title: Altered bone microarchitecture and gene expression profile due to calcium deficiency in a mouse model of myeloma.
abstract: It is not clear why patients with an indolent form of multiple myeloma (MM) develop into an aggressive form with poor prognostic. We investigated the effect of a dietary calcium deficiency on tumor growth, osteolysis and gene expression in the 5T2MM murine model. Two groups of C57BL/KaLwRij mice received 5T2MM cells and started a diet with normal (0.8%; "normal-Ca-MM") or low calcium content (0.05%; "low-Ca-MM"). Two control groups (without 5T2MM cells) received either a normal or low calcium diet (normal-Ca and low-Ca groups). Tumor growth, osteolysis and marrow gene expression of the Wnt pathway, RANKL and MIP-1α were monitored at 6, 8 and 10 weeks (w) after cell injection. In low-Ca mice, serum level of PTH was higher after 10w; microCT showed trabecular bone loss and decrease of cortical thickness at the tibia. A higher M-protein level was evidenced at 10w and 4 mice developed paraplegia at 8/9w in low-Ca-MM group only. Numerous cortical perforations of the tibia were observed in MM groups with a marked decrease in cortical thickness in low-Ca-MM. At 6w, osteoclast number from the endosteum was significantly higher in low-Ca-MM compared to normal-Ca MM. This observation was not found at 8 and 10w. MicroCT of the lumbar vertebrae showed dramatic bone destruction in the low-Ca-MM group. qPCR revealed no difference in RANKL expression whereas differences were obtained in the expression of Lrp5/Lrp6 and MIP-1α from 6w. A low calcium diet induced higher bone destruction in the tibia and vertebra associated with an earlier decrease in bone formation level and a higher increase in bone resorption level at early time in the MM development.
authors.affiliation: GEROM Groupe Etudes Remodelage Osseux et bioMatériaux - IRIS-IBS Institut de Biologie en Santé, Université d'Angers, CHU d'Angers, 49933 Angers Cedex, France. Electronic address: helene.libouban@univ-angers.fr.
authors.forename: Hélène
authors.initials: H
authors.lastname: Libouban
authors.affiliation: GEROM Groupe Etudes Remodelage Osseux et bioMatériaux - IRIS-IBS Institut de Biologie en Santé, Université d'Angers, CHU d'Angers, 49933 Angers Cedex, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chappard
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000502:physiology; D002118:Calcium / Q000172:deficiency*; D002136:Calcium, Dietary; D000071556:Cancellous Bone / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D006961:Hyperparathyroidism / Q000473:pathology; D008159:Lumbar Vertebrae / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009101:Multiple Myeloma / Q000473:pathology*; D010014:Osteolysis / Q000473:pathology*; D013977:Tibia / Q000473:pathology*; D055114:X-Ray Microtomography
chemical_list: D002136:Calcium, Dietary; D002118:Calcium
keywords: Dietary calcium; Hyperperathyroidism; Multiple myeloma; Osteolysis; X-ray microtomography