Anticalcification and antiresorption effects of bisacylphosphonates

Gelder, Joel M. Van; Breuer, Eli; Ornoy, Asher; Schlossman, Ada; Patlas, N.; Golomb, Gershon

doi:10.1016/8756-3282(95)00081-n

Cited by 46 publications

(46 citation statements)

References 30 publications

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“…7,9 In brief, inhibition of spontaneous HAP formation was studied in a solution with a calcium and phosphate concentration product of 9 mM 2 , with a Ca/PO4 ratio of 1.67, as in HAP. Each salt solution was prepared in 0.05 M Tris buffer (pH 7.4), and the drug examined was dissolved in the phosphate solution.…”

Section: Methodsmentioning

confidence: 99%

“…Most of the research data on new compounds to date has been confined only to side chainmodified derivatives of gem bisphosphonates and to bisacylphosphonates. 2,[7][8][9] The most potent phosphonates described until now have been of the gem type, bisphosphonic X Abstract published in Advance ACS Abstracts, February 1, 1997. acids containing nitrogen in the side chain and hydroxyl or halogens on the gem carbon (see Figure 1). Monophosphonates and esters of bisphosphonates are inactive in calcium related disorders.…”

Section: Introductionmentioning

confidence: 99%

“…Monophosphonates and esters of bisphosphonates are inactive in calcium related disorders. 5,7,[9][10][11][12] The capacity of bisphosphonates to accumulate in bone is a consequence of their high affinity to hydroxyapatite (HAP) due to bi-or tridentate interaction with the phosphonic and hydroxyl functions. It seemed logical to speculate that molecules that contain two distant gem bisphosphonic functions would possess improved biological activity due to enhanced interaction with calcium/HAP.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro and In Vivo Effects of Tetrakisphosphonates on Bone Resorption, Tumor Osteolysis, Ectopic Calcification, and Macrophages

Gelder

Breuer

Schlossman

et al. 1997

Journal of Pharmaceutical Sciences

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The biological effects of bisphosphonates in calcium-related disorders are attributed to the incorporation of the bisphosphonates in bone, enabling direct interaction with osteoclasts and/or osteoblasts. The high accumulation of bisphosphonates in bone, due to their high affinity to hydroxyapatite (HAP), is essential for mediating in vitro and in vivo activity. In this study we examined the activity of tetrakisphosphonates, molecules containing two P-C-P type bisphosphonate moieties connected by a carbon chain. The novel compounds were examined in a battery of in vitro and in vivo models including HAP formation and dissolution, ectopic calcification, bone resorption, tumor osteolysis, and of macrophage-like cells (anti- or pro-inflammatory properties). The inhibition of ectopic calcification was ranked as follows: geminal bisphosphonates > bisacylphosphonates > tetrakisphosphonates. Pamidronate, but not the tetrakisphosphonates, was an effective antiosteolytic agent. Neither DNTP (tetrasodium 1,9-dihydroxynonane 1,1,9,9-tetrakisphosphonate) nor the bisacylphosphonate, PiBP (pimeloylbisphosphonate) seem to possess strong macrophage suppressive or inductive effects and can be considered to be relatively inactive in terms of anti- or pro-inflammatory action. A significant anticalcification effect was caused by various phosphonates, such as the tetrakisphosphonates, but DNTP, a tetrakisphosphonate, was found toxic as it impeded somatic growth and bone development.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In Vitro and In Vivo Effects of Tetrakisphosphonates on Bone Resorption, Tumor Osteolysis, Ectopic Calcification, and Macrophages

Gelder

Breuer

Schlossman

et al. 1997

Journal of Pharmaceutical Sciences

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“…In nature there are different forms of chelation between Ca and organic molecules [23] and their molecular nature and structure are still being studied, requiring new techniques in the field of biotechnology [24]. However, these chelation reactions do not always result in molecules with high nutritional bioavailability [25].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Different Calcium Sources on the Performance of Highly Prolific Lactating Sows

Lne¹,

Ban²,

Maiorka³

et al. 2017

J Vet Sci Technol

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Improvements in sow productivity have raised questions regarding dietary mineral recommendations. Current calcium (Ca) levels and/or Ca sources might not support milk requirements of the larger litter in the modern sow. Therefore, four hundred and eighty mixed parity sows of a high prolificacy genetic line were used to evaluate the impact of the calcium source on the performance of highly prolific lactating sows. Sows were distributed in a completely randomized experimental design among six treatments containing different levels of inorganic Ca (INO) and organic calcium carbon-amino-phospho-chelate (CQT) inclusion. The sows were allocated to one of the six treatments represented by increased replacement ratios between sources of calcium: 100% INO; 100% CQT; 80% INO and 20% CQT; 60% INO and 40% CQT; 40% INO and 60% CQT; 20% INO and 80% CQT. Farrowing duration was not influenced (P>0.10) by the treatments, and averaged 185 minutes. Average daily voluntary feed intake did not differ (P>0.10) between treatments (5.54 kg d -1 on average). The lactation BW, backfat losses and chemical composition of body weight loss was not influenced (P>0.10) by the treatments. Litter size and average piglet weight at birth were not influenced (P>0.10) by the treatments (13.7 and 1.26 kg, on average). Litter weight gain, litter size and average piglet weight at weaning were also not influenced (P>0.10) by the treatments. The Treatments did not influence (P>0.10) estimated daily milk yield; which averaged 11.41 kg d -1 . The treatments tended to influence (P<0.10) urinary pH levels at day 7 of lactation, were 100% CQT sows had a lower pH value than other treatments (6.72 vs. 7.27). 100% CQT sows also showed a significantly lower pH level at d 14 and 21 when compared to the other treatments (6.44 vs. 7.09; P<0.05; and 6.48 vs. 7.14; P<0.01; respectively for d 14 and 21 of lactation). Free Ca and parathyroid hormone (PTH) serum levels were not affected (P>0.10) by treatments during lactation and averaged 1.38 mmol/L and 14.62 pg/ml, respectively. In conclusion, this experiment demonstrated that in diets for lactating sows an inorganic Ca source can be fully replaced by a more available Ca source (i.e., calcium carbon-amino-phospho-chelate), without negatively impacting the productive and reproductive performance of these animals or the performance of their litters.

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“…Morever, phosphonates with (P-C) bonds do not hydrolyze in the presence of pyrophosphatase like phosphates and so retain their activity in conditions in which phosphates would be destroyed [16]. Recently, nongeminal bis(phosphonates) with a keto group in the α position have been reported to be active as anticalcification and antiresorption agents [17][18][19]. Furthermore, the calcium coordinating properties of phosphonic acids were examined to arrive at a better understanding of their biological activities (inhibition of metalloenzymes, metabolic regulation, etc.…”

Section: Introductionmentioning

confidence: 97%

Preparation and characterization of new hybrid organic/inorganic systems derived from calcium (α-aminoalkyl)-phosphonates and -phosphonocarboxylates

Al-Ali

Lebugle

Rico‐Lattes

et al. 2005

Journal of Colloid and Interface Science

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We have studied the phenomenon of calcium complexation by lab synthesized amphiphilic (alpha-aminoalkyl)-phosphonocarboxylic or -phosphonic acids. The electrical conductivity of aqueous solutions of sodium salts of all these acids was measured versus the volume of a calcium salt solution added. It appeared that calcium complexes are formed in a Ca/P atomic ratio close to 1. Calcium phosphonocarboxylates and calcium phosphonates were also precipitated by mixing aqueous solutions of disodium salts of phosphorus amphiphiles and calcium nitrate solutions. Before chemical analysis, these complexes were calcined to remove the organic part. In the mineralized products, calcium and phosphate were assayed: the Ca/P atomic ratio was equal to 1. X-ray diffraction and IR spectroscopy showed that they are made entirely of beta pyrophosphate (Ca2P2O7), a result in agreement with previous chemical analysis. The chemical formula of the starting calcium complexes could be written as CaL2H2O (L=ligand). The SEM micrographs of these complexes show plate-like structures. XRD patterns are characteristic of layered structures. These facts suggest that calcium complexes are composed of alternating bimolecular layers of calcium alkylphosphonocarboxylates or calcium alkylphosphonates, the chains being tilted and partially interdigitated.

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Anticalcification and antiresorption effects of bisacylphosphonates

Cited by 46 publications

References 30 publications

In Vitro and In Vivo Effects of Tetrakisphosphonates on Bone Resorption, Tumor Osteolysis, Ectopic Calcification, and Macrophages

In Vitro and In Vivo Effects of Tetrakisphosphonates on Bone Resorption, Tumor Osteolysis, Ectopic Calcification, and Macrophages

Evaluation of Different Calcium Sources on the Performance of Highly Prolific Lactating Sows

Preparation and characterization of new hybrid organic/inorganic systems derived from calcium (α-aminoalkyl)-phosphonates and -phosphonocarboxylates

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