A pragmatic window of opportunity to minimise the risk of MRONJ development in individuals with osteoporosis on Denosumab therapy: a hypothesis

Abstract Denosumab is associated with the development of medication-related osteonecrosis of the jaw (MRONJ), an uncommon but severe oral side effect with a higher prevalence in metastatic cancer patients than in patients with metabolic bone fragility. Although several oral triggers can initiate MRONJ, invasive oral treatments and tooth extraction still remain the most common precipitating event. In general, tooth extraction and oral surgery should be avoided in patients at increased risk of MRONJ, while extraction of non-restorable teeth should be performed based on specific risk reduction protocols to eliminate dental/periodontal infections, still protecting from MRONJ onset. Based on the different pharmacological activity of denosumab and nitrogen-containing bisphosphonates, it is likely that the MRONJ risk profile of patients with osteoporosis could somewhat vary. We hypothesize the chance to maximize the pharmacokinetic of denosumab 60 mg (Prolia®) and identify a time interval in which invasive oral treatments can ideally take place without restrictions in patients with metabolic bone fragility, We propose that dental surgery (e.g. tooth extraction) may be safely performed without additional intra or peri-operative procedures in osteoporosis patients using denosumab provided that careful case selection, adequate communication among specialists, planning of a delayed dosing window (1-month deferral) and rigorous postoperative follow-up are granted. Graphical abstract

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Increased risk of bisphosphonate-related osteonecrosis of the jaw in patients with Sjögren’s syndrome: nationwide population-based cohort study

BMJ Open ◽

10.1136/bmjopen-2018-024655 ◽

2019 ◽

Vol 9 (2) ◽

pp. e024655 ◽

Cited By ~ 2

Author(s):

Min-Tser Liao ◽

Wu-Chien Chien ◽

Jen-Chun Wang ◽

Chi-Hsiang Chung ◽

Shi-Jye Chu ◽

...

Keyword(s):

Cohort Study ◽

Tooth Extraction ◽

Cox Regression ◽

Sjogren’S Syndrome ◽

Population Based ◽

Osteonecrosis Of The Jaw ◽

Sjogren's Syndrome ◽

Control Group ◽

Increased Risk

ObjectiveThe aim of this study was to explore whether patients with Sjögren’s syndrome (SS) were susceptible to bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) after tooth extraction in the entire population of Taiwan.DesignA nationwide population-based retrospective cohort study.SettingData were extracted from Taiwan’s National Health Insurance Research Database (NHIRD).MethodologyMedical conditions for both the study and control group were categorised using the International Classification of Diseases, 9th Revision. ORs and 95% CIs for associations between SS and osteonecrosis of the jaw (ONJ) were estimated using Cox regression.ResultsOverall, 13 398 patients diagnosed with SS were identified from the NHIRD. An additional 53 592 matched patients formed the control group. At the 3-year follow-up, patients with SS started to exhibit a significantly increased cumulative risk of developing BRONJ compared with that of patients without SS (log rank test <0.001). At the end of the follow-up period, patients with SS exhibited a significantly increased incidence of ONJ compared with that of the controls (0.08%vs0.03%, p=0.017). The Cox regression model showed that patients with SS also exhibited a significantly increased risk of developing BRONJ compared with that of the patients without SS (adjusted HR=7.869, 95% CI 3.235 to 19.141, p<0.001).ConclusionPatients with SS exhibit an increased risk of developing BRONJ after tooth extraction. BPs should be used with caution in patients with SS.

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Feasibility of Proton Beam Therapy as a Rescue Therapy in Heavily Pre-Treated Retinoblastoma Eyes

Cancers ◽

10.3390/cancers13081862 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1862

Author(s):

Eva Biewald ◽

Tobias Kiefer ◽

Dirk Geismar ◽

Sabrina Schlüter ◽

Anke Manthey ◽

...

Keyword(s):

Proton Beam ◽

Rescue Therapy ◽

Therapeutic Option ◽

Proton Beam Therapy ◽

External Beam Radiation ◽

Time Interval ◽

Beam Radiation ◽

Primary Tumors ◽

Increased Risk

Despite the increased risk of subsequent primary tumors (SPTs) external beam radiation (EBRT) may be the only therapeutic option to preserve a retinoblastoma eye. Due to their physical properties, proton beam therapy (PBT) offers the possibility to use the effectiveness of EBRT in tumor treatment and to decisively reduce the treatment-related morbidity. We report our experiences of PBT as rescue therapy in a retrospectively studied cohort of 15 advanced retinoblastoma eyes as final option for eye-preserving therapy. The average age at the initiation of PBT was 35 (14–97) months, mean follow-up was 22 (2–46) months. Prior to PBT, all eyes were treated with systemic chemotherapy and a mean number of 7.1 additional treatments. Indication for PBT was non-feasibility of intra-arterial chemotherapy (IAC) in 10 eyes, tumor recurrence after IAC in another 3 eyes and diffuse infiltrating retinoblastoma in 2 eyes. Six eyes (40%) were enucleated after a mean time interval of 4.8 (1–8) months. Cataract formation was the most common complication affecting 44.4% of the preserved eyes, yet 77.8% achieved a visual acuity of >20/200. Two of the 15 children treated developed metastatic disease during follow-up, resulting in a 13.3% metastasis rate. PBT is a useful treatment modality as a rescue therapy in retinoblastoma eyes with an eye-preserving rate of 60%. As patients are at lifetime risk of SPTs consistent monitoring is mandatory.

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Evaluation of Preventive Treatment Protocols for Patients under Antiresorptive Therapy Undergoing Tooth Extraction at a Swiss University Clinic

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18189924 ◽

2021 ◽

Vol 18 (18) ◽

pp. 9924

Author(s):

Ellen Pick ◽

Nicolas Leuenberger ◽

Irina Kuster ◽

Nicole Selina Stutzmann ◽

Bernd Stadlinger ◽

...

Keyword(s):

Tooth Extraction ◽

Wound Closure ◽

Oral Surgery ◽

Preventive Treatment ◽

Osteonecrosis Of The Jaw ◽

Antiresorptive Therapy ◽

Related Factors ◽

Treatment Protocols ◽

Primary Wound Closure ◽

Mucoperiosteal Flap

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a dreaded complication in patients with compromised bone metabolism. The purpose of the present study was to examine the occurrence of ARONJ and its related factors among patients with a history of antiresorptive therapy undergoing tooth extraction using preventive protocols at a Swiss university clinic. Data were retrospectively pooled from health records of patients having received a surgical tooth extraction between January 2015 and April 2020 in the Clinic of Cranio-Maxillofacial and Oral surgery, University of Zurich. A total of 970 patients received an extraction with flap elevation or wound closure during this period. A total of 104 patients could be included in the study. Furthermore, variables including age, gender, smoking, risk profile, choice, indication and duration of antiresorptive therapy, number of extractions, extraction site, surgical technique, choice and duration of antibiotics as well as the presence of postoperative inflammatory complications were assessed. Overall, 4 patients developed ARONJ (incidence of 3.8%) after tooth extraction at the same location, without previous signs of osteonecrosis. Preventive methods included predominantly primary wound closure using a full thickness mucoperiosteal flap and prolonged perioperative antibiotic prophylaxis. In accordance with current literature, the applied protocol showed a reliable outcome in preventing ARONJ when a tooth extraction is required.

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Osteoporosis in Skin Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21134749 ◽

2020 ◽

Vol 21 (13) ◽

pp. 4749 ◽

Cited By ~ 4

Author(s):

Maria Maddalena Sirufo ◽

Francesca De Pietro ◽

Enrica Maria Bassino ◽

Lia Ginaldi ◽

Massimo De Martinis

Keyword(s):

Bone Resorption ◽

Bone Formation ◽

Skin Diseases ◽

Public Health Problem ◽

Bone Fragility ◽

Skeletal Disease ◽

Metabolic Bone ◽

Systemic Treatments ◽

Increased Risk ◽

Skeletal Homeostasis

Osteoporosis (OP) is defined as a generalized skeletal disease characterized by low bone mass and an alteration of the microarchitecture that lead to an increase in bone fragility and, therefore, an increased risk of fractures. It must be considered today as a true public health problem and the most widespread metabolic bone disease that affects more than 200 million people worldwide. Under physiological conditions, there is a balance between bone formation and bone resorption necessary for skeletal homeostasis. In pathological situations, this balance is altered in favor of osteoclast (OC)-mediated bone resorption. During chronic inflammation, the balance between bone formation and bone resorption may be considerably affected, contributing to a net prevalence of osteoclastogenesis. Skin diseases are the fourth cause of human disease in the world, affecting approximately one third of the world’s population with a prevalence in elderly men. Inflammation and the various associated cytokine patterns are the basis of both osteoporosis and most skin pathologies. Moreover, dermatological patients also undergo local or systemic treatments with glucocorticoids and immunosuppressants that could increase the risk of osteoporosis. Therefore, particular attention should be paid to bone health in these patients. The purpose of the present review is to take stock of the knowledge in this still quite unexplored field, despite the frequency of such conditions in clinical practice.

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Osteonecrosis of the jaw (ONJ) in androgen-independent prostate cancer (AIPC) patients receiving ATTP (bevacizumab, docetaxel, thalidomide, and prednisone)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.19594 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 19594-19594 ◽

Cited By ~ 2

Author(s):

J. B. Aragon-Ching ◽

Y. M. Ning ◽

L. Latham ◽

J. Guadagnini ◽

P. M. Arlen ◽

...

Keyword(s):

Prostate Cancer ◽

Risk Factor ◽

Cancer Patients ◽

Oral Surgery ◽

Osteonecrosis Of The Jaw ◽

Phase Iii ◽

Additional Risk Factor ◽

Increased Risk ◽

Vascular Insufficiency ◽

Phase Iii Trials

19594 Background: ONJ has been associated with IV bisphosphonate use in cancer patients (pts) and chemotherapy may be an additional risk factor. ONJ is believed to result from localized vascular insufficiency due to faulty bone remodeling. ONJ incidence in pts not receiving chemotherapy (e.g. Paget's disease) is reportedly only 0.8%; prostate cancer pts have an incidence of 6.5%. Methods: We reviewed data from pts with advanced AIPC who developed ONJ while being treated on a Phase II study of ATTP. Results: Six of 36 (17%) pts treated with ATTP had ONJ confirmed by oral surgery. Four of the 6 pts presented with pain and, in five, the ONJ was mandibular in location. All pts were treated conservatively with either sequestrectomy or oral cleansing with chlorhexidine. All pts had been treated monthly with IV zoledronic acid (ZA). The mean duration of ZA use before diagnosis of ONJ was 20 months (mos). One patient had been treated with oral alendronate for 3 years and then developed ONJ after 5 mos of ZA. Of the 36 pts on-study, previous dental history could be verified in 24 pts. ONJ was diagnosed in 4 of the 5 pts with a prior dental infection or invasive dental procedure. Pts received an average of 11 cycles of ATTP before ONJ was diagnosed. All pts with ONJ had received full doses of bevacizumab and most had received full doses of all medications for all cycles. Conclusions: The possibility exists that the risk for ONJ may be higher with specific chemotherapy regimens, particularly those that include steroids or anti-angiogenic agents. However, at this time prior dental infections or procedures remain the greatest known risk factor. It is also possible that the relatively high incidence of ONJ in prostate cancer patients may reflect increased awareness in this population. Randomized phase III trials in AIPC, specifically addressing the incidence of ONJ, are needed to determine whether specific chemotherapy regimens are associated with an increased risk of this complication. No significant financial relationships to disclose.

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GAMBARAN PEMBERIAN ANESTESI LOKAL BLOK MANDIBULA DENGAN TEKNIK GOW-GATES PADA PEMINUM ALKOHOL

e-GIGI ◽

10.35790/eg.2.1.2014.4015 ◽

2014 ◽

Vol 2 (1) ◽

Author(s):

Devina A. Utomo

Keyword(s):

Experimental Study ◽

Medical Treatment ◽

Social Life ◽

Tooth Extraction ◽

Oral Surgery ◽

Negative Impact ◽

Onset Of Action ◽

Dental Surgery ◽

North Sulawesi ◽

Light Medium

Abstract: In Indonesia, North Sulawesi province has the highest number of alcoholics which causes bad impact on health, social life, and medical treatment. Moreover, North Sulawesi is one of the 5 provinces with the highest prevalence of dental problems in Indonesia. This prevalence is about 29.8%; 35.04% consisted of tooth extraction or oral surgery. Tooth extraction and dental surgery can cause negative impact to the alcoholics who have dental problems that need appropriate anaesthetics. This was an experimental study which aimed to determine the doses and the onset of action of anesthetics which were given to patients who were alcoholics (categorized as light, medium, and heavy). Data were processed non-statistically and were based on the observation and analysis. The results showed that the average anaesthetic dose needed for heavy alcoholics was 4.6cc; medium alcoholics 3.8cc; and light alcoholics 2.66 cc. The average onset of action in heavy alcoholics was 19 minutes; medium alcoholics 16.6 minutes; and light alcoholics 13.6 minutes. Conclusion: The more alcohol the patient consumed, the higher average of the required anesthetic dose and the longer onset of action of the anesthetics.Keywords: mandibular block anesthesia, alcoholic, Gow-Gates techniqueAbstrak: Sulawesi Utara merupakan provinsi dengan jumlah peminum alkohol terbanyak di Indonesia. Perilaku ini berdampak buruk terhadap kesehatan, kehidupan sosial, dan juga terhadap perlakuan medis. Sulawesi Utara termasuk 5 besar provinsi dengan prevalensi masalah gigi dan mulut tertinggi di Indonesia yaitu sebesar 29,8%; 35,04% di antaranya ialah tindakan pencabutan atau bedah gigi. Proses pencabutan atau bedah gigi dapat berdampak negatif terhadap peminum alkohol dengan masalah gigi dan mulut sehingga dibutuhkan tindakan anestesi yang tepat. Penelitian ini bersifat eksperimental dan bertujuan untuk mendapatkan gambaran dosis anestesi dan onset of action pada pasien peminum alkohol yang dibagi dalam kategori peminum ringan, peminum sedang, dan peminum berat. Pengolahan data penelitian ini dilakukan secara deskriptif non-statistik berdasarkan hasil observasi dan analisis. Hasil penelitian menunjukkan bahwa dosis rata-rata yang dibutuhkan oleh pasien kategori peminum berat 4,6cc; peminum sedang 3,8cc; dan peminum ringan 2,66 cc. Rata-rata onset of action pada pasien kategori peminum berat pada menit ke-19; peminum sedang pada menit ke-16,6; dan peminum ringan pada menit ke-13,6. Simpulan: Pada pasien peminum alkohol rata-rata dosis anestesi yang diperlukan lebih tinggi dan onset of action semakin lambat seiring dengan tingginya jumlah alkohol yang dikonsumsi.Kata kunci: anestesi blok mandibula, teknik anestesi Gow-Gates, peminum alkohol

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P0918LONGITUDINAL TRAJECTORIES OF NUTRITIONAL PARAMETERS WITH ORAL NUTRITIONAL SUPPLEMENT USE AMONG NON-DIALYSIS CHRONIC KIDNEY DISEASE PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0918 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Michelle Wong ◽

Dani Renouf ◽

Sophia Zheng ◽

Zainab Sheriff ◽

Adeera Levin

Keyword(s):

Kidney Disease ◽

Serum Albumin ◽

Nutritional Supplement ◽

Time Interval ◽

Protein Energy Wasting ◽

Supplement Use ◽

Longitudinal Trajectories ◽

Increased Risk ◽

Oral Nutritional Supplements

Abstract Background and Aims Malnutrition and protein-energy wasting are complications of advanced CKD associated with increased risk of mortality and morbidity. In the province of British Columbia, Canada, a Nutritional Supplement Policy stewarded by renal dietitians guides prescription of oral nutritional supplements (ONS). To date, there have been a lack of studies assessing the effects of ONS among non-dialysis CKD patients (CKD-ND). The aim of the study was to assess longitudinal trajectories of nutrition, inflammation and associated biochemical parameters following initiation of ONS among CKD-ND patients. Method In this retrospective cohort study of adult CKD-ND patients who initiated follow-up at multidisciplinary Kidney Care Clinics during 2013-2015, we used radar charts to examine longitudinal trajectories of nutritional, inflammation and related parameters over 2 years, among patients who had at least one ONS prescription and who had available lab data for the following 8 parameters within any given time interval: body mass index (BMI), serum albumin, bicarbonate, phosphate, parathyroid hormone, ferritin, neutrophil-to-lymphocyte ratio (NLR) and haemoglobin. Mean values of each parameter were plotted at 6-month intervals from the first prescription of ONS, up to 29 months. Results There were 963, 692, 569, 481, 425 patients with available data during the intervals at month 0-5, 6-11, 12-17, 18-23 and 24-29 following the first ONS prescription, respectively. Mean serum albumin increased from a mean of 37 to 40 g/L over the 29-month period after ONS initiation, while mean NLR declined from 4.5 to 3.6 (Figure). Mean serum ferritin also declined slightly from 293 to 261 µg/L at 3 months and remained stable thereafter. There were small fluctuations in mean BMI (range 24.5 to 25.1 kg/m2), bicarbonate (range 24 to 25 mmol/L), PTH (range 15.5 to 18.0 pmol/L). Mean haemoglobin rose from 108 g/L in the first interval to 116 g/L in the last interval. Mean serum phosphate changed minimally from 1.4 to 1.3 mmol/L. Conclusion Among CKD-ND patients who had at least one ONS prescription, serum albumin increased, while there was a decrease in inflammation parameters (NLR and ferritin), and other variables had small fluctuations over the 2+ year follow-up. Future analyses will include multivariable-adjusted models to assess the associations of ONS treatment with nutritional variables and with clinical outcomes, including progression to end-stage kidney disease.

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Use of Platelet Rich Fibrin (PRF)-Based Autologous Membranes for Tooth Extraction in Patients under Bisphosphonate Therapy: A Case Report

Biomedicines ◽

10.3390/biomedicines7040089 ◽

2019 ◽

Vol 7 (4) ◽

pp. 89 ◽

Cited By ~ 1

Author(s):

Alberto Pispero ◽

Ivan Bancora ◽

Antonious Khalil ◽

Dario Scarnò ◽

Elena M. Varoni

Keyword(s):

Tooth Extraction ◽

Osteonecrosis Of The Jaw ◽

Bisphosphonate Therapy ◽

Surgical Wound ◽

Promising Alternative ◽

Platelet Rich Fibrin ◽

Premolar Extraction ◽

Extraction Site ◽

Antibiotic Coverage

Tooth extraction in patients treated with bisphosphonates (BPs) for osteoporosis or cancer exposes the patient to the risk of osteonecrosis of the jaw. An autologous membrane using platelet-rich fibrin (PRF) is an innovative technique to promote wound healing, which allows obtaining a hermetic closure of the post-extractive surgical site without the need of mucoperiosteal flaps or periosteal releasing incisions. Here, we report the case of a 70-year-old woman, in therapy with alendronate for 12 years, requiring the upper right premolar extraction because of a crown fracture. After the tooth extraction performed under antiseptic and antibiotic coverage, the PRF autologous membrane was placed on the surgical wound to close completely the post-extraction site. Follow-up visits were carried out after one, two, four weeks and two months from the intervention. The complete re-epithelization of the wound was observed without signs of infection. The use of PRF for the closure of post-extraction sockets in patients taking BPs appears to be a promising alternative to the more invasive surgical procedures. Future clinical trials will be pivotal in elucidating the effectiveness of PRF to prevent BP-related osteonecrosis after tooth extraction.

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Abstract 12693: Influence of Resting Heart Rate and Changes in Resting Heart Rate on Cardiovascular Outcomes From the Atherosclerosis Risk in Communities Study

Circulation ◽

10.1161/circ.130.suppl_2.12693 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Ali Vazir ◽

Brian Claggett ◽

Amil Shah ◽

Hicham Skali ◽

Susan Cheng ◽

...

Keyword(s):

Heart Rate ◽

Time Interval ◽

Resting Heart Rate ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk ◽

All Cause Mortality ◽

Increase Risk ◽

Over Time

Background: Resting heart rate (HR) and change in resting heart rate (ΔHR) over time are associated with increased risk of adverse outcome in patients with established heart failure (HF). We assessed whether the most recent HR and ΔHR are associated with cardiovascular (CV) outcomes in participants enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study. Methods: We studied 15,680 participants with HR recorded at baseline (age 54±6 years, women 55%, African American 27%) and over 3 follow-up visits with a median time interval between visits of 3.0 (IQR 2.9-4.0) years. ΔHR from the preceding visit was calculated. Participants were followed up for a median of 22.7 (19.8-23.7) years. We related baseline and most recent resting HR and ΔHR to all cause mortality and CV outcomes adjusting for established baseline and time-updated risk factors and medications. Results: Baseline and most recent HR and ΔHR were associated with all-cause mortality and CV outcomes (table), however most recent HR and ΔHR were more strongly associated with outcomes compared to baseline HR. Every 10bpm increase in HR from the preceding visit was associated with a 29%, 30% 22% and 15% increase risk of all-cause mortality, incident HF, incident MI and stroke respectively. Every 10 bpm higher most recent HR was associated with a 34%, 41% 23% and 14% increase risk of all-cause mortality, incident HF, incident MI and stroke respectively. Conclusion: In a community-based cohort, the most recent resting HR and ΔHR are strongly associated with outcomes; higher resting HR and increases in HR over time are associated with the greatest magnitude of risk.

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The roles of miRNA, lncRNA and circRNA in the development of osteoporosis

Biological Research ◽

10.1186/s40659-020-00309-z ◽

2020 ◽

Vol 53 (1) ◽

Cited By ~ 3

Author(s):

Yang Yang ◽

Wang Yujiao ◽

Wang Fang ◽

Yuan Linhui ◽

Guo Ziqi ◽

...

Keyword(s):

Environmental Factors ◽

Bone Fragility ◽

Circular Rnas ◽

Therapeutic Approaches ◽

Control Of Gene Expression ◽

Metabolic Bone ◽

Increased Risk ◽

Non Coding Rnas ◽

Genetic And Environmental Factors

Abstract Osteoporosis is a common metabolic bone disease, influenced by genetic and environmental factors, that increases bone fragility and fracture risk and, therefore, has a serious adverse effect on the quality of life of patients. However, epigenetic mechanisms involved in the development of osteoporosis remain unclear. There is accumulating evidence that epigenetic modifications may represent mechanisms underlying the links of genetic and environmental factors with increased risk of osteoporosis and bone fracture. Some RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been shown to be epigenetic regulators with significant involvement in the control of gene expression, affecting multiple biological processes, including bone metabolism. This review summarizes the results of recent studies on the mechanisms of miRNA-, lncRNA-, and circRNA-mediated osteoporosis associated with osteoblasts and osteoclasts. Deeper insights into the roles of these three classes of RNA in osteoporosis could provide unique opportunities for developing novel diagnostic and therapeutic approaches to this disease.

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