The classical functions of vitamin D are to regulate calcium-phosphorus homeostasis and control bone metabolism. However, vitamin D deficiency has been reported in several chronic conditions associated with increased inflammation and deregulation of the immune system, such as diabetes, asthma, and rheumatoid arthritis. These observations, together with experimental studies, suggest a critical role for vitamin D in the modulation of immune function. This leads to the hypothesis of a disease-specific alteration of vitamin D metabolism and reinforces the role of vitamin D in maintaining a healthy immune system. Two key observations validate this important non-classical action of vitamin D: first, vitamin D receptor (VDR) is expressed by the majority of immune cells, including B and T lymphocytes, monocytes, macrophages, and dendritic cells; second, there is an active vitamin D metabolism by immune cells that is able to locally convert 25(OH)D3 into 1,25(OH)2D3, its active form. Vitamin D and VDR signaling together have a suppressive role on autoimmunity and an anti-inflammatory effect, promoting dendritic cell and regulatory T-cell differentiation and reducing T helper Th 17 cell response and inflammatory cytokines secretion. This review summarizes experimental data and clinical observations on the potential immunomodulating properties of vitamin D.
Osteoclasts are cells involved in bone reabsorbing and hence in postmenopausal bone loss. There is no evidence of increased in vitro spontaneous osteoclast formation in postmenopausal osteoporosis. The aim of our study was to evaluate spontaneous osteoclastogenesis in osteoporosis. Bone mineral density, markers of bone turnover, and cultures of peripheral blood mononuclear cells (PBMC) on dentine slices with or without the addition of 1,25-OH vitamin D3 ([10(-8) M]) were obtained from 18 osteoporotic women and 15 controls. To verify cytokine production by PBMC cultures, supernatants were collected on days 3 and 6 and tested for TNF-alpha and RANKL. The data obtained were compared between patients and controls by one-way ANOVA and correlated by Pearson's coefficient. We found a significant increase in osteoclast formation and bone reabsorbing activity in patients with respect to controls; in addition, the production of TNF-alpha and RANKL is significantly higher in patients. Furthermore, osteoclast number is inversely correlated with bone mineral density and directly with RANKL in culture supernatants. Our data demonstrated an increased spontaneous osteoclastogenesis in women affected by postmenopausal osteoporosis: this increase may be explained by the higher production of TNF-alpha and RANKL by PBMC cultures of osteoporotic patients.
This paper studies the effect of oral risedronate on osteoclast precursors, osteoclast formation, and cytokine production in 25 osteoporotic women. Risedronate is effective in reducing the number of osteoclast precursors, their formation, vitality, and activity and the level of RANKL and TNF-␣ in cultures.Introduction: Bisphosphonates inhibit bone resorption by acting against osteoclasts. Some in vitro studies suggest that they induce osteoclast apoptosis; others suggest that they exert an effect on the production of pro-osteoclastogenic cytokines. The effect of risedronate on osteoclastogenesis by peripheral blood mononuclear cells (PBMCs) in postmenopausal osteoporosis has not been previously studied. This paper examined the influence of risedronate on the formation of osteoclast precursors and cytokine production within the compass of osteoclastogenesis in osteoporosis. Materials and Methods: This study was conducted on 38 osteoporotic women; 25 patients were treated with risedronate 5 mg/d, whereas 13 were treated with calcium 1 g/d and vitamin D 800 UI/d. The following parameters were assessed: changes in bone turnover, circulating osteoclast precursors, formation of osteoclasts in PBMC cultures, their activity and vitality, and variations in the production of pro-osteoclastogenic cytokines before and after therapy. Results: After 3 mo of risedronate, there was a significant reduction in the number and degree of differentiation of osteoclast precursors, osteoclast formation, vitality and activity, and in the level of RANKL and TNF in cultures and of TNF and osteoprotegerin (OPG) in serum, whereas in the group treated with calcium and vitamin D, there were no significant changes. Conclusions: Our data show that risedronate is effective in lowering the number of circulating osteoclast precursors, their formation, vitality, and activity in cultures, and in reducing the level of pro-osteoclastogenic cytokines in culture supernatants and in serum.
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