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Osteoprotegerin is a glycoprotein that plays a major role in the regulation of bone turnover. The influence of parathyroid hormone, an important regulator of bone remodeling, on osteoprotegerin production is controversial. The purpose of the study was to assess the influence of parathyroid hormone on the circulating level of osteoprotegerin in patients with primary hyperparathyroidism by comparing it with healthy controls.Forty-four patients with biochemical verification of primary hyperparathyroidism scheduled for the surgical cure and 38 healthy subjects were included. Blood samples of the study group were taken before surgery. Levels of serum parathyroid hormone, osteoprotegerin, calcium, 25-hydroxyvitamin D [25(OH)D], and alkaline phosphatase were analyzed. Bone mineral density at the L1-L4 vertebrae and femoral neck was calculated by dual-energy X-ray absorptiometry.Osteoprotegerin levels and bone mineral density values were significantly lower in patients than in the healthy subjects (P=.002 and P.0001, respectively). There was no correlation between osteoprotegerin and parathyroid hormone in the groups. Osteoprotegerin was weakly correlated with bone mineral density in patients. No correlation was noted between osteoprotegerin and bone mineral density in the control group. Furthermore, osteoprotegerin levels were not correlated with calcium, 25(OH)D, and alkaline phosphatase levels in each group.The production of osteoprotegerin appears to be inhibited by parathyroid hormone in patients with primary hyperparathyroidism. A weak positive correlation found among osteoprotegerin and bone mineral density recommends that osteoprotegerin may be a molecule that impacts bone metabolism and finally bone mineral density.