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. 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.
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. 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.
Authors: Marci D Jones; Julie C Liu; Thomas K Barthel; Sadiq Hussain; Erik Lovria; Dengfeng Cheng; Jesse A Schoonmaker; Sudhanshu Mulay; David C Ayers; Mary L Bouxsein; Gary S Stein; Siddhartha Mukherjee; Jane B Lian Journal: Clin Cancer Res Date: 2010-09-15 Impact factor: 12.531
Authors: Jianguo Tao; Venkat Srinivasan; Xiangjiao Yi; Yingchun Zhao; Hengwei Zhang; Xi Lin; Xichao Zhou; Brendan F Boyce; Peter W Villalta; Frank H Ebetino; Koc Kan Ho; Robert K Boeckman; Lianping Xing Journal: J Bone Miner Res Date: 2022-01-22 Impact factor: 6.390
Authors: Shuting Sun; Jianguo Tao; Parish P Sedghizadeh; Philip Cherian; Adam F Junka; Esmat Sodagar; Lianping Xing; Robert K Boeckman; Venkatesan Srinivasan; Zhenqiang Yao; Brendan F Boyce; Brea Lipe; Jeffrey D Neighbors; R Graham G Russell; Charles E McKenna; Frank H Ebetino Journal: Br J Pharmacol Date: 2021-04-10 Impact factor: 8.739