title: Unwrapping microcomputed tomographic images for measuring cortical osteolytic lesions in the 5T2 murine model of myeloma treated by bisphosphonate.
abstract: Multiple myeloma is due to the proliferation of malignant plasma cells which increase the number of osteoclasts leading to trabecular and cortical bone osteolysis. The 5T2MM murine model reproduces the human disease and microcomputed tomography is a precise tool to investigate bone loss. Bisphosphonates (zoledronic acid or pamidronate) are used in preventing osteolysis. However, loss of cortical bone in not possible to quantify by histomorphometry on histological sections or microCT images. Osteolysis was studied in mice grafted with the 5THL subline to see if one drug was more active after 10 weeks. Mice were distributed into 4 groups: control, untreated, treated with pamidronate or with zoledronic acid. The left femurs were embedded undecalcified and sectioned at 7 μm. The right tibias and femurs were analyzed by microCT and trabecular morphometric parameters were obtained. Cortical bone osteolysis was analyzed by developing a new algorithm to unwrap microCT sections of the cortices, allowing measurement of the number of perforations, porosity and mean perforation area. The bisphosphonates had no significant effect on the tumor growth as evidence by the absence of effect on the M-protein level. Cortical perforations were evidenced on histological sections and their number seemed to be reduced by both bisphosphonates. MicroCT was used to quantify the trabecular bone: a bone loss was evidenced in the untreated myeloma group and both bisphosphonates appeared equal to preserve trabecular mass. However, the number and size of cortical perforations cannot be determined on 3D models. Unwrapping microCT images provided flat images allowing a precise determination of cortical perforations. Pamidronate did not reduce the number and size of cortical perforations but significantly reduced porosity. Zoledronic acid appeared significantly superior and considerably reduced all parameters. Unwrapping microCT image is a new method allowing the measurement of cortical perforations in bone malignancies, a parameter that cannot be measured correctly on 2D histological sections.
authors.affiliation: GEROM Groupe Etudes Remodelage Osseux et bioMatériaux, LUNAM Université, IRIS-IBS Institut de Biologie en Santé, CHU d'Angers, 49933 Angers Cedex, France.
authors.forename: Mambaye
authors.initials: M
authors.lastname: N'Diaye
authors.affiliation: GEROM Groupe Etudes Remodelage Osseux et bioMatériaux, LUNAM Université, IRIS-IBS Institut de Biologie en Santé, CHU d'Angers, 49933 Angers Cedex, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Libouban
authors.affiliation: GEROM Groupe Etudes Remodelage Osseux et bioMatériaux, LUNAM Université, IRIS-IBS Institut de Biologie en Santé, CHU d'Angers, 49933 Angers Cedex, France; UPSP "Biologie et Biomatériaux du Tissus Osseux - Chirurgie Expérimentale", ONIRIS - National Veterinary School of Nantes, LUNAM Université, Route de Gâchet, BP 44706, F44307 Nantes cedex 03, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Aguado
authors.affiliation: GEROM Groupe Etudes Remodelage Osseux et bioMatériaux, LUNAM Université, IRIS-IBS Institut de Biologie en Santé, CHU d'Angers, 49933 Angers Cedex, France; Service de Rhumatologie, CHU d'Angers, 49933 Angers Cedex, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bouvard
authors.affiliation: GEROM Groupe Etudes Remodelage Osseux et bioMatériaux, LUNAM Université, IRIS-IBS Institut de Biologie en Santé, CHU d'Angers, 49933 Angers Cedex, France; Service de Rhumatologie, CHU d'Angers, 49933 Angers Cedex, France.
authors.forename: Maurice
authors.initials: M
authors.lastname: Audran
authors.affiliation: GEROM Groupe Etudes Remodelage Osseux et bioMatériaux, LUNAM Université, IRIS-IBS Institut de Biologie en Santé, CHU d'Angers, 49933 Angers Cedex, France. Electronic address: daniel.chappard@univ-angers.fr.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chappard
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D004164:Diphosphonates / Q000008:administration & dosage*; D004195:Disease Models, Animal; D016903:Drug Monitoring / Q000379:methods; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology*; D010014:Osteolysis / Q000473:pathology*; D016896:Treatment Outcome; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates
keywords: Bisphosphonate; Cortical bone; MicroCT; Myeloma; Osteolysis