The Role of Calcitriol in the Treatment of Osteoporosis

Abstract

1,25(OH) 2 D 3 (calcitriol) is the major biologically active metabolite of vitamin D 3 . The principal regulators of 1,25(OH) 2 D 3 production are parathyroid hormone, 1,25(OH) 2 D 3 itself, dietary intake of calcium, and phosphate. There are three primary target organs for circulating 1,25(OH) 2 D 3 : intestine, parathyroid gland, and bone. The overall effects of 1,25(OH) 2 D 3 on mineral metabolism may be summarized as follows: increased intestinal calcium absorption, leading to a rise in serum calcium; decrease of serum parathyroid hormone (PTH) level (both through direct inhibition of PTH secretion from the parathyroid gland and through indirect inhibition of PTH secretion by the raised serum calcium level); decreased bone resorption due to a reduction in the PTH-mediated bone resorption; and under certain conditions, increased bone formation [1][2][3][4].Although there are many factors modulating the progression of age-related bone loss syndromes, the pathogenesis of this process has been attributed to decreased calcium absorption by an "aging intestine" to an associated elevation in circulating PTH, decreased gonadal hormonal and calcitonin, and decreased synthesis of 1,25(OH) 2 D 3 [5-7].Decreased 1,25(OH) 2 D 3 synthesis by the aging kidney results from both age-related progressive loss in the capacity of the renal 1-alpha-hydroxylase to respond to progressive elevation in circulatory PTH and an age-related decrease in the circulating 25OHD which is a precursor to 1,25(OH) 2 D 3 [8,9]. Moreover, a complex array of interactions between the "calciotropic" hormones family, which characterize senescence, is further exemplified by the fact that age-related increases in PTH production are less likely to be suppressed by low circulatory 1,25(OH) 2 D 3 and that defective 1,25(OH) 2 D 3 synthesis by the aging kidney increases the skeletal response to both gonadal hormone deficiency and PTH excess [10,11]. Finally, increments in serum osteocalcin levels observed in humans treated with 1,25(OH) 2 D 3 , and animal studies demonstrating an increased number of bone marrow osteoblast precursors during 1,25(OH) 2 D 3 administration are consistent with the hypothesis that abnormalities in the production and skeletal distribution of 1,25(OH) 2 D 3 must also contribute to the defects in osteoblast function and bone formation observed histologically in both humans and experimental animal models with osteoporotic syndromes [12][13][14][15][16].

Mannitol evaluated mineral absorption and bone retention in ovariectomized rats

“…Postmenopausal women face to the risk of osteoporosis because the production and regulating effects of the related hormones including parathyroid hormone, calcitriol, estrogen were altered after menopause. Bone loss syndrome is mainly modulated by the decreased calcium absorption and bone resorption to an associated elevation in circulating parathyroid hormone and the decrease in calcitriol and estrogen (Nuti et al 2000). In ovariectomized rats, estrogen deficiency caused bone mass loss (Egermann et al 2005).…”