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Modifications de la composition et de la structure moléculaire du tissu osseux sous l'influence des bisphosphonates

Abstract : Biphosphonates are known for their anti-resorptive effects in benign (osteoporosis) and malignant bone diseases (myeloma, bone metastasis). Their clinical properties are based on the net increase of bone mass and mineral density. Their strong affinity for biominerals allows them a targeting for specific bone remodeling sites and a prolonged storage within bone. Little is known about molecular changes upon bisphosphonates uptake in high turnover bone sites. Therefore, the aim of the present work was to examine intrinsic bone material properties in a high cumulative bisphosphonates context such as newly-formed bone and bisphosphonates-related osteonecrosis of the jaws. Our results show that bisphosphonates could be linked to the overmineralization reported in jaw bones. In addition, bisphosphonates cause ultrastructural disorders of both mineral and collagenic components. These modifications could be attributed to: i) bisphosphonates effects on the duration of mineralization processes, ii) to its mineral binding/interaction consequences, and iii) interestingly to its potential contribution on the osteoblastic function. This work contributes to clarify the molecular impacts of high cumulative bisphosphonates uptake on bone quality.
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Cécile Olejnik. Modifications de la composition et de la structure moléculaire du tissu osseux sous l'influence des bisphosphonates. Médecine humaine et pathologie. Université du Droit et de la Santé - Lille II, 2014. Français. ⟨NNT : 2014LIL2S023⟩. ⟨tel-01171630⟩

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