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Cited by 865Bone health and treatmentsBone health and osteoporosis researchBone Metabolism and Diseases

The DOI matches its Crossref record; 71 of the 75 references it cites were found in a registry or an index.

Novel insights into actions of bisphosphonates on bone: Differences in interactions with hydroxyapatite

Nancollas, G.H., Tang, R., Phipps, R.J., Henneman, Z., Gulde, S., Wu, W., Mangood, A., Russell, R.G.G., Ebetino, F.H.·2006·Bone
DOI 10.1016/j.bone.2005.05.003
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Abstract

Bisphosphonates are now the most widely used drugs for diseases associated with increased bone resorption, such as osteoporosis. Although bisphosphonates act directly on osteoclasts, and interfere with specific biochemical processes such as protein prenylation, their ability to adsorb to bone mineral also contributes to their potency and duration of action. The aim of the present study was to compare the binding affinities for hydroxyapatite (HAP) of 6 bisphosphonates currently used clinically and to determine the effects of these bisphosphonates on other mineral surface properties including zeta potential and interfacial tension. Affinity constants (K(L)) for the adsorption of bisphosphonates were calculated from kinetic studies on HAP crystal growth using a constant composition method at 37 degrees C and at physiological ionic strength (0.15 M). Under conditions likely to simulate bisphosphonate binding onto bone, there were significant differences in K(L) among the bisphosphonates for HAP growth (pH 7.4) with a rank order of zoledronate > alendronate > ibandronate > risedronate > etidronate > clodronate. The measurements of zeta potential show that the crystal surface is modified by the adsorption of bisphosphonates in a manner best explained by molecular charges related to the protonation of their side-chain moieties, with risedronate showing substantial differences from alendronate, ibandronate, and zoledronate. The studies of the solid/liquid interfacial properties show additional differences among the bisphosphonates that may influence their mechanisms for binding and inhibiting crystal growth and dissolution. The observed differences in kinetic binding affinities, HAP zeta potentials, and interfacial tension are likely to contribute to the biological properties of the various bisphosphonates. In particular, these binding properties may contribute to differences in uptake and persistence in bone and the reversibility of effects. These properties, therefore, have potential clinical implications that may be important in understanding differences among potent bisphosphonates, such as the apparently more prolonged duration of action of alendronate and zoledronate compared with the more readily reversible effects of etidronate and risedronate.

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Research works printed but not linked: 9

  1. Benedict J.J., The physical chemistry of the diphosphonates—Its relationship to their medical activity. In: Donath A., Courvoisier B., editors. Symposium Cemo, Centre D'Etude des Maladies Osteoarticulatires de Geneve (IV), 1–19. 1982. Geneva, Editions Medicine et Hygiene. Diphosphonates and Bone;1990:7–9.
  2. Sunberg, 1991, Designing drugs for stronger bones, Chemtech, 21, 304
  3. Ebetino, 1998, Mechanisms of action of etidronate and other bisphosphonates, Rev. Contemp. Pharmacother., 9, 233
  4. Traube, 1927, Solubility and surface tension, Ber, 60B, 1808
  5. Semenchenko, 1934, Solubility and surface tension, Uspekhi Khimii, 3, 710
  6. Bagda, 1978, The relation between surface tension and the solubility parameter in liquids, Farbe Lack, 84, 212
  7. Leu, 2004, Relative binding affinities of bisphosphonates for human bone, Bone, 34, S62
  8. Christiansen, 2003, Comparison of risedronate and alendronate pharmacokinetics at clinical doses, Osteoporos Int., 14, S38
  9. Watts, 2004, Treatment discontinuation effects on bone turnover and BMD with risedronate, Bone, 34, S99

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Metadata

Authors
Nancollas, G. H., Tang, R., Phipps, R. J., Henneman, Z., Gulde, S., Wu, W., Mangood, A., Russell, R. G. G., & Ebetino, F. H.
Affiliations
  • University at Buffalo, State University of New York (US)
  • Procter & Gamble (United States) (US)
  • Nuffield Orthopaedic Centre (GB)
Corresponding author
Ebetino, F.H.
ORCID
Venue
Bone
Publisher
Elsevier BV
Published
2006-05
Volume
38
Issue
5
Pages
617-627
ISSN
  • 1873-2763 (ISSN-L)
  • 8756-3282
DOI
10.1016/j.bone.2005.05.003
OpenAlex
W2128778774
Cited by
862
References
75
Citations by year
2026: 17 · 2025: 23 · 2024: 15 · 2023: 24 · 2022: 41 · 2021: 29 · 2020: 45 · 2019: 39 · 2018: 44 · 2017: 40 · 2016: 39 · 2015: 45 · 2014: 55 · 2013: 48 · 2012: 44
FWCI
18.97
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Bone (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Dental and Craniofacial Research (DE03223)
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Oncology › Bone health and treatments
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords
bisphosphonates, hydroxyapatite, drug adsorption, binding affinity, crystal growth inhibition, zeta potential, interfacial tension, zoledronic acid, alendronate, ibandronate, risedronate, etidronate, clodronate, bone mineral, osteoporosis, duration of action, protein prenylation
MeSH terms
Bone and Bones, Crystallization, Diphosphonates, Humans, Stress, Mechanical, Durapatite, Bone Density Conservation Agents

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