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Parathyroid hormone (PTH) affects each arm of skeletal remodeling, with net anabolic or catabolic effects dependent upon duration of exposure.
These initial modeling results are extremely encouraging and lead us to proceed with additional explorations into bone turnover and skeletal remodeling.
Because of the paramount influences that parathyroid hormone and calcitonin have on bone, their effects have been described in detail in the discussions of calcium and phosphate homeostasis and control of skeletal remodeling.
Importantly, the skeletal remodeling analysis in male mice revealed no difference between Lef1+/− and Lef1+/+ animals (Figure 2).
Body weight (total mass relative to height) can be a strong determinant of bone mass, reflecting adaptation of skeletal remodeling to loading.
Together with the role of ZAS3 in osteoblasts [14], our findings suggest that ZAS3 also regulates osteoclast differentiation and thus must be critical in postnatal skeletal remodeling.
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Other endpoints included the percentage change in BMD at hip and forearm sites, as well as changes in biomarkers of skeletal remodelling.
In this context, although macrophages are emerging as indispensable for damage control and tissue remodelling following muscle injury, and as principal mediators of pathological skeletal remodelling in diseases such as IIMs and dystrophies, the involvement of other immune cells in promoting or preventing muscle damage resolution is also emerging.
A 1-year dose-finding trial with a 1-year extension on the same treatment assignment was performed in postmenopausal women with low BMD to evaluate the safety and efficacy of weekly oral doses of placebo or odanacatib 3, 10, 25 or 50 mg on BMD and biomarkers of skeletal remodelling.
Both epigenetic and autophagic regulation of signalling pathways are known to be highly regulated by environmental factors, particularly during skeletal remodelling [13].
These unexpected findings underscore the relevance of a deep systematic phenotypic analysis assessing skeletal remodelling, which should also be applied for other lysosomal storage disorders, whose accompanying skeletal defects are poorly understood.
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