Periodontal disease preceding osteonecrosis of the jaw (ONJ) in cancer patients receiving antiresorptives alone or combined with targeted therapies: report of 5 cases and literature review

Nicolatou‐Galitis, Ourania; Razis, Evangelia; Galiti, Dimitra; Galitis, Evangelos; Labropoulos, Stefanos; Tsimpidakis, Antonios; Sgouros, Joseph; Karampeazis, Athanasios; Migliorati, Cesar A.

doi:10.1016/j.oooo.2015.08.007

Cited by 35 publications

(29 citation statements)

References 23 publications

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“…Recent studies have reported the presence of histologically proven alveolar necrotic bone associated with dental/periodontal infection at the time of the extraction of teeth (Nicolatou-Galitis et al, 2015;Nicolatou-Galitis, Schiødt, et al, 2019). Similarly, animal studies have reported that MRONJ can develop to areas of periodontal infection in the absence of dental extraction surgery (Nowicki et al, 2019; (Patel et al, 2018;Rugani et al, 2014).…”

Section: Controver S Ie S On Ris K Fac Tor Smentioning

confidence: 99%

“…The Group suggested that dental infection might currently be a more common and relevant risk factor for MRONJ compared to extraction and that a notable proportion of MRONJ cases believed to have been triggered by dental extraction in fact represent cases of non‐exposed MRONJ that had already developed because of dental/periodontal infection before the actual extraction took place. Recent studies have reported the presence of histologically proven alveolar necrotic bone associated with dental/periodontal infection at the time of the extraction of teeth (Nicolatou‐Galitis et al, ; Nicolatou‐Galitis, Schiødt, et al, ). Similarly, animal studies have reported that MRONJ can develop to areas of periodontal infection in the absence of dental extraction surgery (Nowicki et al, ; Otto et al, ).…”

Section: Controversies On Risk Factorsmentioning

confidence: 99%

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Workshop of European task force on medication‐related osteonecrosis of the jaw—Current challenges

et al. 2019

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Section: Controver S Ie S On Ris K Fac Tor Smentioning

confidence: 99%

Section: Controversies On Risk Factorsmentioning

confidence: 99%

Workshop of European task force on medication‐related osteonecrosis of the jaw—Current challenges

et al. 2019

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“…Recent data have shown that localized periodontal or dental disease may precede the appearance of MRONJ (Figure 3). 38 Furthermore, alveolar bone necrosis has been documented at the time of dental extraction ( Figure 4), and bacterial diversity within necrotic bone is representative of periodontal microflora. 34,115 Dentists should be aware of the risk of MRONJ when considering invasive procedures (e.g., tooth extraction or implant placement) and in case of pressure sores from ill-fitting prostheses or significant inflammation/infection.…”

Section: Hypercalcemia Of Malignancymentioning

confidence: 99%

“…[33][34][35][36][37] Furthermore, evidence suggests that such infections may precede the appearance of necrotic bone. 38 Dentists of patients receiving bisphosphonates or denosumab have a pivotal role in the prevention and early diagnosis of MRONJ. In recognition of this, American Society of Clinical Oncology and Cancer Care Ontario made the following recommendation: "A dental assessment is recommended, where feasible, before commencement of bisphosphonates, and any pending dental or oral health problems should be dealt with before starting treatment, if possible."…”

mentioning

confidence: 99%

Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment

Nicolatou‐Galitis

Schiødt

Mendes

et al. 2019

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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251

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Skeletal complications caused by osteoporosis or bone metastases are associated with considerable pain, increased mortality, and reduced quality of life. Furthermore, such events place a burden on health care resources. Agents that prevent bone resorption, such as bisphosphonates or denosumab, can reduce the risk of skeletal-related events and are widely used in patients with osteoporosis or bone metastases of cancer. Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but potentially serious, adverse event associated with high cumulative doses of bisphosphonates or denosumab. However, MRONJ can be treated, and the likelihood of the development of this condition can be reduced through prophylactic dental care and the maintenance of good oral hygiene. Dentists, as part of a multiprofessional team, have a critical role in preventing MRONJ. This review describes the incidence and pathophysiology of MRONJ and provides guidance for dental practitioners with regard to the screening, prophylactic treatment, diagnosis, and management of patients with this condition. (Oral Surg Oral Med Oral Pathol Oral Radiol 2019;127:117À135) Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon condition that can occur after exposure to agents used to prevent bone complications, such as bisphosphonates or denosumab, or treatment with other agents, such as angiogenesis inhibitors. 1 In the majority of cases, MRONJ manifests as exposed bone in the maxillofacial region (Figure 1), although non-exposed MRONJ has also been recognized (Figure 2). 2-5 Bisphosphonates and denosumab are predominantly used to reduce the risk of skeletal complications in patients with bone loss, resulting from long-term cancer treatment or osteoporosis, and in patients with malignant bone disease. 6-8 Bisphosphonates are small molecules that dock in hydroxyapatite-binding sites on bone surfaces. When osteoclasts begin to resorb bisphosphonate-impregnated bone, the liberated bisphosphonates bind to farnesyl pyrophosphate synthase inside the osteoclasts, ultimately leading to apoptosis. 8-10 Denosumab is a fully human monoclonal antibody, which has a different mode of action from that of bisphosphonates. It targets and binds to the receptor activator of nuclear factor k-B (RANK) ligand (RANKL); in doing so it prevents the activation of RANK on the surface of osteoclasts and osteoclast precursors. Inhibition of the RANKLÀRANK interaction impedes osteoclast formation, function, and survival, thereby decreasing bone resorption. 11 MRONJ is more prevalent among patients receiving high cumulative doses of bisphosphonates or denosumab than in patients who receive lower doses. 12,13 The first cases Statement of Clinical Relevance Medication-related osteonecrosis of the jaw is a rare, but potentially serious, complication of treatment with bisphosphonates and denosumab. It is important for dentists to be aware of ways to identify and treat patients at risk of this condition.

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“…The most commonly available antiresorptive agents are bisphosphonates, which may be associated with an increased risk for osteonecrosis [5][6][7]. Other medications include antibiotics, such as Arestin and chlorhexidine gluconate mouthwash, that reduce bacteria in the mouth and do not have direct effects on bone.…”

Section: Introductionmentioning

confidence: 99%

A New Anabolic compound, LLP2A-Ale, Reserves Periodontal Bone Loss in Mice Through Augmentation of Bone Formation

Yao¹,

Jiang

Liu

et al. 2020

Preprint

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Aims. Currently, there are no effective medications that reverse periodontal disease (PD)-induced bone loss. The objective of this study was to test a new anabolic compound, LLP2A-Ale, or with the combination treatment of mesenchymal stromal cell (MSC), in the treatment of bone loss secondary to PD. Martials and Methods. PD was induced in mice by placing a ligature around the second right molar. At one week after disease induction, the mice were treated with placebo, LLP2A-Ale, MSCs, or combination of LLP2A-Ale + MSCs, and euthanized at week 4. Results. We found that PD induced alveolar bone loss that was associated with reduced bone formation. LLP2A alone and in combination with MSCs sustained alveolar bone formation and reversed alveolar bone loss. Additionally, PD alone caused systemic inflammation and increased the circulating levels of G-CSF, IP-10, MIP-1a, and MIP2, which were suppressed by LLP2A-Ale +/- MSCs. LLP2A-Ale +/- MSCs increased bone formation at the peripheral skeletal site (distal femur), which was otherwise suppressed by PD. Conclusion. Our findings indicated that LLP2A-Ale treatment rescued alveolar bone loss caused by PD, primarily by increasing bone formation. LLP2A-Ale also attenuated the circulating levels of a series of inflammatory cytokines and reversed the PD-induced suppression of systemic bone formation.

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Periodontal disease preceding osteonecrosis of the jaw (ONJ) in cancer patients receiving antiresorptives alone or combined with targeted therapies: report of 5 cases and literature review

Cited by 35 publications

References 23 publications

Workshop of European task force on medication‐related osteonecrosis of the jaw—Current challenges

Workshop of European task force on medication‐related osteonecrosis of the jaw—Current challenges

Medication-related osteonecrosis of the jaw: definition and best practice for prevention, diagnosis, and treatment

A New Anabolic compound, LLP2A-Ale, Reserves Periodontal Bone Loss in Mice Through Augmentation of Bone Formation

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