TY - JOUR
T1 - Pathogenesis of age-related bone loss in humans
AU - Khosla, Sundeep
N1 - Funding Information:
Funding Supported by National Institutes of Health (Grants AG004875 and AR027065).
PY - 2013/10
Y1 - 2013/10
N2 - Background. Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans.Methods. This review provides an update on mechanisms of age-related bone loss in humans based on the author's knowledge of the field and focused literature reviews.Results. Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF- and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen.Conclusions. There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents.Decision Editor: Luigi Ferrucci, MD, PhD
AB - Background. Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans.Methods. This review provides an update on mechanisms of age-related bone loss in humans based on the author's knowledge of the field and focused literature reviews.Results. Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF- and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen.Conclusions. There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents.Decision Editor: Luigi Ferrucci, MD, PhD
KW - Aging.
KW - Bone
KW - Estrogen
KW - Osteoporosis
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U2 - 10.1093/gerona/gls163
DO - 10.1093/gerona/gls163
M3 - Article
C2 - 22923429
AN - SCOPUS:84880562766
SN - 1079-5006
VL - 68
SP - 1226
EP - 1235
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 10
ER -