Risedronate Reduces Osteoclast Precursors and Cytokine Production in Postmenopausal Osteoporotic Women

Abstract

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.

Osteoclast Formation from Peripheral Blood of Patients with Bone-lytic Diseases

“…In postmenopausal osteoporotic women only the osteoclast precursors expressing avb3 were increased, whereas the percentage of cells expressing CD14 and CD11b was not altered compared to healthy controls [17]. Also, after bisphosphonate therapy the percentage of avb3-positive precursors dropped [16].…”

“…Since the pioneering study of Ritchlin et al [7], osteoclast formation from PBMCs from rheumatic diseases [7][8][9][10][11][12][13], osteoporosis [14][15][16][17][18], periodontitis [19,20], chronic liver disease with osteopenia [21] and osteolytic cancers [22][23][24][25] was investigated. Typically, osteoclast formation of PBMCs from these patients was compared with healthy controls, either unstimulated (in the absence of macrophage colony forming factor (M-CSF) and RANKL) or stimulated (in the presence of M-CSF and RANKL).…”

Soluble CD14 and fracture risk

“…Circulating CD14+ cells are increased in those with osteoporosis compared with healthy controls [44]. In a 3-month study, the bisphosphonate risedronate reduced levels of circulating CD14+ cells in women with osteoporosis [45]. The current study adds to our understanding of sCD14 biology in a population of older, community-dwelling adults.…”

Bisphosphonates Inhibit Pain, Bone Loss, and Inflammation in a Rat Tibia Fracture Model of Complex Regional Pain Syndrome: Erratum

“…5), in agreement with prior reports of bisphosphonate inhibitory effects on monocyte TNF, IL-1, and IL-6 expression in vitro [24][25][26][27][28][29] and on TNF, IL-1, and IL-6 levels in osteoporotic patients. [30][31][32] Previously we demonstrated that epidermal keratinocytes are the primary cellular source for the expression of cutaneous inflammatory mediators in fracture rats and mice and in CRPS patient skin. 20,[52][53][54] Interestingly, TNF and IL-6 levels are also increased in the skin and experimental skin blister fluid of CRPS affected limbs.…”

“…[24][25][26][27][28][29] Bisphosphonate treatment also reduces serum levels of TNF, IL-1, and IL-6 in osteoporosis patients. [30][31][32] Because bisphosphonates can potentially reverse pain, osteoclast activation, bone loss, inflammation, and antigen presentation, they present an attractive therapeutic approach in CRPS. The aim of the current study was to determine whether bisphosphonate treatments could inhibit the post-fracture development of nociceptive sensitization, reverse established pain behaviors, preserve trabecular bone integrity, and prevent the expression of cutaneous inflammatory mediators and immunocomplex deposition in skin and nerve after fracture.…”