Objective
Recently, specific in vitro bisphosphonate concentrations have been established for
reaching a toxic threshold that could result in the induction of bisphosphonate-related
osteonecrosis of the jaw (BRONJ), but these data have not been validated in vivo.
The purpose of this study was to quantify the concentration of bisphosphonates (BPs)
in the diseased jaw bone of patients experiencing BRONJ.
Study Design
We hypothesized that if the average natural nitrogen content of mammalian bone is
known, the excess of nitrogen in the jaw bone of BRONJ patients is likely to reflect
the concentration of amino-BP. To test our hypothesis, jaw bone specimens from patients
with BRONJ were acquired after sequestrectomy and analyzed by energy-dispersive X-ray
spectroscopy (EDS).
Results
The EDS analysis of the bone demonstrated a highly linear correlation between increasing
concentrations of BP and the increasing percentage of nitrogen measured at the bone
surfaces (R2 = .9851, P = .0149).
Conclusions
SEM/EDS can be a valuable tool for assessing BP concentration in jaw bone and provides
important insight into BP pharmacokinetics and BRONJ.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Oral Surgery, Oral Medicine, Oral Pathology and Oral RadiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Discovery, clinical development, and therapeutic uses of bisphosphonates.Ann Pharmacother. 2005; 39: 668-677
- Osteoporosis: now and the future.Lancet. 2011; 377: 1276-1287
- Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 102: 433-441
- Mode of administration-dependent pharmacokinetics of bisphosphonates and bioavailability determination.Int J Pharm. 2001; 220: 1-11
- Osteonecrosis of the jaw and bisphosphonates in cancer: a narrative review.Nat Rev Endocrinol. 2011; 7: 34-42
- Osteonecrosis of the jaw: who gets it, and why?.Bone. 2009; 44: 4-10
- Oral bisphosphonate use and the prevalence of osteonecrosis of the jaw: an institutional inquiry.J Am Dent Assoc. 2009; 140: 61-66
- Zoledronic acid delays wound healing of the tooth extraction socket, inhibits oral epithelial cell migration, and promotes proliferation and adhesion to hydroxyapatite of oral bacteria, without causing osteonecrosis of the jaw, in mice.J Bone Miner Metab. 2010; 28: 165-175
- Pharmacokinetic optimization of antiretroviral therapy in children and adolescents.Clin Pharmacokinet. 2011; 50: 143-189
- Inhibition of oral mucosal cell wound healing by bisphosphonates.J Oral Maxillofac Surg. 2008; 66: 839-847
- A pharmacokinetic and pharmacodynamic model for intravenous bisphosphonate (pamidronate) in osteoporosis.Eur J Clin Pharmacol. 2002; 57: 883-890
- Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase.J Med Chem. 2008; 51: 2187-2195
- Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates.J Pharmacol Exp Ther. 2001; 296: 235-242
- Bisphosphonate action.J Clin Invest. 1991; 88: 2095-2105
- A comparative study on Pb2+ accumulation between Saccharomyces cerevisiae and Aureobasidium pullulans by SEM (scanning electron microscopy) and EDX (energy dispersive X-Ray) analyses.J Biosci Bioeng. 1999; 87: 112-115
- American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws.J Maxillofac Surg. 2007; 65: 369-376
- Microbial biofilms in osteomyelitis of the jaw and osteonecrosis of the jaw secondary to bisphosphonate therapy.J Am Dent Assoc. 2009; 140: 1259-1265
- Identification of microbial biofilms in osteonecrosis of the jaws secondary to bisphosphonate therapy.J Oral Maxillofac Surg. 2008; 66: 767-775
- Genomewide pharmacogenetics of bisphosphonate-induced osteonecrosis of the jaw: the role of RBMS3.Oncologist. 2012; 17: 279-287
- Relative binding affinities of bisphosphonates for human bone and relationship to antiresorptive efficacy.Bone. 2006; 38: 628-636
- Nonenzymatic glucose sensor based on renewable electrospun Ni nanoparticle-loaded carbon nanofiber paste electrode.Biosens Bioelectron. 2009; 24: 3329-3334
- Estrogen reduces the depth of resorption pits by disturbing the organic bone matrix degradation activity of mature osteoclasts.Endocrinology. 2001; 142: 5371-5378
- Bacterial adhesion to bisphosphonate coated hydroxyapatite.J Mater Sci Mater Med. 2005; 16: 283-287
Article info
Publication history
Accepted:
June 10,
2012
Received in revised form:
May 24,
2012
Received:
May 2,
2012
Footnotes
This work has been supported in part by the NIH-NIDCD (5 P-30 DC 006276-03) in addition to an LRP grant to the corresponding author from the National Institutes of Health/National Institute on Minority Health and Health Disparities. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.
Identification
Copyright
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
