Parathyroid Diseases and T Cells

Purpose of Review This review summarizes studies into the permissive role of T cells in the bone catabolic effects of hyperparathyroidism and parathyroid hormone (PTH). Recent Findings Work in animals combined with recent translational studies in humans now highlight the potent amplificatory action of T cells on PTH-induced bone resorption. Mechanistic animal studies reveal a complex pathway by which PTH exploits natural self-renewal functions of CD4(+) T cells, to drive TNF alpha production that promotes formation of IL-17A secreting Th17 T cells. TNF alpha and IL-17 further amplify osteoblastic receptor activator of NF-kappa B ligand (RANKL) production and down-modulate osteoprotegerin (OPG), establishing conditions propitious for osteoclastic bone resorption. Summary These findings are consistent with, and add to, the traditional view of PTH-induced bone loss involving only osteoblast-lineage cells. T cells potently amplify traditional pathways and provide permissive costimulatory signals to bone marrow stromal cells, facilitating the development of an increased RANKL/OPG ratio favourable to bone resorption and bone loss.