Giant cell tumor (GCT) of bone accounts for 20% of all musculoskeletal tumors in Chinese,1 and is well known for its locally aggressive behavior. It most commonly occurs in the metaphyseal-epiphyseal portion of the distal femur and proximal tibia. For treating GCT around the knee, the aim is to completely remove the tumor and restore complete function of the knee. Most studies have indicated that the functional outcome of the knee is worse in patients treated by tumor resection.2-4 Thus, the most attractive procedure for GCT has been extensive curettage with reconstruction.5,6 However, removal of the entire tumor while preserving the joint function can be very difficult to achieve, especially when there is extensive involvement of the subchondral bone. More aggressive curettage and a reduction in the proportion of subchondral bone can jeopardize the articular cartilage and result in secondary degenerative changes in the knee.
Previous research indicated that a reduction in the residual thickness of the subchondral bone was more often associated with secondary osteoarthritis.7 Others claimed a linear trend between a larger area of affected subchondral bone and a worse functional score. However, due to the limited cases, the exact statistical data are still lacking.
This study sought to determine the factors associated with the development of degenerative arthritis in surgically treated patients with GCTs around the knee. We hypothesized that bone grafting in the subchondral area might protect the articular cartilage and reduce degenerative changes in the knee.
Patients and procedures
We retrospectively reviewed 76 patients (40 male; 36 female) with GCT around the knee (39 in the distal femur; 37 in the proximal tibia) that underwent extensive curettage and reconstruction in our institution between February 2000 and November 2008. All patients were histologically confirmed and received the primary operation in our institution. The mean age at first diagnosis was 31.1 (13-65) years.
The surgical procedure of extensive curettage was identical, and performed by four experienced orthopedic oncology surgeons. First, a lateral or medial approach was chosen on the more-affected side. A large cortical window was made to access all possible existing tumors and to avoid having to curette under overhanging bone. The window was 10 mm larger than the tumor in the longitudinal direction, and approximately 1/4-1/5 of the perimeter in cross-section. Soft tissue layers over the destructed bony cortex (capsule) were removed at a thickness of 5 mm. Second, tumors were removed with curettes of various sizes. Third, the residual cavity was burred with a high-speed burr at least 10 mm into the normal cancellous bone or/and 1 mm into the normal cortical bone, except on the articular side where the subchondral bone was maintained at more than 10 mm thickness if healthy bone existed between the tumor and the subchondral bone. When it was less than 10 mm, the subchondral bone of the most-affected area only was removed until only cartilage remained. Finally, the entire curettage field was flushed with a flushing gun. After extensive curettage, bone cement (polymethylmethacrylate PMMA) was used to fill the cavity with or without bone grafts in the subchondral bony area, as decided by the surgeon. For both groups, postoperative functional exercises were the same.
Three experienced orthopedic oncology surgeons independently reviewed the medical records and radiographs. The residual thickness of the subchondral bone area (RT-SCB) was defined as the shortest distance between the articular surface and the tumor. It was measured on anteroposterior and lateral radiographs, and confirmed by CT or MRI images. The subchondral bone area was defined as affected when the thickness of RT-SCB was less than 10 mm. Degenerative arthritic changes were evaluated according to the grading system of osteoarthritis, developed by Aboulafia et al (Table 1).9 Most recent weight-bearing radiographs were used to evaluate the possible degenerative changes.
Patients were followed-up routinely. At each follow-up, an X-ray of the involved area was obtained. CT scans of the involved area were also employed when necessary. The median follow-up was 35 months, ranging from 18 to 113 months.
Statistical analysis was performed with SPSS software version 16.0 (SPSS Inc., Chicago, USA). Factors related to local recurrence or degenerative changes, including age, gender, tumor location, Campanacci grade, and RT-SCB were analyzed by Chi-square test. A P-value of less than 0.05 was considered as statistically significant.
Four of the 76 patients (5.3%) developed local recurrence. Two of the four patients developed recurrence in the soft tissue of the operative field and were successfully treated with soft tissue tumor resection. One patient developed recurrence in the contra-articular side of the distal femur, and received another extensive curettage and cement filling without further local recurrence. The fourth patient showed recurrence in the articular side of the proximal tibia and received tumor resection and massive allograft replacement with no further recurrence at the end of the follow-up. The durations between the recurrence and primary operation were 11, 22, 28, and 40 months, respectively. For this local recurrence, no significant differences were correlated with age, gender, tumor location, Campanacci grade, RT-SCB, or reconstruction method.
According to the radiographic osteoarthritis evaluation scale, all 76 patients were evaluated as grade 0 before surgery. However, 12 (52.2%) cases were evaluated as grade 1, 8 (34.8%) as grade 2, 2 (8.7%) as grade 3, and 1 (4.3%) as grade 4, postoperatively. The overall degenerative change rate in the knee joint at the final follow-up was 30.3% (23/76). Two (grades 3 and 4) out of 23 patients suffered severe pain and received additional surgical procedures. An additional 9 patients (8 of grade 2; 1 of grade 3) complained of mild pain around the knee when walking fast.
The mean RT-SCB of all patients was 7.8 mm, ranging from 1 to 23 mm. To further evaluate the correlation of RT-SCB and secondary osteoarthritis, patients were divided into two groups based on their RT-SCB: ≥10 mm and <10 mm group. The rate of secondary arthritis was 40.4% (23/57) in the <10 mm group, statistically higher than the >10 mm group (0%, 0/19). All osteoarthritic changes occurred in the <10 mm group (Figure 1). There were no significant differences among the other parameters correlated with osteoarthritic change (Table 2).
Given that bone grafting in the subchondral bone area might reduce the development of secondary osteoarthritis after extensive curettage-cementation, this factor was analyzed to correlate with osteoarthritis for patients in the <10 mm RT-SCB group. Degenerative arthritic changes occurred in 56.5% (13/23) of the patients with cementation, but without bone grafting. However, with bone grafting, the secondary osteoarthritis rate significantly dropped to 29.4% (10/34) (P=0.041) (Figure 2).
Curettage and cementation were introduced to treat GCT of bone around the knee in the last century,10 and have remained as the gold-standard. However, the adverse effect of extensive curettage and cementation on the knee joint and the value of bone grafting in the subchondral bone area remain to be determined. GCTs characteristically affect the subchondral bone and can extend into the articular cartilage. Cementation in the subchondral bone may help to eliminate residual tumor cells, facilitate the detection of recurrence, and enable rapid weight-bearing ambulation.11-13 However, this technique can result in degenerative osteoarthritis, and even fractures.
Secondary osteoarthritis as a surgical complication occurs in 33.3% of patients with GCT around the knee.7 usually present in the literature as case reports.6,14,15 Steyern et al16 found no evidence that the long-term presence of cement close to the knee joint was associated with the development of degenerative osteoarthritis. However, nine cases of local recurrence make this interpretation less persuasive, with 44.4% (4/9) requiring re-operation. In the current report, we found degenerative changes in 30% of patients, significantly higher than the reported incidence (0.87%) of primary osteoarthritis in healthy people aged 35 to 44 years in China.17 Our result was based on a large series of 76 cases, with all patients treated with the same technique in one institution. However, the degenerative changes observed were not serious, with half graded as 1. Nevertheless, secondary osteoarthritis after curettage and cementation should not be neglected. One limitation of this study was the lack of MRI assessment for the degenerative changes in the knee joint. However, MRI is unable to help with the early diagnosis of degenerative cartilage.16
The onset of arthritis is thought to be linked to the residual thickness of the subchondral bone7, with alterations to the subchondral bone occurring early in the osteoarthritic process.18 However, until now, this hypothesis was inconclusive. In the current research, we found that the residual thickness of the subchondral bone significantly affected the occurrence of arthritic changes in the knee joint. Patients with less RT-SCB were more likely to develop arthritis, with a cutoff of 10 mm, not 5 mm as reported by Suzuki et al.7 This difference was likely due to our surgical technique. When there was less than 10 mm between the tumor and the cartilage, the subchondral bone of the most-affected area was removed, leaving only cartilage. Thus, both the surgical technique and the tumor led to osteoarthritis. Fortunately, this technique also led to a low local recurrence rate of 5.3%, one of the lowest reported for a large series.1-3,12,19-20 From our standpoint, the local disease was well-controlled through this technique. Additionally, since re-operation due to recurrence was significantly correlated with secondary osteoarthritis, we endorse this surgical technique for the avoidance of local relapse.
Although it is commonly accepted that subchondral bone is reconstructed with autogenous bone graft or allograft between the articular cartilage and cement, the precise role of bone grafting in the prevention of arthritis is unclear.1-3,21 It has been assumed that bone grafting induces a shock absorbing effect in the early stages, postoperatively, and might undergo remodeling later. However, it has never been clinically confirmed with convincing data. In the current report, bone grafting in the subchondral bone area significantly reduced the occurrence of arthritic changes by nearly half (from 56.5% to 29.4%). Moreover, we observed remodeling of the bone graft to subchondral bone (Figure 2). Despite this improvement, some argue against the use of bone grafting to fill the entire cavity since it makes it difficult to distinguish between bone absorption and recurrence and itself is not a rapid stress-bearing reconstruction; furthermore, it could increase the local recurrence (without cementation heating). However, we believe that recurrence reflects incomplete tumor removal, rather than the chosen reconstructive method.
In summary, extensive curettage and cementation provides a favorable outcome for GCTs around the knee, and a low recurrence rate. Patients with reduced thickness of the residual subchondral bone are more likely to develop osteoarthritis after curettage. Thus, we recommend a 10 mm thickness of bone grafting in the subchondral bone area.
1. Niu X, Zhang Q, Hao L, Ding Y, Li Y, Xu H, et al. Giant cell tumor
of the extremity: retrospective analysis of 621 Chinese patients from one institution. J Bone Joint Surg Am 2012; 94: 461-467.
2. Errani C, Ruggieri P, Asenzio MA, Toscano A, Colangeli S, Rimondi E, et al. Giant cell tumor
of the extremity: A review of 349 cases from a single institution. Cancer Treat Rev 2010; 36: 1-7.
3. Campanacci M. Bone and soft tissue tumors: clinical features, imaging, pathology and treatment. 2nd ed. New York, NY: Springer; 1999.
4. Muscolo DL, Ayerza MA, Calabrese ME, Gruenberg M. The use of a bone allograft for reconstruction after resection of giant-cell tumor close to the knee
. J Bone Joint Surg Am 1993; 75: 1656-1662.
5. Vult von Steyern F, Bauer HC, Trovik C, Kivioja A, Bergh P, Holmberg Jörgensen P et al. Treatment of local recurrences of giant cell tumour in long bones after curettage and cementing. A Scandinavian Sarcoma Group study. J Bone Joint Surg Br 2006; 88: 531-535.
6. Bini SA, Gill K, Johnston JO. Giant cell tumor
of bone. Curettage and cement reconstruction. Clin Orthop Relat Res 1995; (321): 245-250.
7. Suzuki Y, Nishida Y, Yamada Y, Tsukushi S, Sugiura H, Nakashima H, et al. Re-operation results in osteoarthritic change of knee
joints in patients with giant cell tumor
of bone. Knee
2007; 14: 369-374.
8. Chen TH, Su YP, Chen WM. Giant cell tumors of the knee
: subchondral bone integrity affects the outcome. Int Orthop 2005; 29: 30-34.
9. Aboulafia AJ, Rosenbaum DH, Sicard-Rosenbaum L, Jelinek JS, Malawer MM. Treatment of large subchondral tumors of the knee
with cryosurgery and composite reconstruction. Clin Orthop Relat Res 1994; (307): 189-199.
10. Wouters HW. Giant cell tumor
of the distal end of the femur with intra-articular fracture of the knee
. Treatment by excochleation and filling with bone cement. Rev Chir Orthop Reparatrice Appar Mot 1974; 60(Suppl 2): 316.
11. Fraquet N, Faizon G, Rosset P, Phillipeau JM, Waast D, Gouin F. Long bones giant cells tumors: treatment by curretage and cavity filling cementation. Orthop Traumatol Surg Res 2009; 95: 402-406.
12. Balke M, Schremper L, Gebert C, Ahrens H, Streitbuerger A, Koehler G, et al. Giant cell tumor
of bone: treatment and outcome of 214 cases. J Cancer Res Clin Oncol 2008; 134: 969-978.
13. Algawahmed H, Turcotte R, Farrokhyar F, Ghert M. High-speed burring with and without the use of surgical adjuvants in the Intralesional Management of giant cell tumor
of bone: a systematic review and meta-analysis. Sarcoma 2010; 2010: pii: 586090.
14. Tejwani SG, Hame SL, Eckardt JJ. Subchondral giant-cell tumor of the proximal tibia: arthroscopic treatment for accelerated articular cartilage and meniscal degeneration in two patients. Arthroscopy 2004; 20: 644-649.
15. Campanacci M, Capanna R, Fabbri N, Bettelli G. Curettage of giant cell tumor
of bone. Reconstruction with subchondral grafts and cement. Chir Organi Mov 1990; 75 (1 Suppl): 212-213.
16. von Steyern FV, Kristiansson I, Jonsson K, Mannfolk P, Heinegård D, Rydholm A. Giant-cell tumour of the knee
: the condition of the cartilage after treatment by curettage and cementing. J Bone Joint Surg Br 2007; 89: 361-365.
17. Fransen M, Bridgett L, March L, Hoy D, Penserga E, Brooks P. The epidemiology of osteoarthritis in Asia. Int J Rheum Dis 2011; 14: 113-121.
18. Kwan Tat S, Lajeunesse D, Pelletier JP, Martel-Pelletier J. Targeting subchondral bone for treating osteoarthritis: what is the evidence? Best Pract Res Clin Rheumatol 2010; 24: 51-70.
19. Unni KK. Dahlin's Bone tumors: general aspects and data on 10,165 cases. Philadelphia, USA: Lippincott Williams & Wilkins; 2009
20. Kivioja AH, Blomqvist C, Hietaniemi K, Trovik C, Walloe A, Bauer HC, et al. Cement is recommended in intralesional surgery of giant cell tumors: a Scandinavian Sarcoma Group study of 294 patients followed for a median time of 5 years. Acta Orthop 2008; 79: 86-93.
21. Klenke FM, Wenger DE, Inwards CY, Rose PS, Sim FH. Giant Cell Tumor
of Bone: Risk Factors for Recurrence. Clin Orthop Relat Res 2010; (469): 591-599.
Keywords:© 2013 Chinese Medical Association
giant cell tumor; bone grafting; secondary osteoarthritis; knee