Orthopedics

Feature Article Supplemental Data

Denosumab for Bone Giant Cell Tumor of the Distal Radius

Shinji Tsukamoto, MD; Andreas F. Mavrogenis, MD; Piergiuseppe Tanzi, MD; Giulio Leone, MD; Giovanni Ciani, MD; Alberto Righi, MD; Manabu Akahane, MD; Kanya Honoki, MD; Yasuhito Tanaka, MD; Davide Maria Donati, MD; Costantino Errani, MD

Abstract

There are conflicting reports regarding the outcome and effect of denosumab for distal radius giant cell tumor of bone (GCTB). The authors performed this study to evaluate the behavior of distal radius GCTB in relation to the type of treatment and the administration of denosumab. The files of 72 patients with distal radius GCTB treated from 1984 to 2018 were reviewed. Fourteen patients were administered denosumab. Surgical treatment consisted of curettage (25 patients) or resection (47 patients) and allograft or vascularized fibular head graft reconstruction. Median follow-up was 63.1 months (interquartile range [IQR], 35.5–107.1 months). The authors evaluated local recurrences, metastasis, function, and complications. The local recurrence rate was 30.6% at a median of 14.0 months (IQR, 10–19 months), with no difference between curettage and resection. The local recurrence rate was significantly higher in the patients who received denosumab. The metastasis rate was 9.7% at a median of 41.0 months (IQR, 15–114 months), with no difference regarding denosumab administration. Function was significantly better in patients after curettage. The complication rate was 25%; vascularized fibular graft reconstruction was associated with fewer complications. This study found that denosumab increases the risk of local recurrence after curettage, function is better after curettage, and vascularized fibular graft is the optimal reconstruction after resection of distal radius GCTB. [Orthopedics. 2020;43(5):284–291.]

Abstract

There are conflicting reports regarding the outcome and effect of denosumab for distal radius giant cell tumor of bone (GCTB). The authors performed this study to evaluate the behavior of distal radius GCTB in relation to the type of treatment and the administration of denosumab. The files of 72 patients with distal radius GCTB treated from 1984 to 2018 were reviewed. Fourteen patients were administered denosumab. Surgical treatment consisted of curettage (25 patients) or resection (47 patients) and allograft or vascularized fibular head graft reconstruction. Median follow-up was 63.1 months (interquartile range [IQR], 35.5–107.1 months). The authors evaluated local recurrences, metastasis, function, and complications. The local recurrence rate was 30.6% at a median of 14.0 months (IQR, 10–19 months), with no difference between curettage and resection. The local recurrence rate was significantly higher in the patients who received denosumab. The metastasis rate was 9.7% at a median of 41.0 months (IQR, 15–114 months), with no difference regarding denosumab administration. Function was significantly better in patients after curettage. The complication rate was 25%; vascularized fibular graft reconstruction was associated with fewer complications. This study found that denosumab increases the risk of local recurrence after curettage, function is better after curettage, and vascularized fibular graft is the optimal reconstruction after resection of distal radius GCTB. [Orthopedics. 2020;43(5):284–291.]

Giant cell tumor of bone (GCTB) accounts for approximately 5% of all primary bone tumors.1 It commonly occurs in the mature skeleton and involves the epiphyseal part of the long bones.1 The distal radius is the third most common site for GCTB, after the distal femur and the proximal tibia.2,3 It is generally accepted that curettage is the appropriate treatment for Campanacci stages I and II GCTB of the distal radius,4–7 but the best treatment for stage III tumors is controversial.4,5,8–10 It seems that stage III tumors with extensive cortical destruction, a large soft tissue component, and joint involvement are better treated with resection5,10; compared with resection, curettage has been associated with a higher rate of local recurrence, better function, and fewer complications in stage III tumors.4–7,10

In the distal radius, there are several surgical procedures for wrist reconstruction after resection of GCTB, including wrist arthrodesis or arthroplasty with an allograft,11 a vascularized or nonvascularized fibular autograft, ulnar translocation, or a custom-made wrist prosthesis.12 However, none of these types of reconstruction has been shown to be superior to the others, and complication rates and function have varied significantly between reports.4,11,13–28 Additionally, many authors have identified the distal radius as being particularly prone to GCTB local recurrence after surgical treatment.4,7,8,21,29–33 Factors that might contribute to the high rate of local recurrence in this area include the anatomic geometry of the distal radius, the complexity of the distal radio-ulnar joint, and the paucity of surrounding muscles coupled with the close proximity of critical structures such as the median nerve, radial artery, and flexor and extensor tendons making complete tumor excision challenging.34

In 2013, the US Food and Drug Administration approved the use of denosumab, a monoclonal antibody that binds to the receptor activator of nuclear factor-kappa beta ligand, for the treatment of adults and skeletally mature adolescents with unresectable GCTB or when resection is likely to result in severe local morbidity.35 Previous clinical studies have suggested that denosumab is associated with tumor response and reduced surgical morbidity in GCTB patients.35–38 However, other studies have reported conflicting results—minimal inhibitory effect of denosumab on GCTB cells39–41 and increased risk for local recurrences by increasing the chances of neoplastic tissue being left behind in the thickened rim of perilesional new bone after curettage.42 Moreover, several cases of malignant transformation during denosumab therapy have been reported.43,44

To address these conflicting reports, the authors performed this study to evaluate the biological behavior of GCTB in the distal radius with respect to the type of treatment and denosumab administration. The primary goal was to study the effect of denosumab on local recurrence. The secondary goal was to evaluate function and complications after curettage and resection in these patients.

Materials and Methods

The authors retrospectively studied the files of 72 patients with histologically confirmed GCTB of the distal radius admitted to and treated at their institutions from 1984 to 2018. There were 36 men and 36 women with a median age of 36 years (interquartile range [IQR], 25.3–45.5 years). The authors staged the tumors on radiographs according to the Campanacci staging for GCTB8 and recorded pathological fractures (12 patients) and lung metastasis (1 patient) at presentation (Table 1). The median follow-up was 63.1 months (IQR, 35.5–107.1 months); no patient was lost to follow-up. All patients gave written informed consent for their data to be included in this study. Institutional review board/ethics committee approval is not necessary for retrospective studies at the authors’ institutions.

Patient Details

Table 1:

Patient Details

Fourteen patients admitted and treated from 2010 to 2018 with large tumors with soft tissue extension that seemed difficult to remove completely with curettage were administered denosumab as adjuvant. These were more commonly patients 30 years and older (P=.046) and patients who had curettage (P<.001). The median follow-up for the patients who were administered denosumab was 42.1 months (IQR, 30.9–63.4 months), compared with 83.7 months (IQR, 38.4–128.6 months) for the patients who were not administered denosumab. Preoperatively, denosumab was administered subcutaneously in a dose of 120 mg once a week for 1 month and then once a month for 3 to 9 months depending on the recommendation for discontinuation by the treating physician, the occurrence of an adverse event, the clinical benefit from treatment, the planning for surgery, and the clinical trial protocol (6 months).41 Surgical treatment was performed 1 month after the last dose of denosumab and included curettage in 12 patients and resection in 2 patients with wrist joint destruction.

Postoperatively, denosumab was administered in the same dose as preoperatively, once a month for 2 to 5 months depending on the recommendation for discontinuation by the treating physician, the occurrence of an adverse event, the absence of clinical benefit and/or evidence of disease progression, the patient’s decision to discontinue, and the clinical trial protocol (6 months).41 In addition to denosumab, patients received calcium (500 mg/d) and vitamin D (≥400 IU/d) supplements. The effect of denosumab was determined by comparing radiographs obtained before denosumab administration with those obtained immediately preoperatively. The GCTB response was evaluated with the modified inverse Choi criteria (density/size)45; 2 of the 14 patients administered denosumab experienced stable disease and 12 patients (85.7%) experienced a partial response. Adverse events and abnormalities in laboratory values were evaluated with the Common Terminology Criteria for Adverse Events version 4.0.46 Two patients experienced a grade III adverse event during denosumab treatment, including a periapical abscess and periodontal disease, and were unable to continue denosumab after surgery. No other patient experienced any denosumab-related complication, and no other denosumab-related complications or side effects were recorded.

Surgical treatment consisted of curettage (25 patients) or resection (47 patients). Curettage was done for GCTB with modest cortical thinning, well-maintained bony architecture, and simple pathological fracture. Curettage was done through a large cortical bone window using sharp curettes that enabled removal of all visible tumor tissue.47 The cavity was then curetted with a high-speed burr and washed with saline to remove all pathological tissue.47 The tumor cavity was then filled with bone allograft (8 patients), polymethylmethacrylate (PMMA) bone cement (14 patients), PMMA and bone allograft (1 patient), or hydroxyapatite graft to support the subchondral bone (2 patients). Resection was done for large tumors with soft tissue extension, pathological fractures with joint invasion, or a complex pattern.47 Reconstruction after resection was done according to the surgeon’s preference with a size-matched osteoarticular allograft biological arthroplasty of the wrist (23 patients) (Figure 1), allograft arthrodesis (17 patients), vascularized fibular head graft biological arthroplasty of the wrist (3 patients), or vascularized fibular graft arthrodesis (4 patients). Allograft arthrodesis was done by removing the cartilage of the lunate and scaphoid down to cancellous bone and fixing a size-matched allograft to the radius, lunate, and scaphoid using a volar locking plate (Figure 2). Vascularized fibular head graft arthroplasty was done with suturing of the remnant fibular collateral ligament to the radial collateral ligament of the wrist48; vascular anastomosis included the lateral inferior genicular artery to the proximal end of the distal radial artery stump, and the anterior tibial artery or peroneal artery to the distal end of the proximal radial artery stump (Figure 3).48 Vascularized fibular graft arthrodesis was done with interposition of the fibular graft between the capitate and the shaft of the radius, and vascular anastomosis as above (Figure 4).49 In all cases with vascularized fibular arthroplasty or arthrodesis, a peroneal flap was transferred with the fibula for coverage of the skin defects and monitoring of vascular circulation.49

Anteroposterior (A) and lateral (B) radiographs of the distal radius after resection and osteoarticular allograft arthroplasty.

Figure 1:

Anteroposterior (A) and lateral (B) radiographs of the distal radius after resection and osteoarticular allograft arthroplasty.

Anteroposterior (A) and lateral (B) radiographs of the distal radius after resection and allograft arthrodesis.

Figure 2:

Anteroposterior (A) and lateral (B) radiographs of the distal radius after resection and allograft arthrodesis.

Anteroposterior (A) and lateral (B) radiographs of the distal radius after resection and vascularized fibular head graft arthroplasty.

Figure 3:

Anteroposterior (A) and lateral (B) radiographs of the distal radius after resection and vascularized fibular head graft arthroplasty.

Anteroposterior (A) and lateral (B) radiographs of the distal radius after resection and vascularized fibular graft arthrodesis.

Figure 4:

Anteroposterior (A) and lateral (B) radiographs of the distal radius after resection and vascularized fibular graft arthrodesis.

Tumor specimens were histologically examined in all patients and re-reviewed for the purpose of this study. The GCTB diagnosis was confirmed in all patients (Figure A, available in the online version of the article). An admixture of neoplastic mononuclear cells and numerous evenly distributed osteoclast-type giant cells associated with hemosiderin deposits and focal reactive bone formation was observed on hematoxylin-eosin staining. After denosumab administration, histological sections of tumor specimens showed pronounced changes and remaining viable tumors in all patients (Figure B, available in the online version of the article). Osteoclast-like giant cells had disappeared, cellular areas characterized by sheets of round/ovoid tumor cells or spindle cells had formed in a storiform pattern with little or no extracellular matrix, and an abundant fibrillary extracellular matrix organized in trabecular structures or with increased honeycomb-pattern bone was observed in other areas.

Histological section of biopsy specimen shows an admixture of neoplastic mononuclear cells and numerous evenly distributed osteoclast-type giant cells associated with hemosiderin deposits and focal reactive bone formation (stain, hematoxylin and eosin; original magnification, 100x).

Figure A:

Histological section of biopsy specimen shows an admixture of neoplastic mononuclear cells and numerous evenly distributed osteoclast-type giant cells associated with hemosiderin deposits and focal reactive bone formation (stain, hematoxylin and eosin; original magnification, 100x).

Histological section of GCTB specimen after denosumab treatment shows residual tumor composed of bland-appearing spindle cells organized in short fascicles with a storiform pattern associated with collagen matrix production. This matrix appears either as thin bands or as thicker connected trabecular structures with a honeycomb appearance (stain, hematoxylin and eosin; original magnification, 100x).

Figure B:

Histological section of GCTB specimen after denosumab treatment shows residual tumor composed of bland-appearing spindle cells organized in short fascicles with a storiform pattern associated with collagen matrix production. This matrix appears either as thin bands or as thicker connected trabecular structures with a honeycomb appearance (stain, hematoxylin and eosin; original magnification, 100x).

Postoperatively, long arm cast immobilization for 4 weeks followed by short arm splint immobilization for another 4 weeks was instituted until bone union was observed on radiographs. The patients were followed every 4 months for the first 2 years, every 6 months for the next 3 years, and annually thereafter. Follow-up evaluation included clinical examination of function using the Musculoskeletal Tumor Society (MSTS) score50 and radiographs of the wrist (at every follow-up examination) and computed tomography (CT) scan of the chest (annually). The occurrence of local recurrence, lung metastases, and complications was recorded. Recurrence-free survival was defined as the interval between the first surgery and the manifestation of local recurrence discovered by radiographic imaging during follow-up. The chi-square test or Fisher’s exact test was used to evaluate the association between two variables, as appropriate. Recurrence-free survival was evaluated with the Kaplan–Meier survival analysis; survival curves were compared with a log-rank test. Multivariate predictors for local recurrence were determined with a Cox proportional hazards regression analysis. The difference between two independent samples was statistically analyzed using the Mann–Whitney U test for nonparametric analyses. All analyses were performed with SPSS version 22.0 (IBM, Armonk, New York) and JMP 14 (SAS Institute, Cary, North Carolina).

Results

Local Recurrence

Overall, local recurrences occurred in 22 patients (30.6%) at a median of 14.0 months (IQR, 10.5–19.0 months); local recurrence occurred in 11 patients (44%) who had curettage (median time to local recurrence, 14.0 months; IQR, 11.0–17.0 months) and in 11 patients (23.4%) who had resection (median time to local recurrence, 12.0 months; IQR, 8.0–22.0 months). There was no significant difference in local recurrence rate between curettage and resection (P=.071).

Local recurrence occurred in 10 patients (71.4%) who were administered denosumab (median time to local recurrence, 14.5 months; IQR, 11.8–17.5 months) and in 12 patients (20.7%) who were not administered denosumab (median time to local recurrence, 11.5 months; IQR, 8.3–21.3 months). The local recurrence rate was significantly higher in the patients who were administered denosumab (P=.001). Ten of the 12 patients treated with curettage and denosumab experienced a local recurrence, compared with none of the 2 patients treated with re-section and denosumab. Seven of the 10 patients who experienced a local recurrence after curettage and denosumab were treated with repeat curettage; 3 of these patients eventually had resection because of repeat local recurrences. Eleven of the 45 patients (24.4%) treated with resection alone experienced a local recurrence, compared with 1 of the 13 patients (7.7%) treated with curettage alone. The 11 patients who experienced local recurrence after resection had curettage of the recurrent tumor, re-resection of the remaining radius, and/or excision of a soft tissue recurrence. None of the patients treated with curettage alone eventually had resection.

Univariate analysis showed that denosumab administration had a significant negative association with recurrence-free survival (P<.001; Table A and Figure C, available in the online version of the article). A stepwise multivariable analysis that was conducted with all of the clinical variables showed that denosumab administration was the only independent prognostic factor for poor recurrence-free survival (hazard risk, 4,96; 95% confidence interval, 2.11–11.68; P<.001).

Univariate predictors for 5-year recurrence-free survival.

Table A.

Univariate predictors for 5-year recurrence-free survival.

A Kaplan-Meier curve shows the 5-year local recurrence-free survival of the patients with GCTB in the distal radius who were treated with and without denosumab administration was 23.6% (95% CI, 7.8–52.8) and 78.1% (95% CI, 65.1–87.2), respectively; local recurrence free survival was significantly better after surgery alone than surgery and denosumab.

Figure C:

A Kaplan-Meier curve shows the 5-year local recurrence-free survival of the patients with GCTB in the distal radius who were treated with and without denosumab administration was 23.6% (95% CI, 7.8–52.8) and 78.1% (95% CI, 65.1–87.2), respectively; local recurrence free survival was significantly better after surgery alone than surgery and denosumab.

Metastasis

Overall, metastases occurred in 7 patients (9.7%). Lung metastases occurred in 6 patients (8.3%), and a metachronous GCTB to the ilium occurred in 1 patient (1.4%). The median time to metastases was 41.0 months (IQR, 15.0–114.0 months). Metastasis occurred in 2 patients who were administered denosumab, compared with 5 patients who were not administered denosumab. There was no significant difference in metastasis rate between the patients who were administered denosumab and those who were not (P=.615). Both patients who experienced lung metastases after receiving denosumab were treated with observation alone and had stable lung disease at the last follow-up. Three patients with lung metastases were treated with open metastasectomy; 2 of these patients had part of their multiple lung metastases resected and since then, their remaining lung metastases have been stable on follow-up CT scans. Three patients with lung metastases were treated with observation alone because their lung metastases were stable. The patient with iliac metastasis was treated with curettage and had stable disease on follow-up CT scans. One patient with lung metastasis had no evidence of disease after treatment of the lung metastasis, 5 patients (1 patient who presented with lung metastasis and 4 patients who experienced lung metastases during treatment) were alive with lung metastases, and another patient died of another disease.

Function

Overall, the median MSTS score of the patients who had curettage was 93.3 points (IQR, 83.8–97.8 points) and the median MSTS score of those who had resection was 83.2 points (IQR, 80.0–90.0 points). The MSTS score was significantly better in the patients who had curettage (P=.032; Figure D, available in the online version of the article). The median MSTS score of the 22 patients who had curettage, the 21 patients who had osteoarticular allograft arthroplasty, the 22 patients who had allograft arthrodesis, the 3 patients who had vascularized fibular head graft arthroplasty, and the 4 patients who had vascularized fibular graft arthrodesis was 93.3 points (IQR, 83.8–97.8 points), 90.0 points (IQR, 78.3–93.3 points), 80.0 points (IQR, 78.3–90.0 points), 97.0 points (IQR, 83.0–100.0 points), and 80.0 points (IQR, 75.5–80.0 points), respectively.

The median MSTS score of the patients with GCTB in the distal radius who were treated with curettage and resection was 93.3 (IQR, 83.8 to 97.8) and 83.2 (IQR, 80.0 to 90.0), respectively; a Mann-Whitney U test showed that MSTS score was significantly better after curettage (p= 0.032).

Figure D:

The median MSTS score of the patients with GCTB in the distal radius who were treated with curettage and resection was 93.3 (IQR, 83.8 to 97.8) and 83.2 (IQR, 80.0 to 90.0), respectively; a Mann-Whitney U test showed that MSTS score was significantly better after curettage (p= 0.032).

Complications

Overall, surgical complications occurred in 18 patients (25%) (Table B, available in the online version of the article). Complication rates associated with curettage, resection and osteoarticular allograft arthroplasty, resection and allograft arthrodesis, resection and vascularized fibular graft arthroplasty, and resection and vascularized fibular graft arthrodesis were 4.0% (1 of 25 patients), 34.8% (8 of 23), 41.2% (7 of 17), 0% (0 of 3), and 50% (2 of 4), respectively. Two patients experienced denosumab-related complications (periapical abscess and periodontal disease) and discontinued denosumab after surgery.

Complications of the patients included in this series.

Table B.

Complications of the patients included in this series.

Discussion

This study of GCTB in the distal radius showed that denosumab administration increased the rate of local recurrence after curettage, similarly to GCTB in other locations.42 A major limitation of the current study was that the patients who received denosumab differed significantly from the patients who did not regarding age and type of surgery (curettage). Although multivariable analysis was used to correct the influence of confounding factors, it might not have been able to correct the influence of the major differences between the two groups. Additionally, the total number of patients and the number of events (local recurrences) were small for the multivariate analysis. Therefore, the current results should be considered with caution.

There have been conflicting reports regarding the effect of denosumab on local recurrence and surgical treatment of patients with GCTB.51–57 A systematic review found a positive clinical response (pain relief) and a decreased surgical morbidity for patients with GCTB who received denosumab, but without any effect on metastasis or local recurrence rates.51 Case reports52,54 and small series53 have reported variable results after denosumab administration for GCTB in the distal radius (Tables C and D, available in the online version of the article). Denosumab may be helpful for avoiding complex reconstructive procedures; a short course of denosumab may result in reconstitution of cortical and subarticular bone and sufficient marginal sclerosis to define the tumor margin while not causing marked intralesional sclerosis that increases the chances of neoplastic tissue being left behind in the thickened rim of perilesional new bone.53 In a relatively large series, denosumab was not found to be an important predictor of local recurrence-free survival57; however, the postoperative follow-up of the patients receiving denosumab was only a few years because of issues related to drug approval in the authors’ country.57 Although the newly formed bone induced by denosumab on the periphery of the lesion offers a mechanical scaffold against which curettage can be done, it may continue to harbor neoplastic cells that may reactivate once the microenvironment is free of denosumab and lead to recurrence.56 Although only rarely is the tumor volume reduced by denosumab,37 in a GCTB with a large soft tissue component in close proximity to neurovascular structures, the osseous rim that forms after denosumab is administered may help decrease the possibility of injury to the adjacent neurovascular structures and may prevent tumor contamination, provided resection is performed.37,58,59 In the current series and in the authors’ practice, denosumab is not administered as stand-alone therapy for GCTB patients. The current authors administer denosumab, when indicated,41,42 and opt for intralesional procedures (curettage) with caution to curette up to margins on pretreatment imaging owing to the potential residual tumor within the denosumab-mediated thick bony shell, which may lead to local recurrence.60 The current authors perform curettage or resection depending on the tumor involvement/destruction of the joint surfaces. If the joint surfaces are preserved, curettage is performed. If they are not, resection may be performed.

Summary of the important published studies on reconstruction with allograft or vascularized fibula graft after resection of GCTB of the distal radius.Summary of the important published studies on reconstruction with allograft or vascularized fibula graft after resection of GCTB of the distal radius.

Table C.

Summary of the important published studies on reconstruction with allograft or vascularized fibula graft after resection of GCTB of the distal radius.

Summary of the published studies on denosumab for GCTB in the distal radius.Summary of the published studies on denosumab for GCTB in the distal radius.

Table D.

Summary of the published studies on denosumab for GCTB in the distal radius.

As in the current study, curettage offers the best preservation of wrist function in patients with GCTB.4–7 In the case of local recurrence, the risk of resection seemed to be higher for patients treated with curettage and denosumab compared with those treated with curettage alone. It is possible that the administration of denosumab before curettage indirectly worsens the functional outcome by increasing the need for resection if local recurrence occurs. The related published studies on patients with GCTB of the distal radius have shown a higher complication rate with the use of osteoarticular allografts compared with vascularized fibular grafts with or without arthrodesis and similar function.4,11,13–28 Compared with arthroplasty, arthrodesis provided better grip strength and function.22,61 Complications such as graft fracture, nonunion, or joint degenerative changes occurred more frequently with allograft compared with vascularized fibular graft reconstructions. Disadvantages of vascularized fibular grafts include the technical difficulty and prolonged time for the surgical procedure and the donor site morbidity, including foot drop, the formation of painful neuromas, ankle instability,62 and ankle valgus deformity.14,19,48,49,62–65 However, because many patients who have a GCTB are young and active, vascularized fibular graft reconstruction can provide the best chances of fusion and long-term durability for reconstruction.

Conclusion

Denosumab increases the risk of local recurrence after curettage of GCTB in the distal radius. In the case of local recurrence after the administration of denosumab, the risk of resection seems to be higher compared with patients treated with curettage without denosumab. In contrast, denosumab facilitates resection and seems to reduce the risk of local recurrence after resection. Function is better after curettage, and vascularized fibular grafts are associated with fewer complications for reconstruction after re-section.

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Patient Details

VariableNo. of Patients (N=72)No.P

DenosumabNo Denosumab
Age, y
  <3027 (37.5%)2 (14.3%)25 (43.1%).046a
  ≥3045 (62.5%)12 (85.7%)33 (56.9%)
Sex
  Male36 (50.0%)7 (50.0%)29 (50.0%)1.000
  Female36 (50.0%)7 (50.0%)29 (50.0%)
Campanacci stage
  I2 (2.7%)0 (0%)2 (3.4%).744b,c
  II19 (26.4%)3 (21.4%)16 (27.6%)
  III51 (70.8%)11 (78.6%)40 (69.0%)
Pathological fracture at presentation
  Yes12 (16.7%)2 (14.3%)10 (17.2%)1.000b
  No60 (83.3%)12 (85.7%)48 (82.8%)
Previous surgery
  None64 (88.9%)12 (85.7%)52 (89.7%).674b
  18 (11.1%)2 (14.3%)6 (10.3%)
Current surgery
  Curettage without PMMA8 (11.1%)4 (28.6%)4 (6.9%)<.001a,b,d
  Curettage with PMMA17 (23.6%)8 (57.1%)9 (15.5%)
  Resection and osteoarticular allograft arthroplasty23 (31.9%)0 (0%)23 (39.7%)
  Resection and allograft arthrodesis17 (23.6%)2 (14.3%)15 (25.9%)
  Resection and vascularized fibular head graft arthroplasty3 (4.2%)0 (0%)3 (5.2%)
  Resection and vascularized fibular graft arthrodesis4 (5.6%)0 (0%)4 (6.9%)

Univariate predictors for 5-year recurrence-free survival.

VariablePatients (n= 72)5-year recurrence-free survival (95% CI)P-value
Age (years)
  <302773.5% (53.7–86.8)0.437
  ≥304563.9% (48.2–77.1)
Gender
  Male3662.5% (45.6–76.9)0.408
  Female3673.4% (56.0–85.6)
Campanacci stage
  I/II2181.0% (58.8–92.7)0.164
  III5162.2% (47.6–74.9)
Pathological fracture at presentation
  Yes1281.8% (49.3–95.4)0.241
  No6064.9% (51.6–76.2)
Previous surgery
  None6470.0% (57.2–80.3)0.191
  1850.0% (20.0–80.0)
Current surgery
  Curettage2554.3% (34.6–72.7)0.075
  Resection4775.0% (60.0–85.6)
Denosumab
  Yes1423.6% (7.8–52.8)<0.001*
  No5878.1% (65.1–87.2)

Complications of the patients included in this series.

ComplicationsCurettage (n= 25)Resection and osteoarticular allograft arthroplasty (n= 23)Resection and allograft arthrodesis (n=17)Resection and vascularized fibula head graft arthroplasty (n= 3)Resection and vascularized fibula graft arthrodesis (n= 4)Total (n= 21)
Fracture1a1b5c007
Non-union02d1d003
Subluxation03b0003
Painful joint03e0003
degeneration
Infection001001
Sensory deficits000011
Impairment of extensor tendons00001f1
Claw toe00001g1
Loosening of screws01h0001

Summary of the important published studies on reconstruction with allograft or vascularized fibula graft after resection of GCTB of the distal radius.

StudyPatients (n)Follow-up (months)ReconstructionLength of resection (cm)MSTS (%)Graft fractureNonunionUlnocarpal impactionPainful implantsImpairment of extensor tendonsUlnar synostosis
Kocher et al. [21]24Mean, 131Osteoarticular allograft arthroplastyNANA404420
Cheng et al. [4]4Mean, 60Osteoarticular allograft arthroplastyNANA000000
Harness et al. [18]15Mean, 168Osteoarticular allograft arthroplastyNANA323200
Bianchi et al. [11]12Median, 52Osteoarticular allograft arthroplastyMean, 7Mean, 92010000
Szabo et al. [26]9Mean, 100Osteoarticular allograft arthroplastyNANA100002
Asavamongkolkul et al. [13]8Mean, 53Osteoarticular allograft arthroplastyMean, 8NA120000
Scoccianti et al. [25]17Mean, 59Osteoarticular allograft arthroplastyMean, 7Mean, 86220000
Duan et al. [17]15Mean, 62Osteoarticular allograft arthroplastyMean, 8NA000000
Pho et al. [24]2Mean, 15Vascularized fibula graft arthrodesisNANA000000
Minami et al. [22]2Mean, 58Vascularized fibula graft arthrodesisNAMean, 87000000
Jaminet et al. [20]3Mean, 34Vascularized fibula graft arthrodesisMean, 7NA000000
Clarkson et al. [16]14NAVascularized fibula graft arthrodesisMean, 7Median,000110
Pho et al. [24]3Mean, 29Vascularized fibula head graft arthroplastyNANA000000
Bajec et al. [14]6NAVascularized fibula head graft arthroplasty8 to 12NA000000
Usui et al. [27]3Mean, 78Vascularized fibula head graft arthroplastyMean, 8.7Mean, 84110000
Ihara et al. [19]1120Vascularized fibula head graft arthroplasty1090000000
Minami et al. [22]2Mean, 174Vascularized fibula head graft arthroplastyNAMean, 47000000
Muramatsu et al. [23]1120Vascularized fibula head graft arthroplasty1090000000
Chung et al. [15]12Mean, 75Vascularized fibula head graft arthroplastyMean, 11Mean, 88000000
Yang et al. [28]17Mean, 52Vascularized fibula head graft arthroplastyMean, 6NA000000
Current study47Median, 63.1Osteoarticular allograft arthroplasty (23 patients), allograft arthrodesis (17 patients), vascularized fibula head graft arthroplasty (3 patients), vascularized fibula graft arthrodesis (4 patients)Median, 9Median, 83.2630110

Summary of the published studies on denosumab for GCTB in the distal radius.

StudyPatients (n)Campanacci gradeDenosumab (patients, regimen)Surgical treatmentFollow-up (months)Local recurrenceMetastasisComplicationsFunction
McCarthy et al.535II/III120 mg sc every 4 weeks with additional loading doses of 120 mg on days 8 and 15 of the first month; total time of medication, 3 months preoperativelyCurettage and cementationMean, 37; range, 17–541 patient (Campanacci grade III, 2 months after denosumab stop; treated with resection and vascularized free fibular graft reconstruction)NoNo serious denosumab-related adverse events No surgical complicationsMMWS increased to 85 points at 3 months
Park et al.541III120 mg sc weekly for 4 weeks, then monthly; total time of medication, 2.5 yearsNo (observation only)42NoNoTransient, asymptomatic hypophosphatemiaROM improved but lagged behind the contralateral (wrist extension, 85 degrees; wrist flexion, 80 degrees; supination, 50 degrees; pronation, 75 degrees)
Zou et al.5758I/II/III8 patients (Campanacci grade III); 120 mg sc on days 1, 8, 15, and 29 for the first month, then monthly, for 4–6 times preoperativelyCurettage (7 patients), resection (1 patient)Mean, 95.3; range, 21–3211 patientNoNo sever denosumab-related complications More surgical complications after resection (dislocation, subluxation of wrist joint, autograft fracture, non-union, infection)VAS pain score significantly improved pre- vs. post-denosuman treatment
Current study72II/III14 patients; 120 mg sc weekly for 1 month, then monthly for 3 to 9 months, preoperatively; 120 mg sc monthly for 2 to 5 months, postoperativelyCurettage with or without cementation (12 patients), resection and allograft arthrodesis (2 patients)Mean, 42.1 months; IQR, 30.9 to 63.4 months10 patients (treated with repeat curettage/resection)2 patientsPeriapical abscess and periodontal disease denosumab-related (2 patients) More surgical complications after resection (fracture, non-union, subluxation, painful joint degeneration, infection, sensory deficits, impairment of extensor tendons, claw toe, loosening of screws)MSTS score was significantly better in the patients who had curettage
Authors

The authors are from the Department of Orthopaedic Surgery (ST, KH, YT) and the Department of Public Health, Health Management and Policy (MA), Nara Medical University, Nara, Japan; the First Department of Orthopaedics (AFM), National and Kapodistrian University of Athens, School of Medicine, Athens, Greece; and the Department of Orthopaedic Oncology (PT, GC, DMD, CE) and the Department of Pathology (AR), Istituto Ortopedico Rizzoli, Bologna, and the Department of Orthopaedic Surgery (GL), San Gerardo Hospital, Monza, Italy.

The authors have no relevant financial relationships to disclose.

Correspondence should be addressed to: Andreas F. Mavrogenis, MD, First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, 41 Ventouri St 15562, Athens, Greece ( afm@otenet.gr).

Received: January 10, 2020
Accepted: April 07, 2020
Posted Online: August 06, 2020

10.3928/01477447-20200721-03

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