The Important Role of Osteoblasts and Citrate Production in Bone Formation: "Osteoblast Citration" as a New Concept for an Old Relationship.

It has been known for about seventy years that bone, in all vertebrates, contains uniquely high citrate levels. However, the role of citrate, its source, its regulation, and its implication in normal bone formation and in bone disorders have remained largely unknown. For the past thirty-five years, the relationship of citrate in bone has been a neglected area of attention and research. It has recently been discovered that citrate is critical for the structure of the apatite nanocrystal, and is required to impart the important properties of bone such as its stability, strength, and resistance to fracture. This brings to focus the need for a renewed interest and research into the relationships of citrate in bone formation. A most fundamental question that must be resolved is "What is the source of citrate in bone?". This presentation provides a historical review of the early research to the present status of citrate implications in bone. This leads to a new concept of the role of osteoblasts as specialized citrate producing cells that provide the source of citrate in bone formation; i.e. the "osteoblast citration" process. This also brings into focus a new insight into the role of zinc in bone in relation to osteoblast citrate production. The genetic/hormonal/metabolic relationships of "net citrate production" are described. The intent of this presentation is to provide the background for a new perspective of the important implications of osteoblasts and citrate in bone formation; which, hopefully, will stimulate a renewed interest and essential research.