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Objectives: There are challenges for the treatment of osteoporosis in patients with kidney failure and monoclonal antibodies (MAb) might be a suitable therapy. However, the efficacy and safety of MAb among patients with osteoporosis and renal insufficiency remains unclear. Methods: We systematically searched PubMed, Embase, and Cochrane Central for studies evaluating the efficacy and safety of the use of MAb in patients with osteoporosis and renal insufficiency. We pooled risk ratios (RR) and 95% confidence intervals (CI) for binary outcomes. Mean difference (MD) was used for continuous outcomes. Results: We included 5 studies with 33,550 patients. MAb therapy decreased the risk of vertebral fractures (RR 0.32; 95% CI 0.26-0.40; P < 0.01) when compared to placebo and no statistical difference was found when comparing to bisphosphonate (RR 0.71; 95% CI 0.49-1.03; P = 0.07). MAb therapy also decreased the risk of nonvertebral fractures (RR 0.79; 95% CI 0.69-0.91; P = 0.0009). Lumbar spine bone mineral density (BMD) was higher in the MAb therapy when compared to both placebo (MD 10.90; 95% CI 8.00-13.80; P < 0.01) and bisphosphonate (MD 7.66; 95% CI 6.19-9.14; P < 0.01). There was no statistically significant difference in the change of estimated glomerular filtration rate and in the incidence of hypocalcemia and serious adverse events between groups. Conclusions: There were reductions in both vertebral and nonvertebral fracture risks, alongside improvements in BMD among patients with renal insufficiency treated with MAb.

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Data on long-term treatment regimens for preventing bone mineral density (BMD) loss that occurs after denosumab (Dmab) withdrawal are scarce. Our aim was to evaluate the long-term changes (12-36 months) in BMD and bone turnover markers in a group of postmenopausal women who had been treated with Dmab and received subsequent treatment with bisphosphonates. Secondary objectives were to evaluate factors associated with BMD loss, to compare the BMD change in patients who received oral vs intravenous bisphosphonates, and to assess the frequency of fragility fractures after Dmab discontinuation. The clinical data of 54 patients, 26 of whom had clinical and DXA assessments at 36 months, were analyzed. After 12 months, the mean LS BMD had decreased by 2.8% (±5.0), FN BMD by 1.9% (±5.8), and TH BMD by 1.9% (±3.7). After 36 months, LS BMD had decreased by 3.7% (±6.7), FN BMD by 2.5% (±7.1), and TH BMD by 3.6% (±5.2). C-terminal cross-linked telopeptide of type I collagen significantly increased during the first 12 months after Dmab withdrawal but then decreased at 36 months. BMD loss at 12 months was higher in patients with more than 30 months of Dmab treatment, but this difference was only statistically significant at FN (-3.3% vs -0.3%, P = .252 at LS, -3.3% vs 0.3%, P = .033 at FN, and -2.1% vs 0.9, P = .091 at TH). There were no statistically significant differences regarding the change in BMD at 12 and 36 months between oral and intravenous treatment. Seven patients suffered incidental vertebral fractures (clinical vertebral fractures: n = 6, morphometric fractures: n = 1) three of which were multiple. None of these patients were treated following international or institutional guidelines or recommendations. In summary, our study suggests that bisphosphonates can help maintain BMD for 36 months after Dmab discontinuation.

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Presentamos un caso de quiste óseo aneurismático (QOA) de ubicación infrecuente y comportamiento agresivo en un paciente masculino de 28 años, en que la resección quirúrgica es controversial por el riesgo de iatrogenia y eventual recurrencia. El tratamiento con denosumab ha sido recientemente propuesto como una alternativa para el manejo de QOAs irresecables o recurrentes; sin embargo, la literatura disponible es escasa. Reportamos nuestra experiencia en un caso y analizamos la bibliografía disponible

We present a case of aneurysmal bone cyst (ABC) of infrequent location and aggressive behavior in a 28-year-old male patient, in which surgical resection is controversial due to the risk of iatrogenicity and eventual recurrence. Treatment with denosumab has been recently proposed as an alternative for the management of unresectable or recurrent ABCs; however, the available literature is sparse. We report our experience with one case and analyze the available literature

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Denosumab has been considered a treatment option for Central Giant Cell Granuloma (CGCG) a benign locally aggressive osteolytic lesion of the jaws. This study aimed to perform a scoping review of CGCG treated with Denosumab. The research question was: What is Denosumab's effectiveness in treating CGCG of the jaws? Studies that used Denosumab as a treatment for CGCGs in the jaws were selected following PRISMA-ScR guidelines, using Pubmed/Medline, Scopus, and Springer Link databases, among others. Demographics, clinical information, dosing, efficacy, adverse drug reactions (ADRs), and imaging tests used to assess the evolution of the lesions were extracted. Twenty-one studies were selected. Sixty patients with a mean age of 23.2 years were treated with Denosumab, 42% with 120 mg subcutaneously monthly, additional doses on days 1, 8, and 15 for month 1 in adults. In children, dosing was adjusted by weight to 60 or 70 mg. To avoid ADRs 500 mg of calcium and 400 IU of vitamin D orally were used. Initial effective response was reported after 1-3 months, with recurrence of 19.6% and ADRs in 74% of cases. Denosumab is effective for CGCG with monthly subcutaneous doses of 120 mg, 60 or 70 mg in patients < 45 or 50 kg for ≥ 12 months with calcium and vitamin D supplementation until remission changes are observed. Extensive or refractory lesions were the main indications. Common ADRs were hypo and hypercalcemia. Further studies are needed to define dose and supplementation protocols to avoid ADRs during and after therapy.

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Evidence on the management of rebound-associated vertebral fractures after denosumab discontinuation is scarce. This study describes seven patients retreated with denosumab, teriparatide or zoledronate for 24 months. Their bone mineral density remained stable or improved and no new fractures occurred suggesting that all three options might be adequate for their treatment. PURPOSE: To describe the densitometric and biochemical changes achieved with osteoactive treatment after 24 months of follow-up in patients who suffered rebound-associated vertebral fractures (RAVFs) after Dmab discontinuation, and to report the occurrence of new vertebral and non-vertebral fractures. METHODS: Patients with RAVFs who received retreatment (RT) for 24 months were included. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), femoral neck (FN) and total hip (TH), along with C-terminal cross-linked telopeptide of type I collagen, osteocalcin, and bone alkaline phosphatase. Data were collected at the start of the RT and after 24 months. RESULTS: Seven female patients were included. RT consisted in Dmab (n = 3), teriparatide (TPT) (n = 3) and zoledronate (Zol) (n = 1). At 24 months, the mean BMD change was 2.2% at LS, 6.8% at FN and 3.8% at TH in the Dmab group, 7.5% at LS, 1.4% at FN and 3.7% at TH in the TPT group and, 5.0% at LS, 0.6% at FN and 3.9% at TH in the patient with Zol. After 24 months of follow-up, no patient suffered new fractures. CONCLUSION: In this series of patients with RAVFs, we did not observe any new fractures and the BMD remained stable after 24 months of RT. Future studies are needed to evaluate the most suitable treatment approach after RAVFs but these preliminary data suggest that all denosumab, zoledronate and teriparatide might be adequate options.

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PURPOSE: Fracture Liaison Services programs reduce mortality and the risk of refracture and increase treatment and adherence rates. Greater coverage is an important priority for the future. The aim was to determine the characteristics of patients over 50 years old who suffered fractures and the effectiveness of a Fracture Liaison Services program in a health care institution in Colombia. METHODS: This was a retrospective follow-up study of a cohort of patients with vertebral and nonvertebral fractures managed in a Fracture Liaison Services program. Sociodemographic, clinical and pharmacological variables were identified. Key performance indicators were used to evaluate the effectiveness of the program. Descriptive and bivariate analysis was performed. RESULTS: A total of 438 patients were analyzed. The average age was 77.5 years, and 78.5% were women. Hip and vertebral fractures were the most common (25.3% and 24.9%, respectively). Vertebral fractures prevailed in men (33.0% vs 22.7%; p = 0.041) and those of the radius/ulna in women (20.3% vs 10.6%; p = 0.031). A total of 29.7% had experienced a previous fracture, and 16.7% had received antiosteoporosis drugs. A total of 63.5% of the cases were managed surgically. At discharge, 58.8% received prescriptions for calcium/vitamin D, and 50.7% with prescriptions of antiosteoporotic therapy, especially teriparatide (21.2%) and denosumab (16.4%), without significant differences by sex. However, in women with hip fractures, anti-osteoporotic management prevailed (83.7% vs 64.0; p = 0.032). The effectiveness of the overall program per year was 74.6%. On follow-up, only 9.1% of patients had experienced a new fall, and of those 3.7% presented a new fracture. A total of 4.3% died during follow-up. CONCLUSIONS: Good adherence to the recommendations of the country's clinical practice guidelines was found, and overall, the effectiveness of the program was very satisfactory, with a low incidence of new fractures during follow-up. Fracture Liaison Services programs reduce mortality and the risk of refracture. A retrospective follow-up study of a cohort of patients with vertebral and nonvertebral fractures managed in a Fracture Liaison Services, showed that the effectiveness was 73.6%. On follow-up, 9.1% of patients had experienced a new fall, and of those 3.7% presented a new fracture.

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Dental implants are a predictable option to replace missing teeth. Patients on antiresorptive medications used to treat disorders associated with bone resorption may need dental implants to replace missing teeth. The data on implant failure in patients on antiresorptive medication requiring dental implants, is conflicting and limited. This systematic review aims to investigate if antiresorptive medications have any clinical impact on dental implant survival. Electronic databases were searched until May 2020. The focus question (PICOS): Participants: humans, Interventions: implant placement surgery in patients on antiresorptive medication, Comparisons: patients on antiresorptive medication vs control (patients not on antiresorptive medication), Outcomes: implant survival, and Study design: clinical studies. The protocol of this systematic review was registered in PROSPERO (CRD42020209083). Fourteen nonrandomized studies were selected for data extraction and risk of bias assessment using the ROBINS-1 tool. Only studies with a control were included for the meta-analysis, 8 articles were included in the meta-analysis using implant-level data, and 5 articles were included in the meta-analysis using patient-level data. There was no statistical significance between the 2 groups at the patient level based on 265 patients. However, there was a statistically significant difference at the implant level based on 2697 implants. Therefore, antiresorptive medications, mainly bisphosphonates (BPs), may significantly contribute to implant failure. Antiresorptive medications, especially BPs may reduce implant survival and impair the osseointegration of dental implants. Failed implants in patients on BPs may not lead to osteonecrosis and may be replaced with success.

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O edema tardio intermitente persistente (ETIP) é uma reação inflamatória imunomediada desencadeada pela aplicação de ácido hialurônico (AH). É classificado clinicamente como não depressível, difuso e de caráter tardio, por aparecer, no mínimo, 30 dias após a aplicação. Ademais, caracteriza-se como intermitente e recorrente, visto que a reação pode reaparecer enquanto a substância perdurar no tecido. O presente estudo tem como objetivo relatar um caso de ETIP desencadeado pelo medicamento Prolia, sua apresentação clínica e evolução do quadro, bem como o tratamento realizado. No presente relato de caso, foi observada essa reação após uso do medicamento Prolia (Denosumabe), um anticorpo monoclonal que reduz a reabsorção óssea, utilizado para o tratamento da osteoporose. A paciente em questão é uma mulher de 56 anos, procedente de Joaçaba (SC), a qual apresentou placas eritematosas infiltradas na região do lábio superior, inferior e sulconasomentual, após cinco meses da aplicação do AH. Após conhecimento das medicações de uso e posterior confirmação histopatológica, foi diagnosticada com ETIP e iniciou conduta médica. A ETIP geralmente apresenta uma progressão benigna, se diagnosticada e tratada corretamente. A paciente em questão apresentou completa melhora clínica e, apesar de ainda não existir um consenso na literatura sobre como manejar a ETIP, o tratamento que melhor se adaptou ao caso foi a administração de Prednisolona por 4 semanas. Por não haver sido descrito anteriormente, na literatura mundial, o aparecimento de ETIP desencadeado pelo Denosumabe, destaca-se a importância do presente estudo para elucidação desta possível inteiração entre os compostos.

Persistent intermittent delayed swelling (PIDS) is an inflammatory reaction immune-mediated by the application of hyaluronic acid (HA). It is clinically classified as non-depressible, diffuse, and delayed, as its onset is in at least 30 days following application. Moreover, it is characterized as intermittent and reocurring, as the reaction may reappear while the substance remains in the tissue. The present study aims to report a case of PIDS caused by the drug Prolia, including its clinical presentation and development, as well as the treatment performed. In this case report the reaction was observed after the use of Prolia (Denosumab), a monoclonal antibody that reduces bone reapsorption, indicated for the treatment of osteoporosis. The patient was 56 years-old woman from Joaçaba (SC) that presented erythematous plaques in the upper and lower lip regions and in the melomental folds five months after the application of HA. After acknowledging the medications under use and histopathological confirmation, the patient was dignosed with PIDS and started medical treatment. PIDS usually has a benign progression if correctly diagnosed and treated. The patient made a full clinical recovery and, despite the lack of consensus in the literature for the management of PIDS, the treatment with best responses for this case was the administration of Prednilosone for four weeks. As the emergence of PIDS triggered by Denosumab was not previously described in the global literature, the current study is important to elucidate the possible interaction between the compounds.

La hinchazón persistente intermitente retardada (PIDS) es una reacción inflamatoria inmunomediada por la aplicación de ácido hialurónico (AH). Clínicamente se clasifica como no depresible, difusa y retardada, ya que su aparición se produce en al menos 30 días tras la aplicación. Además, se caracteriza como intermitente y recidivante, ya que la reacción puede reaparecer mientras la sustancia permanece en el tejido. El presente estudio tiene como objetivo reportar un caso de PIDS causado por el medicamento Prolia, incluyendo su presentación clínica y desarrollo, así como el tratamiento realizado. En este caso clínico la reacción se observó tras el uso de Prolia (Denosumab), un anticuerpo monoclonal que reduce la reabsorción ósea, indicado para el tratamiento de la osteoporosis. La paciente era una mujer de 56 años de Joaçaba (SC) que presentó placas eritematosas en las regiones labial superior e inferior y en los pliegues melomentales cinco meses después de la aplicación del HA. Después del reconocimiento de los medicamentos en uso y de la confirmación histopatológica, la paciente fue dignosticada con PIDS e inició tratamiento médico. El PIDS suele tener una evolución benigna si se diagnostica y trata correctamente. La paciente tuvo una recuperación clínica completa y, a pesar de la falta de consenso en la literatura para el manejo de laIDS, el tratamiento con mejores respuestas para este caso fue la administración de Prednilosona durante cuatro semanas. Como la aparición de PIDS desencadenada por Denosumab no fue descrita anteriormente en la literatura mundial, el presente estudio es importante para dilucidar la posible interacción entre los compuestos.

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ABSTRACT: Currently, there are no guidelines for treating osteoporosis in spinal surgery. The rate of complications such as screw loosening, proximal junction kyphosis, cage subsidence, and loss of reduction in fractures is high. Objective: To evaluate the use of teriparatide and denosumab in planning spinal surgery in an osteoporotic patient with degenerative pathology, emphasizing the fusion rate, bone mineral density, and decreased complications. Method: A systematic search was performed in medical reference databases for comparative studies of teriparatide and denosumab in spinal surgery to evaluate fusion, screw loosening, bone mineral density, and decrease in the incidence of vertebral fractures. χ2 was implemented for the statistical analysis, according to PRISMA (2020). Result: Fusion rate with teriparatide was 79.28% in the first six months, 95% CI (OR 2.62) and decreased screw loosening rate 81.9% 95% CI (OR 0.6). Increase in bone mineral density 15.5% OR 1.49 (0.77 - 2.86) and decrease in vertebral fracture rate 85.4% OR 0.5. Conclusions: Teriparatide and denosumab should be considered in perioperative spinal planning due to their effectiveness, synergism, and low adverse effects; to improve bone mineral density and decrease the rate of complications. Clinical, comparative, and statistically significant studies are required to confirm this. Level of Evidence II; Systematic Review and Meta-analysis.

RESUMO: Atualmente não existem diretrizes para o tratamento da osteoporose em cirurgia da coluna vertebral. A taxa de complicações como afrouxamento de parafuso, cifose da junção proximal, subsidência da gaiola e perda de redução nas fraturas é alta. Objetivo: Avaliar o uso de teriparatida e/ou denosumabe no planejamento da cirurgia da coluna vertebral em pacientes osteoporóticos com patologia degenerativa, enfatizando a taxa de fusão, densidade mineral óssea e diminuição de complicações. Método: Foi realizada uma busca sistemática em bases de dados de referência médica para estudos comparativos de teriparatida e denosumabe em cirurgia da coluna vertebral, a fim de avaliar fusão, soltura de parafuso, densidade mineral óssea e diminuição da incidência de fraturas vertebrais. O χ2 foi implementado para a análise estatística, de acordo com PRISMA (2020). Resultado: A taxa de fusão com teriparatida foi de 79,28% nos primeiros 6 meses IC 95% (OR 2,62) e diminuiu a taxa de afrouxamento do parafuso 81,9% IC 95% (OR 0,6). O aumento da densidade mineral óssea foi de 15,5% OR 1,49 (0,77 - 2,86) e a diminuição da taxa de fratura vertebral atingiu 85,4% OR 0,5. Conclusões: A teriparatida e o denosumabe devem ser considerados no planejamento espinhal perioperatório devido à sua efetividade, sinergismo e baixos efeitos adversos, melhorando a densidade mineral óssea e diminuir a taxa de complicações. Estudos clínicos, comparativos e estatisticamente significativos são necessários para confirmar os achados. Nível de Evidência II; Revisão Sistemática e Meta-análise.

RESUMEN: Actualmente no existen pautas para el tratamiento de la osteoporosis en cirugía espinal. La tasa de complicaciones como el aflojamiento de los tornillos, la cifosis de la unión proximal, el hundimiento del aparato Ilizarov y la pérdida de reducción de las fracturas es alta. Objetivo: Evaluar el uso de teriparatida y/o denosumab en la planificación de la cirugía de columna en el paciente osteoporótico con patología degenerativa haciendo hincapié en la tasa de fusión, la densidad mineral ósea y la disminución de las complicaciones. Método: Se realizó una búsqueda sistemática en bases de datos de referencia médica para estudios comparativos de teriparatida y denosumab en cirugía espinal con el fin de evaluar la fusión, el aflojamiento de tornillos, la densidad mineral ósea y la disminución de la incidencia de fracturas vertebrales. χ2 se implementó para el análisis estadístico, según PRISMA (2020). Resultado: La tasa de fusión con teriparatida fue del 79,28% en los primeros 6 meses IC 95% (OR 2,62) y disminuyó la tasa de aflojamiento del tornillo 81,9% IC 95% (OR 0,6). Aumento de la densidad mineral ósea 15,5% O 1,49 (0,77 - 2,86) y disminución de la tasa de fractura vertebral 85,4% O 0,5. Conclusiones: La teriparatida y el denosumab deben ser considerados en la planificación espinal perioperatoria debido a su efectividad, sinergismo y bajos efectos adversos; con el fin de mejorar la densidad mineral ósea y disminuir la tasa de complicaciones. Se requieren estudios clínicos, comparativos y estadísticamente significativos para confirmarlo. Nivel de Evidencia II; Revisión sistemática y metaanálisis.

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Denosumab is a potent anti-resorptive medication used to treat patients at high risk for osteoporosis; however, its beneficial effects on the skeletal system are quickly reversed after discontinuation. In contrast, bisphosphonates (BPs) are anti-resorptive agents with residual effects on the bone matrix; thus, these are capable of preserving bone mass for a long time. Therefore, subsequent anti-resorptive treatment with BPs is mandatory to prevent rebound fractures. Furthermore, BP administration before denosumab treatment appears to be a reasonable strategy for reducing hyperactivation of bone remodeling. In this review, we summarize the effects of BP administration before denosumab treatment in preventing rebound fractures after denosumab discontinuation.