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The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 7 | Pages 946 - 949
1 Jul 2005
Talwalkar SC Givissis PK Trail IA Nuttall D Stanley JK

We divided 309 patients with an inflammatory arthritis who had undergone primary elbow replacement using the Souter-Strathclyde implant into two groups according to their age. The mean follow-up in the older group (mean age 64 years) was 7.3 years while in the younger patients (mean age 42 years) it was 12 years. Survivorship for three different failure end-points (revision, revision because of aseptic loosening of the humeral component, and gross loosening of the humeral implant), was compared in both groups. Our findings showed that there was no significant difference in the incidence of loosening when young rheumatoid patients were compared with an older age group


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 1 | Pages 77 - 82
1 Jan 2002
Ikävalko M Lehto MUK Repo A Kautiainen H Hämäläinen M

We present the results of 525 primary Souter elbow arthroplasties undertaken in 406 patients between 1982 and 1997. There were 372 women and 34 men with a mean age of 57 years; 119 patients had a bilateral procedure. The elbows were affected by chronic inflammatory disease, usually rheumatoid arthritis, which had been present for a mean of 24.7 years (2 to 70). In about 30% the joints were grossly destroyed with significant loss of bone. In 179 elbows the ulnar components were metal-backed and retentive; in the remaining 346, with better bone stock, non-retentive, all-polyethylene prostheses were used. Because of complications, 108 further operations were required in 82 patients. During the early years the incidence of complications was higher. Dislocation was the indication for 30 further procedures in 26 patients. Thirty patients underwent 33 revision procedures for aseptic loosening, 12 had 29 operations because of deep infection, two for superficial infection, and 14 further operations were done for other reasons. The cumulative rate of success, without aseptic loosening, five and ten years after surgery, was 96% and 85%, respectively


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 4 | Pages 486 - 489
1 Apr 2007
Bassi RS Simmons D Ali F Nuttall D Birch A Trail IA Stanley JK

The Acclaim total elbow replacement is a modular system which allows implantation in both unlinked and linked modes. The results of the use of this implant in primary total elbow replacement in 36 patients, operated on between July 2000 and August 2002, are presented at a mean follow-up of 36 months (24 to 49). Only one patient did not have good relief of pain, but all had improved movement and function.

No implant showed clinical or radiological loosening, although one had a lucent area in three of seven humeral zones. The short-term results of the Acclaim total elbow replacement are encouraging. However, 11 patients (30.5%) suffered an intra-operative fracture of the humeral condyle. This did not affect the outcome, or the requirement for further surgery, except in one case where the fracture failed to unite. This problem has hopefully been addressed by redesigning the humeral resection guide. Other complications included three cases of ulnar neuropathy (8.3%) and one of deep infection (2.8%).


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 6 | Pages 1005 - 1012
1 Nov 1999
Gschwend N Scheier NH Baehler AR

Between 1978 and 1986, 59 patients received a GSB III elbow prosthesis, six of them in both elbows. Rheumatoid arthritis (RA) was the underlying cause in 51 of the patients and post-traumatic osteoarthritis (PTOA) in eight. Of these, 24 patients (28 prostheses) have since died; two, both operated on bilaterally, had had their implants for more than ten years and had already been assessed for inclusion in the long-term follow-up. Two patients, each with one elbow prosthesis, have been lost to follow-up and three males who are still living (two with PTOA, one with juvenile RA) had their prosthesis removed before ten years had elapsed.

The remaining 32 patients (28 RA, 4 PTOA) with 36 GSB III elbows were examined clinically and radiologically after a mean period of 13.5 years. Pain was considerably reduced in 91.6%. Mobility was increased by 37° in those with RA and by 67° in those with PTOA.

There were three cases of aseptic loosening and three of deep infection. The main complication was disassembly of the prosthetic component in nine elbows (13.8%). This last group included two patients with postoperative fractures unrelated to the operative technique and one with neuropathic arthritis. Ulnar neuritis occurred in two patients.

Since 87.7% of all the GSB III prostheses implanted in this period remained in situ, our results are comparable with those for hip and knee arthroplasty.


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 4 | Pages 614 - 619
1 Jul 1998
Baksi DP

From 1984 to 1995, 68 ankylosed elbows and 11 which were unstable after trauma were replaced in India by Baksi sloppy hinge prostheses. The mean age of the patients was 28.6 years (17 to 70) and the mean follow-up 9.6 years (2 to 13.5).

Of the 68 ankylosed elbows, 59 (87%) regained a mean arc of painless movement of 88.5° (27 to 115). The mean improvement of supination was 24° and of pronation 16.5°. There were 54 good results (80%), eight fair and three poor. There were two complete failures due to infection, and one due to a broken humeral stem.

Of the 11 unstable elbows, the nine with good results had a mean arc of 125° (15 to 140) of painless stable movement, with a mean improvement in supination of 26° and of pronation of 19.5°. There was one fair result and one failure due to loosening with subsequent late infection.

There were significant complications in 14 cases with infection in seven and aseptic loosening in four. Patients with loosening or late removal of the prosthesis often retained reasonably stable elbow movement because periprosthetic fibrosis had connected the approximated bone ends, and muscle balance had been restored.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 4 | Pages 509 - 514
1 Apr 2006
Aldridge JM Lightdale NR Mallon WJ Coonrad RW

There have been few reports in the literature of total elbow arthroplasty extending beyond 10 to 15 years. We reviewed 40 patients (41 elbows) with a mean age of 56 years (19 to 83) who had undergone a Coonrad/Coonrad-Morrey elbow arthroplasty by one surgeon for various diagnoses between 1974 and 1994. Surgical selection excluded patients with previous elbow infection or who refused to accept a sedentary level of elbow activity postoperatively. Objective data were collected from charts, radiographs, clinical photographs and supplemented by the referring orthopaedic surgeons’ records and radiographs if health or distance prevented a patient from returning for final review. Subjective outcome was defined by patient satisfaction. Of the 41 elbows, 21 were functional between 10 and 14 years after operation, ten between 15 and 19 years and ten between 20 and 31 years. There were 14 complications and 13 revisions, but no cases of acute infection, or permanent removal of any implant


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 10 | Pages 1348 - 1351
1 Oct 2008
Rispoli DM Athwal GS Morrey BF

Ulnar neuropathy presents as a complication in 5% to 10% of total elbow replacements, but subsequent ulnar neurolysis is rarely performed. Little information is available on the surgical management of persistent ulnar neuropathy after elbow replacement. We describe our experience with the surgical management of this problem. Of 1607 total elbow replacements performed at our institution between January 1969 and December 2004, eight patients (0.5%) had a further operation for persistent or progressive ulnar neuropathy. At a mean follow-up of 9.2 years (3.1 to 21.7) six were clinically improved and satisfied with their outcome, although, only four had complete recovery. When transposition was performed on a previously untransposed nerve the rate of recovery was 75%, but this was reduced to 25% if the nerve had been transposed at the time of the replacement


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 1 | Pages 78 - 83
1 Jan 2006
Sneftrup SB Jensen SL Johannsen HV Søjbjerg JO

We studied retrospectively the results of revision arthroplasty of the elbow using a linked Coonrad-Morrey implant in 23 patients (24 elbows) after a mean follow-up period of 55 months. According to the Mayo Elbow Performance Score, 19 elbows were satisfactory, nine were excellent and ten good. The median total score had improved from 35 points (20 to 75) before the primary arthroplasty to 85 points (40 to 100) at the latest follow-up. There was a marked relief of pain, but the range of movement showed no overall improvement. Two patients had a second revision because of infection and two for aseptic loosening. The estimated five-year survival rate of the prosthesis was 83.1% (95% confidence interval 61.1 to 93.3). Revision elbow arthroplasty using the Coonrad-Morrey implant provided satisfactory results but with complications occurring in 13 cases


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 1 | Pages 47 - 53
1 Jan 2005
Whaley A Morrey BF Adams R

We examined the effects of previous resection of the radial head and synovectomy on the outcome of subsequent total elbow arthroplasty in patients with rheumatoid arthritis. Fifteen elbows with a history of resection and synovectomy were compared with a control group of patients who had elbow arthroplasty with an implant of the same design. The mean age in both groups was 63 years. In the study group, resection of the radial head and synovectomy had been undertaken at a mean of 8.9 years before arthroplasty. The mean radiological follow-up for the 13 available patients in the study group was 5.89 years (0.3 to 11.0) and in the control group was 6.6 years (2.2 to 12.6). There were no revisions in either group. The mean Mayo elbow performance score improved from 29 to 96 in the study group, with similar improvement in the control group (28 to 87). The study group had excellent results in 13 elbows and good results in two. The control group had excellent results in seven and good results in six. Our experience indicates that previous resection of the radial head and synovectomy are not associated with an increased rate of revision following subsequent arthroplasty of the elbow. However, there was a higher rate of complication in the study group compared with the control group


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 2 | Pages 191 - 195
1 Feb 2005
Mighell MA Dunham RC Rommel EA Frankle MA

We present six patients with chronic dislocation of the elbow who were treated by primary semiconstrained total elbow arthroplasty. All were women with a mean age of 65 years (51 to 76), the mean interval between dislocation and surgery was 17 weeks (5 to 52) and the mean follow-up 58 months (24 to 123). The most dramatic improvement was in function. The mean American Shoulder and Elbow Surgeon score was 5.2 times better (p < 0.001) and the mean total range of movement increased from 33° to 121° (p < 0.001) after operation. Three patients developed wear of polyethylene. One required revision for a periprosthetic fracture, and another required a bushing exchange. Primary semiconstrained elbow arthroplasty provides significant, predictable functional improvement. Potential solutions for wear of polyethylene include a different operative technique or design of implant. Despite the high incidence of such wear, total elbow arthroplasty should be considered as a viable treatment option for chronic dislocation of the elbow in elderly patients


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 8 | Pages 1116 - 1120
1 Nov 2002
Sanchez-Sotelo J Morrey BF

Seven patients with chronic insufficiency of the triceps were treated by either a rotation flap using anconeus (4) or an allograft of tendo Achillis (3). The latter procedure was selected for patients with a large defect in whom the anconeus muscle had been devitalised. Five disruptions were in patients who had previously undergone an elbow replacement. The patients were assessed for subjective satisfaction, pain, range of movement and strength, and the results were graded using the Mayo Elbow Performance Score (MEPS). The mean follow-up was for 33 months (9 to 63). One rotation flap failed six months after operation. At the most recent follow-up, the remaining six patients had no or slight pain, restoration of a functional arc of movement and normal or slightly decreased power of extension. All six were satisfied with the outcome and were able to resume their daily activities with no limitations other than those imposed by the previous elbow replacement. The final MEPS was 100 points in five patients and 75 in one


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 2 | Pages 235 - 241
1 Feb 2010
van der Lugt JCT Valstar ER Witvoet-Braam SW Nelissen RGHH

Mechanical loosening which begins with early-onset migration of the prosthesis is the major reason for failure of the Souter-Strathclyde elbow replacement. In a prospective study of 18 Souter-Strathclyde replacements we evaluated the patterns of migration using roentgen stereophotogrammetric analysis. We had previously reported the short-term results after a follow-up of two years which we have now extended to a mean follow-up of 8.2 years (1 to 11.3). Migration was assessed along the co-ordinal axes and overall micromovement was expressed as the maximum total point movement. The alignment of the prosthesis and the presence of radiolucent lines were examined on conventional standardised radiographs. All the humeral components showed increased and variable patterns of migration at the extended follow-up and four humeral components were revised. The maximum total point movement at two years in the revised prostheses was 1.8 mm (. sd. 1.0) and in the non-revised 0.7 mm (. sd. 0.5, p = 0.01). Most humeral components migrated into external rotation resulting in an anterior and varus tilt. The ulnar components remained stable


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 5 | Pages 705 - 710
1 Jul 2000
Yanni ON Fearn CBD Gallannaugh SC Joshi R

We report the results of a series of 59 unconstrained total arthroplasties of the elbow after a mean follow-up of 6.5 years (4 to 10). All the patients had rheumatoid arthritis. The indication for surgery was pain in all but one. Outcome was assessed by the Mayo Elbow Performance Index (MEPI). Of the 59 arthroplasties, two were lost to follow-up. Ten patients died, but as two of their arthroplasties were failures we included them in the results. The outcome in the remaining 49 was excellent in 26 (53%), good in 15 (31%), fair in one (2%) and poor or a failure in seven (14%). There was an improvement in the pain score (p < 0.001), movement (p < 0.001) and function (p < 0.001). Two patients developed instability, but neither required further surgery. There was a mean increase of 21° in flexion and of 7° in extension. The overall rate of complications was 33.9%. Lesions of the ulnar nerve, one of which did not recover, occurred in four patients, deep infection in two and stiffness in five. The rates of complications were similar to those in recent reports of other elbow arthroplasties. We carried out a radiological analysis of 39 arthroplasties which showed radiolucent lines around the humeral component in 22 and the ulnar component in 15. There were lower scores on the MEPI for those with radiolucent lines around the humeral component


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 10 | Pages 1341 - 1346
1 Oct 2006
Gille J Ince A González O Katzer A Loehr JF

This study reviews the predisposing features, the clinical, and laboratory findings at the time of diagnosis and the results of single-stage revision of prosthetic replacement of the elbow for infection.

Deep infection occurred in six of 305 (1.9%) primary total elbow replacements. The mean follow-up after revision was 6.8 years (6 months to 16 years) and the mean age at the time of revision was 62.7 years (56 to 74). All six cases with infection had rheumatoid arthritis and had received steroid therapy. The infective organism was Staphylococcus aureus. Four of the six elbows had a developed radiolucency around one component or the other. Successful single-stage exchange arthroplasty was carried out with antibiotic-loaded cement in five of the six cases. In one, the revision prosthesis had to be removed following recurrence of the infection. The functional result was good in three elbows, fair in one, poor in one and fair in the resection arthroplasty.


The Bone & Joint Journal
Vol. 95-B, Issue 1 | Pages 70 - 74
1 Jan 2013
Dattani R Smith CD Patel VR

We investigated the incidence of and risk factors for venous thromboembolism (VTE) following surgery of the shoulder and elbow and assessed the role of thromboprophylaxis in upper limb surgery. All papers describing VTE after shoulder and elbow surgery published in the English language literature before 31 March 2012 were reviewed. A total of 14 papers were available for analysis, most of which were retrospective studies and case series. The incidence of VTE was 0.038% from 92 440 shoulder arthroscopic procedures, 0.52% from 42 261 shoulder replacements, and 0.64% from 4833 procedures for fractures of the proximal humerus (open reduction and internal fixation or hemiarthroplasty). The incidence following replacement of the elbow was 0.26% from 2701 procedures. Diabetes mellitus, rheumatoid arthritis and ischaemic heart disease were identified as the major risk factors.

The evidence that exists on thromboprophylaxis is based on level III and IV studies, and we therefore cannot make any recommendations on prophylaxis based on the current evidence. It seems reasonable to adopt a multimodal approach that involves all patients receiving mechanical prophylaxis, with chemical prophylaxis reserved for those who are at high risk for VTE.

Cite this article: Bone Joint J 2013;95-B:70–4.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 1 | Pages 80 - 85
1 Jan 2012
Malone AA Sanchez JS Adams R Morrey B

We report the effectiveness of revision of total elbow replacement by re-cementing. Between 1982 and 2004, 53 elbows in 52 patients were treated with re-cementing of a total elbow replacement into part or all of the existing cement mantle or into the debrided host-bone interface, without the use of structural bone augmentation or a custom prosthesis. The original implant revision was still in situ and functional in 42 of 53 elbows (79%) at a mean of 94.5 months (26 to 266) after surgery. In 31 of these 42 elbows (74%) the Mayo Elbow Performance Score was good or excellent. Overall, of the 53 elbows, 18 (34%) required re-operation, ten (19%) for loosening. A classification system was developed to identify those not suitable for revision by this technique, and using this we have showed that successful re-implantation is statistically correlated to properly addressing the bone deficiency for both the humeral (p = 0.005) and the ulnar (p = 0.039) components.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 7 | Pages 950 - 954
1 Jul 2005
Khatri M Stirrat AN

We present the outcome of 47 Souter-Strathclyde replacements of the elbow with a mean follow-up of 82 months (12 to 129). The clinical results were assessed using a condition-specific outcome measure. The mean total score (maximum 100) before the operation was 47.21 and improved to 79.92 (p < 0.001). The mean pain score (maximum 50) improved from 21.41 to 46.70 (p < 0.001) and the mean functional component of the score (maximum 30) from 11.19 to 18.65 (p < 0.001). There was negligible change in the score for the range of movement although a significant improvement in mean flexion from 124° to 136° was noted (p < 0.001).

Revision surgery was required in four patients, for dislocation, wound dehiscence and early infection in one, late infection in two and aseptic loosening in one. The cumulative survival was 75% at nine years for all causes of failure and 97% at ten years for aseptic loosening alone. Our study demonstrates the value of the Souter-Strathclyde total elbow arthroplasty in providing relief from pain and functional improvement in rheumatoid patients.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 1 | Pages 92 - 97
1 Jan 2010
Kulkarni GS Kulkarni VS Shyam AK Kulkarni RM Kulkarni MG Nayak P

Arthrolysis and dynamic splinting have been used in the treatment of elbow contractures, but there is no standardised protocol for treatment of severe contractures with an arc of flexion < 30°. We present our results of radical arthrolysis with twin incisions with the use of a monolateral hinged fixator to treat very severe extra-articular contracture of the elbow. This retrospective study included 26 patients (15 males and 11 females) with a mean age of 30 years (12 to 60). The mean duration of stiffness was 9.1 months (5.4 to 18) with mean follow-up of 5.2 years (3.5 to 9.4). The mean pre-operative arc of movement was 15.6° (0° to 30°), with mean pre-operative flexion of 64.1° (30° to 120°) and mean pre-operative extension of 52.1° (10° to 90°). Post-operatively the mean arc improved to 102.4° (60° to 135°), the mean flexion improved to 119.1° (90° to 140°) and mean extension improved to 16.8° (0° to 30°) (p < 0.001). The Mayo elbow score improved from a mean of 45 (30 to 65) to 89 (75 to 100) points, and 13 had excellent, nine had good, three had fair and one had a poor result. We had one case of severe instability and one wound dehiscence which responded well to treatment. One case had deep infection with poor results which responded well to treatment.

Our findings indicate that this method is very effective in the treatment of severe elbow contracture; however, a randomised controlled study is necessary for further evaluation.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 10 | Pages 1369 - 1374
1 Oct 2005
Athwal GS Chin PY Adams RA Morrey BF

We reviewed 20 patients who had undergone a Coonrad-Morrey total elbow arthroplasty after resection of a primary or metastatic tumour from the elbow or distal humerus between 1980 and 2002. Eighteen patients underwent reconstruction for palliative treatment with restoration of function after intralesional surgery and two after excision of a primary bone tumour. The mean follow-up was 30 months (1 to 192).

Five patients (25%) were alive at the final follow-up; 14 (70%) had died of their disease and one of unrelated causes. Local control was achieved in 15 patients (75%). The mean Mayo Elbow Performance Score improved from 22 (5 to 45) to 75 points (55 to 95). Four reconstructions (20%) failed and required revision. Seven patients (35%) had early complications, the most frequent being nerve injury (25%). There were no infections or wound complications although 18 patients (90%) had radiotherapy, chemotherapy or both.

The Coonrad-Morrey total elbow arthroplasty provides good relief from pain and a good functional outcome after resection of tumours of the elbow. The rates of complications involving local recurrence of tumour (25%) and nerve injury (25%) are of concern.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 10 | Pages 1382 - 1389
1 Oct 2012
Sewell MD Kang SN Al-Hadithy N Higgs DS Bayley I Falworth M Lambert SM

There is little information about the management of peri-prosthetic fracture of the humerus after total shoulder replacement (TSR). This is a retrospective review of 22 patients who underwent a revision of their original shoulder replacement for peri-prosthetic fracture of the humerus with bone loss and/or loose components. There were 20 women and two men with a mean age of 75 years (61 to 90) and a mean follow-up 42 months (12 to 91): 16 of these had undergone a previous revision TSR. Of the 22 patients, 12 were treated with a long-stemmed humeral component that bypassed the fracture. All their fractures united after a mean of 27 weeks (13 to 94). Eight patients underwent resection of the proximal humerus with endoprosthetic replacement to the level of the fracture. Two patients were managed with a clam-shell prosthesis that retained the original components. The mean Oxford shoulder score (OSS) of the original TSRs before peri-prosthetic fracture was 33 (14 to 48). The mean OSS after revision for fracture was 25 (9 to 31). Kaplan-Meier survival using re-intervention for any reason as the endpoint was 91% (95% confidence interval (CI) 68 to 98) and 60% (95% CI 30 to 80) at one and five years, respectively.

There were two revisions for dislocation of the humeral head, one open reduction for modular humeral component dissociation, one internal fixation for nonunion, one trimming of a prominent screw and one re-cementation for aseptic loosening complicated by infection, ultimately requiring excision arthroplasty. Two patients sustained nerve palsies.

Revision TSR after a peri-prosthetic humeral fracture associated with bone loss and/or loose components is a salvage procedure that can provide a stable platform for elbow and hand function. Good rates of union can be achieved using a stem that bypasses the fracture. There is a high rate of complications and function is not as good as with the original replacement.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 11 | Pages 1460 - 1463
1 Nov 2006
Landor I Vavrik P Jahoda D Guttler K Sosna A

We assessed the long-term results of 58 Souter-Strathclyde total elbow replacements in 49 patients with rheumatoid arthritis. The mean length of follow-up was 9.5 years (0.7 to 16.7). The mean pre-operative Mayo Elbow Performance Score was 30 (15 to 80) and at final follow-up was 82 (60 to 95). A total of 13 elbows (22.4%) were revised, ten (17.2%) for aseptic loosening, one (1.7%) for instability, one (1.7%) for secondary loosening after fracture, and one elbow (1.7%) was removed because of deep infection. The Kaplan-Meier survival rate was 70% and 53% at ten and 16 years, respectively. Failure of the ulnar component was found to be the main problem in relation to the loosening. Anterior transposition of the ulnar nerve had no influence on ulnar nerve paresthaesiae in these patients.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 3 | Pages 330 - 334
1 Mar 2007
Cesar M Roussanne Y Bonnel F Canovas F

Between 1993 and 2002, 58 GSB III total elbow replacements were implanted in 45 patients with rheumatoid arthritis by the same surgeon. At the most recent follow-up, five patients had died (five elbows) and six (nine elbows) had been lost to follow-up, leaving 44 total elbow replacements in 34 patients available for clinical and radiological review at a mean follow-up of 74 months (25 to 143). There were 26 women and eight men with a mean age at operation of 55.7 years (24 to 77).

At the latest follow-up, 31 excellent (70%), six good (14%), three fair (7%) and four poor (9%) results were noted according to the Mayo elbow performance score. Five humeral (11%) and one ulnar (2%) component were loose according to radiological criteria (type III or type IV). Of the 44 prostheses, two (5%) had been revised, one for type-IV humeral loosening after follow-up for ten years and one for fracture of the ulnar component. Seven elbows had post-operative dysfunction of the ulnar nerve, which was transient in five and permanent in two.

Despite an increased incidence of loosening with time, the GSB III prosthesis has given favourable mid-term results in patients with rheumatoid arthritis.