title: Markers of bone metabolism in multiple myeloma patients switched from zoledronic acid to denosumab.
abstract: To date, intravenous drip infusion of zoledronic acid (ZA) has mainly been used for the treatment and prevention of skeletal-related events (SRE) in patients with multiple myeloma (MM). Recently, denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL), has also become available for the same purpose, but little is known about the impact of switching from ZA to denosumab. Herein, we present a retrospective study on bone metabolic markers in 10 MM patients initially treated with ZA and then switched to denosumab. Consequently, the levels of bone resorption markers, tartrate-resistant acid phosphatase 5b (TRACP-5b) and serum type-I collagen crosslinked N-telopeptide (sNTX), significantly decreased after denosumab treatment, while the levels of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), showed no apparent changes. No patient developed severe hypocalcemia with denosumab treatment. In one patient not given chemotherapy, the M-protein level increased after switching from ZA to denosumab and plateaued when ZA was restarted. Based on this finding, we anticipate that switching from ZA to denosumab would exert a stronger suppressive effect on osteoclasts, but the anti-myeloma activity of ZA must be taken into consideration.
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Tatekoshi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
authors.forename: Soushi
authors.initials: S
authors.lastname: Ibata
authors.forename: Akari
authors.initials: A
authors.lastname: Hashimoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kamihara
authors.forename: Hiroto
authors.initials: H
authors.lastname: Horiguchi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Ono
authors.forename: Kohichi
authors.initials: K
authors.lastname: Takada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iyama
authors.forename: Rishu
authors.initials: R
authors.lastname: Takimoto
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kobune
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001851:Bone Diseases, Metabolic / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D001862:Bone Resorption / Q000175:diagnosis; D002118:Calcium / Q000097:blood; D002454:Cell Differentiation; D024042:Collagen Type I / Q000097:blood; D000069448:Denosumab; D004164:Diphosphonates / Q000008:administration & dosage*; D057915:Drug Substitution; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications*; D009194:Myeloma Proteins; D010006:Osteoblasts / Q000166:cytology; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis; D010455:Peptides / Q000097:blood; D053245:RANK Ligand / Q000276:immunology*; D012189:Retrospective Studies; D000071681:Tartrate-Resistant Acid Phosphatase; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D007527:Isoenzymes; D009194:Myeloma Proteins; D010455:Peptides; D053245:RANK Ligand; C052929:collagen type I trimeric cross-linked peptide; C085016:multiple myeloma M-proteins; D015675:Osteocalcin; D000069448:Denosumab; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; C000605510:ACP5 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002118:Calcium