Circulating cathepsin K and cystatin C in patients with cancer related bone disease: Clinical and therapeutic implications

The clinical significance of serum cathepsin K and cystatin C was assessed in patients with breast cancer (BCa) or prostate cancer (PCa) with confined disease (MO) or bone metastasis (BM). Cathepsin K and cystatin C circulating levels were determined by ELISAs in 63 cancer patients, in 35 patients with nonmalignant diseases and in 42 healthy blood donors (control group). In BCa patients, cathepsin K serum levels were significantly lower than in sex matched control group (HS: p = 0.0008) or in patients with primary osteoporosis (OP; p = 0.0009). On the contrary, cystatin C levels were significantly higher in BCa patients than in HS (p = 0.0001) or OP (p = 0.017). In PCa patients, cathepsin K concentrations did not significantly differ from those measured in sex matched HS or in patients with benign prostatic hyperplasia (BPH). Conversely, cystatin C was more elevated in cancer patients than in controls (p = 0.0001) or BPH patients (p = 0.0078). Furthermore, in PCa patients, a positive correlation was observed between cystatin C and cathepsin K (r(s) = 0.34; p = 0.047). No further relationship was highlighted between these molecules and the clinicobiological parameters of BCa or PCa progression including the number of bone lesions. Moreover, ROC curve analysis showed a poor diagnostic performance of cathepsin K and cystatin C in the detection of BM patients. Interestingly, the administration of zoledronic acid (ZA), a bisphosphonate derivative endowed with a potent antiosteoclastic activity, induced in BM patients a marked increase of cathepsin K and cystatin C serum levels compared to baseline values. However, this phenomenon was statistically significant only in the PCa group. In conclusion Cystatin C and cathepsin K may be regarded as possible markers to monitor the therapeutic response to bisphosphonate treatments. Nevertheless, their clinical value as specific gauges of skeletal metastasis remains questionable. (c) 2007 Elsevier Masson SAS. All rights reserved.