Intraarticular glucocorticoid injections in rapidly destructive hip osteoarthritis

Joint Bone Spine 73 (2006) 66–71 http://france.elsevier.com/direct/BONSOI/

Original article

Intraarticular glucocorticoid injections in rapidly destructive hip osteoarthritis Caroline Villoutreix a,*, Thao Pham a, Florence Tubach b, Maxime Dougados a, Xavier Ayral a a

Rheumatology B Department, Cochin Teaching Hospital, Assistance Publique des Hôpitaux de Paris, René Descartes Paris V University, Paris, France Department of Epidemiology, Biostatistics, Clinical Research, Bichat-Claude Bernard Teaching Hospital, Assistance Publique des Hôpitaux de Paris, Paris VII University, Paris, France

b

Received 24 February 2004; accepted 25 June 2005 Available online 22 September 2005

Abstract Objective. – To determine whether an intraarticular glucocorticoid injection followed, when possible, by weight-bearing elimination using two crutches reduces the need for total hip arthroplasty (THA) in patients with rapidly destructive hip osteoarthritis (RDHOA). Methods. – A longitudinal retrospective study was conducted in patients admitted for RDHOA, defined as loss of more than 50% of the joint space at the narrowest point between two evaluations 1 year apart. A glucocorticoid injection was performed under fluoroscopic guidance. Patients stayed in bed for the next 24 h then used crutches for 4–6 weeks. Follow-up was at least 6 months. The efficacy criterion was absence of THA. Results. – Twenty-eight patients (22 women) were enrolled between 1993 and 2000. Mean age was 62 years, mean body mass index was 26 kg/m2, mean Lequesne index was 11, and mean joint space width was 1.3 mm. Narrowing was superolateral in 19 of the 28 patients. Cortivazol was injected in seven patients, betamethasone in four, and triamcinolone hexacetonide in 17. Weight-bearing elimination for at least 4 weeks was achieved in 15 patients. THA was performed in 27 patients, including 20 who underwent the procedure within the year after the glucocorticoid injection. Conclusion. – Intraarticular glucocorticoid injection with or without elimination of weight-bearing does not reduce the need for THA in patients with RDHOA. © 2005 Elsevier SAS. All rights reserved. Keywords: Rapidly progressive osteoarthritis of the hip joint; Intraarticular corticosteroid injection; Non weight-bearing period; Total hip replacement

1. Introduction Rapidly destructive hip osteoarthritis (RDHOA) was defined by Lequesne as a greater than 2 mm/year rate of joint space narrowing, i.e. loss of more than 50% of the joint space within 1 year [1]. RDHOA is a rare but serious condition that destroys the joint within a few months, usually creating a need for total hip arthroplasty (THA). Pharmacotherapy consists chiefly of analgesics and nonsteroidal antiinflammatory drugs to alleviate the pain. Intraarticular glucocorticoid therapy may be given [1,2], followed * Corresponding author. Present address: Service de Rhumatologie, Hôpital Saint-Antoine, 184, rue du faubourg Saint Antoine, 75012 Paris, France. Tel.: +33 1 49 28 25 20; fax: +33 1 49 28 25 13. E-mail address: [email protected] (C. Villoutreix). 1297-319X/$ - see front matter © 2005 Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2005.06.002

for 4–6 weeks by simulated walking using crutches to eliminate weight-bearing. The effectiveness of intraarticular glucocorticoid therapy in RDHOA has not been evaluated or compared to systemic therapy. A study of 33 patients with RDHOA suggested that weight-bearing elimination might slow the rate of joint space loss, thereby delaying the need for THA [2]. The objective of this study was to determine whether intraarticular glucocorticoid therapy with or without a period of weight-bearing elimination reduces the need for THA. 2. Methods We retrospectively reviewed the medical records of patients managed at the Rheumatology B Department of the Rheumatology Institute, Cochin Teaching Hospital, Paris, France, to

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identify and to determine outcomes of patients given intraarticular glucocorticoid therapy for RDHOA. The efficacy criterion was absence of THA. Follow-up was 6 months or more after the last injection. We used the department’s patient database to identify patients admitted between 1993 and November 2000. Then, we selected patients retrieved using the keywords “RDHOA”, “hip osteoarthritis”, “intraarticular injection”, or “synovectomy”. Within this population, we identified the patients who experienced an at least 50% reduction in joint space width within the year before the injection, as documented by comparing two radiographs obtained no more than 1 year apart. The last radiograph was taken on the day of the injection, which was defined as D0. Joint space width on D0 was recorded. Finally, the diagnosis of RDHOA was confirmed by a staff physician working in the department, based on loss of at least 50% of the joint space within 1 year, although the time interval between the two radiographs was not consistently supplied. We excluded patients with hip osteoarthritis due to tuberculous or pyogenic arthritis, inflammatory joint disease (e.g. spondyloarthropathy or rheumatoid arthritis), avascular necrosis of the femoral head, Paget’s disease, or neoplasia. In addition, patients with no available imaging studies obtained within the year following the injection were excluded. 2.1. Patient characteristics For each study patient, we recorded the following data: age, sex, body weight, height, body mass index (BMI), and the Lequesne index at the hip on D0 [3]. C-reactive protein (CRP) values on D0 were collected. All radiographs were reviewed by the same observer who used a ruler to measure the joint space width. Joint space width on D0 was measured at the narrowest site on the anteroposterior radiograph of the pelvis and on the Lequesne oblique view (faux profile) in patients with anterosuperior or posterior narrowing. Values were rounded to the nearest half millimeter [4]. When radiographs were digitized, the measurement was corrected according to the scale used to reduce the images. We distinguished hips with superolateral narrowing from those with medial or circumferential narrowing [5]. Radiographs of the pelvis were examined for a calcified line opposite the pubic symphysis indicating chondrocalcinosis. We recorded evidence of hip dysplasia in order to separate patients with primary hip osteoarthritis from those with secondary disease. 2.2. The intraarticular injection procedure All injections were given in the fluoroscopy room of the Radiology B Department, Cochin Teaching Hospital, Paris, France. Three radiologists performed the injections in the study patients. The lateral supratrochanteric route or the anterior route was used, the choice being at the discretion of the operator [6]. Joint fluid was not aspirated. Patients received either a semi-delayed acting glucocorticoid (cortivazol,

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3.75 mg; or betamethasone, 7 mg) or a delayed-acting glucocorticoid (triamcinolone hexacetonide, 40 mg), with or without hyaluronic acid or a radioisotope (Rhenium 186, 3 mCi). Patients stayed in bed on the ward for 24 h in order to potentiate the effect of the glucocorticoid [7]. During the hospital stay, the physiotherapist taught the patients to use the simulated walking technique with two crutches. Patients were instructed to use this technique for at least 4 weeks. Compliance with weight-bearing elimination was evaluated by interviewing the patient after resumption of weight-bearing. 2.3. Primary effıcacy criterion Absence of THA was the primary criterion used to evaluate the effectiveness of pharmacotherapy including intraarticular glucocorticoid therapy. To determine whether THA was performed, we reviewed surgical reports in the medical charts and interviewed the patients on the telephone. 2.4. Statistics Descriptive statistics for the study population were determined. The likelihood of THA over time was evaluated using the Kaplan–Meier method. The log rank test was used to evaluate the risk of THA according to the severity and location of joint space narrowing, the type of glucocorticoid injected into the hip, and whether weight-bearing elimination was achieved. Joint space width, site of narrowing, type of glucocorticoid, and weight-bearing elimination were converted to qualitative variables. Time to THA was a timedependent quantitative variable. Finally, we used the Mann– Whitney test to compare demographic data across groups, as this was a small group of variables having a nonnormal distribution. Statistical tests were run using Statview and PCSM. 3. Results 3.1. Patients Fig. 1 shows the numbers of patients identified during the selection procedure. Of 29 patients with RDHOA, 17 received intraarticular glucocorticoid therapy; among them, three were given injections in both hips. Of 205 patients who had hip osteoarthritis as the main diagnosis or who were only retrieved using the keywords “intraarticular injection” or “synovectomy”, eight patients (including one patient with bilateral disease) were admitted for intraarticular therapy of RDHOA. Thus, 24 patients were included in the study (one patient lost to follow-up); among them, four had bilateral disease, so that 28 cases of RDHOA were available for study. Table 1 reports the demographic data and the clinical, radiological, and laboratory test results. Of the 18 women, four had bilateral disease. The distribution according to joint space width on D0 was as follows: 2 mm in eight hips, 1.5 mm in five hips, 1 mm in nine hips, 0.5 mm in five hips, and complete obliteration in one hip.

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Fig. 1. Patient flow chart.

3.2. Treatment Table 1 Characteristics of RDHOA in 28 hips (24 patients) Variables Demographic variables - Age (years) - Sex (M/F) Clinical variables - BMI - Lequesne index (N = 23) - OA in multiple joints Radiological variables - Joint space width (mm) - Superolateral narrowing - Chondrocalcinosis - Dysplasia Laboratory variables CRP between 5 and 10 mg/l CRP ≤ 5 mg/l CRP ≥ 10 mg/l

Table 2 shows the glucocorticoids used according to the severity of joint space loss on D0. Weight-bearing elimination for at least 4 weeks after the injection was achieved in 15 patients (Table 2).

Mean ± S.D. 62.2 ± 11.9 6/22

3.3. Time to THA

26.3 ± 5.5 11.3 ± 5.4 4 (14%)

Of 28 hips with RDHOA, 27 required THA. The only patient who did not undergo the procedure had a follow-up of 5 years since the injection. Of the 27 THA procedures, 20 were done within 12 months after the injection and the remaining seven within 29.5 ± 11.5 months (mean ± standard deviation (S.D.)). Time to THA in each patient is given in Table 3.

1.3 ± 0.5 19 (67.8%) 2 (7%) 7 (25%) 2 (93%) 26 (93%) 0

2(7%)

BMI: body mass index; OA: osteoarthritis; CRP: C-reactive protein.

3.3.1. Results according to joint space width on D0 Mean time to THA was 5.8 months in patients whose joint space width was > 1 mm and 22.5 months in those whose joint space width on D0 was ≤ 1 mm. The risk for THA was

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Table 2 Characteristics of intraarticular injections for RDHOA (28 hips in 24 patients) Treatments

Number of Joint space width hips (mm) (N = 28)

Glucocorticoid used Total cortivazol - Cortivazol + hyaluronic acid - Cortivazol + rhenium Betamethasone Total triamcinolone hexacetonide - Triamcinolone hexacetonide + hyaluronic acid - Triamcinolone hexacetonide + rhenium Weight-bearing elimination No: (< 4 weeks or none) Yes: - 4 weeks - 5 weeks - 6 weeks - 8 weeks

7 1 1 4 17 1

1.4 ± 0.6

1±0 1.2 ± 0.5

1

13 15 5 1 6 1

1.2 ± 0.5 1.2 ± 0.6

Table 3 Time from glucocorticoid injection to THA (28 hips in 24 patients) Age

Date of GC injection (J0)

Date of THA

73 58 64 77 73 57 46 51 68 50 76 63 42 77 74 58 57 42 64 53 67 55 86 73 42 60 68 68

July-95 December-93 May-97 July-95 October-00 August-96 May-98 January-99 January-98 January-98 April-98 September-99 June-96 July-95 February-00 July-98 August-96 January-94 June-94 April-98 February-98 May-99 December-96 November-97 October-96 June-93 October-96 May-95

July-95 March-94 August-97 November-95 February-01 December-96 September-98 May-99 June-98 June-98 October-98 April-00 January-97 March-96 November-00 April-99 June-97 November-94 May-95 March-99 July-00 December-00 August-98 February-00 January-00 December-96 May-00 Not required

Time from GC injection to THA (months) 0.3 3 3 4 4 4 4 4 5 5 6 7 7 8 9 9 10 10 11 11 17 19 20 27 39 42 43 67a

Fig. 2. Risk of THA according to joint space width on the day of the intraarticular glucocorticoid injection.

whose joint space width was ≤ 1 mm (Fig. 2): patients whose joint space width on D0 was > 1 mm had a 3.1-fold increase in the risk of THA compared to patients with narrower joint space values. Overall, the two groups were similar regarding demographic data, although age was nonsignificantly older in the group with narrower joint space values. 3.3.2. Results according to the compound used Mean time to THA was 14.2 months in patients given triamcinolone hexacetonide versus 15.6 months in those given cortivazol or betamethasone. The log rank test showed no significant risk differences between these two groups (Fig. 3). Two patients received a radioisotope in addition to a glucocorticoid. One of these patients was a 42-year-old woman with RDHOA of the left hip. She received intraarticular cortivazol followed 3 weeks later by three hyaluronic acid injections 10 days apart. Joint space width was 1.5 mm on D0. THA was required 10 months after the glucocorticoid injection. Four years later, RDHOA was diagnosed in her right hip, where the joint space width decreased by 1 mm within

GC: glucocorticoid; THA: THA. a Time from the glucocorticoid injection to last follow-up.

significantly greater among patients with wider joint space values: after 9 months, 93% of hips whose joint space width on D0 was > 1 mm had had THA, compared to 36% of hips

Fig. 3. Risk for THA according to time since the intraarticular glucocorticoid injection.

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Fig. 4. Risk for THA according to whether weight-bearing was eliminated after the intraarticular glucocorticoid injection.

6 weeks. Triamcinolone hexacetonide and 3 mCi of Rhenium 186 were injected, after which weight-bearing was eliminated for 5 weeks. The joint space width decreased by 0.5 mm within the next month. THA was performed 4 months after the glucocorticoid injection. The other patient had a joint space width of 1 mm on D0 and received Rhenium 186. THA was required 9 months later. 3.3.3. Results according to weight-bearing elimination Four patients failed to eliminate weight-bearing and three others complied for only 2 weeks. In six patients, no information on compliance with weight-bearing elimination was available. Mean time to THA was 18.4 months in compliers versus 10.5 months in noncompliers. The log rank test showed no significant risk differences between these two groups (Fig. 4). 3.3.4. Results according to the site of joint space narrowing Joint space narrowing was superolateral in 19 patients and either medial or circumferential in nine cases. Mean time to THA was 12.1 months in the patients with superolateral narrowing and 20.4 months in the other patients (nonsignificant difference). The risk for THA was not significantly different between the two groups (Fig. 5). Demographic data were similar in the two groups. 3.4. Safety and adverse events No infections or allergic reactions were recorded.

4. Discussion This retrospective study showed that intraarticular injection of a semi-delayed- or delayed-acting glucocorticoid with or without weight-bearing elimination did not decrease the need for THA in patients with RDHOA. Of 24 patients, only

Fig. 5. Risk for THA according to the site of joint space narrowing (superolateral or other).

one did not undergo THA; follow-up in this patient was 5 years. Our retrospective design did not allow an evaluation of the symptomatic effect of intraarticular glucocorticoid injection. We evaluated the need for THA, which reflects both the severity of symptoms and the severity of joint destruction. Use of surgery to treat hip osteoarthritis was recently suggested as a reliable and clinically relevant indicator of disease severity [8,9]. The effectiveness of intraarticular glucocorticoid therapy in RDHOA has not been studied previously. Studies in patients with congestive flares of common hip osteoarthritis support an analgesic effect lasting 2 weeks to 3 months [10–12]. In our study of RDHOA, mean time to THA was 15 months, and most patients required the procedure within the first year after the injection. In earlier studies, the time from the diagnosis to THA was 24 months at the most in patients with RDHOA and 7 years in patients with common hip osteoarthritis [13]. A deleterious effect of triamcinolone hexacetonide on the joint cartilage has been suggested [10–12]. In our study, triamcinolone hexacetonide was used in 67% of patients. The time to THA in this group was similar to that in the patients given cortivazol or betamethasone. Thus, we found no evidence that triamcinolone hexacetonide accelerated the course of RDHOA; however, the compound failed to delay the need for THA. When RDHOA escapes diagnosis because serial radiographs are not available, failure of triamcinolone hexacetonide to relieve the symptoms may lead to a mistaken diagnosis of treatment-induced chondrolysis. Joint destruction was severe in our study patients. Unexpectedly, the risk for THA was higher in patients whose joint space width was greater than 1 mm. In contrast, a study of common hip osteoarthritis showed that a joint space width less than 2 mm at presentation predicted THA [8,9]. One possible explanation is that pain may be more severe during rapid chondrolysis. Thus, in our experience, the pain remains severe

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as long as cartilage is left in the joint. Patients whose joint space width is still greater than 1 mm and who have lost 50% of their joint space width within the last year experience a faster rate of chondrolysis than patients whose joint space is less than 1 mm at presentation. In our study, the risk of THA was similar in patients who did and did not comply with elimination of weight-bearing after the glucocorticoid injection. However, two findings suggest that elimination of weight-bearing may be beneficial. On average, time to THA was 8 months longer in compliers than in noncompliers. The only patient who did not require THA was a complier. However, weight-bearing elimination places a heavy burden on the patient. Although the technique was explained during the hospital stay, only half the patients complied fully. Mean age was younger in compliers. In an earlier study [2], loss of joint space width was slower in the patients with RDHOA who eliminated weight-bearing. However, this study used a different definition of RDHOA, and we evaluated the need for THA rather than the rate of joint space loss. Time to THA was shorter in the patients with superolateral disease compared to those with narrowing at other locations (12 versus 20 months), although the difference was not statistically significant. Studies of patients with common hip osteoarthritis showed that superolateral narrowing was associated with worse pain and functional impairment and with faster joint destruction [8,14]. Our results establish that intraarticular glucocorticoid therapy fails to slow joint destruction in patients with RDHOA. Intraarticular glucocorticoid injection requires fluoroscopy and carries a small but nonnegligeable risk of septic arthritis. These drawbacks should be given careful consideration in the light of the fact that THA is usually required within the year following the injection. Thus, the usefulness of intraarticular glucocorticoid therapy in patients with RDHOA seems debatable.

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