent was then injected into the left and right knee joints, and the right knees were exposed to US (MTX+/US+ group), while the left knees were not (MTX+/US− group). The knee joints were evaluated histologically in 7 rabbits at 5 time points up to day 56. Quantitative gene expression of interleukin‐1β (IL‐1β) in synovial tissue was measured on days 7 and 28. Eight rabbits were used for the measurement of MTX concentration in synovial tissue 12 hours after treatment. To evaluate the effect of microbubble‐enhanced US treatment in the absence of MTX, only the microbubble agent was injected into the left and right knee joints of 10 rabbits with or without US exposure, and these animals were evaluated histologically on days 7 and 28.

Results

The MTX concentration in synovial tissue was significantly higher in the MTX+/US+ group than in the MTX+/US− group. Synovial inflammation was less prominent in the MTX+/US+ group compared with the MTX+/US− group, judging from the results of the histologic evaluation and the gene expression levels of IL‐1β in synovial tissue. It also appeared that microbubble‐enhanced US exposure itself did not affect inflammation.

Conclusion

Microbubble‐enhanced US exposure promoted the uptake of MTX into synovial cells, which resulted in enhancement of the antiinflammatory effects of the intraarticular MTX injection. These results suggest that application of this technique may have clinical benefit.

     

Development of the tight‐skin phenotype in immune‐deficient mice

Objective

To determine if cutaneous thickening, a major phenotypic feature of the tight‐skin (Tsk) mutation, could develop in an immune‐deficient mouse.

Methods

Experimental crosses among different strains of mice were conducted to create mice that were genetically Tsk/+, and that were also homozgyous for a mutation at the Prkdc^scid locus and thus lacked mature T and B lymphocytes. Skin samples prepared from experimental and control genotypic groups of mice were evaluated for skin thickness.

Results

The data showed that the Tsk/+ mice developed the Tsk phenotype in the absence of a functional immune system.

Conclusion

Mature T and B cells are not required for the development of the cutaneous thickening in mice carrying the Tsk mutation.

     

Tissue‐engineered composites for the repair of large osteochondral defects

Objective

To test the hypothesis that engineered cartilage can provide a mechanically functional template capable of undergoing orderly remodeling during the repair of large osteochondral defects in adult rabbits, as assessed by quantitative structural and functional methods.

Methods

Engineered cartilage generated in vitro from chondrocytes cultured on a biodegradable scaffold was sutured to a subchondral support and the resulting composite press‐fitted into a 7‐mm long, 5‐mm wide, 5‐mm deep osteochondral defect in a rabbit knee joint. Defects left empty (group 1) or treated with cell‐free composites (group 2) served as controls for defects treated with composites of engineered cartilage and the support, without or with adsorbed bone marrow (groups 3 and 4, respectively).

Results

Engineered cartilage withstood physiologic loading and remodeled over 6 months into osteochondral tissue with characteristic architectural features and physiologic Young's moduli. Composites integrated well with host bone in 90% of cases but did not integrate well with host cartilage. Structurally, 6‐month repairs in groups 3 and 4 were superior to those in group 2 with respect to histologic score, cartilage thickness, and thickness uniformity, but were inferior to those in unoperated control tissue. At 6 months, Young's moduli in groups 2, 3, and 4 (0.68, 0.80, and 0.79 MPa, respectively) approached that in unoperated control tissue (0.84 MPa), whereas the corresponding modulus in group 1 (0.37 MPa) was significantly lower.

Conclusion

Composites of tissue‐engineered cartilage and a subchondral support promote the orderly remodeling of large osteochondral defects in adult rabbits.

     

Effects of pool‐based and land‐based aerobic exercise on women with fibromyalgia/chronic widespread muscle pain

Objective

To examine the effects of pool‐based (PE) and land‐based (LE) exercise programs on patients with fibromyalgia.

Methods

The outcomes were assessed by the Fibromyalgia Impact Questionnaire, the Arthritis Self‐Efficacy Scale, and tests of physical capacity.

Results

Eighteen subjects in the PE group and 16 in the LE group performed a structured exercise program. After 20 weeks, greater improvement in grip strength was seen in the LE group compared with the PE group (P < 0.05). Statistically significant improvements were seen in both groups in cardiovascular capacity, walking time, and daytime fatigue. In the PE group improvements were also found in number of days of feeling good, self‐reported physical impairment, pain, anxiety, and depression. The results were mainly unchanged at 6 months followup.

Conclusion

Physical capacity can be increased by exercise, even when the exercise is performed in a warm‐water pool. PE programs may have some additional effects on symptoms. Arthritis Care Res 45:42–47, 2001. © 2001 by the American College of Rheumatology.

     

Task independence,safety, and adequacy among nondisabled and osteoarthritis‐disabled older women

Objective

To examine the constructs of task independence, safety, and adequacy.

Method

Fifty‐seven nondisabled (ND) and 56 osteoarthritis‐disabled (OAK) women were observed performing daily tasks.

Results

Intercorrelations among the constructs of independence and adequacy were uniformly high, while the relationship of safety to these constructs was moderate and more variable, although stronger in the OAK group. Task performance of the OAK group was consistently less adequate and independent than that of the ND group; however, the groups were generally equivalent in safety. For individual tasks, adequacy best differentiated between the groups. In both groups, those who performed independently also performed safely, but fewer independent OAK participants also performed totally adequately.

Conclusion

The majority of older women who perform tasks independently also perform them safely and adequately; for a clinically significant minority, independence is not always synonymous with safe and adequate performance. Patients may be placed at risk if independence is the only construct used to determine disability.

     

Smad3 controls β‐1,3‐glucuronosyltransferase 1 expression in rat nucleus pulposus cells: Implications of dysregulated expression in disc disease

Objective

To study the regulation of expression of β‐1,3‐glucuronosyltransferase 1 (GlcAT‐1), an important regulator of glycosaminoglycan (GAG) synthesis, by Smad3 in nucleus pulposus (NP) cells.

Methods

GlcAT‐1 expression was examined in rat NP and anulus fibrosus (AF) cells treated with transforming growth factor β (TGFβ). The effects of Smad signaling and Smad suppression on GlcAT‐1 were examined in rat NP cells. GlcAT‐1 expression was analyzed in the discs of Smad3‐null mice and in degenerated human NP tissue.

Results

TGFβ increased the expression of GlcAT‐1 in rat NP but not rat AF cells. Suppression of GlcAT‐1 promoter activity was evident with dominant‐negative ALK‐5 (DN‐ALK‐5). Cotransfection with Smad3 strongly induced promoter activity independent of TGFβ. Bioinformatics analysis indicated the presence of several Smad binding sites in the promoter; deletion analysis showed that the region between −274 and −123 bp was required for Smad3 response. DN‐Smad3, Smad 3 small interfering RNA, and Smad7 strongly suppressed basal as well as TGFβ‐induced promoter activity. Induction of promoter activity by Smad3 was significantly blocked by DN‐Smad3; Smad7 had a very small effect. Lentiviral transduction of NP cells with short hairpin RNA Smad3 resulted in a decrease in GlcAT‐1 expression and accumulation of GAG. Compared to wild‐type mice, significantly lower expression of GlcAT‐1 was seen in the discs of Smad3‐null mice. Analysis of degenerated human NP tissue specimens showed no positive correlation between GlcAT‐1 and TGFβ expression. Moreover, isolated cells from degenerated human tissue showed a lack of induction of GlcAT‐1 expression following TGFβ treatment, suggesting an altered response.

Conclusion

Our findings demonstrate that in healthy NP cells, the TGFβ–Smad3 axis serves as a regulator of GlcAT‐1 expression. However, an altered responsiveness to TGFβ during disc degeneration may compromise GAG synthesis.

     

Effects of low‐dose,noncytotoxic, intraarticular liposomal clodronate on development of erosions and proteoglycan loss in established antigen‐induced arthritis in rabbits

Objective

To assess the clinical and histologic effects of an intraarticular application of low‐dose (noncytotoxic) liposomal clodronate in established antigen‐induced monarthritis (AIA) in rabbits.

Methods

AIA was monitored by assessments of joint swelling, C‐reactive protein levels, and radiographic changes in 17 NZW rabbits for 8 weeks during the course of weekly intraarticular injections of liposomal clodronate (0.145 mg/injection, low dose) or “empty” liposomes. The contralateral knee was injected with liposome buffer alone as the control. End‐point analyses included macroscopic joint examination, immuno‐ and TUNEL staining, Safranin O staining/microspectrophotometry, and tumor necrosis factor α (TNFα) convertase enzyme (TACE) inhibition assay.

Results

Liposomal clodronate–treated rabbits showed a reduction and delay in joint swelling during the first 3 injections. Expression of matrix‐bound (solubilized) TNFα, lining cell hyperplasia, and levels of RAM‐11+ macrophages were low in the synovium of the liposomal clodronate treatment group, but the proportion of apoptotic lining cells was not affected. The radiologic score was low at the end of weeks 2 and 4, but at 8 weeks, no difference, compared with controls, was found in pannus formation or in the extent of joint erosion; also, joint swelling was higher than before initiation of treatment. Injections of liposomal clodronate prevented cartilage proteoglycan loss, which was significant in the superficial zone only. TACE activity was not inhibited by clodronate.

Conclusion

Liposomal clodronate had temporary antiinflammatory and antierosive effects on established AIA in rabbits. Over the long‐term, the loss of cartilage proteoglycans was halted. This observed treatment effect may be related to the inhibition of TNFα production and processing in the synovium.

     

A home‐based two‐year strength training period in early rheumatoid arthritis led to good long‐term compliance: A five‐year followup

Objective

To evaluate the impact of a 2‐year home‐based strength‐training program on physical function in patients with early rheumatoid arthritis (RA) after a subsequent 3‐year followup.

Methods

Seventy patients with early RA were randomized to perform either strength training (experimental group [EG]) or range‐of‐motion exercises (control group [CG]). Maximal strength values were recorded by dynamometers. The Modified Disease Activity Score (DAS28), pain, Health Assessment Questionnaire (HAQ), walking speed, and stair‐climbing speed were also measured.

Results

The maximum strength of assessed muscle groups increased by 19–59% in the EG during the training period and remained at the reached level throughout the subsequent 3 years. Muscle strength improved in the CG by 1–31%, but less compared with the EG. During the 2‐year training period, DAS28 decreased by 50% and 45% and pain by 67% and 39% in the EG and CG, respectively. The differences in muscle strength, DAS28, and HAQ were significantly in favor of the EG both at the 2‐year and 5‐year followup assessments.

Conclusions

The improvements achieved during the 2‐year strength‐training period were sustained for 3 years in patients with early RA.

     

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.

     

Quality of well‐being in older people with osteoarthritis

Objective

To examine the sensitivity of the Quality of Well‐Being Scale (QWB) as a measure of health‐related quality of life (HRQOL) in people with osteoarthritis (OA).

Methods

The QWB was administered, along with the Arthritis Impact Measurement Scale (AIMS) and other health measures. Health care utilization data were also obtained.

Results

People with OA had a mean QWB score of 0.643. The QWB scores were significantly correlated with total AIMS scores, self‐rated health status, health care costs, depression scores, and most AIMS subscales. In addition, changes in QWB scores after 1 year were significantly correlated with changes in total AIMS scores and some AIMS subscales.

Conclusion

The QWB appears to be a useful and sensitive generic, utility‐based measure of HRQOL in people with OA.

     

Surgical decompression versus local steroid injection in carpal tunnel syndrome: A one‐year,prospective, randomized,open, controlled clinical trial

Objective

Optimal treatment of carpal tunnel syndrome (CTS) has not been established. This study compared the effects of local steroid injection versus surgical decompression in new‐onset CTS of at least 3 months' duration.

Methods

In a 1‐year, prospective, randomized, open, controlled clinical trial, we studied the effects of surgical decompression versus local steroid injection in 163 wrists with a clinical and neurophysiologic diagnosis of CTS. Clinical assessments were done at baseline and at 3, 6, and 12 months after treatment. The primary end point was the percentage of wrists that reached a ≥20% improvement in the visual analog scale score for nocturnal paresthesias at 3 months of followup. Statistical analysis was done by Student's t‐test for continuous variables and by chi‐square test for categorical variables. Analyses were performed on an intent‐to‐treat basis. P values less than 0.05 were considered statistically significant.

Results

Both treatment groups had comparable severity of CTS at baseline. Eighty wrists were randomly assigned to the surgery group and 83 wrists to the local steroid injection group. In the intent‐to‐treat analysis, at 3 months of followup, 94.0% of the wrists in the steroid injection group versus 75.0% in the surgery group reached a 20% response for nocturnal paresthesias (P = 0.001). At 6 and 12 months, the percentages of responders were 85.5% versus 76.3% (P = 0.163) and 69.9% versus 75.0% (P = 0.488), for local steroid injection and surgical decompression, respectively.

Conclusion

Over the short term, local steroid injection is better than surgical decompression for the symptomatic relief of CTS. At 1 year, local steroid injection is as effective as surgical decompression for the symptomatic relief of CTS.

     

Efficacy of traditional and biologic agents in different clinical phenotypes of adult‐onset Still's disease

Objective

To evaluate the efficacy of antiinflammatory agents, steroids, immunosuppressants, and biologic agents in patients with adult‐onset Still's disease (AOSD) who have either chronic articular disease or nonchronic disease.

Methods

Forty‐five patients with AOSD were seen and followed up for at least 2 years at our institution, from 1991 to 2008. The majority of patients were treated with several therapeutic regimens; a total of 152 efficacy trials were administered. Data regarding the type of medication, the dosage used, and the outcome of these trials were collected and analyzed.

Results

Our data showed that the efficacy of monotherapy with a nonsteroidal antiinflammatory drug was very low (16%) and confirmed good efficacy of steroid therapy (63%), particularly in patients without chronic articular disease (78%). Patients whose disease did not respond to steroid therapy at the time of disease onset were at risk of the subsequent development of chronic arthritis. Disease‐modifying antirheumatic drug (DMARD) monotherapy was successful in controlling steroid‐resistant or steroid‐dependent disease in 60% of patients. Methotrexate and cyclosporine showed the best response rates. The combination of high‐dose steroids and cyclosporine was administered to successfully control some acute life‐threatening complications. Only 6 patients had disease that was both steroid resistant and DMARD resistant. Treatment with biologic agents eventually led to satisfactory control of disease manifestations in 5 (83%) of these 6 patients.

Conclusion

Steroids were less effective in patients with chronic articular disease than in those with nonchronic disease. The administration of DMARDs early after disease onset could be beneficial in patients with steroid‐resistant disease who are at risk of the development of chronic articular disease. Biologic agents proved to be highly effective in both steroid‐resistant and DMARD‐resistant AOSD.

     

Combined effects of an anticoagulant and a lipid-lowering agent on the prevention of steroid-induced osteonecrosis in rabbits

OBJECTIVE: To investigate the effects of combination treatment with an anticoagulant (warfarin) plus a lipid-lowering agent (probucol) on the prevention of steroid-induced osteonecrosis (ON) in rabbits. METHODS: Adult male Japanese white rabbits were injected once intramuscularly with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle. The rabbits were then divided into 4 groups and treated as follows: one group received warfarin plus probucol (WP; n = 25), one received probucol alone (PA; n = 30), one received warfarin alone (WA; n = 26), and one received no treatment (nonprophylactic [NP]; n = 20). Two weeks after the steroid injection, the femora and humeri were examined histopathologically for the presence of ON. The sizes of the bone marrow fat cells were examined morphologically. Hematologic examinations were performed before and after the steroid injection. RESULTS: The incidence of ON in the WP group (5%) was significantly lower than that observed in the NP group (70%). While the incidence rates of ON in the PA (38%) and WA (33%) groups were also significantly lower than that in the NP group, they were significantly higher than that observed in the WP group. The sizes of the bone marrow fat cells in both the WP (53.5 +/- 4.1 microm) and the PA (52.0 +/- 5.0 microm) groups were significantly smaller than those in the NP group (60.0 +/- 4.0 microm). We also observed a prolongation of the prothrombin time and a reduction in the plasma lipid levels in the WP group during the study. CONCLUSION: This study experimentally confirmed that the combined use of an anticoagulant and a lipid-lowering agent helps prevent steroid-induced ON in rabbits.     

The transcription factors hypoxia‐inducible factor 1α and Ets‐1 colocalize in the hypoxic synovium of inflamed joints in adjuvant‐induced arthritis

Objective

To determine the relationship between hypoxia and the expression of Ets‐1 and hypoxia‐inducible factor 1α (HIF‐1α) in both normal and inflamed joints. Adjuvant‐induced arthritis (AIA) was used as the model system, since it mirrors many aspects of the pathology of rheumatoid arthritis.

Methods

Adjuvant arthritis was induced in a group of 10 female Lewis rats. A second group of 10 uninjected female Lewis rats served as naive controls. When a maximum clinical joint score was achieved in the AIA group, all 20 rats were injected with the specific hypoxic cell marker Hypoxyprobe‐1 and subsequently killed. Hypoxyprobe‐1 adducts, Ets‐1, and HIF‐1α were localized in the joints of the hind feet from these groups using immunohistochemistry.

Results

Compared with the joints from control rats, inflamed joints contained markedly more cells with Hypoxyprobe‐1 adduct immunoreactivity, Ets‐1–immunoreactive nuclei, and nuclear immunoreactivity for both Ets‐1 and HIF‐1α.

Conclusion

Our results demonstrate the presence of hypoxia in inflamed joints in this experimental model of arthritis. The colocalization of Ets‐1 and HIF‐1α in these hypoxic areas suggests that hypoxia may induce Ets‐1 and HIF‐1α expression during joint inflammation.

     

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.”