Endocrine Abstracts

Bone has three main components: matrix, mostly made up of type 1 collagen, mineral, which is laid down on the matrix by osteoblasts, and bone cells: osteoclasts, which are derived from haemopoietic precursors, osteoclasts, which are of fibroblast precursor origin, and osteocytes, the most numerous, which are derived from osteoblasts.

Osteoblasts operate under the influence of several humoral factors including PTH, 1,25(OH)₂D and cytokines which act via specific receptors on the cell surface to stimulate osteoblast development and function with the aid of a number of other proteins such as LRP5, Sclerostin and Wnt signalling. Bone matrix formation is under genetic control by several genes including COL1A1, COL1A2, IFITM5, CRTAP, LEPRE1 and PPIB, mutations in any of which can cause OI.

Osteoclasts are controlled by osteoblasts under the influence of RANK and its natural inhibitor osteoprotegerin which acts via the RANK ligand on the surface of osteoclasts. Bone resorption is achieved by maintaining an acid environment using TCIRG1, CAII, OSTM1, CLCN7 and PLEKHM1 (mutations cause osteopetrosis), whilst cathepsin K removes demineralised matrix (mutations cause pyknodysostosis).

Osteocytes play a major role in maintaining phosphate mainly via the action of FGF23 which is under the influence of several genes including PHEX, DMP1, GALNT3, FGFR1c, Klotho and NaPi1. Mutations in any of these genes may cause either hypophosphataemic rickets or familial tumoral calcinosis.

This talk will give an overview of these processes and show how they link together and will concentrate on the newer aspects of phosphate physiology.