title: Serum cathepsin K concentrations reflect osteoclastic activity in women with postmenopausal osteoporosis and patients with Paget's disease.
abstract: BACKGROUND
  Cathepsin K, a cysteine protease, plays an essential role in osteoclast-mediated collagen degradation. Recently, an immunoassay to quantify cathepsin K in serum has been developed. We assessed the usefulness of serum cathepsin K as a marker of bone turnover in cross-sectional and longitudinal studies of patients with metabolic bone disease.
  
  
  METHODS
  The study cohort consisted of 40 healthy subjects, 21 women with postmenopausal osteoporosis [66.1 +/- 7.9 yrs] and 10 patients with Paget's disease of bone [67.1 +/- 11.6 yrs]. All patients were started on oral or intravenous bisphosphonate treatment and were followed prospectively over 6 months. Circulating cathepsin K levels were determined by a specific sandwich enzyme immunoassay (Biomedica, Vienna, Austria). In addition, serum carboxyterminal cross-linked telopeptide of type I collagen (betaCTX-I) and bone-specific alkaline phosphatase (BALP) were measured for comparison.
  
  
  RESULTS
  When compared to healthy subjects, mean serum cathepsin K levels were significantly elevated in women with postmenopausal osteoporosis (3.1 +/- 1.9 vs. 11.3 +/- 13.1 pmol/L, p = 0.01) and in patients with Paget's disease of bone (6.2 +/- 4.4 pmol/L, p = 0.04). In postmenopausal osteoporotic women, both oral and intravenous bisphosphonate treatment resulted in a significant reduction in serum cathepsin K levels (p = 0.03) with most of the effect occurring after one month (mean% change: -33%). In patients with mild Paget's disease, serum cathepsin K levels decreased during bisphosphonate treatment.
  
  
  CONCLUSIONS
  Serum concentrations of cathepsin K appear to reflect osteoclastic activity in patients with postmenopausal osteoporosis and Paget's disease of bone and may hold promise as a marker of osteoclast activity.
authors.affiliation: Bone Research Program, ANZAC Research Institute, University of Sydney, Australia.
authors.forename: Christian
authors.initials: C
authors.lastname: Meier
authors.forename: Udo
authors.initials: U
authors.lastname: Meinhardt
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Greenfield
authors.forename: James
authors.initials: J
authors.lastname: De Winter
authors.forename: Tuan V
authors.initials: TV
authors.lastname: Nguyen
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dunstan
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Seibel
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001862:Bone Resorption / Q000097:blood*; D056657:Cathepsin K; D002403:Cathepsins / Q000097:blood*; D002922:Ciguatoxins / Q000097:blood; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008875:Middle Aged; D010001:Osteitis Deformans / Q000097:blood*; D015663:Osteoporosis, Postmenopausal / Q000097:blood*; D018709:Statistics, Nonparametric
chemical_list: C454647:ciguatoxin 1B (CTX 1B); D002922:Ciguatoxins; D000469:Alkaline Phosphatase; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K