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The Bone & Joint Journal
Vol. 96-B, Issue 5 | Pages 673 - 676
1 May 2014
Han I Choi ES Kim H

Monostotic fibrous dysplasia of the proximal femur has a variable clinical course, despite its reported limited tendency to progress. We investigated the natural history and predisposing factors for progression of dysplasia in a group of 76 patients with a mean follow-up of 8.5 years (2.0 to 15.2). Of these, 31 (41%) presented with an asymptomatic incidental lesion while 45 (59%) presented with pain or a pathological fracture. A group of 23 patients (30%) underwent early operative treatment for pain (19: 25%) or pathological fracture (4: 5%). Of the 53 patients who were initially treated non-operatively, 45 (85%) remained asymptomatic but eight (15%) needed surgery because of pain or fracture. The progression-free survival of the observation group was 81% (. sd. 6.4%) at five-years follow-up. An initial presentation of pain (p < 0.001), a limp (p < 0.001), radiological evidence of microfracture (p = 0.001) and younger age (< 17 years) (p = 0.016) were significant predisposing factors for disease progression. The risk of experiencing pain or pathological fracture is considerable in monostotic fibrous dysplasia of the proximal femur. Patients presenting with pain, a limp or radiological evidence of microfracture have a high chance of needing surgical treatment. Cite this article: Bone Joint J 2014;96-B:673–6


The Bone & Joint Journal
Vol. 97-B, Issue 7 | Pages 1007 - 1011
1 Jul 2015
Kim H Im SB Han I

Deformity of the proximal femur in fibrous dysplasia leads to deviation of the mechanical axis of the hip, which may lead to the development of secondary osteoarthritis (OA). This study investigated the prevalence and predisposing factors for the development of OA in patients with fibrous dysplasia of the proximal femur. We reviewed the records of 209 patients from our institutional database with fibrous dysplasia of the proximal femur, investigating possible predisposing factors including patient demographics, the extent of the coxa vara deformity, the presence of peri-articular disease, and the overall burden of skeletal disease. Of the 209 patients, 24 (12%) had radiological evidence of OA in the ipsilateral hip. The prevalence was significantly higher in patients with polyostotic fibrous dysplasia compared with those with monostotic disease (p < 0.001). In a subgroup analysis of patients with polyostotic disease, the extent of deformity (quantified using the neck–shaft angle), and the presence of peri-articular disease (whether in the head of the femur or the acetabulum) were significant predictors of osteoarthritis (neck–shaft angle likelihood ratio (LR) = 0.847 per 1° increase, p = 0.004; presence of lesion in the head of the femur LR = 9.947, p = 0.027; presence of lesion in the acetabulum LR = 11.231, p = 0.014). . Our data suggest that patients with polyostotic fibrous dysplasia have a high risk of developing secondary OA of the hips. This risk is higher in patients with peri-articular disease, and those with a more severe deformity of proximal femur. Cite this article: Bone Joint J 2015;97-B:1007–11


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 99 - 106
1 Jan 2024
Khal AA Aiba H Righi A Gambarotti M Atherley O'Meally AO Manfrini M Donati DM Errani C

Aims

Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes.

Methods

We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder’s grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome.


Bone & Joint Research
Vol. 1, Issue 10 | Pages 272 - 280
1 Oct 2012
De Mattos CBR Binitie O Dormans JP

Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 5 | Pages 648 - 651
1 May 2008
George B Abudu A Grimer RJ Carter SR Tillman RM

We report our experience of treating 17 patients with benign lesions of the proximal femur with non-vascularised, autologous fibular strut grafts, without osteosynthesis. The mean age of the patients at presentation was 16.5 years (5 to 33) and they were followed up for a mean of 2.9 years (0.4 to 19.5). Histological diagnoses included simple bone cyst, fibrous dysplasia, aneurysmal bone cysts and giant cell tumour. Local recurrence occurred in two patients (11.7%) and superficial wound infection, chronic hip pain and deep venous thrombosis occurred in three. Pathological fracture did not occur in any patient following the procedure. We conclude that non-vascularised fibular strut grafts are a safe and satisfactory method of treating benign lesions of the proximal femur


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 8 | Pages 1077 - 1083
1 Aug 2007
Tsuchiya H Morsy AF Matsubara H Watanabe K Abdel-Wanis ME Tomita K

We present a retrospective study of patients suffering from a variety of benign tumours in whom external fixators were used to treat deformity and limb-length discrepancy, and for the reconstruction of bone defects. A total of 43 limbs in 31 patients (12 male and 19 female) with a mean age of 14 years (2 to 54) were treated. The diagnosis was Ollier’s disease in 12 limbs, fibrous dysplasia in 11, osteochondroma in eight, giant cell tumour in five, osteofibrous dysplasia in five and non-ossifying fibroma in two. The lesions were treated in the tibia in 19 limbs, in the femur in 16, and in the forearm in eight. The Ilizarov frame was used in 25 limbs, the Taylor Spatial Frame in seven, the Orthofix fixator in six, the Monotube in four and the Heidelberg fixator in one. The mean follow-up was 72 months (22 to 221). The mean external fixation period was 168 days (71 to 352). The mean external fixation index was 42 days/cm (22.2 to 102.0) in the 22 patients who required limb lengthening. The mean correction angle for those with angular deformity was 23° (7° to 45°). At final follow-up all patients had returned to normal activities. Four patients required a second operation for recurrent deformity of further limb lengthening. Local recurrence occurred in one patient, requiring further surgery


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 8 | Pages 1134 - 1137
1 Aug 2010
Kalson NS Gikas PD Aston W Miles J Blunn G Pollock R Skinner J Briggs TWR Cannon SR

Disarticulation of the hip in patients with high-grade tumours in the upper thigh results in significant morbidity. In patients with no disease of the proximal soft tissue a femoral stump may be preserved, leaving a fulcrum for movement and weight-bearing. We reviewed nine patients in whom the oncological decision would normally be to disarticulate, but who were treated by implantation of an endoprosthesis in order to create a functioning femoral stump. The surgery was undertaken for chondrosarcoma in four patients, pleomorphic sarcoma in three, osteosarcoma in one and fibrous dysplasia in one. At follow-up at a mean of 80 months (34 to 132), seven patients were alive and free from disease, one had died from lung metastases and another from a myocardial infarction. The mean functional outcome assessment was 50 (musculoskeletal tumor society), 50 and 60 (physical and mental Short-form 36 scores). Implantation of an endoprosthesis into the stump in carefully selected patients allows fitting of an above-knee prosthesis and improves wellbeing and the functional outcome


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXX | Pages 13 - 13
1 Jul 2012
Grimer R Carter S Tillman R Abudu A Jeys L
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Aim. To estimate the risk of bone malignancy arising in premalignant conditions. Methods. There are quite a number of possible premalignant conditions with considerable uncertainty about the actual risk of a bone sarcoma developing. The incidence of these malignant conditions was identified from a prospective database containing 3000 primary bone sarcomas. Results. 178 of the 3000 patients with newly diagnosed bone sarcomas had a pre-exiting condition which in all probability led to the sarcoma. These included 50 with previous radiotherapy treatment and 47 with Paget's disease. 31 patients developed malignancy in HME, 8 with neurofibromatosis and 7 each with Ollier's disease and retinoblastoma. There were 4 malignancies in patients with Mafucci's syndrome, 3 in patients with fibrous dysplasia, 3 in patients with synovial chondromatosis and 2 in patients with Rothmund-Thomson syndrome. Given that the incidence of bone sarcomas is 9/million population per year, our 3000 patients represent 333 million population years. When the incidence of a condition is known in the population this allows an estimation of the risk of malignancy compared with the normal population. Retinoblastoma for instance is known to arise in 1 in 16000 births. The 7 malignancies we saw thus represents a risk to individuals with retinoblastoma of 336/million/yr - a figure 37 times the risk of the normal population. Approximate figures of risk have been calculated for other entities. Conclusion. Data from a supra-regional register allows an approximate estimate of the increased risk of bone tumours in premalignant conditions


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XIV | Pages 59 - 59
1 Apr 2012
Picci P Sieberova G Alberghini M Vanel D Hogendoorn P Mercuri M
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Aim. To report late development of sarcomas on sites of previously curetted and grafted benign tumours. Rare cases of development of sarcomas in sites of previous benign lesions are documented, and the development is generally considered secondary to progression of benign lesions, even without radiotherapy. Methods and Results. In our files, 12 cases curetted and grafted, without radiotherapy addition developed sarcomas from 6 to 28 years from curettage (median 18). Age at first diagnosis (9 GCT, 1 benign fibrous histiocytoma, ABC and solitary bone cyst) ranged from 13 to 55 (median 30). For all cases radiographic and clinic documentation was available. Histology was available for 7 of the benign lesions and for all malignant lesions. The type of bone used to fill cavities was autoplastic in 4 cases, homoplastic in 2 cases, homoplastic and tricalciumphosphate/hydrossiapatite in 1 case, autoplastic and homoplastic in 1 cases, heteroplastic in 1 case. In 3 cases the origin was not reported. Secondary sarcomas, all high grade, were 8 OS, 3 MFH, and 1 fibrosarcoma. Conclusions. It is impossible to calculate the exact incidence of this transformation, but from a comparison with 137 secondary sarcomas treated in the same years (1975-2005) at the Rizzoli Institute, it is similar to the risk of a sarcoma on fibrous dysplasia or lower than a sarcoma on bone infarcts or on Paget's disease. Recurrence with progression from benign tumours can occur, but the very long intervals reported in the present series suggest a possible different pathogenesis. Recent preclinical papers report development of sarcoma in mice after transplantation of mesenchymal stem cells, independently from the type of scaffold used. The fact that reparative proliferative changes occuring in the area of dead bone, with stimulation of mesenchymal stem cells, could cause malignant transformation, is a new hypothesis


The Bone & Joint Journal
Vol. 102-B, Issue 1 | Pages 64 - 71
1 Jan 2020
Tsuda Y Fujiwara T Stevenson JD Parry MC Tillman R Abudu A

Aims

The purpose of this study was to report the long-term results of extendable endoprostheses of the humerus in children after the resection of a bone sarcoma.

Methods

A total of 35 consecutive patients treated with extendable endoprosthetic replacement of the humerus in children were included. There were 17 boys and 18 girls in the series with a median age at the time of initial surgery of nine years (interquartile range (IQR) 7 to 11).


The Bone & Joint Journal
Vol. 100-B, Issue 12 | Pages 1640 - 1646
1 Dec 2018
Medellin MR Fujiwara T Clark R Jeys LM

Aims

The aim of this study was to describe, analyze, and compare the survival, functional outcome, and complications of minimally invasive (MI) and non-invasive (NI) lengthening total femoral prostheses.

Patients and Methods

A total of 24 lengthening total femoral prostheses, 11 MI and 13 NI, were implanted between 1991 and 2016. The characteristics, complications, and functional results were recorded. There were ten female patients and ten male patients. Their mean age at the time of surgery was 11 years (2 to 41). The mean follow-up was 13.2 years (seven months to 29.25 years). A survival analysis was performed, and the failures were classified according to the Modified Henderson System.


The Bone & Joint Journal
Vol. 99-B, Issue 3 | Pages 409 - 416
1 Mar 2017
Scholfield DW Sadozai Z Ghali C Sumathi V Douis H Gaston L Grimer RJ Jeys L

Aims

The aim of this study was to identify any progression between benign osteofibrous dysplasia (OFD), OFD-like adamantinoma and malignant adamantinoma, and to investigate the rates of local recurrence, metastases and survival, in order to develop treatment algorithms for each.

Patients and Methods

A single institution retrospective review of all patients presenting with OFD, OFD-like adamantinoma and adamantinoma between 1973 and 2012 was undertaken. Complete data were available for 73 patients (42 with OFD; ten with an OFD-like adamantinoma and 21 with an adamantinoma). The mean follow-up was 10.3 years (3 to 25) for OFD, 9.2 years (3.0 to 26.3) for OFD-like and 11.6 years (0.25 to 33) for adamantinoma.


The Bone & Joint Journal
Vol. 97-B, Issue 1 | Pages 121 - 128
1 Jan 2015
Kang S Han I Hong SH Cho HS Kim W Kim H

Cancellous allograft bone chips are commonly used in the reconstruction of defects in bone after removal of benign tumours. We investigated the MRI features of grafted bone chips and their change over time, and compared them with those with recurrent tumour. We retrospectively reviewed 66 post-operative MRIs from 34 patients who had undergone curettage and grafting with cancellous bone chips to fill the defect after excision of a tumour. All grafts showed consistent features at least six months after grafting: homogeneous intermediate or low signal intensities with or without scattered hyperintense foci (speckled hyperintensities) on T1 images; high signal intensities with scattered hypointense foci (speckled hypointensities) on T2 images, and peripheral rim enhancement with or without central heterogeneous enhancements on enhanced images. Incorporation of the graft occurred from the periphery to the centre, and was completed within three years. Recurrent lesions consistently showed the same signal intensities as those of pre-operative MRIs of the primary lesions. There were four misdiagnoses, three of which were chondroid tumours.

We identified typical MRI features and clarified the incorporation process of grafted cancellous allograft bone chips. The most important characteristics of recurrent tumours were that they showed the same signal intensities as the primary tumours. It might sometimes be difficult to differentiate grafted cancellous allograft bone chips from a recurrent chondroid tumour.

Cite this article: Bone Joint J 2015;97-B:121–8.


The Bone & Joint Journal
Vol. 96-B, Issue 11 | Pages 1436 - 1440
1 Nov 2014
Henderson ER O’Connor MI Ruggieri P Windhager R Funovics PT Gibbons CL Guo W Hornicek FJ Temple HT Letson GD

Previous classification systems of failure of limb salvage focused primarily on endoprosthetic failures and lacked sufficient depth for the effective study of the causes of failure. In order to address these inadequacies, the International Society of Limb Salvage (ISOLS) formed a committee to recommend revisions of the previous systems. The purpose of this study was to report on their recommendations. The modifications were prepared using an earlier, evidence-based model with subclassification based on the existing medical literature. Subclassification for all five primary types of failure of limb salvage following endoprosthetic reconstruction were formulated and a complementary system was derived for the failure of biological reconstruction. An additional classification of failure in paediatric patients was also described.

Limb salvage surgery presents a complex array of potential mechanisms of failure, and a complete and precise classification of types of failure is required. Earlier classification systems lacked specificity, and the evidence-based system outlined here is designed to correct these weaknesses and to provide a means of reporting failures of limb salvage in order to allow the interpretation of outcome following reconstructive surgery.

Cite this article: Bone Joint J 2014;96-B:1436–40.


Bone & Joint Research
Vol. 4, Issue 9 | Pages 154 - 162
1 Sep 2015

Objective

Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours.

Methods

We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens.


The Bone & Joint Journal
Vol. 97-B, Issue 6 | Pages 853 - 861
1 Jun 2015
Hilven PH Bayliss L Cosker T Dijkstra PDS Jutte PC Lahoda LU Schaap GR Bramer JAM van Drunen GK Strackee SD van Vooren J Gibbons M Giele H van de Sande MAJ

Vascularised fibular grafts (VFGs ) are a valuable surgical technique in limb salvage after resection of a tumour. The primary objective of this multicentre study was to assess the risk factors for failure and complications for using a VFG after resection of a tumour.

The study involved 74 consecutive patients (45 men and 29 women with mean age of 23 years (1 to 64) from four tertiary centres for orthopaedic oncology who underwent reconstruction using a VFG after resection of a tumour between 1996 and 2011. There were 52 primary and 22 secondary reconstructions. The mean follow-up was 77 months (10 to 195).

In all, 69 patients (93%) had successful limb salvage; all of these united and 65 (88%) showed hypertrophy of the graft. The mean time to union differed between those involving the upper (28 weeks; 12 to 96) and lower limbs (44 weeks; 12 to 250). Fracture occurred in 11 (15%), and nonunion in 14 (19%) patients.

In 35 patients (47%) at least one complication arose, with a greater proportion in lower limb reconstructions, non-bridging osteosynthesis, and in children. These complications resulted in revision surgery in 26 patients (35%).

VFG is a successful and durable technique for reconstruction of a defect in bone after resection of a tumour, but is accompanied by a significant risk of complications, that often require revision surgery. Union was not markedly influenced by the need for chemo- or radiotherapy, but should not be expected during chemotherapy. Therefore, restricted weight-bearing within this period is advocated.

Cite this article: Bone Joint J 2015;97-B:853–61.


The Bone & Joint Journal
Vol. 96-B, Issue 4 | Pages 555 - 561
1 Apr 2014
Igarashi K Yamamoto N Shirai T Hayashi K Nishida H Kimura H Takeuchi A Tsuchiya H

In 1999, we developed a technique for biological reconstruction after excision of a bone tumour, which involved using autografts of the bone containing the tumour treated with liquid nitrogen. We have previously reported the use of this technique in 28 patients at a mean follow up of 27 months (10 to 54).

In this study, we included 72 patients who underwent reconstruction using this technique. A total of 33 patients died and three were lost to follow-up, at a mean of 23 months (2 to 56) post-operatively, leaving 36 patients available for a assessment at a mean of 101 months 16 to 163) post-operatively. The methods of reconstruction included an osteo-articular graft in 16, an intercalary in 13 and, a composite graft with prosthesis in seven.

Post-operative function was excellent in 26 patients (72.2%), good in seven (19.4%), and fair in three (8.3%) according to the functional evaluation system of Enneking. No recurrent tumour occurred within the grafts. The autografts survived in 29 patients (80.6%), and the rates of survival at five and ten years were 86.1% and 80.6 %, respectively. Seven of 16 osteo-articular grafts (44%) failed because of fracture or infection, but all the composite and intercalary grafts survived.

The long-term outcomes of frozen autografting, particularly using composite and intercalary grafts, are satisfactory and thus represent a good method of treatment for patients with a sarcoma of bone or soft tissue.

Cite this article: Bone Joint J 2014;96-B:555–61.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 7 | Pages 980 - 983
1 Jul 2011
Malhas AM Grimer RJ Abudu A Carter SR Tillman RM Jeys L

We investigated the eventual diagnosis in patients referred to a tertiary centre with a possible diagnosis of a primary bone malignancy.

We reviewed our database from between 1986 and 2010, during which time 5922 patients referred with a suspicious bone lesion had a confirmed diagnosis. This included bone sarcoma in 2205 patients (37%), benign bone tumour in 1309 (22%), orthopaedic conditions in 992 (17%), metastatic disease in 533 (9%), infection in 289 (5%) and haematological disease in 303 (5%). There was a similar frequency of all diagnoses at different ages except for metastatic disease. Only 0.6% of patients (17 of 2913) under the age of 35 years had metastatic disease compared with 17.1% (516 of 3009) of those over 35 years (p < 0.0001). Of the 17 patients under 35 years with metastatic disease, only four presented with an isolated lesion, had no past history of cancer and were systematically well.

Patients under the age of 35 years should have suitable focal imaging (plain radiography, CT or MRI) and simple systemic studies (blood tests and chest radiography). Reduction of the time to biopsy can be achieved by avoiding an unnecessary investigation for a primary tumour to rule out metastatic disease.


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 6 | Pages 838 - 845
1 Jun 2013
Oliveira VC van der Heijden L van der Geest ICM Campanacci DA Gibbons CLMH van de Sande MAJ Dijkstra PDS

Giant cell tumours (GCTs) of the small bones of the hands and feet are rare. Small case series have been published but there is no consensus about ideal treatment. We performed a systematic review, initially screening 775 titles, and included 12 papers comprising 91 patients with GCT of the small bones of the hands and feet. The rate of recurrence across these publications was found to be 72% (18 of 25) in those treated with isolated curettage, 13% (2 of 15) in those treated with curettage plus adjuvants, 15% (6 of 41) in those treated by resection and 10% (1 of 10) in those treated by amputation.

We then retrospectively analysed 30 patients treated for GCT of the small bones of the hands and feet between 1987 and 2010 in five specialised centres. The primary treatment was curettage in six, curettage with adjuvants (phenol or liquid nitrogen with or without polymethylmethacrylate (PMMA)) in 18 and resection in six. We evaluated the rate of complications and recurrence as well as the factors that influenced their functional outcome.

At a mean follow-up of 7.9 years (2 to 26) the rate of recurrence was 50% (n = 3) in those patients treated with isolated curettage, 22% (n = 4) in those treated with curettage plus adjuvants and 17% (n = 1) in those treated with resection (p = 0.404). The only complication was pain in one patient, which resolved after surgical removal of remnants of PMMA. We could not identify any individual factors associated with a higher rate of complications or recurrence. The mean post-operative Musculoskeletal Tumor Society scores were slightly higher after intra-lesional treatment including isolated curettage and curettage plus adjuvants (29 (20 to 30)) compared with resection (25 (15 to 30)) (p = 0.091). Repeated curettage with adjuvants eventually resulted in the cure for all patients and is therefore a reasonable treatment for both primary and recurrent GCT of the small bones of the hands and feet.

Cite this article: Bone Joint J 2013;95-B:838–45.