Interaction between bone, the neuroendocrine system and metabolism

Classically, the skeleton is defined by its mechanical properties, as a site for hematopoiesis and in mineral homeostasis. In recent years, a further-reaching role has been suggested for the skeleton. In this thesis, we investigate three novel aspects of human bone metabolism. In the first part we performed a series of experiments to investigate the role of the sympathetic nervous system in human bone remodeling. There was no effect of a beta-adrenergic agonist and an antagonist on bone turnover in healthy, postmenopausal women in a randomized controlled trial. Next, we showed that bone resorption is increased in healthy volunteers receiving a selective alpha-2 adrenergic receptor agonist (clonidine). In vitro osteoclast formation and activity was not affected by clonidine. Furthermore, we did not find an association between polymorphisms in the alpha-2 adrenergic receptor and fracture risk or bone mineral density in a large international consortium. In the second part of this thesis we focused on the humoral control of bone. 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. In addition, we showed that an eucaloric high-fat, low-carbohydrate diet decreases, while an eucaloric low-fat, high-carbohydrate diet increases bone resorption. Finally, we investigated the role of osteocalcin, a bone-specific protein synthesized by osteoblasts, in the regulation of glucose homeostasis and testosterone levels in humans, but could not find an endocrine or metabolic role for bone