Clinical Trial: OPG/Soluble RANKL (sRANKL) and Bone Mineral Density in Primary Hyperparathyroidism
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Osteoprotegerin/sRANKL Ratio and Bone Mineral Density in Patients With Primary Hyperparathyroidism Treated With Parathyroidectomy or Alendronate
Brief Summary: The purpose of this study is to determine whether osteoprotegerin and RANKL (receptor activator of nuclear factor-κB ligand) are involved in bone remodeling in patients with primary hyperparathyroidism (PHPT), and whether alendronate may be useful in treatment of the patients with PHPT who are not treated with parathyroidectomy.
Detailed Summary:
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.
Sponsor: Wroclaw Medical University
Current Primary Outcome: Change from baseline in osteoprotegerin/sRANKL ratio at month 12 [ Time Frame: 12 months ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Changes from baseline in bone mineral density values at month 12 [ Time Frame: 12 months ]
- Change from baseline in PTH serum concentration at month 12 [ Time Frame: 12 months ]
Original Secondary Outcome: Same as current
Information By: Wroclaw Medical University
Dates:
Date Received: June 21, 2013
Date Started: January 2009
Date Completion:
Last Updated: June 25, 2013
Last Verified: June 2013
