This study aims to investigate whether long-term bisphosphonate use for benign bone diseases is associated with impaired dental healing. A case-control study will be conducted comparing 54 cases of delayed dental healing in bisphosphonate users to 215 age-and visit period-matched controls without healing issues. Potential cases will be identified through dental records and confirmed by an adjudication panel. Data on demographics, bisphosphonate use, medical history and dental details will be collected through interviews and records. This study seeks to provide evidence on the relationship between bisphosphonates and dental complications to inform osteoporosis management for a growing aging population.
This document describes a retrospective study conducted at a tertiary care center that analyzed data on cases of osteomyelitis from 2006 to 2016. The study found that the number of female patients was equal to male patients, and most patients were between 30-45 years old. Unlike typical presentations where the mandible is more commonly affected, this study found that the maxilla was more commonly involved than the mandible. The posterior region of the maxilla was more frequently affected than the anterior region. The study aims to help optimize local treatment protocols by assessing epidemiological data from this specific tertiary care center.
This document provides an overview of medication-related osteonecrosis of the jaw (MRONJ), including descriptions of antiresorptive and antiangiogenic medications, diagnostic criteria, theories of pathophysiology, risk estimates, and management strategies. It discusses bisphosphonates, denosumab, tyrosine kinase inhibitors, diagnostic criteria requiring exposed bone for over 8 weeks, and proposed mechanisms including inhibition of bone remodeling, inflammation, angiogenesis, and immune dysfunction. Risk factors include medication type/duration, dentoalveolar surgery, oral disease, anatomy, and systemic factors. Management involves preventive dental treatment and is based on clinical staging from asymptomatic exposed bone to extensive necrosis.
BRONJ bisphosphonates osteonecrosis of jawWeam Faroun
This document discusses bisphosphonate-related osteonecrosis of the jaws (BRONJ) and provides guidance on dental management of patients taking bisphosphonates. It notes that bisphosphonates are commonly used to treat osteoporosis and bone metastases but can increase the risk of BRONJ, especially after dental surgery. The document recommends conservative dental treatment and antibiotic prophylaxis for high-risk patients. It identifies risk factors for BRONJ and advises monitoring of bone turnover markers like CTX to further assess surgical risk. The goal is to minimize but not eliminate the low risk of BRONJ from oral bisphosphonate use through preventative dental care and cautious management of invasive procedures.
This document provides an updated definition and guidelines for medication-related osteonecrosis of the jaw (MRONJ) from the American Association of Oral and Maxillofacial Surgeons (AAOMS). It recommends changing the term from bisphosphonate-related osteonecrosis of the jaw (BRONJ) to MRONJ to include cases involving other antiresorptive and antiangiogenic medications. It defines MRONJ as exposed bone in the jaw for over 8 weeks in a patient taking these medications, without radiation or metastasis to the jaw. The document discusses risk factors, potential mechanisms including inhibited bone remodeling and inflammation/infection, and provides guidance on prevention and management based on disease stage.
This document presents a case of a 70-year-old male diagnosed with medication-related osteonecrosis of the jaw (MRONJ) due to monthly denosumab injections for metastatic cancer since 2011. Clinical and radiographic findings were consistent with MRONJ including exposed bone in the area of teeth #34 and #36 that had been extracted in 2012. The patient's stage 1 MRONJ was managed conservatively with chlorhexidine rinses and referral for surgical debridement if infection develops. The document discusses denosumab versus bisphosphonates, diagnosing and staging MRONJ, potential pathophysiology, presentation, treatment guidelines, and recommendations for preventing MRONJ in patients taking anti-resor
Bisphosphonates are medications used to treat bone conditions like osteoporosis. They can cause a rare condition called bisphosphonate-related osteonecrosis of the jaw (BRONJ) characterized by exposed bone in the jaw that does not heal. BRONJ risk increases with more potent bisphosphonates used for longer durations. Dental procedures also increase BRONJ risk. Doctors should optimize oral health and extract teeth needing treatment before starting bisphosphonates when possible to reduce BRONJ risk. For patients with BRONJ, treatment focuses on pain relief and stopping progression.
This document provides an overview of bisphosphonate-induced osteonecrosis of the jaws (BIONJ). It begins with definitions and a brief history, noting BIONJ was first discussed in 2001 and has similarities to "phossy jaw" seen in early match factory workers exposed to white phosphorus. The document covers the mechanism of action, classification, and structure of bisphosphonates. It discusses the clinical use of bisphosphonates to treat osteoporosis, Paget's disease, and complications of malignant bone disease. Potential risk factors and pathophysiology of BIONJ are presented. The document provides detail on diagnosing and staging BIONJ as well as treatment guidelines.
This document discusses medicine-related osteonecrosis of the jaw (MRONJ), a serious side effect of antiresorptive therapy involving exposed necrotic bone in the jaw. It notes that MRONJ risk is associated with dental procedures and is most common in the mandible. It provides guidelines for prevention, including dental evaluation prior to starting therapy, conservative treatment of at-risk teeth, and use of antibiotic prophylaxis for high-risk patients undergoing invasive procedures. For management of exposed bone, it recommends a conservative approach for asymptomatic cases and use of analgesics and antibiotics for symptomatic cases or those with infection.
This document describes a retrospective study conducted at a tertiary care center that analyzed data on cases of osteomyelitis from 2006 to 2016. The study found that the number of female patients was equal to male patients, and most patients were between 30-45 years old. Unlike typical presentations where the mandible is more commonly affected, this study found that the maxilla was more commonly involved than the mandible. The posterior region of the maxilla was more frequently affected than the anterior region. The study aims to help optimize local treatment protocols by assessing epidemiological data from this specific tertiary care center.
This document provides an overview of medication-related osteonecrosis of the jaw (MRONJ), including descriptions of antiresorptive and antiangiogenic medications, diagnostic criteria, theories of pathophysiology, risk estimates, and management strategies. It discusses bisphosphonates, denosumab, tyrosine kinase inhibitors, diagnostic criteria requiring exposed bone for over 8 weeks, and proposed mechanisms including inhibition of bone remodeling, inflammation, angiogenesis, and immune dysfunction. Risk factors include medication type/duration, dentoalveolar surgery, oral disease, anatomy, and systemic factors. Management involves preventive dental treatment and is based on clinical staging from asymptomatic exposed bone to extensive necrosis.
BRONJ bisphosphonates osteonecrosis of jawWeam Faroun
This document discusses bisphosphonate-related osteonecrosis of the jaws (BRONJ) and provides guidance on dental management of patients taking bisphosphonates. It notes that bisphosphonates are commonly used to treat osteoporosis and bone metastases but can increase the risk of BRONJ, especially after dental surgery. The document recommends conservative dental treatment and antibiotic prophylaxis for high-risk patients. It identifies risk factors for BRONJ and advises monitoring of bone turnover markers like CTX to further assess surgical risk. The goal is to minimize but not eliminate the low risk of BRONJ from oral bisphosphonate use through preventative dental care and cautious management of invasive procedures.
This document provides an updated definition and guidelines for medication-related osteonecrosis of the jaw (MRONJ) from the American Association of Oral and Maxillofacial Surgeons (AAOMS). It recommends changing the term from bisphosphonate-related osteonecrosis of the jaw (BRONJ) to MRONJ to include cases involving other antiresorptive and antiangiogenic medications. It defines MRONJ as exposed bone in the jaw for over 8 weeks in a patient taking these medications, without radiation or metastasis to the jaw. The document discusses risk factors, potential mechanisms including inhibited bone remodeling and inflammation/infection, and provides guidance on prevention and management based on disease stage.
This document presents a case of a 70-year-old male diagnosed with medication-related osteonecrosis of the jaw (MRONJ) due to monthly denosumab injections for metastatic cancer since 2011. Clinical and radiographic findings were consistent with MRONJ including exposed bone in the area of teeth #34 and #36 that had been extracted in 2012. The patient's stage 1 MRONJ was managed conservatively with chlorhexidine rinses and referral for surgical debridement if infection develops. The document discusses denosumab versus bisphosphonates, diagnosing and staging MRONJ, potential pathophysiology, presentation, treatment guidelines, and recommendations for preventing MRONJ in patients taking anti-resor
Bisphosphonates are medications used to treat bone conditions like osteoporosis. They can cause a rare condition called bisphosphonate-related osteonecrosis of the jaw (BRONJ) characterized by exposed bone in the jaw that does not heal. BRONJ risk increases with more potent bisphosphonates used for longer durations. Dental procedures also increase BRONJ risk. Doctors should optimize oral health and extract teeth needing treatment before starting bisphosphonates when possible to reduce BRONJ risk. For patients with BRONJ, treatment focuses on pain relief and stopping progression.
This document provides an overview of bisphosphonate-induced osteonecrosis of the jaws (BIONJ). It begins with definitions and a brief history, noting BIONJ was first discussed in 2001 and has similarities to "phossy jaw" seen in early match factory workers exposed to white phosphorus. The document covers the mechanism of action, classification, and structure of bisphosphonates. It discusses the clinical use of bisphosphonates to treat osteoporosis, Paget's disease, and complications of malignant bone disease. Potential risk factors and pathophysiology of BIONJ are presented. The document provides detail on diagnosing and staging BIONJ as well as treatment guidelines.
This document discusses medicine-related osteonecrosis of the jaw (MRONJ), a serious side effect of antiresorptive therapy involving exposed necrotic bone in the jaw. It notes that MRONJ risk is associated with dental procedures and is most common in the mandible. It provides guidelines for prevention, including dental evaluation prior to starting therapy, conservative treatment of at-risk teeth, and use of antibiotic prophylaxis for high-risk patients undergoing invasive procedures. For management of exposed bone, it recommends a conservative approach for asymptomatic cases and use of analgesics and antibiotics for symptomatic cases or those with infection.
This case report describes a rare case of a 56-year-old female patient who presented with four isolated gingival enlargements, one on each side of her upper and lower molars. Histopathological examination determined the lesions were epulides. This finding of four separate epulides was termed "Quadra Epulis". The epulides were surgically excised and antibiotics were prescribed. Follow up was recommended to minimize recurrence. This report describes a unique presentation of multiple epulis lesions not previously reported in the literature.
Implants can be placed in irradiated jaws to support prostheses, but success rates are lower than in non-irradiated jaws. Key factors affecting osseointegration include implant placement timing after radiation (6-24 months ideal), radiation dose received, implant length and surface properties. Rough surfaces and longer implants promote osseointegration. Implant-supported fixed prostheses are preferable to removable dentures for irradiated patients. Close follow-up is needed due to higher risks of complications like osteoradionecrosis.
Localized aggressive periodontitis (LAP) and generalized aggressive periodontitis (GAP) are severe forms of periodontitis that primarily affect young, systemically healthy individuals. LAP is characterized by rapid bone loss affecting the first molars and incisors. GAP involves more generalized and episodic bone loss. Both are associated with small amounts of plaque harboring bacteria like Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Risk factors include specific microbes, immune defects, genetic factors, and smoking. Treatment involves scaling, root planing, surgery, and systemic antibiotics like tetracycline to eliminate bacterial pathogens from tissues.
The document discusses aggressive periodontitis, specifically localized aggressive periodontitis (LAP). It provides:
1) A historical background on LAP, formerly known as localized juvenile periodontitis, describing its identification and classification over time.
2) Key diagnostic criteria for LAP including an early age of onset typically around puberty, involvement of first molars and incisors, and a rapid rate of attachment loss and bone destruction.
3) Typical clinical characteristics of LAP such as minimal visible inflammation despite deep pockets and bone loss out of proportion to plaque levels. Radiographs often show vertical bone loss around first molars and incisors. Prevalence is typically below 1% with some studies finding higher rates in black males
Dental extractions in irradiated patientsUjwal Gautam
Dental extractions in patients undergoing radiotherapy carry risks of osteoradionecrosis and impaired wound healing due to radiation damage to vasculature, bone marrow, and fibroblasts. Extraction after radiotherapy requires preventive measures like antibiotics and atraumatic technique. Hyperbaric oxygen therapy has been used preventively for extractions, though its effectiveness is less than 100%. Where possible, extractions in irradiated patients should be avoided or meticulous preventive measures undertaken due to osteoradionecrosis risk.
Periodontal diseases Classifications and treatmentsRiad Mahmud
Prof. Dr. Md. Zahid Hossain, Division of Periodontology, Department of Preventive Dental Sciences, College of Dentistry, Najran University, Saudi Arabia.Former Professor of Periodontology, City Dental College, Dhaka
Osteoradionecrosis is bone necrosis that occurs in the radiation treatment volume months after treatment. It is caused by loss of vasculature due to radiation damage. Risk factors include radiation dose over 6500 cGy, chemotherapy, brachytherapy, and post-radiation dental extractions. Advanced cases can lead to fistulas, fractures, and discontinuity defects impacting functions like speech and swallowing.
2007 daher tratamiento no quirurgico en un adulto con clase iiimarangelroque
This case report describes the nonsurgical treatment of a 43-year-old man with a Class III malocclusion and crossbite. Treatment options included orthognathic surgery, nonextraction treatment, premolar extractions, and mandibular incisor extraction. The patient opted for nonsurgical treatment, which included maxillary expansion and extraction of a mandibular central incisor. Over 2 years of treatment with braces and a facemask, the crossbite was corrected and a good occlusion was achieved without the need for surgery.
Its very important for dentists to differentiate aggressive periodontitis and chronic periodontitis. This presentation includes basics of Aggressive periodontitis which can be very useful for undergraduate students of dental school for reference.
Infezione, vascolarizzazione, rimodellamento – le cellule staminali sono la r...Merqurio
1. Osteonecrosis of the jaw (ONJ) can result from craniofacial radiation, osteomyelitis, or bisphosphonate use, and the underlying pathophysiology of each condition is still unclear.
2. While infection, reduced blood flow, and impaired bone remodeling have all been proposed as causes, stem cell therapy may offer a promising new treatment by modulating the immune system and promoting bone and blood vessel growth.
3. Mesenchymal stem cells in particular have shown ability to both prevent and cure bisphosphonate-related ONJ in mouse models, indicating stem cells warrant further study as a potential solution for these challenging bone diseases of the jaw.
Localized aggressive periodontitis patients were treated with nonsurgical debridement and a 7-day course of amoxicillin and metronidazole. Over 4 years of follow-up, clinical parameters like probing depth and clinical attachment level were reduced by over 50% at most time points. Compliance with treatment and follow-up appointments was important for outcomes. Retrospective analysis found bone loss in primary dentition, suggesting early disease onset. The treatment was effective long-term but comparison to other approaches was lacking.
This document summarizes the effects of radiation therapy on oral tissues. Radiation is commonly used to treat oral cancers. It is delivered in small daily doses over 6-7 weeks for a total of 60-70 Gy. This causes damage to oral mucosa, taste buds, salivary glands, teeth, bone, and muscles. Oral mucositis is a common side effect, along with loss of taste, xerostomia, and rampant dental caries due to changes in saliva. Teeth may have arrested development. Long term risks include osteoradionecrosis and trismus. Management involves oral hygiene, pain control, fluoride application, and sometimes surgery.
This case report describes the endo-surgical management of a large radicular cyst in the maxillary anterior region that had completely resorbed the maxillary nasal floor. After non-surgical root canal treatment of teeth 11 and 12, surgical enucleation of the cyst was performed, followed by apicoectomy and retrograde filling of the root canals with mineral trioxide aggregate. The cyst had extended supero-posteriorly into the maxilla and nasal cavity. Complete removal of the cyst was achieved while preserving surrounding structures. Post-operative healing was uneventful. This case demonstrates the effective treatment of a large cyst using a combined nonsurgical endodontic and surgical approach.
AGGRESSIVE PERIODONTITIS
PRESENTER
DR. REBICCA RANJIT
DEPT. OF PERIODONTOLOGY & ORAL IMPLANTOLOGY
Why is there localisation of disease to 1st molars and incisors in LAP?
Often subjects present with attachment loss that does not fit the specific diagnostic criteria (AP or chronic periodontitis).
Schenkein et al. 1995: cigarette smoking was shown to be a risk factor for patients with generalized forms of AgP.
Smokers with GAP had more affected teeth and greater mean levels of attachment loss than patients with GAP who did not smoke.
IgG2 serum levels as well as antibody levels against A.a. are significantly depressed in subjects with GAP who smoked.
This document discusses osteoradionecrosis of the jaws, which is bone necrosis caused by radiation therapy for head and neck cancer. It defines osteoradionecrosis and describes its classification, types, risk factors, and theories of pathophysiology. The document outlines protocols for preventing and treating osteoradionecrosis, including conservative management, hyperbaric oxygen therapy, pentoxifyllin and tocopherol supplements, and surgical interventions. Hyperbaric oxygen therapy is described as an adjuvant treatment involving intermittent high-pressure oxygen sessions to promote revascularization and healing.
Abstract—This study was aimed to present a case report of a case of peripheral ossifying fibroma which is a rare case. This case was a 30 years non smoker male with the chief complaint of growth of gum tissue, moderately large in the mandibular posterior region. On intraoral examination, a peduncalated growth of 17 x 12 x 6 mm on marginal and attached gingiva with respect to tooth number 47 considerably hard in consistency and movable was seen. The lesion was erythmatous having a smooth non ulcerated surface. It was asymptomatic with no sign of pain. Intra oral periapical radiograph was taken which revealed slight erosion of crest of bone which was later confirmed during surgical excision. The possible reason of crestal bone erosion may be constant pressure of the growth. Differential diagnosis of irritation fibroma, pyogenic granuloma and peripheral giant cell granuloma was considered. However, clinical appearance and consistency was of a hard fibrous growth, which therefore led to a provisional diagnosis of peripheral ossifying fibroma or peripheral odontogenic fibroma.
This document discusses trauma from occlusion (TFO), defined as pathological alterations or adaptive changes that develop in the periodontium due to excessive occlusal forces. It provides historical context on TFO research dating back to 1901, classifications of TFO, stages of tissue response to TFO including injury and repair, and factors that can increase occlusal forces or decrease the periodontium's resistance to forces. TFO can be acute or chronic and primary (due to occlusal factors) or secondary (due to reduced periodontal support). Excessive forces can cause tissue injury through thrombosis, hemorrhage or necrosis while the body attempts repair through new tissue formation and bone remodeling.
Medication-Related Osteonecrosis of the jaws (MRONJ).pptxHadi Munib
The document provides information on Medication-Related Osteonecrosis of the Jaws (MRONJ). It discusses the AAOMFS definition, predisposing factors like dentoalveolar surgery, staging of MRONJ from 0-3, bisphosphonate medications and recommendations for patients receiving or about to start these medications. It also covers osteomyelitis including classification, pathogenesis, clinical presentation, investigations and surgical management. Overall, the document is an overview of MRONJ and osteomyelitis of the jaws for oral and maxillofacial surgery residents.
ADA - Updated recommendations for managing the care of patients receiving ora...clmaxidex
The document summarizes recommendations from an expert panel on managing dental care for patients taking oral bisphosphonate drugs. The panel concludes that the risk of developing bisphosphonate-associated osteonecrosis of the jaw (BON) from oral bisphosphonates is very low compared to intravenous bisphosphonates. Routine dental treatment and procedures can generally be performed as normal with some conservative approaches recommended. Patients should be informed of the very low risk and importance of oral health and regular dental care.
This case report describes a rare case of a 56-year-old female patient who presented with four isolated gingival enlargements, one on each side of her upper and lower molars. Histopathological examination determined the lesions were epulides. This finding of four separate epulides was termed "Quadra Epulis". The epulides were surgically excised and antibiotics were prescribed. Follow up was recommended to minimize recurrence. This report describes a unique presentation of multiple epulis lesions not previously reported in the literature.
Implants can be placed in irradiated jaws to support prostheses, but success rates are lower than in non-irradiated jaws. Key factors affecting osseointegration include implant placement timing after radiation (6-24 months ideal), radiation dose received, implant length and surface properties. Rough surfaces and longer implants promote osseointegration. Implant-supported fixed prostheses are preferable to removable dentures for irradiated patients. Close follow-up is needed due to higher risks of complications like osteoradionecrosis.
Localized aggressive periodontitis (LAP) and generalized aggressive periodontitis (GAP) are severe forms of periodontitis that primarily affect young, systemically healthy individuals. LAP is characterized by rapid bone loss affecting the first molars and incisors. GAP involves more generalized and episodic bone loss. Both are associated with small amounts of plaque harboring bacteria like Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Risk factors include specific microbes, immune defects, genetic factors, and smoking. Treatment involves scaling, root planing, surgery, and systemic antibiotics like tetracycline to eliminate bacterial pathogens from tissues.
The document discusses aggressive periodontitis, specifically localized aggressive periodontitis (LAP). It provides:
1) A historical background on LAP, formerly known as localized juvenile periodontitis, describing its identification and classification over time.
2) Key diagnostic criteria for LAP including an early age of onset typically around puberty, involvement of first molars and incisors, and a rapid rate of attachment loss and bone destruction.
3) Typical clinical characteristics of LAP such as minimal visible inflammation despite deep pockets and bone loss out of proportion to plaque levels. Radiographs often show vertical bone loss around first molars and incisors. Prevalence is typically below 1% with some studies finding higher rates in black males
Dental extractions in irradiated patientsUjwal Gautam
Dental extractions in patients undergoing radiotherapy carry risks of osteoradionecrosis and impaired wound healing due to radiation damage to vasculature, bone marrow, and fibroblasts. Extraction after radiotherapy requires preventive measures like antibiotics and atraumatic technique. Hyperbaric oxygen therapy has been used preventively for extractions, though its effectiveness is less than 100%. Where possible, extractions in irradiated patients should be avoided or meticulous preventive measures undertaken due to osteoradionecrosis risk.
Periodontal diseases Classifications and treatmentsRiad Mahmud
Prof. Dr. Md. Zahid Hossain, Division of Periodontology, Department of Preventive Dental Sciences, College of Dentistry, Najran University, Saudi Arabia.Former Professor of Periodontology, City Dental College, Dhaka
Osteoradionecrosis is bone necrosis that occurs in the radiation treatment volume months after treatment. It is caused by loss of vasculature due to radiation damage. Risk factors include radiation dose over 6500 cGy, chemotherapy, brachytherapy, and post-radiation dental extractions. Advanced cases can lead to fistulas, fractures, and discontinuity defects impacting functions like speech and swallowing.
2007 daher tratamiento no quirurgico en un adulto con clase iiimarangelroque
This case report describes the nonsurgical treatment of a 43-year-old man with a Class III malocclusion and crossbite. Treatment options included orthognathic surgery, nonextraction treatment, premolar extractions, and mandibular incisor extraction. The patient opted for nonsurgical treatment, which included maxillary expansion and extraction of a mandibular central incisor. Over 2 years of treatment with braces and a facemask, the crossbite was corrected and a good occlusion was achieved without the need for surgery.
Its very important for dentists to differentiate aggressive periodontitis and chronic periodontitis. This presentation includes basics of Aggressive periodontitis which can be very useful for undergraduate students of dental school for reference.
Infezione, vascolarizzazione, rimodellamento – le cellule staminali sono la r...Merqurio
1. Osteonecrosis of the jaw (ONJ) can result from craniofacial radiation, osteomyelitis, or bisphosphonate use, and the underlying pathophysiology of each condition is still unclear.
2. While infection, reduced blood flow, and impaired bone remodeling have all been proposed as causes, stem cell therapy may offer a promising new treatment by modulating the immune system and promoting bone and blood vessel growth.
3. Mesenchymal stem cells in particular have shown ability to both prevent and cure bisphosphonate-related ONJ in mouse models, indicating stem cells warrant further study as a potential solution for these challenging bone diseases of the jaw.
Localized aggressive periodontitis patients were treated with nonsurgical debridement and a 7-day course of amoxicillin and metronidazole. Over 4 years of follow-up, clinical parameters like probing depth and clinical attachment level were reduced by over 50% at most time points. Compliance with treatment and follow-up appointments was important for outcomes. Retrospective analysis found bone loss in primary dentition, suggesting early disease onset. The treatment was effective long-term but comparison to other approaches was lacking.
This document summarizes the effects of radiation therapy on oral tissues. Radiation is commonly used to treat oral cancers. It is delivered in small daily doses over 6-7 weeks for a total of 60-70 Gy. This causes damage to oral mucosa, taste buds, salivary glands, teeth, bone, and muscles. Oral mucositis is a common side effect, along with loss of taste, xerostomia, and rampant dental caries due to changes in saliva. Teeth may have arrested development. Long term risks include osteoradionecrosis and trismus. Management involves oral hygiene, pain control, fluoride application, and sometimes surgery.
This case report describes the endo-surgical management of a large radicular cyst in the maxillary anterior region that had completely resorbed the maxillary nasal floor. After non-surgical root canal treatment of teeth 11 and 12, surgical enucleation of the cyst was performed, followed by apicoectomy and retrograde filling of the root canals with mineral trioxide aggregate. The cyst had extended supero-posteriorly into the maxilla and nasal cavity. Complete removal of the cyst was achieved while preserving surrounding structures. Post-operative healing was uneventful. This case demonstrates the effective treatment of a large cyst using a combined nonsurgical endodontic and surgical approach.
AGGRESSIVE PERIODONTITIS
PRESENTER
DR. REBICCA RANJIT
DEPT. OF PERIODONTOLOGY & ORAL IMPLANTOLOGY
Why is there localisation of disease to 1st molars and incisors in LAP?
Often subjects present with attachment loss that does not fit the specific diagnostic criteria (AP or chronic periodontitis).
Schenkein et al. 1995: cigarette smoking was shown to be a risk factor for patients with generalized forms of AgP.
Smokers with GAP had more affected teeth and greater mean levels of attachment loss than patients with GAP who did not smoke.
IgG2 serum levels as well as antibody levels against A.a. are significantly depressed in subjects with GAP who smoked.
This document discusses osteoradionecrosis of the jaws, which is bone necrosis caused by radiation therapy for head and neck cancer. It defines osteoradionecrosis and describes its classification, types, risk factors, and theories of pathophysiology. The document outlines protocols for preventing and treating osteoradionecrosis, including conservative management, hyperbaric oxygen therapy, pentoxifyllin and tocopherol supplements, and surgical interventions. Hyperbaric oxygen therapy is described as an adjuvant treatment involving intermittent high-pressure oxygen sessions to promote revascularization and healing.
Abstract—This study was aimed to present a case report of a case of peripheral ossifying fibroma which is a rare case. This case was a 30 years non smoker male with the chief complaint of growth of gum tissue, moderately large in the mandibular posterior region. On intraoral examination, a peduncalated growth of 17 x 12 x 6 mm on marginal and attached gingiva with respect to tooth number 47 considerably hard in consistency and movable was seen. The lesion was erythmatous having a smooth non ulcerated surface. It was asymptomatic with no sign of pain. Intra oral periapical radiograph was taken which revealed slight erosion of crest of bone which was later confirmed during surgical excision. The possible reason of crestal bone erosion may be constant pressure of the growth. Differential diagnosis of irritation fibroma, pyogenic granuloma and peripheral giant cell granuloma was considered. However, clinical appearance and consistency was of a hard fibrous growth, which therefore led to a provisional diagnosis of peripheral ossifying fibroma or peripheral odontogenic fibroma.
This document discusses trauma from occlusion (TFO), defined as pathological alterations or adaptive changes that develop in the periodontium due to excessive occlusal forces. It provides historical context on TFO research dating back to 1901, classifications of TFO, stages of tissue response to TFO including injury and repair, and factors that can increase occlusal forces or decrease the periodontium's resistance to forces. TFO can be acute or chronic and primary (due to occlusal factors) or secondary (due to reduced periodontal support). Excessive forces can cause tissue injury through thrombosis, hemorrhage or necrosis while the body attempts repair through new tissue formation and bone remodeling.
Medication-Related Osteonecrosis of the jaws (MRONJ).pptxHadi Munib
The document provides information on Medication-Related Osteonecrosis of the Jaws (MRONJ). It discusses the AAOMFS definition, predisposing factors like dentoalveolar surgery, staging of MRONJ from 0-3, bisphosphonate medications and recommendations for patients receiving or about to start these medications. It also covers osteomyelitis including classification, pathogenesis, clinical presentation, investigations and surgical management. Overall, the document is an overview of MRONJ and osteomyelitis of the jaws for oral and maxillofacial surgery residents.
ADA - Updated recommendations for managing the care of patients receiving ora...clmaxidex
The document summarizes recommendations from an expert panel on managing dental care for patients taking oral bisphosphonate drugs. The panel concludes that the risk of developing bisphosphonate-associated osteonecrosis of the jaw (BON) from oral bisphosphonates is very low compared to intravenous bisphosphonates. Routine dental treatment and procedures can generally be performed as normal with some conservative approaches recommended. Patients should be informed of the very low risk and importance of oral health and regular dental care.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
Bisphosphonates are pyrophosphate analogues that are resistant to enzymatic destruction and bind strongly to bone. They are used to treat osteoporosis, Paget's disease, and bone metastases. Newer generations of bisphosphonates are more potent and selectively inhibit bone resorption over formation. They work by inhibiting enzymes in the HMG-CoA reductase pathway, preventing osteoclast function. Clinical trials demonstrate bisphosphonates' ability to increase bone mineral density and reduce fracture risk. While generally well-tolerated, they can cause jaw necrosis or atypical femoral fractures with prolonged use.
This document discusses aggressive periodontitis, including its definition, classification, clinical characteristics, diagnostic criteria, and treatment modalities. Aggressive periodontitis is defined as a rare, severe form of periodontitis characterized by early onset and familial aggregation. It can be localized or generalized. Treatment involves nonsurgical and surgical therapies like scaling and root planing as well as adjunctive systemic or local antibiotics. Maintaining frequent periodontal maintenance visits is important for long-term disease control.
The primary search resulted in 17 articles but only 6 studies met the inclusion criteria, including 2 animal studies and 4 human trials. The studies showed that metformin administered intraperitoneally or intramuscularly in animal models reduced bone loss and increased bone formation. In human studies, the use of 1% metformin gel as an adjunct to scaling and root planning or open-flap debridement resulted in better clinical and radiographic outcomes compared to those treatments alone. A meta-analysis of the 6 studies found that the combination of metformin and periodontal therapy led to greater reductions in intrabony defect depth and increases in intrabony defect fill compared to periodontal therapy alone.
Dental clearance of cancer patients - A preventive step in oncology therapy.RavinaBarrett
This document discusses the importance of dental clearance for cancer patients prior to starting cancer therapy. Certain medications used in cancer treatment like bisphosphonates and monoclonal antibodies have been linked to osteonecrosis of the jaw (ONJ). Dental clearance, which involves treating any existing dental issues, can help prevent ONJ and other dental complications that can negatively impact a cancer patient's quality of life. The document emphasizes that all cancer patients should receive dental clearance before starting treatment given the risks to oral health posed by various cancer therapies and medications.
- The document summarizes the influence of various drugs on orthodontic tooth movement. It discusses how analgesics, bisphosphonates, fluorides, corticosteroids, thyroid hormones, sex hormones, parathyroid hormone, anti-convulsants, alcohol, and prostaglandins can impact the rate and stability of tooth movement during orthodontic treatment.
- Many drugs like NSAIDs, bisphosphonates, fluorides can slow down the rate of tooth movement by inhibiting osteoclast activity and bone resorption. Corticosteroids and thyroid hormones can increase the rate but decrease the stability of tooth movement.
- The document provides details on the mechanisms of action of these drugs and recommends
1. Dental implant risk assessment involves evaluating local, systemic, and behavioral factors that may increase the risk of implant failure.
2. A comprehensive risk assessment includes taking a thorough medical and dental history, and performing a complete intraoral examination to identify any variables that could complicate implant treatment or survival.
3. The goal of risk assessment is to avoid high failure rates by determining suitable implant candidates, identifying issues that may impact osseointegration or long-term maintenance, and minimizing future problems.
1) The document discusses how various drugs can influence orthodontic tooth movement, including analgesics like NSAIDs, acetaminophen, bisphosphonates, fluorides, corticosteroids, and vitamin D.
2) NSAIDs and bisphosphonates can reduce the pace of tooth movement by inhibiting prostaglandin synthesis and osteoclast activity. Acetaminophen does not significantly affect tooth movement.
3) Vitamin D, corticosteroids, and fluorides can impact bone metabolism and influence the rate and stability of tooth movement to varying degrees. Corticosteroids in particular may increase short-term movement but decrease long-term stability.
Multidisciplinary approach in the rehabilitation of congenitally missing late...Abu-Hussein Muhamad
Agenesis, the absence of permanent teeth, is a common occurrence among dental patients. The total incidence of tooth agenesis is about 4.2% among patients that are seeking orthodontic treatment and with the exception of third molars, the maxillary lateral incisors are the most common congenitally missing teeth with about a 2% incidence. The maxillary lateral incisor is the second most common congenitally absent tooth. There are several treatment options for replacing the missing maxillary lateral incisor, including canine substitution, tooth-supported restoration, or single-tooth implant. Dental implants are an appropriate treatment option for replacing missing maxillary lateral incisor teeth in adolescents when their dental and skeletal development is complete. This case report presents the treatment of a patient with congenitally missing maxillary lateral incisor using dental implants. The paper discusses the aspects of pre-prosthetic orthodontic diagnosis and the treatment that needs to be considered with conservative and fixed prosthetic replacement.
In pharmacology,bisphosphonates (also called:diphosphonates) are a class of drugs that inhibit osteoclast action and the resorption of bone.
Its uses include the prevention and treatment of osteoporosis, osteitis deformans ("Paget's disease of bone"), bone metastasis (with or without hypercalcaemia), multiple myeloma and other conditions that feature bone fragility.
Austin Pediatric Oncology is an open access, peer reviewed, scholarly journal dedicated to publish articles covering all areas of pediatric oncology.
The journal aims to promote research communications and provide a forum for doctors, researchers, physicians and healthcare professionals to find most recent advances in all areas of pediatric oncology. Austin Pediatric Oncology accepts original research articles, reviews, mini reviews, case reports and rapid communication covering all aspects of pediatric oncology.
Austin Pediatric Oncology strongly supports the scientific up gradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Periodontio-integrated implants: A revolutionary conceptMinkle Gulati
Though the fields of regenerative dentistry and tissue engineering have undergone significant
advancements, yet its application to the field of implant-dentistry is lacking; in the sense that
presently the implants are being placed with the aim of attaining osseointegration without giving consideration to the regeneration of periodontium around the implant. The following article reveals the clinical benefits of such periodontio-integrated implants and reviews the relevant
scientific proofs. A comprehensive research to provide scientific evidence supporting the feasibility of periodontio-integrated implants was carried out using various online resources such as PubMed, Wiley-Blackwell, Elsevier etc., to retrieve studies published between 1980 and 2012 using the following key words: “implant,” “tissue engineering,” “periodontium,” “osseo-integration,” “osseoperception,” “regeneration” (and their synonyms) and it was found that in the past three
decades, several successful experiments have been conducted to devise “implant supported by the periodontium” that can maintain form, function and potential proprioceptive responses similar to a natural tooth. Based on these staunch evidences, the possibility of the future clinical use of such implant can be strongly stated which would revolutionize the implant dentistry and will be favored by the patients as well. However, further studies are required to validate the same.
A D I S D R U G E V A L U A T I O NDenosumab A Review of .docxransayo
A D I S D R U G E V A L U A T I O N
Denosumab: A Review of its Use in Postmenopausal Women
with Osteoporosis
Lesley J. Scott
Published online: 17 June 2014
� Springer International Publishing Switzerland 2014
Abstract Subcutaneous denosumab (Prolia� [USA,
Europe]; Pralia
�
[Japan]) once every 6 months is indi-
cated in several countries for the treatment of postmen-
opausal women with osteoporosis at increased or high
risk for fractures (featured indication). In some countries,
it is also indicated for use in postmenopausal women who
have failed or are intolerant to other osteoporosis treat-
ments. In several international, phase III trials (B3 years’
duration) involving more than 12,000 women with post-
menopausal osteoporosis or low bone mineral density
(BMD), including Asian studies, denosumab was an
effective and generally well tolerated treatment. Relative
to placebo, denosumab treatment significantly reduced the
risk of vertebral, nonvertebral and hip fractures and
increased BMD at all skeletal sites evaluated, including
the lumbar spine and total hip. Furthermore, the benefits
of denosumab treatment were generally evident after the
first dose and were maintained during up to 8 years of
treatment in an ongoing extension study. The tolerability
profile of denosumab during this extension phase was
consistent with that observed during the initial 3-year
FREEDOM trial. At 12 months, denosumab treatment
increased BMD at the total hip, lumbar spine and/or
femoral neck and reduced markers of bone turnover to a
significantly greater extent than oral bisphosphonates in
women who were essentially bisphosphonate-naive and in
those who had switched from alendronate to denosumab
treatment. Further clinical experience, including an
ongoing postmarketing safety study, will more fully
define the long-term safety of denosumab. In the mean-
time, denosumab is an important option for the treatment
of women with postmenopausal osteoporosis at increased
or high-risk of fractures, including in women at increased
risk of fracture who are unable to take other osteoporosis
treatments.
Denosumab in postmenopausal women with osteo-
porosis: a summary
Human monoclonal antibody targeting RANKL, a
key mediator of bone resorption
Relative to placebo, denosumab reduces the
incidence of vertebral, nonvertebral and hip fractures
Reduces bone resorption, increases bone mineral
content, bone mass and bone strength
Increases BMD to a significantly greater extent than
oral alendronate, ibandronate or risedronate
Generally well tolerated (B8 years treatment), with
most adverse events of mild to moderate severity;
long-term safety studies are ongoing
The manuscript was reviewed by: J-P. Devogelaer, Universite
Catholique de Lovain, Service de Rheumatologie, Cliniques
Universitaires Saint-Luc, Brussels, Belgium; M. Kleerekoper,
University of Toledo Medical School, Department of Internal
Medicine, Endocrinology Division, Ru.
The document discusses laparoscopy procedures for various gynecological conditions such as infertility, chronic pelvic pain, ectopic pregnancy, and oncological issues. It notes that laparoscopy can be used for both diagnostic and operative purposes. It then discusses different techniques for laparoscopic access such as direct trocar insertion versus Verres needle insertion. It reviews studies comparing complication rates between different access techniques. The document emphasizes the importance of evidence-based medicine and following guidelines from organizations like NICE when determining appropriate diagnostic tests and treatments for conditions like infertility.
The document discusses laparoscopy procedures for various gynecological conditions. It begins by outlining conditions that can be diagnosed or treated via laparoscopy, including infertility, ectopic pregnancy, adhesions, endometriosis, ovarian masses, hysterectomy, uterine fibroids, and gynecological oncology issues. It then discusses different laparoscopy access techniques such as direct trocar insertion, open laparoscopy, and Verres needle insertion. It provides data on complication rates for different access methods. The document also discusses techniques for avoiding major vascular injuries during access. In summary, the document provides an overview of laparoscopy procedures and techniques for gynecological conditions.
Nuovo metodo ad ultrasuoni per il trattamento dei calcoli renaliMerqurio
This document describes a novel method using focused ultrasound to reposition kidney stones. Researchers created a kidney phantom with an artificial collecting system and lower pole. Both artificial and human kidney stones were placed in the lower pole. An ultrasound imaging probe was used to locate the stones, while a separate focused ultrasound probe could deliver bursts of ultrasound to move the stones. In experiments, stones were successfully repositioned from the lower pole to the collecting system in seconds, moving at about 1 cm/s. This noninvasive method shows promise for aiding stone clearance after surgery or during medical expulsive therapy.
Litotrissia percutanea laparoscopica nel rene pelvico casi cliniciMerqurio
This document describes a novel technique of laparoscopically assisted percutaneous pyelolithotomy for treating kidney stones in pelvic kidneys. The technique was used in 3 patients with large pelvic kidney stones who were not suitable candidates for standard percutaneous or laparoscopic approaches. The procedure involves using laparoscopy to expose the renal pelvis, then inserting a needle percutaneously into the pelvis under direct visualization. The tract is dilated and a nephroscope is used to remove stones without needing to incise or suture the pelvis. This approach provides direct access to the pelvis without risks of standard percutaneous or laparoscopic techniques. All 3 patients were successfully treated with no complications and no
Chirurgia di preservazione dell'udito. lento progresso e nuove strategieMerqurio
This study evaluated hearing outcomes for 115 patients who underwent hearing preservation surgery for acoustic neuromas. The goal was to determine the tumor size and level of pre-operative hearing that resulted in high rates of preserved hearing. Two groups of patients were evaluated based on tumor size - those with tumors ≤ 10mm and those >10mm. Patients with tumors ≤ 10mm and good pre-operative hearing (≤20dB PTA, ≥80% SDS) had a 76% success rate of preserved hearing. Patients with smaller tumors but poorer pre-operative hearing had lower success rates. The authors concluded that hearing preservation surgery is most effective for acoustic neuromas ≤10mm with good pre-operative hearing and can be an optimal treatment
Il trattamento chirurgico dei tumori del labbroMerqurio
This document summarizes a study on the surgical management of lip cancer. The study examined 32 patients treated for lip cancer over 5 years. Most cases involved squamous cell carcinoma of the lower lip. Surgical excision of the tumor was performed with oncologically appropriate margins. Reconstruction after surgery posed challenges, especially for advanced or extensive lesions. Local flaps from the lip or surrounding tissues were often used for reconstruction. Neck dissection was also performed in some cases to control lymph node metastases. While early stage tumors had good postoperative outcomes, advanced lesions resulted in greater functional impairments like drooling or chewing difficulties after surgery. The document discusses the surgical and reconstructive techniques used to treat lip cancers while aiming to preserve lip appearance and
Il trattamento chirurgico dei tumori del labbroMerqurio
The document summarizes the surgical management of lip cancer. It discusses that lip cancer is most commonly squamous cell carcinoma, usually originating in the lower lip. The management of lip cancer involves controlling the primary tumor with appropriate margins while allowing for oral competence, as well as potential neck metastases. Reconstruction is challenging, especially for advanced lesions, requiring preoperative planning and various surgical techniques. Early stage tumors have better prognostic and functional outcomes after surgery compared to advanced lesions. The authors report their experience treating lip tumors and managing neck metastases.
Effetti degli integratori di calcio sul rischio di infarto del miocardio e di...Merqurio
This meta-analysis investigated whether calcium supplements increase the risk of cardiovascular events. It analyzed 15 eligible randomized controlled trials involving over 11,000 participants who took calcium supplements for an average of 4 years. The analysis found a small increased risk of myocardial infarction among those taking calcium supplements compared to placebo, with 143 people experiencing a heart attack in the calcium group versus 111 in the placebo group. There was also a non-significant trend towards increased risks of stroke and cardiovascular death. These modest increases in risk could translate to a significant burden of disease at the population level given widespread calcium supplement use. The results suggest a reassessment of calcium supplements for osteoporosis is warranted.
Il trattamento chirurgico dei tumori del labbroMerqurio
This document summarizes a study on the surgical management of lip cancer. The most common type of lip cancer is squamous cell carcinoma, usually occurring on the lower lip. Treatment involves complete excision of the primary tumor with oncologically appropriate margins while preserving lip structure and function during reconstruction. For early-stage tumors, surgery results in good aesthetic and functional outcomes. More advanced tumors require complex reconstruction techniques using local or regional flaps to restore lip shape, texture, and mobility. Management of possible neck metastases is also important, as lymph node involvement significantly reduces survival rates. The authors report their experience treating 32 cases of lip cancer with surgical excision and various reconstructive procedures.
La sindrome rino bronchiale. indagine conoscitiva sio-aimar.Merqurio
This study aimed to standardize the diagnosis and treatment of rhino-bronchial syndrome (RBS), which links inflammation of the upper and lower airways. 159 patients meeting criteria for RBS underwent a two-level diagnostic protocol including endoscopy and spirometry. RBS was confirmed in 116 patients who had higher rates of allergic and infectious diseases than unconfirmed cases. Common symptoms were nasal obstruction, rhinorrhea, cough, and dyspnea. After 3 months of treatment including steroids, antibiotics, and nasal lavage, 96% of patients recovered. The study proposes a diagnostic workflow and highlights the importance of correct diagnosis through multidisciplinary evaluation for effective treatment of RBS.
La sindrome rino bronchiale. indagine conoscitiva sio-aimar.Merqurio
This document describes a survey conducted by the Italian Society of Otorhinolaryngology and the Interdisciplinary Scientific Association for the Study of Respiratory Diseases to better understand the epidemiology, diagnosis, and treatment of rhino-bronchial syndrome. 159 patients from 9 ENT and pulmonology centers were enrolled based on clinical history and symptoms. 116 patients received a confirmed diagnosis based on examinations of the upper and lower airways. Allergic and infectious diseases were more common in patients with a confirmed diagnosis. After 3 months of standard treatment, 96% of patients recovered. The study proposes a diagnostic workflow and emphasizes the importance of correct diagnosis through multidisciplinary evaluation and treatment.
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Strategies for Effective Upskilling is a presentation by Chinwendu Peace in a Your Skill Boost Masterclass organisation by the Excellence Foundation for South Sudan on 08th and 09th June 2024 from 1 PM to 3 PM on each day.
How to Manage Your Lost Opportunities in Odoo 17 CRMCeline George
Odoo 17 CRM allows us to track why we lose sales opportunities with "Lost Reasons." This helps analyze our sales process and identify areas for improvement. Here's how to configure lost reasons in Odoo 17 CRM
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
How to Add Chatter in the odoo 17 ERP ModuleCeline George
In Odoo, the chatter is like a chat tool that helps you work together on records. You can leave notes and track things, making it easier to talk with your team and partners. Inside chatter, all communication history, activity, and changes will be displayed.
How to Build a Module in Odoo 17 Using the Scaffold MethodCeline George
Odoo provides an option for creating a module by using a single line command. By using this command the user can make a whole structure of a module. It is very easy for a beginner to make a module. There is no need to make each file manually. This slide will show how to create a module using the scaffold method.
2. Borromeo et al. BMC Musculoskeletal Disorders 2011, 12:71 Page 2 of 10
http://www.biomedcentral.com/1471-2474/12/71
highlighted the possible association between bispho- Although ONJ associated with bisphosphonate use
sphonate use, especially intravenous (IV) zoledronate or appears to resemble osteoradionecrosis seen following
pamidronate, and jaw osteonecrosis [15-21]. Other stu- jaw radiotherapy, they are now considered different dis-
dies have not found any association between bishospho- ease entities [33]. Conventional therapy of this latter
nate use and ONJ [6]. A study assessing once yearly complication involves local debridement, irrigation and
zoledronate for osteoporosis management in 8000 indi- antibiotics [34]. However, this strategy has yielded
viduals reported, following separate case adjudication, a mixed results in bisphosphonate-associated osteonecro-
single episode of ONJ in each of the placebo and zole- sis, and may contribute to further tissue breakdown,
dronic acid groups [6]. The length of this study was resulting in large fistulas [35].
only three years whereas most ONJ has been reported While jaw osteonecrosis is a devastating end-stage out-
in patients taking bisphosphonates for longer periods of come that is currently difficult to manage, various forms
time. In a recent survey of over 8000 respondents, ONJ of delayed dental healing may be a less clinically dramatic
had a prevalence of 0.10% (95% confidence interval and, therefore, poorly-recognised complications of
0.05% to 2.0%) [22]. Previously, similar but less frequent bisphosphonate use. Currently, the likelihood of dental
presentations with jaw osteonecrosis occurred following complications during bisphosphonate therapy for treat-
radiotherapy (Ruggerio et al., 2004) or occupational ment of post-menopausal osteoporosis or other benign
exposure to phosphorus [23]. In many of the reports, bone disease is uncertain. It is unclear what factors pre-
jaw osteonecrosis occurred in the setting of malignancy, dispose patients to these events [36,37]. Given the large
in particular, multiple myeloma [24-26] or breast cancer numbers of patients receiving long-term bisphosphonate
[18,19,26]. Recent work has suggested that in myeloma therapy, particularly in benign bone disease, that a high
patients, zoledronate and pamidronate are associated level of professional and public concern has arisen about
with a 10% and 3% incidence of jaw osteonecrosis at the issue, and the fact that we are living in an ageing
36 months, respectively [25]. In contrast, the prevalence population making the likelihood of levels of osteoporosis
of jaw osteonecrosis with bisphosphonate treatment in a increasing, understanding the prevalence and risk of
large retrospective case series was 2.4% among myeloma bisphosphonates and jaw osteonecrosis is paramount.
patients and 1.2% among breast cancer patients [26].
There is some published evidence that chronic low- Hypothesis
dose bisphosphonate treatment for osteoporosis or other The hypothesis to be tested is that long-term (more
benign bone disease is associated with jaw osteonecrosis than 1 year’s duration) bisphosphonate use for the treat-
[18,27]. However, randomised controlled trials of ment of post-menopausal osteoporosis or other benign
bisphosphonates in osteoporosis have not demonstrated bone disease is associated with impaired dental healing.
an increased risk of jaw osteonecrosis. The development
of ONJ has been linked to duration of exposure to Methods
bisphosphonates, and hence a higher cumulative dose, Study design
longer duration of treatment, hence prolonged survival, A case-control study has been chosen to test the
as well as potential co-morbidities such as prednisolone hypothesis as the outcome event rate is likely to be very
or thalidomide use [26]. Poor periodontal status low (Figure 1).
together with dental interventions, in particular extrac-
tions, implants or trauma from dentures for example, Definitions
significantly increase the risk of developing ONJ in this Delayed dental healing
patient cohort [17,19,20,26,28]. Delayed dental healing (a precursor to osteonecrosis of
The exact mechanism by which bisphosphonates may the jaw) is defined as a persistent breach in the oral
contribute to impaired resistance to injury or impaired mucosa and/or exposure of bone in the mandible or
healing of the maxilla or mandible and to osteolytic maxilla that:
destruction, remains unclear. However, suppression of • fails to heal within 6 weeks as documented by a den-
bone turnover via actions on osteoclasts seems to play a tist despite usual therapy;
substantial role [29,30]. Bisphosphonates are not the • occurs either following a dental procedure, for
only medications with this action. Other drugs such as example a tooth extraction or crown insertion, or spon-
denosumab (a RANKL antibody which is indicated in taneously, with or without osteonecrosis.
cancer patients) and bevacizumab (a human monoclonal Osteonecrosis of the jaw
antibody to vascular endothelial growth factor) have the • Exposed bone in the maxillofacial area that occurred
potential to alter osteoclast differentiation and function in association with dental surgery or spontaneously with
and as such has also been implicated in ONJ [31,32]. no evidence of healing
3. Borromeo et al. BMC Musculoskeletal Disorders 2011, 12:71 Page 3 of 10
http://www.biomedcentral.com/1471-2474/12/71
Outcome
CASES CONTROLS
(disease = impaired (no disease = normal
dental healing) dental healing)
Exposure of interest Exposed to oral
bisphosphonate ?? ??
therapy
not exposed to oral
bisphosphonate ?? ??
therapy
XX YY
Figure 1 Case-controlled study design.
• No evidence of healing after 6 weeks of appropriate Dental Specialist Recruitment
evaluation and dental care Specialist dental recruitment will involve contacting
• No evidence of the following bone pathology that all registered oral and maxillofacial surgeons and
might explain the findings: metastatic disease in the jaw special needs dentists who were actively practicing dur-
or osteoradionecrosis. ing March 2006 through to the end of August 2006.
All registered specialists listed in the Yellow Pages
Setting and study time frames telephone directory will be cross-matched with those
The study will take place in Victoria, the second most currently registered with the Australian Health Prac-
populous State in Australia with a population of titioner Regulation Agency. The researchers will
approximately 5 million people. The visit window period also present the study to a Victorian Branch meeting of
study period will be March 1st 2006 until August 31st the Australian and New Zealand Association of Oral
2006. Participants in the study will have been treated in and Maxillofacial Surgeons. All public hospital dental
specialist oral and maxillofacial and special needs dentis- specialty clinics in Victoria and associated specialist
try settings during the visit window period. Control sub- dental practitioners will be identified. All registered
jects will have attended local community based referring specialist dental practitioners will be invited to partici-
dental practices. A flow diagram of the study protocol is pate in the case-controlled study via introductory
depicted in Figure 2. mail out.
4. Borromeo et al. BMC Musculoskeletal Disorders 2011, 12:71 Page 4 of 10
http://www.biomedcentral.com/1471-2474/12/71
All OMFS in All SND Specialists in
Victoria Victoria
Decline Agree to Agree to Decline
participation participation participation participation
Screening of files meeting age and
visit window criteria
Identified potential cases to
present to CAP
no further No not a Yes a potential
data case case
collection
invitation to
participate
Agree to participate Decline to participate
(participating case) (non-participating case)
telephone interview and no telephone
medical information interview
review
Match for controls Match for controls
from practice where from practice where
case was referred case was referred
(1:4 case:controls) (1:4 case:controls)
Figure 2 Flow diagram of study protocol.
Follow up of specialist non-respondents would occur by visit window period will be screened and only those meet-
mail at 2-weeks and telephone at 4-weeks. Once specialists ing the age and visit window criteria will be reviewed for
agree to participate, then the respective practice will be further potential case information. Once potential cases
contacted to determine a suitable time to view patient files are determined then they will be presented to the Case
and identify potential cases. All files within the 6-month Adjudication Panel (CAP) (see further details below).
5. Borromeo et al. BMC Musculoskeletal Disorders 2011, 12:71 Page 5 of 10
http://www.biomedcentral.com/1471-2474/12/71
Case Recruitment Once verified as a definite case by the CAP, the indivi-
Recruitment of individuals for the study is a two-step dual will be contacted via mail to seek informed written
process, ascertainment of potential cases through dental consent for participation in the study. Non-responders
record review then verification by a case adjudication will consist of two main groups; individuals who do not
panel (CAP). The research team would visit each partici- wish to participate and those who cannot be contacted
pating practice to identify potential cases from the den- (e.g. changed address or deceased).
tal records, which could then in turn be presented to
the case adjudication panel. Each specialist practitioner Recruitment of Control Subjects
would be required to give consent to have patients in Each case will be matched with four controls randomly
their practice contacted by the research team. selected from those who have undergone dental treat-
Participant ascertainment will occur through consecu- ment at the same dental practice from which the case
tive screening of oral and maxillofacial and special originated. If access cannot be obtained to records
needs dental specialist records in private practices and from the originating dental practice, then a similar
public hospitals by trained research staff. Once a case type of practice e.g. private practice or hospital - based
has been confirmed by CAP, each specialist practitioner practice, within a 10 km radius will be approached to
would be required to give consent to have patients in provide control subjects. They will be matched for age
their practice contacted by the research team. (>50 years), gender and visit window period and will
To be eligible for participation, the dental record have no known defect in dental wound healing. If con-
should indicate that the potential participant is: trols cannot be matched to the 6-month visit window
• age ≥ 50 years period then they will be matched to within 12 months
• has a dental wound that failed to heal within 6 weeks of the visit window period. Controls will be contacted
• had a qualifying visit during the window period. by mail as for cases to obtain informed consent to
The exclusion criteria are: study participation.
• A history of active malignancy or malignancy within
five years (excluding basal or squamous cell carcinoma). Data Collection Methods
• Previous radiotherapy field that included the jaws. Data collection will involve collecting information per-
• Bisphosphonate use for any indication other than taining to demographics, delayed dental healing, bispho-
post-menopausal osteoporosis or other benign bone sphonate history and medical history. Data collection
disease. forms and telephone interviews for controls will be the
In order for potential cases to be identified from the same as that used for cases.
patient files, the research team reviewing the clinical Part 1: Demographic information
notes need to be able to identify delayed dental healing. Specialist information, patient details (name, date of
It is expected that the term “delayed dental healing” as a birth, gender, address and telephone number), name of
potential descriptor is unlikely to appear in the clinical referring practitioner, referring practitioner contact
notes, as there would be variability in clinical descrip- details, date of presentation of oral problem and referral
tions amongst specialists. As such a number of file ter- to specialist date will be collected initially. A list of all
minology descriptors will be used to help identify dates within the visit window period together with an
potential cases of DDH and these are outlined within outline of each visit will be recorded. The demographic
‘data collection methods’ below. data will be coded for each individual and the code used
All records identified as potential cases of delayed in all subsequent data collection in order to de-identify
dental healing will be presented to the CAP for verifica- information as per ethical requirements.
tion for inclusion or exclusion. The CAP will include a Part two: Delayed dental healing information
Chair who will be an independent specialist endocrinol- Each patient file identified within the visit window per-
ogist, 2 other medical practitioners and three dentists iod will be analysed and information relating to the pre-
(one Oral Medicine Specialist, one oral and maxillofacial sence of an oral diagnosis (diagnosis, site, precipitant,
surgeon and one forensic dentist/bone biologist). treatment, outcome, biopsy report, radiographic investi-
A quorum of 4 (2 dental and 2 medical) will be required gation), bisphosphonate history and medical history (co-
at each CAP meeting. morbidities and medications) will be recorded.
At each CAP meeting all de-identified potential cases The diagnosis will consist of the presence of either
will be presented without the panel’s knowledge of oral ulceration (“break in mucosa but no bone visible”)
bisphosphonate history and medical status. The records or bone necrosis defined as “bone on view”. A number
presented will be assessed according to the previously of key words will be used when reviewing patient
stated inclusion and exclusion criteria. histories as a number of descriptors can be used to
6. Borromeo et al. BMC Musculoskeletal Disorders 2011, 12:71 Page 6 of 10
http://www.biomedcentral.com/1471-2474/12/71
describe delayed dental healing. These will include non- medical history check including bisphosphonate history,
healing socket, pus, exudate, swelling, draining sinus, medication profile and smoking history. The telephone
dry socket, bone sloughing, sore sockets, OAC, oroantral interview will last approximately 10 minutes. The tele-
communication, healing not completed, fistula, OAF, phone questionnaire will be modelled on the Adult Oral
oroantral fistula, exposed bone and infection. Health Survey [38] and include questions relating
Information regarding site of the lesion will be further to dental health and general information such as socio-
subdivided into single versus multiple sites, quadrant economic status and educational status. A medication
involved, palatal, lingual, buccal or labial orientation and check list will also be completed with each case regard-
tooth area (one to eight). The main precipitants listed less of the data collected in the original data collection
can include tooth extraction, implant insertion, removal form in order to cross match bisphosphonate history,
of pathological lesion, denture use, spontaneous, no other medical history which could contribute to
obvious precipitant or other. In each case the date of impaired wound healing and smoking history.
the precipitant will be recorded. If the precipitant is not
recorded in the history this will be marked as such on Ethics Approval
the data collection form. Human Research and Ethics Committee approvals have
Outcome of the delayed dental healing will be been obtained from: Melbourne Health (2005.242) (hos-
recorded by including treatment modalities such as anti- pital and private practice cases and controls), Austin
biotics, mouthwashes/irrigation, debridement or other, Heath (H2006/02599; H2010/03794), The Alfred (17/
date of the last review together with wound status 09), Barwon Heath (10/99), Dental Health Services Vic-
(healed completely, healed partially, no healing or not toria (197), Southern Health (09069A), St Vincent’s
recorded) and progress of the wound at the last visit Hospital (009/09) and Western Health (2005.242).
(worse, stable, improving or not recorded). Details
regarding any biopsy or radiographic analysis will also Statistical Analysis
recorded. Demographic and clinical characteristics of cases and
Part 3: Medical History controls will be presented to assess whether these vari-
Detailed information relating to potential cancer history ables are associated with delayed dental healing.
including type, date of diagnosis, remission status, radio- Power and sample size
therapy to the jaw and chemotherapy will be recorded The sample size estimate is based upon the assumption
as this is a key exclusion criterion. Other co-morbidities that the overall prevalence of bisphosphonate use in
will be recorded including lung disease, heart disease, post-menopausal women is around 10%. Based on Aus-
kidney disease, organ transplant, diabetes, rheumatoid tralian Pharmaceutical Benefits Scheme (PBS) and Aus-
arthritis or other connective tissue conditions together tralian Bureau of Statistics (ABS) data the upper limit
with smoking, tobacco and alcohol intake as these may estimate is 19% [39]. Assuming that approximately 50%
contribute to delayed dental healing. of these patients have used bisphosphonate for at least
Part 4: Medication history one year, then 10% prevalence of long-term use in this
A detailed description of oral glucocorticoids (start/stop population appears to be a reasonable estimate. It is
dates, current dose and cumulative dose), hormone hypothesised that the prevalence of bisphosphonate use
replacement therapy and other medications including among those with delayed dental healing may be greater
raloxifene, calcitriol, tibolone, teriparatide and strontium than 10%. A recent case series of patients with frank jaw
will be recorded. necrosis found that all were treated with bisphospho-
If a bisphosphonate has been prescribed, the type will nates [19]. We infer from this that the true proportion
be recorded including alendronate, risedronate, tiludro- of women with DDH taking bisphosphonates may be
nate, pamidronate, zoledronate or etidronate together greater than 30% - 50%. Given the expected low preva-
with indication for use (osteoporosis, Paget’s disease, lence of DDH, the study plans to recruit ‘controls’ and
glucorticoid-induced osteoporosis, metastatic disease, ‘cases’ in a ratio of 4:1. An observed prevalence of
hypercalcemia). Doses of all bisphosphonates including greater than or equal to 30% bisphosphonate use
start and stop dates and current doses will be recorded amongst women with DDH would correspond to an
to allow calculation of cumulative drug doses. odds ratio of around 3.85. Hence, for the purpose of
Telephone interview this study, the minimum detectable difference will corre-
A telephone interview will be conducted with all con- spond to an OR greater than or equal to 3.85. This
senting participants in order to confirm inclusion/exclu- value is based upon a conservative estimate of the effect
sion criteria (most of which may already be evident expected, rather than what is considered clinically
from the patient’s dental file) and to determine socio- important. The most relevant measure of clinical impor-
economic status, dental health information and a tance will be one derived from a cohort study, that
7. Borromeo et al. BMC Musculoskeletal Disorders 2011, 12:71 Page 7 of 10
http://www.biomedcentral.com/1471-2474/12/71
is where the effect of bisphosphonate use can be repre- including bone sequestration, intraoral and extraoral fis-
sented in terms of a relative and/or absolute risk of tula formation, secondary paraesthesia and pathological
delayed dental healing. Whilst ideal, this would require jaw fractures. The link between this and bisphosphonate
a very large sample and long-term follow-up. use is paramount as there are a number of studies
A total sample of around 269 subjects (54 cases and reporting the incidence of jaw osteonecrosis (a potential
215 controls) will provide 90% power to detect a true sequelae for delayed dental healing) to be as high as
OR of at least 3.85, given the expected prevalence of 0.09 - 0.34% in patients receiving oral and 6.7-9.1% in
10% bisphosphonate use amongst post-menopausal patients receiving intravenous bisphosphonates following
women in the community. dental procedures [40]. Furthermore, whilst the inci-
The relationship between bisphosphonate use and dence of ONJ in osteoporosis patients in relation to
delayed dental healing will be assessed using a multivari- bisphosphonate use has been reported to occur after
ate logistic model incorporating age, duration of expo- prolonged treatment (greater than 3 years), it has been
sure, relevant co morbidities, concurrent treatment, and reported following 6-month use [41]. On the other
other potential confounders as covariates. hand, other data suggest an extremely low prevalence/
The prevalence of DDH in the target population will incidence of ONJ in patients treated with bisphospho-
be estimated using data collected to determine case nates for osteoporosis and other metabolic bone dis-
numbers in both bisphosphonate-treated and non- orders. Although an association between ONJ and
bisphosphonate-treated patients. We will also record bisphosphonate use has been suggested by case series,
cases of DDH occurring in non-bisphosphonate-treated professional surveys and register data, there is a lack of
patients with a diagnosis of benign bone disease where controlled, population-based data. A key aim of the pre-
bisphosphonates may be indicated (i.e. osteoporosis, sent study is to obtain such controlled data. By record-
Paget’s disease of the bone). ing the prevalence of delayed dental healing and ONJ
that occur in the absence of bisphosphonate use we
Outcome measures hope to be able to estimate the true risk of these disor-
Primary outcome measures ders in association with bisphosphonate exposure.
The primary outcome will be the incidence of delayed A case-controlled study design has been selected over
dental healing that occurs either spontaneously or fol- a prospective cohort study. Whilst both are observa-
lowing dental treatment such as extractions, implant tional studies that could further knowledge of delayed
placement, or denture use. dental healing, ONJ and bisphosphonate use, the former
Potential covariates study design has a number of advantages. First, it will
Potential covariates include those data collected, which allow us to study an outcome with a potentially low
increase our knowledge of the potential to develop incidence, less than 1% in patients with osteoporosis or
DDH. These include co-morbidities (medication his- Paget’s disease [42]. Second, this approach will minimize
tory, smoking history, other medical conditions), oral the problem posed by a long latency between exposure
hygiene habits and demographics (socioeconomic to bisphosphonate therapy and the outcome of delayed
status, nationality). healing and subsequent ONJ, something which cannot
Bisphosphonate use is considered an explanatory vari- be accounted for easily in a prospective cohort study,
able, which is also our exposure of interest. except by extended follow-up. Third, we will be able to
study the effects of other potential risk factors for
Discussion delayed healing such as medical history including
The present study seeks to determine the level of bisphosphonate usage, smoking history, dental hygiene,
delayed dental healing that occurs either spontaneously dental trauma including tooth extractions and implant
or after dental procedures such as tooth extraction and placement, and denture usage on the outcome of inter-
how this relates to bisphosphonate usage. Delayed den- est, namely delayed dental healing. It is understood that
tal healing may be an earlier or less advanced lesion a prospective cohort study would provide the most reli-
compared to ONJ but with a similar pathogenesis. By able assessment of the incidence of delayed healing,
observing delayed dental healing as well as ONJ we may ONJ and bisphosphonates but to date such studies have
therefore more broadly describe bisphosphonate asso- not been conclusive [14].
ciated dental disorders and increase our power to find One of the major limitations of this case-controlled
an association between bisphosphonate use and asso- study design is that it is reliant on information as it is
ciated dental disorders. It is imperative to obtain a bet- recorded in the medical or dental history that may be
ter understanding of this condition and its potential incomplete and is subject to clinician bias and
links to bisphosphonate use as it is often refractory to researcher interpretation. This is compounded by the
treatment and can lead to significant morbidity fact that in 2006 there was considerable controversy
8. Borromeo et al. BMC Musculoskeletal Disorders 2011, 12:71 Page 8 of 10
http://www.biomedcentral.com/1471-2474/12/71
regarding the role played by bisphosphonates in ONJ healing from complications such as a dry socket.
and the definition of the condition. Furthermore, Furthermore, in 2008, a report from the task force of
resources required to access and collect data from thou- the American Society for Bone and Mineral Research
sands of medical and dental histories could result in a proposed that a “suspected” case of ONJ would be
prolonged study period. defined as “an area of exposed bone in the maxillofacial
The present study also relies on recruitment of specia- region that had been identified by a health care provider
lists to allow access to patient records followed by and have been present for less that 8 weeks” which was
recruitment of cases and controls. All oral and maxillo- supported by others [42,44]. By this time, soft tissue clo-
facial specialists and special needs dentists in the state sure and exposed bone would no longer be present.
of Victoria will be invited to participate in the study but ONJ would then be the definitive diagnosis if greater
it will be difficult to control for ascertainment bias. Are than 8 weeks had lapsed for healing to occur [42,45,46].
practitioners who see delayed dental healing and ONJ The current definition for bisphosphonate associated
more willing to allow review of their patient records? ONJ includes the following features:
Are those who have a greater interest in the role played 1. Current or previous treatment with a bisphosphonate
by bisphosphonates more likely to want to become 2. Exposed bone in the maxillofacial region that per-
involved? It is difficult to control for this even with the sisted for greater than 8 weeks and
use of random sampling because practitioners’ consent 3. No history of radiation therapy to the jaws [47].
is required to allow file review. To some degree the An attempt also has been made to define clinical
same can also be said for patients with delayed dental stages of ONJ [45,48] (AAOMS, 2007). Stage 1 involved
healing. The patient information and consent brochure the presence of exposed or necrotic bone that is asymp-
stipulates that this is an important study to further our tomatic with no evidence of infection. Stage 2 related to
understanding of the link between delayed dental heal- the presence of exposed necrotic bone and infection,
ing and bisphosphonate use. Whether an individual who erythema and the presence or absence of a purulent dis-
has taken a bisphosphonate may be more or less likely charge. Finally stage 3, the most severe form of ONJ,
to participate is difficult to determine. Another potential contained all the characteristics of stage 2 but in addi-
limitation of the study is recollection bias given that tion, the presence of features such as a pathological
some data will be collected via participant telephone fracture, draining sinus or communication either intra
interview. Furthermore, control subjects reading the oral or extraoral and osteolysis. Since then, Stage 0 has
patient information and consent brochure may feel that been included to encompass patients with signs of ONJ
the study does not really benefit them and hence may but no exposed bone [46].
be less likely to respond. The same can also be said for Potential covariates to be collected in this study are in
the general dental practitioners via whom the control line with those suggested as risk factors for ONJ and
subjects will be identified. If they have little experience include dental factors such as tooth extraction, implant
with patients taking bisphosphonates or delayed dental placement and denture use, treatment factors such as
healing, then they may have little motivation to allow a use of glucocortocoids and smoking status [26,29,49].
third party to access their patient records. A critical component to the success or failure of any
A key feature of the present study relates to the defi- case-controlled study is recruitment of participants. The
nition of DDH and ONJ. In 2005 the definition of osteo- study was designed as a two-step recruitment process
necrosis of the jaw was unclear and constantly changing requiring not only patient participation but also clinician
in the literature and as such it was difficult to adhere to participation otherwise access to patient data and poten-
a single definition. The main disparity at the time was tial cases would have not been possible without employ-
related to the length of time a wound took to heal ing more complex recruitment protocols. It is also
before it fell into the category of osteonecrosis of the imperative we seek the assistance of specialist practi-
jaw. Initial healing, that is re-epithelialisation, of dental tioners in order to gain permission to screen consecutive
wounds such as those from dental extractions usually patient records during the defined study time period in
takes between 1 and 2 weeks [43]. Once the clot forms, order to avoid selection bias associated with specialist
fibrin and connective tissue begins to develop before the recall of individual patient cases. Hence there are two
wound (in this case a dental socket) is closed over by potential problems with recruitment. The first lies with
epithelium. It then takes some weeks for the underlying recruiting specialists. A number of key features have been
socket to fill with bone and healing to be complete. identified to be essential to increase response rates in
Hence up to 6 weeks for healing of a dental wound postal questionnaires [50]. A number of these features
would be reasonable taking into account potential are also pertinent in the following study. Firstly, Edwards
effects of delayed healing from medical co-morbidities et al., (2002) suggested that contacting participants before
such as steroid use or development and subsequent sending out questionnaires would be important. In the
9. Borromeo et al. BMC Musculoskeletal Disorders 2011, 12:71 Page 9 of 10
http://www.biomedcentral.com/1471-2474/12/71
current study, the researchers presented the study outline and Academic Associate Professor. CB is a consultant Physician,
Rheumatologist and Health Services Researcher and JDW is an
and requirements of participants (clinician and patient) Endocrinologist and Professor of Medicine with major interest in bone and
to oral and maxillofacial surgeons at a continuing profes- mineral disorders. WT and EF are research assistants.
sional development meeting. It is considered crucial to
Competing interests
the study to recruit a high proportion of oral and maxil- The authors declare that they have no competing interests.
lofacial surgeons as these are recognized as the group
most likely to treat patients delayed dental healing follow- Received: 13 March 2011 Accepted: 10 April 2011
Published: 10 April 2011
ing dental procedures. During this presentation the
potential benefits of determining incidence of delayed References
dental healing with reference to bisphosphonate usage 1. Lindsay R: Modeling the benefits of pamidronate in children with
were discussed, which was considered to be of great osteogenesis imperfecta. J Clin Invest 2002, 110(9):1239-1241.
2. Hillner BE, Ingle JN, Berenson JR, Janjan NA, Albain KS, Lipton A, Yee G,
interest to practicing specialists. This has also been deter- Biermann JS, Chlebowski RT, Pfister DG: American Society of Clinical
mined as a potential method to increase response rate to Oncology guideline on the role of bisphosphonates in breast cancer.
postal surveys [50]. American Society of Clinical Oncology Bisphosphonates Expert Panel.
J Clin Oncol 2000, 18(6):1378-1391.
Other key factors employed to increase clinician 3. Durie BG: Use of bisphosphonates in multiple myeloma: IMWG response
recruitment included using personalized introductory to Mayo Clinic consensus statement. Mayo Clin Proc 2007, 82(4):516-517,
letters, short questionnaires, follow-up letters to non- author reply 517-518.
4. Berenson JR: Zoledronic acid in cancer patients with bone
respondents and telephone follow-up. These are recog- metastases: results of Phase I and II trials. Semin Oncol 2001, 28(2
nized strategies to increase recruitment [50]. Similar Suppl 6):25-34.
measures were also employed when recruiting potential 5. Delmas PD, Munoz F, Black DM, Cosman F, Boonen S, Watts NB, Kendler D,
Eriksen EF, Mesenbrink PG, Eastell R: Effects of yearly zoledronic acid 5 mg
cases and controls. on bone turnover markers and relation of PINP with fracture reduction
in postmenopausal women with osteoporosis. J Bone Miner Res 2009,
Conclusions 24(9):1544-1551.
The study uses a case-controlled design to assess the 6. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F,
Lakatos P, Leung PC, Man Z, et al: Once-yearly zoledronic acid for
hypothesis that long-term (more than 1 year’s duration) treatment of postmenopausal osteoporosis. N Engl J Med 2007,
bisphosphonate use for the treatment of postmenopausal 356(18):1809-1822.
osteoporosis or other benign bone disease is associated 7. Reid DM, Devogelaer JP, Saag K, Roux C, Lau CS, Reginster JY,
Papanastasiou P, Ferreira A, Hartl F, Fashola T, et al: Zoledronic acid and
with impaired dental healing and subsequent develop- risedronate in the prevention and treatment of glucocorticoid-induced
ment of ONJ. All Victorian Oral and Maxillofacial Sur- osteoporosis (HORIZON): a multicentre, double-blind, double-dummy,
geons and Special Needs Dentists, by far the largest randomised controlled trial. Lancet 2009, 373(9671):1253-1263.
8. Sambrook P, Cooper C: Osteoporosis. Lancet 2006, 367(9527):2010-2018.
groups managing these patients, will be invited to parti- 9. Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D,
cipate making this the largest such study in Australia. Tugwell P: Alendronate for the primary and secondary prevention of
osteoporotic fractures in postmenopausal women. Cochrane Database
Syst Rev 2008, , 1: CD001155.
Acknowledgements 10. Cranney A, Waldegger L, Zytaruk N, Shea B, Weaver B, Papaioannou A,
This study is funded by the National Health and Medical Research Council Robinson V, Wells G, Tugwell P, Adachi JD, et al: Risedronate for the
(Project number 454683) and part-funded by a grant-in-aid from Novartis prevention and treatment of postmenopausal osteoporosis. Cochrane
Pharmaceuticals. Database Syst Rev 2003, , 4: CD004523.
None of the funders have any role other than to provide funding. The 11. Wells G, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D,
authors would like to acknowledge Dr Peter Wong for initial involvement in Tugwell P: Risedronate for the primary and secondary prevention of
protocol design and assistance in securing funding. The authors would also osteoporotic fractures in postmenopausal women. Cochrane Database
like to acknowledge Ms Lisa Crighton for initial involvement in the project Syst Rev 2008, , 1: CD004523.
and assistance in recruiting oral and maxillofacial surgeons. 12. Schweitzer DH, Oostendorp-van de Ruit M, Van der Pluijm G, Lowik CW,
Papapoulos SE: Interleukin-6 and the acute phase response during
Author details treatment of patients with Paget’s disease with the nitrogen-containing
1
Melbourne Dental School, The University of Melbourne, 720 Swanston bisphosphonate dimethylaminohydroxypropylidene bisphosphonate.
Street Victoria, 3010, Australia. 2University of Melbourne, Department of J Bone Miner Res 1995, 10(6):956-962.
Medicine, and Bone and Mineral Service Royal Melbourne Hospital, Parkville, 13. Chapurlat RD, Delmas PD: Drug insight: Bisphosphonates for
3050, Australia. 3Clinical Epidemiology and Health Service Evaluation Unit, postmenopausal osteoporosis. Nat Clin Pract Endocrinol Metab 2006,
Royal Melbourne Hospital, Parkville, 3050, Australia. 2(4):211-219, quiz following 238.
14. Pazianas M, Cooper C, Ebetino FH, Russell RG: Long-term treatment with
Authors’ contributions bisphosphonates and their safety in postmenopausal osteoporosis. Ther
GLB conceived the project and has been involved in co-ordination of the Clin Risk Manag 6:325-343.
project. GLB, CB, JC, MM and JDW assisted with protocol design and 15. Cetiner S, Sucak GT, Kahraman SA, Aki SZ, Kocakahyaoglu B, Gultekin SE,
obtaining funding. GLB, WT, EF and MM are involved in data collection. GLB, Cetiner M, Haznedar R: Osteonecrosis of the jaw in patients with multiple
CB and JDW wrote the manuscript. All authors provided feedback on drafts myeloma treated with zoledronic acid. J Bone Miner Metab 2009,
of this paper and read and approved the final draft before submission. 27(4):435-443.
16. Fehm T, Beck V, Banys M, Lipp HP, Hairass M, Reinert S, Solomayer EF,
Authors’ information Wallwiener D, Krimmel M: Bisphosphonate-induced osteonecrosis of the
GLB is a Special Needs Dentist, senior lecturer and researcher, JC is a Bone jaw (ONJ): Incidence and risk factors in patients with breast cancer and
Biologist and Forensic Dentist and MM is an Oral Medicine Clinical Specialist gynecological malignancies. Gynecol Oncol 2009, 112(3):605-609.
10. Borromeo et al. BMC Musculoskeletal Disorders 2011, 12:71 Page 10 of 10
http://www.biomedcentral.com/1471-2474/12/71
17. Carter G, Goss AN, Doecke C: Bisphosphonates and avascular necrosis of 38. Slade GSA, Roberts-Thompson K: Australia’s dental generations: the
the jaw: a possible association. Med J Aust 2005, 182(8):413-415. National Surveyof Adult oral 2004-6. Canberra: Australian Institute of Health
18. Purcell PM, Boyd IW: Bisphosphonates and osteonecrosis of the jaw. Med and Welfare (Dental Statistics and Research Series No 34) 2007.
J Aust 2005, 182(8):417-418. 39. Statistics ABo: National Health Survey: Summary of results, Australia.
19. Bagan JV, Murillo J, Jimenez Y, Poveda R, Milian MA, Sanchis JM, Silvestre FJ, 2004.
Scully C: Avascular jaw osteonecrosis in association with cancer 40. Mavrokokki T, Cheng A, Stein B, Goss A: Nature and frequency of
chemotherapy: series of 10 cases. J Oral Pathol Med 2005, 34(2):120-123. bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral
20. Marx RE: Pamidronate (Aredia) and zoledronate (Zometa) induced Maxillofac Surg 2007, 65(3):415-423.
avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 41. Takagi Y, Sumi Y, Harada A: Osteonecrosis associated with short-term oral
2003, 61(9):1115-1117. administration of bisphosphonate. J Prosthet Dent 2009, 101(5):289-292.
21. Aragon-Ching JB, Ning YM, Chen CC, Latham L, Guadagnini JP, Gulley JL, 42. Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D,
Arlen PM, Wright JJ, Parnes H, Figg WD, et al: Higher incidence of Gagel RF, Gilsanz V, Guise T, Koka S, et al: Bisphosphonate-associated
Osteonecrosis of the Jaw (ONJ) in patients with metastatic castration osteonecrosis of the jaw: report of a task force of the American Society
resistant prostate cancer treated with anti-angiogenic agents. Cancer for Bone and Mineral Research. J Bone Miner Res 2007, 22(10):1479-1491.
Invest 2009, 27(2):221-226. 43. Vinckier F, Vermylen J: Wound healing following dental extractions in
22. Lo JC, O’Ryan FS, Gordon NP, Yang J, Hui RL, Martin D, Hutchinson M, rabbits: effects of tranexamic acid, warfarin anti-coagulation, and socket
Lathon PV, Sanchez G, Silver P, et al: Prevalence of osteonecrosis of the packing. J Dent Res 1984, 63(5):646-649.
jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 44. Bagan J, Blade J, Cozar JM, Constela M, Garcia Sanz R, Gomez Veiga F,
68(2):243-253. Lahuerta JJ, Lluch A, Massuti B, Morote J, et al: Recommendations for the
23. Hellstein JW, Marek CL: Bisphosphonate osteochemonecrosis (bis-phossy prevention, diagnosis, and treatment of osteonecrosis of the jaw (ONJ)
jaw): is this phossy jaw of the 21st century? J Oral Maxillofac Surg 2005, in cancer patients treated with bisphosphonates. Med Oral Patol Oral Cir
63(5):682-689. Bucal 2007, 12(4):E336-340.
24. Wang EP, Kaban LB, Strewler GJ, Raje N, Troulis MJ: Incidence of 45. American Association of Oral and Maxillofacial Surgeons position paper
osteonecrosis of the jaw in patients with multiple myeloma and breast on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac
or prostate cancer on intravenous bisphosphonate therapy. J Oral Surg 2007, 65(3):369-376.
Maxillofac Surg 2007, 65(7):1328-1331. 46. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B:
25. Durie BG, Katz M, Crowley J: Osteonecrosis of the jaw and American Association of Oral and Maxillofacial Surgeons position paper
bisphosphonates. N Engl J Med 2005, 353(1):99-102, discussion 199-102. on bisphosphonate-related osteonecrosis of the jaws–2009 update.
26. Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M, Nooka A, J Oral Maxillofac Surg 2009, 67(5 Suppl):2-12.
Sayegh G, Guarneri V, Desrouleaux K, et al: Frequency and risk factors 47. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B:
associated with osteonecrosis of the jaw in cancer patients treated with American Association of Oral and Maxillofacial Surgeons position paper
intravenous bisphosphonates. J Bone Miner Res 2008, 23(6):826-836. on bisphosphonate-related osteonecrosis of the jaw - 2009 update. Aust
27. Migliorati CA: Bisphosphonate-associated oral osteonecrosis. Oral Surg Endod J 2009, 35(3):119-130.
Oral Med Oral Pathol Oral Radiol Endod 2005, 99(2):135. 48. Ruggiero SL, Fantasia J, Carlson E: Bisphosphonate-related osteonecrosis
28. Wilkinson GS, Kuo YF, Freeman JL, Goodwin JS: Intravenous of the jaw: background and guidelines for diagnosis, staging and
bisphosphonate therapy and inflammatory conditions or surgery of the management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006,
jaw: a population-based analysis. J Natl Cancer Inst 2007, 102(4):433-441.
99(13):1016-1024. 49. Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME:
29. Ruggiero S, Gralow J, Marx RE, Hoff AO, Schubert MM, Huryn JM, Toth B, Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum
Damato K, Valero V: Practical guidelines for the prevention, diagnosis, 2002, 32(2):94-124.
and treatment of osteonecrosis of the jaw in patients with cancer. 50. Edwards P, Roberts I, Clarke M, DiGuiseppi C, Pratap S, Wentz R, Kwan I:
J Oncol Pract 2006, 2(1):7-14. Increasing response rates to postal questionnaires: systematic review.
30. Fleisch H: Bisphosphonates in osteoporosis. Eur Spine J 2003, 12(Suppl 2): Bmj 2002, 324(7347):1183.
S142-146.
31. Estilo CL, Fornier M, Farooki A, Carlson D, Bohle G, Huryn JM: Osteonecrosis Pre-publication history
of the jaw related to bevacizumab. J Clin Oncol 2008, 26(24):4037-4038. The pre-publication history for this paper can be accessed here:
32. Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, http://www.biomedcentral.com/1471-2474/12/71/prepub
Lichinitser M, Fujiwara Y, Yardley DA, Viniegra M, et al: Denosumab
compared with zoledronic acid for the treatment of bone metastases in doi:10.1186/1471-2474-12-71
patients with advanced breast cancer: a randomized, double-blind Cite this article as: Borromeo et al.: Is bisphosphonate therapy for
study. J Clin Oncol 28(35):5132-5139. benign bone disease associated with impaired dental healing? A case-
33. Hansen T, Kirkpatrick CJ, Walter C, Kunkel M: Increased numbers of controlled study. BMC Musculoskeletal Disorders 2011 12:71.
osteoclasts expressing cysteine proteinase cathepsin K in patients with
infected osteoradionecrosis and bisphosphonate-associated
osteonecrosis–a paradoxical observation? Virchows Arch 2006,
449(4):448-454.
34. Greenberg MS: Intravenous bisphosphonates and osteonecrosis. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod 2004, 98(3):259-260.
35. Ruggiero SL, Mehrotra B: Bisphosphonate-related osteonecrosis of the Submit your next manuscript to BioMed Central
jaw: diagnosis, prevention, and management. Annu Rev Med 2009, and take full advantage of:
60:85-96.
36. Grbic JT, Black DM, Lyles KW, Reid DM, Orwoll E, McClung M, Bucci-
• Convenient online submission
Rechtweg C, Su G: The incidence of osteonecrosis of the jaw in patients
receiving 5 milligrams of zoledronic acid: data from the health • Thorough peer review
outcomes and reduced incidence with zoledronic acid once yearly • No space constraints or color figure charges
clinical trials program. J Am Dent Assoc 141(11):1365-1370.
37. Jung TI, Hoffmann F, Glaeske G, Felsenberg D: Disease-specific risk for an • Immediate publication on acceptance
osteonecrosis of the jaw under bisphosphonate therapy. J Cancer Res • Inclusion in PubMed, CAS, Scopus and Google Scholar
Clin Oncol 136(3):363-370.
• Research which is freely available for redistribution
Submit your manuscript at
www.biomedcentral.com/submit