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 (M0) 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 sig- nificantly lower than in sex matched control group (HS; p ¼ 0.0008) or in patients with primary osteoporosis (OP; p ¼ 0.0009). On the contrary, cystatin C levels were significantly higher in BCa patients than in HS ( p ¼ 0.0001) or OP ( p ¼ 0.017). In PCa patients, cathepsin K concen- trations 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 ¼ 0.0001) or BPH patients ( p ¼ 0.0078). Furthermore, in PCa patients, a pos- itive correlation was observed between cystatin C and cathepsin K (rS ¼ 0.34; p ¼ 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 zole- dronic 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.