PTH and Hypercalcemia: In particular, gain-of-function mutations are responsible for parathyroid hyperplasia/adenoma with a constant over-secretion of Parathyroid Hormone (PTH) and hypercalcemia, resulting in increased osteoclast activity, a continuous release of calcium ion from bone tissue and a subsequent reduction in mineralized bone mass, leading to early onset osteopenia and osteoporosis with an enhanced praecox risk of fragility fractures.