Sinus Tracts-An Early Sign of Bisphosphonate-Associated Osteonecrosis of the Jaws?

Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons (Impact Factor: 1.43). 04/2009; 67(3):593-601. DOI: 10.1016/j.joms.2008.09.031
Source: PubMed


Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is defined as the presence of exposed bone for at least 8 weeks in patients with exposure to bisphosphonates and no history of radiotherapy to the jaw. We report 5 patients with a history of bisphosphonate use, sinus tracts or deep periodontal pockets and radiographic findings typical for BONJ but with no evidence of exposed necrotic bone at the first evaluation visit.
The mean age was 70 years (range 66-77) and all were males. Patients had multiple myeloma (2), multiple myeloma and prostate cancer (1), monoclonal gammopathy of unknown significance (1) and osteoporosis (1). Three cases involved the mandible and 2 the maxilla. Four patients were on intravenous pamidronate and/or zoledonic acid and 1, alendronate. All cases except 1 (with deep periodontal pockets) presented with intraoral draining sinus tracts.
Radiographic findings included persistence of extraction socket (2), mottled radio-opacity and radiolucency (1), presence of sequestrum (1) and no significant findings (1). Subsequently, 4 patients developed exposed bone and 1 patient had necrotic bone removed from the jaws.
We report 5 patients with a history of bisphosphonate therapy where 4 patients had persistent sinus tracts and a fifth, severe bone loss. Four patients had radiographic findings typical for BONJ, and all subsequently developed necrotic bone. We propose modifying the definition of BONJ to include a category of "suspected BONJ" Stage 0(sa) where patients have persistent sinus tracts or localized deep periodontal pockets and typical radiographic findings for BONJ but are asymptomatic, and Stage 0(ss) for those who are symptomatic.

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    • "In addition, placing such cases in Stage 3 makes immediate antibiotic therapy appropriate, even according to older guidelines. Other recent studies reported that bone exposure was not always observed in a subset of cases that otherwise exhibited the characteristic hallmarks of BRONJ [28] [29] [30] [31]. In this series, four patients (#1, #3, #12 and #18) with Stage 2 or 3 BRONJ demonstrated paranasal sinusitis. "
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    ABSTRACT: BRONJ has become a well-known, occasionally severe side effect of bisphosphonate therapy, as well as a clinical problem. Although treatment recommendations exist, no standard therapy has yet been established for BRONJ. Also, these recommendations identify several limitations that prevent clinicians from confidently diagnosing BRONJ. The aim of the present study was to establish a treatment approach in which all patients with exposed, infected bone or intraoral/extraoral fistulas were treated with sitafloxacin (STFX). We examined 20 BRONJ patients, fourteen with cancer and six with osteoporosis. We used the current updated definition of BRONJ (12), except that we included patients who had shown symptoms for a minimum of only one month, rather than two months. Thus half our patients had infection with no exposed, necrotic bone in the oral cavity. We purposely excluded all patients exhibiting no signs of infection (current Stage 0 and 1). In addition, each potentially causative organism was isolated from pus collected from an intraoral or extraoral fistula in ten patients on their first visit to our department. 90% of the patients had received a course of treatment with common antibiotics. STFX was administered to all patients. We then re-evaluated the lesion every other week, to determine whether epithelialization was present. We recommended surgical treatment for cases without epithelialization within 4weeks after the onset of administration of STFX even if bone was not exposed at the lesion. 19 of our 20 cases of Stage 2-3 BRONJ responded to 2-10 weeks of STFX treatment by entering either a remission or healed phase. While surgery was done on thirteen cases, seven others reached such phases without surgery. Every patient had at least one bacterial species that showed resistance to common antibiotics. All species in all patients were susceptible to STFX. Our results indicate that STFX, with or without minor surgery, gives a high probability of controlling infection in BRONJ patients with persistent infection after use of common antibiotics, leading to remission and/or complete healing in 95% of patients. Copyright © 2014. Published by Elsevier Inc.
    Bone 12/2014; 73. DOI:10.1016/j.bone.2014.12.021 · 3.97 Impact Factor
    • "j c m f s . c o m function are, overall, rare aspects of ONJ in the lower jaw, the course of the disease in the upper jaw can be complicated by maxillary sinusitis and oral-antral or oral-nasal communications (Otto et al., 2009, Abu-Id et al., 2008, Mawardi et al., 2009, Ruggiero et al., 2009). Although the clinical features of ONJ are well-described and widely accepted, quantitative analyses are still rare. "
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    ABSTRACT: Osteonecrosis of the jaw (ONJ) is a serious side-effect of intravenous nitrogen-containing bisphosphonate therapy frequently used in the treatment of malignant diseases. Despite numerous case series published so far studies with detailed investigations into risk factors, the precise localization of ONJ and impact of ONJ on the oncological treatment remain sparse. This single-centre study collated medical records (2003-2009) of all patients that suffered from ONJ within the Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Germany. In total, 126 patients fulfilled the case criteria of ONJ and were examined clinically. The complete medical history including detailed questionnaires was collected of 66 patients, focussing in particular on the identification of underlying risk factors, clinical features, ONJ localization as well as the impact on the oncological treatment. The majority of ONJ cases occurred in patients suffering from malignant diseases (n=117; 92.8%), in particular breast cancer (n=57; 45.2%), multiple myeloma (n=37; 29.4%) and prostate cancer (n=13; 10.3%), all received nitrogen-containing bisphosphonates intravenously. ONJ was also diagnosed in 9 patients (7.1%) suffering from osteoporosis or rheumatoid arthritis. The most prevalent clinical feature was exposed necrotic bone (93.9%) in the oral cavity which was accompanied in 78.8% of cases by pain. A predilection for the mandible and in particular for molar and premolar regions in both jaws was shown. Although no recommendation concerning the oncologic treatment was made, the manifestation of ONJ resulted (in a significant proportion of the patients) in a change of medication and schedule. The most frequent co-medications were steroids and anti-angiogenetic drugs, such as thalidomide. The predilection for mandibular molar and premolar regions, and the infectious conditions that often precede the onset of ONJ support recent pathogenesis theories stating that local inflammation and associated pH-changes may trigger the release and activation of nitrogen-containing bisphosphonates ultimately resulting in necrosis. The development of ONJ has a multi-factorial aetiology and the clinical presentation can vary markedly. ONJ cannot only impair the quality of life but also the treatment of the underlying disease.
    Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 06/2011; 40(4):303-9. DOI:10.1016/j.jcms.2011.05.003 · 2.93 Impact Factor
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    • "The inability to repair physiologic microfractures that occur daily in the oral cavity would result in the occurrence of the BRONJ (Migliorati et al. 2005). Because in the last years, the reports regarding the association of nitrogencontaining bisphosphonates with the occurrence of BRONJ have increased substantially (Sarathy et al. 2005; Dimitrakopoulos et al. 2006; Farrugia et al. 2006; Merigo et al. 2006; Marx 2008; Ruggiero 2008; Mawardi et al. 2009), our results warrant further investigation concerning the alteration of early bone formation and remodeling due to bisphosphonate administration. Within the limitations of this study, it may be concluded that oestrogen deficiency negatively affected the amount of bone around implants. "
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    ABSTRACT: This study evaluated the influence of oestrogen deficiency and its therapies on bone tissue around osseointegrated implants. Implants were placed in 66 female rats tibiae. The animals were assigned into five groups: control (CTL), sham, ovariectomy (OVX), oestrogen (EST), and alendronate (ALE). While CTL was sacrificed 60 days after implant placement, other groups were subjected to ovariectomy or sham surgery according to group and euthanized after 90 days. Blood and urine samples were collected at sacrifice day for osteocalcin (OCN) and deoxypyridinoline (DPD) quantification. Densitometry of femur and lumbar vertebrae was performed in order to evaluate rats' skeletal impairment. Non-decalcified sections were referred to fluorescent and light microscopy for analyses of mineral apposition rate (MAR), eroded and osteoclastic surfaces, bone-to-implant contact (BIC), and bone area fraction occupancy (BAFO). Results from the OVX group showed significantly lower bone mineral density (BMD), BIC, BAFO, and MAR, while OCN, deoxipiridinoline, eroded surface and ostecoclastic surface were increased compared with the other groups of the study. ALE reduced OCN and DPD concentrations, MAR, osteoclastic and eroded surfaces, and no difference was in BIC and BAFO relative to SHAM. EST and CTL showed similar results to SHAM for measurements. Oestrogen deficiency exerted a negative influence on bone tissue around implants, while oestrogen replacement therapy and alendronate were effective against its effects. Although alendronate therapy maintained the quantity of bone around implants, studies evaluating bone turnover kinetics are warranted.
    Clinical Oral Implants Research 10/2010; 22(3):259-64. DOI:10.1111/j.1600-0501.2010.01989.x · 3.89 Impact Factor
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