Osteoporosis and the Endocrinology of Aging

Osteoporosis, Endocrinology of Aging and the Menopausal Transition

Professor Rivka Dresner-Pollak and her research group investigate the following topics:

Elucidating the factors and molecular pathways which cause bone to age:
While Alzheimer’s disease and Diabetes occur in some individuals with age, bone loss and fragility occur virtually in everyone if they live long enough, and maybe part of an intrinsic aging program which involves multiple organ systems. We discovered that Sirtuin 1, a key player in aging and metabolism, regulates bone mass and bone quality in mice and humans. Moreover, the activation of Sirtuin1 restored bone mass and mechanical strength in osteoporotic mice. We now extend these findings to studies in humans.

Sirt1 is a regulator of bone mass and a repressor of Sost encoding for sclerostin, a bone formation inhibitor

The Sirtuin1 activator SRT3025 down-regulates sclerostin and rescues ovariectomy-induced bone loss and biomechanical deterioration in female mice

Reduced Sirtuin1 expression at the femoral neck in women who sustained an osteoporotic hip fracture

The role of bone marrow fat in bone turnover and in whole body energy metabolism:
Initially thought to be a filler only, it is now known that bone marrow fat is metabolically active, influencing bone turnover in the marrow micro-environment, and participating in whole body energy metabolism. We discovered that Sirtuin 1 induces browning of bone marrow fat cells in mice and humans. Browning of fat is associated with beneficial metabolic effects in other fat depots. We are now investigating the implications of our findings for local bone and whole body energy metabolism in mouse models and in human bone marrow cells.

Sirt1 Promotes a Thermogenic Gene Program in Bone Marrow Adipocytes: From Mice to (Wo)Men

The underlying mechanisms of skeletal fragility in Type 1 Diabetes Mellitus:
Skeletal fragility with concomitant fractures is a newly recognized serious diabetic complication which is more severe in patients with type 1 diabetes (T1D). Hip fracture risk is dramatically higher in T1D patients compared to age- and sex-matched controls, and the associated morbidity and mortality are significantly higher. The underlying mechanisms of increased skeletal fragility in T1D are still unknown.

We are investigating molecular pathways of skeletal fragility in a mouse model of T1D. This research program was recently awarded a research grant from BIRAX (Britain Israel Research and Academic Exchange Partnership) in collaboration with Prof. Lynn Cox of Oxford University.

Investigation of novel targets to combat the metabolic derangements associated with the menopausal transition:
With a life expectancy of 90 years and an average age at menopause of 50 years, women now spend close to half their lives postmenopausal. Menopause is associated with a number of metabolic derangements such as weight gain, an increase in visceral fat, blood pressure and insulin resistance. These unfavorable changes result in increased risk of cardiovascular disease, dementia, diabetes and osteoporosis. Currently, estrogen replacement therapy is only option to combat some of these changes, however the safety of its broad use is still controversial. Using state of the art technologies such as deep sequencing and epigenetic mapping of key endocrine tissues, we identified novel targets to ameliorate these unfavorable metabolic changes.

SUN-033 RNA-Seq Analysis of Ovariectomy-Induced Changes in Mouse Liver Reveals New Targets for Menopause-Associated Metabolic Derangement