title: High-dose therapy improves the bone remodelling compartment canopy coverage and bone formation in multiple myeloma.
abstract: Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling. Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed that a good response to anti-myeloma treatment increased the extent of formative bone surfaces with canopy, and reduced the extent of eroded surfaces without canopy, reverting the uncoupled bone remodelling, while improving canopy coverage. The association between improved coupling and the canopy coverage supports the notion that canopies are critical for the coupling of bone formation to resorption. Furthermore, this study supports the observation that systemic bone disease in MM can be reversed in MM patients responding to anti-myeloma treatment.
authors.affiliation: Department of Clinical Cell Biology, Vejle/Lillebaelt Hospital, Institute of Regional Health Research, University of Southern Denmark, Vejle, Denmark.|Department of Internal Medicine, Section of Haematology, Vejle/Lillebaelt Hospital, Institute of Regional Health Research, University of Southern Denmark, Vejle, Denmark.
authors.forename: Maja
authors.initials: M
authors.lastname: Hinge
authors.affiliation: Department of Clinical Cell Biology, Vejle/Lillebaelt Hospital, Institute of Regional Health Research, University of Southern Denmark, Vejle, Denmark.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Delaisse
authors.affiliation: Department of Internal Medicine, Section of Haematology, Vejle/Lillebaelt Hospital, Institute of Regional Health Research, University of Southern Denmark, Vejle, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Plesner
authors.affiliation: Department of Pathology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Erik
authors.initials: E
authors.lastname: Clasen-Linde
authors.affiliation: Department of Haematology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Salomo
authors.affiliation: Department of Clinical Cell Biology, Vejle/Lillebaelt Hospital, Institute of Regional Health Research, University of Southern Denmark, Vejle, Denmark.
authors.forename: Thomas Levin
authors.initials: TL
authors.lastname: Andersen
mesh_terms: D064592:Autografts; D001853:Bone Marrow / Q000473:pathology; D016723:Bone Remodeling; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D009101:Multiple Myeloma / Q000473:pathology / Q000628:therapy; D010012:Osteogenesis; D010014:Osteolysis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D033581:Stem Cell Transplantation
chemical_list: D008558:Melphalan
keywords: MGUS; bone formation; bone remodelling compartment canopies; histomorphometry; multiple myeloma