Sost deficiency leads to greater bone vascular porosity, but similar osteocyte lacunar properties with increasing age

Sclerostin neutralizing antibody is an approved anabolic drug used to increase bone mass. Numerous preclinical studies examined bone mass and microstructural changes in mice receiving sclerostin neutralizing antibodies or mice lacking sclerostin, such as Sost knock out mice. Surprisingly no preclinical studies examined the effect of sclerostin deficiency with aging, despite the treatment being used primarily in older individuals. Thus, our primary aim was to examine the effect of long-term Sost deficiency on bone microstructure, including osteocyte lacunar and bone vascular porosity properties across ages. Our results show that Sost deletion led to sustained bone formation across the mouse's lifespan, whereas wild-type control mice experienced bone maturation followed by age-related declines in bone volume. Lacunar parameters were also affected due to Sost deletion, with altered lacunar density and volume in young mice, but these differences were not present in old mice. Our secondary aim was to examine the effect of short-term sclerostin deficiency on bone microporosity in woven and cortical bone after an osteotomy in adult female C57BL6J mice. Short term sclerostin antibody treatment did not alter vascular or lacunar porosity within lamellar or newly formed woven bone, suggesting that timing and duration are critical for therapeutic efficacy. In summary, Sost KO mice exhibit sustained cortical thickening and pronounced bone vascular porosity, particularly as the mice aged. As sclerostin neutralizing antibody becomes more widely used in an aging population, for extended periods of time, this work helps us understand the effects of long-term inhibition.

Content

Subjects

Aging

Bone vascular porosity

Fracture healing

Lacunar properties

Sclerostin neutralizing antibody

Sost knockout

Synchrotron tomography

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616.0: Pathology, Deseaeses, Treatment

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https://creativecommons.org/licenses/by-nc/4.0/

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publishedVersion

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