The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins

Hewitt, Rachel E.; Lissina, Anna; Green, A. E.; Slay, E. S.; Price, David A.; Sewell, Andrew K.

doi:10.1111/j.1365-2249.2005.02665.x

Cited by 215 publications

(159 citation statements)

References 87 publications

(137 reference statements)

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“…It was more probably linked to local 17 mucosal inflammation and bone necrosis, thus being the consequence of the induction of osteoclast differentiation and 18 activity, due to the increased RANKL/OPG ratio. IL-6 is considered to be an osteoclastogenic cytokine, and thus an isopentenyl pyrophosphate, which is a potent activator of human peripheral blood γδ T cells [28]. Moreover, this latter 23 study found a correlation between the mevalonate pathway and γδ T cell activation by statin administration: statins 24 inhibited the activation of human peripheral blood γδ T cells in response to endogenous non-sterol mevalonate products.…”

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confidence: 81%

Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid

et al. 2012

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confidence: 81%

Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid

et al. 2012

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“…This threshold might be used for implementing preventing strategies for APR, for example, based on the administration of statins in conjunction with aminobisphosphonates. (13) It is known that both the risk of APR (12) and the number and proportion of gd T cells decreases with aging. (14,15) However, we found that also the age-adjusted gd T cell number and proportion remain significant determinants of the occurrence of APR.…”

Section: Discussionmentioning

confidence: 99%

Circulating γδ T cells and the risk of acute-phase response after zoledronic acid administration

Rossini

Adami

Viapiana

et al. 2011

Journal of Bone and Mineral Research

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The use of intravenous nitrogen-containing bisphosphonates (N-BPs) is associated with the appearance of an acute phase response (APR) in a proportion of the patients for reasons that are poorly understood. The APR was attributed to the indirect activation of gd T cells with the release of interferon-g and tumor necrosis factor (TNF). Forty patients with postmenopausal or senile osteoporosis (age range ¼ 53-91 years) never previously treated with intravenous (iv) bisphosphonate, received a single 5-mg zoledronic acid (ZOL) iv infusion over 15 minutes. White blood cells were counted and analyzed with an automated hematology analyzer (ADVIA 2120i Siemens, New York, USA) and by flow cytometer (BD FACSCanto, Becton Dickinson). The occurrence of APR was defined by the occurrence of fever (>37 8C) during the next 2 days. Forty-two percent of patients (17 of 40) receiving the infusion of ZOL experienced an APR. Compared with the others they were younger (69 AE 7 years versus 74 AE 8 years; p ¼ 0.06), and both the proportion and absolute number of gd T cells were significant higher ( p ¼ 0.02 and p ¼ 0.013, respectively). Nonsignificant differences were found between the two groups for white blood cells and for the other circulating lymphocyte subpopulations. Age was inversely correlated with circulating gd T cells (p ¼ 0.003) but the difference between the two groups in circulating gd T cells persisted for age-adjusted values and vice versa. In conclusion, the results of this study indicate that the number of circulating gd T cells, together with age, are important determinant of the occurrence of APR after intravenous infusion of ZOL and possibly of any other N-BPs. ß

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“…In contrast, another study has demonstrated that zoledronate did not reduce the population of osteoclast precursor after 18 months of treatment in osteopenic women, (27) There are also conflicting in vitro data regarding the effect of bisphosphonates on osteoclastogenic cytokines such as IL-1, TNF and circulating levels of RANKL and osteoprotegerin (OPG) (28)(29)(30)(31)). RANKL is produced by the osteoblasts and binds to the receptor RANK which is located on the osteoclast precursor cells as well as the mature osteoclast (32).…”

Section: Introductionmentioning

confidence: 97%

The effect of bisphosphonate treatment on osteoclast precursor cells in postmenopausal osteoporosis: The TRIO study

Gossiel

Hoyle

McCloskey

et al. 2016

Bone

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Bisphosphonates are used to treat bone disease characterised by increased bone resorption by inhibiting the activity of mature osteoclasts, resulting in decreased bone turnover.Bisphosphonates may also reduce the population of osteoclast precursor cells. Our aims were to investigate the effect of bisphosphonates on i) osteoclast precursor cells and ii) circulating cytokine and cytokine receptor in postmenopausal women with osteoporosis compared with healthy premenopausal women. Participants were 62 postmenopausal women (mean age 66) from a 48-week parallel group trial of bisphosphonates. They received ibandronate 150mg/month (n=22), alendronate 70mg/week (n=19) or risedronate 35mg/week (n=21). Fasting blood was collected at baseline, weeks 1 and 48. At baseline, blood was also collected from 25 healthy premenopausal women (mean age 37) to constitute a control group. Peripheral blood mononuclear cells were extracted and stained for CD14, M-CSFR, CD11b and TNFRII receptors. Flow cytometry was used to identify cells expressing CD14+ and M-CSF+ or CD11b+ or TNFRII+. RANKL and OPG were measured to evaluate potential mediation of the bisphosphonate effect. After 48 weeks of treatment, there was a decrease in the percentage of cells expressing M-CSFR and CD11b receptors by 53% and 49% respectively (p<0.01). Cells expressing M-CSFR and CD11b were decreased with ibandronate and risedronate after 48 weeks to the lower part of the premenopausal reference interval. These effects were not significantly different between each of the treatment groups. There was no significant effect on RANKL and OPG throughout the study period. Bisphosphonates inhibit bone resorption in the short-term by direct action on mature osteoclasts. There is also a later effect mediated in part by a reduction in the population of circulating osteoclast precursors.

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The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins

Cited by 215 publications

References 87 publications

Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid

Oral mucosa produces cytokines and factors influencing osteoclast activity and endothelial cell proliferation, in patients with osteonecrosis of jaw after treatment with zoledronic acid

Circulating γδ T cells and the risk of acute-phase response after zoledronic acid administration

The effect of bisphosphonate treatment on osteoclast precursor cells in postmenopausal osteoporosis: The TRIO study

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