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1.
Medicine (Baltimore) ; 99(30): e21089, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791682

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) is a very tricky orthopedic disorder. If such condition cannot be managed fairly well, it may significantly affect quality of life and even leads to disability among such population. A variety of studies have reported that alendronate is utilized for the treatment of AS. However, their results are still contrary, and no systematic review has addressed on this topic. Thus, this study will systematically assess the efficacy and safety of alendronate for the treatment of patients with AS. METHODS: A comprehensive literature search will be performed from the below electronic databases from their commencement to the January 31, 2020 without language and publication status limitations: PubMed, Embase, Cochrane Library, Web of Science, Allied and Complementary Medicine Database, WANGFANG, and China National Knowledge Infrastructure. Only randomized controlled trials focusing on the alendronate for the treatment of patients with AS will be considered for inclusion in this study. Two authors will independently select all identified records, extract essential data from all included studies, and appraise study quality for each eligible trial using Cochrane risk of bias. If any differences occur, another experienced author will be invited to solve them by discussion and a consensus decision will be made. We will implement RevMan 5.3 software to analyze the extracted data. RESULTS: This study will summarize high-quality randomized controlled trials to assess the efficacy and safety of alendronate for the treatment of patients with AS through primary outcome of bone densitometry; and secondary outcomes of pain intensity, quality of life, disease activity, functional status, and adverse events. CONCLUSION: This study will provide evidence to help determine whether alendronate is an effective and safe management for patient with AS or not. STUDY REGISTRATION: INPLASY202040153.


Assuntos
Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Alendronato/efeitos adversos , Densidade Óssea , Conservadores da Densidade Óssea/efeitos adversos , Humanos , Metanálise como Assunto , Dor Musculoesquelética/etiologia , Medição da Dor , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Espondilite Anquilosante/complicações , Revisões Sistemáticas como Assunto
2.
J Bone Miner Metab ; 38(6): 859-867, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32719981

RESUMO

INTRODUCTION: Older people aged over 75 are more prone to falls because physical functions become deteriorated along with aging, and also fracture risk is strongly correlated with age. We evaluated the effects of anti-osteoporosis agents, eldecalcitol (ELD) and alendronate (ALN) on physical functions by assessing dynamic and static postural balance in aged patients with osteoporosis. MATERIALS AND METHODS: A randomized, open-label, controlled clinical trial has been conducted with 124 female patients aged 65 or over with osteoporosis. Patients were randomly assigned to receive either 0.75 µg of ELD once-a-day or 35 mg of ALN once-a-week for 24 weeks. The primary endpoint was the change in a postural balance index, adjusted composite equilibrium score (CES) of sensory organization test (SOT). The SOT equilibrium scores, leg muscle strength, and other physical functions were also evaluated. RESULTS: The Adjusted CES increased from baseline by 6.10% in the ELD group and 6.28% in the ALN group. There was no statistically significant difference between the two groups. The static postural balance at fixed platform were maintained in the ELD group, but declined in the ALN group. The dynamic postural balance at swaying platform and knee extension power increased from baseline in both groups. CONCLUSIONS: These results suggest that ELD and ALN treatments may each be beneficial to improve postural balance control in older patients with osteoporosis via different mechanisms of action.


Assuntos
Alendronato/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/fisiopatologia , Equilíbrio Postural , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Alendronato/efeitos adversos , Alendronato/farmacologia , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Feminino , Humanos , Equilíbrio Postural/efeitos dos fármacos , Vitamina D/efeitos adversos , Vitamina D/farmacologia , Vitamina D/uso terapêutico
3.
Medicine (Baltimore) ; 99(2): e18698, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914073

RESUMO

INTRODUCTION: Alendronate sodium is used to reduce the risk of bone fracture in aged osteoporosis patients. However, its side effects should be recognized, especially for those aged patients with one or more basic cardiovascular diseases. PATIENT CONCERNS: A 90-year-old and a 75-year-old male patient were admitted to our department. These 2 patients were examined by dual energy X-ray absorptiometry (DXA). DIAGNOSIS: Both patients were diagnosed with osteoporosis, they also had history of atrial fibrillation (AF) and had long term use of warfarin. INTERVENTIONS: Alendronate sodium was prescribed to the two patients at 70 mg once a week. OUTCOMES: The 2 patients had experienced dramatic increase of international normalized ratio (INR) to 4.69∼4.86 within 24 hours and gradual decrease in the next 5 days. Both patients experienced spontaneous ecchymoses and petechiae in the skin at the first 72 hours. CONCLUSION: Alendronate sodium can transiently increase the INR over 50%, induce spontaneous ecchymoses and petechiae in the skin of aged male osteoporosis patients with AF who took warfarin. Clinicians should pay enough attention when using alendronate sodium on these kinds of patients and be aware of the consequent potential bleeding risk.


Assuntos
Alendronato/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Conservadores da Densidade Óssea/efeitos adversos , Osteoporose/tratamento farmacológico , Varfarina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Sinergismo Farmacológico , Humanos , Coeficiente Internacional Normatizado , Masculino
4.
BMC Musculoskelet Disord ; 21(1): 19, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31926548

RESUMO

BACKGROUND: Bone mineral density of the humeral head is an independent determining factor for postoperative rotator cuff tendon healing. Bisphosphonates, which are commonly used to treat osteoporosis, have raised concerns regarding their relationships to osteonecrosis of the jaw and to atypical fracture of the femur. In view of the prevalence of rotator cuff tear in osteoporotic elderly people, it is important to determine whether bisphosphonates affect rotator cuff tendon healing. However, no studies have investigated bisphosphonates' cytotoxicity to human rotator cuff tendon fibroblasts (HRFs) or bisphosphonates' effects on rotator cuff tendon healing. The purpose of this study was to evaluate the cytotoxicity of alendronate (Ald), a bisphosphonate, and its effects on HRF wound healing. METHODS: HRFs were obtained from human supraspinatus tendons, using primary cell cultures. The experimental groups were control, 0.1 µM Ald, 1 µM Ald, 10 µM Ald, and 100 µM Ald. Alendronate exposure was for 48 h, except during a cell viability analysis with durations from 1 day to 6 days. The experimental groups were evaluated for cell viability, cell cycle and cell proliferation, type of cell death, caspase activity, and wound-healing ability. RESULTS: The following findings regarding the 100 µM Ald group contrasted with those for all the other experimental groups: a significantly lower rate of live cells (p < 0.01), a higher rate of subG1 population, a lower rate of Ki-67 positive cells, higher rates of apoptosis and necrosis, a higher number of cells with DNA fragmentation, higher caspase-3/7 activity (p < 0.001), and a higher number of caspase-3 positive staining cells. In scratch-wound healing analyses of all the experimental groups, all the wounds healed within 48 h, except in the 100 µM Ald group (p < 0.001). CONCLUSIONS: Low concentrations of alendronate appear to have little effect on HRF viability, proliferation, migration, and wound healing. However, high concentrations are significantly cytotoxic, impairing cellular proliferation, cellular migration, and wound healing in vitro.


Assuntos
Alendronato/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Fibroblastos/efeitos dos fármacos , Manguito Rotador/citologia , Cicatrização/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células
5.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674644

RESUMO

CONTEXT: The ACTIVE study demonstrated the antifracture efficacy of abaloparatide in postmenopausal women with osteoporosis. ACTIVExtend demonstrated sustained fracture risk reduction with alendronate in abaloparatide-treated participants from ACTIVE. A direct comparison of the efficacy of abaloparatide and antiresorptive therapies has not been performed. OBJECTIVE: The objective of this analysis is to compare the antifracture efficacy of abaloparatide in ACTIVE with that of alendronate in ACTIVExtend. DESIGN: In this post hoc analysis, the rate of new vertebral fractures for women in ACTIVExtend (N = 1139) was calculated based on baseline and endpoint radiographs for placebo or abaloparatide in ACTIVE and alendronate in ACTIVExtend. Vertebral fracture rates between abaloparatide and alendronate were compared in a Poisson regression model. Fracture rates for nonvertebral and clinical fractures were compared based on a Poisson model during 18 months of abaloparatide or placebo treatment in ACTIVE and 18 months of alendronate treatment in ACTIVExtend. RESULTS: The vertebral fracture rate was lower during abaloparatide treatment in ACTIVE (0.47 fractures/100 patient-years) than alendronate treatment in ACTIVExtend (1.66 fractures/100 patient-years) (relative risk reduction 71%; P = .027). Although the comparisons did not meet statistical significance, after switching from placebo (ACTIVE) to alendronate (ACTIVExtend), the rate of new vertebral fractures decreased from 2.49 to 1.66 fractures per 100 patient-years, and after switching from abaloparatide to alendronate from 0.47 to 0.19 fractures per 100 patient-years. The rates of nonvertebral fractures and clinical fractures were not significantly different. CONCLUSION: Initial treatment with abaloparatide may result in greater vertebral fracture reduction compared with alendronate in postmenopausal women with osteoporosis.


Assuntos
Alendronato/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Proteína Relacionada ao Hormônio Paratireóideo/administração & dosagem , Fraturas da Coluna Vertebral/prevenção & controle , Idoso , Alendronato/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Proteína Relacionada ao Hormônio Paratireóideo/efeitos adversos , Placebos/administração & dosagem , Placebos/efeitos adversos , Radiografia , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Resultado do Tratamento
6.
Aust Dent J ; 65(1): 100-103, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31769879

RESUMO

Bisphosphonates (BPs) have long been used for the treatment of osteoporosis and diseases like bone malignancies, active Paget's disease of bone, severe osteogenesis imperfecta and fibrous dysplasia among others. They bond highly to the bone surface and inhibit bone resorption. As BPs have a long half-life in bone because of their irreversible binding to bone, patients retain their risk profile even after drug cessation. This property also explains the complications wherein the cessation of bone resorption leads to halt in bone turnover. Usually with alendronate the risk of bisphosphonate-related osteonecrosis of jaw (BRONJ) wears off after 12 months. Reporting of the development of BRONJ is commonly associated with the intravenous BPs. Invasive surgical procedure associated with the placement of implants has been shown to be a major reason for the occurrence or initiation of BRONJ in susceptible patients. The prognosis of implants placed in the jaws of patients under or past BP medication is still uncertain. The present case report describes a patient on long-term oral BP therapy with spontaneous exfoliation of implant supported bone due to osteonecrosis.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Implantes Dentários/efeitos adversos , Osteonecrose/induzido quimicamente , Alendronato/efeitos adversos , Difosfonatos/efeitos adversos , Humanos
7.
Artigo em Português | Coleciona SUS, CONASS, SES-GO | ID: biblio-1117753

RESUMO

Tecnologia: Ácido zoledrônico e bifosfonados orais (alendronato e risedronato de sódio). Indicação: Prevenção de fraturas em pessoas com osteoporose. Pergunta: Em pessoas com osteoporose, o ácido zoledrônico é mais eficaz e seguro que os bifosfonados orais para prevenção de fraturas e outros desfechos de interesse? Métodos: Levantamento bibliográfico foi realizado nas bases eletrônicas Pubmed e BVS usando estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta Assessing the Methodological Quality of Systematic Reviews (AMSTAR). Resultados: Foram selecionadas e incluídas 5 revisões sistemáticas. Conclusão: O ácido zoledrônico é similar aos bifosfonados orais para prevenir fraturas em mulheres com osteoporose. Seu efeito sobre a densidade mineral óssea femoral é similar ao do alendronato e superior ao do risedronato. Um tratamento por 3 anos com ácido zoledrônico ou por 5 anos com alendronato de sódio é suficiente para prevenir fraturas vertebrais e não vertebrais. Bifosfonados têm similar risco de eventos adversos que o placebo, incluindo transtornos cardiovasculares e taxa de abandono do tratamento devido a distúrbios gastrointestinais. O ácido zoledrônico tem maior incidência de sintomas influenza-like que o placebo. O ácido zoledrônico não provoca eventos adversos do tipo esofágicos, gastrointestinais sérios ou do trato gastrointestinal superior, mas tem maior risco de náuseas, que pode estar relacionada à infusão intravenosa de grandes doses


Technology: Zoledronic acid and oral bisphosphonates. Indication: Prevention of osteoporotic fractures. Question: In people with osteoporosis, is zoledronic acid more effective and safer than oral bisphosphonates for preventing fractures and other outcomes? Methods: Bibliographic search was performed on PUBMED and BVS, using predefined search strategies. Evaluation of the methodological quality of systematic reviews was done by the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool. Results: 5 systematic reviews were selected and included. Conclusion: Zoledronic acid is similar to bisphosphonates for preventing fractures in women with osteoporosis and his effect on femoral bone mineral density is similar to that of alendronate and superior to risedronate. A 3 years treatment with zoledronic acid or for 5 years with sodium alendronate is sufficient to prevent vertebral and non-vertebral fractures. Bisphosphonates have a similar risk of adverse events than placebo, including cardiovascular disorders and risk of attrition due to gastrointestinal events. Zoledronic acid has a higher incidence of influenza-like symptoms (myalgia and arthralgia) than placebo, limited to the first dose and lasting a few days. Zoledronic acid does not cause esophageal, serious gastrointestinal or upper gastrointestinal tract adverse events, but has a higher risk of nausea, which can be caused by large doses of intravenous infusion


Assuntos
Humanos , Feminino , Osteoporose/tratamento farmacológico , Alendronato/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Ácido Risedrônico/uso terapêutico , Ácido Zoledrônico/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Resultado do Tratamento , Alendronato/efeitos adversos
8.
Artigo em Português | LILACS, Coleciona SUS, CONASS, SES-GO | ID: biblio-1118551

RESUMO

Tecnologia: Denosumabe e bifosfonados. Indicação: tratamento de osteoporose para prevenção de fraturas. Pergunta: O denosumabe é mais eficaz e seguro que os bifosfonados orais para tratamento da osteoporose e prevenção de fraturas secundárias à osteoporose? Métodos: Levantamento bibliográfico realizado na PUBMED seguindo estratégia de busca predefinida. Avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta AMSTAR (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas e incluídas 3 revisões sistemáticas, com pontuação de 9 a 11 no AMSTAR. Conclusão: Denosumabe tem menor risco relativo que alendronato e risedronato de sódio para fraturas vertebrais e maior efeito sobre densidade óssea mineral femoral, com risco similar de outros tipos de fratura e eventos adversos (infecções, transtornos cardiovasculares, óbito por infecção, morte cardiovascular ou por qualquer causa). Denosumabe evita 0,00154 fraturas, previne 0,00025 institucionalizações (ou cuidados permanentes de enfermagem no domicílio) e promove um ganho de 0,0018 anos de vida a mais que o alendronato de sódio por paciente tratado. Denosumabe é um pouco mais eficaz e tão seguro quanto os bifosfonados, mas a diferença de eficácia é mínima


Technology: Denosumab and bisphosphonates. Indication: osteoporosis treatment for fracture prevention. Question: Denosumab is more effective and safer than oral bisphosphonates for treating osteoporosis and preventing fractures related to osteoporosis? Methods: Bibliographic search was performed on PUBMED, following predefined search strategies. Evaluation of the methodological quality of systematic reviews was carried out using the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool. Results: We selected and included 3 systematic reviews. Their scores ranged from 9 to 11 on AMSTAR. Conclusion: Denosumab has a lower relative risk than sodium alendronate and risedronate for vertebral fractures and greater effect on femoral mineral bone density, with a similar risk for non-vertebral fractures and adverse events (infections, cardiovascular disorders, death caused by infection, cardiovascular death or any cause mortality). Denosumab avoids 0.00154 fractures, prevents 0.00025 nursing home/ residential care admissions and get 0.0018 years of life gained per treated patient more than sodium alendronate. Denosumab is slightly more effective and as safe as bisphosphonates, but the effectiveness difference is minimal


Assuntos
Humanos , Osteoporose/tratamento farmacológico , Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Ácido Risedrônico/uso terapêutico , Denosumab/uso terapêutico , Resultado do Tratamento , Alendronato/efeitos adversos , Medicina Baseada em Evidências , Ácido Risedrônico/efeitos adversos , Denosumab/efeitos adversos
9.
BMJ Case Rep ; 12(7)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340943

RESUMO

A 35-year-old man with juvenile idiopathic arthritis since childhood presented with bilateral atypical tibial fractures, followed by a later, single atypical fracture of the femur. The fractures were associated with 6 years of oral alendronate treatment immediately followed by subcutaneous denosumab therapy and later teriparatide therapy for osteoporosis. Atypical fractures are known to occur in the femur following bisphosphonate therapy; however, there are only a few documented cases of atypical fractures in the tibia. Our case highlights a rare but serious complication of a commonly prescribed antiresorptive agent. It also shows that teriparatide, while helpful in increasing bone mass, does not fully prevent the development of atypical fractures. Careful investigation should be considered in patients on long-term antiresorptive therapy presenting with bony tenderness to exclude an atypical fracture.


Assuntos
Alendronato/efeitos adversos , Denosumab/efeitos adversos , Fraturas Espontâneas/induzido quimicamente , Osteoporose/tratamento farmacológico , Teriparatida/efeitos adversos , Absorciometria de Fóton/métodos , Adulto , Alendronato/uso terapêutico , Densidade Óssea/fisiologia , Denosumab/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/diagnóstico por imagem , Seguimentos , Fraturas Espontâneas/diagnóstico por imagem , Humanos , Masculino , Osteoporose/diagnóstico por imagem , Medição de Risco , Teriparatida/uso terapêutico , Fraturas da Tíbia/induzido quimicamente , Fraturas da Tíbia/diagnóstico por imagem
10.
Cir Cir ; 87(4): 396-401, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31264983

RESUMO

Background: The use of osteoclast inhibitors in metastatic bone disease, increase bone mineral density and reduce the risk of fracture, patients with osteonecrosis have been reported after the chronic use of these inhibitors. In our country, the use of osteoclast inhibitors is in the context of osteoporosis and bone metastases, so it is important to describe the incidence of this complication in Mexican population. Objective: To describe the incidence of osteonecrosis of the jaws at the Centro Médico Nacional 20 de Noviembre, during the period from January 1st, 2010 to June 1st, 2016. Methods: This is a retrospective cohort study developed at the Centro Medico Nacional 20 Noviembre, ISSSTE, Mexico. We included all patients who received bisphosphonates or denosumab in the context of metastatic bone disease due to solid tumors and who had osteonecrosis of the jaw. Results: A 802 patients who used bisphosphonates or denosumab in metastatic bone disease (699 bisphosphonates and 103 denosumab). Of these, 28 (3.5%) patients presented osteonecrosis. The median use of zoledronic acid for the presence of osteonecrosis was 25 months (15-49 months) and for Denosumab it was 16 months (11-35 months), without finding significant differences between the use of drugs p = 0.511 and the risk of osteonecrosis. Conclusions: Drug-induced osteonecrosis has a low incidence in Mexican population, denosumab does not show a greater number of cases of osteonecrosis compared to bisphosphonates; no association was found between functional status, number of metastatic bone sites, nor use of antigenic or tyrosine kinase inhibitors as factor associated with osteonecrosis of the jaws.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Denosumab/efeitos adversos , Difosfonatos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alendronato/efeitos adversos , Neoplasias Ósseas/secundário , Feminino , Humanos , Incidência , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Osteoclastos/efeitos dos fármacos , Estudos Retrospectivos , Ácido Risedrônico/efeitos adversos , Fatores de Tempo , Ácido Zoledrônico/efeitos adversos
11.
Rehabilitación (Madr., Ed. impr.) ; 53(2): 121-125, abr.-jun. 2019. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-185468

RESUMO

La osteoporosis es una enfermedad con una alta prevalencia e importantes consecuencias. Los bifosfonatos son los fármacos más utilizados para controlarla, sin embargo, su uso durante periodos prolongados se asocia con el riesgo de fracturas atípicas. Se presentan los casos de 2 pacientes en tratamiento con bifosfonatos que presentaron fracturas femorales atípicas bilaterales; en un caso fueron simultáneas, sin traumatismo desencadenante, y en el otro fueron diferidas tras sendos traumatismos banales. En ambos casos la fractura fue precedida de clínica dolorosa. Fueron tratadas mediante enclavado intramedular y supresión de los bifosfonatos, con buenos resultados. Aunque los bifosfonatos han demostrado su eficacia en la prevención de fracturas por fragilidad, su uso prolongado se ha asociado paradójicamente a fracturas atípicas. Estas fracturas suelen estar precedidas de dolor, por lo que ante ello es necesario realizar estudios de imagen, en los que pueden evidenciarse fracturas incompletas que podrían beneficiarse de un enclavamiento profiláctico antes de que se produzca la fractura completa


Osteoporosis is a highly prevalent disease with important consequences. The most widely used drugs to control this disease are bisphosphonates but their prolonged use is associated with the risk of atypical fractures. We report the cases of two patients under bisphosphonate treatment with bilateral atypical femoral fractures. In one patient the fractures occurred simultaneously, unprovoked by trauma, and in the other, they occurred as delayed fractures after mild trauma. In both cases, the fractures were preceded by pain. The fractures were treated with intramedullary nailing and bisphosphonate withdrawal with good outcomes. Although bisphosphonates have demonstrated effectiveness in preventing frailty-related fractures, their prolonged use has paradoxically been associated with atypical fractures. These fractures are usually preceded by pain. Consequently, when faced with this clinical picture, physicians should request imaging studies that could show incomplete fractures that could benefit from prophylactic nailing before becoming complete fractures


Assuntos
Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Fraturas do Fêmur/induzido quimicamente , Difosfonatos/efeitos adversos , Osteoporose/tratamento farmacológico , Osteoporose/complicações , Suspensão de Tratamento , Ácido Risedrônico/efeitos adversos , Alendronato/efeitos adversos , Denosumab/efeitos adversos
12.
Eur J Pharmacol ; 856: 172410, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31132357

RESUMO

Alendronate is a bisphosphonate widely used for the treatment of osteoporosis; however, one of its main adverse reactions is gastric ulcer. Metformin is an oral antihyperglycemic agent that has several beneficial effects, including healing, gastroprotective and anti-tumoral action. This study aimed to evaluate the gastroprotective activity of metformin in alendronate-induced gastric damage in normoglycemic and hyperglycemic rats. The treatment with 100 mg/kg of metformin showed a significant gastroprotective effect in damage induced by alendronate (50 mg/kg) in macroscopic analysis and the analysis of light microscopy and atomic force microscopy. The results suggested metformin decreased the inflammatory response by reducing the expression of proinflammatory cytokines (TNF-α, IL-1ß and IL-6), myeloperoxidase activity, and malondialdehyde levels. Also, the results suggested that metformin induces the maintenance of basal levels of collagen and increase the production of mucus. Interestingly, with the presence of the AMPK inhibitor (Compound C), metformin presented impairment of its gastroprotective action. The gastroprotective effect of metformin might be related to the activation of the AMPK pathway. These findings revealed that metformin has a gastroprotective action and may be considered a therapeutic potential for the prevention and treatment of gastric lesions induced by alendronate.


Assuntos
Alendronato/efeitos adversos , Glicemia/metabolismo , Citoproteção/efeitos dos fármacos , Hiperglicemia/patologia , Metformina/farmacologia , Estômago/efeitos dos fármacos , Estômago/patologia , Alendronato/antagonistas & inibidores , Animais , Colágeno/metabolismo , Citocinas/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Malondialdeído/metabolismo , Peroxidase/metabolismo , Ratos , Ratos Wistar
13.
Osteoporos Int ; 30(8): 1627-1634, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31089764

RESUMO

We aimed to determine patients' reasons for continuing alendronate therapy over 5 years by administering a questionnaire. Bone mineral density, fractures, drugs, Charlson comorbidity index, and lifestyle factors were also considered. Education and awareness of the disease appeared highly associated with good alendronate adherence while worsening health status with discontinuation. INTRODUCTION: Aim of this study was to investigate patients' reasons for adhering to long-term alendronate therapy (more than 5 years), as data is not available in the current literature regarding the reasons behind long-term adherence. METHODS: We studied 204 long-term adherent alendronate users: 65 postmenopausal outpatients still adherent (group C, years on treatment = 8.70 ± 1.31) were compared to 139 age-matched patients who discontinued therapy (group S, years on treatment = 8.64 ± 1.43). We evaluated main biochemical parameters, BMD values, fractures, and Charlson comorbidity index (CCI). A questionnaire was administered to analyze the reasons for long-term adherence. RESULTS: There were no significant differences between groups concerning baseline DXA values, number of fractures, and CCI. A higher education level was observed in group C (C 54% vs S 35% of patients, p = 0.001). At the time of interview, there was a significantly higher number of patients with a CCI of two in group S compared to the beginning of treatment (56% vs 43%, p = 0.04), together with a higher number of patients taking more than 3 drugs (22% vs 11%, p = 0.01) compared to basal evaluation. Forty-seven percent of patients reported new diseases during the treatment as the main reason for stopping alendronate. A multivariate, stepwise logistic regression analysis showed that awareness of the disease was highly associated with adherence (OR = 0.20; 95% CI 0.045-0.93, p = 0.04) followed by higher education (OR = 0.526, 95% CI 0.345-0.801, p = 0.003). Worsening of CCI was associated with discontinuation (OR = 2.75, 95% CI 1.033-7.324, p = 0.04). CONCLUSIONS: Education and disease awareness are associated with long-term alendronate adherence while competing health problems negatively impact adherence.


Assuntos
Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação/psicologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Adulto , Idoso , Alendronato/administração & dosagem , Alendronato/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Esquema de Medicação , Escolaridade , Feminino , Humanos , Itália , Estudos Longitudinais , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/prevenção & controle , Estudos Retrospectivos
14.
J Bone Miner Metab ; 37(6): 996-1003, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30976915

RESUMO

Thalassemia, as the most prevalent genetic blood disorder, has many associated comorbidities including low bone mass. We studied the comparative effectiveness of alendronate (AL) and zoledronic acid (ZOL) on bone mass improvement in transfusion-dependent thalassemia (TDT) patients a year after treatment. Three hundred seventy-five TDT patients with low bone mass were enrolled in this study. After a year of treatment with either AL or ZOL, a second bone mineral density (BMD) test was ordered to compare the effectiveness of the two aforementioned drugs. Body mass index (BMI), physical activity, sun exposure, and biochemical laboratory data were also considered as associated factors in this study. The BMD test of both groups was almost the same at the baseline and it increased comparably after a year of treatment with AL and ZOL. However, there was a significant difference in lumbar spine BMD delta Z score between both groups of female patients. ZOL was more effective in increasing the lumbar spine BMD of female patients. The choice of bisphosphonates therapy (oral versus parenteral) should be individually selected by considering patient's preference, compliance and the physician's decision. Given the longer administration interval, and TDT patients' compliance issue, it is justified to recommend ZOL as the drug of choice for patients suffering from low bone mass.


Assuntos
Alendronato/uso terapêutico , Transfusão de Sangue , Densidade Óssea , Osso e Ossos/patologia , Talassemia/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Absorciometria de Fóton , Adolescente , Adulto , Alendronato/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Talassemia/diagnóstico por imagem , Adulto Jovem , Ácido Zoledrônico/efeitos adversos
15.
Ann Intern Med ; 171(1): 37-50, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31009947

RESUMO

Background: Optimal long-term osteoporosis drug treatment (ODT) is uncertain. Purpose: To summarize the effects of long-term ODT and ODT discontinuation and holidays. Data Sources: Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies. Study Selection: 48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB). Data Extraction: Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy. Data Synthesis: Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapy reduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE). Limitation: No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays. Conclusion: Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-term bisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms. Primary Funding Source: National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Alendronato/efeitos adversos , Alendronato/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/tratamento farmacológico , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Esquema de Medicação , Duração da Terapia , Feminino , Fraturas do Quadril/prevenção & controle , Humanos , Osteoporose Pós-Menopausa/complicações , Fraturas da Coluna Vertebral/prevenção & controle , Ácido Zoledrônico/efeitos adversos , Ácido Zoledrônico/uso terapêutico
16.
J Bone Miner Res ; 34(6): 1014-1024, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30690785

RESUMO

Mineral and bone disorders including osteoporosis are common in dialysis patients and contribute to increased morbimortality. However, whether denosumab and alendronate are effective and safe treatments in hemodialysis patients is not known. Thus, we conducted a prospective, three-center study of 48 hemodialysis patients who were diagnosed as having osteoporosis and had not received anti-osteoporotic agents previously. Participants were randomized to either denosumab or intravenous alendronate, and all subjects received elemental calcium and calcitriol during the initial 2 weeks. The primary endpoint was the percent change in lumbar spine bone mineral density (LSBMD) at 12 months of treatment. The secondary endpoints included the following: change in BMD at other sites; change of serum bone turnover markers (BTM), coronary artery calcium score (CACS), ankle-brachial pressure index (ABI), brachial-ankle pulse wave velocity (baPWV), flow mediated dilation (FMD), and intima-media thickness at the carotid artery (CA-IMT); change from day 0 to day 14 in serum levels of Ca and P; time course of serum calcium (Ca), phosphorus (P), and intact parathyroid hormone (i-PTH); new fractures; and adverse events. Initial supplementation with elemental calcium and calcitriol markedly ameliorated the decrease of serum corrected calcium (cCa) levels induced by denosumab during the first 2 weeks, whereas serum cCa levels in the alendronate group were increased. Denosumab and alendronate markedly decreased serum levels of BTM and increased LSBMD at 12 months compared with baseline. However, no significant differences were found in the changes in LSBMD between the two groups. The serum cCa, P, and i-PTH levels in the two groups were maintained within the appropriate range. In contrast to the anti-osteoporotic effects, no significant differences after 12 months of treatment were found in the CACS, CA-IMT, ABI, baPWV, and FMD compared with pretreatment in both groups. Denosumab and alendronate treatment improved LSBMD, reduced BTM, and appeared to be safe in hemodialysis patients with osteoporosis. © 2019 American Society for Bone and Mineral Research.


Assuntos
Alendronato/farmacologia , Vasos Sanguíneos/fisiologia , Osso e Ossos/fisiologia , Denosumab/farmacologia , Diálise Renal , Idoso , Alendronato/efeitos adversos , Arteriosclerose/fisiopatologia , Biomarcadores/metabolismo , Vasos Sanguíneos/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Calcinose/fisiopatologia , Denosumab/efeitos adversos , Feminino , Humanos , Masculino , Minerais/metabolismo
17.
Intern Med ; 58(8): 1049-1056, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30626809

RESUMO

Objective The incidence of osteoporosis is increasing with the rapid aging of the Japanese population. Bisphosphonates are first-line agents used for the treatment of osteoporosis, but they can cause upper gastrointestinal mucosal injury. This study investigated symptoms and upper gastrointestinal mucosal injury associated with oral bisphosphonates. Methods Symptoms were evaluated using the F-scale questionnaire, and esophageal mucosal injury and gastroduodenal ulceration were assessed by endoscopy. Patients were stratified by the type of bisphosphonate (alendronate, risedronate, or minodronate), treatment schedule (once weekly or every four weeks), and the concomitant use of other medications [antithrombotic agents, nonsteroidal anti-inflammatory drugs (NSAIDs), or acid suppressants]. Patients The subjects included 221 patients treated with oral bisphosphonates for at least one month. Results The median F-scale total score was 4 (0-34), reflux score was 2 (0-20), and the mean dyspepsia score was 2 (0-16). Endoscopy showed esophageal mucosal injury of Grade A or worse (Los Angeles classification) in 22/221 patients (10.0%) and gastroduodenal ulcers in 9 patients (4.1%). The dyspepsia score in patients who took minodronate every four weeks was significantly lower (p<0.05) in comparison to patients who took other bisphosphonates. The dyspepsia score was significantly higher (p<0.05) and mucosal injury was significantly more frequent in patients who also used antithrombotic agents and NSAIDs. Conclusion Symptoms and upper gastrointestinal mucosal damage were not necessarily frequent or severe in patients treated with bisphosphonates. However, the concomitant use of bisphosphonates with antithrombotic agents and NSAIDs increased both symptoms and mucosal injury. The symptoms were milder in patients using minodronate once monthly.


Assuntos
Alendronato/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Trato Gastrointestinal/efeitos dos fármacos , Membrana Mucosa/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Ácido Risedrônico/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Trato Gastrointestinal/lesões , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Membrana Mucosa/lesões , Ácido Risedrônico/uso terapêutico
18.
J Vet Intern Med ; 33(2): 862-867, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30663796

RESUMO

A 12-year-old, neutered female, domestic medium hair cat was evaluated for a nonhealing, oral mucosal ulceration. The cat had a history of idiopathic hypercalcemia that had been treated with a bisphosphonate for 41 months. Oral examination identified exposed maxillary bone adjacent to a previous extraction site. Histopathology of the exposed bone and associated mucosa was most consistent with medication-related osteonecrosis of the jaw. Treatment involved both medical and surgical interventions. Oral mucosal healing occurred after 6 months of treatment.


Assuntos
Alendronato/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/veterinária , Doenças do Gato/induzido quimicamente , Difosfonatos/efeitos adversos , Alendronato/uso terapêutico , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Doenças do Gato/tratamento farmacológico , Gatos , Difosfonatos/uso terapêutico , Feminino , Hipercalcemia/tratamento farmacológico , Hipercalcemia/veterinária , Úlceras Orais/etiologia , Úlceras Orais/veterinária
20.
J Bone Miner Res ; 34(5): 810-816, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30536713

RESUMO

An ASBMR Task Force recommends a drug holiday for certain women treated for ≥5 years with oral alendronate or ≥3 years with intravenous zoledronic acid, with reassessment 2 to 3 years later. It is not known whether changes in bone mineral density (BMD) or bone turnover markers differ after oral or intravenous therapy. Our goal was to compare changes in BMD and procollagen type I N propeptide (PINP) after oral or intravenous bisphosphonate use. In the Fracture Intervention Trial Long-term Extension (FLEX), women who received a mean 5 years of alendronate were randomized to placebo or continued treatment. In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial Extension I (HORIZON-PFT E1), women who received 3 years of zoledronic acid were randomized to placebo or continued treatment. We examined the proportion of participants with BMD loss or PINP gain ≥ least significant change (LSC) and those whose values exceeded a threshold (T-score ≤-2.5 or PINP ≥36.0 ng/mL, a premenopausal median value). After 3 years of placebo, the FLEX group had greater mean total hip BMD decreases (-2.3% versus -1.2% in the HORIZON-PFT E1 group, p < 0.01) and greater rises in PINP (+11.6 ng/mL versus +6.7 ng/mL, p < 0.01). There was a greater proportion of individuals in FLEX with total hip BMD loss and PINP increases that exceeded LSC, and PINP values ≥36.0 ng/mL. In contrast, there were small changes in the proportion of women with femoral neck T-scores ≤-2.5 in both groups. In conclusion, 3 years after bisphosphonate discontinuation, a considerable proportion of former alendronate and zoledronic acid users had meaningful declines in total hip BMD and elevations in PINP. Despite a longer treatment course, alendronate may have a more rapid offset of drug effect than zoledronic acid. © 2018 American Society for Bone and Mineral Research.


Assuntos
Alendronato/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ácido Zoledrônico/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Alendronato/efeitos adversos , Biomarcadores , Feminino , Colo do Fêmur , Humanos , Ácido Zoledrônico/efeitos adversos
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