The effect of alendronate on the osteoclastogenic potential of the bone marrow in mice

Beek, Ermond van; Löwik, C.W.G.M.; Papapoulos, Socrates E.

doi:10.1016/8756-3282(96)87975-0

Cited by 2 publications

(3 citation statements)

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“…This results in the accumulation of constitutively active unprenylated GTPases in the cytoplasm of the osteoclast, which causes inappropriate activation of downstream signaling pathways, leading to the disruption of normal osteoclast function and survival [7]. Thus, N-BPs suppress bone resorption by a direct effect on osteoclasts and their precursors [1,2,7].…”

Section: Introductionmentioning

confidence: 98%

“…N-BPs such as alendronate, ibandronate, risedronate, and zoledronate inhibit the enzyme farnesyl diphosphate synthase (FPPS) and block prenylation of small GTPases such as Ras, Rac, Rho, and cdc42 [3][4][5][6]. This results in the accumulation of constitutively active unprenylated GTPases in the cytoplasm of the osteoclast, which causes inappropriate activation of downstream signaling pathways, leading to the disruption of normal osteoclast function and survival [7]. Thus, N-BPs suppress bone resorption by a direct effect on osteoclasts and their precursors [1,2,7].…”

Section: Introductionmentioning

confidence: 99%

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The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts

Enjuanes

Ruiz-Gaspà

Peris

et al. 2009

Endocr

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Alendronate is a well-established treatment for osteoporosis and suppresses bone resorption by a direct effect on osteoclasts and their precursors. The effect of alendronate on osteoclasts is produced, at least in part, by the receptor activator of nuclear factor kappaB ligand (RANKL) and the osteoprotegerin (OPG) synthesized by the osteoblasts. This study analyzes the effect of alendronate in cell viability, phosphatase alkaline (ALP) activity and RANKL, and OPG expression in primary human osteoblasts (hOB). Alendronate at concentrations lower than 10(-5) M did not have a toxic effect on hOB in vitro and did not modify the ALP activity at least for 72 h. Alendronate did not change OPG expression in basal, 10% FBS, and vitamin D-treated cultures. Similar results were observed at the protein level. Unexpectedly, alendronate at 10(-7) and 10(-5) M concentrations increased the RANKL expression with the presence of vitamin D in differentiated hOB and this induction of RANKL mRNA levels by alendronate was dose-dependent. However, this effect was not observed in basal and 10% FBS culture conditions. Thus, we conclude that alendronate does not affect the ALP activity and OPG gene expression in differentiated hOB, but may increase RANKL gene expression induced by vitamin D.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts

Enjuanes

Ruiz-Gaspà

Peris

et al. 2009

Endocr

View full text Add to dashboard Cite

show abstract

“…Depletion of FPP levels also results in diminished cellular levels of geranylgeranyl diphosphate (GGPP), and the cellular effects observed may result from an impact on the downstream process of protein geranylgeranylation. [18][19][20][21][22] Many forms of cancer exhibit abnormalities in prenylated GTPases, 23 Our labs have reported the synthesis of mono-and dialkyl isoprenoid bisphosphonates (e.g., 5, Fig. 2) that selectively target geranylgeranyl diphosphate synthase (GGDPS, EC 2.5.1.29) over FDPS.…”

Section: Introductionmentioning

confidence: 99%