Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.
TLDR
Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging.Abstract:
The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that rediscovering a phenomenon that was first observed more half a century ago will have an important impact on our understanding of how new antifracture treatments work.read more
Citations
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Osteoblast-Osteoclast Communication and Bone Homeostasis
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TL;DR: A systematic parallelization of fundamental well-established biology of bone, updated and recent advances on the understanding of biological phenomena occurring in native and injured tissue, and critical discussion of how individual aspects have been translated into tissue regeneration strategies using biomaterials and other tissue engineering approaches are suggested.
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3D printing of Haversian bone-mimicking scaffolds for multicellular delivery in bone regeneration.
Meng Zhang,Rongcai Lin,Xin Wang,Jianmin Xue,Cuijun Deng,Chun Feng,Hui Zhuang,Jingge Ma,Chen Qin,Li Wan,Jiang Chang,Chengtie Wu +11 more
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Matrix Metalloproteinases in Bone Resorption, Remodeling, and Repair.
TL;DR: The functions of MMPs and their inhibitors in bone cells, during bone remodeling, pathological bone resorption (osteoporosis and bone metastasis), bone repair/regeneration, and emergent roles in bone bioengineering are discussed.
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Fracture Risk and Management of Discontinuation of Denosumab Therapy: A Systematic Review and Position Statement by ECTS
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TL;DR: An updated systematic review of existing literature on changes of bone turnover, bone mineral density, and fracture risk after denosumab discontinuation provided advice on management based on expert opinion and indicated partial efficacy of subsequent antiresorptive treatment with results seemingly dependent on duration of denosUMab treatment.
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