Serum prolidase I activity and some bone metabolic markers in patients with breast cancer: in relation to menopausal status Zeynep O ¨ zbek Kır a , Pernur O ¨ ner a, *, Yıldız O ¨ ner Iyidog ˘an a , Sembol Tu ¨rkmen b , Hikmet Koc ¸ak a , Murat Kos ¸er a , Seden O ¨ zbilen Ku ¨c ¸u ¨cu ¨k c a Department of Biochemistry, Istanbul Faculty of Medicine, Istanbull University, C ¸ apa, Istanbul 34093, Turkey b Department of Clinical Chemistry, SSK OkmeydanıTraining Hospital, Okmeydanı, Istanbul, Turkey c Department of Radiation Oncology, Institute of Oncology, Istanbul University, C ¸ apa, Istanbul 34093, Turkey Received 30 July 2002; received in revised form 5 February 2003; accepted 5 February 2003 Abstract Objectives: The purpose of this study was to investigate the diagnostic value of some osteoblastic/osteoclastic biochemical markers and serum prolidase I activity in breast cancer (BC). Design and methods: Serum bone gla protein (BGP), prolidase I activity, urinary deoxypyridinoline (Dpy) and calcium excretions were measured, in metastatic and nonmetastatic BC patients, and in 52 healthy women. Results: In patients with metastases, bone turnover markers were found to be significantly higher than those in the control group and in patients without metastases. Serum prolidase activity in patients with and without metastases was also significantly higher than those in the control group, but there was no difference between the two patient groups. Conclusions: Bone turnover has been suggested to be accelerated in BC patients with the more pronounced osteolytic activation, especially in metastatic state. Serum prolidase in premenopausal period appears to be valuable in discriminating cancer patients from controls. BGP and to a lesser degree of Dpy, may be useful markers for predicting the metastatic bone involvement, as well as for the more cost effective management of BC patients and monitoring the effects of antiresorptive therapy of malignant osteolysis before any metastasis could be detected by other invasive techniques. © 2003 The Canadian Society of Clinical Chemists. All rights reserved. Keywords: Breast cancer; Bone involvement; Bone turnover markers; Bone metastases; Serum prolidase I; Menopausal status 1. Introduction Breast cancer (BC), placed at the top of malignant dis- eases affecting women, has also taken precedence among the carcinoma implicated in bone metastases stimulating osteoclastic bone resorption [1]. One of the consequences of neoplastic transformation is deregulation of tissue collagen metabolism. The last step of collagen degradation is medi- ated by prolidase (E.C.3.4.13.9), which is a cytosolic ex- opeptidase. Prolidase, plays an important role in the recy- cling of proline for collagen synthesis and cell growth. The role of prolidase in the metabolism of collagen is shown by pathologic conditions such as prolidase deficiency [2] liver cirrhosis [3,4], lung adenocarcinoma [5], uterine leiomyoma [6], and is also studied in breast cancer cell lines [7]. Prolidase I activity, which is present solely in plasma [8], was reported to be elevated in conditions which are char- acterized by the accumulation of collagen [9]. On the other hand, some protease inhibitors such as plasminogen activa- tor inhibitor-2 have been shown to be affected according to the menopausal status, which is one of the classical prog- nostic factors (e.g., histologic grade, steroid receptors, UICC stage,...) in malignant tumors [10]. Even if biochemical bone metabolic markers have been studied in BC patients with and without metastasis [3,11– 16] none of these studies included the determination of serum prolidase activity, a marker for collagen catabolism [4] and the relationship of this enzyme and bone markers to menopausal status. Therefore, the goal in the present study, is to assess the relation of this enzyme to the other known indices of some biochemical markers of bone turnover such as bone gla protein (BGP), a marker of osteogenesis or bone formation, * Corresponding author. Fax: +902126311323-115. E-mail address: pernuron@hotmail.com (P. Oner). Clinical Biochemistry 36 (2003) 289 –294 0009-9120/03/$ – see front matter © 2003 The Canadian Society of Clinical Chemists. All rights reserved. doi:10.1016/S0009-9120(03)00028-6