title: Bortezomib increases osteoblast activity in myeloma patients irrespective of response to treatment.
abstract: OBJECTIVE
  Myeloma bone disease is a result of excessive osteoclast activation and impaired osteoblast function. Recent in vitro studies suggested that proteasome inhibitors might increase osteoblast function.
  
  
  METHODS
  We analyzed serum markers of osteoblast activity in 25 patients with multiple myeloma receiving bortezomib alone or in combination with dexamethasone. As control, serum samples from 58 consecutive myeloma patients receiving a therapy different than bortezomib (i.e. adriamycin/dexamethasone, melphalan/prednisone or thalidomide) were evaluated. The serum concentrations of bone-specific alkaline phosphatase (BAP) and osteocalcin were quantified before initiation of treatment and after 3 months.
  
  
  RESULTS
  In patients treated with bortezomib, mean serum levels of osteocalcin significantly increased from 6.3 to 10.8 microg/L (P = 0.024), while mean BAP levels increased from 19.7 to 30.2 U/L (P < 0.0005). Of interest, the increase in BAP was significant both in responders and non-responders. In contrast, the control group did not show a statistically significant change in BAP (24.8 U/L vs. 23.3 U/L) and osteocalcin (6.8 microg/L vs. 6.5 microg/L) before and after the treatment.
  
  
  CONCLUSIONS
  These data show that treatment with bortezomib leads to enhanced markers of osteoblast activity in patients with myeloma. The comparison with the control group suggests that the effect on osteoblasts is unique to the proteasome inhibitor.
authors.affiliation: Department of Hematology and Oncology, University Hospital Charité, Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heider
authors.forename: Martin
authors.initials: M
authors.lastname: Kaiser
authors.forename: Christian
authors.initials: C
authors.lastname: Müller
authors.forename: Christian
authors.initials: C
authors.lastname: Jakob
authors.forename: Ivana
authors.initials: I
authors.lastname: Zavrski
authors.forename: Carsten-Oliver
authors.initials: CO
authors.lastname: Schulz
authors.forename: Claudia
authors.initials: C
authors.lastname: Fleissner
authors.forename: Monica
authors.initials: M
authors.lastname: Hecht
authors.forename: Orhan
authors.initials: O
authors.lastname: Sezer
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001897:Boronic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology*; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology*; D015675:Osteocalcin / Q000097:blood; D010014:Osteolysis / Q000517:prevention & control; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D015675:Osteocalcin; D000069286:Bortezomib; D003907:Dexamethasone; D000469:Alkaline Phosphatase