Molecular profiling of oral microbiota in jawbone samples of bisphosphonate‐related osteonecrosis of the jaw

Wei, Xiaoyuan; Pushalkar, Smruti; Estilo, Cherry L.; Wong, Cho Lee; Farooki, Azeez; Fornier, Monica; Bohle, George C.; Huryn, Joseph M.; Li, Yihong; Doty, Steven B.; Saxena, Deepak

doi:10.1111/j.1601-0825.2012.01916.x

Cited by 60 publications

(51 citation statements)

References 65 publications

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“…The importance of bacterial biofilm formation in the pathogenesis of BRONJ was reported previously, but the mechanisms responsible for bacterial colonization of denuded bone in patients on BPs were unclear (Sedghizadeh et al, 2008;Kos et al, 2010;Wei et al, 2012). Based on our experiments, one may suppose that BP-mediated bacterial adhesion plays an important role in this process.…”

Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 58%

“…There are reports confirming an increased infection rate in these patients with bacterial species known to be etiological factors of bone infections (Sedghizadeh et al, 2008;Wei et al, 2012). System for testing bacterial adherence under flow conditions.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 97%

“…At the same time, infection of the denuded bone with creation of biofilm M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT composed of Gram-positive and Gram-negative strains as well as anaerobes has been documented in pathological and microbiological reports concerning BRONJ (Sedghizadeh et al, 2008;Wei et al, 2012). Moreover, microbial colonization in BRONJ cases was also significantly higher than in bone necrosis occurring in the absence of BPs, raising the possibility that BPs could enhance bacterial colonization and biofilm formation in patients treated with these drugs (Kos et al, 2010).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Bisphosphonates enhance bacterial adhesion and biofilm formation on bone hydroxyapatite

Kos

Junka

Smutnicka

et al. 2015

Journal of Cranio-Maxillofacial Surgery

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Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 58%

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 97%

Section: Accepted Manuscriptmentioning

confidence: 99%

See 1 more Smart Citation

Bisphosphonates enhance bacterial adhesion and biofilm formation on bone hydroxyapatite

Kos

Junka

Smutnicka

et al. 2015

Journal of Cranio-Maxillofacial Surgery

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“…Although bisphosphonates have seen clinical efficacy in a variety of pathologies, such as cancer metastases, multiple myeloma, Paget's disease of the bone, and osteoporosis, they can also cause serious side effects, most notably osteonecrosis of the jaw [1]. Given the high affinity of bisphosphonates for bone, some hypothesize that the accumulation of intravenously administered bisphosphonates in bone can lead to later necrosis of soft tissue and bone in the mandible and maxilla, especially following dental procedures [1,23,24]. As seen in Fig.…”

Section: Pleiotropic Effects Of Statinsmentioning

confidence: 99%

Novel applications of statins for bone regeneration

Shah

Werlang

Kasper

et al. 2014

National Science Review

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The use of statins for bone regeneration is a promising and growing area of research. Statins, originally developed to treat high cholesterol, are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl, the rate-limiting enzyme of the mevalonate pathway. Because the mevalonate pathway is responsible for the synthesis of a wide variety of important biochemical molecules, including cholesterol and other isoprenoids, the effects of statins are pleiotropic. In particular, statins can greatly affect the process of bone turnover and regeneration via effects on important cell types, including mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts. Statins have also been shown to have anti-inflammatory and antimicrobial properties that may be useful since infection can derail normal bone healing. This review will explore the pleiotropic effects of statins, discuss the current use of statins for bone regeneration, particularly with regard to biomaterials-based controlled delivery, and offer perspectives on the challenges and future directions of this emerging area of bone tissue engineering.

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“…19,20,24 The presence of bacterial biofilms, most commonly, Actinomyces at BRONJ sites, has been demonstrated by histomorphometric and histological studies. 6,10,25,26,27,28,29 Our previous studies, for the first time, using 16S rRNA sequencing, have shown the presence of polymicrobial communities, both cultivable and uncultivable, in a broader perspective in the soft tissues 19 and jaw bone 24 sites of BRONJ lesions which otherwise, could go undetected by histomorphometric or histopathological analyses. Nevertheless, the ubiquitous influence of bacterial biofilms at the site of BRONJ lesions may impact the pathogenesis of BRONJ.…”

Section: Introductionmentioning

confidence: 99%

Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw

Pushalkar

Kurago

et al. 2014

Int J Oral Sci

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Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts (n=30); patients with periodontal disease without a history of BP therapy (Control, n=10), patients with periodontal disease having history of BP therapy but without ONJ (BP, n=5) and patients with BRONJ (BRONJ, n=15). Denaturing gradient gel electrophoresis of polymerase chain reaction (PCR)-amplified 16S rRNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ (71.6%), BP (70.3%) and Control (59.1%). Significant differences (P<0.05) in genera were observed, between Control/BP, Control/BRONJ and BP/BRONJ cohorts. Enzyme-linked immunosorbent assay (ELISA) results indicated that the levels of myeloperoxidase were significantly lower, whereas interleukin-6 and tumor necrosis factor-alpha levels were moderately elevated in BRONJ patients as compared to Controls. PCR array showed significant changes in BRONJ patients with downregulation of host genes, such as nucleotide-binding oligomerization domain containing protein 2, and cathepsin G, the key modulators for antibacterial response and upregulation of secretory leukocyte protease inhibitor, proteinase 3 and conserved helix–loop–helix ubiquitous kinase. The results suggest that colonization of unique bacterial communities coupled with deficient innate immune response is likely to impact the pathogenesis of ONJ.

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Molecular profiling of oral microbiota in jawbone samples of bisphosphonate‐related osteonecrosis of the jaw

Abstract: This study using limited sample size indicated that the jawbone associated with BRONJ was heavily colonized by specific oral bacteria and there were apparent differences between the microbiota of BRONJ and controls.

Cited by 60 publications

References 65 publications

Bisphosphonates enhance bacterial adhesion and biofilm formation on bone hydroxyapatite

Bisphosphonates enhance bacterial adhesion and biofilm formation on bone hydroxyapatite

Novel applications of statins for bone regeneration

Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw

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