Uptake of a fluorinated bisphosphonate by cultured bones

Rowe, Dorothy J.; Etre, Lois A.

doi:10.1016/8756-3282(88)90013-0

Cited by 8 publications

(3 citation statements)

References 16 publications

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“…Our previous results using the electron probe to detect the fluorine of F2MBP indicated that after 15 rain of incubation, a greater amount of fluorine was evident in F2MBP-treated bones than in the controls (29). The current study determined the actual, rather than relative, amounts taken up by the bones after short exposures.…”

Section: Discussionmentioning

confidence: 79%

Relationship between bisphosphonate concentration and osteoclast activity and viability

Rowe

Etre

Lovdahl

et al. 1999

In Vitro Cell.Dev.Biol.-Animal

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Difluoromethylidene bisphosphonate (F2MBP) is one of the many bisphosphonates known to inhibit bone resorption in vitro and in vivo. We have developed an analytical method, employing anion exchange and postcolumn indirect fluorescence detection, by which F2MBP can be quantified in bone samples. The objective of this study was to relate the concentration of F2MBP in embryonic bones treated in organ culture to the physiological effects of the compound, such as bone resorption (i.e., the amount of 45Ca released into the medium from prelabeled bones) and viability of the osteoclast population (i.e., the incidence of abnormal osteoclasts). Osteoclasts in bones treated with F2MBP exhibited morphological features of apoptosis, such as nuclear fragmentation. Both the number and percentage of these abnormal cells increased with dose of F2MBP and duration of incubation. The decrease in normal osteoclasts was correlated with the decreased amount of 45Ca released into the medium. Bones treated with F2MBP for only the first 5 min of the 48-h incubation period had similar numbers of abnormal osteoclasts and amounts of 45Ca released, as had bones incubated with F2MBP continuously for 48 h. The uptake of F2MBP into the bone was rapid. Bones treated with F2MBP for 6 h were similar to bones treated with F2MBP for the entire 48-h incubation period, both in F2MBP concentration and the 45Ca release ratios. These relationships between concentrations of F2MBP within bone and osteoclast activity and viability implicate apoptosis in the mechanism by which this bisphosphonate inhibits bone resorption.

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Section: Discussionmentioning

confidence: 79%

Relationship between bisphosphonate concentration and osteoclast activity and viability

Rowe

Etre

Lovdahl

et al. 1999

In Vitro Cell.Dev.Biol.-Animal

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“…A correlation between increasing acidity and antiresorptive activity of BPs has been reported [30]. Yet a strongly acidic BP such as 1,1,2,2-tetrafluoroethane-1,2-bisphosphonate (pKa 1 ‫ס‬ 1.07; pKa 2 ‫ס‬ 1.97, pKa 3 ‫ס‬ 4.49, pKa 4 ‫ס‬ 6.30) [31], was not found active as an inhibitor of bone resorption [32]. We synthesized bisphosphonate 6, with a chain length similar to that of AdBP, with difluoro groups replacing the keto groups in positions next to the phos-phonic groups.…”

Section: Figurementioning

confidence: 99%

Long-chain functional bisphosphonates: synthesis, anticalcification, and antiresorption activity

Chen¹,

Schlossman²,

Breuer³

et al. 2000

Heteroatom Chem.

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Bisacylphosphonates have previously been shown to possess in vitro activity with regard to hydroxyapatite (HAP) formation and dissolution, and in vivo on tissue calcification and bone resorption. This work was aimed at elucidating the role of the keto groups in the biological activity of these compounds. For this purpose, we have synthesized a series of long‐chain bisphosphonates possessing different functional groups adjacent to the phosphonic functions and examined them in some in vitro and in vivo models. The functional groups introduced into the newly synthesized bisphosphonates (hydroxyl, amide, and difluoromethylene) were chosen as to represent certain isolated aspects of the keto groups in the original compounds. None of the functional groups introduced into the long chain bisphosphonates bestowed higher activity on the molecules than the carbonyl groups. The unique effect of the α‐keto groups in rendering long‐chain bisphosphonates active is presumably attained through a combination of chelating ability with sufficiently low pKa values to enable the bisacylphosphonate molecules to be fully ionized at physiological pH. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:470–479, 2000

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Section: Figurementioning

confidence: 99%

Long‐chain functional bisphosphonates: synthesis, anticalcification, and antiresorption activity

Chen¹,

Schlossman²,

Breuer³

et al. 2000

Heteroatom Chem.

View full text Add to dashboard Cite

show abstract

Uptake of a fluorinated bisphosphonate by cultured bones

Cited by 8 publications

References 16 publications

Relationship between bisphosphonate concentration and osteoclast activity and viability

Relationship between bisphosphonate concentration and osteoclast activity and viability

Long-chain functional bisphosphonates: synthesis, anticalcification, and antiresorption activity

Long‐chain functional bisphosphonates: synthesis, anticalcification, and antiresorption activity

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