Bortezomib increases osteoblast activity in myeloma patients irrespective of response to treatment.
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.
Heider
Ulrike
U
Department of Hematology and Oncology, University Hospital Charité, Berlin, Germany.
Kaiser
Martin
M
Müller
Christian
C
Jakob
Christian
C
Zavrski
Ivana
I
Schulz
Carsten-Oliver
CO
Fleissner
Claudia
C
Hecht
Monica
M
Sezer
Orhan
O
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*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D015675:Osteocalcin; D000069286:Bortezomib; D003907:Dexamethasone; D000469:Alkaline Phosphatase