Neuroendocrine regulation of human bone metabolism

The skeleton is perhaps the most multifunctional part of our body. It not only provides outer strength, a protective shell and enables locomotion, but it also hosts the bone marrow and serves many metabolic and endocrine functions. This thesis investigates two aspects of human bone metabolism, firstly the role of the sympathetic nervous system (SNS) in human bone metabolism and hematopoiesis and secondly the hormonal control and activity of bone and bone marrow. In the first part of this thesis we used a clinical approach, a genetic approach, and a pharmacological approach to study the SNS and bone metabolism. We showed that bone resorption is increased in pheochromocytoma patients as a model of sympathetic overstimulation and decreases following adrenalectomy. But we did not find an association between polymorphisms in the beta-2 adrenergic receptor and fracture risk or bone mineral density in two large, Dutch cohorts and a large international consortium. Furthermore, there was no effect of a beta-adrenergic agonist and an antagonist on bone turnover or circulating CD34+ hematopoietic stem cells in healthy, postmenopausal women in a randomized controlled trial. In the second part of this thesis we described the variation in bone marrow fat during the menstrual cycle and we showed a large decrease in bone marrow fat during two weeks of estradiol treatment in postmenopausal women. Finally, we put into clinical perspective the evidence concerning the interaction between human bone metabolism and glucose metabolism