dr Maaike Schilperoort (LUMC/Colombia University) was presented with the Kyowa Kyrin best thesis award 2021 for her thesis: it’s about time.
The thesis targets various consequences of disruption of the internal biological clock, including the consequences on bone. A consistent circadian rhythm is essential for long-term health, and chronic circadian disturbances have been strongly associated with cardiometabolic diseases and metabolic bone disturbances in humans. This thesis provides insight into the role of circadian rhythm in the development of (cardio)metabolic diseases, and elucidates novel approaches to prevent diseases associated with circadian disturbances. She discovered that strong rhythms in the expression of circadian clock genes within the bones of mice, were clearly disrupted by shifting light-dark cycles. Repeated shifts in light-dark cycle decreased plasma levels of markers for bone formation and resorption, indicative of a reduced bone turnover. Consistent with these observations, abnormalities in trabecular bone structure and an increased cortical bone mineralization were found. Altogether, the bones of mice exposed to shifting light-dark cycles show an osteoporotic phenotype that may explain the increased incidence of bone fractures in shift workers.
Furthermore a disturbed glucocorticoid rhythm could also underlie the association between circadian disruption and osteoporosis. Experimental flattening of the corticosterone rhythm in mice tilted the balance in bone remodeling towards bone resorption, thereby reducing bone volume and density. The observed alterations in bone structure negatively affected the mechanical properties of bone, as reflected by a decreased bone strength and stiffness. Together, these results indicate that a disturbed glucocorticoid rhythm can indeed increase the risk of osteoporotic fractures. .This is not only relevant for shiftworkers, but also for patients that have a blunted endogenous glucocorticoid rhythm due to exogenous glucocorticoid administration. In these patients, well-designed chronotherapy with glucocorticoids may reduce osteoporotic adverse effects. The full thesis is available here.
Dr. Maaike Schilperoort is currently working as a postdoctoral researcher at Colombia University, USA and therefore her award was collected by the supervisor of her bone experiments, dr Liesbeth Winter (LUMC).