Osteoarthritis (OA) affects all vertebrates, and the prevalence of the disease increases exponentially with age. Estimates of the prevalence of hip OA in humans range from 2% at age 35 years to 35% at age 85 years or older (1), and autopsies have shown that cartilage degeneration can be detected in patients as early as the second decade of life (2). A disease prevalence estimate of 3% among North Americans older than age 55 years has been commonly quoted, but this may well be an underestimate of the true burden of hip OA in the general population (3, 4). The prevalence of the disease has significant fiscal implications, since it has been shown that populations with OA incur significantly increased direct health care costs when compared with a similar cohort without arthritis (5).
Management of OA is generally focused on symptomatic OA, and if a cause can be identified, it should be treated, when possible. Because the main symptoms are pain and restriction of activity, medical therapy for OA is directed toward alleviation of these symptoms. Patient education, weight loss, and unloading of weight-bearing joints are recommended approaches that are often helpful, and analgesia, antiinflammatory drugs, and/or physiotherapy are usually prescribed.
The role of intraarticular (IA) injection of corticosteroids (henceforth referred to as steroids) in the treatment of OA is controversial. The main indication for IA steroid use is to provide pain relief and suppression of synovitis in patients whose condition remains unresponsive to or intolerant of oral systemic medication. The major objective of this therapy is to aspirate any effusion and instill the steroid preparation that provides the most effective relief for the longest period of time.
Only 3 randomized, controlled trials of steroid injection in hip OA have been reported, with mixed results (6–8). In one trial, only a dichotomous outcome was used (6), which limits interpretation of the results; in the 2 other trials, peak effects of the steroid were observed by 2 or 3 weeks postinjection (7, 8). Despite these observations, the use of IA steroids is common in clinical practice. In 1995, the American College of Rheumatology (ACR) issued guidelines for the medical management of OA (9), which included specific recommendations for the routine use of IA steroids for knee OA. However, the hip joint is more difficult to inject than the knee, and the ACR has recommended against routine use of IA steroids in the hip, with the caveat that if this technically difficult procedure is proposed, it should be performed under fluoroscopic guidance (10).
The hip is a joint that is difficult to inject, and therefore entry of the therapeutic agent into the synovial space cannot be ensured without fluoroscopic guidance. Placement of the IA steroid (without imaging guidance) is frequently inaccurate, and this may have a significant effect on clinical response (11). Controversy persists regarding the claim that good results can be achieved without fluoroscopy (12). In addition, the European League Against Rheumatism has proposed treatment recommendations for the management of hip OA in which the use of IA injection of steroids constitutes the eighth of their 10 propositions (13). It was acknowledged that evidence in support of this proposition was not robust, and that placebo-controlled trials would be required.
The purpose of the present study was to resolve the controversy with respect to the efficacy of IA steroid injection in the management of hip OA. To accomplish this, we conducted a randomized, placebo-controlled trial in patients with hip OA whose disease was previously unresponsive to conventional medical therapy.
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- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
This study showed that the group of patients receiving IA steroid injection of the hip, administered under fluoroscopic guidance, not only had significantly better outcomes than the placebo group, but also demonstrated significant gains from baseline to 2 months in all measures of pain, stiffness, and physical function. In addition, an improvement of 20% in the WOMAC pain score was seen in 68% of the IA steroid group compared with 24% of the placebo group. Of more importance was the 50% improvement in the WOMAC pain scale observed in 61% of the steroid injection group compared with 14% of the placebo group, indicating that most of the elicited responses were clinically significant (23). Moreover, these benefits extended to measures of quality of life, and significant differences in treatment effects as compared with placebo were still evident 3 months after treatment.
Our experience in this study highlights the difficulties in recruiting patients to placebo-controlled trials of interventions that are even minimally invasive. The majority of patients had severe disease (clinically and radiographically), were receiving substantial daily doses of combination acetaminophen/codeine therapy, and were on waiting lists for hip arthroplasty, which may have further deterred patients from being included in a trial designed with a placebo treatment arm. This might also explain the observation that the placebo responses were somewhat lower than those recorded in previous trials in which disease severity was more moderate. The relatively low placebo response rate in this study might also be a reflection of the primary end point being at 2 months, as opposed to the earlier time points chosen in prior studies (7). Clinically significant responses were nevertheless seen in a majority of our patients. The finding of no correlation between treatment response and disease severity suggests that patients who experience treatment failure with oral medication should be offered steroid injection therapy, regardless of disease severity.
Decreases in analgesic intake and improvements in joint motion were also observed in the steroid injection group, although the differences in these outcomes compared with those in the placebo group were not statistically significant. This is likely a reflection of the small sample size, disease severity, and irreversibility of the disease in this patient population.
The OARSI/OMERACT responder criteria (21) were not prespecified outcomes for this trial, because the design of the trial and the initial recruitment of patients began prior to the publication of these criteria. Nevertheless, it is noteworthy that use of the WOMAC pain 20% improvement criterion identified virtually all patients who were also considered responders according to the OARSI/OMERACT criteria. One patient in the placebo group who was a responder by the WOMAC20 criterion was not defined as a responder according to the OARSI/OMERACT criteria. Conversely, 1 patient in the steroid treatment group was a responder by the OARSI/OMERACT criteria but not by the WOMAC20 criterion.
Nearly all patients in the placebo group who failed to achieve a response by the 2-month primary end point opted for an open-label injection of the steroid and were subsequently recorded as having achieved a WOMAC20 response 1 month thereafter. It is unclear why the nonresponders in the steroid injection group who opted for open-label injection were also recorded as responders 1 month thereafter. This could represent a placebo response to open-label injection, although the response rate (7 of 9 patients) appears somewhat high for a placebo response alone. It is possible that there was a cumulative effect from the second steroid injection that led to a clinical benefit. It may be worthwhile trying to address this in future studies by using serial magnetic resonance imaging to evaluate the inflammatory response.
Figure 1 illustrates the potential difficulty in ensuring that a hip injection is reliably administered into the synovial space. In this trial, the intrasynovial flow of contrast material and that of the steroid were separately confirmed in every case. However, in a severely diseased joint, it is not easy to prove that the entire injectate is intrasynovial, and some variability in patient response may be related to the degree of difficulty of the injection. Postinjection leakage of injectate may also account for any variability in patient response.
Previous placebo-controlled studies demonstrated mixed results from steroid injection into the hip. The earliest study reported used imaging and contrast injection to guide needle placement in patients who were on a waiting list for hip arthroplasty (6). Of 36 patients injected, a similar proportion of those who received saline, anesthetic alone, or a steroid (20 mg triamcinolone) plus anesthetic reported improvement in the first month, which rapidly declined by month 3. A major limitation of that study was that patients were told that they would receive priority for inclusion in the study based on the severity of their pain. A rather large volume of fluid (10 ml) was injected into the joint, which could have extravasated outside the synovial space. The incidence of postinjection flares was not reported. In addition, patients received active and passive physiotherapy 3 hours postinjection and on each of the following 2 mornings. Recent data indicate that immobilization for 24 hours after injection of weight-bearing joints confers longer-lasting benefit from steroid injection (24).
A second trial recruited 80 patients who were on a waiting list for hip replacement. These patients received either 80 mg triamcinolone acetonide or local anesthetic (1% mepivacaine), under fluoroscopic guidance (7). Patients were instructed to rest on the day of the injection and then to resume normal activities. Significant reductions in VAS scores for pain at rest and during weight bearing of the joint were noted in the steroid injection group at 3 weeks, which were maintained at 3 months, and the range of joint motion was increased in all directions. No significant improvement in pain or function was observed in the placebo group. A potential problem with this particular trial design was the omission of any local anesthetic from the injection for the steroid treatment group. Consequently, an immediate response to injection of local anesthetic would almost certainly unblind the assessor, and potentially the subject, and reveal the fact that steroid had not been administered.
In the third trial, 101 patients received 3 ultrasound-guided IA injections of steroid administered at 14-day intervals (8). Randomization was into 1 of 3 treatment groups: a single injection (1 ml) of steroid (40 mg depomedrol) followed by 2 sham injections, or 3 injections (2 ml) of sodium hyaluronate, or 3 injections (2 ml) of saline. All patients also received 1 ml of lidocaine. No bed rest was required postinjection. Most patients had Kellgren/Lawrence grades of <3, and patients who had previously received steroid injections were allowed into the trial, although responses to previous injections were not stated. A significant improvement in the primary outcome, pain on walking, was observed in the groups receiving either steroid or sodium hyaluronate compared with the placebo group, at 14 and 28 days but not at 3 months. No significant differences between treatment groups were observed in secondary outcomes such as WOMAC scores, although, after 28 days, 53%, 66%, and 44% of patients in the sodium hyaluronate, steroid, and placebo groups, respectively, were responders according to the OARSI/OMERACT responder criteria (21). The radiographic severity of OA did not influence the response to treatment. Differences between the study by those investigators and our study include their use of 3 ultrasound-guided use of a steroid preparation of lower potency, the absence of postinjection bed rest, and the inclusion of patients with less severe disease.
Investigations of the effects of steroids on cartilage metabolism suggest that a mechanism exists through which steroids may be inferred to have a positive effect in degenerative arthropathy (25–27), and specifically, triamcinolone has been shown to protect against cartilage fibrillation and osteophyte formation (28). The metabolic pathway of intrasynovial corticosteroids has not been fully elucidated. The rate of absorption and duration of action are related to solubility of the compound, and triamcinolone hexacetonide is the most insoluble preparation currently available (16). Depending on the formulation, a steroid can be detected in synovial fluid up to 14 days after injection (29).
Adverse effects of IA injection of steroids have been reported previously, and it is recommended that weight-bearing joints should not be injected more than once per month or more than 4 times per year (9). Judicious use of this approach would indicate that IA steroid injection appears to convey an extremely small risk of joint damage. Infectious arthritis is a rare complication resulting from joint injection; the number of reported cases is small and the incidence is as low as 1:50,000 (30). Postinjection flare or crystal-induced arthritis are more common, but symptoms are usually mild and rarely last more than 48 hours. Of course, postinjection flare may also occur following injection of radiographic contrast material. Overall, when steroid treatment is compared with alternative strategies such as NSAIDs, its safety profile can be considered favorable, particularly in the age group of patients in whom symptomatic OA develops.
In conclusion, the results of this randomized, placebo-controlled trial show that fluoroscopically guided IA injection of steroids is an effective treatment for the management of hip OA, with improvement lasting up to 3 months. Future studies should address questions related to the benefits of repeated injection. Most importantly, imaging studies should be conducted to investigate the effects of IA steroid injection on disease modification.
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
Dr. Lambert had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study design. Lambert, Jhangri, Maksymowych.
Acquisition of data. Lambert, Hutchings, Maksymowych.
Analysis and interpretation of data. Lambert, Grace, Jhangri, Maksymowych.
Manuscript preparation. Lambert, Grace, Jhangri, Maksymowych.
Statistical analysis. Lambert, Grace, Jhangri, Conner-Spady, Maksymowych.
Review of protocol. Hutchings.