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1.
J Bone Miner Metab ; 38(6): 894-902, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32656645

RESUMO

INTRODUCTION: Rapid descent in bone mineral density (BMD) and ascent in bone turnover marker (BTM) occur within the short period following denosumab (Dmab) discontinuation. In addition, the incidence of vertebral fracture also rises within the short period. The purpose of this study is to investigate the effects of sequential therapy using zoledronic acid (ZOL) on any adverse events after Dmab discontinuation. MATERIALS AND METHODS: This study was a multicenter retrospective observational study, and the subjects were osteoporosis patients who visited our institutions between 2013 and 2018. We performed sequential therapy using ZOL for 30 patients who had difficulty continuing Dmab, due to physical or social reasons, and investigated the fracture incidence and BMD/BTM changes at 4 time points (at the start of Dmab, the start of ZOL, 6 months after ZOL and 12 months after ZOL). RESULTS: No new vertebral/nonvertebral fractures were observed at each time point after switching from Dmab to ZOL in any of the 30 patients. The BMD/BTM changes were evaluated in 18 of the 30 cases, since all data of lumbar/femoral neck BMDs and TRACP-5b at 4 time points was only available in 18 cases. BMDs significantly increased at each time point compared with that at the start of Dmab. Serum TRACP-5b significantly decreased at each time point compared with that at the start of Dmab. CONCLUSION: It was suggested that sequential therapy using ZOL could suppress the decrease of BMD, and increase of BTM, if the period of Dmab administration was less than 3 years.


Assuntos
Denosumab/uso terapêutico , Suspensão de Tratamento , Ácido Zoledrônico/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Denosumab/efeitos adversos , Feminino , Fraturas Ósseas/sangue , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Estudos Retrospectivos , Fosfatase Ácida Resistente a Tartarato/sangue , Ácido Zoledrônico/efeitos adversos
2.
J Bone Miner Metab ; 38(2): 230-239, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31586241

RESUMO

INTRODUCTION: Zoledronic acid infusion is used to treat osteoporosis but patients, especially Japanese patients, often experience acute-phase reactions (APRs). In this multicenter, randomized, open-label, parallel-group study, we examined the efficacy of the most commonly used non-steroidal anti-inflammatory drug loxoprofen in Japan in reducing the incidence rate of zoledronic acid-induced APRs and body temperature, and investigated risk/protective factors for APRs in this population. MATERIALS AND METHODS: Patients aged ≥ 60 years with primary osteoporosis (n = 368) were allocated randomly to zoledronic acid plus loxoprofen (ZOL + LOX) or zoledronic acid alone (ZOL). All patients received 5-mg zoledronic acid infusion on day 1, and patients in the ZOL + LOX group also received 120 mg and 180 mg of oral loxoprofen on days 1 and 2, respectively. Adverse events and body temperature were recorded during the 7-day observation period. RESULTS: The incidence rates of APRs were 34.4% (64/186 patients) and 47.8% (87/182 patients) in the ZOL + LOX and ZOL groups, respectively (P = 0.0109). The proportions of patients with increased body temperature (≥ 1 °C and ≥ 37.5 °C) were similar in both groups (P = 0.1186). Past bisphosphonate users had a significantly lower incidence rate of APRs than treatment-naïve patients (odds ratio 0.444, 95% confidence interval 0.285-0.692, P = 0.0003). CONCLUSIONS: Zoledronic acid-induced APRs appeared to be suppressed by loxoprofen. Known risk/protective factors, including prior osteoporosis treatment, were applicable to Japanese patients.


Assuntos
Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Conservadores da Densidade Óssea/uso terapêutico , Ácido Zoledrônico/efeitos adversos , Reação de Fase Aguda/epidemiologia , Idoso , Temperatura Corporal , Difosfonatos/uso terapêutico , Feminino , Humanos , Incidência , Japão , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Fatores de Risco , Resultado do Tratamento , Ácido Zoledrônico/uso terapêutico
3.
Health Sci Rep ; 2(1): e107, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30697599

RESUMO

Background and aims: Clinical data regarding alendronate jelly are limited. We compared the efficacy and safety of once-weekly alendronate oral jelly with once-weekly alendronate tablet formulations in the context of primary osteoporosis. Methods: In this 6-month, open-label, prospective, observational study, Japanese patients aged ≥60 years with primary osteoporosis were included from 14 primary care centres in Japan. The effects of once-weekly alendronate oral jelly and tablet formulations on bone mineral density (BMD), bone turnover markers, and quality of life related to gastrointestinal symptoms were assessed at baseline and 6 months. Treatment was allocated by patient preference. This potentially confounding factor was adjusted for statistically. Results: In total, 170 patients were enrolled (jelly, n = 97; tablet, n = 73). Mean percent changes in radius, lumbar spine, femoral neck, and hip BMD were similar in both treatment groups at 6 months. Both formulations decreased tartrate-resistant acid phosphatase 5b (TRACP-5b) and procollagen 1 N-terminal peptide (P1NP) between baseline and 6 months (by about 50% and 60%, respectively); no significant differences in mean changes were noted in these markers between groups. At 6 months, no significant differences were noted in visual analogue scale or EuroQOL five-dimension questionnaire scores between groups. The jelly group had significantly lower scores than the tablet group in the Izumo scale domains of heartburn (-0.81, P = 0.0040), epigastralgia (-0.94, P = 0.0003), and epigastric fullness (-0.49, P = 0.044). During treatment, more patients discontinued for upper gastrointestinal symptoms in the tablet group (n = 4) than the jelly group (n = 1). Conclusions: Once-weekly alendronate oral jelly 35 mg may be a suitable alternative therapeutic agent for primary osteoporosis in Japan.

4.
Eur Spine J ; 20(2): 240-6, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21197553

RESUMO

With the aging of the population in developed countries, spine surgeons have recently been more likely to encounter elderly patients in need of treatment. This study investigated whether decompression surgery for cervical spondylotic myelopathy (CSM) in elderly patients aged 80 years or older would likely be a reasonable treatment. We retrospectively reviewed 605 consecutive patients with cervical myelopathy who underwent decompression surgery between 2004 and 2008. Patients with other conditions that could affect functional status or compression factors other than spondylosis were excluded from this study. Of the remaining 189 patients, 161 with CSM whose condition could be evaluated 6 months after surgery were analyzed. The patients were divided into two age groups: 80 years or older (Group A, 37 patients) and younger than 80 years of age (Group B, 124 patients). We evaluated the differences in symptom duration, clinical data, involved levels, surgical outcome, comorbidities, and postoperative complications between the two groups. The symptom duration was significantly shorter in Group A. The average JOA scores preoperatively and 6 months postoperatively were significantly lower in Group A; however, there was no significant difference in the recovery ratio. There were no significant differences in the percentages of patients with comorbidities or those with postoperative complications. Elderly patients aged 80 years or older regained approximately 40% of their function postoperatively, and the incidence of postoperative complication was similar to that in younger patients. Since this age group shows a rapid deterioration after onset, prompt decompression surgery is required.


Assuntos
Vértebras Cervicais/cirurgia , Compressão da Medula Espinal/cirurgia , Espondilose/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais/patologia , Descompressão Cirúrgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Recuperação de Função Fisiológica , Estudos Retrospectivos , Compressão da Medula Espinal/patologia , Espondilose/patologia , Resultado do Tratamento
5.
J Orthop Res ; 27(12): 1652-8, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19489046

RESUMO

It is assumed that there are systemic changes in mineral metabolism during fracture healing that may cause a predisposition to sequential fractures in osteoporotic patients who suffered from previous fractures. Initial therapies for patients with osteoporotic fractures are important to prevent disabilities in daily life consequent to bone and muscle atrophies, and sequential fractures, although systemic and local bone metabolism during fracture healing have not been well understood. We evaluated the effects of bone injury and elcatonin injection as an initial therapy on systemic and local bone turnover and bone wound healing. Two drill holes were made in the diaphysis of the left femur and tibia of 12-week-old male C57BL/6J mice. They were treated with three doses of elcatonin or a vehicle thrice a week until the end of the 28-day experiment. Urinary crosslinked C-telopeptide of type I collagen (CTX) increased and the bone mineral densities (BMDs) in the lumbar vertebrae decreased in the vehicle-treated mice. Elcatonin injection prevented increases in urinary CTX and reduction of the BMDs. In the noninjured femoral metaphysis, osteoclast surface increased until day 28, whereas elcatonin suppressed it. In the fracture site, elcatonin facilitated osteoblast proliferation and did not delay the healing of the bone defect. Bone injuries accelerated bone turnover systemically and locally, and the elcatonin injections suppressed the systemic acceleration of bone resorption without a delay of filling regenerated cortical bone in the bone defect.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Regeneração Óssea/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Calcitonina/análogos & derivados , Fêmur/efeitos dos fármacos , Absorciometria de Fóton , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Regeneração Óssea/fisiologia , Reabsorção Óssea/metabolismo , Calcitonina/farmacologia , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo I/urina , Modelos Animais de Doenças , Fêmur/diagnóstico por imagem , Fêmur/lesões , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteocalcina/genética , Osteocalcina/metabolismo , Peptídeos/urina , RNA Mensageiro/metabolismo , Cicatrização/efeitos dos fármacos
6.
J Bone Miner Metab ; 23(1): 8-14, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15616888

RESUMO

We tested the hypothesis that signaling of parathyroid hormone (PTH) facilitates osteoclastogenesis in bone marrow cells after immobilization, thereby reducing trabecular bone volume. We performed histomorphometric analyses in immobilized limbs after right sciatic neurectomy (IM) and in the contralateral limbs after sham surgery (M). Mice underwent thyroparathyroidectomy (TPTX) and then 0.2 microg/body of thyroxine was given three times a week, or the mice were subjected to sham surgery (sham). Six-week-old male ddY mice were assigned to four groups, as follows, after acclimatization for 1 week: M + sham, IM + sham; M + TPTX, and IM + TPTX. Bilateral tibial samples were used for analysis. Trabecular bone volume (BV/TV) in the secondary spongiosa of the proximal tibias in IM + sham was significantly reduced compared to that in M + sham. Osteoclast surface (Oc.S/BS) and number (Oc.N/BS) in IM + sham transiently increased at 3 and 4 weeks after IM. In contrast, TPTX partially prevented the IM-related reduction of BV/TV and completely suppressed the transient increases of Oc.S/BS and Oc.N/BS. In the bone marrow cells, the mRNA expression of RANKL was elevated in IM + sham, but not in IM + TPTX, compared to that in M + sham. The percentage of Mac-1-positive bone marrow cells, osteoclast precursors, was not altered after IM. There were no significant differences in the concentrations of interleukin (IL)-1alpha in the tibial bone marrow cell culture medium between M + sham and IM + sham. Our data demonstrated that significant increases in osteoclast surface and number after IM were suppressed in TPTX mice, closely associated with a reduction in the high expression of RANKL mRNA in the tibial bone marrow cells. We speculate that enhanced osteoclastogenesis due to limb immobilization may be related to the elevation of RANKL expression by the facilitation of parathyroid hormone signaling in bone marrow cells.


Assuntos
Osso e Ossos/citologia , Diferenciação Celular , Elevação dos Membros Posteriores , Osteoclastos/citologia , Paratireoidectomia , Animais , Células da Medula Óssea/metabolismo , Osso e Ossos/anatomia & histologia , Cálcio/sangue , Proteínas de Transporte/genética , Células Cultivadas , Citocinas/análise , Glicoproteínas/genética , Masculino , Glicoproteínas de Membrana/genética , Camundongos , Tamanho do Órgão , Osteoclastos/metabolismo , Osteoprotegerina , Fósforo/sangue , Ligante RANK , RNA Mensageiro/genética , Receptor Ativador de Fator Nuclear kappa-B , Receptores Citoplasmáticos e Nucleares/genética , Receptores do Fator de Necrose Tumoral
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