Osteonecrosis of the jaws in patients treated with bisphosphonates – histomorphologic analysis in comparison with infected osteoradionecrosis

Hansen, Torsten; Kunkel, Martin; Weber, Achim; Kirkpatrick, Charles James

doi:10.1111/j.1600-0714.2006.00391.x

Cited by 310 publications

(211 citation statements)

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“…The abnormal oral epithelial hyperplasia referred to as pseudoepitheliomatous hyperplasia (PEH) was reported in 60% of human ONJ biopsy specimens (24,31) and was associated with the more aggressive ONJ phenotype with necrotic bone exposure. Akilov et al (41) reported the development of PEH in mouse ear skin by the injection of TNF-␣ and IFN-␥, suggesting that overproduction of Th1 cytokines in the barrier immunity stimulated the unregulated proliferation and migration of epidermal basal cells.…”

Section: Discussionmentioning

confidence: 99%

“…At the small distal root areas, where the oral mucosa wound was closed based on gross observation, histological evaluations revealed definitive bone exposure facilitated by the abnormal migration of oral epithelial cells. The abnormal proliferation and migration of epithelial cells resembling pseudoepitheliomatous hyperplasia (24,31) resulted in direct epithelial contact with the partially necrotic alveolar bone. Reduced new bone formation was noted in the extraction socket, and densely localized inflammatory cell infiltration was observed on the surface of the palatal bone adjacent to the tooth extraction site (Fig.…”

Section: Onj-like Lesions In Wtmentioning

confidence: 99%

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Osteonecrosis of the Jaw Developed in Mice

Park

Kanayama

Kaur

et al. 2015

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Section: Onj-like Lesions In Wtmentioning

confidence: 99%

Osteonecrosis of the Jaw Developed in Mice

Park

Kanayama

Kaur

et al. 2015

Journal of Biological Chemistry

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“…It has also been proposed that NBPs may have an antiangiogenic effect, reducing blood flow and thus inducing bone cell necrosis and apoptosis [10,11]. One alternative explanation is an "outside-in" process in which mucosal damage provides oral bacteria with access to the underlying bone, leading to bone infection and necrosis [12]. NBP soft tissue toxicity would thus be the trigger leading to necrosis of the mucosa and bone [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Bisphosphonate-associated osteonecrosis of the jaw: A key role of inflammation?

Lesclous

Najm

Carrel

et al. 2009

Bone

192

140

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Osteonecrosis of the jaw (ONJ) can be associated with nitrogen-containing bisphosphonates (NBPs) therapy. Various mechanisms of NBP-associated ONJ have been proposed and there is currently no consensus of the underlying pathogenesis. The detailed medical and dental histories of 30 ONJ patients treated with NBPs for malignant diseases (24) or osteoporosis (6) were analyzed. The necrotic bone was resected and analyzed histologically after demineralization. In 10 patients the perinecrotic bone was also resected and processed without demineralization. Alveolar bone samples from 5 healthy patients were used as controls. In 14 ONJ patients, serial technetium-99m-methylene diphosphonate scintigraphic scans were also available and confronted to the other data. Strong radionuclide uptake was detected in some patients several months before clinical diagnosis of ONJ. The medullary spaces of the necrotic bone were filled with bacterial aggregates. In the perinecrotic bone, the bacteria-free bone marrow characteristically showed an inflammatory reaction. The number of medullary inflammatory cells taken as an index of inflammation allowed us to discriminate two inflammation grades in the ONJ samples. Low-grade inflammation, characterized by marrow fibrosis and low inflammatory cells infiltration, increased numbers of TRAP + monoand multineacleated cells was seen in patients with bone exposure b 2 cm 2 . High-grade inflammation, associated with larger lesions, showed amounts of tartrate-resistant acid phosphatase + /calcitonin receptor − mono-and multinucleated cells, osteocyte apoptosis, hypervascularization and high inflammatory cell infiltration. The clinical extent of ONJ was statistically linked to the numbers of inflammatory cell. Taken together these data suggest that bone necrosis precedes clinical onset and is an inflammation-associated process. We hypothesize that from an initial focus, bone damage spreads centrifugally, both deeper into the jaw and towards the mucosa before the oral bone exposure and the clinical diagnosis of ONJ.

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“…The pathogenesis of these lesions is not known. Although it is hypothesized that reduced bone turnover is the cause of this problem, reduced bone turnover has not been demonstrated in these patients, and bone scans suggested increased bone turnover at the affected sites (56,57). If there is an association of jaw osteonecrosis with oral bisphosphonate therapy, the incidence is very low.…”

Section: Osteonecrosis Of the Jawmentioning

confidence: 94%

Bisphosphonates

McClung

2006

Arq Bras Endocrinol Metab

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Osteoporosis is the result of bone loss due to an imbalance in bone turnover such that bone resorption exceeds bone formation. Bisphosphonates are potent inhibitors of osteoclast activity that reduce bone turnover and re-establish the balance between bone resorption and formation. In clinical studies, several bisphosphonates prevent bone loss, preserve bone structure, improve bone strength and, in patients with osteoporosis, substantially reduce fracture risk. They are effective in multiple clinical settings including postmenopausal osteoporosis, low bone mass in men and drug-induced bone loss. Intermittent oral dosing and intravenous administration are more convenient than the original daily dosing regimen. These drugs are generally well tolerated and have an excellent safety profile in that serious side effects are uncommon. Potent bisphosphonates are generally the preferred treatment option for most patients with or at risk for osteoporosis. RESUMO Bisfosfonatos.Osteoporose é o resultado da perda óssea devida a um imbalanço no turnover ósseo, onde a reabsorção óssea excede sua formação. Os bisfosfonatos são inibidores potentes da atividade osteoclástica, que reduzem o turnover ósseo e restabelecem o balanço entre a reabsorção e a formação óssea. Em estudos clínicos, vários bisfosfonatos previnem a perda óssea, preservam sua estrutura, melhoram sua força e substancialmente reduzem o risco de fraturas em pacientes com osteoporose. Eles são efetivos em várias situações clínicas, incluindo a osteoporose pós-menopáusica, a reduzida massa óssea em homens e perda óssea induzida por drogas. Doses orais intermitentes e administração intravenosa são mais convenientes do que o esquema original de doses diárias. Essas drogas são geralmente bem toleradas e têm um excelente perfil de segurança, no qual efeitos colaterais sérios são incomuns. Os bisfosfonatos potentes são geralmente a opção terapêutica preferida para a maioria dos pacientes com ou em risco de osteoporose. O STEOPOROSIS IS A DISORDER of skeletal fragility due a combination of low bone mass, deteriorated bone architecture and perhaps alterations in other aspects of bone quality (1). Osteoporosis is usually the result of bone loss that occurs after menopause in women and in older men and women. This bone loss is a consequence of increased and unbalanced bone review article Bisphosphonates

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Osteonecrosis of the jaws in patients treated with bisphosphonates – histomorphologic analysis in comparison with infected osteoradionecrosis

Abstract: We conclude that Actinomyces is involved in the chronic, non-healing inflammatory processes as a characteristic feature of both diseases. Together with the associated presence of increased osteoclast numbers, we suggest that both factors may be involved in osteolytic mechanisms.

Cited by 310 publications

References 20 publications

Osteonecrosis of the Jaw Developed in Mice

Osteonecrosis of the Jaw Developed in Mice

Bisphosphonate-associated osteonecrosis of the jaw: A key role of inflammation?

Bisphosphonates

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