The Open Orthopaedics Journal




ISSN: 1874-3250 ― Volume 13, 2019

Tartrate-Resistant Acid Phosphatase 5b is a Useful Serum Marker for Diagnosis and Recurrence Detection of Giant Cell Tumor of Bone



Tetsuya Shinozaki*, Kenichi Saito, Tsutomu Kobayashi, Takashi Yanagawa, Kenji Takagishi
Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, Japan

Abstract

Serum tartrate-resistant acid phosphatase (TRACP) 5b was investigated for use as a marker for diagnosis of giant cell tumor (GCT) of bone and for detection of its recurrence.

Four patients with GCT of bone who were initially referred to our hospital were classified as a primary group. Three patients who had local recurrence following curettage were classified as a local recurrence group. Five with no recurrence were classified as a no-recurrence group. Eighteen patients with primary and metastatic malignant bone tumors were also enrolled in the study as a control group. Serum TRACP 5b was measured before the biopsy in all patients and was measured periodically after the operation in patients with GCT of bone. Student t-tests were used for statistical analyses.

TRACP 5b was greater than 1500 Um/dL in all primary group patients. Mean TRACP 5b values decreased gradually with post-operative time, showing lower values until local recurrence. The mean value of TRACP 5b of the local recurrence group (753 ± 68.7 mU/dL) was significantly higher than that of the no-recurrence group (340.6 ± 78.3 mU/dL). The mean value of TRACP 5b of the control group (466.9 ± 130.3 mU/dL) was much lower than that of the primary group and markedly lower than that of the local recurrence group. However, no significant difference was found between the no-recurrence group and the control group.

Serum TRACP 5b is a useful and convenient marker for diagnosing GCT of bone and for predicting its recurrence.

Keywords:: acid phosphatase, diagnosis, giant cell tumor, serum marker, TRACP 5b.


Article Information


Identifiers and Pagination:

Year: 2012
Volume: 6
First Page: 392
Last Page: 399
Publisher Id: TOORTHJ-6-392
DOI: 10.2174/1874325001206010392

Article History:

Received Date: 19/3/2012
Revision Received Date: 25/7/2012
Acceptance Date: 6/8/2012
Electronic publication date: 3/9/2012
Collection year: 2012

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© Shinozaki et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.


* Address correspondence to this author at the Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma 371-8511, Japan; Tel.: 81-27-220-7111, Ext. 8261; Fax: 81-27-220-8275; E-mail: tshinoza@showa.gunma-u.ac.jp





INTRODUCTION

Giant-cell tumor (GCT) of bone is an extremely common primary bone tumor that occurs mostly at the epiphyseal region of long bones in patients at the age of 20-40 years [1 Mirra JM, Picci P, Gold RH, Eds. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger 1989; pp. 942-92.]. Although radiological modalities such as plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI) are used for its diagnosis, histological analysis must be conducted for a definite diagnosis [1 Mirra JM, Picci P, Gold RH, Eds. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger 1989; pp. 942-92., 2 Zhen W, Yaotian H, Songjian L, Qingliang LGeW. Giant-cell tumour of bone: The long term results of treatment by curettage and bone graft J Bone Joint Surg 2004; 86-B(2): 212-6.]. Curettage is the most popular treatment of the tumor [1 Mirra JM, Picci P, Gold RH, Eds. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger 1989; pp. 942-92.-5 Klenke FM, Wenger DE, Inwards CY, Rose PS, Sim FH. Recurrent giant cell tumor of long bones. Analysis of surgical management Clin Orthop Relat Res 2011; 469(4): 1181-7.]. However, local recurrence following curettage is reported [1 Mirra JM, Picci P, Gold RH, Eds. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger 1989; pp. 942-92., 6 Takeuchi A, Tsuchiya H, Niu X, et al. The prognostic factors of recurrent GCT: a cooperative study by Eastern Asian Musculoskeletal Oncology Group J Orthop Sci 2011; 16: 196-202.]. Furthermore, earlier detection of local recurrence by careful follow-up is important before an opportunity for successful re-curettage is lost [6 Takeuchi A, Tsuchiya H, Niu X, et al. The prognostic factors of recurrent GCT: a cooperative study by Eastern Asian Musculoskeletal Oncology Group J Orthop Sci 2011; 16: 196-202.]. Multinucleated cells of giant cell tumors contain acid phosphatase of a specific secretory type [7 McCarthy EF, Serrano JA, Wasserkrug HL, Dorfman HD. The ultrastructural localization of secretory acid phosphatase in giant cell tumor of bone Clin Orthop 1979; 141: 295-302.]. Serum acid phosphatase values have been used for diagnosis and for evaluation of the efficacy of treatment for GCT of bone [8 Goto T, Iijima T, Kawano H, et al. Serum acid phosphatase as a tumour marker in giant cell tumour of bone Arch Orthop Trauma Surg 2001; 121: 411-3.-10 Akahane T, Isobe K, Shimizu T. Serum total acid phosphatase for monitoring the clinical course of giant cell tumors of bone-26 patients with 5 local recurrences Acta Orthop 2005; 76(5): 651-3.].

Acid phosphatases are discriminated by tartrate, which is the most effective inhibitor of prostatic acid phosphatase. Cells of monocyte origin, including macrophages, dendritic cells, and osteoclasts, express abundant tartrate-resistant acid phosphatase (TRACP) in mammals [11 Janckila AJ, Yam LT. Biology and clinical significance of tartrate-resistant acid phosphatases: new perspective on an old enzyme Calcif Tissue Int 2009; 85: 465-83.]. Apparently, osteoclasts mostly express type 5b of TRACP in the serum. Osteoclasts secrete TRACP 5b, implying that serum TRACP 5b has unique specificity as a marker of osteoclast activity, and that it is therefore a useful marker of bone resorption [11 Janckila AJ, Yam LT. Biology and clinical significance of tartrate-resistant acid phosphatases: new perspective on an old enzyme Calcif Tissue Int 2009; 85: 465-83., 12 Halleen JM, Yipahkala H, Alatalo SL, et al. Serum tartrate-resistant acid phosphatase 5b, but not 5a, correlates with other markers of bone turnover and bone mineral density Calcif Tissue Int 2002; 71: 20-5.]. Based on those facts, serum TRACP 5b has been used clinically as a serum marker for diagnosing osteoporosis. Recently, serum TRACP 5b has been used clinically as a specific and sensitive marker of bone resorption for the diagnosis of cancer patients with bone metastasis [11 Janckila AJ, Yam LT. Biology and clinical significance of tartrate-resistant acid phosphatases: new perspective on an old enzyme Calcif Tissue Int 2009; 85: 465-83., 13 Kamiya N, Suzuki H, Yano M, et al. Implications of serum bone turnover markers in prostate cancer patients with bone metastasis Oncology 2010; 75: 1446-51., 14 Tauchert S, di Liberto A, Cordes T, et al. Tartrate-resistant acid phosphatase (TRAP) as a serum marker for bone resorption in breast cancer patients with bone metastases Clin Exp Obstet Gynecol 2009; 36(4): 219-5.], for the evaluation of the aggressiveness of osteosarcoma [15 Avnet S, Longhi A, Salerno M, et al. Increased osteoclast activity is associated with aggressiveness of osteosarcoma Int J Oncol 2008; 33: 1231-8.], and as a marker of late loosening of total hip arthroplasty [16 Savarino L, Avnet S, Greco M, Giunti A, Baldini N. Potential role of tartrate-resistant acid phosphatase 5b (TRACP 5b) as a surrogate marker of late loosening in patients with total hip arthroplasty: a cohort study J Orthop Res 2010; 28: 887-92.]. Histologically, GCT of bone consists of uniform mononuclear cells, with osteoclast-like giant cells scattered among them [1 Mirra JM, Picci P, Gold RH, Eds. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger 1989; pp. 942-92., 17 Broadhead ML, Clark JC, Dass CR, Choong PF, Myers DE. Therapeutic targeting of osteoclast function and pathways Expert Opin Ther Targets 2011; 15(2): 169-81.]. These facts suggest that serum TRACP 5b values have some relation to GCT of bone. This study was undertaken to investigate the usefulness of serum TRACP 5b as a specific marker for both the diagnosis and recurrence of GCT of bone.

MATERIALS AND METHODS

The Institutional Ethics Committee on human research of the university approved the study design. All patients who were referred to our clinic presenting the osteolytic lesion and who had been diagnosed with histologically confirmed GCT of bone during March 2009 - April 2011 were enrolled in this study. Blood chemistry data, including those for TRACP 5b, were obtained before operation. After the operative treatment, serum TRACP 5b was followed by plain radiography, computed tomography (CT), and MR imaging to assess the respective probabilities of local recurrence and pulmonary metastases. For cases in which local recurrence was suspected from radiological findings, serum TRACP 5b was measured following operative treatment.

As a primary group, four patients were referred initially to our hospital for bone tumor treatment. They were subsequently diagnosed as having GCT of bone based on histology of the needle biopsy. The one man and three women had mean age of 43 years (21-74) at the time of enrollment (Table 1). Of these four GCT of bone cases, two were located in the distal femur, one in the proximal tibia, and one in the distal radius. No pulmonary metastasis was observed in any patient. Three patients underwent curettage without bone graft. One underwent wide resection.

Table 1

Clinical Characteristics of GCT of Bone Patients




Patients with GCT of bone who underwent curettage without bone graft at our hospital before March 2009 and who were referred to our clinic for follow-up during that period were also enrolled in the study as a local recurrence group (Table 1). No pulmonary metastasis was observed in the patients. Three women with mean age of 43 years (36-52) had local recurrence. Of these cases of local recurrence, two were in the proximal tibia and one in the distal radius.

Three men and two women with GCT of bone who underwent operative treatment at our hospital before March 2009 without local recurrence or pulmonary metastasis were enrolled in the study as a no-recurrence group (Table 1). Their mean age was 40 years (25-67). Of their primary lesions, two were in the distal femur, two in the proximal humerus, and one in the ischial tuberosity. Of the four GCT of bone, curettage without bone graft was performed in addition to one wide resection for the operative treatment. The mean follow-up period after the operation was 5 yr and 2 mo (3 yr, 4 mo - 9 yr, 5 mo).

The control group comprised patients who had been referred to our clinic presenting osteolytic lesions and for whom a histological diagnosis other than GCT of bone or chondroblastoma had been made (Table 2). These 8 men and 10 women had mean age of 62 years (32-79). Histological diagnoses were nine of primary and nine of metastatic malignant bone tumors. TRACP 5b was determined using commercial enzyme immunoassay (fragments absorbed immunocapture enzymatic assay, Osteolinks; DS Pharma Biochemical Co. Ltd.). Patients who had received bisphosphonates, selective estrogen receptor modulators (SERMs), or calcitonin therapy were excluded from the study. Patients who had undergone a fracture before operation or who showed hormonal abnormality were also excluded from the study. Student t-tests were used to compare the values of serum TRACP 5b, inferring p < 0.05 as significant.

Table 2

Clinical Characteristics of the Control Patients




RESULTS

TRACP 5b showed more than 1500 Um/dL with no relation to the tumor location or the size of osteolytic lesion in any patient of the primary group (Table 1). Mean TRACP 5b values decreased gradually at one week (783.8 ± 225.8, 526-1050 mU/dL) and at one month (501.3 ± 169.8, 274-760 mU/dL) after the operation and exhibited low values until local recurrence (Fig. 1). The TRACP 5b value increased gradually with development of local recurrence in a patient.

Fig. (1)

TRACP 5b values in the primary group. Each case number is the same as that shown in Table 1. TRACP 5b was measured immediately before the biopsy. The TRACP 5b value of case 1 increased gradually during 9 months after the curettage, implying local recurrence. However, the TRACP 5b value decreased dramatically after re-curettage. Case 3 showed a pathological fracture during curettage following bone union with no complication. Preop: before curettage.



Plain radiography also demonstrated that the progression of the osteolytic change and the lesion was enhanced extremely by Gd in MRI (Fig. 2). TRACP 5b decreased again immediately in the patient after a week of curettage (Fig. 1). The mean value of TRACP 5b of the local recurrence group was 753 ± 68.7 (656-856 mU/dL; Table 1).

Fig. (2)

Radiographic findings for case 1. This preoperative plain radiograph shows the osteolytic lesion at the proximal tibia (A, white arrow). Bone formation is apparent at 8 months after curettage (B, white arrow). However, osteolytic change had progressed at 16 months after the curettage. A plain radiograph shows osteolytic lesions at 20 months after curettage (C, white arrow). The osteolytic lesion was enhanced extremely by Gd in MRI simultaneously (D, white arrow).



The time between the operation and the local recurrence did not affect the TRACP 5b value. However, TRACP 5b values increased gradually with the progression of local recurrence (Fig. 3). The osteolytic change also developed gradually on plain radiographs, as shown by case 5 (Fig. 4). In the no-recurrence group, the mean value of TRACP 5b was 340.6 ± 78.3 (168-493 mU/dL; Table 1).

Fig. (3)

TRACP 5b values in the patient with local recurrence (case 5). When TRACP 5b was measured initially at 73 months after curettage, local recurrence was suspected from both clinical and MRI findings. The patient refused re-curettage for personal reasons. TRACP 5b values increased gradually thereafter.



Fig. (4)

Plain radiographic findings for case 5. Plain radiography shows progressive osteolytic lesions (73 months (A) and 96 months (B) after curettage, arrows).



Statistically significant differences were found between the no-recurrence group and the local recurrence group (Fig. 5, p = 0.0017). Neither the follow-up period nor patient age showed any effect on the TRACP 5b value. The mean value of TRACP 5b of the control group was 466.9 ± 130.3 (158-995 mU/dL; Table 2). Little relation was observed between the TRACP 5b value and patient age. The mean value of the control group was much lower than that of the primary group. Moreover, it was significantly lower than that of the local recurrence group (Fig. 5, p = 0.006). However, no significant difference was found between the no-recurrence group and the control group (Fig. 5, p = 0.094).

Fig. (5)

Values of TRACP 5b in each group. Statistically significant differences were found between the no-recurrence group and the local recurrence group (*: p = 0.0017). Values of local recurrence were significantly higher than those of the control group (**: p = 0.006). However, no significant difference was found between the no-recurrence group and the control group (p = 0.094).



DISCUSSION

Although GCT of bone is locally aggressive, curettage is the most popular operative treatment for preserving the adjacent joint. Of all GCT of bone cases, 10-50% show recurrence following curettage [1 Mirra JM, Picci P, Gold RH, Eds. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger 1989; pp. 942-92., 2 Zhen W, Yaotian H, Songjian L, Qingliang LGeW. Giant-cell tumour of bone: The long term results of treatment by curettage and bone graft J Bone Joint Surg 2004; 86-B(2): 212-6., 4 Klenke FM, Wenger DE, Inwards CY, Rose PS, Sim FH. Giant cell tumor of bone. Risk factors for recurrence Clin Orthop Relat Res 2011; 469(2): 591-9.-6 Takeuchi A, Tsuchiya H, Niu X, et al. The prognostic factors of recurrent GCT: a cooperative study by Eastern Asian Musculoskeletal Oncology Group J Orthop Sci 2011; 16: 196-202., 18 Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone J Bone Joint Surg Am 1987; 69(1): 106-4.]. Some cases have multiple local recurrences. Repeat recurrence correlates with lung metastasis [6 Takeuchi A, Tsuchiya H, Niu X, et al. The prognostic factors of recurrent GCT: a cooperative study by Eastern Asian Musculoskeletal Oncology Group J Orthop Sci 2011; 16: 196-202.]. Histological grading described by Campanacci et al. [18 Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone J Bone Joint Surg Am 1987; 69(1): 106-4.] has been used for its prognosis [2 Zhen W, Yaotian H, Songjian L, Qingliang LGeW. Giant-cell tumour of bone: The long term results of treatment by curettage and bone graft J Bone Joint Surg 2004; 86-B(2): 212-6.], although histological grading does not correlate with local recurrence [6 Takeuchi A, Tsuchiya H, Niu X, et al. The prognostic factors of recurrent GCT: a cooperative study by Eastern Asian Musculoskeletal Oncology Group J Orthop Sci 2011; 16: 196-202., 19 Sulh MA, Greco MA, Jiang T, et al. Proliferation index and vascular density of giant cell tumors of bone: are they prognostic markers? Cancer 1996; 77(10): 2044-51.]. To predict local recurrence, DMA cytometry [20 Sun D, Biesterfeld S, Adler CP, Böcking A. Prediction of recurrence in giant cell bone tumors by DNA cytometry Anal Quant Cytol Histol 1992; 14(4): 341-5.], gene [21 Pazzaglia L, Conti A, Chiechi A, et al. Differential gene expression in classic giant cell tumours of bone: Tenascin C as biological risk factor for local relapses and metastases Histopathology 2010; 57: 59-72.], and protein [22 Conti A, Rodrigues GC, Chiechi A, et al. Identification of potential biomarkers for giant cell tumor of bone using comparative proteomics analysis Am J Pathol 2010; 178(1): 88-97.] analyses of the tumor are useful in addition to contrast-enhanced dynamic MRI [23 Libicher M, Bernd L, Schenk JP, et al. Characteristic perfusion pattern of osseous giant cell tumor in dynamic contrast-enhanced MRI Radiology 2001; 41(7): 577-82., 24 Waldman BJ, Zerhouni EA, Frassica FJ. Recurrence of giant cell tumor of bone: The role of MRI in diagnosis Orthopedics 1997; 20(1): 67-9.], but an important problem is that the genetic and biochemical methodologies used to detect those markers are complicated. Moreover, local recurrence is missed by MRI when no appropriate range of interest (ROI) is selected [23 Libicher M, Bernd L, Schenk JP, et al. Characteristic perfusion pattern of osseous giant cell tumor in dynamic contrast-enhanced MRI Radiology 2001; 41(7): 577-82.]. A new marker that can yield results easily is necessary to diagnose and to predict the local recurrence of GCT of bone. Serum total acid phosphatase was useful for the diagnosis and the detection of local recurrence [8 Goto T, Iijima T, Kawano H, et al. Serum acid phosphatase as a tumour marker in giant cell tumour of bone Arch Orthop Trauma Surg 2001; 121: 411-3.-10 Akahane T, Isobe K, Shimizu T. Serum total acid phosphatase for monitoring the clinical course of giant cell tumors of bone-26 patients with 5 local recurrences Acta Orthop 2005; 76(5): 651-3.]. However, it contains secretory acid phosphatase of various types including that from the osteoclasts [11 Janckila AJ, Yam LT. Biology and clinical significance of tartrate-resistant acid phosphatases: new perspective on an old enzyme Calcif Tissue Int 2009; 85: 465-83.]. Recently, serum TRACP 5b, a sensitive marker of bone resorption, was detected as secreted from osteoclasts [11 Janckila AJ, Yam LT. Biology and clinical significance of tartrate-resistant acid phosphatases: new perspective on an old enzyme Calcif Tissue Int 2009; 85: 465-83., 25 Halleen JM, Alatalo SL, Janckila AJ, et al. Serum tartrate-resistant acid phosphatase 5b is a specific and sensitive marker of bone resorption Clin Chem 2001; 47(3): 597-600.]. Osteoclast-like giant cells are prominent among the histological features of GCT of bone [1 Mirra JM, Picci P, Gold RH, Eds. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger 1989; pp. 942-92.]. Based on these facts, serum TRACP 5b became a specific marker for GCT of bone, measured in patients with GCT of bone and other bone tumors presenting osteolytic lesions.

Serum TRACP 5b has been used for bone quality evaluation in patients with osteoporosis (normal range 170-590 mU/dL for men, 120-420 mU/dL for women). A commercial enzyme immunoassay kit for serum TRACP 5b was not applied initially to measure extremely high values such as 1500 mU/dL in patients with GCT of bone because the kit is used exclusively for measurement of serum TRACP 5b in patients with osteoporosis. However, more precise results have become obtainable recently. Serum TRACP 5b is present at much higher concentrations in patients with GCT of bone than in patients with local recurrence or some other bone tumor such as a primary malignant tumor and metastases. Statistical analyses were not performed because of the lack of precise values in the primary group. The apparent difference between the primary group and the other groups was found to be clinically significant. Neither tumor size, skeletal distribution of the tumor, nor patient age affected the serum TRACP 5b level. Similar results were obtained for the control group. Furthermore, serum TRACP 5b decreased dramatically at one week after curettage and remained at a similar level when no local recurrence was observed.

In these patients, plain radiography showed bone formation of the cured lesion. Little enhancement effect was observed in contrast-enhanced MRI. However, its level increased gradually with the progression of local recurrence. Plain radiography showed that osteolytic lesions developed gradually. Local enhancement became readily apparent in MRI compared to images obtained from cases without local recurrence [24 Waldman BJ, Zerhouni EA, Frassica FJ. Recurrence of giant cell tumor of bone: The role of MRI in diagnosis Orthopedics 1997; 20(1): 67-9.]. Compared to radiological [24 Waldman BJ, Zerhouni EA, Frassica FJ. Recurrence of giant cell tumor of bone: The role of MRI in diagnosis Orthopedics 1997; 20(1): 67-9.] or biomolecular [20 Sun D, Biesterfeld S, Adler CP, Böcking A. Prediction of recurrence in giant cell bone tumors by DNA cytometry Anal Quant Cytol Histol 1992; 14(4): 341-5.-22 Conti A, Rodrigues GC, Chiechi A, et al. Identification of potential biomarkers for giant cell tumor of bone using comparative proteomics analysis Am J Pathol 2010; 178(1): 88-97.] methods, serum TRACP 5b value is a more objective and smart specific strategy for use in cases of progression of GCT of bone.

An important limitation of the study is that the patients were few. However, these results need not be applicable for all forms of GCT. Some patients with GCT do not express a high level of serum TRACP 5b. Furthermore, heterogeneity of multinuclear or mononuclear cells in GCT affects the serum TRACP 5b level. Nevertheless, these results are noteworthy as a preliminary report: every patient with GCT in this study showed a similar tendency of the TRACP 5b value depending on the clinical course. Additional studies must be conducted to accumulate data for patients with GCT. Another limitation of this study is that patients with pulmonary metastases of giant cell tumor of bone are not included in this series. Fewer than 10% of the patients with giant cell tumor of bone develop lung metastases [1 Mirra JM, Picci P, Gold RH, Eds. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger 1989; pp. 942-92., 2 Zhen W, Yaotian H, Songjian L, Qingliang LGeW. Giant-cell tumour of bone: The long term results of treatment by curettage and bone graft J Bone Joint Surg 2004; 86-B(2): 212-6., 4 Klenke FM, Wenger DE, Inwards CY, Rose PS, Sim FH. Giant cell tumor of bone. Risk factors for recurrence Clin Orthop Relat Res 2011; 469(2): 591-9., 6 Takeuchi A, Tsuchiya H, Niu X, et al. The prognostic factors of recurrent GCT: a cooperative study by Eastern Asian Musculoskeletal Oncology Group J Orthop Sci 2011; 16: 196-202., 18 Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone J Bone Joint Surg Am 1987; 69(1): 106-4.]. Results for local recurrence demonstrated that serum TRACP 5b can increase in patients with pulmonary metastases because of the similar histologies of primary and metastatic lesions. Another point of interest is how the serum TRACP 5b level is affected similarly by metastatic progression and by local recurrence.

Although the histological features of these tumors differ from those of GCT of bone, brown tumors, especially solitary lesions, and aneurysmal bone cysts show similar radiological findings to those of a giant cell tumor of bone. They are important for differential diagnosis [1 Mirra JM, Picci P, Gold RH, Eds. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger 1989; pp. 942-92., 26 Hong WS, Sung MS, Chun K-A, et al. Emphasis on the MR imaging findings of brown tumor: a report of five cases Skeletal Radiol 2011; 40: 205-13.]. These lesions were not examined in the study, but serum TRACP 5b values of these tumors are interesting. Chondroblastomas, which also occur at the epiphyseal region of the long bone, show similar histology to that of GCT of bone. They are invariably associated with osteoclast-like giant cells [27 Mirra JM, Picci P, Gold RH, Eds. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger 1989; pp. 589-623.]. Although the incidence of chondroblastomas is much less frequent than that of GCT of bone [1 Mirra JM, Picci P, Gold RH, Eds. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger 1989; pp. 942-92., 27 Mirra JM, Picci P, Gold RH, Eds. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger 1989; pp. 589-623.], similar results can be expected because of their histological characteristics. Further studies must be undertaken to evaluate these possibilities.

In conclusion, serum TRACP 5b is a more useful and more convenient specific marker for the diagnosis and prediction of the recurrence of GCT of bone than methods and markers presented in previous reports describing MRI and DNA analysis.

ACKNOWLEDGEMENT

Declared none.

CONFLICT OF INTEREST

The authors confirm that this article content has no conflicts of interest.

REFERENCES

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[3] Takeda N, Kobayashi T, Tandai S, et al. Treatment of giant cell tumors in the sacrum and spine with curettage and argon beam coagulator J Orthop Sci 2009; 14: 210-4.
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[6] Takeuchi A, Tsuchiya H, Niu X, et al. The prognostic factors of recurrent GCT: a cooperative study by Eastern Asian Musculoskeletal Oncology Group J Orthop Sci 2011; 16: 196-202.
[7] McCarthy EF, Serrano JA, Wasserkrug HL, Dorfman HD. The ultrastructural localization of secretory acid phosphatase in giant cell tumor of bone Clin Orthop 1979; 141: 295-302.
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[10] Akahane T, Isobe K, Shimizu T. Serum total acid phosphatase for monitoring the clinical course of giant cell tumors of bone-26 patients with 5 local recurrences Acta Orthop 2005; 76(5): 651-3.
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[13] Kamiya N, Suzuki H, Yano M, et al. Implications of serum bone turnover markers in prostate cancer patients with bone metastasis Oncology 2010; 75: 1446-51.
[14] Tauchert S, di Liberto A, Cordes T, et al. Tartrate-resistant acid phosphatase (TRAP) as a serum marker for bone resorption in breast cancer patients with bone metastases Clin Exp Obstet Gynecol 2009; 36(4): 219-5.
[15] Avnet S, Longhi A, Salerno M, et al. Increased osteoclast activity is associated with aggressiveness of osteosarcoma Int J Oncol 2008; 33: 1231-8.
[16] Savarino L, Avnet S, Greco M, Giunti A, Baldini N. Potential role of tartrate-resistant acid phosphatase 5b (TRACP 5b) as a surrogate marker of late loosening in patients with total hip arthroplasty: a cohort study J Orthop Res 2010; 28: 887-92.
[17] Broadhead ML, Clark JC, Dass CR, Choong PF, Myers DE. Therapeutic targeting of osteoclast function and pathways Expert Opin Ther Targets 2011; 15(2): 169-81.
[18] Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone J Bone Joint Surg Am 1987; 69(1): 106-4.
[19] Sulh MA, Greco MA, Jiang T, et al. Proliferation index and vascular density of giant cell tumors of bone: are they prognostic markers? Cancer 1996; 77(10): 2044-51.
[20] Sun D, Biesterfeld S, Adler CP, Böcking A. Prediction of recurrence in giant cell bone tumors by DNA cytometry Anal Quant Cytol Histol 1992; 14(4): 341-5.
[21] Pazzaglia L, Conti A, Chiechi A, et al. Differential gene expression in classic giant cell tumours of bone: Tenascin C as biological risk factor for local relapses and metastases Histopathology 2010; 57: 59-72.
[22] Conti A, Rodrigues GC, Chiechi A, et al. Identification of potential biomarkers for giant cell tumor of bone using comparative proteomics analysis Am J Pathol 2010; 178(1): 88-97.
[23] Libicher M, Bernd L, Schenk JP, et al. Characteristic perfusion pattern of osseous giant cell tumor in dynamic contrast-enhanced MRI Radiology 2001; 41(7): 577-82.
[24] Waldman BJ, Zerhouni EA, Frassica FJ. Recurrence of giant cell tumor of bone: The role of MRI in diagnosis Orthopedics 1997; 20(1): 67-9.
[25] Halleen JM, Alatalo SL, Janckila AJ, et al. Serum tartrate-resistant acid phosphatase 5b is a specific and sensitive marker of bone resorption Clin Chem 2001; 47(3): 597-600.
[26] Hong WS, Sung MS, Chun K-A, et al. Emphasis on the MR imaging findings of brown tumor: a report of five cases Skeletal Radiol 2011; 40: 205-13.
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Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


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