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Article in English | WPRIM | ID: wpr-929144


Bacterial infection is a common finding in patients, who develop medication-related osteonecrosis of the jaw (MRONJ) by the long-term and/or high-dose use of anti-resorptive agents such as bisphosphonate (BPs). However, pathological role of bacteria in MRONJ development at the early stage remains controversial. Here, we demonstrated that commensal microbiota protects against MRONJ development in the pulp-exposed periapical periodontitis mouse model. C57/BL6 female mice were treated with intragastric broad-spectrum antibiotics for 1 week. Zoledronic acid (ZOL) through intravenous injection and antibiotics in drinking water were administered for throughout the experiment. Pulp was exposed on the left maxillary first molar, then the mice were left for 5 weeks after which bilateral maxillary first molar was extracted and mice were left for additional 3 weeks to heal. All mice were harvested, and cecum, maxilla, and femurs were collected. ONJ development was assessed using μCT and histologic analyses. When antibiotic was treated in mice, these mice had no weight changes, but developed significantly enlarged ceca compared to the control group (CTL mice). Periapical bone resorption prior to the tooth extraction was similarly prevented when treated with antibiotics, which was confirmed by decreased osteoclasts and inflammation. ZOL treatment with pulp exposure significantly increased bone necrosis as determined by empty lacunae and necrotic bone amount. Furthermore, antibiotics treatment could further exacerbate bone necrosis, with increased osteoclast number. Our findings suggest that the commensal microbiome may play protective role, rather than pathological role, in the early stages of MRONJ development.

Animals , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Bone Density Conservation Agents , Diphosphonates , Female , Humans , Mice , Microbiota , Periapical Diseases , Zoledronic Acid
Rev. cuba. med ; 60(1): e1354, tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1156553


Introducción: El ácido zoledrónico mejora la calidad de vida en pacientes con metástasis óseas por cáncer prostático. Objetivo: Evaluar la calidad de vida relacionada con la salud con el cuestionario EORTC QLQ-BM22 en pacientes con metástasis óseas por cáncer prostático tratados con ácido zoledrónico. Métodos: Se realizó un estudio prospectivo-descriptivo de 71 pacientes con cáncer prostático metastásico a hueso tratados en el servicio de oncología del Hospital Clínico Quirúrgico "Hermanos Ameijeiras" con: edades 18-80 años, ECOG<3, expectativa de vida >6 meses, y seguimiento de al menos doce meses. Se administró ácido zoledrónico cada 21-28 días. Se aplicó la escala visual análoga y el módulo EORTC QLQ-BM22. Resultados: Los pacientes tenían una mediana de 71 años de edad, Gleason ≥ 8: en 57,7 % de los pacientes, PSA al diagnóstico ≥ 20 ng/mL: 70,4 por ciento, ECOG 1: 67,6 por ciento, y estadio IV como presentación inicial: 50,7 por ciento. Metástasis óseas sin toma visceral: 84,5 por ciento, en vértebras 36,6 por ciento, <3 sitios 66,2 por ciento, y metástasis óseas blásticas 60,6 por ciento. Eventos esqueléticos relacionados previos al ácido zoledrónico 7,9 por ciento (fractura), y posteriores, 5,6 por ciento (radioterapia anti-álgica). A doce meses, acorde a la escala visual análoga, se alcanzó respuesta completa: 71 por ciento, y parcial: 29 por ciento (p<0,05). Luego de la aplicación del módulo EORTC QLQ-BM22, se comprobó disminución significativa tanto en la escala de síntomas como en la funcional, independientemente de otros factores. Conclusiones: Los tratamientos específicos para cáncer prostático combinado a zoledrónico mejoran significativamente el dolor y calidad de vida relacionada con la salud en pacientes con metástasis óseas(AU)

Introduction: Zoledronic Acid improves the quality of life of patients suffering from prostate cancer. Objectives: To assess the health-related quality of life using EORTC QLQ-BM22 questioner in patients suffering from prostate cancer, treated with zoledronic acid. Method: A prospective-descriptive study was carried out in 71 patients suffering from prostate cancer involving bones, with ages ranging between 18 and 80 years, and who were treated in the oncology service at Hermanos Ameijeiras Hospital. The ECOG was less than 3, life expectancy> 6 months, and follow-up of at least twelve months. Zoledronic acid was administered every 21-28 days. The visual analog scale and EORTC QLQ-BM22 module were applied. Results: The patients had median age of 71 years, Gleason ≥ 8: in 57.7% of the patients, PSA at diagnosis ≥ 20 ng / mL: 70.4%, ECOG 1: 67.6 percent, and stage IV as initial presentation: 50.7 percent. Bone metastases without visceral intake: 84.5 percent, in vertebrae 36.6 percent, <3 sites 66.2 percent, and blast bone metastases 60.6 percent. Skeletal events related to zoledronic acid before 7.9 percent (fracture), and after 5.6 percent (anti-allergic radiotherapy). At twelve months, according to the visual analog scale, a complete response was achieved, 71 percent, and a partial response, 29 percent (p <0.05). After the application of EORTC QLQ-BM22 module, a significant decrease was found in both the symptom and functional scales, regardless of other factors. Conclusions: Specific treatments for prostate cancer combined with zoledronic significantly improve pain and health-related quality of life in patients with bone metastases(AU)

Humans , Male , Prostatic Neoplasms/drug therapy , Quality of Life , Bone Neoplasms , Zoledronic Acid/therapeutic use , Neoplasm Metastasis/diagnosis , Epidemiology, Descriptive , Prospective Studies
Acta cir. bras ; 36(6): e360603, 2021. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1278113


ABSTRACT Purpose To evaluate the influence of bioactive glass and photobiomodulation therapy (PBMT) in calvarial bone repair process in rats submitted to zoledronic acid therapy. Methods Twenty-four rats were selected and treated with the dose of 0.035 mg/kg of zoledronic acid every two weeks, totalizing eight weeks, to induce osteonecrosis. After the drug therapy, surgical procedure was performed to create 5-mm diameter parietal bone defects in the calvarial region. The rats were then randomly assigned to groups according to the following treatments: AZC: control group, treated with blood clot; AZBIO: bone defect filled with bioactive glass; AZL: treated with blood clot and submitted to PBMT; and AZBIOL: treated with bioactive glass S53P4 and submitted to PBMT. Tissue samples were collected and submitted to histomorphometric analysis after 14 and 28 days. Results At 14 days, bone neoformation in the AZBIO (52.15 ± 9.77) and AZBIOL (49.77 ± 13.58) groups presented higher values (p ≤ 0.001) compared to the AZC (23.35 ± 10.15) and AZL groups (23.32 ± 8.75). At 28 days, AZBIO (80.24 ± 5.41)still presented significant higher bone recovery values when compared to AZC (59.59 ± 16.92)and AZL (45.25 ± 5.41) groups (p = 0.048). In the 28-day period, the AZBIOL group didn't show statistically significant difference with the other groups (71.79 ± 29.38). Conclusions The bioactive glass is an effective protocol to stimulate bone neoformation in critical defects surgically created in rats with drug induced osteonecrosis, in the studied periods of 14 and 28 days.

Animals , Rats , Low-Level Light Therapy , Bone Regeneration , Zoledronic Acid , Glass
Rev. bras. ortop ; 55(5): 543-550, Sept.-Oct. 2020. graf
Article in English | LILACS | ID: biblio-1144202


Abstract Objective The aim of the present study was to determine the effect of combined zoledronic acid and alendronate therapy on bone edema and knee pain in cases of spontaneous osteonecrosis of the knee. We report our experience with this treatment. Methods A retrospective case series of 11 patients with spontaneous osteonecrosis of the knee confirmed by magnetic resonance image (MRI). The patients were treated with a single dose of 5 mg of intravenous zoledronic acid combined with 35 mg twice a week of oral alendronate, for 16 weeks. The visual analogue scale scores were noted before the beginning of the therapy, at 8 weeks, and at 16 weeks of follow-up. The size of the bone marrow edema adjacent to the lesion was measured on T2-weighted MRI coronal images at the beginning of the therapy and at 16 weeks. Results The average visual analogue scale score at 0 weeks was of 7.72, and of 0.81 at 16 weeks of therapy; the difference was statistically significant (p= 0.03). The mean bone marrow involvement at 0 weeks was of 80%, which reduced to 11.81% at 16 weeks of therapy. This change was statistically significant (p= 0.03). Conclusion Our data shows that the combination therapy causes early pain relief and reduction of the bone edema, and it is safe, effective and well-tolerated for a painful disease entity like spontaneous osteonecrosis of the knee.

Resumo Objetivo Determinar o efeito do tratamento combinado de ácido zoledrônico e alendronato no edema ósseo e na dor no joelho em casos de osteonecrose espontânea do joelho. A experiência dos autores com este tratamento é relatada. Métodos Série de casos retrospectiva, incluindo 11 pacientes com osteonecrose espontânea do joelho confirmada por ressonância magnética. Os pacientes foram tratados com uma dose intravenosa única de 5 mg de ácido zoledrônico combinada com 35 mg de alendronato oral, 2 vezes por semana, por 16 semanas. Os escores da escala visual analógica foram aferidos antes do começo do tratamento, em 8 semanas e em 16 semanas de acompanhamento. O tamanho do edema da medula óssea adjacente à lesão foi medido em imagens de ressonância magnética coronal ponderadas em T2 no início do tratamento e em 16 semanas. Resultados O escore médio da escala visual analógica em 0 semanas foi de 7,72, contra 0,81 em 16 semanas de tratamento, uma diferença estatisticamente significativa (p= 0,03). O envolvimento médio da medula óssea em 0 semanas foi de 80%, e foi reduzido para 11,81% em 16 semanas de tratamento, uma diferença também estatisticamente significativa (p= 0,03). Conclusão Os dados mostram que a terapia combinada proporciona alívio da dor inicial e redução do edema ósseo, sendo segura, eficaz e bem tolerada em uma enfermidade dolorosa como a osteonecrose espontânea do joelho.

Humans , Male , Female , Adult , Middle Aged , Osteoarthritis , Pain , Bone and Bones , Bone Marrow , Magnetic Resonance Spectroscopy , Combined Modality Therapy , Alendronate , Diphosphonates , Dosage , Visual Analog Scale , Zoledronic Acid , Knee Joint , Necrosis
Braz. dent. j ; 31(3): 304-309, May-June 2020. graf
Article in English | LILACS, BBO | ID: biblio-1132294


Abstract Among other factors, types of bisphosphonates and treatment regimens seem to be strongly associated with the success or failure of installation of osseointegrated implants. This study investigated the influence of two bisphosphonates, sodium alendronate (SA) and zoledronic acid (ZA), on the metabolism of osteoblasts. Human osteoblasts (Saos-2) were seeded onto machined or acid-treated titanium discs previously placed on 24-well plates in complete culture medium. After 24 h, cells were exposed to bisphosphonates at 0.5, 1 or 5 µM for 24 h, 48 h or 7 days. The effects of SA and ZA on osteoblasts were assessed based on the adhesion of these cells to the titanium surfaces by direct fluorescence, cell viability, total protein and collagen synthesis. Alkaline phosphatase activity and mineral nodule deposition by these cells were also evaluated. Data were evaluated by ANOVA and Tukey tests (α=0.05). Decreased adhesion of cells to the titanium discs was observed when exposed to both bisphosphonates; however, this lack of cell adhesion was more evident for ZA-treated cells. In addition, the exposure of osteoblasts to ZA decreased the viability, ALP activity and mineral nodule deposition, which may be related to poor osseointegration after implant installation.

Resumo Entre outros fatores, os tipos de bisfosfonatos bem como os regimes de tratamento parecem estar diretamente associados com o sucesso ou falhas na instalação de implantes osseointegrados. Este estudo avaliou a influência de dois bisfosfonatos, o alendronato de sódio (AS) e o ácido zoledrônico (AZ), no metabolismo de osteoblastos. Osteoblastos humanos (Saos-2) foram cultivados sobre discos de titânio polidos ou submetidos a tratamento ácido superficial, previamente alocados em placas de 24 compartimentos, utilizando meio de cultura completo. Após 24 horas, as células foram expostas aos bisfosfonatos, nas concentrações de 0,5, 1 ou 5 µM, por 24 h, 48 h, ou 7 dias. Os efeitos do AZ e AZ sobre os osteoblastos foram determinados considerando a adesão destas células às superfícies de titânio, por meio de fluorescência direta, a viabilidade celular, produção de proteína total e síntese de colágeno. A atividade de fosfatase alcalina e a deposição de nódulos mineralizados também foram avaliadas. Os dados foram analisados por meio do teste ANOVA complementado por Tukey (α = 0.05). Menor adesão dos osteoblastos foi observada quando estas células foram expostas a ambos os bisfosfonatos, porém, esta falha na adesão foi mais evidente para as células tratadas com AZ. Além disso, a exposição dos osteoblastos ao AZ também resultou em diminuição da viabilidade, atividade de ALP e deposição de nódulos mineralizados, o que pode estar relacionado a uma pobre osseointegração após a instalação do implante.

Humans , Titanium , Diphosphonates , Osteoblasts , Surface Properties , Cell Adhesion , Cell Differentiation , Cells, Cultured , Cell Proliferation , Alkaline Phosphatase , Zoledronic Acid
J. bras. econ. saúde (Impr.) ; 12(1): 16-22, Abril/2020.
Article in Portuguese | LILACS, ECOS | ID: biblio-1096402


Objetivo: Estimar o custo por evento relacionado ao esqueleto (ERE) e o impacto econômico anual da adoção de denosumabe em pacientes com metástases ósseas secundárias ao câncer de mama, próstata e outros tumores sólidos ou mieloma múltiplo sob a perspectiva do sistema de saúde privado brasileiro. Métodos: Um modelo econômico foi desenvolvido para comparar os custos relacionados com denosumabe versus ácido zoledrônico na prevenção de EREs. O modelo incluiu os seguintes custos: medicamento, administração, monitoramento e manejo de ERE. O custo anual foi apresentado em reais (BRL) para 100 pacientes. Os custos do manejo de ERE [fratura vertebral (FV), fratura não vertebral (FNV), radiação óssea (RO), cirurgia óssea (CO) e compressão da medula espinhal (CME)] foram estimados a partir dos recursos e procedimentos coletados da revisão de literatura, bases de dados e painel Delphi. Dados coletados dos estudos clínicos randomizados relacionados com cada tipo de tumor na análise e de um estudo prospectivo observacional foram utilizados para estimar a eficácia clínica de denosumabe versus ácido zoledrônico. Resultados: O custo por cada tipo de ERE variou de BRL 27.246 a BRL 28.035 para FV, BRL 18.023 a BRL 18.811 para FNV, BRL 42.750 a BRL 43.538 para RO, BRL 18.023 a BRL 18.811 para CO e BRL 12.472 a BRL 13.260 para CME. A introdução de denosumabe foi estimada em economia anual por 100 pacientes de até BRL 1.072.043,14 para câncer de mama, BRL 1.212.822,79 para outros tumores sólidos, BRL 1.929.660,67 para câncer de próstata e BRL 77.965,07 para mieloma múltiplo. Conclusão: Esta análise sugere que EREs adicionam custos substanciais no manejo de pacientes com metástases ósseas. Dessa forma, o uso de denosumabe pode prevenir e retardar EREs em pacientes com câncer e pode possivelmente levar à redução do impacto econômico associado aos EREs sob a perspectiva dos pagadores de saúde privada brasileira.

Objective: To estimate the cost per SRE and annual economic impact of denosumab adoption in patients with bone metastases (BM) secondary to breast cancer, prostate cancer, other solid tumors or multiple myeloma from the Brazilian private healthcare system's perspective. Methods: An economic model was developed to compare the cost outcomes associated with denosumab instead of zoledronic acid for SRE prevention. The model included the following costs: drug, administration, monitoring and SRE management. Annual costs per 100 patients were reported in 2019 Brazilian currency (BRL). The SRE management costs (vertebral fracture (VF), non-vertebral fracture (NVF), radiation to bone (RB), surgery to bone (SB) and spinal cord compression (SCC)) were estimated from the resources and procedures collected from literature review, official database, and a Delphi panel. Data collected from randomized clinical trials related to each tumor type in the analysis and from a prospective observational study was used to estimate the clinical efficacy of denosumab vs zoledronic acid. Results: The cost per each type of SREs across all tumors ranged BRL 27,246 ­ BRL 28,035 for VF, BRL 18,023 ­ BRL 18,811 for NVF, BRL 42,750 ­ BRL 43,538 for RB, BRL 18,023 ­ BRL 18,811 for SB and BRL 12,472 ­ BRL 13,260 for SCC. The introduction of denosumab was estimated to result in annual savings per 100 patients of up to BRL 1,072,043.14 for breast cancer, BRL 1,212,822.79 for other solid tumors, BRL 1,929,660.67 for prostate cancer and BRL 77,965.07 for multiple myeloma. Conclusion: This analysis suggests that SREs add substantial costs to the management of patients with bone metastases. In this way, the use of denosumab would prevent and delay SREs in cancer patients and might possibly lead to reduce the economic burden associated with SREs, borne by Brazilian private healthcare payers.

Prostatic Neoplasms , Breast Neoplasms , Denosumab , Zoledronic Acid , Multiple Myeloma , Neoplasm Metastasis
Acta cir. bras ; 35(10): e202001005, 2020. tab, graf
Article in English | LILACS | ID: biblio-1141932


Abstract Purpose: To assess the effect of a collagen matrix (Mucograft®) on the inflammatory process in a semi-critical experimental defect model in rats treated with bisphosphonates. Methods: Eighteen Wistar rats were randomly divided into three groups: saline (CG), alendronate (ALD) 5mg/kg (AG) or zoledronic acid (ZA) 0.2mg/kg (ZG). ALD was administered orally for 10 weeks and ZA was administered intravascularly on days 0, 7 and 14 and 49. On day 42, a 2mm defect was created and filled with Mucograft® collagen matrix. The contralateral side was filled with a clot (control side). The animals were euthanized 70 days after the beginning of the experiment and the hemimandibles were radiographically and histologically (counting of empty osteocyte lacunae (%), apoptotic (%) and total osteoclasts, neutrophil and mononuclear inflammatory cells) analyzed. The variables were submitted to ANOVA/Bonferroni and t test (parametric data) (p <0.05, GraphPad Prism 5.0). Results: Significant bone repair occurred in the groups treated with Mucograft®. High number of total inflammatory cells and neutrophils cells were showed in AG (p=0.026 and p=0.035) and AZ groups (p=0.005, p=0.034) on the control sides associated with delayed bone repair and the presence of devitalized bone tissue in AG and ZG on the Mucograft® side. Conclusion: Mucograft® collagen matrix attenuated the inflammatory process in a mandible defect in rats submitted to the use of bisphosphonates (AG and ZG).

Animals , Rats , Collagen , Diphosphonates , Rats, Wistar , Zoledronic Acid , Mandible
J. appl. oral sci ; 28: e20200204, 2020. tab, graf
Article in English | LILACS, BBO | ID: biblio-1134802


Abstract Objective This study aims to evaluate bone repair and the development of the medication related osteonecrosis of the jaw (MRONJ) associated with the use of zoledronic acid in Wistar rats. Methodology 48 male Wistar rats were divided into four groups: ZA, treated with intraperitoneal zoledronic acid, 0.6 mg/kg every 28 days, totaling five doses; control (C), treated with 0.9% sodium chloride; ZA-surgical (SZA) and C-surgical (SC), submitted to extraction of the right upper molars 45 days after the first application. Alveolar bone repair was evaluated by macroscopic and histological analysis. Protein expression evaluations were performed by qPCR. Results Macroscopic evaluation showed that 91.66% (11) of the animals in the SZA group and 41.66% (5) from the SC group presented solution of epithelium continuity (P<0.05). All animals in the SZA group and none in the SC group had bone sequestration. The area of osteonecrosis was higher in the SZA group than in the SC group (P<0.05). In molecular evaluation, the SZA group presented changes in the expression of markers for osteoclasts, with increased RANK and RANKL, and a decrease in OPG. Conclusion The results highlighted strong and evident interference of zoledronic acid in bone repair of the socket, causing osteonecrosis and delayed bone remodeling.

Animals , Male , Rats , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/physiopathology , Zoledronic Acid/adverse effects , Tooth Extraction/adverse effects , Rats, Wistar
Article in Chinese | WPRIM | ID: wpr-880772


OBJECTIVE@#To investigate the effect of zoledronate (ZOL) on osteoclast differentiation and bone resorption under high glucose, and the regulation mechanism of p38 mitogen activated kinase (p38 MAPK) signaling pathway in this process.@*METHODS@#RAW264.7 cells were divided into four groups: low group, high group, low+ZOL group and high+ZOL group after induced into osteoclasts. Cell proliferation activity was determined by MTT assay. The migration of RAW264.7 cells were examined Optical microscopy. Immunofluorescence microscopy was used to observe the cytoskeleton and sealing zones of osteoclasts. After adding group 5: high + ZOL + SB203580 group, trap staining was used to identify the number of positive osteoclasts in each group. The number and area of resorption lacunae were observed by SEM. The mRNA and protein expression of osteoclast related factors were detected by real-time PCR and Western blotting.@*RESULTS@#The cells in the 5 groups showed similar proliferative activity. High glucose promoted the migration of RAW264.7 cells (@*CONCLUSIONS@#High glucose inhibits osteoclast differentiation and bone resorption. ZOL inhibits osteoclast differentiation and bone resorption in high-glucose conditions by regulating p38 MAPK pathway, which can be a new pathway for ZOL to regulate diabetic osteoporosis.

Animals , Bone Resorption , Cell Differentiation , Glucose , MAP Kinase Signaling System , Mice , NFATC Transcription Factors , Osteoclasts , RANK Ligand , Zoledronic Acid/pharmacology , p38 Mitogen-Activated Protein Kinases
Article in Chinese | WPRIM | ID: wpr-827250


OBJECTIVE@#To explore the clinical effect of zoledronic acid combined with vitamin K2 regimen in percutaneous vertebroplasty for multi-segment osteoporotic vertebral compression fractures(OVCFs).@*METHODS@#This study was a retrospective control study. A total of 364 patients with OVCFs who were admitted to our spinal surgery department from January 2014 to January 2017 were selected as the study subjects. According to whether zoledronic acid combined with vitamin K2 was used to treat osteoporosis after surgery, the patients were divided into control group and experimental group. Among them, 257 patients in the control group were treated with calcium carbonate and vitamin D regimen, while 107 patients in the experimental group were treated with zoledronic acid combined with vitamin K2 regimen on the basis of the control group. Visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were used to evaluate the clinical effect. Pre- and post-operative bone mineral density of lumbar spine and proximal femur, vertebral height ratio of responsible vertebral body and Cobb angle of vertebral body were observed by image data. Serological indicators related to bone metabolism were detected by laboratory. The complications such as fever, dizziness, osteoarthritis, muscular and soft tissue pain and adjacent vertebral re-fracture were compared between two groups.@*RESULTS@#There was no significant difference in general data between the two groups (0.05);VAS score in the experimental group was significantly lower than that in the control group 1 month, 3 months and 1 year after operation(0.05), and at the 24 hours, 3 months, 1 year after operation, the experimental group was significantly lower than the control group (0.05). The vertebral height ratio of the responsible vertebral body in experimental group was significantly higher than that in control group and Cobb angle in experimental group was significantly lower than that in control group at 3 months and 1 year after operation (0.05), but at 3 months and 1 year after operation, the bone mineral density of lumbar spine and proximal femur in experimental group was significantly lower than that in control group (0.05). At 1 year after operation the total type I collagen amino-terminal elongation peptide and β-collagen degradation products in experimental group was significantly lower than that in the control group (<0.05), but the 25-hydroxyvitamin D operation in experimental group was significantly higher than that in control group(<0.05). The incidence of postoperative complications such as fever, dizziness, osteoarthritis, muscle and soft tissue pain and adjacent vertebral re-fracture in experimental group was significantly lower than that in control group (<0.05).@*CONCLUSION@#Zoledronic acid injection combined with vitamin K2 regimen can be used for anti-osteoporosis treatment of OVCFs vertebroplasty. It has a definite curative effect and a high safety factor. It is worth popularizing.

Bone Cements , Fractures, Compression , Humans , Kyphoplasty , Osteoporotic Fractures , Retrospective Studies , Spinal Fractures , Treatment Outcome , Vertebroplasty , Vitamin K 2 , Zoledronic Acid
Article in Chinese | WPRIM | ID: wpr-827249


OBJECTIVE@#To investigate the clinical efficacy of vertebral body stent (VBS) system and percutanous kyphoplasty (PKP) combined with zoledronic acid for the treatment of severely osteoporotic compression vertebral fractures (OVCFs).@*METHODS@#The clinical data of 48 patients with osteoporotic thoracolumbar fractures treated from December 2017 to December 2018 were retrospectively analyzed, including 13 males and 35 females, aged 55 to 92 years old with an average (71.2±10.5) years. All patients were treated with VBS system PKP surgery, and zoledronic acid injection was used for anti-osteoporosis treatment after operation. The VAS scores ODI, the height of diseasedvertebral lost were compared before operation, 3 d and half a year after operation, and whether there was re-fracture of diseased or adjacent vertevrae after operation was observed.@*RESULTS@#Before operation, 3 d and half a year after operation, VAS scores were 7.60±0.12, 3.00±0.46, 1.20±0.23, ODI were(82.00±0.32)%, (30.00±1.50) %, (18.00±0.16) %, the height of diseased vertebral lost were (12.00±0.43) mm, (3.00± 0.15) mm, (3.60±0.51) mm respectively. Postoperative VAS score, ODI, the height of diseased vertebral lost were obviously improved (0.05). All the 48 patients were followed up with an average time of (6.6±0.5) months. All the incisions healed at grade A after operation, and no re-fracture of diseased vertebrae or adjacent vertebrae was found at the final follow-up.@*CONCLUSION@#VBS system and PKP combined with zoledronic acid in the treatment of OVCFs not only may effectively relieve the pain in the thoracolumbar back, improve the mobility of the thoracolumbar, but also can restore the height of the vertebral body to the maximum extent, and prevent the re-fracture of the affected vertebrae and adjacent vertebrae, which is worthy to spread in clinic.

Aged , Aged, 80 and over , Bone Cements , Female , Fractures, Compression , Humans , Kyphoplasty , Male , Middle Aged , Osteoporotic Fractures , Retrospective Studies , Spinal Fractures , Stents , Treatment Outcome , Zoledronic Acid
s.l; RedARETS; ago. 2019. tab.
Non-conventional in Spanish | LILACS, BRISA | ID: biblio-1095359


CONTEXTO: La osteoporosis es un trastorno esquelético caracterizado por resistencia óssea comprometida, predisposición pacientes a un mayor riesgo de fractura. La prevalência aumenta del 6% de las mujeres de edad 50 a 59 años a más del 40% de las mujeres de edad 80 años y mayores.1 Consecuencias de mantener una fractura puede ser grave e incluir un aumento riesgo de fracturas posteriores, hospitalización o institucionalización, disminución de la calidad de vida, y mortalidad prematura, con una carga relacionada com el sistema de salud. DESCRIPCIÓN DE LA TECNOLOGÍA: El denosumab es un anticuerpo monoclonal que inhibe la resorción ósea producida por los osteoclastos. Fue comercializado en 2010 para el tratamiento de la osteoporosis. En estos años se han identificado varios efectos adversos potencialmente graves: predisposición a infecciones, cáncer, reacciones de hipersensibilidad, transtornos autoinmunes, e incremento de la incidencia de múltiples fracturas vertebrales espontáneas al suspender el tratamiento. En este número revisamos estas novedades. TECNOLOGÍAS ALTERNATIVAS: Los agentes antirresortivos como los bifosfonatos orales son el estándar tratamiento para la osteoporosis posmenopáusica, en conjunto con medidas no farmacológicas y sobre todo el énfasis en la prevención de las caídas. Otras opciones de tratamiento incluyen un bisfosfonatos intravenoso (ácido zoledrónico), un agente formador de hueso (teriparatida) y un modulador selectivo del receptor de estrógeno (raloxifeno). MÉTODOS: Se realizó una búsqueda bibliográfica utilizando las siguientes bases de datos bibliográficas: MEDLINE, EMBASE, The Cochrane Library, y PubMed. Aplicaron filtros metodológicos para evaluaciones de tecnología sanitaria, estudios económicos, revisiones sistemáticas, metanálisis, y ensayos controlados aleatorios (ECA). La búsqueda también se limitó a Idioma en Inglés y humanos. Se excluyeron los resúmenes de congresos en los resultados de búsqueda. Se identificó la literatura gris (literatura que no se publica comercialmente) fue identificado mediante la búsqueda de secciones relevantes de la Lista de verificación de Grey Matters ( Google y otros motores de búsqueda de internet fueron se utiliza para buscar en la web adicional materiales Estas búsquedas se complementaron con revisar las bibliografías de documentos clave y a través de contactos con expertos apropiados. ESTRATEGIA DE BÚSQUEDA: Se realizó una búsqueda con última fecha 26/08/2019 en diversas bases de datos, incluidas PubMed y Embase, así como la biblioteca Cochrane, y bases de datos de revisiones sistematicas Epistemonikos. La búsqueda sólo incluyó documentos escrito en ingles y espanol. RESULTADOS: Denosumab comparado con placebo para pacientes con osteoporosis. El riesgo en el grupo de intervención (y su intervalo de confianza del 95%) se basa en el riesgo asumido en el grupo de comparación y en el efecto relativo de la intervención (y su intervalo de confianza del 95%). Eficacia frente a bifosfonatos: comparaciones directas. Se evalúa el perfil de evidencia GRADE donde se evidencia el metaanálisis entre cuatro ECA 5-8 que comprendieron 2071 participantes con un rango de seguimiento de 12 a 24 meses y compararon el uso de Denosumab con bifosfonatos orales (Alendronato,Etidronato). Existe incertidumbre en el efecto de denosumab sobre el riesgo de fracturas en comparación con bifosfonatos. La certeza em la evidencia va desde BAJA A MUY BAJA considerando la presencia de imprecisión muy seria y el potencial riesgo de sesgo de publicación. Eficacia frente a bifosfonatos: comparaciones indirectas. No se han encontrado en la literatura comparaciones directas entre Denosumab y otros fármacos distintos. Esta recomendación de cobertura otorga más peso a la incertidumbre en la eficacia comparada con bifosfonatos, al potencial impacto presupuestario de su uso y la potencial reducción de la equidad; que a la preferencia de los pacientes respecto de la forma de administración de las drogas para osteoporosis.

Humans , Female , Osteoporosis, Postmenopausal/drug therapy , Teriparatide/therapeutic use , Raloxifene Hydrochloride/therapeutic use , Diphosphonates/therapeutic use , Osteoporotic Fractures/drug therapy , Denosumab/therapeutic use , Zoledronic Acid/therapeutic use , Technology Assessment, Biomedical , Cost-Benefit Analysis/economics
Actual. osteol ; 15(1): 57-64, ene. abr. 2019. ilus., tab.
Article in Spanish | LILACS | ID: biblio-1049428


Los tratamientos para osteoporosis se indican por tiempo variable dependiendo del tipo de droga, anabólica o anticatabólica, y de la gravedad de la enfermedad. Denosumab es un anticuerpo monoclonal totalmente humano que inhibe a RANK-L evitando de esa manera la interacción entre RANKL-RANK, con la consiguiente inhibición de la formación de los osteoclastos, su activación y sobrevida. Disminuye la resorción ósea cortical y trabecular. Su administración subcutánea de 60 mg cada 6 meses al cabo de 3 años ha demostrado reducción de la resorción ósea, incremento de la densidad mineral ósea y disminución de las fracturas vertebrales, no vertebrales y de cadera. Está indicado para el tratamiento de la osteoporosis con alto riesgo de fractura. Su mecanismo de acción es reversible. Se han descripto pérdida de la DMO y elevación de los marcadores de remodelado óseo postsuspensión. Una situación clínica grave son las fracturas vertebrales múltiples postsuspensión. Este evento es infrecuente y se lo atribuye a un rebote del remodelado óseo, postulándose se postula una predisposición especial, probablemente relacionada con microRNA. Se escriben dos mujeres con osteoporosis que presentaron este cuadro. Las fracturas ocurrieron entre 7 y 10 meses posteriores a la última dosis de denosumab. Registraron elevación de C-telopéptidos y disminución de la DMO conjuntamente con las fracturas vertebrales agudas en cascada. (AU)

The duration of osteoporosis treatments depends on the drug type, anabolic or anticatabolic, and the severity of the disease. Denosumab is a fully human monoclonal antibody that inactivates RANK-L, inhibiting the RANKL-RANK interaction . This inhibits osteoclast formation, activation, and survival. It also reduces cortical and trabecular bone resorption. Subcutaneous administration of 60 mg every 6 months for 3 years has reduced bone resorption, increased bone mineral density (BMD) and decreased vertebral, non-vertebral and hip fractures. It is indicated for the treatment of osteoporosis with high risk of fracture. Denosumab mechanism of action is reversible. After discontinuation, loss of BMD and elevation of bone turnover markers have been observed. In addition, multiple vertebral fractures after the suspension of the drug have been reported. These rebound-associated vertebral fractures are rare. A special genetic predisposition related to miRNA has been proposed. Two women with this clinical presentation are described. Fractures occurred between 7 and 10 months respectively after the last dose of denosumab. They presented with an increase in circulating C-telopeptid levels and a decrease inBMD with acute multiple vertebral fractures. (AU)

Humans , Female , Middle Aged , Aged , Spinal Fractures/drug therapy , Denosumab/adverse effects , Osteoporosis/drug therapy , Quality of Life , Menopause , Biomarkers , Bone Density/drug effects , Calcium/administration & dosage , Spinal Fractures/prevention & control , Charybdotoxin/analysis , Calcium Citrate/administration & dosage , Alendronate/administration & dosage , MicroRNAs/metabolism , Diphosphonates/adverse effects , Diphosphonates/therapeutic use , RANK Ligand/drug effects , Denosumab/administration & dosage , Tobacco Smoking , Zoledronic Acid/administration & dosage , Ibandronic Acid/administration & dosage , Indapamide/administration & dosage
Braz. oral res. (Online) ; 33: e086, 2019. tab, graf
Article in English | LILACS | ID: biblio-1019605


Abstract Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient's symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.

Humans , Animals , Female , Parathyroid Hormone/pharmacology , Chitosan/pharmacology , Bone Density Conservation Agents/pharmacology , Maxilla/drug effects , Parathyroid Hormone/therapeutic use , Rats, Sprague-Dawley , Poloxamer/administration & dosage , Poloxamer/chemistry , Models, Animal , Delayed-Action Preparations , Chitosan/therapeutic use , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/therapeutic use , Bisphosphonate-Associated Osteonecrosis of the Jaw , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Zoledronic Acid/adverse effects , Maxilla/pathology , Microspheres
Acta cir. bras ; 33(12): 1052-1060, Dec. 2018. graf
Article in English | LILACS | ID: biblio-973489


Abstract Purpose: To establish a method for the preparation of zoledronate liposome and to observe its effect on inducing the apoptosis of rat liver Kupffer cells. Methods: Zoledronate was encapsulated in liposomes, and then the entrapment rate was detected on a spectrophotometer. The prepared Zoledronate liposome (0.01 mg/mL) was injected into the tail vein of SD rats. Three days later, the number of Kupffer cells (CD68 positive) in rat liver tissue was detected by immunohistochemistry. Flow cytometry was used to detect the apoptosis rate of the isolated liver Kupffer cell cultured in vitro. Results: The entrapment rate of Zoledronate was 43.4±7.8%. Immunohistochemistry revealed that the number of Kupffer cells was 19.3±2.1 in PBS group and 5.5±1.7 in Zoledronate liposome group, with a significant difference (P<0.05). The apoptosis rate of Kupffer cells was 4.1±0.8% in PBS group, while it was 9±2.2% and 23.3±5.9% in Zoledronate liposomes groups with different concentrations of Zoledronate liposome (P<0.05). Conclusions: Zoledronate liposomes can effectively induce the apoptosis of Kupffer cells in vivo and in vitro, and the apoptosis rate is related to the concentration of Zoledronate liposome. To establish a rat liver Kupffer cell apoptosis model can provide a new means for further study on Kupffer cell function.

Animals , Male , Apoptosis/drug effects , Zoledronic Acid/pharmacology , Kupffer Cells/drug effects , Liver/cytology , Immunohistochemistry , Random Allocation , Cell Count , Reproducibility of Results , Treatment Outcome , Rats, Sprague-Dawley , Drug Compounding/methods , Flow Cytometry , Zoledronic Acid/administration & dosage , Zoledronic Acid/chemical synthesis , Liposomes/chemical synthesis
Actual. osteol ; 14(3): 168-177, sept. - dic. 2018. ilus., graf., tab.
Article in English | LILACS | ID: biblio-1049519


Zoledronic acid (ZA) is an antiresorptive drug used in children with bone diseases like osteogenesis imperfecta, juvenil osteoporosis, fibrous dysplasia and primary bone tumors. The aim of the present study was to evaluate the effects of ZA dose accumulation on growing bone during different periods of treatment in normal rats. Methods: A 4x2 factorial design was used to study the effect of the dose of ZA (D: 0-2.5-12.5-25 µg Z/kg body weight/s.c. weekly) and the length of treatment (T: 15-30 days) in normal female Sprague Dawley rats. Bone morphometric, histomorphometric, densitometric and biomechanical studies were performed. Results: Femoral length and cross-sectional area were affected by both D and T. A significant interaction between D and T was observed in length with a lower value at higher dose and 30 days of treatment. Growth plate of the tibia showed a decrease in total thickness with D and T. Histomorphometric and connectivity parameters of trabecular bone were significantly increased with D and several parameters were also affected by T. Cortical bone strength was increased only with T. Biomechanical parameters of trabecular bone showed significant interaction with greater effect at higher D and T. Conclusion: Even though a mild negative effect of the highest dose of ZA on linear and appositional growth was observed, the other bone parameters evaluated were improved. A careful risk/benefit analysis would lead us to conclude that the mild deleterious effects of ZA during growth are outweighed by the benefit obtained with treatment. (AU)

El ácido zoledrónico (AZ) es un fármaco antirresortivo utilizado en niños con enfermedades óseas como osteogénesis imperfecta, osteoporosis juvenil, displasia fibrosa y tumores óseos primarios. El objetivo del presente estudio fue evaluar los efectos de las dosis acumuladas de AZ en el hueso en crecimiento de ratas hembras normales durante diferentes períodos de tratamiento. Métodos: se utilizó un diseño factorial de 4x2 para estudiar el efecto de la dosis de AZ (D: 0-2,5-12,5-25 µg Z / kg de peso corporal /sc semanalmente) y el período de tratamiento (T: 15-30 días) en ratas Sprague Dawley. Se realizaron estudios óseos morfométricos, histomorfométricos, densitométricos y biomecánicos. Resultados: la longitud y el área de sección transversal del fémur se vieron afectadas tanto por D como por T. Se observó una interacción significativa entre D y T en la longitud obteniéndose un valor más bajo a la dosis más alta y a 30 días de tratamiento. El cartílago de crecimiento de la tibia mostró una disminución en el espesor total con D y T. Los parámetros histomorfométricos y de conectividad del hueso trabecular aumentaron significativamente con D y varios parámetros también se vieron afectados por T. La fortaleza ósea cortical aumentó solo con T. Los parámetros biomecánicos del hueso trabecular mostraron una interacción significativa con un mayor efecto a mayor D y T. Conclusión: a pesar que se observó un leve efecto negativo de la dosis más alta de AZ sobre el crecimiento lineal y aposicional, el resto de los parámetros óseos evaluados mejoraron. Un análisis cuidadoso del riesgo /beneficio permite concluir que los efectos negativos leves del AZ durante el crecimiento son superados por el beneficio obtenido con el tratamiento. (AU)

Animals , Bone and Bones/drug effects , Zoledronic Acid/adverse effects , Growth Plate/drug effects , Osteogenesis Imperfecta/drug therapy , Bone and Bones/diagnostic imaging , Bone Neoplasms/drug therapy , Rats, Sprague-Dawley/physiology , Femur/drug effects , Femur/diagnostic imaging , Fibrous Dysplasia of Bone/drug therapy , Zoledronic Acid/administration & dosage
Actual. osteol ; 13(2): 104-115, Mayo - Ago. 2017. ilus, graf, tab
Article in Spanish | LILACS | ID: biblio-1117988


La osteonecrosis de maxilar asociada a aminobisfosfonatos (BRONJ) constituye un efecto secundario del tratamiento crónico con los más potentes. Un modelo experimental permitiría determinar la patogenia de dicha alteración. La oveja presenta características orales y del metabolismo óseo similar al humano y permite realizar manipulaciones bucales. Se evaluaron cambios clínicos, remodelación ósea y masa ósea maxilar en ovejas hembras adultas tratadas con zolendronato (ZOL), durante 22 meses y utilizando dosis equivalente al tratamiento de neoplasias. Seis ovariectomizadas (OVX) recibieron ZOL; 5 OVX y 4 SHAM (control) recibieron solución fisiológica. Al inicio, 4 y 22 meses se evaluó calcemia, fosfatemia, crosslaps (CTX) y fosfatasa alcalina ósea. Al final, se evaluó contenido mineral óseo de la hemimandíbula superior (CMO: mg/cm2). Al final del estudio, CTX disminuyó significativamente en ZOL (p<0,05) sin diferencias entre SHAM y OVX. En maxilar, los contenidos de Ca y P (g/g tejido) y CMO (g/cm2 ) disminuyeron en OVX vs. SHAM (p<0,05) y solo Ca y CMO respecto de ZOL (p<0,05). ZOL incrementó el contenido de Ca y CMO, mientras que el de P permaneció significativamente disminuido respecto de SHAM. La sobrevida en SHAM y OVX fue del 100% y en ZOL 77% (2 muertes); 2 ovejas del grupo ZOL presentaron necrosis de maxilar. Conclusiones: fue posible obtener desarrollo de BRONJ por tratamiento crónico con ZOL, el cual redujo notablemente la resorción y, según la relación Ca/P, posiblemente haya afectado la mineralización ósea. (AU)

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a complication of chronic treatment with the most powerful aminobisphosphonates (BPs). An experimental animal model would allow to determine the pathogenesis of this complication. Ewes exhibit similar oral cavity characteristics and bone metabolism as humans, and they are suitable for oral cavity interventions. We examined herein the clinical manifestations, bone remodeling status, and maxillary bone mass in adult female ewes treated with zoledronate (ZOL) for 22 months. Six ovariectomized (OVX) ewes received ZOL; and 5 OVX and 4 SHAM animals received saline solution. At the start of the experiment, and at the 4 and 22 month-time points serum Ca, P, crosslaps (CTX), and bone alkaline phosphatase were measured. Bone mineral content (BMC) of the superior hemimandible was measured at the end of the experiment. At this time point, CTX was significantly decreased only in the ZOL group (p<0.05). Ca and P content (g/g tissue) and BMC in the mandible were significantly decreased in the OVX group compared to SHAM animals (p<0.05) and only Ca content and BMC were decreased when compared to ZOL (p<0.05). ZOL treatment increased the Ca content and BMC, whereas the P content remained low compared to the SHAM group (p<0.05). All ewes from the SHAM and OVX groups and 77% of the animals from the ZOL group survived until the end of the experiment, whereas two ewes of ZOL group exhibited BRONJ. Conclusion: under our experimental conditions, it was possible to induce BRONJ by the chronic ZOL administration, which in turn induced a high reduction in bone resorption as well as possibly impaired bone mineralization, based on the Ca/P ratio in the mandible. (AU)

Animals , Diphosphonates/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/pathology , Zoledronic Acid/adverse effects , Tooth Extraction , Bone Diseases, Metabolic/chemically induced , Sheep/metabolism , Sheep/blood , Biomarkers/blood , Bone Density/drug effects , Bone Remodeling/drug effects , Densitometry , Experimental Development , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bisphosphonate-Associated Osteonecrosis of the Jaw/immunology , Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control , Zoledronic Acid/administration & dosage , Glucocorticoids/therapeutic use , Analgesics/therapeutic use , Ilium/cytology , Anesthetics, Dissociative/therapeutic use , Lidocaine/therapeutic use , Maxilla/cytology , Maxilla/drug effects , Maxilla/metabolism , Maxilla/diagnostic imaging , Anti-Bacterial Agents/therapeutic use
Rev. cir. traumatol. buco-maxilo-fac ; 17(1): 40-45, jan.-mar. 2017. ilus, tab
Article in Portuguese | LILACS, BBO | ID: biblio-1282005


Os bifosfonatos são uma classe de medicamentos, que têm por função a inibição da atividade dos osteoclastos, interferindo na remodelação e no turnover ósseo. São indicados para retardar a metástase óssea em algumas condições malignas, como em mielomas múltiplos, câncer de mama e próstata, e outras condições benignas, como no tratamento da doença de Paget e da osteoporose. Desde 2003, estudos têm associado a osteonecrose avascular dos ossos maxilares ao uso dos bifosfonatos. Dentre os mecanismos de ação dos bifosfonatos, podemos citar a sua atividade antiosteoclástica e antiangiogênica, que altera o metabolismo ósseo, inibindo a reabsorção óssea e diminuindo o turnover ósseo. As exposições ósseas maxilo-mandibulares ocorrem após procedimentos cirúrgicos odontológicos ou, menos comumente, após o uso de próteses apoiadas na fina mucosa de revestimento ósseo da cavidade bucal. O tratamento da osteonecrose associada aos bifosfonatos (OAB) é bastante variado, controverso e desafiador, visto que nenhum tratamento efetivo tem sido proposto até o momento. O objetivo desse relato de caso é descrever a ocorrência de áreas de exposição óssea mandibular em um paciente que fez uso do ácido zolendrônico (Zometa®) bem como apresentar a abordagem terapêutica realizada que resultou em completo recobrimento mucoso das áreas ósseas expostas... (AU)

Biphosphonates are a class of drugs whose function is the inhibition of osteoclast activity, interfering in remodeling and bone turnover. They are indicated to delay bone metastases in some malignancies such as multiple myeloma, prostate cancer and other benign conditions such as in the treatment of Paget's disease and osteoporosis. Since 2003, studies associate avascular osteonecrosis of the jaws to the use of bisphosphonates, especially intra venous. Among the mechanisms of action of bisphosphonates are their osteoclastic and antiangionenic activity which alters bone metabolism, inhibiting bone resorption and reducing bone turnover. Maxillo-mandibular bone exposures occur after surgical dental procedures or less commonly after the use of prostheses supported on thin bone lining mucosa of the buccal cavity. The treatment of osteonecrosis associated with biphosphonates (OAB) is quite varied, controversial and challenging, since no effective treatment has been proposed until this moment. The purpose of this case report is to describe the occurrence of areas of mandibular bone exposure in a patient with history of use of Zolendronic Acid (Zometa) and present the therapeutic approach undertaken which resulted in full mucous covering of the exposed bony áreas... (AU)

Humans , Male , Middle Aged , Bone Density Conservation Agents/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/diagnostic imaging , Zoledronic Acid/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/surgery
Rev. Hosp. Ital. B. Aires (2004) ; 37(2): 63-67, jun. 2017. graf., ilus.
Article in Spanish | LILACS | ID: biblio-1087149


Presentamos un paciente de 63 años con cáncer renal y aumento de fosfatasa alcalina sérica de tipo óseo de acuerdo con su reactividad con anticuerpos monoclonales específicos. Se descartaron las causas conocidas de aumento de la isoenzima, incluyendo metástasis óseas. Los niveles enzimáticos cayeron abruptamente con la remoción del tumor, por lo que consideramos a este último como su origen. Diversas isoenzimas de fosfatasa alcalina pueden ser producidas y secretadas por tumores como manifestación paraneoplásica. El conocimiento de esto puede, en ocasiones, orientarnos hacia la presencia de una neoplasia oculta. Además, los cambios en los niveles séricos de esas isoenzimas pueden ser indicadores de respuesta al tratamiento o de recidiva tumoral. (AU)

A 63-year old man was seen in the outpatient clinic because of renal cancer and elevation in bone alkaline phosphatase measured by monoclonal antibodies assay. Known causes of bone isoenzyme augmentation, including bone metastases, were ruled out. The tumoral origin of the isoenzyme was diagnosed because after removal of the tumor the enzymatic levels fell sharply. Several alkaline phosphatase isoenzymes can be produced and secreted by tumors as a paraneoplasic manifestation and their elevation could be a manifestation of an occult neoplasia. Furthermore the monitoring of their blood levels can be useful means of treatment response and a tool to monitoring recurrence if a sharp decrease after removal of the tumor is observed. (AU)

Humans , Male , Middle Aged , Alkaline Phosphatase/biosynthesis , Kidney Neoplasms/metabolism , Osteitis Deformans/diagnostic imaging , Atenolol/therapeutic use , Biomarkers , Erythropoietin/therapeutic use , Simvastatin/therapeutic use , Alkaline Phosphatase/analysis , Alkaline Phosphatase/radiation effects , Alkaline Phosphatase/physiology , Everolimus/therapeutic use , Sunitinib/therapeutic use , Zoledronic Acid/therapeutic use , Hypercholesterolemia/drug therapy , Hypertension/drug therapy , Ilium/diagnostic imaging , Anemia/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/drug therapy , Kidney Neoplasms/diagnostic imaging , Antibodies, Monoclonal/radiation effects