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1.
Bone Joint J ; 101-B(10): 1285-1291, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31564154

RESUMO

AIMS: Currently, periprosthetic fractures are excluded from the American Society for Bone and Mineral Research (ASBMR) definition of atypical femoral fracture (AFFs). This study aims to report on a series of periprosthetic femoral fractures (PFFs) that otherwise meet the criteria for AFFs. Secondary aims were to identify predictors of periprosthetic atypical femoral fractures (PAFFs) and quantify the complications of treatment. PATIENTS AND METHODS: This was a retrospective case control study of consecutive patients with periprosthetic femoral fractures between 2007 and 2017. Two observers identified 16 PAFF cases (mean age 73.9 years (44 to 88), 14 female patients) and 17 typical periprosthetic fractures in patients on bisphosphonate therapy as controls (mean age 80.7 years (60 to 86, 13 female patients). Univariate and multivariate analysis was performed to identify predictors of PAFF. Management and complications were recorded. RESULTS: Interobserver agreement for the PAFF classification was excellent (kappa = 0.944; p < 0.001). On univariate analysis compared with controls, patients with PAFFs had higher mean body mass indices (28.6 kg/m2 (sd 8.9) vs 21.5 kg/m2 (sd 3.3); p = 0.009), longer durations of bisphosphonate therapy (median 5.5 years (IQR 3.2 to 10.6) vs 2.4 years (IQR 1.0 to 6.4); p = 0.04), and were less likely to be on alendronate (50% vs 94%; p = 0.02) with an indication of secondary osteoporosis (19% vs 0%; p = 0.049). Duration of bisphosphonate therapy was an independent predictor of PAFF on multivariate analysis (R2 = 0.733; p = 0.05). Following primary fracture management, complication rates were higher in PAFFs (9/16, 56%) than controls (5/17, 29%; p = 0.178) with a relative risk of any complication following PAFF of 1.71 (95% confidence interval (CI) 0.77 to 3.8) and of reoperation 2.56 (95% CI 1.3 to 5.2). CONCLUSION: AFFs do occur in association with prostheses. Longer duration of bisphosphonate therapy is an independent predictor of PAFF. Complication rates are higher following PAFFs compared with typical PFFs, particularly of reoperation and infection. Cite this article: Bone Joint J 2019;101-B:1285-1291.


Assuntos
Artroplastia de Quadril/efeitos adversos , Difosfonatos/efeitos adversos , Osteoporose/tratamento farmacológico , Fraturas Periprotéticas/induzido quimicamente , Fraturas Periprotéticas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/métodos , Estudos de Casos e Controles , Intervalos de Confiança , Difosfonatos/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/cirurgia , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Variações Dependentes do Observador , Osteoporose/complicações , Fraturas Periprotéticas/diagnóstico por imagem , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Estados Unidos
2.
J Assoc Physicians India ; 67(9): 87-90, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31561698

RESUMO

Pachydermoperiostosis is a rare genetic disorder which commonly presents with clubbing, bone pains and skin changes. The treatment is mostly unsatisfactory. We tried bisphosphonates in our case with encouraging results. We suggest that parenteral bisphosphonates should be tried early in treatment of Pachydermoperiostosis.


Assuntos
Difosfonatos/uso terapêutico , Osteoartropatia Hipertrófica Primária/tratamento farmacológico , Humanos , Pele
3.
J Biol Regul Homeost Agents ; 33(3 Suppl. 1): 43-50, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31538449

RESUMO

Customization of post-and-cores using computer-aided-design and computer-aided-manufacturing (CAD-CAM) requires the scanning of a pattern and the subsequent digital design. This case report describes the production of a CAD-CAM customized post-and-core designed from an intraoral scan and milled from a metal block. The use of an intraoral scanner (IOS) for post-endodontic rehabilitation could lead to a faster and more efficient CAD-CAM customized post-and-core realization. The use of a high resistance material such as metal is paramount in cases with high loss of coronal structure. The patient has been treated with bisphosphonate (BP) for years. The risk of osteonecrosis of the jaw after extraction was high.


Assuntos
Projeto Auxiliado por Computador , Implantes Dentários , Fluxo de Trabalho , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Implantação Dentária Endo-Óssea Endodôntica , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Humanos , Metais
4.
Orthop Clin North Am ; 50(4): 433-443, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31466660

RESUMO

This article serves to provide an overview of molecular and surgical interventions to minimize the progression of posttraumatic arthritis following high-energy intra-articular fractures. The roles of cartilage and the microcellular environment are discussed, as well as the response of the joint and cartilage to injury. Molecular therapies, such as glucocorticoids, mesenchymal stem cells, and bisphosphonates, are presented as potential treatments to prevent progression to posttraumatic arthritis. High-energy intra-articular fractures of the elbow, hip, knee, and ankle are discussed, with emphasis on restoring anatomic alignment, articular reduction, and stability of the joint.


Assuntos
Cartilagem Articular/lesões , Fraturas Intra-Articulares/complicações , Osteoartrite/terapia , Artroplastia , Difosfonatos/uso terapêutico , Progressão da Doença , Glucocorticoides/uso terapêutico , Humanos , Ácido Hialurônico/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Osteoartrite/etiologia
5.
Braz Oral Res ; 33: e050, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31269114

RESUMO

The present study aimed to investigate the use of platelet-rich plasma (PRP) on tooth extraction sites in rats treated with bisphosphonates. Thirty Albinus Wistar male rats were administered 0.035 mg/kg zoledronic acid intravenously for 8 weeks, divided into four administrations with a 2-week interval between each application, after which their upper right central incisors were extracted to induce the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). The samples were divided into the following two groups: Group 1 (G1) underwent marginal resection of BRONJ followed by the use of PRP, while Group 2 (G2) underwent resection of BRONJ but without the use of PRP. The treatment groups were evaluated after 14, 28, and 42 days. Clinical, microtomographic, microscopic, and immunohistochemical (IHC) evaluations were performed. Microtomography results revealed no significant difference between the groups (p <0.05) in any time period. Histomorphometric analysis showed increased bone formation over time for both groups (p < 0.001). G1 demonstrated a greater amount of new bone formation than G2 at 28 and 42 days (p < 0.001), with G1 presenting greater vascularization and a slightly higher VEGF expression. For both groups, RANKL/OPG expression levels were sufficient as a parameter for indicating the rate of bone remodeling in a previously treated area of osteonecrosis groups. Taken together, our findings indicated that the use of PRP improves the resolution process of BRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Plasma Rico em Plaquetas , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/fisiopatologia , Modelos Animais de Doenças , Masculino , Osteoclastos/efeitos dos fármacos , Ratos , Ratos Wistar , Extração Dentária/efeitos adversos , Cicatrização
6.
BMC Vet Res ; 15(1): 211, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234844

RESUMO

BACKGROUND: Bisphosphonates (BPs) are a family of molecules characterized by two key properties: their ability to bind strongly to bone mineral and their inhibitory effects on mature osteoclasts and thus bone resorption. Chemically two groups of BPs are recognized, non-nitrogen-containing and nitrogen-containing BPs. Non-nitrogen-containing BPs incorporate into the energy pathways of the osteoclast, resulting in disrupted cellular energy metabolism leading to cytotoxic effects and osteoclast apoptosis. Nitrogen-containing BPs primarily inhibit cholesterol biosynthesis resulting in the disruption of intracellular signaling, and other cellular processes in the osteoclast. BODY: BPs also exert a wide range of physiologic activities beyond merely the inhibition of bone resorption. Indeed, the breadth of reported activities include inhibition of cancer cell metastases, proliferation and apoptosis in vitro. In addition, the inhibition of angiogenesis, matrix metalloproteinase activity, altered cytokine and growth factor expression, and reductions in pain have been reported. In humans, clinical BP use has transformed the treatment of both post-menopausal osteoporosis and metastatic breast and prostate cancer. However, BP use has also resulted in significant adverse events including acute-phase reactions, esophagitis, gastritis, and an association with very infrequent atypical femoral fractures (AFF) and osteonecrosis of the jaw (ONJ). CONCLUSION: Despite the well-characterized health benefits of BP use in humans, little is known regarding the effects of BPs in the horse. In the equine setting, only non-nitrogen-containing BPs are FDA-approved primarily for the treatment of navicular syndrome. The focus here is to discuss the current understanding of the strengths and weaknesses of BPs in equine veterinary medicine and highlight the future utility of these potentially highly beneficial drugs.


Assuntos
Doenças Ósseas/veterinária , Difosfonatos/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Animais , Doenças Ósseas/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Previsões , Cavalos , Humanos , Coxeadura Animal/tratamento farmacológico , Osteocondrose/tratamento farmacológico , Osteocondrose/veterinária , Osteoclastos/efeitos dos fármacos
7.
Drugs Aging ; 36(7): 625-638, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31066015

RESUMO

In patients with osteoporosis and severely reduced bone mass and/or recurring fractures, antiresorptive therapy may not be the optimal first-line treatment. Two recent clinical trials comparing bone-forming treatment with antiresorptive therapy have demonstrated that bone-forming treatment is superior in reducing the fracture risk in patients with severe osteoporosis. All of the currently available bone-forming agents-teriparatide, abaloparatide, and romosozumab-increase bone mineral density (BMD) and reduce the fracture risk; however, the effect wears off with time and treatment is therefore only transient. Thus, a bone-forming therapy should be followed by antiresorptive treatment with a bisphosphonate or denosumab. The BMD response to bone-forming treatment is reduced in patients previously treated with antiresorptive drugs; however, based on the findings of the VERO trial, the anti-fracture efficacy of bone-forming treatment in comparison with antiresorptives seems to be preserved. This review provides an overview of the existing bone-forming therapies for osteoporosis including considerations of sequential and combination therapy.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Quimioterapia Combinada , Humanos , Osteogênese/efeitos dos fármacos , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Teriparatida/uso terapêutico
8.
Expert Opin Pharmacother ; 20(11): 1377-1386, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31063415

RESUMO

INTRODUCTION: Complex regional pain syndromes (CRPS) are rare painful conditions characterized by considerable variability in possible triggering factors, usually traumatic, and in the clinical scenario. The limited knowledge of the pathophysiological mechanisms has led to countless treatment attempts with multiple conservative and surgical options that act by different mechanisms of action. AREAS COVERED: In this narrative review, the authors discuss key points about CRPS definitions, diagnostic criteria and pitfalls, pathophysiological hypotheses, and treatment strategies with particular reference to pharmacotherapy. The article was based on a literature search using PubMed while the available guidelines for the management of CRPS were also examined. EXPERT OPINION: According to the quality of evidence, pharmacological interventions for CRPS seem to be more effective all the more so when they act on peripheral mechanisms, particularly on nociceptive pain, and when applied early in the disease, while reliable evidence about central mechanisms of chronic pain in CRPS is lacking. In our opinion, drug therapy should be preferred as early as possible, particularly in warm forms of CRPS to prevent significant functional limitation, psychological distress, and social and economic fallout.


Assuntos
Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Síndromes da Dor Regional Complexa/tratamento farmacológico , Toxinas Botulínicas/uso terapêutico , Síndromes da Dor Regional Complexa/diagnóstico , Síndromes da Dor Regional Complexa/fisiopatologia , Suplementos Nutricionais , Difosfonatos/uso terapêutico , Humanos
9.
Cancer Treat Rev ; 76: 57-67, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31136850

RESUMO

Patients with solid tumours are at risk of impaired bone health from metastases and cancer therapy-induced bone loss (CTIBL). We review medical management of bone health in patients with solid tumours over the past 30 years, from first-generation bisphosphonates to the receptor activator of nuclear factor κB ligand (RANKL)-targeted monoclonal antibody, denosumab. In the 1980s, first-generation bisphosphonates were shown to reduce the incidence of skeletal-related events (SREs) in patients with breast cancer. Subsequently, more potent second- and third-generation bisphosphonates were developed, particularly zoledronic acid (ZA). Head-to-head studies showed that ZA was significantly more effective than pamidronate for reducing SREs in patients with breast and castrate-resistant prostate cancer (CRPC), becoming the standard of care for more than a decade. The RANKL inhibitor denosumab was licensed in 2010, and head-to-head studies and integrated analyses confirmed its superiority to ZA for preventing SREs, particularly in breast cancer and CRPC. Bisphosphonates and denosumab have also been investigated for prevention of CTIBL in patients receiving hormonal therapy for breast and prostate cancer, and denosumab is licensed in this indication. Despite advances in management of bone health, several issues remain, notably the optimal time to initiate therapy, duration of therapy, and dosing frequency, and how to avoid toxicity, particularly with long-term treatment. In summary, introduction of ZA and denosumab has protected patients with bone metastasis from serious bone complications and improved their quality of life. Ongoing research will hopefully guide the optimal use of these agents to help maintain bone health in patients with solid tumours.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Difosfonatos/uso terapêutico , Animais , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/etiologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Denosumab/uso terapêutico , Feminino , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Ácido Zoledrônico/uso terapêutico
10.
Expert Opin Ther Pat ; 29(5): 315-325, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31023104

RESUMO

INTRODUCTION: Bisphosphonates (BPs) are widely used to manage a variety of bone disorders, including osteoporosis, metastatic bone disease and myeloma bone disease. The nitrogen-containing BPs (NBPs) target osteoclast activity by disrupting protein prenylation via inhibition of farnesyl diphosphate synthase (FDPS). AREAS COVERED: This review summarizes the recent advances in BPs with a focus on the latest patents (2015-2018). Patents involving novel BPs, new modes of BP delivery, as well as use of BPs to deliver other drugs to bone are discussed. A review of phosphonate-based drugs targeting geranylgeranyl diphosphate synthase (GGDPS) or geranylgeranyl transferase II (GGTase II) as alternative strategies to disrupt protein geranylgeranylation is provided. EXPERT OPINION: While the NBPs remain the mainstay of treatment for most bone disorders, further understanding of their pharmacological properties could lead to further refinement of their chemical structures and optimization of efficacy and safety profiles. In addition, the development of NBP analogs or drug delivery mechanisms that allow for nonbone tissue exposure could allow for the use of these drugs as direct anticancer agents. The development of GGDPS and GGTase II inhibitors represents alternative heterocycle phosphonate-based strategies to disrupt protein geranylgeranylation and may have potential as anticancer agents and/or as bone-targeted therapies.


Assuntos
Doenças Ósseas/tratamento farmacológico , Difosfonatos/uso terapêutico , Prenilação de Proteína/efeitos dos fármacos , Animais , Doenças Ósseas/fisiopatologia , Difosfonatos/farmacologia , Sistemas de Liberação de Medicamentos , Desenvolvimento de Medicamentos , Farnesiltranstransferase/antagonistas & inibidores , Geraniltranstransferase/antagonistas & inibidores , Humanos , Osteoclastos/efeitos dos fármacos , Patentes como Assunto , Transferases/antagonistas & inibidores
11.
Expert Opin Pharmacother ; 20(9): 1123-1134, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30958709

RESUMO

INTRODUCTION: Pharmacological options to address the imbalance between bone resorption and accrual in osteoporosis include anti-resorptive and osteoanabolic agents. Unique biologic pathways such as the Wnt/ß-catenin pathway have been targeted in the quest for new emerging therapeutic strategies. AREAS COVERED: This review provides an overview of existing pharmacotherapy for osteoporosis in women and explore state-of-the-art and emerging therapies to prevent bone loss, with an emphasis on the mechanism of action, indications and side effects. EXPERT OPINION: Bisphosphonates appear to be a reliable and cost-effective option, whereas denosumab has introduced a simpler dosing regimen and may achieve a linear increase in bone mineral density (BMD) with no plateau being observed, along with continuous anti-fracture efficacy. Abaloparatide, a parathyroid-hormone-related peptide (PTHrP)-analogue, approved by the FDA in April 2017, constitutes the first new anabolic osteoporosis drug in the US for nearly 15 years and has also proven its anti-fracture efficacy. Romosozumab, a sclerostin inhibitor, which induces bone formation and suppresses bone resorption, has also been developed and shown a significant reduction in fracture incidence; however, concerns have arisen with regard to increased cardiovascular risk.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Conservadores da Densidade Óssea/farmacologia , Difosfonatos/farmacologia , Feminino , Humanos
12.
Brasília; CONITEC; abr. 2019. ilus, tab.
Não convencional em Português | BRISA/RedTESA | ID: biblio-997099

RESUMO

INTRODUÇÃO: A doença de Paget óssea (DPO) ou osteíte deformante é uma doença osteometabólica local em que ocorre remodelação óssea intensa, uni ou multifocal. A reabsorção óssea aumentada se associa subsequentemente à atividade de neoformação óssea, mediada por osteoblastos, produzindo um osso estruturalmente inferior nos locais afetados, facilmente deformado por sobrecargas ou forças tensionais musculares. Atualmente, os bisfosfonatos IV são considerados tratamento de escolha para a DPO por serem altamente efetivos em suprimir o turnover ósseo aumentado, sendo o ácido zoledrônico (ZOL) a melhor alternativa na falha ou contraindicação dos bisfosfonatos orais. A CONITEC avaliou as evidências do ZOL para o tratamento da Doença de Paget óssea, conforme relatório de recomendação Nº 416, e recomendou sua incorporação no tratamento da DPO como primeira linha de tratamento. TECNOLOGIA: pamidronato dissódico (pamidronato dissódico e Pamidron®, Fauldpami®). PERGUNTA: O uso do pamidronato dissódico é eficaz, seguro e custo-efetivo em pacientes com Doença de Paget óssea quando comparado aos bisfosfonatos disponíveis no SUS? EVIDÊNCIAS CIENTÍFICAS: Foram selecionados quatro estudos que avaliaram o pamidronato na Doença de Paget. O ZOL demonstrou ser superior ao pamidronato nos desfechos de resposta terapêutica e na dor óssea. Houve melhora leve e não significativa na qualidade de vida para os dois bisfosfonatos intravenosos. A resposta ao ZOL é independente da idade, do sexo, da Faz basal e de tratamento anterior para a DPO, ao contrário do pamidronato cuja resposta é influenciada negativa e significativamente pelos níveis basais de FAs e pelo tratamento prévio com bisfosfonatos. Em relação aos eventos adversos, o ZOL apresentou o mesmo perfil de eventos do pamidronato. No entanto, houve resistência ao pamidronato em número substancial de pacientes, o que não está descrito para o ácido zoledrônico. Os achados mostram um regime de tratamento com o ZOL mais efetivo, conveniente e sustentado ao comparar com pamidronato. AVALIAÇÃO ECONÔMICA: No processo de incorporação do ZOL para DPO no SUS, foi realizada uma análise de custo-efetividade comparando os bisfosfonatos entre si. A razão de custo efetividade incremental (RCEI) indicou que o risedronato dominou o alendronato e o pamidronato, mas não o ZOL, que foi mais efetivo que o risedronato, porém com maior custo. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Observou-se um declínio dos registros de utilização do pamidronato para DPO no SUS entre 2013 e 2017 e a ausência de registros de sua utilização nos anos de 2016 e 2017. Com isso, supõe-se que não haveria um impacto econômico significativo com a exclusão do pamidronato do SUS para doença de Paget. CONSIDERAÇÕES GERAIS: O ZOL demonstrou ser superior ao pamidronato nos desfechos de resposta terapêutica e na dor óssea. Houve melhora leve e não significativa na qualidade de vida para os dois bisfosfonatos intravenosos. Em relação aos eventos adversos, o ZOL apresentou o mesmo perfil de eventos do pamidronato. No entanto, houve resistência ao pamidronato em número substancial de pacientes. Os achados mostram um regime de tratamento com o ZOL mais efetivo, conveniente e sustentado ao comparar com pamidronato. RECOMENDAÇÃO PRELIMINAR DA CONITEC: O plenário, em reunião da CONITEC realizada no dia 06 de fevereiro de 2019, recomendou que o tema fosse submetido à consulta pública com recomendação preliminar favorável à exclusão no SUS do pamidronato dissódico para Doença de Paget. Considerou-se que o ácido zoledrônico, incorporado recentemente, demonstrou superioridade ao pamidronato e que o mesmo apresenta benefícios quanto ao esquema terapêutico, visto que é administrado em dose única, sem necessidade de repetição antes de 12 meses, enquanto o pamidronato requer múltiplas doses e o tratamento estendido até 6 semanas e repetido de 6 em 6 meses. CONSULTA PÚBLICA: Foram recebidas apenas 2 contribuições, sendo uma delas não referente ao tema apresentado. A outra contribuição foi contrária à recomendação inicial da Conitec, no entanto não apresentou comentários para sua discordância. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da CONITEC presentes na 76ª reunião ordinária, nos dias 03 e 04 de abril de 2019, deliberaram, por unanimidade, por recomendar a exclusão ao SUS do pamidronato para tratamento de pacientes com Doença de Paget. Foi assinado o Registro de Deliberação nº 433/2019. DECISÃO: Excluir o pamidronato dissódico para o tratamento da doença de Paget, no âmbito do Sistema Único de Saúde - SUS. Dada pela Portaria nº 75, seção 1, página 142, em 18 de abril de 2019.


Assuntos
Humanos , Osteíte Deformante/tratamento farmacológico , Difosfonatos/uso terapêutico , Administração Intravenosa , Avaliação da Tecnologia Biomédica , Avaliação em Saúde/economia , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
13.
Int J Surg ; 66: 1-11, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30890377

RESUMO

OBJECTIVE: This meta-analysis aims to compare the efficacy of teriparatide and bisphosphonates for reducing vertebral fracture risk and bone mineral density (BMD) in lumbar spine and femoral neck in postmenopausal women with osteoporosis. METHODS: We searched the literature, via PubMed, Embase, Cochrane Library, Web of Science and Google database to screen citations from inception to April 2018 for inclusion in this study. Only randomized controlled trials that compared teriparatide and bisphosphonates for reducing vertebral fracture risk in postmenopausal women with osteoporosis were included. Stata 12.0 was used for meta-analysis. RESULTS: Our meta-analysis results indicated that, compared with bisphosphonates, teriparatide was associated with a reduction of the vertebral fracture risk (risk ratio (RR) = 0.57, 95% confidence interval (CI): 0.35, 0.93, P = 0.024). Furthermore, teriparatide therapy increased the mean percent change in BMD in lumbar spine of 6 months, 12 months and 18 months than bisphosphonates with statistically significant (P < 0.05). And, teriparatide has only beneficial in increasing the mean percent change in BMD in femoral neck of 18 months (P < 0.05). There was no significant difference between teriparatide and bisphosphonates in terms of the adverse events (AEs, RR = 1.09, 95% CI 0.89, 1.33, P = 0.424). CONCLUSIONS: Teriparatide is an effective agent in reducing the risk of vertebral fracture in postmenopausal women with osteoporosis. Furthermore, teriparatide can increase the BMD in lumbar spine and femoral neck in long-terms duration.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Teriparatida/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Feminino , Humanos , Vértebras Lombares/fisiopatologia , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/fisiopatologia , Viés de Publicação , Comportamento de Redução do Risco , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/fisiopatologia , Fraturas da Coluna Vertebral/prevenção & controle
14.
Orthop Clin North Am ; 50(2): 193-209, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30850078

RESUMO

Osteogenesis imperfecta is a genetically and phenotypically heterogeneous disorder related to a defect or deficiency in the production of type I collagen. It is characterized by brittle bones, fractures, spine and extremity deformity, and a host of extraskeletal manifestations. Type I collagen is present in bone, tendons, ligaments, skin, dentin, and the sclera of the eye and other connective tissues. Osteogenesis imperfecta includes a multitude of disease manifestations that may be present at birth or develop over time and vary depending on the severity of the disease. This article describes the disease presentation and management considerations from a pediatric orthopedic perspective.


Assuntos
Doenças do Desenvolvimento Ósseo/genética , Deformidades Congênitas dos Membros/diagnóstico , Osteogênese Imperfeita/diagnóstico , Osteogênese Imperfeita/genética , Adolescente , Doenças do Desenvolvimento Ósseo/patologia , Doenças do Desenvolvimento Ósseo/fisiopatologia , Cálcio/administração & dosagem , Cálcio/uso terapêutico , Criança , Pré-Escolar , Difosfonatos/administração & dosagem , Difosfonatos/uso terapêutico , Exercício/fisiologia , Feminino , Órtoses do Pé/normas , Fraturas Ósseas/complicações , Fraturas Ósseas/terapia , Humanos , Lactente , Comunicação Interdisciplinar , Deformidades Congênitas dos Membros/etiologia , Deformidades Congênitas dos Membros/cirurgia , Deformidades Congênitas dos Membros/terapia , Masculino , Osteogênese Imperfeita/tratamento farmacológico , Osteogênese Imperfeita/patologia , Escoliose/patologia , Escoliose/cirurgia , Coluna Vertebral/anormalidades , Coluna Vertebral/patologia , Vitamina D/uso terapêutico
15.
Medicine (Baltimore) ; 98(9): e14701, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30817607

RESUMO

RATIONALE: We present 2 cases of lateral incomplete impending fracture of the femoral neck without trauma in elderly patients taking long-term bisphosphonate (BP) treatment, and we defined it as atypical femoral neck fracture (AFNF). To the best of our knowledge, this is the first report on the follow-up results of AFNF. PATIENT CONCERNS: Patients in both cases had been taking BP drugs for a long time with osteoporosis. The duration of BP treatment was 6 years, and there was no history of repeated stresses. DIAGNOSES: All fractures were linear at the lateral aspect of the mid portion of the femoral neck, and the BMD of the femoral neck was -0.9, and -1.8, respectively. INTERVENTIONS: Internal fixation was performed in both cases (73 years, 68 years) using cannulated screws. OUTCOMES: In both patients who underwent screw fixation, the fracture line started to extend distally at 4 weeks and 2 weeks following surgery. In the 3-month follow-up image, the length of the fracture increased by 20.1 mm and 9.9 mm, respectively. There was a problem with active rehabilitation, and the possibility of revision was also found to be a burden in terms of mortality and cost in older patients. LESSONS: In the case of AFNF, guidelines for treatment should be set in consideration of the decreased bone healing, even when the fracture pattern is simple. Arthroplasty based on a wider indication may be worth considering.


Assuntos
Difosfonatos/efeitos adversos , Fraturas do Colo Femoral/induzido quimicamente , Fraturas do Colo Femoral/cirurgia , Consolidação da Fratura/fisiologia , Idoso , Difosfonatos/uso terapêutico , Feminino , Fixação Interna de Fraturas , Humanos , Osteoporose/tratamento farmacológico
16.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(2): 108-116, feb. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-175802

RESUMO

La osteogénesis imperfecta (OI) es una enfermedad genética que cursa con baja densidad mineral y fragilidad ósea. Varios trabajos han demostrado la eficacia de los bisfosfonatos para mejorar la densidad mineral ósea (DMO). El objetivo de este estudio es evaluar la evolución de la DMO y parámetros bioquímicos de metabolismo óseo, en pacientes adultos con OI tratados con ácido zoledrónico intravenoso (iv) durante un periodo medio de 5 años, así como valorar la seguridad de dicho tratamiento. Pacientes y métodos: Estudio prospectivo, observacional en pacientes adultos con OI con osteoporosis u osteopenia, con T-score<-2, a los que se administró ácido zoledrónico (4mg iv) cada 6 meses durante 3 años y posteriormente de forma anual. Se registraron a las 24 y 48 h los cambios agudos en calcio, fósforo, creatinina y hemograma así como los efectos secundarios tras la infusión. Se realizó densitometría basal y cada año. Se determinaron basal y anualmente calcio, fósforo, paratohormona (PTHi), 25OH-vitamina D y marcadores de remodelado óseo (fosfatasa alcalina ósea, ß-cross-lap y deoxipiridolina en orina). Se registraron las nuevas fracturas. Resultados: Se trataron 20 pacientes, 6 hombres y 14 mujeres con una mediana de seguimiento de 5 años. Los niveles de calcio y las plaquetas disminuyeron significativamente a las 24 y 48 h tras la primera infusión. El recuento de hematíes disminuyó a las 24h. Estos cambios no fueron clínicamente relevantes. Siete pacientes presentaron un cuadro pseudogripal tras la primera dosis. La DMO medida en columna lumbar mostró un aumento significativo (6,7%) a los 12 meses de seguimiento (0,741±0,178 vs. 0,791±0,140g/cm2; p=0,003) así como a los tres (5,7%) y 5 años (9%) de seguimento. En cuello femoral se evidenció incremento significativo de la DMO a los 3 años (11,1%): 0,648±0,148 vs. 0,720±0,138g/cm2; p=0,01. En cadera total el incremento (10,1%) resultó significativo a los 3 años de tratamiento (0,706±0,118 vs. 0,720±0,138; p=0,01). No se evidenciaron diferencias significativas en los niveles de calcio y 25OH-vitamina D largo del seguimiento, el fósforo disminuyó significativamente al año y PTHi aumentó a los 3 años. ß-cross-lap disminuyó al año de tratamiento. Solo un paciente ha presentado nuevas fracturas. Conclusiones: El ácido zoledrónico es un tratamiento cómodo, seguro y eficaz para mejorar la DMO en pacientes adultos con OI


Osteogenesis imperfecta (OI) is an inherited disorder that causes low mineral density and bone fragility. Previous studies have shown the efficacy of bisphosphonates to increase bone mineral density (BMD). This study assessed changes over time in BMD and biochemical markers of bone metabolism in adult patients with osteogenesis imperfecta treated with intravenous zoledronic acid and the safety of this treatment. Patients and methods: A prospective, observational study in patients with OI, osteoporosis or osteopenia (T score <-2) who were administered zoledronic acid infusions (4mg IV) every 6 months for three years and annually thereafter. Densitometry was performed annually. Acute changes in complete blood count and calcium, phosphate, and creatinine levels, as well as side effects of the infusion, were recorded 24 and 48h after treatment. Calcium, phosphate, parathyroid hormone (iPTH), 25OH-vitamin D and bone turnover markers (bone alkaline phosphatase, ß-crosslaps and urinary deoxypyridinoline) were measured at baseline and every 12 months. Adverse events and new fractures were recorded. Results: Twenty patients (6 men and 14 women) were treated. Median follow-up time was five years. Calcium levels and platelet counts significantly decreased 24 and 48hours after the first infusion, and the red blood cell count decreased at 24hours. These changes were not clinically relevant. Seven patients experienced a flu-like episode after the first dose. Treatment induced significant increases in BMD in the lumbar spine (6.7%) after 12 months of follow-up (0.791±0.178 vs. 0.791±0.140g/cm2, p=.003) and at three (5.7%) and five years (9%) of follow-up. Femoral neck BMD significantly increased after 3 years (11.1%): 0.648±0.148 vs. 0.720±0.138g/cm2; p=.01. In total hip, increase in BMD (10.1%) was significant after three years of treatment (0.706±0.118 vs. 0.720±0.138, p=.01). There were no significant differences in calcium and 25OH-vitamin D levels during follow-up, phosphorus significantly decreased after one year, and iPTH increased at three years. ß-crosslaps decreased after one year of treatment. Only one patient sustained new fractures. Conclusions: Zoledronic acid is a convenient, safe, and effective treatment that increases BMD in adult patients with OI


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Osteogênese Imperfeita/tratamento farmacológico , Efeitos Adversos de Longa Duração , Densidade Óssea , Osso e Ossos/metabolismo , Difosfonatos/efeitos adversos , Adulto , Difosfonatos/metabolismo , Difosfonatos/uso terapêutico , Estudo Observacional , Estudos Prospectivos , Densitometria
18.
Expert Opin Pharmacother ; 20(6): 657-666, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30730775

RESUMO

INTRODUCTION: Prostate cancer remains the most common solid tumor afflicting men in the developed world. Metastatic prostate cancer is a source of great morbidity and mortality especially due to osseous involvement that gives rise to significant symptoms of pain or pathologic fractures or cord compression. Bisphosphonates had been widely used in the treatment of metastatic prostate bone metastases given their demonstrated benefit with a delay of skeletal-related events (SREs) but without prostate-specific antigen (PSA) response or overall survival benefit. Areas covered: In this review, the authors summarize the available literature on the clinical studies that led to the development and regulatory approval of zoledronic acid in men with metastatic prostate cancer. The authors also provide their expert opinion and future perspectives on this therapeutic. Expert opinion: Zoledronic acid is an established adjunctive treatment and bone-targeted therapy for the supportive care of men with metastatic castration-resistant prostate cancer. Efforts to study its utility in earlier phases of metastatic hormone-sensitive prostate cancer has not shown superior outcomes compared with standard androgen deprivation therapy (ADT) or docetaxel alone.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Neoplasias Ósseas/secundário , Difosfonatos/uso terapêutico , Docetaxel/uso terapêutico , Humanos , Masculino
19.
Int J Mol Sci ; 20(3)2019 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-30699924

RESUMO

Skeletal systems provide support, movement, and protection to the human body. It can be affected by several life suffering bone disorders such as osteoporosis, osteoarthritis, and bone cancers. It is not an easy job to treat bone disorders because of avascular cartilage regions. Treatment with non-specific drug delivery must utilize high doses of systemic administration, which may result in toxicities in non-skeletal tissues and low therapeutic efficacy. Therefore, in order to overcome such limitations, developments in targeted delivery systems are urgently needed. Although the idea of a general targeted delivery system using bone targeting moieties like bisphosphonates, tetracycline, and calcium phosphates emerged a few decades ago, identification of carrier systems like viral and non-viral vectors is a recent approach. Viral vectors have high transfection efficiency but are limited by inducing immunogenicity and oncogenicity. Although non-viral vectors possess low transfection efficiency they are comparatively safe. A number of non-viral vectors including cationic lipids, cationic polymers, and cationic peptides have been developed and used for targeted delivery of DNA, RNA, and drugs to bone tissues or cells with successful consequences. Here we mainly discuss such various non-viral delivery systems with respect to their mechanisms and applications in the specific targeting of bone tissues or cells. Moreover, we discuss possible therapeutic agents that can be delivered against various bone related disorders.


Assuntos
Doenças Ósseas/terapia , Animais , Doenças Ósseas/tratamento farmacológico , Difosfonatos/química , Difosfonatos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas/química , Transfecção/métodos
20.
BMJ Case Rep ; 12(2)2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30765453

RESUMO

Osteonecrosis, also known as avascular necrosis, is a condition that causes significant morbidity and loss of function. It is a common complication seen with supraphysiological steroid use. Early diagnosis is critical as it impacts prognosis. We report a 20-year-old man who developed bilateral osteonecrosis of the hip following 6 years of low-dose steroid replacement therapy for panhypopituitarism secondary to a transsphenoidal resection of a growth hormone-secreting pituitary macroadenoma. The patient presented with several weeks of right-sided hip pain and significant loss of function. X-ray and MRI showed bilateral osteonecrosis of the hips with the right side more severely affected than the left. He was initiated on analgesics and bisphosphonates and underwent right hip total arthroplasty followed 1 year later by left hip arthroplasty. Postsurgery, the patient is mobilising well and his pituitary hormones are well balanced. He continues on low-dose glucocorticoid replacement which will continue lifelong.


Assuntos
Necrose da Cabeça do Fêmur/terapia , Hipopituitarismo/tratamento farmacológico , Esteroides/efeitos adversos , Analgésicos/uso terapêutico , Artroplastia de Quadril/métodos , Difosfonatos/uso terapêutico , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Humanos , Hipopituitarismo/etiologia , Masculino , Neoplasias Hipofisárias/cirurgia , Resultado do Tratamento , Adulto Jovem
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