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Osteonecrosis
Kinds of Osteonecrosis Selected AbstractsTreatment results of bisphosphonate-related osteonecrosis of the jaws,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2008Arno Wutzl MD Abstract Background. Osteonecrosis of the jaws occurs after the administration of bisphosphonates. An unequivocal treatment strategy is yet to be devised. We assess the treatment of patients with bisphosphonate-related osteonecrosis of the jaws (BRONJ). Methods. The investigators studied a prospective cohort of 58 patients 6 months after surgical treatment of BRONJ. Outcome variables were the status of the mucosa, the visual analog score of pain, and prosthetic rehabilitation. Preoperative staging results were compared with the postoperative outcome and statistically evaluated. Results. Of 58 patients, 41 surgically treated patients could be followed up after a mean period of 189 (±23) days. Twenty-four (58.5%) were free of pain and had an intact mucosa. A statistically significant improvement was registered between preoperative and postoperative staging (p <.01); 11 of 12 patients who had been treated with a flap procedure for soft tissue closure had an intact mucosa. Conclusions. This is the first prospective study to report the outcome of treatment in a cohort of patients with BRONJ. Minimal resection of necrotic bone and local soft tissue closure might be a feasible treatment strategy in patients with established BRONJ. © 2008 Wiley Periodicals, Inc. Head Neck 2008 [source] Patients with bisphosphonates-associated osteonecrosis of the jaw have reduced circulating endothelial cellsHEMATOLOGICAL ONCOLOGY, Issue 4 2007A Allegra Abstract Osteonecrosis of the jaws (ONJ) associated with the use of bisphosphonates is a newly described entity. To elucidate the mechanism leading to ONJ and to test the hypothesis that in patients with ONJ the bisphosphonates may interfere with endothelial cell proliferation, using flow cytometric analysis we evaluated the number of circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) in eight patients with bisphosphonate treatment and osteonecrosis, eight multiple myeloma (MM) patients with bisphosphonates treatment without ONJ and five normal subjects. MM patients showed an increase of CD34+ cells with respect the control subjects and ONJ subjects. EPCs and CECs were higher in MM patients compared to controls and ONJ patients. ONJ patients showed a decrease of EPCs compared to control subjects while CECs were similar to the controls group. Our results seem to show the possibility that bisphosphonates could have a antiangiogenic effect and a suppressive effect on CECs of patients with ONJ. Copyright © 2007 John Wiley & Sons, Ltd. [source] Perspective: Assessing the Clinical Utility of Serum CTX in Postmenopausal Osteoporosis and Its Use in Predicting Risk of Osteonecrosis of the Jaw,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2009Sanford Baim Abstract Bone turnover markers (BTMs) have become increasingly important in the management of postmenopausal osteoporosis (PMO). In bisphosphonate-treated women with PMO, BTMs can provide early indications of treatment efficacy, are predictors of BMD response and fracture risk reduction, and are potentially useful for monitoring patient compliance. The bone resorption marker serum C-telopeptide cross-link of type 1 collagen (sCTX) has shown high sensitivity and specificity for the detection of increased bone resorption. Recently, sCTX has been singled out as a potential indicator of risk of osteonecrosis of the jaw (ONJ) in patients receiving oral bisphosphonates who require oral surgery. However, whether BTMs are capable of predicting ONJ risk and whether sCTX is usable for this purpose are controversial questions. This article presents an overview of the current literature regarding critical issues affecting the clinical utility of BTMs (including variability and reference ranges) and the current applications of BTMs in PMO management, with a focus on sCTX. Last, the appropriateness of using sCTX to predict ONJ risk in women receiving oral bisphosphonates for PMO is evaluated. [source] Bisphosphonate-Associated Osteonecrosis of the Jaw: Report of a Task Force of the American Society for Bone and Mineral Research,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2007Sundeep Khosla (Chair) Abstract ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force. Introduction: The increasing recognition that use of bisphosphonates may be associated with osteonecrosis of the jaw (ONJ) led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address a number of key questions related to this disorder. Materials and Methods: A multidisciplinary expert group reviewed all pertinent published data on bisphosphonate-associated ONJ. Food and Drug Administration drug adverse event reports were also reviewed. Results and Conclusions: A case definition was developed so that subsequent studies could report on the same condition. The task force defined ONJ as the presence of exposed bone in the maxillofacial region that did not heal within 8 wk after identification by a health care provider. Based on review of both published and unpublished data, the risk of ONJ associated with oral bisphosphonate therapy for osteoporosis seems to be low, estimated between 1 in 10,000 and <1 in 100,000 patient-treatment years. However, the task force recognized that information on incidence of ONJ is rapidly evolving and that the true incidence may be higher. The risk of ONJ in patients with cancer treated with high doses of intravenous bisphosphonates is clearly higher, in the range of 1,10 per 100 patients (depending on duration of therapy). In the future, improved diagnostic imaging modalities, such as optical coherence tomography or MRI combined with contrast agents and the manipulation of image planes, may identify patients at preclinical or early stages of the disease. Management is largely supportive. A research agenda aimed at filling the considerable gaps in knowledge regarding this disorder was also outlined. [source] Osteonecrosis of the Jaw: More Research Needed,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2006Elizabeth Shane No abstract is available for this article. [source] Bilateral Femoral Head Osteonecrosis After Septic Shock and Multiorgan Failure,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2004Mark J Bolland Abstract A case of bilateral femoral head osteonecrosis after septic shock is presented. We suggest that the osteonecrosis was caused by ischemic insults to the proximal femora. The association between septic shock and osteonecrosis has not been previously reported. Introduction: Osteonecrosis is an uncommon disorder characterized by the in situ death of bone. A diverse range of conditions has been associated with osteonecrosis. We present a case of bilateral femoral head osteonecrosis that occurred after an episode of septic shock. Materials and Methods: A 66-year-old woman presented with a left-sided renal stone and a urinary tract infection. Her condition rapidly progressed to a life-threatening illness with septic shock complicated by multiorgan failure, which necessitated prolonged intensive care and inotropic support. She made a full recovery but 3 months later developed bilateral osteonecrosis of the femoral heads requiring bilateral total hip joint replacement. Results and Conclusions: We propose that the osteonecrosis was caused by ischemic insults to the femoral heads as a result of the widespread systemic ischemia that occurred during her initial illness. To our knowledge, septic shock has not been previously described as a cause of osteonecrosis. Clinicians should be aware of this association, particularly in patients presenting with bone pain after episodes of sepsis. [source] Dental management of patients at risk of osteochemonecrosis of the jaws: a critical reviewORAL DISEASES, Issue 8 2009S Fedele Osteonecrosis of the jaw bones is a complication of bisphosphonate (BP) drug usage characterised by trans-mucosal exposure of necrotic bone, often followed by infection and pain. Osteonecrosis is observed in cancer patients on high-potency intravenous BP more frequently than in osteoporotic individuals using low-potency oral BP. The management of osteonecrosis caused by BP is often unsatisfactory and control of risk factors is considered the most effective means of prevention. Surgical manipulation and dental infection of the jawbone are the major risk factors, hence it is suggested that careful management of oral health and relevant dental procedures may decrease the risk of osteonecrosis in individuals on BP. Recommendations for dentists and oral surgeons have been suggested by different groups of clinicians but they are often controversial and there is no clear evidence for their efficacy in reducing the likelihood of osteonecrosis development. This report critically reviews current dental recommendations for individuals using BP with the aim of helping the reader to transfer them into practice as part of pragmatic and non-detrimental clinical decisions making. [source] Updates on bisphosphonates and potential pathobiology of bisphosphonate-induced jaw osteonecrosisORAL DISEASES, Issue 3 2008J Sarin Osteonecrosis of the jaws is a major complication associated with long-term use of bisphosphonates. While osteonecrosis can arise from other precipitating conditions, bisphosphonate-induced jaw osteonecrosis (BJON) is highly associated with long-term administration of pamidronate (Arediaź) and zoledronic acid (Zometaź), which are two intravenous bisphosphonate formulations. The underlying pathogenesis of BJON and its site-specific presentation still remain to be fully elucidated. This review will discuss clinically available bisphosphonates, current opinions, pathogenesis, and management guidelines for bisphosphonate-induced jaw osteonecrosis. [source] Herpes zoster in HIV infection with osteonecrosis of the jaw and tooth exfoliationORAL DISEASES, Issue 5 2006P Siwamogstham Background:, Herpes zoster (HZ) infection of the trigeminal nerve is associated with complications such as postherpetic neuralgia, facial scarring, loss of hearing ability and conjunctivitis. Until 2005, postherpetic alveolar necrosis and spontaneous tooth exfoliation have been described in 20 cases unrelated to HIV infection. Objective:, The aim of this study was to describe HIV infection in patients (two women, two men, average age 30 years) who suffered from HZ attacks to their trigeminal nerves. Main outcome measures:, None of the patients had received antiherpetic medications or antiretroviral therapy. HIV infection was only diagnosed after the development of HZ. Facial scarring with depigmentation and hyperesthesia (postherpetic neuralgia) was diagnosed in all four patients. Oral findings consisted of spontaneous loss of both maxillary or mandibular teeth. Osteonecrosis of varying extent was also found. Treatment consisted of extractions of teeth and administration of antibiotics and analgesics. Healing of alveolar wounds was unremarkable. Conclusion:, Complications affecting the alveolar bone and teeth seem to be rare in HIV-infected patients. [source] Bisphosphonates and oral surgeryORAL SURGERY, Issue 2 2009R. Oliver Abstract Osteonecrosis of the jaws, or the threat of it, because of the use of bisphosphonates, is an increasing problem facing all dentists and oral surgeons. The link is somewhat circumstantial but compelling and there are emerging risk factors that increase a patient's susceptibility to developing osteonecrosis including the use of intravenous bisphosphonates, length of time taking the drug, smoking and possibly a genetic predisposition. There is a lack of randomised trial evidence regarding the best strategies for prevention and treatment of the condition. This article discusses current evidence, largely from observational studies on the development, prevention and management of bisphosphonate-related osteonecrosis. [source] Osteonecrosis in children with acute lymphoblastic leukemia: A 10-year study from northern GreecePEDIATRIC BLOOD & CANCER, Issue 5 2007Athanassios Tragiannidis MD No abstract is available for this article. [source] Osteonecrosis of the Mandible or Maxilla Associated with the use of New Generation BisphosphonatesTHE LARYNGOSCOPE, Issue 1 2006Matthew C. Farrugia DO Objective: The use of bisphosphonates is well established for the treatment of patients with metastatic bone disease, osteoporosis, and Paget's disease. Osteonecrosis of the mandible or maxilla associated with the use of bisphosphonates is a newly described entity never before discussed in the otolaryngology literature. In this paper, we review a series of patients diagnosed with osteonecrosis, all treated with new generation bisphosphonates. Our objective is to inform and educate others, particularly otolaryngologists/head and neck surgeons, about this drug induced entity, a condition that should be recognized early to avoid potential devastating consequences. Study Design: Retrospective chart review of a series of patients from a tertiary referral center. Methods: Pathology reports of specimens submitted from either the mandible or maxilla were reviewed from the previous 12 months. Any patient diagnosed with osteonecrosis without evidence of metastatic disease at that site was included; those with a previous history of radiation therapy were excluded. Each patient's medical history and profile were reviewed. Results: Twenty-three patients were identified with osteonecrosis of the mandible or maxilla. All of these were associated with the use of new generation bisphosphonates: zolendronate (Zometa, Novartis), pamidronate (Aredia, Novartis), and alendronate (Fosamax, Merck). Eighteen patients with known bone metastases had been treated with the intravenous form, whereas five patients with either osteoporosis or Paget's disease were using oral therapy. Patients typically presented with a nonhealing lesion, often times the result of previous dental intervention. Although the majority of these patients were treated with conservative surgical debridement, we present a case requiring a near total maxillectomy. Conclusions: Drug induced osteonecrosis of the mandible or maxilla has been recently recognized as a sequelae of treatment with the new generation of bisphosphonates. Most patients can be treated with conservative surgical debridement and cessation of bisphosphonate therapy, whereas a few may require radical surgical intervention. Other recommendations include regimented prophylactic care with an assessment of dental status before the administration of bisphosphonates, avoidance of dental procedures, and close monitoring of oral hygiene. [source] Association of a Polymorphism in the Intron 7 of the SREBF1 Gene with Osteonecrosis of the Femoral Head in KoreansANNALS OF HUMAN GENETICS, Issue 1 2009H.-J. Lee Summary Reduction or disruption of the blood supply to the bone is involved in the pathogenesis of osteonecrosis of the femoral head (ONFH). An altered lipid metabolism is one of the major risk factors for ONFH. Sterol regulatory element binding protein, SREBF1 activates genes regulating lipid biosynthesis. The aim of this study was to examine the association between the polymorphisms of the SREBF1 gene and ONFH susceptibility in the Korean population. The SREBF1 gene in 24 unrelated Korean individuals was sequenced and two polymorphisms were detected. Two variants, IVS6 , 48 C > T and IVS7 + 117 A > G, were genotyped in 423 ONFH patients and 348 controls. The genotype frequency of IVS7 + 117 A > G in ONFH patients was significantly different from that of the control group with P value < 0.0001 (Adjusted OR; 6.88, 95% CI; 3.74-12.67). Moreover, the IVS7 + 117 A > G genotype showed an association with men, and further analysis stratified by etiological factors indicated that the genotype data was significantly associated with a high risk for patients with alcohol-induced ONFH (P < 0.0001). We found that the IVS7 + 117 A > G polymorphism of the SREBF1 gene is associated with an increased risk of ONFH in the Korean population. [source] Age at time of corticosteroid administration is a risk factor for osteonecrosis in pediatric patients with systemic lupus erythematosus: A prospective magnetic resonance imaging studyARTHRITIS & RHEUMATISM, Issue 2 2010Junichi Nakamura Objective To clarify whether age at the time of the initial administration of corticosteroids is a risk factor for corticosteroid-associated osteonecrosis in children with systemic lupus erythematosus (SLE), using magnetic resonance imaging (MRI). Methods From 1986 to 2007, MRI was used to prospectively study 676 joints, including 72 joints (36 hips and 36 knees) in 18 pediatric patients with SLE (<15 years old), 100 joints (50 hips and 50 knees) in 25 adolescent patients with SLE (15,20 years old), and 504 joints (252 hips and 252 knees) in 126 adult patients with SLE (>20 years old), beginning just after corticosteroid administration, for at least 1 year. The followup rate was 100%. Results In pediatric patients, osteonecrosis developed in 4 joints (6%; all hips). In adolescent patients, osteonecrosis developed in 49 joints (49%; 18 hips and 31 knees). In adult patients, osteonecrosis developed in 207 joints (41%; 95 hips and 112 knees). The rate of osteonecrosis was significantly lower in pediatric patients than in adolescent or adult patients (P = 0.0001). Logistic regression analysis revealed that adolescent and adult patients had a significantly higher risk for osteonecrosis compared with pediatric patients, with an odds ratio of 10.3 (P < 0.0001). The youngest patients with osteonecrosis in the hip and knee were 14.9 years old and 15.5 years old, respectively. Osteonecrosis did not develop in patients younger than age 14 years. Conclusion Our results suggest that age at the time of the initial administration of corticosteroids is associated with osteonecrosis in pediatric patients with SLE. [source] Oral sodium clodronate induced osteonecrosis of the jaw in a patient with myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2007Amir H Montazeri Abstract Bisphosphonate therapy has been shown to significantly reduce the incidence of skeletal complications in patients with myeloma. Several recent reports have described osteonecrosis of the jaw (ONJ) associated with bisphosphonates. These reports mainly demonstrate an association between ONJ and potent i.v. bisphosphonates. We report a case of ONJ in a patient with myeloma, who had only been treated with oral sodium clodronate. While the degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as clodronate, remains uncertain it would be prudent to consider carefully the indications for the use of these agents to minimise the risk of ONJ. [source] Treatment results of bisphosphonate-related osteonecrosis of the jaws,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2008Arno Wutzl MD Abstract Background. Osteonecrosis of the jaws occurs after the administration of bisphosphonates. An unequivocal treatment strategy is yet to be devised. We assess the treatment of patients with bisphosphonate-related osteonecrosis of the jaws (BRONJ). Methods. The investigators studied a prospective cohort of 58 patients 6 months after surgical treatment of BRONJ. Outcome variables were the status of the mucosa, the visual analog score of pain, and prosthetic rehabilitation. Preoperative staging results were compared with the postoperative outcome and statistically evaluated. Results. Of 58 patients, 41 surgically treated patients could be followed up after a mean period of 189 (±23) days. Twenty-four (58.5%) were free of pain and had an intact mucosa. A statistically significant improvement was registered between preoperative and postoperative staging (p <.01); 11 of 12 patients who had been treated with a flap procedure for soft tissue closure had an intact mucosa. Conclusions. This is the first prospective study to report the outcome of treatment in a cohort of patients with BRONJ. Minimal resection of necrotic bone and local soft tissue closure might be a feasible treatment strategy in patients with established BRONJ. © 2008 Wiley Periodicals, Inc. Head Neck 2008 [source] Definitive radiotherapy with interstitial implant boost for squamous cell carcinoma of the tongue baseHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2005Omur Karakoyun-Celik MD Abstract Background. The purpose of this study was to examine the long-term outcome of a cohort of patients with unresected base of tongue carcinoma who received interstitial brachytherapy after comprehensive external beam radiation therapy. Methods. Between 1983 and 2000, 122 patients with primary or recurrent squamous cell carcinoma of the oropharynx or oral cavity received interstitial brachytherapy as part of their overall management. Forty patients had primary, unresected carcinoma of the base of tongue and are the subjects of this analysis. The median age was 54 years. Fifty-four percent had T3 or T4 disease, and 70% had clinical or radiographic lymphadenopathy. Twenty-four (60%) received two to three cycles of neoadjuvant chemotherapy. The oropharynx, bilateral neck, and supraclavicular fossae were comprehensively irradiated, and the tongue base received a median external beam dose of 61.2 Gy (50,72 Gy). The primary site was then boosted with an interstitial 192Iridium implant by use of a gold-button single-strand technique and three-dimensional treatment planning. The dose rate was prescribed at 0.4 to 0.5 Gy/hr. The median implant dose was 17.4 Gy (9.6,24 Gy) and adjusted to reach a total dose to the primary tumor of 80 Gy. N2 to 3 disease was managed by a planned neck dissection performed at the time of the implant. Results. The median follow-up for all patients was 56 months, and the overall survival rates were 62% at 5 years and 27% at 10 years. The actuarial primary site control was 78% at 5 years and 70% at 10 years. The overall survival and primary site control were independent of T classification, N status, or overall stage. Systemic therapy was associated with an improvement in overall survival (p = .04) and a trend toward increased primary site control with greater clinical response. There were seven documented late effects, the most frequent being grade 3 osteonecrosis (n = 2), grade 2 swallowing dysfunction (n = 2), trismus (n = 2), and chronic throat pain (n = 1). Conclusions. In an era of greatly improved dose distributions made possible by three-dimensional treatment planning and intensity-modulated radiation therapy, brachytherapy allows a highly conformal dose to be delivered in sites such as the oropharynx. If done properly, the procedure is safe and delivers a dose that is higher than what can be achieved by external beam radiation alone with the expected biologic advantages. The long-term data presented here support an approach of treating advanced tongue base lesions that includes interstitial brachytherapy as part of the overall management plan. This approach has led to a 78% rate of organ preservation at 5 years, with a 5% incidence of significant late morbidity (osteonecrosis) that has required medical management. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Patients with bisphosphonates-associated osteonecrosis of the jaw have reduced circulating endothelial cellsHEMATOLOGICAL ONCOLOGY, Issue 4 2007A Allegra Abstract Osteonecrosis of the jaws (ONJ) associated with the use of bisphosphonates is a newly described entity. To elucidate the mechanism leading to ONJ and to test the hypothesis that in patients with ONJ the bisphosphonates may interfere with endothelial cell proliferation, using flow cytometric analysis we evaluated the number of circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) in eight patients with bisphosphonate treatment and osteonecrosis, eight multiple myeloma (MM) patients with bisphosphonates treatment without ONJ and five normal subjects. MM patients showed an increase of CD34+ cells with respect the control subjects and ONJ subjects. EPCs and CECs were higher in MM patients compared to controls and ONJ patients. ONJ patients showed a decrease of EPCs compared to control subjects while CECs were similar to the controls group. Our results seem to show the possibility that bisphosphonates could have a antiangiogenic effect and a suppressive effect on CECs of patients with ONJ. Copyright © 2007 John Wiley & Sons, Ltd. [source] When managing established osteonecrosis of the jaw, don't forget the not-infrequent chronic refractory painINTERNAL MEDICINE JOURNAL, Issue 3 2010P. Poon No abstract is available for this article. [source] Cell-based immunotherapy with mesenchymal stem cells cures bisphosphonate-related osteonecrosis of the jaw,like disease in miceJOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2010Takashi Kikuiri Abstract Patients on high-dose bisphosphonate and immunosuppressive therapy have an increased risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ); despite the disease severity, its pathophysiology remains unknown, and appropriate therapy is not established. Here we have developed a mouse model of BRONJ-like disease that recapitulates major clinical and radiographic manifestations of the human disease, including characteristic features of an open alveolar socket, exposed necrotic bone or sequestra, increased inflammatory infiltrates, osseous sclerosis, and radiopaque alveolar bone. We show that administration of zoledronate, a potent aminobisphosphonate, and dexamethasone, an immunosuppressant drug, causes BRONJ-like disease in mice in part by suppressing the adaptive regulatory T cells, Tregs, and activating the inflammatory T-helper-producing interleukin 17 cells, Th17. Most interestingly, we demonstrate that systemic infusion with mesenchymal stem cells (MSCs) prevents and cures BRONJ-like disease possibly via induction of peripheral tolerance, shown as an inhibition of Th17 and increase in Treg cells. The suppressed Tregs/Th17 ratio in zoledronate- and dexamethasone-treated mice is restored in mice undergoing salvage therapy with Tregs. These findings provide evidence of an immunity-based mechanism of BRONJ-like disease and support the rationale for in vivo immunomodulatory therapy using Tregs or MSCs to treat BRONJ. © 2010 American Society for Bone and Mineral Research [source] Perspective: Assessing the Clinical Utility of Serum CTX in Postmenopausal Osteoporosis and Its Use in Predicting Risk of Osteonecrosis of the Jaw,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2009Sanford Baim Abstract Bone turnover markers (BTMs) have become increasingly important in the management of postmenopausal osteoporosis (PMO). In bisphosphonate-treated women with PMO, BTMs can provide early indications of treatment efficacy, are predictors of BMD response and fracture risk reduction, and are potentially useful for monitoring patient compliance. The bone resorption marker serum C-telopeptide cross-link of type 1 collagen (sCTX) has shown high sensitivity and specificity for the detection of increased bone resorption. Recently, sCTX has been singled out as a potential indicator of risk of osteonecrosis of the jaw (ONJ) in patients receiving oral bisphosphonates who require oral surgery. However, whether BTMs are capable of predicting ONJ risk and whether sCTX is usable for this purpose are controversial questions. This article presents an overview of the current literature regarding critical issues affecting the clinical utility of BTMs (including variability and reference ranges) and the current applications of BTMs in PMO management, with a focus on sCTX. Last, the appropriateness of using sCTX to predict ONJ risk in women receiving oral bisphosphonates for PMO is evaluated. [source] Bisphosphonate-Associated Osteonecrosis of the Jaw: Report of a Task Force of the American Society for Bone and Mineral Research,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2007Sundeep Khosla (Chair) Abstract ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force. Introduction: The increasing recognition that use of bisphosphonates may be associated with osteonecrosis of the jaw (ONJ) led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address a number of key questions related to this disorder. Materials and Methods: A multidisciplinary expert group reviewed all pertinent published data on bisphosphonate-associated ONJ. Food and Drug Administration drug adverse event reports were also reviewed. Results and Conclusions: A case definition was developed so that subsequent studies could report on the same condition. The task force defined ONJ as the presence of exposed bone in the maxillofacial region that did not heal within 8 wk after identification by a health care provider. Based on review of both published and unpublished data, the risk of ONJ associated with oral bisphosphonate therapy for osteoporosis seems to be low, estimated between 1 in 10,000 and <1 in 100,000 patient-treatment years. However, the task force recognized that information on incidence of ONJ is rapidly evolving and that the true incidence may be higher. The risk of ONJ in patients with cancer treated with high doses of intravenous bisphosphonates is clearly higher, in the range of 1,10 per 100 patients (depending on duration of therapy). In the future, improved diagnostic imaging modalities, such as optical coherence tomography or MRI combined with contrast agents and the manipulation of image planes, may identify patients at preclinical or early stages of the disease. Management is largely supportive. A research agenda aimed at filling the considerable gaps in knowledge regarding this disorder was also outlined. [source] Retention, Distribution, and Effects of Intraosseously Administered Ibandronate in the Infarcted Femoral Head,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2007James Aya-ay Abstract The local distribution, retention, and effects of intraosseous administration of ibandronate in the infarcted femoral heads were studied. Intraosseous administration effectively delivered and distributed ibandronate in the infarcted femoral heads and decreased the femoral head deformity in a large animal model of Legg-Calve-Perthes disease. Introduction: Bisphosphonate therapy has gained significant attention for the treatment of ischemic osteonecrosis of the femoral head (IOFH) because of its ability to inhibit osteoclastic bone resorption, which has been shown to contribute to the pathogenesis of femoral head deformity. Because IOFH is a localized condition, there is a need to explore the therapeutic potential of local, intraosseous administration of bisphosphonate to prevent the femoral head deformity. The purpose of this study was to investigate the distribution, retention, and effects of intraosseous administration of ibandronate in the infarcted head. Materials and Methods: IOFH was surgically induced in the right femoral head of 27 piglets. One week later, a second operation was performed to inject 14C-labeled or unlabeled ibandronate directly into the infarcted head. 14C-ibandronate injected heads were assessed after 48 h, 3 weeks, or 7 weeks later to determine the distribution and retention of the drug using autoradiography and liquid scintillation analysis. Femoral heads injected with unlabeled ibandronate were assessed at 7 weeks to determine the degree of deformity using radiography and histomorphometry. Results: Autoradiography showed that 14C-Ibandronate was widely distributed in three of the four heads examined at 48 h after the injection. Liquid scintillation analysis showed that most of the drug was retained in the injected head, and almost negligible amount of radioactivity was present in the bone and organs elsewhere at 48 h. At 3 and 7 weeks, 50% and 30% of the 14C-drug were found to be retained in the infarcted heads, respectively. Radiographic and histomorphometric assessments showed significantly better preservation of the infarcted heads treated with intraosseous administration of ibandronate compared with saline (p < 0.001). Conclusions: This study provides for the first time the evidence that local intraosseous administration is an effective route to deliver and distribute ibandronate in the infarcted femoral head to preserve the femoral head structure after ischemic osteonecrosis. In a localized ischemic condition such as IOFH, local administration of bisphosphonate may be preferable to oral or systemic administration because it minimizes the distribution of the drug to the rest of the skeleton and bypasses the need for having a restored blood flow to the infarcted head for the delivery of the drug. [source] Bilateral Femoral Head Osteonecrosis After Septic Shock and Multiorgan Failure,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2004Mark J Bolland Abstract A case of bilateral femoral head osteonecrosis after septic shock is presented. We suggest that the osteonecrosis was caused by ischemic insults to the proximal femora. The association between septic shock and osteonecrosis has not been previously reported. Introduction: Osteonecrosis is an uncommon disorder characterized by the in situ death of bone. A diverse range of conditions has been associated with osteonecrosis. We present a case of bilateral femoral head osteonecrosis that occurred after an episode of septic shock. Materials and Methods: A 66-year-old woman presented with a left-sided renal stone and a urinary tract infection. Her condition rapidly progressed to a life-threatening illness with septic shock complicated by multiorgan failure, which necessitated prolonged intensive care and inotropic support. She made a full recovery but 3 months later developed bilateral osteonecrosis of the femoral heads requiring bilateral total hip joint replacement. Results and Conclusions: We propose that the osteonecrosis was caused by ischemic insults to the femoral heads as a result of the widespread systemic ischemia that occurred during her initial illness. To our knowledge, septic shock has not been previously described as a cause of osteonecrosis. Clinicians should be aware of this association, particularly in patients presenting with bone pain after episodes of sepsis. [source] Bisphosphonate-associated osteonecrosis of the jaw.JOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 5 2010Knowledge, attitudes of dentists, dental students: a preliminary study Abstract Objective, The objective was to determine the knowledge of dentists and dental students of bisphosphates and osteonecrosis of the jaw (ONJ) in the Autonomous Community of Murcia, Spain. Material and method, A structured questionnaire was elaborated on knowledge, attitude and practice regarding aspects of the aetiology, diagnosis and prevention of bisphosphonate-associated ONJ. The questionnaire was administered to two groups: group I with 60 dental students and group II, 60 dentists with well-established professional activity. Results, As regards the subjects' knowledge of bisphosphonate-associated osteonecrosis, 30 (50%) students and 41 (68.36%) dentists (P = 0.0041) had up to date knowledge. Most correctly identified risk factors involved. Only eight (13.33%) students and 20 (33.33%) dentists (P = 0.010) knew how to treat osteonecrosis once established. Conclusions, Training strategies need to be established as regards bisphosphonate-associated ONJ. [source] No osteonecrosis in jaws of young patients with osteogenesis imperfecta treated with bisphosphonatesJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 4 2008Barbro Malmgren Background:, Recent reports of osteonecrosis of the jaw (ONJ) after dental surgery in patients treated with second- and third-generation nitrogen-containing bisphosphonates instigated this retrospective study. As treatment with bisphosphonates in patients with osteogenesis imperfecta (OI) has become an important symptomatic therapy, especially for severe forms of the disease, we found it important to investigate whether healing after surgical exposure of jaw bone was influenced by the bisphosponate treatment in our group of children, adolescents and young adults with OI. Subjects and methods:, Disodiumpamidronate was given as monthly intravenous infusion to 64 patients with OI aged 3 months to 20.9 years at the start of treatment (mean 8.1, median 7.7). During 0.5,12.5 years of treatment (mean 4.5, median 4.0), a total individual dose of 140,4020 mg/m2 disodiumpamidronate was given (mean 1623 and median 1460). Ten patients continued with oral alendronate and two with zoledronic acid therapy. In 22 of these patients, 38 dental surgery procedures were performed at the age of 3.4,31.9 years (mean 12.2, median 12.3) after 0.03,7.9 years of treatment (mean 3.6, median 3.4). Results:, Despite long-term intravenous monthly disodiumpamidronate treatment, none of the 64 patients had any clinical signs of ONJ. Conclusions:, The risk of ONJ in these patients must be considered so low that the patients with indications for treatment should be treated and get the chance to experience the well-documented beneficial effect for children with severe OI. [source] Precooling of the femoral canal enhances shear strength at the cement,prosthesis interface and reduces the polymerization temperatureJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2006Pang-Hsin Hsieh Abstract Preheating of the femoral stem in total hip arthroplasty improves the cement,prosthesis bond by decreasing the interfacial porosity. The main concern, however, is the potential thermal osteonecrosis because of an increased polymerization temperature. In this study, the effects of femoral canal precooling on the characteristics of the cement,stem interface were evaluated in an experimental model for three test conditions: precooling of the femoral canal, preheating of the stem (44°C), and a control in which stems were inserted at room temperature without thermal manipulation of the implant, cement, or bone. Compared to the control group, precooling of the femoral canal and preheating of the stem had similar effects on the cement,stem interface, with greater interfacial shear strength and a reduced porosity. Femoral canal precooling also produced a lower temperature at the cement,bone interface. No difference was found in the ultimate compressive strength of bone cement for the three preparation conditions. Based on this laboratory model, precooling of the femoral canal could improve shear strength and porosity at the stem,cement interface, minimize thermal injury, and maintain the mechanical strength of the cement. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Endothelial nitric oxide synthase gene polymorphisms in patients with nontraumatic femoral head osteonecrosisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 8 2006Kyung-Hoi Koo Abstract As endothelial nitric oxide synthase (eNOS) has beneficial effects on skeletal, vascular, and thrombotic systems, the association between nontraumatic femoral head osteonecrosis (FHON) and eNOS gene polymorphisms was investigated in Korean patients with FHON. Genomic DNA from 103 patients with nontraumatic FHON (idiopathic in 50, steroid-induced in 29, and alcohol abuse in 24) and 103 control subjects matched for gender and age (3-year range) was analyzed for the 27-bp repeat polymorphism in intron 4 and Glu298Asp polymorphism in exon 7. The frequencies of alleles and genotypes were compared between patients and control subjects. The frequency of 4a allele was significantly higher in total patients than control subjects [6.8% vs. 2.4%, p,=,0.0345, odds ratio (OR) 2.931]. In subgroup analysis, the 4a allele significantly increased in patients with idiopathic FHON versus control subjects (9.0% vs. 2.4%, p,=,0.0297, OR 3.976). The frequency of the 4a/b genotype in total patients (13.6% vs. 4.9%, p,=,0.0302, OR 3.083) as well as patients with idiopathic FHON (18.0% vs. 4.9%, p,=,0.0246, OR 4.302) was higher than control subjects. The distribution of Glu298Asp polymorphisms was not significantly different between patients and control subjects. Microstellate polymorphism in intron 4 of eNOS polymorphism was significantly associated with idiopathic FHON in Korean patients. Because 4a allele is associated with lower synthesis of eNOS, these results suggest that carrier state of 4a allele in intron 4 might be a genetic risk factor of FHON and could provide insight into the protective role of nitric oxide in the pathogenesis of FHON. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1722,1728, 2006 [source] Longitudinal quantitative evaluation of lesion size change in femoral head osteonecrosis using three-dimensional magnetic resonance imaging and image registrationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2006Masaki Takao Abstract It remains controversial whether some lesions of femoral head osteonecrosis regress during the natural course of the disease. With image registration, accurately matched image sets of the same subject can be acquired at different times. We applied image registration to evaluate lesion size change and assessed accuracy and usefulness compared to volume measurements and a conventional method. We also investigated whether lesions regress with this technique and with volume measurements. Baseline and 1 year minimum follow-up scans were conducted on 25 patients (31 hips) without radiological evidence of collapse. A three-dimensional (3D) spoiled gradient recalled echo sequence was used in the coronal direction (slice thickness,=,2 mm; slice pitch,=,1 mm). Size change was evaluated on all contiguous pairs of matched images after image registration. As a conventional method, coronal images (slice thickness,=,5 mm) were reconstructed, and size change was evaluated on the five representative coronal slices. Evaluation with the conventional method identified eight lesions with apparent reduction; assessments using image registration and volume measurements identified three lesions, all within a year of initial steroid treatment and remaining at ARCO stage I at follow up. Evaluation of lesion size change using image registration was comparable to volume measurements. Inaccurate estimation of lesion size change due to mismatching of slice planes can be excluded. We demonstrated that some early lesions detected less than a year after initial steroid treatment can show size reduction with image registration as well as with volume measurements. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1231,1239, 2006 [source] Zoledronic acid improves femoral head sphericity in a rat model of perthes diseaseJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2005David G. Little Abstract We hypothesized that the bisphosphonate zoledronic acid (ZA) could improve femoral head sphericity in Perthes disease by changing the balance between bone resorption and new bone formation. This study tests the effect of ZA in an established model of Perthes disease, the spontaneously hypertensive rat (SHR). One hundred and twenty 4-week old SHR rats were divided into three groups of 40: saline monthly, 0.015 mg/kg ZA weekly, or 0.05 mg/kg ZA monthly. At 15 weeks DXA measurements documented that femoral head BMD was increased by 18% in ZA weekly and 21% in ZA monthly compared to controls (p < 0.01). Femoral head sphericity in animals with osteonecrosis was improved in ZA-treatment groups (p < 0.01) as measured by epiphyseal quotient (EQ). The proportion of "flat" heads (EQ ± 0.40) was significantly reduced from 32% in saline-treated animals to 12% in weekly ZA and 3% in monthly ZA (p < 0.01). Histologically there was a similar prevalence of osteonecrosis in all groups. The prevalence of ossification delay was significantly reduced by ZA treatment (p < 0.01). Zoledronic acid favorably altered femoral head shape in this spontaneous model of osteonecrosis in growing rats. Translation of these results to Perthes disease could mean that deformity of the femoral head may be modified in children, perhaps reducing the need for surgical intervention in childhood and adult life. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. 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