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Introduction-Aging is associated not only with bone loss but also with increases in bone marrow adipocytes. Since osteoblasts and adipocytes are derived from a common precursor, it is possible that with aging, there is a preferential "switch" in commitment of this precursor to the adipocyte over the osteoblast lineage. We tested the hypothesis that the apparent "age-related" increase in marrow adipocytes is due, at least in part, to estrogen (E) deficiency.

ER␣ acts either through classical (ERE-mediated) or nonclassical (non-ERE) pathways. The generation of mice carrying a mutation that eliminates classical ER␣ signaling presents a unique opportunity to study the relative roles of these pathways in bone. This study defines the skeletal phenotype and responses to ovariectomy and estrogen replacement in these mice.Introduction: Estrogen receptor ␣ (ER␣) can act either through classical estrogen response elements (EREs) or through non-ERE (nonclassical) pathways. To unravel these in bone, we crossed mice heterozygous for a knock-in mutation abolishing ERE binding (nonclassical ER␣ knock-in [NERKI]) with heterozygote ER␣ knockout mice and studied the resulting female ER␣

In recent decades the population of both elderly men and women has grown substantially worldwide. Aging is associated with a number of pathologies involving various organs including the skeleton. Age-related bone loss and resultant osteoporosis put the elderly population at an increased risk for fractures and morbidity. Fortunately, in parallel our understanding of this malady has also grown substantially in recent years. A number of clinical as well as translational studies have been pivotal in providing us with an understanding of the pathophysiology of this condition. This article discusses the current concepts of age-related modulation of the skeleton involving intrinsic factors such as genetics, hormonal changes, levels of oxidative stress, and changes in telomere length, as well as extrinsic factors such as nutritional and lifestyle choices. It also briefly outlines recent studies on the relationship between bone and fat in the marrow as well as the periphery.