Osteoprotegerin/sRANKL Ratio and Bone Mineral Density in Patients With Primary Hyperparathyroidism Treated With Parathyroidectomy or Alendronate

Study background and rationale

Receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) play key roles in regulating bone turnover. They are involved in the mechanism of "crosstalk" between osteoblasts and osteoclasts. After binding with RANK, RANKL induces bone loss, whereas OPG prevents RANKL-RANK interaction and increases bone mass and strength. The expression of RANKL has been found on the surface of many cell types including cells of the osteoblast lineage, osteocytes, activated T cells and vascular endothelial cells. RANK is a cell bound receptor for RANKL. Its expression has been detected mainly on cells of the macrophage/monocytic lineage, including pre-osteoclastic cells. OPG is produced and secreted by many different cell types including osteoblasts and vascular cells. The OPG/RANKL/RANK system is regulated by many hormones and cytokines among which parathormone (PTH) is one of the most important.

Primary hyperparathyroidism (PHPT) is characterized by sustained secretion of PTH from the parathyroid glands which is excessively disproportionate to calcium levels. This leads to enhanced bone turnover, predominantly resorption, resulting in low bone mass, hypercalcemia, hypercalciuria and hypophosphatemia. Successful parathyroidectomy (PTX) reverses these pathological conditions and is the treatment of choice in PHPT. Alternatively, the bone disease in PHPT may be treated pharmacologically by using bisphosphonates which are able to diminish bone turnover. The mechanism by which PTH exerts its effects in bone and the mechanism of bone loss in PHPT in humans have not been fully explained. PHPT with enhanced PTH seems to be a suitable model to observe possible relationships between PTH, OPG and RANKL.

Study objectives

The primary objective of this study is to investigate the serum Osteoprotegerin/sRANKL (soluble RANKL) ratio in patients with primary hyperparathyroidism who will be treated with parathyroidectomy or with alendronate