title: Multiple myeloma: changes in serum C-terminal telopeptide of collagen type I and bone-specific alkaline phosphatase can be used in daily practice to detect imminent osteolysis.
abstract: OBJECTIVE
  Monitoring of bone disease in multiple myeloma is becoming increasingly important because bone-protecting treatment with bisphosphonate is becoming restricted after the awareness of osteonecrosis of the jaw. Despite the potential of biochemical markers of bone remodeling to monitor dynamic bone turnover, they are not used in everyday practice. Here, we investigate their usefulness to detect imminent progressive osteolysis in relapsing patients with multiple myeloma.
  
  
  METHODS
  In an unselected cohort of 93 patients, we measured the bone resorption markers C-terminal telopeptide of collagen type I (CTX-I), C-terminal cross-linked telopeptide of type-I collagen generated by MMPs (ICTP), N-terminal cross-linked telopeptide of type-I collagen (NTX-I), and the bone formation marker bone-specific alkaline phosphatase (bALP) monthly for 2 yr. Retrospectively, we identified 40 cases where patients had progressive disease. We investigated how the bone markers developed prior to disease progression.
  
  
  RESULTS
  We observed that CTX-I and bALP changed significantly before progressive disease were recognized. More interestingly, these changes differed depending on whether concurrent progressive osteolysis was present. In patients with progressive osteolysis, there was a large increase in bone resorption which was not compensated by increased bone formation. In contrasts, patients with stable bone disease had only a slight increase in bone resorption which was compensated by concurrent increased bone formation. By calculating a patient-specific CTX-I/bALP ratio, we quantified the risk a patient experiences if the ratio increases.
  
  
  CONCLUSIONS
  By analyzing patient-specific changes in the ratio of CTX-I/bALP, we might tailor treatment with bone-protecting agents in the individual patient.
authors.affiliation: Department of Haematology, Vejle Hospital, Vejle, Denmark. thomas.lund@slb.regionsyddanmark.dk
authors.forename: Thomas
authors.initials: T
authors.lastname: Lund
authors.forename: Niels
authors.initials: N
authors.lastname: Abildgaard
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Andersen
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Delaisse
authors.forename: Torben
authors.initials: T
authors.lastname: Plesner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood*; D016723:Bone Remodeling; D015331:Cohort Studies; D024042:Collagen Type I; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000201:enzymology / Q000503:physiopathology; D010014:Osteolysis; D010446:Peptide Fragments / Q000097:blood*; D010455:Peptides; D011347:Procollagen / Q000097:blood*
chemical_list: D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; D000469:Alkaline Phosphatase