Intravenous Bisphosphonate-Related Osteonecrosis of the Jaw: Bone Scintigraphy as an Early Indicator

O’Ryan, Felice; Khoury, Sam; Liao, Wendy; Han, Myo; Hui, Rita L.; Baer, David; Martin, D.C.; Liberty, Donald; Lo, Joan C.

doi:10.1016/j.joms.2009.03.005

Cited by 160 publications

(114 citation statements)

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“…Recent clinical studies showed that the radiolabeled probes used in bone scintigraphy localize to the areas of the ONJ lesions (Zanglis et al, 2007;Dore et al, 2009;O'Ryan et al, 2009). The radiolabeled probes, 99m Tc-labeled BP, utilize the bone-seeking property of BP which binds to the active turnover sites of the bone.…”

Section: Senescent Cells Are Physiologically Relevant In Vivomentioning

confidence: 99%

Bisphosphonates Induce Senescence in Normal Human Oral Keratinocytes

et al. 2011

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Bisphosphonate-related osteonecrosis of the jaw (BRONJ) commonly occurs in individuals receiving bisphosphonates (BPs) with clinical manifestations of the exposed necrotic bone. Although defective wound healing of soft tissue is frequently, if not always, observed in BRONJ, the effects of BPs on oral soft tissue or cells remain unknown. To investigate the effects of BPs on cells of oral mucosal tissue, we studied the effect of pamidronate (PAM), one of the BPs most commonly administered to cancer patients, on the phenotypes of normal human oral keratinocytes (NHOK) and fibroblasts (NHOF). When exposed to PAM at 10 µM, NHOK, not NHOF, underwent senescence: NHOK overexpressed senescence-associated β-galactosidase (SA-β-Gal), p16INK4A, IL-6, and IL-8. When exposed to a higher level (50 µM) of PAM, NHOK maintained senescent phenotypes, but NHOF underwent apoptosis. PAM-induced senescence in NHOK is mediated, in part, via geranylgeranylation of the mevalonate pathway. Our in vitro 3D oral mucosal tissue construction studies further demonstrated that PAM induced senescence and impaired re-epithelialization of oral mucosa. Analysis of these data indicates that premature senescence of oral mucosal cells and subsequent defective soft-tissue wound healing might be partly responsible for the development of BRONJ in individuals receiving PAM or other BPs.

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Section: Senescent Cells Are Physiologically Relevant In Vivomentioning

confidence: 99%

Bisphosphonates Induce Senescence in Normal Human Oral Keratinocytes

et al. 2011

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“…Multiple factors account for developing BONJ, including route of drug administration, dosage, duration, and local oral and systemic status [8,9,10]. Besides, the role of genetic factors should be taken into consideration.…”

Section: Introductionmentioning

confidence: 99%

Association between <b><i>CYP2C8</i></b> (rs1934951) Polymorphism and Bisphosphonate-Related Osteonecrosis of the Jaws in Patients on Bisphosphonate Therapy: A Meta-Analysis

Zhong

Wu²,

Li³

2012

Acta Haematol

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Aims: Bisphosphonate-related osteonecrosis of the jaws (BONJ) is a severe complication in patients on bisphosphonate therapy. The study was conducted to verify the association between CYP2C8 (rs1934951) polymorphism and BONJ predisposition. Methods: The relative epidemiologic studies were identified in PubMed and Embase to conduct a meta-analysis using STATA. Results: In the pooled analysis with multiple cancer types, patients carrying the CYP2C8 rs1934951 AA or AG genotype showed no significantly increased BONJ susceptibility compared with those carrying the wild GG genotype [dominant: odds ratio (OR) = 2.05, 95% confidence interval (CI) = 0.67–6.29, p = 0.209; recessive: OR = 1.88, 95% CI = 0.23–15.6, p = 0.560; AG vs. GG: OR = 2.07, 95% CI = 0.80–5.32, p = 0.133, and AA vs. GG: OR = 1.34, 95% CI = 0.48–3.74, p = 0.578]. A significant association between AA and AG genotypes of CYP2C8 (rs1934951) and BONJ risk was found in the subgroup analysis of multiple myeloma (dominant: OR = 5.77, 95% CI = 1.21–27.63, p = 0.028; AG vs. GG: OR = 5.02, 95% CI = 2.06–12.23, p = 0.001, and AA vs. GG: OR = 16.23, 95% CI = 1.72–78.7, p = 0.015). Conclusion: The results indicated that AA and AG genotypes of CYP2C8 (rs1934951) might be predictors for multiple myeloma patients at high risk to develop BONJ.

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“…When c li n i c al l y u n ex p o s ed n e cr o ti c b on e i s s een , fu r t he r examinationse.g., bone scintigraphy, positron emission tomography, magnetic resonance imaging (MRI)may help identify early areas of bone involvement 10,11) . Imaging modalities such as radiography, scintigraphy, CT, and MRI are used for diagnostic bone marrow imaging.…”

Section: Surgeons (Aaoms)mentioning

confidence: 99%

Change in the Magnetic Resonance Imaging Signal of the Mandibular Condyle Due to Bisphosphonate-Related Osteonecrosis of the Jaw

Hirahara

Muraoka

Noda

et al. 2017

J. Hard Tissue Biology.

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Marx was the first to report osteonecrosis of the jaw due to administration of BPs in 2003. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the result of an adverse drug reaction. Moreover, many studies worldwide have reported an association between a range of serious dental diseases and the use of bisphosphonates (BPs). Few studies, however, have evaluated BRONJ based on an abnormal signal detected by MRI in the bone marrow of the mandibular condyle. The aim of this study was to assess changes in the magnetic resonance imaging (MRI) signal from the mandibular condyle that could be due to BRONJ. In particular, we focused on the presence of an abnormal MRI signal emanating from mandibular condyle bone marrow. Twenty-eight patients (11 men, 17 women; 56 temporomandibular joints) with BRONJ were evaluated for jaw pain. The patients, whose mean age was 72.9 ± 9.4 years (range 48 -88 years), underwent MRI examination of the jawbone at our hospital from August 2006 to December 2015 and were included in the study. Overall, 80.0% of the patients diagnosed with BRONJ exhibited an abnormal bone marrow signal in the mandibular condyle on the same side of the face that suffered jaw pain. This abnormal signal was present significantly more frequently on the side of the face with the jaw symptoms than on the side without symptoms. Patients with BRONJ displayed an abnormal MRI signal in the mandibular condyle on the side of the face with jaw symptoms, suggesting that MRI findings could be useful clinically for detecting BRONJ in the mandibular condyle.

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Intravenous Bisphosphonate-Related Osteonecrosis of the Jaw: Bone Scintigraphy as an Early Indicator

Cited by 160 publications

References 20 publications

Bisphosphonates Induce Senescence in Normal Human Oral Keratinocytes

Bisphosphonates Induce Senescence in Normal Human Oral Keratinocytes

Association between <b><i>CYP2C8</i></b> (rs1934951) Polymorphism and Bisphosphonate-Related Osteonecrosis of the Jaws in Patients on Bisphosphonate Therapy: A Meta-Analysis

Change in the Magnetic Resonance Imaging Signal of the Mandibular Condyle Due to Bisphosphonate-Related Osteonecrosis of the Jaw

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