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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.
Osteoporos Sarcopenia ; 4(2): 61-68, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30775544

RESUMO

Objectives: The purpose of this study was to investigate the influences of interruption and reinitiation of monthly minodronate therapy on the bone mineral density (BMD) and bone metabolism markers in postmenopausal women with osteoporosis. Methods: Study patients were included if they had been administered monthly minodronate therapy for ≥6 months, interrupted the therapy, and reinitiated the therapy for ≥12 months. The BMD and bone metabolism markers were assessed at 4 time points: initiation, interruption, reinitiation and 1 year after reinitiation of therapy. Results: A total of 23 patients were enrolled. The mean monthly minodronate treatment period was 23.8 ±â€¯12.9 months following a mean interruption period of 11.9 ±â€¯5.4 months. Once increased by monthly minodronate treatment for 2 years on average, the BMD of lumbar spine and radius did not significantly decrease even after an interruption for 1 year on average. However, the BMD of the femoral neck did decrease after interruption. The BMD of the lumbar spine and radius increased further after 1 year of monthly minodronate retreatment. The BMD of the femoral neck did not change. Once decreased after the treatment for an average of 2 years followed by an interruption for 1 year, bone metabolism markers increased gradually but did not recover to baseline levels. A potent suppressive effect on bone resorption was noted. The change rate was greater for the bone formation marker procollagen 1 N-terminal propeptide. Conclusions: Monthly minodronate treatment increases BMD and reduces bone metabolism markers. The effect lessens after treatment interruptions, and can be restored by retreatment.

4.
J Bone Miner Metab ; 23(5): 341-50, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16133683

RESUMO

The study was performed to clarify the effects of active vitamin D (alfacalcidol) and/or alendronate (ALN) on bone tissue turnover in glucocorticoid (GC)-treated growing minipigs. Göttingen minipigs aged 8 months were divided into six groups (n = 5 each): group BC, killed for baseline control; group GC, injected subcutaneously with prednisolone (0.5 mg/kg body weight [BW] per day, 5 days/week for 24 weeks); group VC, treated with vehicle alone; group alf, treated with oral alfacalcidol at 0.1 microm/kg BW per day, 5 days/week; group ALN, treated with alendronate 1 mg/kg BW per day; and group alf* ALN, treated with both alf and ALN as above. Biochemical examinations dual-energy X-ray absorptiometry, micro-computed tomography, peripheral quantitative computed tomography, and histomorphometry were performed. In group GC, all bone chemical markers were lower than in group VC. GC treatment reduced the age-dependent augmentation of bone mass and structure by reducing the bone formation rate (BFR) and activation frequency (Ac.f) relative to VC in lumbar bone and femoral cortex. Trabecular and osteonal wall thickness values did not change by GC. Treatments with alf, ALN, and alf* ALN did not have substantial effects on bone mass or structure. Alf treatment maintained lumbar BFR and Ac.f, while ALN reduced osteoclasts. Femoral cortical Ac.f values were not affected by these treatments. GC caused reduced bone formation, leading to low tissue turnover and imbalance of bone formation and resorption. Modulation of bone tissue turnover by alfacalcidol and/or alendronate failed to maintain the growth-dependent increases in mass and structure in GC-treated young minipigs.


Assuntos
Adjuvantes Imunológicos/farmacologia , Alendronato/farmacologia , Glucocorticoides/metabolismo , Hidroxicolecalciferóis/farmacologia , Osteoporose/metabolismo , Absorciometria de Fóton/métodos , Animais , Peso Corporal , Densidade Óssea/efeitos dos fármacos , Regeneração Óssea , Reabsorção Óssea , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Fêmur/patologia , Vértebras Lombares/metabolismo , Prednisolona/farmacologia , Suínos , Porco Miniatura , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos
5.
J Bone Miner Metab ; 22(6): 530-40, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15490262

RESUMO

Estrogen deficiency causes reduction of bone mass and abnormal bone microarchitecture, consequently reducing bone strength. Human parathyroid hormone (hPTH) (1-34) increases bone mass and strength. To clarify the factors that determine the recovery of bone strength in the lumbar vertebrae of ovariectomized rats by intermittent hPTH administration, we analyzed the relationship between skeletal measurements and bone strength. Human PTH (1-34) administration resulted in recovery of cortical bone mineral content (BMC) and cortical bone area to sham the levels, but in resulted in a less pronounced recovery of trabecular BMC and no increase in the total cross-sectional area of the vertebral body. Of the three-dimensional (3D) trabecular bone parameters, hPTH (1-34) increased trabecular thickness (Tb.Th). The cortical shell area of L4, determined by histomorphometry, was also increased. In hPTH-treated rats, the only determinant of the compressive load of L5 was the cortical shell BMC, in the early recovery period (days 42-84). Our data suggest that increased cortical bone mass contributes more than trabecular bone mass and structure to the recovery of bone strength in response to hPTH therapy in the rat lumbar vertebral body after ovariectomy.


Assuntos
Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Vértebras Lombares/metabolismo , Teriparatida/administração & dosagem , Animais , Feminino , Humanos , Vértebras Lombares/patologia , Osteocalcina/sangue , Osteoporose/sangue , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Ovariectomia , Ratos , Ratos Sprague-Dawley
6.
Bone ; 33(5): 779-87, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14623053

RESUMO

The present study was designed to determine the effects of glucocorticoid (GC) on bone turnover, minerals, structure, and bone mechanical properties in minipigs. Six 8-month-old Göttingen minipigs were subcutaneously injected with prednisolone (PN, 0.5 mg/kg body wt (BW)/day, 5 days/week for 26 weeks (Group GC)), 6 were treated with vehicle alone (Group VC), and 4 were sacrificed at start of the study for baseline controls (Group BC). The increase in BW was similar in all groups. PN significantly reduced serum osteocalcin and urinary type-1 collagen N-telopeptide levels at 13 weeks and thereafter, compared with baseline and control, and also reduced serum bone specific alkaline phosphatase levels relative to baseline. At 26 weeks, the longitudinal axis of the lumbar bone and length of femur were smaller in Group GC than Group VC. The total cross-sectional area of femur, but not the lumbar bone, in Group GC was significantly different from Group VC. BMD of the femur, but not L2, measured by DXA, was lower in Group GC than in Groups BC and VC. The cortical shell structure measured by 2D-micro-CT deteriorated and age-dependent increases in trabecular bone structure 3D micro-CT were reduced by PN. PN also caused deterioration of the cortical structure of the mid-femur. In L2 and femur, PN significantly reduced the ultimate load and maximum absorption energy of the femur and L2 compared with Group VC. The structural modulus in Group GC was lower than in Group BC. Regression analyses revealed that bone minerals, bone structure, and chemical markers correlated with mechanical properties of L2 and mid-femur. Our results indicate that PN reduced systemic bone formation and resorption and suppressed the age-dependent increases in bone minerals, structure, and mechanical properties of L2 and mid-femur. Reduced bone turnover seemed to be associated with a reduction in mechanical properties. The growing minipig could be a suitable model of GCs-induced osteoporosis in humans.


Assuntos
Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Vértebras Lombares/efeitos dos fármacos , Prednisolona/farmacologia , Animais , Fenômenos Biomecânicos , Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Feminino , Fêmur/fisiologia , Glucocorticoides/farmacologia , Vértebras Lombares/fisiologia , Suínos , Porco Miniatura
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