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The Bone & Joint Journal
Vol. 97-B, Issue 2 | Pages 160 - 163
1 Feb 2015
Biemond JE Venkatesan S van Hellemondt GG

The long-term survival of the cementless Spotorno CLS femoral component in patients aged > 50 years at the time of arthroplasty was investigated. Survivorship analysis of a consecutive series of 85 patients (100 hips; under 50 years of age at a mean follow-up of 18.4 years (16.3 to 20.8)) was performed. The clinical and radiographic outcomes were satisfactory. The overall rate of survival of the femoral component was 93.5% (95% confidence interval (CI), 90.9 to 96.1) after 19 years. Survival with revision for aseptic loosening as the end point was 95.7% (95% CI 93.6 to 97.8%) at 19 years.

This study demonstrates an excellent long-term survival of the Spotorno CLS femoral component after 16 to 20 years in young patients undergoing total hip arthroplasty.

Cite this article: Bone Joint J 2015;97-B:160–3.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 2 | Pages 229 - 236
1 Feb 2011
Briffa N Pearce R Hill AM Bircher M

We report the outcome of 161 of 257 surgically fixed acetabular fractures. The operations were undertaken between 1989 and 1998 and the patients were followed for a minimum of ten years. Anthropometric data, fracture pattern, time to surgery, associated injuries, surgical approach, complications and outcome were recorded. Modified Merle D’Aubigné score and Matta radiological scoring systems were used as outcome measures. We observed simple fractures in 108 patients (42%) and associated fractures in 149 (58%).

The result was excellent in 75 patients (47%), good in 41 (25%), fair in 12 (7%) and poor in 33 (20%). Poor prognostic factors included increasing age, delay to surgery, quality of reduction and some fracture patterns. Complications were common in the medium- to long-term and functional outcome was variable. The gold-standard treatment for displaced acetabular fractures remains open reduction and internal fixation performed in dedicated units by specialist surgeons as soon as possible.


The Bone & Joint Journal
Vol. 98-B, Issue 3 | Pages 341 - 348
1 Mar 2016
Ogonda L Hill J Doran E Dennison J Stevenson M Beverland D

Aims

The aim of this study was to present data on 11 459 patients who underwent total hip (THA), total knee (TKA) or unicompartmental knee arthroplasty (UKA) between November 2002 and April 2014 with aspirin as the primary agent for pharmacological thromboprophylaxis.

Patients and Methods

We analysed the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) then compared the 90-day all-cause mortality with the corresponding data in the National Joint Registry for England and Wales (NJR).


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 1 | Pages 107 - 110
1 Jan 2006
Watts AC Howie CR Simpson AHRW

The risk of venous thromboembolism in patients following arthroplasty may be reduced by continuing chemical thromboprophylaxis for up to 35 days post-operatively. This prospective cohort study investigated the compliance of 40 consecutive consenting patients undergoing lower limb arthroplasty with self-administration of a recommended subcutaneous chemotherapeutic agent for six weeks after surgery. Compliance was assessed by examination of the patient for signs of injection, number of syringes used, and a self-report diary at the end of the six-week period. A total of 40 patients, 15 men and 25 women, were recruited. One woman was excluded because immediate post-operative complications prevented her participation. Self-administration was considered feasible in 87% of patients (95% confidence interval (CI) 76 to 98) at the time of discharge. Among this group of 34 patients, 29 (85%) were compliant (95% CI 73 to 97). Patients can learn to self-administer subcutaneous injections of thromboprophylaxis, and compliance with extended prophylaxis to six weeks is good.


The Bone & Joint Journal
Vol. 97-B, Issue 7 | Pages 905 - 910
1 Jul 2015
Hsu C Lin P Kuo F Wang J

Tranexamic acid (TXA), an inhibitor of fibrinolysis, reduces blood loss after total knee arthroplasty. However, its effect on minimally invasive total hip arthroplasty (THA) is not clear. We performed a prospective, randomised double-blind study to evaluate the effect of two intravenous injections of TXA on blood loss in patients undergoing minimally invasive THA.

In total, 60 patients (35 women and 25 men with a mean age of 58.1 years; 17 to 84) who underwent unilateral minimally invasive uncemented THA were randomly divided into the study group (30 patients, 20 women and ten men with a mean age of 56.5 years; 17 to 79) that received two intravenous injections 1 g of TXA pre- and post-operatively (TXA group), and a placebo group (30 patients, 15 women and 15 men with a mean age of 59.5 years; 23 to 84). We compared the peri-operative blood loss of the two groups. Actual blood loss was calculated from the maximum reduction in the level of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism.

The TXA group had a lower mean intra-operative blood loss of 441 ml (150 to 800) versus 615 ml (50 to 1580) in the placebo (p = 0.044), lower mean post-operative blood loss (285 ml (120 to 570) versus 392 ml (126 to 660) (p = 0.002), lower mean total blood loss (1070 ml (688 to 1478) versus 1337 ml (495 to 2238) (p = 0.004) and lower requirement for transfusion (p = 0.021). No patients in either group had symptoms of venous thromboembolism or wound complications.

This prospective, randomised controlled study showed that a regimen of two intravenous injections of 1 g TXA is effective for blood conservation after minimally invasive THA.

Cite this article: Bone Joint J 2015;97-B:905–10.


The Bone & Joint Journal
Vol. 97-B, Issue 5 | Pages 675 - 680
1 May 2015
Domeij-Arverud E Labruto F Latifi A Nilsson G Edman G Ackermann PW

Deep vein thrombosis is a common complication of immobilising the lower limb after surgery. We hypothesised that intermittent pneumatic compression (IPC) therapy in outpatients who had undergone surgical repair of acute ruptures of the Achilles tendon could reduce the incidence of this problem.

A total of 150 patients who had undergone surgical repair of the Achilles tendon were randomised to either treatment with IPC for six hours per day (n = 74) under an orthosis or treatment as usual (n = 74) in a plaster cast without IPC. At two weeks post-operatively, the incidence of deep vein thrombosis was assessed using blinded, double-reported compression duplex ultrasound. At this point, IPC was discontinued and all patients were immobilised in an orthosis for a further four weeks. At six weeks post-operatively, a second compression duplex ultrasound scan was performed.

At two weeks, the incidence of deep vein thrombosis was 21% in the treated group and 37% in the control group (p = 0.042). Age over 39 years was found to be a strong risk factor for deep vein thrombosis (odds ratio (OR) = 4.84, 95% confidence interval (CI) 2.14 to 10.96). Treatment with IPC, corrected for age differences between groups, reduced the risk of deep vein thrombosis at the two-week point (OR = 2.60; 95% CI 1.15 to 5.91; p =0.022). At six weeks, the incidence of deep vein thrombosis was 52% in the treated group and 48% in the control group (OR 0.94, 95% CI 0.49 to 1.83). IPC appears to be an effective method of reducing the risk of deep vein thrombosis in the early stages of post-operative immobilisation of outpatients. Further research is necessary to elucidate whether it can confer similar benefits over longer periods of immobilisation and in a more heterogeneous group of patients.

Cite this article: Bone Joint J 2015;97-B:675–80.


The Bone & Joint Journal
Vol. 96-B, Issue 11 | Pages 1515 - 1519
1 Nov 2014
Allen D Sale G

Although patients with a history of venous thromboembolism (VTE) who undergo lower limb joint replacement are thought to be at high risk of further VTE, the actual rate of recurrence has not been reported.

The purpose of this study was to identify the recurrence rate of VTE in patients who had undergone lower limb joint replacement, and to compare it with that of patients who had undergone a joint replacement without a history of VTE.

From a pool of 6646 arthroplasty procedures (3344 TKR, 2907 THR, 243 revision THR, 152 revision TKR) in 5967 patients (68% female, mean age 67.7; 21 to 96) carried out between 2009 and 2011, we retrospectively identified 118 consecutive treatment episodes in 106 patients (65% female, mean age 70; 51 to 88,) who had suffered a previous VTE. Despite mechanical prophylaxis and anticoagulation with warfarin, we had four recurrences by three months (3.4% of 118) and six by one year (5.1% of 118). In comparison, in all our other joint replacements the rate of VTE was 0.54% (35/6528).

The relative risk of a VTE by 90 days in patients who had undergone a joint replacement with a history of VTE compared with those with a joint replacement and no history of VTE was 6.3 (95% confidence interval, 2.3 to 17.5). There were five complications in the previous VTE group related to bleeding or over-anticoagulation.

Cite this article: Bone Joint J 2014;96-B:1515–19.


The Bone & Joint Journal
Vol. 97-B, Issue 2 | Pages 177 - 184
1 Feb 2015
Felden A Vaz G Kreps S Anract P Hamadouche M Biau DJ

Conventional cemented acetabular components are reported to have a high rate of failure when implanted into previously irradiated bone. We recommend the use of a cemented reconstruction with the addition of an acetabular reinforcement cross to improve fixation.

We reviewed a cohort of 45 patients (49 hips) who had undergone irradiation of the pelvis and a cemented total hip arthroplasty (THA) with an acetabular reinforcement cross. All hips had received a minimum dose of 30 Gray (Gy) to treat a primary nearby tumour or metastasis. The median dose of radiation was 50 Gy (Q1 to Q3: 45 to 60; mean: 49.57, 32 to 72).

The mean follow-up after THA was 51 months (17 to 137). The cumulative probability of revision of the acetabular component for a mechanical reason was 0% (0 to 0%) at 24 months, 2.9% (0.2 to 13.3%) at 60 months and 2.9% (0.2% to 13.3%) at 120 months, respectively. One hip was revised for mechanical failure and three for infection.

Cemented acetabular components with a reinforcement cross provide good medium-term fixation after pelvic irradiation. These patients are at a higher risk of developing infection of their THA.

Cite this article: Bone Joint J 2015;97-B:177–84.


The Bone & Joint Journal
Vol. 95-B, Issue 11_Supple_A | Pages 144 - 147
1 Nov 2013
Jones RE Russell RD Huo MH

Satisfactory primary wound healing following total joint replacement is essential. Wound healing problems can have devastating consequences for patients. Assessment of their healing capacity is useful in predicting complications. Local factors that influence wound healing include multiple previous incisions, extensive scarring, lymphoedema, and poor vascular perfusion. Systemic factors include diabetes mellitus, inflammatory arthropathy, renal or liver disease, immune compromise, corticosteroid therapy, smoking, and poor nutrition. Modifications in the surgical technique are necessary in selected cases to minimise potential wound complications. Prompt and systematic intervention is necessary to address any wound healing problems to reduce the risks of infection and other potential complications.

Cite this article: Bone Joint J 2013;95-B, Supple A:144–7.


The Bone & Joint Journal
Vol. 96-B, Issue 8 | Pages 1062 - 1069
1 Aug 2014
Sultan MJ Zhing T Morris J Kurdy N McCollum CN

In this randomised controlled trial, we evaluated the role of elastic compression using ankle injury stockings (AIS) in the management of fractures of the ankle. A total of 90 patients with a mean age of 47 years (16 to 79) were treated within 72 hours of presentation with a fracture of the ankle, 31 of whom were treated operatively and 59 conservatively, were randomised to be treated either with compression by AIS plus an Aircast boot or Tubigrip plus an Aircast boot. Male to female ratio was 36:54. The primary outcome measure was the functional Olerud–Molander ankle score (OMAS). The secondary outcome measures were; the American Orthopaedic Foot and Ankle Society score (AOFAS); the Short Form (SF)-12v2 Quality of Life score; and the frequency of deep vein thrombosis (DVT).

Compression using AIS reduced swelling of the ankle at all time points and improved the mean OMAS score at six months to 98 (95% confidence interval (CI) 96 to 99) compared with a mean of 67 (95% CI 62 to 73) for the Tubigrip group (p < 0.001). The mean AOFAS and SF-12v2 scores at six months were also significantly improved by compression. Of 86 patients with duplex imaging at four weeks, five (12%) of 43 in the AIS group and ten (23%) of 43 in the Tubigrip group developed a DVT (p = 0.26).

Compression improved functional outcome and quality of life following fracture of the ankle. DVTs were frequent, but a larger study would be needed to confirm that compression with AISs reduces the incidence of DVT.

Cite this article: Bone Joint J 2014; 96-B:1062–9.


The Bone & Joint Journal
Vol. 97-B, Issue 3 | Pages 337 - 345
1 Mar 2015
Jaroma AVJ Soininvaara TA Kröger H

Total knee arthroplasty (TKA) is known to lead to a reduction in periprosthetic bone mineral density (BMD). In theory, this may lead to migration, instability and aseptic loosening of the prosthetic components. Bisphosphonates inhibit bone resorption and may reduce this loss in BMD. We hypothesised that treatment with bisphosphonates and calcium would lead to improved BMD and clinical outcomes compared with treatment with calcium supplementation alone following TKA. A total of 26 patients, (nine male and 17 female, mean age 67 years) were prospectively randomised into two study groups: alendronate and calcium (bisphosphonate group, n = 14) or calcium only (control group, n = 12). Dual energy X-ray absorptiometry (DEXA) measurements were performed post-operatively, and at three months, six months, one, two, four, and seven years post-operatively.

Mean femoral metaphyseal BMD was significantly higher in the bisphosphonate group compared with controls, up to four years following surgery in some areas of the femur (p = 0.045). BMD was observed to increase in the lateral tibial metaphysis in the bisphosphonate group until seven years (p = 0.002), and was significantly higher than that observed in the control group throughout (p = 0.024). There were no significant differences between the groups in the central femoral metaphyseal, tibial medial metaphyseal or diaphyseal regions of interest (ROI) of either the femur or tibia.

Bisphosphonate treatment after TKA may be of benefit for patients with poor bone quality. However, further studies with a larger number of patients are necessary to assess whether this is clinically beneficial.

Cite this article: Bone Joint J 2015;97-B:337–45.


The Bone & Joint Journal
Vol. 96-B, Issue 6 | Pages 845 - 850
1 Jun 2014
Romanò CL Logoluso N Meani E Romanò D De Vecchi E Vassena C Drago L

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed.

In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups.

After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate.

Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes.

Cite this article: Bone Joint J 2014; 96-B:845–50.


The Bone & Joint Journal
Vol. 96-B, Issue 8 | Pages 1005 - 1015
1 Aug 2014
Alshryda S Sukeik M Sarda P Blenkinsopp J Haddad FS Mason JM

Intravenous tranexamic acid (TXA) has been shown to be effective in reducing blood loss and the need for transfusion after joint replacement. Recently, there has been interest in applying it topically before the closure of surgical wounds. This has the advantages of ease of application, maximum concentration at the site of bleeding, minimising its systemic absorption and, consequently, concerns about possible side-effects.

We conducted a systematic review and meta-analysis which included 14 randomised controlled trials (11 in knee replacement, two in hip replacement and one in both) which investigated the effect of topical TXA on blood loss and rates of transfusion. Topical TXA significantly reduced the rate of blood transfusion (total knee replacement: risk ratio (RR) 4.51; 95% confidence interval (CI): 3.02 to 6.72; p < 0.001 (nine trials, I2 = 0%); total hip replacement: RR 2.56; 95% CI: 1.32 to 4.97, p = 0.004 (one trial)). The rate of thromboembolic events with topical TXA were similar to those found with a placebo. Indirect comparison of placebo-controlled trials of topical and intravenous TXA indicates that topical administration is superior to the intravenous route.

In conclusion, topical TXA is an effective and safe method of reducing the need for blood transfusion after total knee and hip replacement. Further research is required to find its optimum dose for topical use.

Cite this article: Bone Joint J 2014;96-B:1005–15.


The Bone & Joint Journal
Vol. 95-B, Issue 9 | Pages 1280 - 1284
1 Sep 2013
Yamaguchi T Matsumine A Niimi R Nakamura T Matsubara T Asanuma K Hasegawa M Sudo A

The aim of this study was to define the incidence of venous thromboembolism (VTE) and risk factors for the development of deep-vein thrombosis (DVT) after the resection of a musculoskeletal tumour. A total of 94 patients who underwent resection of a musculoskeletal tumour between January 2003 and December 2005 were prospectively studied. There were 42 men and 52 women with a mean age of 54.4 years (18 to 86). All patients wore intermittent pneumatic compression devices and graduated compression stockings. Ultrasound examination of the lower limbs was conducted to screen for DVT between the fifth and ninth post-operative days.

DVT was detected in 21 patients (22%). Of these, two were symptomatic (2%). One patient (1%) had a fatal pulmonary embolism. Patients aged ≥ 70 years had an increased risk of DVT (p = 0.004).

The overall incidence of DVT (both symptomatic and asymptomatic) after resection of a musculoskeletal tumour with mechanical prophylaxis was high. It seems that both mechanical and anticoagulant prophylaxis is needed to prevent VTE in patients who have undergone the resection of a musculoskeletal tumour.

Cite this article: Bone Joint J 2013;95-B:1280–4.


The Bone & Joint Journal
Vol. 95-B, Issue 4 | Pages 558 - 562
1 Apr 2013
Kim SM Park JM Shin SH Seo SW

It is important to be able to identify patients with an increased risk of venous thromboembolism (VTE) in order to minimise the risk of an event. We investigated the incidence and risk factors for post-operative VTE in 168 consecutive patients with a malignancy of the lower limb. The period of study included ten months before and 12 months after the introduction of chemical thromboprophylaxis. All data about the potential risk factors were identified and classified into three groups (patient-, surgery- and tumour-related). The outcome measure was a thromboembolic event within 90 days of surgery.

Of the 168 patients, eight (4.8%) had a confirmed symptomatic deep-vein thrombosis and one (0.6%) a fatal pulmonary embolism. Of the 28 variables tested, age > 60 years, higher American Society of Anesthesiologists grade and metastatic tumour were independent risk factors for VTE. The overall rate of symptomatic VTE was not significantly different between patients who received chemical thromboprophylaxis and those who did not. Knowledge of these risk factors may be of value in improving the surgical outcome of patients with a malignancy of the lower limb.

Cite this article: Bone Joint J 2013;95-B:558–62.


The Bone & Joint Journal
Vol. 96-B, Issue 4 | Pages 479 - 485
1 Apr 2014
Pedersen AB Mehnert F Sorensen HT Emmeluth C Overgaard S Johnsen SP

We examined the risk of thrombotic and major bleeding events in patients undergoing total hip and knee replacement (THR and TKR) treated with thromboprophylaxis, using nationwide population-based databases. We identified 83 756 primary procedures performed between 1997 and 2011. The outcomes were symptomatic venous thromboembolism (VTE), myocardial infarction (MI), stroke, death and major bleeding requiring hospitalisation within 90 days of surgery.

A total of 1114 (1.3%) and 483 (0.6%) patients experienced VTE and bleeding, respectively. The annual risk of VTE varied between 0.9% and 1.6%, and of bleeding between 0.4% and 0.8%. The risk of VTE and bleeding was unchanged over a 15-year period. A total of 0.7% of patients died within 90 days, with a decrease from 1% in 1997 to 0.6% in 2011 (p < 0.001). A high level of comorbidity and general anaesthesia were strong risk factors for both VTE and bleeding, with no difference between THR and TKR patients. The risk of both MI and stroke was 0.5%, which remained unchanged during the study period.

In this cohort study of patients undergoing THR and TKR patients in routine clinical practice, approximately 3% experienced VTE, MI, stroke or bleeding. These risks did not decline during the 15-year study period, but the risk of dying fell substantially.

Cite this article: Bone Joint J 2014;96-B:479–85.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 11_Supple_A | Pages 3 - 7
1 Nov 2012
Barrack RL

Venous thromboembolism (VTE) remains an immediate threat to patients following total hip and knee replacement. While there is a strong consensus that steps should be taken to minimise the risk to patients by utilising some forms of prophylaxis for the vast majority of patients, the methods utilised have been extremely variable. Clinical practice guidelines (CPGs) have been published by various professional organisations for over 25 years to provide recommendations to standardise VTE prophylaxis. Historically, these recommendations have varied widely depending in underlying assumptions, goals, and methodology of the various groups. This effort has previously been exemplified by the American College of Chest Physicians (ACCP) and the American Academy of Orthopaedic Surgeons (AAOS). The former group of medical specialists targeted minimising venographically proven deep vein thrombosis (DVT) (the vast majority of which are asymptomatic) as their primary goal prior to 2012. The latter group of surgeons targeted minimising symptomatic VTE. As a result prior to 2012, the recommendations of the two groups were widely divergent. In the past year, both groups have reassessed the current literature with the principal goals of minimising symptomatic VTE events and bleeding complications. As a result, for the first time the CPGs of these two major subspecialty organisations are in close agreement.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 11_Supple_A | Pages 36 - 41
1 Nov 2012
Aderinto J Lulu OB Backstein DJ Safir O Gross AE

Eighteen hip fusions were converted to total hip replacements. A constrained acetabular liner was used in three hips. Mean follow up was five years (two to 15). Two (11%) hips failed, requiring revision surgery and two patients (11%) had injury to the peroneal nerve. Heterotopic ossification developed in seven (39%) hips, in one case resulting in joint ankylosis. No hips dislocated.

Conversion of hip fusion to hip replacement carries an increased risk of heterotopic ossification and neurological injury. We advise prophylaxis against heterotropic ossification. When there is concern about hip stability we suggest that the use of a constrained acetabular liner is considered. Despite the potential for complications, this procedure had a high success rate and was effective in restoring hip function.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 9 | Pages 1178 - 1182
1 Sep 2011
Davis AM Wood AM Keenan ACM Brenkel IJ Ballantyne JA

Studies describing the effect of body mass index (BMI) on the outcome of total hip replacement have been inconclusive and contradictory. We examined the effect of BMI on medium-term outcome in a cohort of 1617 patients who underwent a primary total hip replacement for osteoarthritis. These patients were followed prospectively for five years with the outcomes of dislocation, revision, duration of surgery and deep and superficial infection studied, as well as collecting Harris hip scores (HHS) and Short-Form 36 (SF-36) questionnaires pre-operatively and at review. A multivariate analysis was performed to see whether BMI is an independent predictor of poor outcome.

We found that patients with a BMI of ? 35 kg/m2 have a 4.42 times higher rate of dislocation than those with a BMI < 25 kg/m2. Increasing BMI is also associated with superficial infection and poorer HHS and SF-36 scores at five years. These trends remain significant even when multivariate analysis adjusts for age, gender, prosthesis, operating consultant, pre-operative HHS and SF-36, and comorbidities including diabetes mellitus, cardiac disease and osteoporosis.

Despite the increased risks, the five-year outcome scores indicate that obese patients have much to gain from total hip replacement. Thus total hip replacement should not be withheld from patients solely on the grounds of an elevated BMI. However, longer-term follow-up of this cohort is required to establish whether adverse outcomes become more evident with time.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 6 | Pages 807 - 810
1 Jun 2010
Sansone V Morandi A Dupplicato P Ungaro E

There are few reports of the surgical treatment for late stage Freiburg’s disease with flattening of the metatarsal head and osteoarthritis. We describe the results of the surgical treatment of ten consecutive patients with advanced stage Freiburg’s disease (Smillie’s stage V), using a technique that has not been published previously.