Dental health status and patient-reported outcomes at baseline in patients participating in the osteonecrosis of the jaw registry study, SWOG S0702.

PURPOSE: SWOG S0702 was a cohort study of patients with cancer with bone metastases due to any cancer. Using baseline data from S0702, this report characterizes the oral health and oral health-related quality of life (OHRQoL) of patients with advanced cancer. METHODS: S0702 case report forms captured dental assessment and patient-reported outcome (PRO) data. This analysis compares PRO dental discomfort with selected clinical assessments of dental health. This analysis focuses on the 2294 patients who underwent baseline dental examination prior to study registration, but also reports on the 1235 patients for whom only OHRQol data are available. Dental characteristics including the number of teeth and the presence of gingivitis and periodontal disease were examined for correlation with PRO of oral pain, interference with eating, smiling, speech, or quality of life. RESULTS: The median age of the study participants was 62. Greater than 60% of the 2294 patients with baseline dental assessments had none to mild plaque, calculus, gingivitis, or periodontal disease, suggesting that most of this cohort had good oral hygiene. However, in each of these same categories, approximately 6% had dental findings classified as severe conditions (poor oral hygiene). There was strong evidence that the presence of periodontal disease, gingivitis, and number of teeth was correlated with lower OHRQoL across multiple domains, including pain (mouth or jaw), interference with eating, smiling and speech, and overall quality of life. CONCLUSIONS: This report characterizes the oral health and OHRQoL of patients with advanced bone metastases receiving palliative therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00874211.

An unusual complication of tooth exfoliation and osteonecrosis following herpes zoster infection of trigeminal nerve: a case report and literature review.

Osteonecrosis following herpes zoster infection is a rare but severe complication, and clinicians' awareness is important for early detection and management of this condition. A case of herpes zoster of the left maxillary division of the trigeminal nerve is reported in a young female having no concurrent predisposing factors, with accompanying rare complications of alveolar bone necrosis and rapid tooth exfoliation. Acyclovir was used to manage the case effectively. The previously reported similar cases in the literature have been reviewed and the pathophysiology of tooth exfoliation and osteonecrosis by varicella zoster viruses is discussed.

Pathophysiology of atypical femoral fractures and osteonecrosis of the jaw.

In recent years, atypical femoral fractures and osteonecrosis of the jaw have emerged as potential complications of long-term bisphosphonate therapy; osteonecrosis of the jaw has also been reported in patients receiving high doses of denosumab. The pathophysiology of both conditions is poorly defined, and the underlying mechanisms are likely to differ. The initiation of atypical fractures in the lateral femoral shaft suggests that reduced tensile strength, possibly secondary to alterations in the material properties of bone resulting from low bone turnover, may be an important pathogenetic factor. Osteonecrosis of the jaw is characterised by infection, inflammation, bone resorption and bone necrosis, but the sequence in which these occur has not been established. However, the observation that bone resorption occurs in close proximity to microbial structures suggests that infection may be the most important trigger, often as a result of dental disease. Other possible pathogenetic factors include suppression of bone turnover, altered immune status and adverse effects of bisphosphonates on the oral mucosa.

Is bisphosphonate therapy for benign bone disease associated with impaired dental healing? A case-controlled study.

BACKGROUND: Bisphosphonates are common first line medications used for the management of benign bone disease. One of the most devastating complications associated with bisphosphonate use is osteonecrosis of the jaws which may be related to duration of exposure and hence cumulative dose, dental interventions, medical co-morbidities or in some circumstances with no identifiable aggravating factor. While jaw osteonecrosis is a devastating outcome which is currently difficult to manage, various forms of delayed dental healing may be a less dramatic and, therefore, poorly-recognised complications of bisphosphonate use for the treatment of osteoporosis. It is hypothesised that long-term (more than 1 year's duration) bisphosphonate use for the treatment of post-menopausal osteoporosis or other benign bone disease is associated with impaired dental healing. METHODS/DESIGN: A case-control study has been chosen to test the hypothesis as the outcome event rate is likely to be very low. A total of 54 cases will be recruited into the study following review of all dental files from oral and maxillofacial surgeons and special needs dentists in Victoria where potential cases of delayed dental healing will be identified. Potential cases will be presented to an independent case adjudication panel to determine if they are definitive delayed dental healing cases. Two hundred and fifteen controls (1:4 cases:controls), matched for age and visit window period, will be selected from those who have attended local community based referring dental practices. The primary outcome will be the incidence of delayed dental healing that occurs either spontaneously or following dental treatment such as extractions, implant placement, or denture use. DISCUSSION: This study is the largest case-controlled study assessing the link between bisphosphonate use and delayed dental healing in Australia. It will provide invaluable data on the potential link between bisphosphonate use and osteonecrosis of the jaws.

Zoledronic acid delays wound healing of the tooth extraction socket, inhibits oral epithelial cell migration, and promotes proliferation and adhesion to hydroxyapatite of oral bacteria, without causing osteonecrosis of the jaw, in mice.

Nitrogen-containing bisphosphonates such as zoledronic acid (ZOL) and pamidronate have been widely and successfully used for the treatment of cancer patients with bone metastases and/or hypercalcemia. Accumulating recent reports have shown that cancer patients who have received these bisphosphonates occasionally manifest bisphosphonate-related osteonecrosis of the jaw (BRONJ) following dental treatments, including tooth extraction. However, little is known about the pathogenesis of BRONJ to date. Here, to understand the underlying pathogenesis of BRONJ, we examined the effects of ZOL on wound healing of the tooth extraction socket using a mouse tooth extraction model. Histomorphometrical analysis revealed that the amount of new bone and the numbers of blood vessels in the socket were significantly decreased in ZOL-treated mice compared to control mice. Consistent with these results, ZOL significantly inhibited angiogenesis induced by vascular endothelial growth factor in vivo and the proliferation of endothelial cells in culture in a dose-dependent manner. In contrast, etidronate, a non-nitrogen-containing bisphosphonate, showed no effects on osteogenesis and angiogenesis in the socket. ZOL also suppressed the migration of oral epithelial cells, which is a crucial step for tooth socket closure. In addition, ZOL promoted the adherence of Streptococcus mutans to hydroxyapatite and the proliferation of oral bacteria obtained from healthy individuals, suggesting that ZOL may increase the bacterial infection. In conclusion, our data suggest that ZOL delays wound healing of the tooth extraction socket by inhibiting osteogenesis and angiogenesis. Our data also suggest that ZOL alters oral bacterial behaviors. These actions of ZOL may be relevant to the pathogenesis of BRONJ.

A novel animal model to study non-spontaneous bisphosphonates osteonecrosis of jaw.

The aim of this study was to evaluate a novel animal model of bisphosphonates-associated osteonecrosis, which realistically recapitulates the same pathological human condition. Five Wistar rats were given intravenous zoledronic acid 0.04 mg once a week for 5 weeks. After 2 weeks, the animals underwent the extraction of an upper molar, producing a 4 mm-diameter bone defect on the same site. After 7 weeks from the extraction, the animals were clinically examined and a bone scintigraphy was carried out. After an additional week, the rats were killed and both Computerized Tomography and histological analysis were performed. Five rats, not treated with zoledronic acid and exposed to the same surgical treatment, were used as controls. At 7 weeks after the extraction, all the rats treated with zoledronic acid showed expansion of the defect and bone exposure. These features were confirmed by bone scintigraphy. The rats of the control group demonstrated epithelialization of the bone defect and a normal uptake of the contrast medium during the scan. The Computerized Tomography scan disclosed irregularity of the cortical margin and bone destruction, which were not evident in the control group. On microscopy, the samples showed necrotic bone, loss of osteocytes and peripheral resorption without inflammatory infiltrate, while the controls showed normal bone healing. The rat treated with zoledronic acid can be considered a novel, reliable and reproducible animal model to understand better the pathophysiology of osteonecrosis of the jaw and to develop a therapeutic approach.

Case report: osteonecrosis of the mandible after laryngoscopy and endotracheal tube placement.

Four patients underwent laryngoscopy and general anesthesia surgery without apparent perioperative complications. Within days of their procedure, throat and mouth pain were reported and intraoral examination in all cases revealed exposed bone in the posterior mandible. The sequestra were easily removed and healing was uneventful. These lesions are likely associated with localized oral trauma during intubation causing periosteal damage, compromised blood supply, and subsequent bone necrosis. Because trauma to the mylohyoid ridge during intubation is likely more common than previously appreciated, anesthesiologists should be aware of this potential complication and refer patients to a specialist for management.

Lack of correlation between duration of osteonecrosis of the jaw and sequestra tissue morphology: what it tells us about the condition and what it means for future studies.

PURPOSE: More studies have begun to investigate properties of tissue obtained from patients with osteonecrosis of the jaw (ONJ). Because of the relatively low incidence of ONJ, these studies necessitate the use of specimens from patients who have had ONJ for various durations. The goal of this study was to determine if properties, specifically bone morphology assessed by microcomputed tomography, were influenced by the duration of ONJ. MATERIALS AND METHODS: Sequestra from 31 patients with confirmed ONJ for 3 weeks to 42 months before obtaining the tissue were scanned using microcomputed tomography to determine bone volume/tissue volume and bone surface/tissue volume. RESULTS: There was no significant correlation between the sequestra bone morphology (bone volume/tissue volume or bone surface/tissue volume) and the duration of ONJ. CONCLUSION: The findings indicated that studies should not be concerned about assessing tissue properties from patients who have had ONJ for different durations. In addition, the lack of difference in morphology with continued duration of ONJ suggests that most changes to bone tissue occur early in the disease progression.

Inhibition of necrotic actions of nitrogen-containing bisphosphonates (NBPs) and their elimination from bone by etidronate (a non-NBP): a proposal for possible utilization of etidronate as a substitution drug for NBPs.

PURPOSE: Nitrogen-containing bisphosphonates (NBPs) have powerful anti-bone-resorptive effects (ABREs). However, recent clinical applications have disclosed an unexpected side effect, osteonecrosis of the jaw. We previously found in mice that etidronate (a non-NBP), when coadministered with alendronate (an NBP), inhibited the latter's inflammatory effects. However, etidronate also reduced the ABRE of alendronate. The present study examined in mice the modulating effects of etidronate on the inflammatory and necrotic actions of zoledronate (the NBP with the strongest anti-bone-resorptive activity and the highest incidence of osteonecrosis of the jaw) and on ABREs of various NBPs including zoledronate. MATERIALS AND METHODS: NBPs were subcutaneously injected into ear pinnas of mice and ensuing inflammation and necrosis at the site of the injection were evaluated. ABREs of NBPs were evaluated by analyzing sclerotic bands induced in mouse tibias. RESULTS: Coinjection of etidronate reduced inflammatory and necrotic reactions induced by zoledronate, and also reduced the amount of zoledronate retained within the ear tissue. When both agents were intraperitoneally injected, etidronate reduced the ABRE of zoledronate and those of other NBPs. Notably, etidronate reduced the ABRE of zoledronate even when this non-NBP was injected 16 hours after the injection of zoledronate. Bone scintigram indicated that etidronate reduced the amount of zoledronate that had already bound to bone. CONCLUSIONS: These results suggest that etidronate may 1) inhibit the entry of NBPs into cells related to inflammation and/or necrosis, 2) inhibit the binding of NBPs to bone hydroxyapatite, 3) at least partly eliminate (or substitute for) NBPs that have already accumulated within bones, and thus 4) if used as a substitution drug for NBPs, be effective at treating or preventing NBP-associated osteonecrosis of the jaw.

Bisphosphonate-related osteonecrosis of the jaw: tip of the iceberg.

The World Health Organization predicts that people aged older than 65 years will comprise 20% of the world's population by 2030. One of the most commonly prescribed medications for the elderly are the bisphosphonates, which have been shown to significantly reduce debilitating and fatal fractures by preserving bone density and consequently saving governments billions of dollars annually. Despite rigorous testing, 190 million prescriptions worldwide and US$8000 million in revenue, there is a serious adverse effect called bisphosphonate-related osteonecrosis of the jaw, which is poorly described and difficult to treat. The difficulty is compounded by the inability of medical personnel to recognize and adequately refer these patients or take adequate precautions before instituting bisphosphonate therapy. A myriad of differentials and a lack of consensus on how to definitively treat these patients have made this new presentation a worrying precursor for millions of other consumers who will reach the 5-year oral half life of bisphosphonates, which is when they generally start to present. In this paper, we explore historical parallels and provide the most comprehensive review to date in the literature about the presentation, diagnosis, treatment, pathophysiology, oncogenic associations, and best practice guidelines. Legal action pursuant to bisphosphonate-related osteonecrosis of the jaw is underway on 3 continents, and we believe that every health care professional should become au fait with this condition for which our growing case series represents merely the tip of the iceberg.

Jawbone remodeling: a conceptual study based on Synchrotron High-resolution Tomography.

One of the most important aspects of bone remodeling is the constant turnover mainly driven by the mechanical loading stimulus. The remodeling process produces changes not only in the bone microarchitecture but also in the density distribution of the mineralized matrix - i.e. in calcium concentrations- and in the osteocyte lacunar network. Synchrotron radiation-based X-ray microtomography (microCT) has proven to be an efficient technique, capable to achieve the analysis of 3D bone architecture and of local mineralization at different hierarchical length scales, including the imaging of the lacuno-canalicular network. In the present study, we used microCT within a conceptual study of jawbone remodeling, demonstratively focusing the investigation in two critical contexts, namely in the peri-dental and the peri-implant tissues. The microCT analysis showed that a relevant inhomogeneity was clearly present in both peri-dental and peri-implant biopsies, not only in terms of microarchitecture and mineralization degree, but also considering the lacunar network, i.e. size and numerical density of the osteocyte lacunae. The correlated histological results obtained on the same samples confirmed these observations, also adding information related to non-mineralized tissues. Despite its demonstrative nature, it was concluded that the proposed method was powerful in studying jawbone remodeling because it revealed a direct correlation of its rate with the lacunar density, as achieved by the analysis of the osteocyte lacunar network, and an inverse correlation with the local bone mineral density, as revealed with the Roschger approach.

Clinical observation of two bone cement distribution modes of percutaneous vertebroplasty in the treatment of thoracolumbar Kümmell's disease.

BACKGROUND: In recent years, percutaneous vertebroplasty (PVP) has provided a new option for the treatment of Kümmell's disease (KD). This retrospective study aimed to investigate the differences in clinical characteristics, clinical efficacy, and related complications between two types of bone cement distribution patterns in the PVP treatment of KD. METHODS: A total of 63 patients with KD from January 2016 to February 2018 who received PVP treatment were examined at least 24 months. According to X-ray distribution modes of bone cement after PVP treatment, they were divided into 2 groups: blocky group (30 cases) and spongy group (33 cases). Clinical features and disease severity preoperatively, and clinical efficacy and related complications postoperatively were statistically compared between the two groups. RESULTS: The two groups were followed for at least 24 months. The duration of disease, age, Cobb angle, and vertebral compression rate preoperatively were significantly higher in the blocky group than in the spongy group (P < 0.05, respectively). The height of vertebral anterior margin and BMD were significantly lower in the blocky group than in the spongy group (P < 0.05, respectively). The amount of bone cement injected was significantly greater in the blocky group than in the spongy group (P = 0.000). VAS and ODI of the two groups were significantly reduced at the first day, the first year, and the last follow-up postoperatively (all P = 0.000) and were maintained at the last follow-up. VAS and ODI postoperatively decreased significantly in the spongy group compared with the blocky group (P = 0.000). The correction degrees of kyphosis and vertebral compression postoperatively in the two groups were significantly corrected, but gradually decreased over time (P < 0.05), and these correction degrees were significantly higher in the blocky group than in the spongy group, and the postoperative losses were also more serious. CONCLUSIONS: The disease was more serious in the blocky group than in the spongy group. The amount of bone cement, correction degrees of postoperative kyphosis and vertebral compression were significantly higher in the blocky group than in the spongy group, but its postoperative losses of the correction degrees of kyphosis and vertebral compression were also more serious. However, for pain relief and functional recovery, the spongy group was superior to the blocky group. Therefore, the spongy distribution pattern should be formed during the injection of bone cement to obtain better therapeutic effect.

Osteoporosis treatments and adverse events.

PURPOSE OF REVIEW: Osteoporosis treatments will be used with increasing frequency as the population ages; however, relatively little is known about their long-term safety. Recent case reports cite a range of potential adverse events. We review data regarding atrial fibrillation, bone pain, osteonecrosis of the jaw (ONJ), atypical fractures, and osteosarcoma. RECENT FINDINGS: Incidence of bisphosphonate-related ONJ in osteoporosis patients is unclear, but several studies suggest rates may be higher than one in 100,000. Severe bone pain and esophageal cancer have been described among bisphosphonate users, but their relationship has not been carefully studied. The relationship between atrial fibrillation and bisphosphonates is unclear based on existing data, but the Food and Drug Administration's (FDA) analyses suggest no clear association. Although several case series discuss atypical fractures associated with bisphosphonate use, one epidemiologic study found no association. Finally, one case of osteosarcoma has been reported in a woman using teriparatide. One case in over 200,000 users suggests no increase in risk beyond background risk, but further evaluation is necessary. SUMMARY: Although case reports of adverse events with osteoporosis medications suggest potential links, epidemiological analyses have largely failed to illuminate a strong, clear link between osteoporosis therapies and many adverse events, with ONJ an exception. Until further data are available, providers should be aware of these potential side effects, and inform their patients accordingly.

Bisphosphonates and osteonecrosis of the jaw: moving from the bedside to the bench.

Osteonecrosis of the jaw (ONJ) has received significant attention as a potential side effect of bisphosphonate treatment. The limited understanding of the underlying pathophysiology of the condition emphasizes the need to transition ONJ research from the bedside to the bench, supplementing ongoing clinical research with animal/basic science studies. The goal of this review is to briefly highlight the most commonly proposed mechanisms for ONJ and then summarize our laboratory's recent efforts to begin transitioning ONJ research to an animal model. Remodeling suppression, disrupted angiogenesis and infection have all been proposed to connect bisphosphonates to ONJ, although most supportive data for each of these are either indirect or nonexistent. Our laboratory has begun studying the dog as a potential model of ONJ. We have shown regions of necrotic bone matrix within the mandible of dogs treated with oral or intravenous bisphosphonate. We hypothesize these regions are the result of remodeling suppression, and if combined with additional factors such as dental intervention or infection, would result in manifestation of exposed oral lesions, the clinical definition of ONJ. Although these findings suggest the dog may be a viable animal model to study ONJ, many questions remain unanswered. No matter what animal model is found to mimic the clinical presentation of ONJ, once established it will allow significant progress toward understanding the specific role of bisphosphonates in the pathophysiology of ONJ and if/how the entity of ONJ can best be treated and prevented.

Refractory healing after surgical therapy of osteonecrosis of the jaw: associated risk factors in aged patients.

Purpose: Osteonecrosis of the jaw (ONJ), both medication-related and non medication-related, mainly occurs in aged patients. It needs surgical intervention. Refractory healing after an operation of ONJ can significantly lower the quality of life of elderly patients. The purpose of this study was to determine risk factors associated with refractory healing in aged patients. Patients and methods: We performed a retrospective study of ONJ in aged patients who underwent surgical treatments in a single institute during a 12-year period. Multiple logistic regression analysis was used to determine independent risk factors associated with refractory healing. Results: A total of 122 patients were included. Of them, 25 patients were identified as the refractory group and 97 patients as the control group. Diabetes mellitus (DM) (AOR=5.03, 95% CI: 1.74-14.52) and glucocorticoid administration (AOR=7.97, 95% CI: 2.52-25.23) were found to be significant risk factors for refractory healing of ONJ. Conclusion: DM and medication of glucocorticoid might be risk factors for refractory healing of ONJ.

Is hydroxyapatite a reliable fixation option in unicompartmental knee arthroplasty? A 5- to 13-year experience with the hydroxyapatite-coated unix prosthesis.

Hydroxyapatite-coated unicompartmental knee arthroplasty (UKA) is a debatable approach to unicompartmental knee arthritis because UKA isoften viewed as a short-term solution, at best, fora condition that will eventually require a total knee arthroplasty (TKA). Unicompartmental knee arthroplasty is a more technically demanding procedure than TKA, and appropriate patient selection, careful surgical technique, and correct choice of implant geometry are all critical components to its success. A fundamental issue surrounding UKA is whether hydroxyapatite-coated unicompartmental components can provide a long-term solution to unicondylar arthritis. We address this issue in the current study, which is based on a prospective series of 125 hydroxyapatite-coated Unix knee prostheses implanted consecutively between 1994 and 2002, with a 5-year minimum follow-up and a 13-year maximum follow-up. The results of our study indicate that uncemented hydroxyapatite-coated UKA can be successful in the long term.

Osteonecrosis of the jaws secondary to bisphosphonate therapy: a case series.

AIM: The objective of this report is to present the clinical experiences of several patients affected with osteonecrosis (ONJ) secondary to bisphosphonate (BP) therapy and to provide a discussion of the specific BPs implicated in this condition. BACKGROUND: ONJ secondary to BP therapy is becoming an increasingly reported complication following dental therapy. This is particularly true of surgical dental procedures such as extractions. BPs are a class of pharmaceuticals used in the treatment of numerous disorders affecting bone, including osteoporosis, cancer metastases to bone, hypercalcemia of malignancy, and multiple myeloma. Although ONJ is a more recently described phenomenon, it is an emerging problem that may be associated with significant morbidity such as oral dysfunction, impaired eating ability, pain, and compromised esthetics resulting in a poor quality of life in affected patients. CASE REPORT: This is a description of 13 patients affected with ONJ secondary to BP therapy managed at the Orofacial Pain & Oral Medicine Center, Special Patients Clinic, and Oral and Maxillofacial Surgery Clinic at the University of Southern California, School of Dentistry between October 2005 and April 2007, with a discussion of the specific BPs implicated in this condition, the clinical presentation, management, and follow-up. SUMMARY: Thorough reporting of every case of ONJ is important to help advance the understanding of this poorly understood condition. The authors' approach to care represents a more conservative mode to management than previously described by many investigators.

Porous composite scaffold incorporating osteogenic phytomolecule icariin for promoting skeletal regeneration in challenging osteonecrotic bone in rabbits.

Steroid-associated osteonecrosis (SAON) often requires surgical core decompression (CD) in the early stage for removal of necrotic bone to facilitate repair where bone grafts are needed for filling bone defect and avoiding subsequent joint collapse. In this study, we developed a bioactive composite scaffold incorporated with icariin, a unique phytomolecule that can provide structural and mechanical support and facilitate bone regeneration to fill into bone defects after surgical CD in established SAON rabbit model. An innovative low-temperature 3D printing technology was used to fabricate the poly (lactic-co-glycolic acid)/ß-calcium phosphate/icariin (PLGA/TCP/Icariin, PTI) scaffold. The cytocompatibility of the PTI scaffold was tested in vitro, and the osteogenesis properties of PTI scaffolds were assessed in vivo in the SAON rabbit models. Our results showed that the fabricated PTI scaffold had a well-designed biomimic structure that was precisely printed to provide increased mechanical support and stable icariin release from the scaffold for bone regeneration. Furthermore, our in vivo study indicated that the PTI scaffold could enhanced the mechanical properties of new bone tissues and improved angiogenesis within the implanted region in SAON rabbit model than those of PLGA/TCP (PT) scaffold. The underlying osteoblastic mechanism was investigated using MC3T3-E1 cells in vitro and revealed that icariin could facilitate MC3T3-E1 cells ingrowth into the PTI scaffold and regulate osteoblastic differentiation. The PTI scaffold exhibited superior biodegradability, biocompatibility, and osteogenic capability compared with those of PT scaffold. In summary, the PTI composite scaffold which incorporated bioactive phyto-compounds is a promising potential strategy for bone tissue engineering and regeneration in patients with challenging SAON.

Bisphosphonates and osteomyelitis of the jaw: a pathogenic puzzle.

The maxillary and mandibular bones undergo high-turnover remodeling to maintain mechanical competence. Common dental or periodontal diseases can increase local bone turnover. Bisphosphonates (BPs) accumulate almost exclusively in skeletal sites that have active bone remodeling. The maxillary and mandibular bones are preferential sites for accumulation of BPs, which become buried under new layers of bone and remain biologically inactive for a long time. Surgical odontostomatological procedures create open bony wounds that heal quickly and without infection, as a result of activation of osteoclasts and subsequently osteoblasts. Once BPs are removed from the bone via activation of osteoclasts after a tooth extraction or a periodontal procedure, they induce osteoclast apoptosis. This inhibition of osteoclast bone resorption impairs bone wound healing because of decreased production of cytokines derived from the bone matrix, and the bone is exposed to the risk of osteomyelitis and necrosis. The pathogenic relationship between BPs and osteonecrosis of the jaw is unclear, but there is evidence to indicate an association between high-dose BP treatment and exposure to dental infections or oral surgical procedures. A better knowledge of the interactions between BPs and jaw and maxillary bone biology will improve clinical and therapeutic approaches.