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1.
N Engl J Med ; 383(8): 743-753, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32813950

RESUMO

BACKGROUND: Bisphosphonates are effective in reducing hip and osteoporotic fractures. However, concerns about atypical femur fractures have contributed to substantially decreased bisphosphonate use, and the incidence of hip fractures may be increasing. Important uncertainties remain regarding the association between atypical femur fractures and bisphosphonates and other risk factors. METHODS: We studied women 50 years of age or older who were receiving bisphosphonates and who were enrolled in the Kaiser Permanente Southern California health care system; women were followed from January 1, 2007, to November 30, 2017. The primary outcome was atypical femur fracture. Data on risk factors, including bisphosphonate use, were obtained from electronic health records. Fractures were radiographically adjudicated. Multivariable Cox models were used. The risk-benefit profile was modeled for 1 to 10 years of bisphosphonate use to compare associated atypical fractures with other fractures prevented. RESULTS: Among 196,129 women, 277 atypical femur fractures occurred. After multivariable adjustment, the risk of atypical fracture increased with longer duration of bisphosphonate use: the hazard ratio as compared with less than 3 months increased from 8.86 (95% confidence interval [CI], 2.79 to 28.20) for 3 years to less than 5 years to 43.51 (95% CI, 13.70 to 138.15) for 8 years or more. Other risk factors included race (hazard ratio for Asians vs. Whites, 4.84; 95% CI, 3.57 to 6.56), height, weight, and glucocorticoid use. Bisphosphonate discontinuation was associated with a rapid decrease in the risk of atypical fracture. Decreases in the risk of osteoporotic and hip fractures during 1 to 10 years of bisphosphonate use far outweighed the increased risk of atypical fracture among Whites but less so among Asians. After 3 years, 149 hip fractures were prevented and 2 bisphosphonate-associated atypical fractures occurred in Whites, as compared with 91 and 8, respectively, in Asians. CONCLUSIONS: The risk of atypical femur fracture increased with longer duration of bisphosphonate use and rapidly decreased after bisphosphonate discontinuation. Asians had a higher risk than Whites. The absolute risk of atypical femur fracture remained very low as compared with reductions in the risk of hip and other fractures with bisphosphonate treatment. (Funded by Kaiser Permanente and others.).


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Fraturas do Quadril/prevenção & controle , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Americanos Asiáticos , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Grupo com Ancestrais do Continente Europeu , Feminino , Fraturas do Fêmur/epidemiologia , Fraturas do Fêmur/etnologia , Fraturas do Quadril/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Análise Multivariada , Osteoporose Pós-Menopausa/complicações , Fraturas por Osteoporose/induzido quimicamente , Fraturas por Osteoporose/epidemiologia , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fatores de Tempo
2.
Expert Opin Pharmacother ; 21(14): 1725-1737, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32605401

RESUMO

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic disabling disease characterized by a symmetrical articular involvement due to ongoing joint inflammation, if left insufficiently treated. Local and generalized bone loss is one of the main extra-articular complications of RA and leads to an increased risk for fragility fractures, which further impair functional ability, quality of life, and life expectancy. Therefore, there is an urgent need for good fracture risk management in the vulnerable RA patient. AREAS COVERED: The authors review: the epidemiology and pathophysiology (i.e. risk factors) of osteoporosis (OP), fracture, and vertebral fracture risk assessment, the effects of anti-rheumatic drugs on bone loss, pharmacological treatment of OP in RA including both bisphosphonates (BP) and newer drugs including anti-resorptives and osteoanabolic treatment options. EXPERT OPINION: Patients with active RA have elevated bone resorption and local bone loss. Moreover, these patients are at increased risk for generalized bone loss, vertebral and non-vertebral fractures. Since general risk factors (such as low BMI, fall risk) and RA-related factors play a role, optimal fracture prevention in RA patients is based on optimal diagnostics based on both of these factors, and on the use of adequate non-medical and medical treatment options.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Difosfonatos/uso terapêutico , Fraturas Ósseas/prevenção & controle , Glucocorticoides/uso terapêutico , Osteoporose/tratamento farmacológico , Absorciometria de Fóton , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Densidade Óssea/efeitos dos fármacos , Feminino , Fraturas Ósseas/etiologia , Humanos , Osteoporose/complicações , Osteoporose/epidemiologia , Qualidade de Vida , Fatores de Risco , Resultado do Tratamento
3.
J Transl Med ; 18(1): 261, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600410

RESUMO

Amino-bisphosphonates such as zoledronic acid (ZA) can possibly ameliorate or prevent severe COVID-19 disease by at least three distinct mechanisms: (1) as immunostimulants which could boost γδ T cell expansion, important in the acute response in the lung; (2) as DC modulators, limiting their ability to only partially activate T cells; and (3) as prenylation inhibitors of small GTPases in the endosomal pathway of the DC to prevent expulsion of lysosomes containing SARS-CoV-2 virions. Use of ZA or other amino-bisphosphonates as modulators of COVID-19 disease should be considered.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Células Dendríticas/virologia , Difosfonatos/uso terapêutico , Endossomos/metabolismo , Fatores Imunológicos/farmacologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Animais , Células Dendríticas/efeitos dos fármacos , Endossomos/efeitos dos fármacos , Humanos , Pandemias
5.
Arch Endocrinol Metab ; 64(4): 331-336, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32725062

RESUMO

Osteoporosis is a systemic skeletal disease characterized by reduced bone mass and deterioration of bone tissue microarchitecture leading to an increased risk of fractures. Fragility fractures, especially hip fractures, are associated with a significant reduction in the physical function and quality of life of affected patients, as well as increased mortality, leading to a major financial impact on health care. Many drugs have been registered for the treatment of osteoporosis and very recently, a new anabolic agent, romosozumab, has been approved in some countries. Despite the expansion of efficacious antiresorptive and anabolic therapies in recent years, a concomitant increase in concerns have been raised by physicians, patients and the lay press about the potential for adverse events, especially atypical femoral fractures (AFF) following prolonged use of bisphosphonates. Whatever the mechanism(s) may be, direct or indirect, linking prolonged bisphosphonate use to atypical femoral fractures, this adverse event is very rare in comparison to the magnitude of risk reduction of typical osteoporotic fractures. An estimated 162 osteoporosis-related fractures are prevented for each atypical femoral fracture associated with an anti-resorptive medication. Until a risk calculator for predicting risk of atypical fractures, becomes available in clinical practice, and we view this as an unlikely scenario, it is up to the physician to consider continuing or discontinuing bisphosphonate use after the critical 3-5 year period of treatment with zoledronic acid or alendronate, but close monitoring for the residual bone effects overtime should be planned. For other bisphosphonates, in which no residual effects are expected, drug holiday is usually not applied.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Osteoporose Pós-Menopausa , Alendronato , Feminino , Humanos , Qualidade de Vida
6.
PLoS One ; 15(7): e0235163, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730257

RESUMO

OBJECTIVES: The purpose of this study was to reconfirm the association between the risk of fracture and proton pump inhibitor use and to establish evidence for defining a high-risk group of patients among proton pump inhibitor users. METHODS: A nested case-control study was performed using data from the National Health Insurance Sharing Service database from the period January 2007 to December 2017. The study population included elderly women aged ≥65 years with claims for peptic ulcer or gastro-esophageal reflux disease. The cases were all incidental osteoporotic fractures, and up to two controls were matched to each case by age, osteoporosis, and Charlson comorbidity index. Conditional logistic regression was used to calculate the adjusted odds ratio and 95% confidence interval (CI). RESULTS: A total of 21,754 cases were identified, and 43,508 controls were matched to the cases. The adjusted odds ratio of osteoporotic fractures related to the use of proton pump inhibitors was 1.15 (95% CI: 1.11-1.20). There was a statistically significant interaction between proton pump inhibitor and bisphosphonate use (p<0.01). The risk of fracture in patients using proton pump inhibitors was 1.15 (95% CI: 1.08-1.92) in bisphosphonate users and 1.11 (95% CI: 1.03-1.20) in bisphosphonate non-users. CONCLUSION: Concomitant use of bisphosphonates and proton pump inhibitors will likely increase the risk of osteoporotic fractures in women aged 65 and over, and caution should be exercised in this high-risk group of patients.


Assuntos
Difosfonatos/farmacologia , Refluxo Gastroesofágico/tratamento farmacológico , Fraturas por Osteoporose/epidemiologia , Úlcera Péptica/tratamento farmacológico , Inibidores da Bomba de Prótons/farmacologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Difosfonatos/uso terapêutico , Interações Medicamentosas , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Fraturas por Osteoporose/prevenção & controle , Inibidores da Bomba de Prótons/uso terapêutico , República da Coreia/epidemiologia , Fatores de Risco
7.
J Allergy Clin Immunol ; 146(2): 300-306, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32561389

RESUMO

The coronavirus disease 2019 (COVID-19) (caused by severe acute respiratory syndrome coronavirus 2) pandemic has massively distorted our health care systems and caused catastrophic consequences in our affected communities. The number of victims continues to increase, and patients at risk can only be protected to a degree, because the virulent state may be asymptomatic. Risk factors concerning COVID-19-induced morbidity and mortality include advanced age, an impaired immune system, cardiovascular or pulmonary diseases, obesity, diabetes mellitus, and cancer treated with chemotherapy. Here, we discuss the risk and impact of COVID-19 in patients with mastocytosis and mast cell activation syndromes. Because no published data are yet available, expert opinions are, by necessity, based on case experience and reports from patients. Although the overall risk to acquire the severe acute respiratory syndrome coronavirus 2 may not be elevated in mast cell disease, certain conditions may increase the risk of infected patients to develop severe COVID-19. These factors include certain comorbidities, mast cell activation-related events affecting the cardiovascular or bronchopulmonary system, and chemotherapy or immunosuppressive drugs. Therefore, such treatments should be carefully evaluated on a case-by-case basis during a COVID-19 infection. In contrast, other therapies, such as anti-mediator-type drugs, venom immunotherapy, or vitamin D, should be continued. Overall, patients with mast cell disorders should follow the general and local guidelines in the COVID-19 pandemic and advice from their medical provider.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Gerenciamento Clínico , Mastocitose Cutânea/tratamento farmacológico , Mastocitose Sistêmica/tratamento farmacológico , Pandemias , Pneumonia Viral/epidemiologia , Betacoronavirus/imunologia , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Difosfonatos/uso terapêutico , Prova Pericial , Glucocorticoides/efeitos adversos , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/patologia , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/epidemiologia , Mastocitose Cutânea/patologia , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/patologia , Agonistas Mieloablativos/efeitos adversos , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Medicina de Precisão/métodos , Fatores de Risco , Vitamina D/uso terapêutico
9.
Med Clin North Am ; 104(3): 405-413, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32312406

RESUMO

Older adults, particularly those late in life, are at higher risk for medication misadventure, yet bear the burden of increasing polypharmacy. It is incumbent on practitioners who care for this vulnerable population to use one or more approaches to deprescribe medications that impose a greater burden than benefit, including medically futile medications. It is essential that health care providers use compassionate communication skills when explaining these interventions with patients and families, pointing out that this is a positive, patient-centric intervention.


Assuntos
Estado Terminal/terapia , Pessoal de Saúde/ética , Prescrição Inadequada/efeitos adversos , Assistência Centrada no Paciente/métodos , Idoso , Idoso de 80 Anos ou mais , Inibidores da Colinesterase/uso terapêutico , Comunicação , Desprescrições , Diabetes Mellitus/tratamento farmacológico , Difosfonatos/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Serviços de Saúde para Idosos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Prescrição Inadequada/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Assistência Centrada no Paciente/normas , Polimedicação
10.
J Bone Miner Metab ; 38(5): 678-686, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32236684

RESUMO

The aim of this study was to investigate the effect of bisphosphonates on preventing osteoporotic hip fracture in patients with or without prior major osteoporotic fracture. Randomized controlled trials (RCTs) and observational studies (OSs) based on electronic health records were used to assess bisphosphonate efficacy and were searched using PubMed, Scopus, and the Cochrane Library databases. Eight RCT studies and 14 OSs were extracted from the studies and quantitatively combined by random-effects meta-analysis. The odds ratio (OR) for all hip fractures in RCTs of 0.66, with a 95% confidence interval (CI) of 0.55-0.79, was lower than that in the OSs (OR 0.83; CI 0.74-0.94). The OR in patients with prior fracture was significantly reduced by bisphosphonates in both RCTs and OSs. Conversely, significant fracture reduction was not apparent in patients without prior fracture. A moderate relationship between prior major fracture rates and OR in hip fractures was defined. In patients with an average age of over 80 years, similar results were confirmed. In this meta-analysis, the efficacy of bisphosphonates was significant in patients with prior major fracture, recommending to prescribe for such patients. Their effect in patients without prior fracture, in contrast, remains unclear.


Assuntos
Difosfonatos/uso terapêutico , Fraturas do Quadril/tratamento farmacológico , Fraturas do Quadril/prevenção & controle , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/uso terapêutico , Humanos , Masculino , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
11.
Immunol Med ; 43(3): 103-106, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32301686

RESUMO

Bone is one of the most common distant organs in which tumor cells tend to metastasize depending on complicated immune system and bone microenvironments. Clinical symptoms such as severe pain and bone fractures associated with bone metastases severely affect patients' quality of life. According to the pathological types of bone destruction caused by the biological characteristics of different primary cancer cells, bone metastases are classified as osteolytic, osteoblastic and mixed types. Herein, we discuss the molecular mechanisms of bone metastasis and the therapeutic strategy with focus on bone metabolism.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Osso e Ossos/metabolismo , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Microambiente Tumoral , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Osso e Ossos/patologia , Humanos , Terapia de Alvo Molecular , Osteoblastos/patologia , Osteólise , Qualidade de Vida
12.
Medicine (Baltimore) ; 99(15): e18964, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282692

RESUMO

BACKGROUND: We performed a systematic review and meta-analysis of the efficacy and safety of teriparatide and bisphosphonates in managing postmenopausal osteoporosis. METHODS: PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure were searched for relevant randomized controlled trials that were published before April 2018 and compared teriparatide and bisphosphonates in treating postmenopausal osteoporosis. Stata 12.0 was used for the meta-analysis. The pooled risk ratio (RR) or weighted mean difference and 95% confidence interval (CI) were calculated using a fixed effects or random effects meta-analysis. RESULTS: A total of 14 randomized controlled trials were included in this meta-analysis. The teriparatide group was associated with a lower total occurrence of vertebral fractures (RR = 0.55, 95% CI: 0.40-0.77; P = .001) and nonvertebral fractures (RR = 0.65, 95% CI: 0.46-0.90; P = .009) than the bisphosphonate group. Moreover, compared with the bisphosphonate group, the teriparatide group had improved bone mineral density at the lumbar spine and femoral neck at the final follow-up (P < .05). There was no significant difference between the teriparatide and bisphosphonate groups in terms of complications (RR = 1.05, 95% CI: 0.90, 1.22, P = .516). CONCLUSIONS: Teriparatide significantly reduced the occurrence of vertebral and nonvertebral fractures in osteoporosis patients. More studies should focus on the quality of life of patients using these 2 drugs.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Difosfonatos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Teriparatida/uso terapêutico , Conservadores da Densidade Óssea/farmacologia , Difosfonatos/farmacologia , Colo do Fêmur/efeitos dos fármacos , Humanos , Vértebras Lombares/efeitos dos fármacos , Osteoporose Pós-Menopausa/complicações , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/prevenção & controle , Teriparatida/farmacologia
13.
Nat Rev Endocrinol ; 16(6): 333-339, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32203407

RESUMO

Approximately 50% of women experience at least one bone fracture postmenopause. Current screening approaches target anti-fracture interventions to women aged >60 years who satisfy clinical risk and bone mineral density criteria for osteoporosis. Intervention is only recommended in 7-25% of those women screened currently, well short of the 50% who experience fractures. Large screening trials have not shown clinically significant decreases in the total fracture numbers. By contrast, six large clinical trials of anti-resorptive therapies (for example, bisphosphonates) have demonstrated substantial decreases in the number of fractures in women not identified as being at high risk of fracture. This finding suggests that broader use of generic bisphosphonates in women selected by age or fracture risk would result in a reduction in total fracture numbers, a strategy likely to be cost-effective. The utility of the current bone density definition of osteoporosis, which neither corresponds with who suffers fractures nor defines who should be treated, requires reappraisal.


Assuntos
Osteoporose Pós-Menopausa/terapia , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/epidemiologia , Osteoporose Pós-Menopausa/prevenção & controle , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Pós-Menopausa , Padrões de Prática Médica/organização & administração , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/tendências
14.
J Bone Miner Metab ; 38(4): 469-480, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32020290

RESUMO

INTRODUCTION: Cold intolerance is defined as abnormal pain resulting from exposure to cold stimulation after trauma. However, the pathophysiology remains unclear. We recently demonstrated that regional osteoporotic changes accompanied by high bone turnover were involved in causing pain-like behaviors in the unloaded hind limbs of tail-suspended mice. Bisphosphonate prevented pain-like behaviors and high bone turnover conditions in tail-suspended mice. The aims of this study were to examine the relationship between regional osteoporotic changes and the induction of hypersensitivity to cold stimulation. MATERIALS AND METHODS: The hind limbs of tail-suspended mice were unloaded for 2 weeks. The von Frey test and paw-flick test assessed pain-like behaviors and cold plate test evaluated cold escape behaviors. Furthermore, we examined whether cold hypersensitivity associated with regional osteoporotic changes could be improved by bisphosphonate, TRPV1 and TRPA1 antagonists. RESULTS: Hypersensitivity to cold stimulation was induced more noticeably in the tail-suspended mice, and this effect was related to the increased expression of bone metabolism markers. In addition, the cold hypersensitivity was improved by the resumption of weight bearing and prevented by bisphosphonate or a TRPV1 antagonist, and was accompanied with a decrease in the expression of bone metabolism markers. TRPA1 antagonist significantly improved the cold escape behavior, but had no significant effects on the expression of those markers. CONCLUSION: We demonstrated that the regional osteoporotic changes accompanying a high bone turnover state could be involved in the induction of hypersensitivity to cold stimulation in the tail-suspended mice.


Assuntos
Temperatura Baixa , Síndromes Periódicas Associadas à Criopirina/complicações , Elevação dos Membros Posteriores , Osteoporose/complicações , Animais , Comportamento Animal , Diferenciação Celular , Difosfonatos/uso terapêutico , Elevação dos Membros Posteriores/efeitos adversos , Masculino , Camundongos Endogâmicos C57BL , Osteoblastos/patologia , Osteoclastos/patologia , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Dor/patologia , Pele/patologia , Medula Espinal/patologia , Canal de Cátion TRPA1/antagonistas & inibidores , Canal de Cátion TRPA1/metabolismo , Canais de Cátion TRPM/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo
15.
Nurse Pract ; 45(3): 50-55, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32068658

RESUMO

Bisphosphonates have been safely used to treat osteoporosis, effectively reducing fracture risk after 3 to 5 years of treatment. Recent concerns about long-term safety coupled with posttreatment fracture risk reduction have increased support for drug holidays. The decision to start low-risk patients on drug holidays must be based on current fracture risk assessment.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Suspensão de Tratamento , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Esquema de Medicação , Duração da Terapia , Fraturas Ósseas/prevenção & controle , Humanos , Osteoporose/tratamento farmacológico , Medição de Risco
16.
Spine (Phila Pa 1976) ; 45(13): 863-871, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32049937

RESUMO

STUDY DESIGN: Multicenter, prospective randomized study. OBJECTIVE: Evaluate the impact of weekly teriparatide (WT) and bone contact (BC) status of grafted bone in patients recovering from multilevel lumbar interbody fusion (M-LIF). SUMMARY OF BACKGROUND DATA: WT has been reported to significantly improve bone fusion following posterior or transforaminal interbody fusion in osteoporosis patients. METHODS: Patients older than 50 years and osteoporotic were recruited. We defined the fusion of two or more consecutive intervertebral levels as M-LIF. All patients were instrumented with pedicle, iliac, or S-2 alar iliac screws after transplanting cages and autogenous bone between vertebral bodies. After surgical indication for M-LIF, the subjects were randomly allocated to receive either subcutaneous WT from 1 week to 6 months postoperatively (WT arm, N = 50) or a bisphosphonate (BP; BP arm, N = 54). Blinded radiological evaluations were performed using computed tomography (CT). Evaluation of bone fusion was performed at the intervertebral disc located at the bottom of the fixed range. The degree of bone fusion was calculated as a score from 2 to 6 points, with 2 defined as complete fusion. Bone fusion rate was also compared at 6 months postoperatively based on BC status of the grafted bone on CT immediately after surgery. RESULTS: Mean bone fusion score at 6 months postoperatively was 3.9 points in the WT group and 4.2 points in the BP group. The bone fusion rate at 6 months postoperatively tended to be higher in the WT group (46.8% vs. 32.7% in the BP group). The 6-month postoperative fusion rate of immediately postoperative of BC+ patients was significantly higher than that of BC- patients (47.4% vs. 9.5%). CONCLUSION: In M-LIF, there were no significant differences in bone fusion score between WT- and BP-treated patients. In contrast, BC status immediately postoperatively had a major impact on 6-month bone fusion. LEVEL OF EVIDENCE: 1.


Assuntos
Difosfonatos/uso terapêutico , Disco Intervertebral/efeitos dos fármacos , Vértebras Lombares/efeitos dos fármacos , Osteoporose/cirurgia , Teriparatida/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Ílio/transplante , Disco Intervertebral/cirurgia , Articulações , Vértebras Lombares/cirurgia , Região Lombossacral/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Distribuição Aleatória , Fusão Vertebral/métodos , Resultado do Tratamento
17.
Expert Opin Pharmacother ; 21(6): 721-732, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32004105

RESUMO

INTRODUCTION: Glucocorticoid (GC) induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. It develops in a dose and time dependent manner, due to a rapid and transient increase in bone resorption, followed by the inhibition of bone formation. AREAS COVERED: In this review, the authors summarize the pathophysiology of GIOP and give discussion to the clinical management of patients taking GCs, focusing on the currently available drugs that have antiresorptive or anabolic activity on bone. EXPERT OPINION: Despite the widespread use of GCs and their well-established detrimental skeletal effects, GIOP remains an under-diagnosed and under-treated condition. Indeed, the clinical management of GIOP is still debated, so that the recent guidelines differ in their indications for pharmacological intervention. Either bone mineral density (BMD) or algorithms such as FRAX do not completely account for the remarkable and rapid increase in fracture risk of most GC-treated patients. Moreover, while oral bisphosphonates remain the most used and cost-effective option, the potential increased benefits of more potent antiresorptive agents (e.g. denosumab and zoledronate) or anabolic compounds (e.g. teriparatide) warrant further investigation. Despite the above limitations, the assessment of fracture risk is recommended for all individuals committed to receiving oral GCs for 3 months or longer.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/prevenção & controle , Fraturas Ósseas/prevenção & controle , Glucocorticoides/efeitos adversos , Osteoporose/tratamento farmacológico , Algoritmos , Conservadores da Densidade Óssea/administração & dosagem , Análise Custo-Benefício , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas Ósseas/complicações , Glucocorticoides/uso terapêutico , Humanos , Osteoporose/induzido quimicamente , Teriparatida/uso terapêutico
18.
Arch Osteoporos ; 15(1): 21, 2020 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-32088774

RESUMO

We compared the cumulative network meta-analyses with the recommendations in postmenopausal osteoporosis practice guidelines and actual prescribing practices in the USA. There was no apparent discrepancy between guideline recommendations and drug prescribing rankings, with the exception of vitamin D and calcium, when we used cumulative NMAs as references. PURPOSE: To compare the results of cumulative network meta-analyses (NMAs) with the recommendations in postmenopausal osteoporosis practice guidelines and actual prescribing practices in the USA. METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus were searched to retrieve randomized controlled trials (RCTs) in July 2017. The Agency for Healthcare Research and Quality's National Guideline Clearinghouse and associated society websites were searched to retrieve guidelines in June 2018. We used the Medical Expenditure Panel Survey (MEPS) to analyze prescription data from 1996 to 2015. Two independent investigators selected eligible RCTs. One investigator selected potential eligible guidelines, which were confirmed by another investigator. Two independent investigators extracted data from included RCTs. One investigator extracted recommendations from guidelines, which were confirmed by another investigator. (Registration: UMIN000031894) RESULTS: We analyzed data from 1995, 2000, 2005, 2010, and 2015. We chose hip fracture as the primary outcome of cumulative NMAs. We included 51 trials, 17 guidelines, and 5099 postmenopausal osteoporosis patients from the MEPS. Bisphosphonate, including alendronate, and combination of vitamin D and calcium (vDCa) were consistently recommendable from an efficacy viewpoint in NMAs and recommended in guidelines. Alendronate was the most prescribed drug (more than 30% over the observation period); however, vDCa was seldom prescribed. The maximum proportion was 5.3% from 2011 to 2015. CONCLUSIONS: In postmenopausal osteoporosis, there was no apparent discrepancy between guideline recommendations and drug prescribing rankings, with the exception of vDCa, when we used cumulative NMAs as references.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Osteoporose Pós-Menopausa/tratamento farmacológico , Guias de Prática Clínica como Assunto , Idoso , Idoso de 80 Anos ou mais , Alendronato/uso terapêutico , Cálcio na Dieta/uso terapêutico , Difosfonatos/uso terapêutico , Estudos Epidemiológicos , Feminino , Fraturas do Quadril , Humanos , Pessoa de Meia-Idade , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos/epidemiologia , Vitamina D/uso terapêutico
19.
J Bone Miner Metab ; 38(4): 511-521, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31970477

RESUMO

INTRODUCTION: This study compared the clinical usefulness of minodronate (50 mg/4 weeks) plus alfacalcidol (1 µg/day) (Group M) with that of alfacalcidol alone (1 µg/day) (Group A) for treating glucocorticoid-induced osteoporosis. MATERIALS AND METHODS: The primary endpoints were the changes from baseline in lumbar spine (LS) bone mineral density (BMD) and the cumulative incidence of vertebral fracture at 24 months; secondary endpoints included the changes from baseline in total hip (TH) BMD and bone turnover markers. RESULTS: Of 164 patients enrolled, 152 (Group M, n = 75; Group A, n = 77) were included in the analysis of efficacy. At each time point and at 24 months, LS BMD and TH BMD were significantly higher in Group M than in Group A. The 152 patients were divided into two subgroups that were previously treated with glucocorticoids for ≤ 3 months or > 3 months. In both subgroups, the changes from baseline in LS BMD and TH BMD from baseline at 24 months had increased more in Group M than in Group A. There were no differences found in the incidence of vertebral fracture between the groups, because the number of enrolled patients was lesser than that initially expected. In Group M, both bone formation and resorption markers significantly decreased from baseline at 3 months and maintained at 6, 12, and 24 months. CONCLUSIONS: Minodronate plus alfacalcidol was more effective than alfacalcidol alone in increasing BMD and was effective in increasing BMD for both prevention and treatment. Therefore, minodronate can be a good candidate drug for the treatment of glucocorticoid-induced osteoporosis.


Assuntos
Difosfonatos/uso terapêutico , Glucocorticoides/efeitos adversos , Hidroxicolecalciferóis/uso terapêutico , Imidazóis/uso terapêutico , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Difosfonatos/efeitos adversos , Difosfonatos/farmacologia , Quimioterapia Combinada , Feminino , Humanos , Hidroxicolecalciferóis/efeitos adversos , Hidroxicolecalciferóis/farmacologia , Imidazóis/efeitos adversos , Imidazóis/farmacologia , Masculino , Pessoa de Meia-Idade , Osteoporose/fisiopatologia , Fraturas da Coluna Vertebral/tratamento farmacológico , Fraturas da Coluna Vertebral/fisiopatologia , Adulto Jovem
20.
Yakugaku Zasshi ; 140(1): 63-79, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-31902887

RESUMO

Since the first report in 2003, bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been increasing, without effective clinical strategies. Osteoporosis is common in elderly women, and bisphosphonates (BPs) are typical and widely used anti-osteoporotic or anti-bone-resorptive drugs. BRONJ is now a serious concern in dentistry. As BPs are pyrophosphate analogues and bind strongly to bone hydroxyapatite, and the P-C-P structure of BPs is non-hydrolysable, they accumulate in bones upon repeated administration. During bone-resorption, BPs are taken into osteoclasts and exhibit cytotoxicity, producing a long-lasting anti-bone-resorptive effect. BPs are divided into nitrogen-containing BPs (N-BPs) and non-nitrogen-containing BPs (non-N-BPs). N-BPs have far stronger anti-bone-resorptive effects than non-N-BPs, and BRONJ is caused by N-BPs. Our murine experiments have revealed the following. N-BPs, but not non-N-BPs, exhibit direct and potent inflammatory/necrotic effects on soft-tissues. These effects are augmented by lipopolysaccharide (the inflammatory component of bacterial cell-walls) and the accumulation of N-BPs in jawbones is augmented by inflammation. N-BPs are taken into soft-tissue cells via phosphate-transporters, while the non-N-BPs etidronate and clodronate inhibit this transportation. Etidronate, but not clodronate, has the effect of expelling N-BPs that have accumulated in bones. Moreover, etidronate and clodronate each have an analgesic effect, while clodronate has an anti-inflammatory effect via inhibition of phosphate-transporters. These findings suggest that BRONJ may be induced by phosphate-transporter-mediated and infection-promoted mechanisms, and that etidronate and clodronate may be useful for preventing and treating BRONJ. Our clinical trials support etidronate being useful for treating BRONJ, although additional clinical trials of etidronate and clodronate are needed.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Conservadores da Densidade Óssea/metabolismo , Conservadores da Densidade Óssea/uso terapêutico , Ensaios Clínicos como Assunto , Ácido Clodrônico/química , Ácido Clodrônico/metabolismo , Ácido Clodrônico/farmacologia , Ácido Clodrônico/uso terapêutico , Difosfonatos/química , Difosfonatos/metabolismo , Difosfonatos/uso terapêutico , Ácido Etidrônico/química , Ácido Etidrônico/metabolismo , Ácido Etidrônico/farmacologia , Ácido Etidrônico/uso terapêutico , Humanos , Inflamação , Arcada Osseodentária/metabolismo , Camundongos , Nitrogênio , Proteínas de Transporte de Fosfato/antagonistas & inibidores , Ratos
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