![(a) The patient appeared with an asymmetrical face with moderate swelling of the tissues in the left emi-mandibular region. The clinical aspect of our patient was similar to the necrosis of the jaws observed in workers exposed to white phosphorus and so called phossy jaw [1] ; (b) the intraoral examination revealed a wide exposure of the left emi-mandibular body, which was freely mobile protruding from the mouth](https://www.researchgate.net/profile/Giuseppina-Campisi/publication/235669072/figure/fig2/AS:393554330439690@1470842073183/a-The-patient-appeared-with-an-asymmetrical-face-with-moderate-swelling-of-the-tissues_Q320.jpg)
![The wide bone sequestration of the left mandibular body obtained after sequestrectomy remembering the phosphorus necrosis of entire lower jaw excised by Mr McCarthy in 1884 (London Hospital Medical College Museum) [1]](https://www.researchgate.net/profile/Giuseppina-Campisi/publication/235669072/figure/fig1/AS:393554330439688@1470842072527/The-wide-bone-sequestration-of-the-left-mandibular-body-obtained-after-sequestrectomy_Q320.jpg)
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Spontaneous bisphosphonate-related osteonecrosis of the left hemi-mandible: Similarities with phossy jaw
Abstract and Figures
Intravenous bisphosphonates (BP) play a key role in the treatment of bone metastases. As a long-term side effects BP, a form of avascular osteonecrosis of the jaw has been reported. Although, invasive oral local procedures are often present in clinical history of patients suffering from bisphosphonates-related osteonecrosis of the jaws (BRONJ), about up to 50% of BRONJ are spontaneous. We report a case of a 68-year-old female with a spontaneous wide bone sequestration of the left mandibular body onset after infusion of zoledronic acid for 18 cycles for osseous metastasis due to metastatic anaplastic thyroidal carcinoma. Surprisingly the clinical aspects of the patient initially reminded us of the famous pathology described in 1899 called phossy jaw. This case is remarkable not only for the spontaneity of the osteonecrosis, but, above all, for the clinical similarity with cases of phossy jaw, described for the first time in the literature, thereby suggesting a potential common pathogenesis.
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... Currently, the exact mechanism behind PNJ remains elusive. Some scholars hypothesize that PNJ shares similar clinical and pathological features to medical-related osteonecrosis of the jaw (MRONJ), a condition with an increasing prevalence rate in recent years [1][2][3][4][5], but there are few specific clinical studies in this field. Therefore, this study aims to compare the clinical and pathological features of PNJ and MRONJ, illuminating light on potential similarities and differences to aid in the clinical diagnosis and treatment of PNJ. ...
... In conclusion, PNJ and MRONJ share numerous clinical and pathological characteristics [1][2][3][4][5], offering new therapeutic possibilities for PNJ. For instance, recent studies have shown that parathyroid hormone has an osteogenic-inducing function and can stimulate osteogenesis [28]. ...
Background
Phosphorous necrosis of the jaw (PNJ) exhibits similar clinical and pathological features as medical-related osteonecrosis of the jaw (MRONJ). This study aims at comparing the similarities and differences between PNJ and MRONJ regarding pathological features and to provide a theoretical basis for the clinical diagnosis and management of PNJ.
Material and methods
A retrospective analysis was conducted to assess clinical differences among 38 PNJ patients and 31 MRONJ patients, who were diagnosed and treated between January 2009 and October 2022. Pathological alterations in bone tissue were evaluated using EDS, H&E, Masson, and TRAP staining on five specimens from both MRONJ and PNJ cases; furthermore, immunohistochemistry was used to determine the expression levels of OPG, RANKL, and Runx2. The mandibular coronoid process was removed from individuals with temporomandibular joint ankylosis to serve as a control.
Results
CBCT imaging demonstrated necrotic bone formation in block, strip, or plaque shapes. EDS analysis showed that the calcium/phosphorus ratio in the bone tissue of PNJ and MRONJ was significantly lower than that of the control group (P < 0.05). Additionally, staining indicated reduced osteoblast counts, disrupted bone trabecular structure, and decreased collagen fiber content in the bone tissues of PNJ and MRONJ. Immunohistochemistry demonstrated that RANKL expression was significantly lower in MRONJ compared to PNJ and control groups (P < 0.05). Conversely, Runx2 expression was significantly higher in PNJ than in MRONJ and control groups (P < 0.05), and there was no significant difference in OPG expression.
Conclusion
PNJ and MRONJ demonstrate comparable clinical manifestations and pathological traits, although disparities may exist in their underlying exhibit comparable clinical manifestations, pathological traits, and molecular mechanisms.
... Currently, the exact mechanism behind PNJ remains unidenti ed. Some scholars speculate that PNJ shares similar clinical and pathological features to medical-related osteonecrosis of the jaw (MRONJ), a condition with an increasing prevalence rate in recent years [1][2][3][4][5] , but there are few speci c clinical studies in this eld. ...
... In conclusion, PNJ and MRONJ share numerous clinical and pathological characteristics [1][2][3][4][5] , offering new therapeutic possibilities for PNJ. For instance, recent studies have shown that parathyroid hormone has an osteogenic-inducing function and can stimulate osteogenesis [28] . ...
Background: Phosphorous necrosis of the jaw (PNJ) shares similar clinical and pathological features to medical-related osteonecrosis of the jaw (MRONJ). This study aims to compare the similarities and differences between PNJ and medical-related osteonecrosis of the jaw (MRONJ) in terms of clinical and pathological features, and to provide a theoretical basis for the clinical diagnosis and management of PNJ.
Material and Methods: A retrospective analysis assessed clinical differences among 38 PNJ patients and 31 MRONJ patients diagnosed and treated between January 2009 and October 2022. Pathological alterations in bone tissue were assessed using EDS, H&E, Masson and TRAP staining on five specimens from both MRONJ and PNJ cases, and immunohistochemistry was used to determine the expression levels of OPG, RANKL, and Runx2. The mandibular coronoid process was removed from individuals with temporomandibular joint ankylosis as control.
Results: CBCT imaging indicated necrotic bone formation in block, strip, or plaque shapes. EDS analysis revealed that the calcium/phosphorus ratio in the bone tissue of PNJ and MRONJ was significantly lower than that of the control group (P<0.05). Additionally, staining indicated reduced osteoblast counts, disrupted bone trabecular structure, and decreased collagen fiber content in the bone tissues of PNJ and MRONJ. Immunohistochemistry revealed that RANKL expression was significantly lower in MRONJ compared to PNJ and control groups (P<0.05). Conversely, Runx2 expression was significantly higher in PNJ than in MRONJ and control groups (P<0.05), with no significant difference in OPG expression.
Conclusion: PNJ and MRONJ exhibit comparable clinical manifestations and pathological traits, although disparities may exist in their underlyingexhibit comparable clinical manifestations and pathological traits, although disparities may exist in their underlying molecular mechanisms.
... These confounding factors are believed to be risk factors in developing ONJ. However, in the majority of cases, a precipitating factor is usually required and this is in most cases an invasive dental procedure [8][9][10]. However, ONJ is also known to occur spontaneously with studies quoting between 16 -40% of ONJ occurring without any identifiable precipitating factor [9,10]. ...
... However, in the majority of cases, a precipitating factor is usually required and this is in most cases an invasive dental procedure [8][9][10]. However, ONJ is also known to occur spontaneously with studies quoting between 16 -40% of ONJ occurring without any identifiable precipitating factor [9,10]. The most common precipitating factor is oral surgery or extraction of teeth which leaves a nonhealing area of exposed bone. ...
To conduct a systematic review of epidemiological literature to determine the incidence of bisphosphonate related osteonecrosis of the jaw occurring either spontaneously or after dental surgery, in children and adolescents diagnosed with osteogenesis imperfecta.
MEDLINE, HMIC and EMBASE were used to search for English-language articles published from 1946 - 2013. Inclusion criteria consisted of population based studies of children and adolescents (24 years and younger) diagnosed with osteogenesis imperfecta, only studies which included a dental examination, and patients treated with intravenous bisphosphonates were included. Articles were excluded if patients had any other co-morbidity which could affect osteonecrosis of the jaw, and those which treated patients with oral bisphosphonates only.
Five studies consisting of four retrospective cohort studies and one case series were identified. Study populations ranged from 15 to 278 patients and number of subjects with osteogenesis imperfecta ranged from 15 to 221. Mean duration of intravenous bisphosphonate use ranged from 4.5 to 6.8 years. All patients were clinically examined and no patients were found to have osteonecrosis of the jaw.
There is no evidence to support hypothesis of causal relationship between bisphosphonates and osteonecrosis of the jaw in children and adolescents with osteogenesis imperfecta. More prospective studies on bisphosphonate use in osteogenesis imperfecta needs to be carried out.
... Although the dentoalveolar surgery is not contraindicated in absolute terms, it exposes the patient to the possibility of BRONJ onset [21]. Due to the persistence of infections of the jaws, avoid the surgical treatment, in some cases, increase the possibility of spontaneous BRONJ and, simultaneously, exposes the patient to the onset of infectious complications [9]. ...
Prevention of bisphosphonate related osteonecrosis of the jaws (BRONJ) represents an important challenge for clinicians. Dent alveolar surgery is usually performed to reduce the risk local and systemic complications, In fact, removing the tooth that is the source of the infectious outbreak, brings to the removal of the infected tissue and determines a correct healing of the disease. However, in patients are undergoing bisphosphonate this procedure expose patients to an increased risk of BRONJ. However, in patients who are in treatment with systemic bisphosphonates, this procedure exposes them to an increased risk of BRONJ. When possible, avoid the surgical interventions in favors of endodontic treatment could be an important clinical options in reducing the possibility of BRONJ occurrence. In this paper, we report a case of endodontic re-treatment in a tooth with a floor perforation in a patient was assuming oral alendronate. Limits and advantages of performing endodontic retreatment for the prevention of BRONJ development have still not well elucidated. Due to the very low power of this study, no conclusions should be made to perform an endodontic retreatment instead of performing a tooth extraction. However, this case report support the execution of future studies related to the calculation of BRONJ incidence after surgical extraction vs endodontic retreatment.
This report describes an unusual and extreme case of osteonecrosis of the jaw (ONJ) affecting the entire mandible, which was attempting to self exfoliate. A 76‐year old male presented clinically with all aspects of the mandible, except the condylar heads, necrotic and exposed in the oral cavity. The mandible had elevated out of the mucosa and was attempting to exfoliate through the mouth. As it was obstructing his oral cavity, the necrotic mandible was sectioned posteriorly allowing the patient to speak and eat comfortably, as well regain an oral seal. The use of intravenous bisphosphonates for metastatic prostate cancer coupled glucocorticosteroids, diabetes mellitus and hyperlipidaemia are likely to have contributed this extensive medication related ONJ. This complication is well‐recognised in association with bisphosphonates, however, this case is unique due to its severity, its spontaneous occurrence and the oral cavity's natural response to manage it, through near complete self exfoliation.
This paper describes the pathological changes observed on the skeleton of a c.12–14 year old person buried in a north-east England Quaker cemetery dated to AD 1711–1857. Bone formation (woven and lamellar) and destruction are present mainly on the mandible, clavicles, sternum and scapulae, long bones of the right arm, left ribs, spine, ilia, and the femora and tibiae. Differential diagnoses of tuberculosis and other pulmonary diseases, smallpox, actinomycosis, neoplastic disease, and “phossy jaw” are considered. While the pathological changes could represent all previously described diseases and thus be associated with the insalubrious conditions in which this person lived, it is also possible that this person worked in the matchmaking industry known to be present in the region at the time. Attention is drawn to the previously overlooked condition “phossy jaw” caused by phosphorus poisoning, which was strongly associated with this industry. While matchstick making was an industry often associated with women and girls, DNA analysis of a bone sample from the skeleton did not successfully identify biological sex. Two dental calculus samples from this person were analysed for phosphorus, and comparisons were made with samples from the same and a different site; the levels did not indicate the person was more exposed to phosphorus than any of the other people at Coach Lane. However, the pathological lesions described also have relevance in a clinical context, because “phossy jaw” has been observed in living populations, arising as a consequence of ingesting phosphorous contained within some pharmaceuticals used for treating neoplastic disease and osteoporosis.
To report a case series of patients with the nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw-a form of jaw osteonecrosis that does not manifest with necrotic bone exposure/mucosal fenestration.
Among 332 individuals referred to 5 clinical centers in Europe because of development of jawbone abnormalities after or during exposure to bisphosphonates, we identified a total of 96 patients who presented with the nonexposed variant of osteonecrosis. Relevant data were obtained via clinical notes; radiological investigations; patients' history, and referral letters.
The most common clinical feature of nonexposed osteonecrosis was jaw bone pain (88/96; 91.6%); followed by sinus tract (51%), bone enlargement (36.4%); and gingival swelling (17.7%). No radiological abnormalities were identified in 29.1% (28/96) of patients. In 53.1% (51/96) of the patients; nonexposed osteonecrosis subsequently evolved into frank bone exposure within 4.6 months (mean; 95% confidence interval; 3.6-5.6).
Clinicians should be highly vigilant to identify individuals with nonexposed osteonecrosis, as the impact on epidemiological data and clinical trial design could be potentially significant. Although the present case series represents approximately 30% of all patients with bisphosphonates-associated osteonecrosis observed at the study centers, further population-based prospective studies are needed to obtain robust epidemiological figures.
The infamous "phossy jaw" that created an epidemic of exposed bone osteonecrosis exclusively in the jaws began around 1858 and continued until 1906, with only a few cases appearing since that time. This epidemic of osteonecrosis produced pain, swelling, debilitation, and a reported mortality of 20% and was linked to "yellow phosphorous," the key ingredient in "strike-anywhere" matches. In match-making factories, workers called "mixers," "dippers," and "boxers" were exposed to heated fumes containing this compound. Related to the duration of exposure, many of these workers developed painful exposed bone in the mouth, whereas their office-based counterparts did not. The exposed bone and clinical course were eerily similar to what modern day oral and maxillofacial surgeons see due to bisphosphonates used to treat metastatic cancer deposits in bone or osteoporosis. Although yellow phosphorus has a simple chemistry of P(4)O(10), when combined with H(2)O and CO(2) from respiration and with common amino acids, such as lysine, bisphosphonates almost identical to alendronate (Fosamax; Novartis Pharmaceuticals, East Hanover, NJ) and pamidronate (Aredia; Novartis Pharmaceuticals) result. Forensic evidence directly points to conversion of the yellow phosphorus in patients with "phossy jaw" to potent amino bisphosphonates by natural chemical reactions in the human body. Thus, the cause of phossy jaw in the late 1800s was actually bisphosphonate-induced osteonecrosis of the jaws, long before clever modern pharmaceutical chemists synthesized bisphosphonates. Today's bisphosphonate-induced osteonecrosis represents the second epidemic of "phossy jaw." Case closed.
TO THE EDITOR: Osteonecrosis of the jaw, recently reported in patients treated with bisphosphonates, may be analogous to the historic occupational disease "phossy jaw".1,2 Phossy jaw was osteonecrosis of the jaw caused by exposure to white phosphorus during the manufacture of matches. "Luci- fer" strike-anywhere matches were first pro- duced in 1833. They were made by dipping the match ends into a mixture containing white phosphorus.3 Workers were exposed to fumes from the white phosphorus during mixing and spreading of the dip material, and dipping, drying and boxing of the matches.3,4
We present current knowledge of bisphosphonate-associated osteonecrosis, a new oral complication in oncology. It was first described in 2003, and hundreds of cases have been reported worldwide. The disorder affects patients with cancer on bisphosphonate treatment for multiple myeloma or bone metastasis from breast, prostate, or lung cancer. Bisphosphonate-associated osteonecrosis is characterised by the unexpected appearance of necrotic bone in the oral cavity. Osteonecrosis can develop spontaneously or after an invasive surgical procedure such as dental extraction. Patients might have severe pain or be asymptomatic. Symptoms can mimic routine dental problems such as decay or periodontal disease. Intravenous use of pamidronate and zoledronic acid is associated with most cases. Other risk factors include duration of bisphosphonate treatment (ie, 36 months and longer), old age in patients with multiple myeloma, and a history of recent dental extraction. We also discuss pathobiology, clinical features, management, and future directions for the disorder.
Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: A case series How to cite this article Spontaneous bisphosphonate-related osteonecrosis of the left hemi-mandible: Similarities with phossy jaw
- S Fedele
- Porter
- D Sr
- F Aiuto
- S Aljohani
- P Vescovi
- M Manfredi
Fedele S, Porter SR, D'Aiuto F, Aljohani S, Vescovi P, Manfredi M, et al. Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: A case series. Am J Med 2010:123:1060-4. How to cite this article: Campisi G, Compilato D, Angelo I, Muzio LL, Colella G. Spontaneous bisphosphonate-related osteonecrosis of the left hemi-mandible: Similarities with phossy jaw. Indian J Dent Res 2012;23:683-5. Source of Support: Nil, Conflict of Interest: None declared.
Surgery-triggered and non surgery triggered Bisphosphosonate-related Osteonecrosis of the Jaws
- P Vescovi
- G Campisi
- V Fusco
- G Mergoni
- M Manfredi
- E Merigo
Vescovi P, Campisi G, Fusco V, Mergoni G, Manfredi M,
Merigo E, et al. Surgery-triggered and non surgery triggered
Bisphosphosonate-related Osteonecrosis of the Jaws (BRONJ):