Bortezomib inhibits osteoclast activity in patients with multiple myeloma.
BACKGROUND
The antimyeloma agent bortezomib functions as an inhibitor of nuclear factor (NF)-kappaB. Although NF-kappaB inhibition is predicted to affect osteoclast function, preclinical and clinical studies have primarily reported an effect on osteoblasts.


METHODS
We examined parameters of bone turnover prospectively in patients with multiple myeloma treated with bortezomib before and after autologous transplantation. Thirty-nine patients received 2 cycles of bortezomib on days 1, 4, 8, and 11 of a 21-day cycle. After high-dose melphalan with autologous stem cell transplantation, bortezomib 1.3 mg/m2 on days 1, 8, 15, and 22 of a 5-week cycle was administered as maintenance therapy.


RESULTS
During posttransplantation bortezomib, decreases in the urinary excretion of collagen N-telopeptide indicated that bortezomib suppresses osteoclast function.


CONCLUSIONS
The effects on osteoclasts occurred in the absence of bisphosphonate treatment and independently of changes in monoclonal protein levels. Further studies exploring the role of bortezomib as a bone protective agent could be warranted.
Uy
Geoffrey L
GL
Section of Bone Marrow Transplant and Leukemia, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Trivedi
Rachna
R
Peles
Shachar
S
Fisher
Nicholas M
NM
Zhang
Qin Jean
QJ
Tomasson
Michael H
MH
DiPersio
John F
JF
Vij
Ravi
R
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001781:Blood Component Removal; D001897:Boronic Acids / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D000069286:Bortezomib; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008558:Melphalan / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000473:pathology*; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology*; D018579:Patient Selection; D011719:Pyrazines / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D016179:Granulocyte Colony-Stimulating Factor; D000069286:Bortezomib; D008558:Melphalan