Bortezomib inhibits osteoclast activity in patients with multiple myeloma

Background: The antimyeloma agent bortezomib functions as an inhibitor of nuclear factor (NF)-κB. Although NF-κB inhibition is predicted to affect osteoclast function, preclinical and clinical studies have primarily reported an effect on osteoblasts. Patients and 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. Conclusion: 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.