Bortezomib Inhibits Osteoclast Activity in Patients with Multiple Myeloma

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