Osteofertility: Nexus between bone health and fertility

Conventionally, bone was considered a static organ that only serves the protective and locomotive functions. However, our understanding of bone has evolved significantly during the past few decades. From an uninteresting scaffold, bone has become a fascinating organ that regulates various local and systemic functions. Recent research suggests that the skeleton is an important endocrine organ, with osteocalcin being the most prominent hormone produced by bone-forming osteoblast cells. Osteocalcin controls several physiological functions, such as glucose homeostasis, energy expenditure, and brain development. Another intriguing role of osteocalcin is that it regulates male fertility by enhancing testosterone biosynthesis independently of the hypothalamus-pituitary axis. This demonstrates that bone is an endocrine regulator of reproduction and expands the functional repertoire of osteocalcin. Furthermore, osteocalcin interconnects the bone, energy metabolism, and reproduction to form the novel pancreas-bone-testis axis. This review summarizes the current knowledge of osteocalcin-mediated regulation of different biological functions with special reference to its role in regulating male reproduction. This will provide deep insights into the underlying mechanisms involved in male fertility and improve our understanding of the relationship between bone and reproduction.