Alendronate reduces osteoclast precursors in osteoporosis

D’Amelio, Patrizia; Grimaldi, Anastasia; Ma, Cristofaro; Ravazzoli, Marco; Molinatti, P. A.; Pescarmona, Gianpiero; Isaia, Giovanni Carlo

doi:10.1007/s00198-009-1129-1

Cited by 43 publications

(33 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As an antiresorptive (antianabolic) agent, it is known to inhibit the enzyme farnesyl pyrophosphate synthase (FPPS), inducing apoptosis in osteoclasts and consequently suppressing osteoclast-mediated bone resorption. (34)(35)(36)(37) Because we observed a significant increase in the percentage and number of LKS cells in the bone marrow and spleen (Fig. 5) and an increase in the activity of osteoclasts in vitro (Figs.…”

Section: Resultsmentioning

confidence: 88%

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Jacome-Galarza

Lee

Lorenzo

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Parathyroid hormone (PTH) increases both the number of osteoclast in bone and the number of early hematopoietic stem cells (HSCs) in bone marrow. We previously characterized the phenotype of multiple populations of bone marrow cells with in vitro osteoclastogenic potential in mice. Here we examined whether intermittent administration of PTH influences these osteoclast progenitor (OCP) populations. C57BL/6 mice were treated with daily injections of bPTH(1-34) (80 mg/kg/day) for 7 or 14 days. We found that PTH caused a significant increase in the percentage of TN/CD115 þ CD117 high and TN/CD115 þ CD117 int cells ( p < .05) in bone marrow on day 7. In contrast, PTH decreased the absolute number of TN/CD115 þ CD117 low cells by 39% on day 7 ( p < .05). On day 14, there was no effect of PTH on osteoclast progenitor distribution in vivo. However, PTH treatment for 7 and 14 days did increase receptor activator of NF-kB ligand (RANKL)-and macrophage colony-stimulating factor (M-CSF)-stimulated in vitro osteoclastogenesis and bone resorption in TN/ CD115 þ cells. In the periphery, 14 days of treatment increased the percentage and absolute numbers of HSCs (Lin À CD117 þ Sca-1 þ ) in the spleen ( p < .05). These data correlated with an increase in the percent and absolute numbers of HSCs in bone marrow on day 14 ( p < .05). Interestingly, the effects on hematopoietic progenitors do not depend on osteoclast resorption activity. These results suggest that in vivo PTH treatment increased in vitro osteoclastogenesis and resorption without altering the number of osteoclast precursors. This implies that in vivo PTH induces sustained changes, possibly through an epigenetic mechanism, in the in vitro responsiveness of the cells to M-CSF and RANKL. ß

show abstract

Section: Resultsmentioning

confidence: 88%

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Jacome-Galarza

Lee

Lorenzo

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…As we observed that the uptake of ALN by macrophages was reduced as the pH decreased, we could assume that conjugation to BSP could affect the endocytosis of ALN and eventually influence its activity. Interestingly, such findings provide a new clue to explain why ALN has rarely been reported to successfully kill TAM in vivo e though it is well known to do so in vitro [39e41] and has recently excited much interest as potential inhibitors of TAMs [5,42,43]. To date, no study has confirmed that ALN could directly eliminate TAMs in vivo, despite some studies suggesting its effect in stimulating dendritic cells (DCs) [44] or inhibiting angiogenesis and lymph node invasion [45].…”

Section: Discussionmentioning

confidence: 99%

Targeted depletion of tumour-associated macrophages by an alendronate–glucomannan conjugate for cancer immunotherapy

et al. 2014

View full text Add to dashboard Cite

“…These were identified by their expression of CD14/CD11b and were decreased after 12 months of treatment in osteoporotic women (26). 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)).…”

Section: Introductionmentioning

confidence: 99%

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

Gossiel

Hoyle

McCloskey

et al. 2016

Bone

View full text Add to dashboard Cite

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.

show abstract

Alendronate reduces osteoclast precursors in osteoporosis

Abstract: We suggest that alendronate mainly acts on mature bone resorbing osteoclasts in the short term, whereas, its long-term administration diminishes their formation by reducing their precursors and serum RANKL.

Cited by 43 publications

References 49 publications

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Targeted depletion of tumour-associated macrophages by an alendronate–glucomannan conjugate for cancer immunotherapy

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

Contact Info

Product

Resources

About