The Effect of Bortezomib On Bone Metabolism of Patients with Multiple Myeloma: a Korean Multicenter Prospective Study.
Authors: Min Chang-Ki , Kim Seok Jin , Lee Je-Jung , Suh Cheolwon , Kim Jin Seok , Yoon Sung-Soo , Kim Byung Soo , Kang Hye Jin , Choi Young Jin , Kim Cheol Soo , Kim Yang Soo , Kwak Jae-Yong , Kim Yoo Jin , Joo Young Don , Mun Yeung-Chul , Jo Deog Yeon , Park Joon Seong , Park Chi-Young , Kim Sung Hyun 
Published: October 2019

Abstract
Abstract 4871

BACKGROUND
Bortezomib is increasingly being employed as an important treatment for relapsed/refractory patients with multiple myeloma (MM) who have received at least one prior therapy. Osteolytic bone disease is a major problem in the management of MM. Myeloma bone disease is a result of excessive osteoclast activation and impaired osteoblast function.

METHODS
This study aimed to evaluate the effect of bortezomib on bone remodeling in the patients with MM who received one prior therapy. Total 104 patients were enrolled and serum samples were collected from 81 patients at baseline and after 4 cycles of bortezomib treatment, respectively. An enzyme linked immunosorbent assay (ELISA) was used for the detection of the following serum markers; (1) the osteoblastic markers including serum osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), (2) dickkopf-1 (DKK-1), an osteoblastic inhibitor and (3) a main inducer of osteoclast activity, receptor activator nuclear factor κB ligand (RANKL) and its soluble decoy receptor, osteoprotegerin (OPG).

RESULTS
There was no correlation between bone disease status and the concentrations of the bone markers; patients with myeloma bone disease at baseline did not have increased values of DKK-1, RANKL and RANKL/OPG ratio as well as decreased levels of OC and BAP when compared with those without osteolytic bone lesions. To our surprise, there was also a strong tendency towards a negative correlation with serum levels of OC (P=.009) and BAP (P=.049) and disease duration (≥ vs. < 6 months). Moreover, DKK-1 concentrations were positively associated with disease duration (P=.047). The objective response rate (≥ partial response) after four cycles of therapy was 58%. Bortezomib administration significantly reduced serum DKK-1 (P=.011) and sRANKL/OPG ratio (P=.034) after 4 cycles irrespective of treatment response. OPG levels were significantly different according to the type of previous therapy (stem cell transplantation vs. alkylator-based, P=.029)

CONCLUSIONS
This study suggests that bortezomib can inhibit the down-regulation of osteoblastic response and bone resorption by reducing circulating levels of DKK-1 and sRANKL/OPG ratio. Serum concentrations of the bone-remodeling markers can be different according to the disease duration rather than the status of bone disease. Bortezomib treatment early after diagnosis may benefit myeloma patients with bone disease considering that the change of bone markers was bound up with disease duration.

Disclosures
Min: Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Lee:Janssen Korea: Research Funding. Suh:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Yoon:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Kang:Janssen Korea: Research Funding. Choi:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Kwak:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding. Joo:Janssen Korea: Research Funding. Mun:Janssen Korea: Research Funding. Jo:Janssen Korea: Research Funding. Park:Janssen Korea: Research Funding. Park:Janssen Korea: Research Funding. Kim:Janssen Korea: Research Funding.