Meta-analysis of efficacy and safety of terlipatide and bisphosphate in the treatment of postmenopausal osteoporosis fractures / 中国组织工程研究

OBJECTIVE:To compare the efficacy and safety of terlipatide and bisphosphate in the treatment of postmenopausal osteoporosis fractures through a Meta-analysis. METHODS:By searching PubMed,Cochrane Library,EMbase,CNKI,WanFang and VIP databases,18 randomized controlled studies on terlipatide and bisphosphate in the treatment of postmenopausal osteoporosis fractures were included according to inclusion and exclusion criteria.Endnote X9 software was used to manage the literature and Revman 5.3 software was used to perform a Meta-analysis on the extracted data.The incidences of vertebral fracture,non-vertebral fracture and adverse reaction in postmenopausal osteoporosis patients treated with terlipatide and bisphosphate were analyzed. RESULTS:A total of 18 randomized controlled studies were included,of which 10 were of medium and high quality and 8 were of low quality.Meta-analysis results showed that the fracture incidence in the teriparatide group[risk ratio(RR)=0.56,95%confidence interval(CI):0.48-0.66,P＜0.000 01]was lower than that in the bisphosphonate group,and teriparatide was superior to alendronate in preventing fractures in postmenopausal women with osteoporosis(RR=0.50,95%CI:0.35-0.69,P＜0.000 1)and other bisphosphonates(RR=0.58,95%CI:0.49-0.70,P＜0.000 01).During the follow-up over 18 months,teriparatide was superior to bisphosphonates in preventing fractures in postmenopausal women with osteoporosis(RR=0.56,95%CI:0.48-0.69,P＜0.000 01).In addition,we found that teriparatide was superior to bisphosphonates in preventing vertebral fractures(RR=0.48,95%CI:0.37-0.62,P＜0.000 01)and non-vertebral fractures(RR=0.63,95%CI:0.51-0.78,P＜0.000 1)in postmenopausal women with osteoporosis.Teriparatide was superior to bisphosphonates in increasing lumbar bone density[odds ratio=4.16,95%CI:2.96-5.36,P＜0.000 1)and femoral neck bone density(odds ratio=1.02,95%CI:0.04-2.01,P=0.04).There was no significant difference in adverse reactions between teriparatide and bisphosphonates(RR=0.95,95%CI:0.85,1.06,P=0.37). CONCLUSION:Teriparatide is superior to bisphosphonates in preventing vertebral and non-vertebral fractures in postmenopausal women with osteoporosis,but the safety and adverse drug reactions of teriparatide and bisphosphonates are basically similar.Teriparatide is superior to bisphosphonate in preventing fracture and improving lumbar and femoral neck bone density regardless of short-term(＜18 months)or long-term(≥18 months)use.

Early Dental Failure and Medication-related Osteonecrosis of the Jaw in Patients Treated with Bisphosphonates:A Meta-analysis of Pro-portions / 医学研究杂志

Objective To assess the early dental failure rate and medication-related osteonecrosis of the jaw(MRONJ)incidence in patients treated with bisphosphonates(BPs),and provide evidence for evaluation of clinical risk.Methods Electronic databases,in-cluding Cochrane Library,Wiley Online Library,PubMed,CNKI and Wanfang Data were searched to collect clinical studies concerning early dental failure and medication-related osteonecrosis of the jaw in patients treated with bisphosphonates.The data were collected from inception until May 2022.The meta-analysis was conducted using Stata 15.Osoftware.Results A total of 13 clinical observational stud-ies involving 1261 implants,wherein 1182 implants were placed in patients who took bisphosphonate orally,and 79 implants were placed in patients treated with intravenous bisphosphonate.In patients who had orally administrated bisphosphonates,the pooled early dental fail-ure rate was 1.7％(95％CI:0.3％-3.9％),and the MRONJ incidence was 0.Among patients treated with intravenous bisphospho-nate,the pooled early dental failure rate was 0,and the MRONJ incidence was 5.6％.Conclusion The early dental failure rate and MRONJ incidence in patients who take bisphosphonates orally is as low as in a healthy population.On account of the relatively high risk of post-operative MRONJ in patients treated with intravenous bisphosphonates,clinical indications must be opted prudently.

Literature Review of Using Bisphosphonates in the Treatment of Calciphylaxis / 罕见病研究

Objective To analyze the effectiveness and safety of bisphosphonates in the treatment of patients with calcification defense. Methods PubMed, Embase databases, CNKI and Wanfang were searched to collect the case reports and clinical studies of bisphosphonates for calcification defense. Then, the relevant information of patients was extracted for statistical analysis. Results A total of 18 case reports were selected involving 20 patients. Thirteen patients (65.0%) were treated with pamidronate, four (20.0%) were treated with etidronate, two (10.0%) were treated with alendronate, and one (5.0%) was treated with zoledronic acid. Thirteen patients (65.0%) recovered completely, the recovery time of whom ranged from half month to nine months. The tolerance of bisphosphonates in most patients(90.0%)was good, while one patient who did not tolerate pamidronate recovered after the frequency of administration was adjusted and one patient with high dosage of etidronate returned to normal after the discontinuation of the usage. Conclusions Bisphosphonates, an inhibitor of bone resorption, is effective and safe in the treatment of patients with calcification defense.

Knowledge of Brazilian dentists about bisphosphonate-associated osteonecrosis of the jaw / Conhecimento de dentistas brasileiros sobre a osteonecrose dos maxilares associada ao uso de bisfosfonatos

Osteonecrosis of the jaw associated with bisphosphonate use is a matter of utmost importance in clinical practice for the safe treatment of patients using this medication. Objective: The aim of this study was to evaluate the level of knowledge of dentists who carry out clinical practice about bisphosphonate-associated jaw osteonecrosis. Material and Methods: The methodology used in the present research consisted of a non-probability sampling approach for the selection of participants. To conduct the study, a questionnaire created on the Google Forms platform was sent via Direct on Instagram to the professionals who agreed to participate. The data were sent for analysis, using the frequency for each response, and the professionals were divided into subcategories according to their time of professional practice. Results: Participants were familiar with the purpose of the medication (65%) or had heard of it (34%); regarding the professionals' opinion on their knowledge and practice about bisphosphonate-related osteonecrosis a significant percentage (93.24%) responded positively regarding the existence of side effects resulting from the therapeutic use of bisphosphonates and 48.65% self-evaluated their level of knowledge on the subject as insufficient. Conclusion: The study reveals that almost all participating dentists have good knowledge about the effects caused by bisphosphonates, but some of them still do not feel specifically confident about the management and knowledge of jaw osteonecrosis (AU)

A osteonecrose dos maxilares associada ao uso de bisfosfonatos é um assunto de suma importância na prática clínica para o atendimento seguro dos pacientes que fazem uso terapêutico do medicamento. Objetivo: O objetivo deste trabalho foi avaliar o nível de conhecimento de cirurgiões dentistas que realizam atendimento clínico acerca da osteonecrose dos maxilares associada ao uso dos bisfosfonatos. Material e Métodos: A metodologia utilizada na presente pesquisa consistiu em uma abordagem de amostragem não probabilística para a seleção dos participantes. Para conduzir o estudo, enviamos um questionário criado na plataforma Google Forms via Direct no Instagram para os profissionais que concordaram em participar. Os dados foram enviados para análise, usando a frequência para cada resposta, sendo que os profissionais foram divididos em subcategorias por tempo de formação. Resultados: Os participantes estavam familiarizados com a finalidade do medicamento (65%) ou já haviam ouvido falar deles (34%); em relação à opinião dos profissionais sobre seu conhecimento e prática acerca da osteonecrose relacionada aos bisfosfonatos, observou-se que 48,65% autoavaliaram seu nível de conhecimento sobre o assunto como insuficiente e uma parcela expressiva (93,24%) respondeu positivamente em relação à existência de efeitos colaterais decorrentes ao uso terapêutico dos bisfosfonatos. Conclusão: O estudo revela que quase todos os dentistas participantes possuem um bom conhecimento acerca dos efeitos causados pelos bisfosfonatos, mas que parte deles ainda não se sentem seguros especificamente em relação ao manejo e conhecimento da osteonecrose dos maxilares (AU)

Photodynamic therapy repairs medication-related osteonecrosis of the jaw by reducing NF-kB protein in rats

Abstract Objective To evaluate whether antimicrobial photodynamic therapy (aPDT) repairs bisphosphonate-related osteonecrosis of the jaw (BRONJ) modulated by the reduction of NF-kB protein in a murine model. Methodology Male Wistar rats (N=30) were divided into the following groups (n=6/group): negative control (NC); experimental osteonecrosis (ONE); ONE + photosensitizer (PS); ONE + photobiomodulation (PBM); and ONE + aPDT. Over 8 weeks, ONE was induced by zoledronic acid 250 µg/kg injections, except in the NC group, which received sterile 0.9% saline, followed by extraction of the lower left first molar. Red light laser irradiation (wavelength ~660 nm, power 50 mW, energy of 2 J, energy dose of 66.67 J/cm2 for 40 s) was performed once a week for 4 weeks. Methylene blue 0.3% was used as PS. The animals were euthanized and examined macroscopically for the presence of exposed bone and epithelial repair and microscopically by histochemical (hematoxylin-eosin and Masson's trichrome staining) and immunohistochemical (anti-NF-kB) methods. Macroscopic and histomorphometric data were analyzed by one-way ANOVA and Tukey's post-test (p<0.05). Results Mucosal repair, viable osteocytes, and NF-kB immunostaining were observed in the NC, ONE+PS, ONE+PBM, and ONE+aPDT groups. The ONE group showed no mucosal repair, showing empty lacunae and multifocal immunostaining for NF-kB. The ONE+PBM and ONE+aPDT groups had greater deposition of extracellular matrix and less necrotic bone tissue (p<0.05). Conclusion PBM and aPDT treatments for BRONJ were effective for bone and epithelial repair, in addition to reducing inflammation mediated by the decrease of NF-kB protein in the irradiated regions.

Influence of zoledronic acid and low-intensity laser on collagen fibers during the bone repair process

Purpose: To evaluate collagen fibers during the bone repair process in critical defects created in the tibias of rats, treated with zoledronic acid (AZ) associated with low-level laser therapy (LLLT). Methods: Ten rats were distributed according to treatment: group 1) saline solution; group 2) LLLT; group 3) AZ; group 4) AZ and LLLT. AZ was administered at the dose of 0.035 mg/kg at fortnightly intervals over eight weeks. Next, 2-mm bone defects were created in the tibias of all animals. The bone defects in groups 2 and 4 were irradiated LLLT in the immediate postoperative period. After periods 14 and 28 of application, the animals were euthanized, and birefringence analysis was performed. Results: Approximately 90% of the total area was occupied by collagen fibers within the red color spectrum, this area being statistically larger in relation to the area occupied by collagen fibers within the green and yellow spectrum, in the four groups. Over the 14-day period, there was no statistically significant difference between the groups. In the 28-day period, group 2 (14.02 ± 15.9%) was superior in quantifying green birefringent fibers compared to group 1 (3.06 ± 3.24%), with p = 0.009. Conclusions: LLLT associated with ZA is effective in stimulating the neoformation of collagen fibers. The LLLT group without the association with ZA showed a greater amount of immature and less organized matrix over a period of 28 days.

Impacto do uso sistêmico de estatinas e de bisfosfonatos nos tecidos periodontais: revisão narrativa / Impact of the systemic use of statins and bisphosphonates in the periodontal tissues: narrative review

Introdução: A literatura tem apontado uma possível relação entre diversas condições sistêmicas e as doenças periodontais. Dentro das doenças sistêmicas que podem gerar o uso crônico de medicamentos, com potencial associação com as doenças periodontais, destacam-se a hipercolesterolemia e o uso de estatinas; e as doenças do metabolismo ósseo e o uso de bisfosfonatos. Objetivo: Dessa maneira, o presente estudo objetivou revisar a literatura sobre o efeito das estatinas e dos bisfosfonatos nos parâmetros clínicos e radiográficos periodontais de indivíduos adultos. Resultados: Apenas estudos observacionais em humanos foram incluídos. Um estudo mostrou que, em pacientes que apresentam doença periodontal e usam estatina, houve 37% menos bolsas periodontais (profundidade de sondagem ≥4mm) quando comparadas aos que não utilizam a medicação, além de apresentarem menor índice de carga inflamatória e menor perda de inserção clínica. Em relação aos bisfosfonatos em indivíduos com doenças que envolvem o metabolismo ósseo, sugere-se que a utilização do fármaco tem obtido resultados positivos nos parâmetros periodontais, como menores sinais clínicos de inflamação gengival, menor profundidade de sondagem, menor perda de inserção clínica e maior nível de osso alveolar, quando comparados aos que nunca realizam essa terapia. Conclusão: Dessa forma, as estatinas e os bisfosfonatos apresentam efeitos promissores, em pacientes sob tratamento para suas respectivas condições sistêmicas, na melhoria dos parâmetros periodontais, porém é importante salientar que são necessários mais estudos sobre o assunto para melhor entender os reais efeitos a longo prazo do uso desses fármacos.(AU)

Introduction: The literature showed a possible relationship between several systemic conditions and periodontal diseases. Within the systemic diseases that can generate the chronic use of these drugs, potentially related with periodontal diseases, it may be cited the hypercholesterolemia and the use of statins; and bone metabolism diseases and the use of bisphosphonates. Objective: In this sense, the present study aimed to review the literature about the effect of statins and bisphosphonates in the periodontal parameters of adults individuals. Results: Only observational studies in humans were included. A study showed that, in patients with periodontal disease and users of statins, there 37% fewer periodontal pockets (probing depth ≥4mm) when compared to those who do not use the medication, as well as having a lower rate of inflammatory burden and less loss of clinical insertion. Regarding the bisphosphonates in individuals diagnosed with diseases involving bone metabolism, it was suggested that the use of the drug has obtained positive results in periodontal parameters, such as a greater absence of plaque, less clinical signs of gingival inflammation, less probing depth, lower level of clinical insertion and higher level of alveolar bone when compared to those who never undergo this therapy. Conclusion: Thus, statins and bisphosphonates have promising effects in patients under treatment for their respective systemic condition in improving periodontal parameters, but it is important to emphasize that further studies on the subject are needed to better understand the long-term effects of the use of these drugs.(AU)

Descriptive assessment of 54 cases with complex regional pain syndrome in lower limbs / Evaluación descriptiva de 54 casos con síndrome dolo roso regional complejo en miembros inferiores

Abstract Introduction: Complex regional pain syndrome (CRPS), also known as Sudeck syndrome, is a chronic painful condition usually affecting the limbs after trauma or surgery. Its presentation is heterogeneous and its physio pathology, diagnosis and treatment remain controversial. The objective of this study was to analyze a group of patients with this rare syndrome, describing in detail the results of the dual energy X-ray absorptiometry (DXA) and the response to bisphosphonate treatment. Method: We retrospectively analyzed 54 patients with CRPS, taking into account their demographic features, inciting events and diagnostic tests. As regards treat ment, we analyzed the results and adverse events of the use of bisphosphonates Results: We found a female predominance (74%), with 55 ± 13 years. The most common inciting event was trauma (59%), followed by surgery. The difference in bone mineral density between the affected limb and the healthy one was 12 to 15%. Forty-four patients were treated with bisphosphonates (pamidronate, iban dronate, zoledronic acid) and showed a clinical im provement, mainly in terms of pain intensity. Only six patients presented with adverse events, like pseudoflu syndrome and acute phase symptoms. Conclusion: In our cohort, lower limbs CRPS pre dominantly affects middle aged women. DXA scans are tests used to quantify bone loss and the response to treatment. The use of bisphosphonates is an interest ing therapeutic option to improve clinical symptoms in most patients. Future prospective randomized studies will be needed to confirm our results.

Resumen Introducción: El síndrome doloroso regional complejo (SDRC), también conocido como síndrome de Sudeck, es una enfermedad dolorosa crónica que generalmente afecta a las extremidades luego de un trauma o cirugía. Su presentación es heterogénea y existen controversias sobre su fisiopatología, adecuado diagnóstico y trata miento. El objetivo de este trabajo es describir un grupo de pacientes con SDRC en miembros inferiores, describi endo los resultados de la densitometría mineral ósea (DMO) y la respuesta al tratamiento con bifosfonatos. Método: Analizamos retrospectivamente 54 pacientes con SDRC, teniendo en cuenta características demográ ficas, factores desencadenantes y estudios diagnósticos. En relación al tratamiento, analizamos los resultados y efectos adversos del uso de bifosfonatos. Resultados: Encontramos un predominio femenino (74%), con una edad de 55 ± 13 años. Los factores des encadenantes más comunes fueron los traumatismos (59%) y la cirugía. La diferencia de densidad mineral ósea entre el miembro comprometido y el sano fue 12 a 15%. En los 44 pacientes fueron tratados con bifosfona tos (pamidronato, ibandronato y ácido zoledrónico), su uso se asoció a mejoría clínica, especialmente del dolor. Seis pacientes tuvieron efectos adversos como sindrome pseudogripal y síntomas de fase aguda. Conclusión: En nuestra población, el SDRC de miem bros inferiores predomina en mujeres de edad media. La DMO es un método que permite cuantificar la pérdida ósea y la respuesta al tratamiento. Los bifosfonatos son una buena opción terapéutica para el control de síntomas. Son necesarios futuros estudios de naturaleza prospectiva y aleatorizada para confirmar nuestros resultados.

Osteonecrose dos maxilares associada ao uso de bifosfonatos: uma revisão de literatura / Osteonecrosis of the jaws associated with the use of bisphosphonates: a literature review

Este trabalho tem como objetivo apresentar aos profissionais de odontologia, através de uma revisão de literatura, os principais aspectos da osteonecrose dos maxilares associada ao uso de bifosfonatos, bem como a importância da prevenção e as principais alternativas de tratamento. Foi realizada uma busca por artigos científicos publicados nos anos de 2003 a 2022, nas bases de dados Scientific Electronic Library Online (SciELO), US National Library of Medicine (Pubmed) e Google Scholar. Foram coletados artigos em inglês e português. As palavras-chave, escolhidas com base nos Descritores em Ciências da Saúde (DeCS) foram "Osteonecrose da Arcada Osseodentária Associada a Difosfonatos" e "Bisphosphonate-Associated Osteonecrosis of the Jaw". Embora seja raro, os pacientes submetidos a terapia prolongada com bifosfonatos correm grande risco de desenvolver osteonecrose, principalmente quando não há prevenção. O tratamento preventivo, o controle das condições bucais, e a atuação de uma equipe multidisciplinar é imprescindível para minimizar os riscos de OMB.

This article aims to present to dental professionals, through a literature review, the main aspects of osteonecrosis of the jaws associated with the use of bisphosphonates, as well as the importance of prevention and the main treatment alternatives. A search was carried out for scientific articles published between 2003 and 2022, in the Scientific Electronic Library Online (SciELO), US National Library of Medicine (Pubmed) and Google Scholar databases. Articles in English and Portuguese were collected. The keywords, chosen based on Health Sciences Descriptors (DeCS) were "Osteonecrosis of the Dental Arch Associated with Diphosphonates" and "Bisphosphonate-Associated Osteonecrosis of the Jaw". Although it is rare, patients undergoing prolonged therapy with bisphosphonates are at high risk of developing osteonecrosis, especially when there is no prevention. Preventive treatment, control of oral conditions, and the performance of a multidisciplinary team are essential to minimize the risks of OMB.

O uso de bisfosfonatos causa implicações na movimentação dentária ortodôntica? / Does the use of biophosphonates cause implications on the orthodontic tooth movement?

Bisfosfonatos são medicamentos que reduzem a reabsorção óssea, inibindo a atividade enzimática dos osteoclastos. Por essa razão, são amplamente utilizados no tratamento de várias doenças, como a osteoporose. Durante o tratamento ortodôntico, a aplicação de forças compressivas no dente promove a reabsorção e remodelação óssea, permitindo sua movimentação. Vários estudos in vivo observaram a diminuição da movimentação ortodôntica por bisfosfonatos, tornando o tema relevante devido à crescente demanda de tratamento ortodôntico em idosos ­ principais usuários dessa droga. Assim sendo, o objetivo deste trabalho é avaliar evidências do uso de bisfosfonatos no decorrer do tratamento ortodôntico e, mais especificamente, examinar seus efeitos na movimentação ortodôntica através de mensurações clínico-laboratoriais. Para isso, foi realizada uma revisão sistematizada na base de dados Pubmed através dos descritores Ortodontia e Bisfosfonatos. Buscou-se estudos em inglês entre 2015 e 2020. De 39 artigos compatíveis à proposta, 8 artigos passaram pelos critérios de inclusão e exclusão. Desses, a maioria dos autores é categórica em se referir ao uso de bisfosfonatos como um fator relevante para índices inferiores de movimentação. Porém, tais dados devem ser vistos com cautela, pois os métodos utilizados são variados, havendo uma grande heterogeneidade. Ademais, pequenas amostras e tempo curto dos experimentos não permitem uma generalização para pacientes de rotina. Como conclusão temos que a administração de bisfosfonatos associada à movimentação ortodôntica aparenta provocar uma duração prolongada no tratamento devido, fundamentalmente, aos índices inferiores de movimentação dentária planejada. Entretanto, os fatores específicos para tal não estão plenamente explicados.

Bisphosphonates are drugs that provide bone resorption by inhibiting the enzyme activity of osteoclasts. For this reason, they are widely used in the treatment of various diseases, such as osteoporosis. During orthodontic treatment, the application of compressive forces on the tooth promotes bone resorption and remodeling, allowing its movement. Several in vivo studies observed a decrease in orthodontic movement caused by bisphosphonates, making the topic relevant due to the growing demand for orthodontic treatment in the elderly - the main users of this drug. Therefore, the aim of this study is to evaluate evidence of the use of bisphosphonates during orthodontic treatment and, more specifically, to examine their effects on orthodontic movement through clinical and laboratory measurements. For this, a systematized review was performed in the Pubmed database using the descriptors Orthodontics and Bisphosphonates. Studies in English between 2015 and 2020 were sought. Of 39 articles compatible with the proposal, 8 articles passed the inclusion and exclusion criteria. Most authors are categorical in referring to the use of bisphosphonates as a relevant factor for lower movement rates. However, such data must be viewed with caution, as the methods used are sundry, with great heterogeneity. Furthermore, small administrations and short experimental times do not allow generalization to routine patients. In conclusion, the administration of bisphosphonates associated with orthodontic movement seems to cause a prolonged duration of treatment, fundamentally due to the lower rates of planned tooth movement. However, the specific factors for this are not fully explained.

Persistent bilateral atypical femoral fractures in an antiresorptive-naïve Singaporean Chinese patient with Graves’ Disease / Journal of the ASEAN Federation of Endocrine Societies

@#Atypical femoral fractures (AFFs) are rare adverse effects of bisphosphonate therapy. We report an unusual case of bilateral diaphyseal AFFs in an antiresorptive-naïve Singaporean Chinese female with Graves’ disease. She presented with complete right AFF requiring surgical fixation, and persistent left incomplete AFF for over four years. Femoral bowing, varus femoral geometry, and ethnic influence likely contributed to the AFFs’ formation. This case may provide insights into the pathogenesis of AFFs in high-risk Asian populations.

Osteonecrosis of the jaw induced by arsenic trioxide therapy in acute promyelocytic leukemia patient: a case report and literature review / 口腔疾病防治

Objective @#To investigate the etiology, clinical manifestations, treatment and prevention of jaw necrosis caused by arsenic trioxide to provide a reference for clinical diagnosis and treatment. @*Methods@#To analyze the clinical data and related literature of patients with jaw necrosis caused by acute promyelocytic leukemia treated with arsenic trioxide@*Results@#We report a case of jaw necrosis caused by the use of arsenic trioxide (10 mg once a day for one month) during the treatment of acute promyelocytic leukemia. About 20 days after treatment, the patient developed right maxillary pain accompanied by gingival redness and swelling and mucosal ulcer, 14-17 teeth had buccal and palatal alveolar bone exposed, gingival mucosa was missing, gingival tissue was damaged to the bottom of vestibular groove, and palatal soft tissue was damaged to 5-8 mm of palatal suture. Due to the unstable condition of acute promyelocytic leukemia, the patient was given conservative treatment such as oral vitamin and Kangfuxin liquid gargle to keep his mouth clean. Drug induced jaw necrosis reported in the literature can be caused by bisphosphonates. Arsenic trioxide can also cause local jaw necrosis. Clinically, it is often manifested as long-term wound nonunion, pus, alveolar bone or jaw bone exposure, dead bone formation, accompanied by pain, loose teeth, facial swelling and other symptoms. Anti inflammation, debridement and surgical removal of dead bone are commonly used treatment methods.@*Conclusion @# In clinical practice, we should be alert to drug-induced jaw necrosis and strengthen prevention.

Efficacy and safety of denosumab versus bisphosphonates in the treatment of osteoporosis：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of denosumab versus bisphosphonates in the treatment of osteoporosis， and to provide evidence-based reference for clinical treatment. METHODS Randomized controlled trials （RCTs） about denosumab （trial group） versus bisphosphonates （control group） in the treatment of osteoporosis were retrieved from PubMed， Embase， Medline， the Cochrane Library， Chinese Journal Fulltext Database， Chinese Science and Technology Journal Database， Wanfang database from January 2012 to December 2022. After the data extraction of included clinical studies， the quality of included studies was evaluated with Cochrane Handbook for Systematic Review 5.1.0， and meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 6 RCTs were included， involving 3 145 patients. Meta-analysis showed that the improvement rate of lumbar bone mineral density （BMD） [MD＝1.78， 95%CI（1.13， 2.43）， P＜0.000 01]， femoral neck BMD [MD＝1.26， 95%CI （1.08， 1.45）， P＜0.000 01] and total hip BMD [MD＝1.16，95%CI（0.93，1.39），P＜0.000 01] in trial group were significantly better than control group. C-terminal telopeptide of type Ⅰ collagen after 6 months [MD＝－0.09， 95%CI （－0.16， －0.02）， P＝0.01] and N-terminal propeptide of type Ⅰ collagen after 12 months [MD＝－9.07， 95%CI （－11.22， －6.92）， P＜ 0.001] in trial group were significantly higher than control group. There was no statistical difference in the fracture incidence rate after 12 months [OR＝1.02， 95%CI （0.67，1.54）， P＝0.92] and the incidence of adverse reaction [OR＝0.99， 95%CI （0.67，1.46）， P＝0.97] between 2 groups. CONCLUSIONS Denosumab has more advantages in improving BMD and bone metabolism， compared with bisphosphonates.

Evaluation of trabecular bone changes according to the type of prosthesis in patients using bisphosphonates: a retrospective study

Abstract The objective of the study was to retrospectively compare the fractal size values calculated in the trabecular bone according to the type of complete removable denture, removable partial denture, and partial fixed prosthesis between patients using bisphosphonates and healthy patients, retrospectively. Panoramic radiographs of a total of 200 patients, (100 using bisphosphonates,100 control group), were taken from the right and left molar regions before and after treatment with 72 × 72 pixels. The fractal dimension (FD) was computed by using ImageJ Software using the box-counting method on the images obtained. There was an interaction effect between the trabecular bone change-patient group-the type of prosthesis used and the parameters of the area (p < 0.05). In patients using complete removable dentures and removable partial dentures in the maxilla and mandibula in the molar region, a greater decrease in FD values was observed in the control group than in the patient group using bisphosphonates. An increase in FD values over time was observed in the patient group using bisphosphonates with partial fixed maxillary and mandibular prostheses compared to the control group. Partial fixed prostheses should be preferred primarily instead of complete removable or removable partial dentures in patients using bisphosphonates to prevent osteonecrosis due to dental trauma.

Estudo in vivo do efeito da ozonioterapia como prevenção e/ou tratamento da osteonecrose dos maxilares induzida por medicamentos / In vivo study of the effect of ozone therapy as a prevention and/or treatment of druginduced osteonecrosis of the jaws

O ozônio tem sido utilizado no processo de reparo ósseo em condições desfavoráveis, como na osteonecrose dos maxilares induzida por medicamentos (OMIM). O objetivo deste trabalho foi avaliar a aplicação de ozonioterapia como prevenção e/ou o tratamento da OMIM. Cento e vinte ratos wistar foram distribuídos entre os grupos tratamentos: eles foram induzidos com Zoledronato e receberam ozonioterapia antes da exodontia (prevenção ­ GOP), após exodontia (tratamento ­ GOT), em ambos momentos (prevenção e tratamento ­ GOPT), um grupo não recebeu ozônio (ZOL), e outro recebeu soro fisiológico ao invés da indução (SAL). Após 14 e 28 dias pós-operatórios foram eutanasiados e as peças submetidas as análises histológicas com eosina e hematoxilina, imunoistoquímica, microtomográfica computadorizada (microCT), confocal a LASER e histomorfométrica. Em 14 dias observamos o início do reparo em GOT, assim como um epitélio presente em SAL e GOT, o mesmo ocorre em 28 dias, e uma intensa imunomarcação de osteocalcina (OC) em GOPT em 14 dias. A microCT demostrou maiores médias de BV/TV em todos grupos quando comparados a ZOL (p< 0,05), seguido pelo grupo SAL (66,039±28,379) e ZOL (60,856±28,425). Diante dos resultados pode-se observar que a ozonioterapia pode modular o reparo alveolar em animais induzidos com ácido zoledrônico(AU)

Ozone has been used in the bone repair process under unfavorable conditions, such as in druginduced osteonecrosis of the jaws (OMIM). The objective of this work was to evaluate the application of ozone therapy as prevention and/or treatment of OMIM. One hundred and twenty wistar rats were distributed among treatment groups: they were induced with Zoledronate and received ozone therapy before tooth extraction (prevention - GOP), after tooth extraction (treatment - GOT), at both times (prevention and treatment - GOPT), one group I did not receive ozone (ZOL), and another received saline instead of induction (SAL). After 14 and 28 days postoperatively, they were euthanized and the pieces submitted to histological analysis with eosin and hematoxylin, immunohistochemistry, computed microtomography (microCT), confocal LASER and histomorphometric analysis. In 14 days we observed the beginning of repair in GOT, as well as an epithelium present in SAL and GOT, the same occurs in 28 days, with intense immunostaining of osteocalcin (OC) in GOPT in 14 days. The microCT showed higher BV/TV means in all groups when compared to the ZOL (p< 0.05), followed by the SAL group (66.039±28.379) and ZOL (60.856±28.425). In view of the results, it can be observed that ozone therapy can modulate alveolar repair in animals induced with zoledronic acid(AU)

Estudo in vivo do efeito da ozonioterapia como prevenção e/ou tratamento da osteonecrose dos maxilares induzida por medicamentos / In vivo study of the effect of ozone therapy as a prevention and/or treatment of druginduced osteonecrosis of the jaws

O ozônio tem sido utilizado no processo de reparo ósseo em condições desfavoráveis, como na osteonecrose dos maxilares induzida por medicamentos (OMIM). O objetivo deste trabalho foi avaliar a aplicação de ozonioterapia como prevenção e/ou o tratamento da OMIM. Cento e vinte ratos wistar foram distribuídos entre os grupos tratamentos: eles foram induzidos com Zoledronato e receberam ozonioterapia antes da exodontia (prevenção ­ GOP), após exodontia (tratamento ­ GOT), em ambos momentos (prevenção e tratamento ­ GOPT), um grupo não recebeu ozônio (ZOL), e outro recebeu soro fisiológico ao invés da indução (SAL). Após 14 e 28 dias pós-operatórios foram eutanasiados e as peças submetidas as análises histológicas com eosina e hematoxilina, imunoistoquímica, microtomográfica computadorizada (microCT), confocal a LASER e histomorfométrica. Em 14 dias observamos o início do reparo em GOT, assim como um epitélio presente em SAL e GOT, o mesmo ocorre em 28 dias, e uma intensa imunomarcação de osteocalcina (OC) em GOPT em 14 dias. A microCT demostrou maiores médias de BV/TV em todos grupos quando comparados a ZOL (p< 0,001), ZOL apresentou maior porosidade (p=0,03) e o espaçamento trabecular foi maior no grupo GOT quando comparado ao GOP (p< 0,05). A taxa de aposição mineral (MAR) dos grupos GOP foram maiores (21,46±14,12), seguida do grupo GOT (19,66± 13,23). GOT apresentou a maior média de %NBA (68,322±25,296), quando comparado ao grupo ZOL (p < 0,05), seguido pelo grupo SAL (66,039±28,379) e ZOL (60,856±28,425). Diante dos resultados pode-se observar que a ozonioterapia pode modular o reparo alveolar em animais induzidos com ácido zoledrônico(AU)

Ozone has been used in the bone repair process under unfavorable conditions, such as in druginduced osteonecrosis of the jaws (OMIM). The objective of this work was to evaluate the application of ozone therapy as prevention and/or treatment of OMIM. One hundred and twenty wistar rats were distributed among treatment groups: they were induced with Zoledronate and received ozone therapy before tooth extraction (prevention - GOP), after tooth extraction (treatment - GOT), at both times (prevention and treatment - GOPT), one group I did not receive ozone (ZOL), and another received saline instead of induction (SAL). After 14 and 28 days postoperatively, they were euthanized and the pieces submitted to histological analysis with eosin and hematoxylin, immunohistochemistry, computed microtomography (microCT), confocal LASER and histomorphometric analysis. In 14 days we observed the beginning of repair in GOT, as well as an epithelium present in SAL and GOT, the same occurs in 28 days, with intense immunostaining of osteocalcin (OC) in GOPT in 14 days. The microCT showed higher BV/TV means in all groups when compared to the ZOL (p< 0.001), ZOL showed greater porosity (p=0.03) and the trabecular spacing was greater in the GOT group when compared to the GOP (p< 0 .05). The mineral apposition rate (MAR) of the GOP groups were higher (21,46±14,12), followed by the GOT group (19,66± 13,23). GOT had the highest average of %NBA (68.322±25.296), when compared to the ZOL group (p < 0.05), followed by the SAL group (66.039±28.379) and ZOL (60.856±28.425). In view of the results, it can be observed that ozone therapy can modulate alveolar repair in animals induced with zoledronic acid(AU)

Risk factors for medication-related osteonecrosis of the jaw and salivary IL-6 IN cancer patients / Fatores de risco para osteonecrose dos maxilares relacionada à medicação e níveis salivares de IL-6 em pacientes com câncer

Abstract Introduction Medication-related osteonecrosis of the jaws is a severe complication of the use of antiresorptive and antiangiogenic therapy, with limited treatment options and great impact on patient's quality pf life. Objective The aim of this study was to assess the risk factors associated with medication-related osteonecrosis of the jaws in oncologic patients undergoing bisphosphonate treatment. In addition, salivary levels of interleukin-6, IL-6, were measured to investigate their association with severity and risk of medication-related osteonecrosis of the jaws. Methods Case-control study with 74 patients with bone metastases from solid tumors and multiple myeloma was included. Patients were divided into three groups: 1) those undergoing bisphosphonate treatment with medication-related osteonecrosis of the jaws; 2) those undergoing bisphosphonate without medication-related osteonecrosis of the jaws; and 3) those with bisphosphonate pretreatment. The demographic and medical data of the patients were collected to assess risk. The clinical evaluation was performed to diagnose medication-related osteonecrosis of the jaws and unstimulated saliva was collected for quantification of IL-6. Results As result, it was observed that patients diagnosed with medication-related osteonecrosis of the jaws were submitted to higher number of bisphosphonate doses (p= 0.001) and monthly infusion protocol (p= 0.044; OR = 7.75). Patients who did not have routine followup with specialized dentists during therapy with bisphosphonate and smoking were associated with medication-related osteonecrosis of the jaws (p= 0.019; OR = 8.25 and p= 0.031; OR = 9.37 respectively). Group 1 had a higher frequency of treatment with chemotherapy and corticosteroids concomitant with bisphosphonate, and surgical dental procedures (p= 0.129). Salivary IL-6 levels showed no statistically significant difference between the groups (p= 0.571) or association with medication-related osteonecrosis of the jaws severity (p= 0.923). Conclusion A higher number of bisphosphonate cycles, monthly infusion protocol, no dental follow-up for oral health maintenance and smoking were associated with medication-related osteonecrosis of the jaws. Specialized dental follow up during bisphosphonate treatment has been shown to be an important factor in preventing this complication.

Resumo Introdução A osteonecrose dos maxilares relacionada à medicação é uma complicação grave da terapia antirreabsortiva e antiangiogênica, com opção de tratamento limitada e grande impacto na qualidade de vida do paciente. Objetivo Avaliar os fatores de risco associados à osteonecrose dos maxilares relacionada à medicação em pacientes oncológicos em tratamento com bifosfonato Além disso, os níveis salivares de interleucina-6 (IL-6) foram medidos para investigar sua associação com a gravidade e o risco de osteonecrose dos maxilares relacionada à medicação. Método Estudo caso-controle com 74 pacientes com metástases ósseas de tumores sólidos e mieloma múltiplo. Os pacientes foram divididos em três grupos: 1) em tratamento por bifosfonato com osteonecrose dos maxilares relacionada à medicação; 2) submetidos ao bifosfonato sem osteonecrose dos maxilares relacionada à medicação; e 3) pré-tratamento de bifosfonato. Os dados demográficos e médicos dos pacientes foram coletados para avaliar o risco. A avaliação clínica foi feita para diagnosticar osteonecrose dos maxilares relacionada à medicação e a saliva não estimulada foi coletada para quantificação da IL-6. Resultados Observou-se que os pacientes diagnosticados com osteonecrose dos maxilares relacionada à medicação foram submetidos a maior número de doses de bifosfonato (p = 0,001) e protocolo de infusão mensal (p = 0,044; OR = 7,75). Pacientes que não tiveram acompanhamento de rotina com dentistas especializados durante a terapia com bifosfonato e tabagismo foram associados ao osteonecrose dos maxilares relacionada à medicação (p = 0,019; OR = 8,25 e p = 0,031; OR = 9,37, respectivamente). O grupo 1 apresentou maior frequência de tratamento com quimioterapia e corticosteroides concomitantes ao bifosfonato e procedimentos odontológicos cirúrgicos (p = 0,129). Os níveis salivares de IL-6 não apresentaram diferença estatisticamente significante entre os grupos (p = 0,571) ou associação com a gravidade do osteonecrose dos maxilares relacionada à medicação (p = 0,923). Conclusão Maior número de ciclos de bifosfonato, protocolo de infusão mensal, ausência de acompanhamento odontológico para manutenção da saúde bucal e tabagismo foram associados ao osteonecrose dos maxilares relacionada à medicação. O acompanhamento odontológico especializado durante o tratamento demonstrou ser importante na prevenção dessa complicação.

Clinical features, diagnostic evaluation and responses to treatment in Paget's disease of bone in a center specialized in bone metabolism / Características clínicas, evaluación diagnóstica y respuestas al tratamiento de la enfermedad de Paget ósea en un centro especializado en metabolismo óseo

Abstract The epidemiology of Paget's disease of bone (PDB) has changed in the last years but there is no update data on its clinical presentation, diagnosis and management in Latin America. Our aim was to describe its clinical features, diagnostic evaluation and responses to treatment in a group of PDB patients treated between June 2012 and December 2019 in an institution specialized in bone diseases, in Buenos Aires, Argentina. The frequency of PDB (180/10 714) was 1.68%. Median age was 67 (range 39-97) years and 59.5% were women. Most patients were asymptomatic (58.6%) and had monostotic disease (54.3%). Favorable responses were obtained in all patients who were treated with zoledronate (n = 36), in 10 out of 14 treated with pamidronate, in 9 out of 10 who received intravenous ibandronate and in 12 out of 13 who received oral bisphosphonates. The response rates were not significantly different when we compared monostotic vs. polyostotic disease. Among the biochemical parameters, mean values of bone specific and total alkaline phosphatase, and C-terminal cross-linked telopeptide of type I collagen decreased significantly after treatment with bisphosphonates. It seems that our results reflect the change in PDB epidemiology towards a more indolent disease. In the future, this would probably allow physicians to use lower doses of bisphosphonates than the ones historically recommended for these patients.

Resumen La epidemiología de la en fermedad de Paget ósea (EPO) ha cambiado en los últimos años. Son necesarios datos actualizados sobre su forma de presentación clínica, diagnóstico y tratamiento en nuestra región. Nuestro objetivo fue describir las características clínicas, evaluación diagnóstica y respuestas al tratamiento de un grupo de pacientes con EPO en un centro especializado en salud ósea de Buenos Aires, Argentina. Se evaluaron todos los pacientes que fueron atendidos en nuestra institución por enfermedades óseas entre junio de 2012 y diciembre de 2019. La frecuencia de EPO (180/10 714) fue de 1.68%. La mediana de edad fue de 67 (rango 39-97) años. El 59.5% eran mujeres. La mayoría se encontraba asintomático (58.6%) y tenían enfermedad monostótica (54.3%). Se objetivaron respuestas favorables en todos los que recibieron zoledronato (n = 36), en 10 de 14 pacientes que recibieron pamidronato, en 9 de 10 que utilizaron ibandronato endovenoso y en 12 de 13 con bifosfonatos orales. Los porcentajes de respuesta no variaron significativamente entre pacientes con formas monostóticas y poliostóticas. Entre los parámetros bioquímicos, los valores de fosfatasa alcalina total y ósea y de β cross-laps disminuyeron significativamente luego del tratamiento con bifosfonatos. Nuestros resultados reflejarían un cambio en la epidemiología de la EPO hacia una forma de presentación más indolente. Esto permitiría probablemente el uso de dosis más bajas de bifosfonatos que las históricamente recomendadas para estos pacientes.

Osteonecrosis mandibular: hallazgos clínicos e imagenológicos en un paciente tratado con denosumab / Mandibular osteonecrosis: clinical and imaging findings in a patient treated with denosumab

Introducción: La administración de bifosfonatos y medicamentos antiangiogénicos en pacientes con cáncer es un esquema terapéutico usual en oncología. Existen reportes de osteonecrosis de los maxilares en pacientes sometidos a este esquema de tratamiento, luego de realizar un procedimiento dental invasivo. Objetivo: A partir de las características clínicas e imagenológicas de la patología, ilustrar al odontólogo sobre los medicamentos para el tratamiento del cáncer, susceptibles de generar osteonecrosis de los maxilares. Presentación de caso: Paciente masculino de 89 años, con cáncer de próstata tratado con denosumab, que desarrolló osteonecrosis del maxilar inferior posterior a una extracción dental. Es de vital importancia que el odontólogo identifique los medicamentos, factores de riesgo y las medidas para minimizar el riesgo de osteonecrosis de los maxilares en pacientes susceptibles(AU)

Introduction: The administration of bisphosphonates and antiangiogenic drugs in cancer patients is a usual therapeutic scheme in oncology. There are reports of osteonecrosis of the jaws in patients undergoing this treatment scheme, after performing an invasive dental procedure. Objective: Show the dentist from the clinical and imaging characteristics of the pathology on the drugs for the treatment of cancer sensitivity to generate osteonecrosis of the jaws. Case presentation: An 89-year-old male patient with prostate cancer treated with denosumab developed osteonecrosis of the lower jaw after tooth extraction. It is vitally important that the dentist identifies medications, risk factors and measures to minimize the risk of osteonecrosis of the jaws in sensitivy patients(AU)

Osteonecrosis de los Maxilares, Puesta al Día

RESUMEN: La osteonecrosis también conocida como una necrosis avascular del hueso, es una condición degenerativa producida por la pérdida en la irrigación sanguínea, debido a la toxicidad directa en los tejidos óseos provocadas por quimioterapia, radioterapia, daño térmico, fumar y en la última década con la aparición de medicamentos como los bifosfonatos (BF), denosumab y medicamentos antigiogénicos, con los cuales hemos ido conociendo más sobre esta patología. La principal hipótesis de la fisiopatología de esta enfermedad es la inhibición de la angiogénesis, pero también se considera como hipótesis la toxicidad de los tejidos blandos o la disfunción adquirida de la inmunidad. En el año 2003 fue relatada por primera vez la relación entre BF y osteonecrosis maxilar (ONM). Ese mismo año fue descrito que pacientes con mieloma múltiple que recibían pamidronato podrían desarrollar necrosis avascular de los maxilares. Otras publicaciones informaban sobre pacientes que requerían tratamiento para necrosis ósea intra-oral de ocurrencia espontánea después de extracciones dentales o trauma oral. La primera denominación a esta patología fue (BRONJ) por sus siglas en inglés, se refería a ONM relacionada a BF. En 2014 la Asociación Americana de Cirujanos Orales y Maxilofaciales (AAOMS) publicó una nueva definición (position paper) renombrándolo como MRONJ (osteonecrosis de los maxilares relacionada a medicamentos) ONMRM. El rol en la identificación de pacientes con riesgo de ONMRM es fundamental. Los estudios han demostrado que el riesgo de desarrollar la afección se puede reducir sustancialmente si los pacientes son evaluados por un profesional dental y se toman medidas preventivas. La presente revisión narrativa realiza un recorrido desde la historia, los medicamentos involucrados, y diferentes estrategias de tratamientos propuestos, haciendo hincapié en la conducta que debemos seguir los cirujanos dentistas para enfrentar estos casos de forma temprana y prevenir su evolución.

ABSTRACT: Osteonecrosis is also known as avascular necrosis of the bone, it is a degenerative condition produced by the loss of blood flow, due to direct toxicity in the bone tissues caused by chemotherapy, radiotherapy, thermal damage, smoking and in the last decade with the arrival of drugs such as bisphosphonates (BP), denosumab and antigiogenic drugs we have been learning more about this pathology. The main hypothesis of the pathophysiology of this disease is the inhibition of angiogenesis, but soft tissue toxicity or acquired immunity dysfunction are also considered as hypotheses. In 2003, the relationship between BP and osteonecrosis of the jaws (ONJ) was reported for the first time. In the same year it was described that multiple myeloma patients receiving pamidronate could develop avascular necrosis of the jaws. Other publications reported about patients requiring treatment for spontaneously intra-oral bone necrosis after dental extractions or oral trauma. The first name for this pathology was (BRONJ) for its English acronym, it referred to ONJ related to BF. In 2014 the American Association of Oral and Maxillofacial Surgeons (AAOMS) published a new definition (position paper) renaming it MRONJ (drug-related osteonecrosis of the jaws) ONMRM. The role of identifying patients at risk of ONMRM is fundamental. Studies have shown that the risk of developing the condition can be substantially reduced if patients are evaluated by a dental professional and preventive measures are taken Exposure of bone or fistula that can be probed down to the bone in the maxillofacial region that persists for more than 8 weeks, with these conditions it is considered that there is a diagnosis of ONMRM This narrative review takes a journey from history, the drugs involved, and different proposed treatment strategies, emphasizing the behavior that dental surgeons must follow to face these cases early and prevent their evolution.