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1.
Cells ; 12(13)2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37443755

RESUMO

With the introduction of more and more monoclonal antibodies selectively targeting various mediators of the immune system, together with Janus-Kinase (JAK)-inhibitors with variable affinities towards different JAK subtypes, the available therapeutic options for the treatment of inflammatory bowel diseases (IBD) have undergone an acceleration in the last five years. On the other hand, the prevalence of IBD patients over 65-years-old is steadily increasing, and, with this, there is a large population of patients that presents more comorbidities, polypharmacy, and, more frequently, frailty compared to younger patients, exposing them to potentially major risks for adverse events deriving from newer therapies, e.g., infections, cardiovascular risks, and malignancies. Unfortunately, pivotal trials for the commercialization of new therapies rarely include older IBD patients, and those with serious comorbidities are virtually excluded. In the present review, we focus on existing literature from pivotal trials and real-world studies, analyzing data on efficacy/effectiveness and safety of newer therapies in older IBD patients with special emphasis on comorbidities and frailty, two distinct but intercorrelated aspects of the older population since age by itself seems to be of minor importance.


Assuntos
Fragilidade , Doenças Inflamatórias Intestinais , Inibidores de Janus Quinases , Humanos , Idoso , Inibidores de Janus Quinases/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Terapia Biológica
2.
Nutrients ; 13(6)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072655

RESUMO

Vitamin D modulates bisphosphonate (BP) efficacy, but its contribution to bone mineral density (BMD) after BP discontinuation is not known. To address this topic, we performed a retrospective analysis of postmenopausal women exposed to alendronate (ALN) to treat osteoporosis who regularly continued the supplementation of cholecalciferol or calcifediol at recommended doses. In the ninety-six recruited women (age 61.1 ± 6.9 years), ALN was administered for 31.2 ± 20.6 months and then discontinued for 33.3 ± 18.9 months. The modification of 25(OH)D serum levels over time was associated with a change of alkaline phosphatase (r = -0.22, p = 0.018) and C-terminal collagen type 1 telopeptide (r = -0.3, p = 0.06). Women in the tertile of the highest increase in 25(OH)D level showed a 5.7% BMD gain at lumbar spine, that was twice as great in comparison with participants with a lower 25(OH)D variation. At a multiple regression analysis, BMD change was associated with time since menopause (ß = 2.28, SE 0.44, p < 0.0001), FRAX score for major fracture (ß = -0.65, SE 0.29, p = 0.03), drug holiday duration (ß = -2.17, SE 0.27, p < 0.0001) and change of 25(OH)D levels (ß = 0.15, SE 0.03, p = 0.0007). After ALN discontinuation, improving the vitamin D status boosts the ALN tail effect on BMD.


Assuntos
Alendronato , Densidade Óssea/efeitos dos fármacos , Osteoporose Pós-Menopausa/tratamento farmacológico , Vitamina D , Idoso , Alendronato/administração & dosagem , Alendronato/farmacologia , Alendronato/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Vitamina D/administração & dosagem , Vitamina D/sangue , Vitamina D/farmacologia , Vitamina D/uso terapêutico
3.
Eur J Clin Invest ; 45(2): 144-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25483366

RESUMO

BACKGROUND: Low vitamin D serum levels have been associated with unfavourable lipid profile and poorer response to atorvastatin. Aims of this study were to test the effects of 25-hydroxyvitamin D3 (calcifediol) compared to parental vitamin D3 (cholecalciferol) supplementation on modifications of plasma 25(OH)D levels and lipid profile. MATERIALS AND METHODS: Fifty-seven postmenopausal women (aged 59.03 ± 6.73 years) who were at low risk of fracture and with basal plasma 25(OH)D < 30 ng/mL were included if they were on atorvastatin treatment prescribed as appropriate. Recruited women were randomized to receive oral calcifediol or cholecalciferol, both at a dose of 140 µg according to a weekly regimen. RESULTS: At baseline, 25(OH)D was negatively associated with BMI (r = -0.37; P = 0.004), total cholesterol (r = -0.31; P = 0.01) and LDL-C (r = -0.32; P = 0.02). After 24 weeks, 25(OH)D increased significantly in both groups (P < 0.001), although higher levels were obtained with calcifediol as compared with cholecalciferol (P < 0.001). Only in the calcifediol group, a significant reduction of LDL-C (P = 0.01) and an increase of HDL-C (P = 0.02) were obtained, even after adjustment for age, and baseline BMI, 25(OH)D and lipid levels (P < 0.05). The percentage changes in 25(OH)D levels were associated with the variations of LDL-C (r = -0.44; P = 0.01) and HDL-C levels (r = 0.30; P = 0.10). CONCLUSION: Calcifediol administration in osteopenic and dyslipidemic postmenopausal women with low 25(OH)D improves lipid profile when added to an ongoing atorvastatin treatment.


Assuntos
Calcifediol/administração & dosagem , Colecalciferol/administração & dosagem , Ácidos Heptanoicos/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Pós-Menopausa/efeitos dos fármacos , Pirróis/administração & dosagem , Vitaminas/administração & dosagem , Administração Oral , Atorvastatina , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/tratamento farmacológico , Suplementos Nutricionais , Quimioterapia Combinada , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Pessoa de Meia-Idade , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico
4.
J Clin Endocrinol Metab ; 98(5): 1911-5, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23596142

RESUMO

CONTEXT: Sclerostin is a circulating inhibitor of the Wnt-signaling pathway produced by osteocytes, which acts as a negative regulator of bone formation. Effects of zoledronic acid on sclerostin serum levels in postmenopausal osteoporosis are unknown. OBJECTIVE: The purpose of this study was to evaluate sclerostin serum levels after zoledronic acid administration and correlate variations with bone turnover markers. DESIGN AND SETTING: We conducted a prospective intervention study in an ambulatory care setting. PARTICIPANTS AND INTERVENTION: Forty women (mean age 62.6 ± 4.9 years) with postmenopausal osteoporosis were enrolled in this study and randomized into 2 groups to receive zoledronic acid (5 mg) or placebo. MAIN OUTCOMES MEASURES: At baseline and then at 2, 7, 30, and 360 days after zoledronic acid or placebo administration, serum levels of sclerostin, bone-specific alkaline phosphatase (BSAP), as a bone formation marker, and serum C-telopeptide of type 1 collagen (CTX), as a bone resorption marker, were measured. RESULTS: Sclerostin serum levels increased by day 2, reached a peak at day 7 (3-fold baseline, P < .001), and then decreased at day 30 and returned near to baseline after 360 days in the zoledronic acid group. Both CTX and BSAP were reduced, and a significant negative correlation was observed between the percentage changes of sclerostin and the variation in BSAP and CTX at all time points in the zoledronic acid group (P < .05). No changes were observed in the placebo group. CONCLUSIONS: Our data demonstrate that zoledronic acid increases sclerostin serum levels and that sclerostin could play a role in coupling bone resorption to bone formation.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Proteínas Morfogenéticas Ósseas/sangue , Osso e Ossos/efeitos dos fármacos , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Regeneração Óssea/efeitos dos fármacos , Reabsorção Óssea/etiologia , Reabsorção Óssea/prevenção & controle , Osso e Ossos/metabolismo , Carbonato de Cálcio/uso terapêutico , Colecalciferol/uso terapêutico , Colágeno Tipo I/sangue , Colágeno Tipo I/metabolismo , Terapia Combinada , Suplementos Nutricionais , Difosfonatos/administração & dosagem , Feminino , Marcadores Genéticos , Humanos , Imidazóis/administração & dosagem , Infusões Intravenosas , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/dietoterapia , Osteoporose Pós-Menopausa/fisiopatologia , Fator de Transcrição PAX5/sangue , Fator de Transcrição PAX5/metabolismo , Peptídeos/sangue , Peptídeos/metabolismo , Fatores de Tempo , Ácido Zoledrônico
5.
Calcif Tissue Int ; 90(4): 279-85, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22350110

RESUMO

The acute-phase response (APR) is a frequent occurrence after infusion of zoledronic acid and is caused by activation of γδ T cells. Vitamin D receptor is expressed in immune cells, and vitamin D has immunomodulatory properties. The aim of this prospective study was to test the effect of vitamin D (cholecalciferol) on the incidence of APR and intensity of pain in women undergoing infusion of zoledronic acid for postmenopausal osteoporosis. 60 women were enrolled and randomized into two groups. At baseline, 30 women received an oral bolus of cholecalciferol (300,000 IU), while another 30 women received placebo. On day 5 both groups were treated with a single infusion of zoledronic acid (5 mg) and received a daily supplementation of calcium (1,000 mg) and vitamin D (800 IU). Patients were clinically evaluated and inflammatory markers were assayed before zoledronic acid administration and every 24 h for the following 2 days. The onset of APR has been defined by the occurrence of fever or at least one of the typical symptoms, such as musculoskeletal pain after zoledronic acid infusion. Intensity of pain was measured by a one-dimensional scale (0 = no pain, 10 = unbearable pain). APR developed in 66.6% of patients, with no significant difference between groups. The vitamin group experienced less musculoskeletal pain [median 1 (0-4) vs. 2 (1-8), P < 0.05] and exhibited lower inflammatory markers (P < 0.005 vs. placebo). Our data demonstrate that cholecalciferol at a dose of 300,000 IU reduces the intensity of musculoskeletal pain after infusion of zoledronic acid for postmenopausal osteoporosis.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Dor Musculoesquelética/tratamento farmacológico , Osteoporose Pós-Menopausa/tratamento farmacológico , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Imidazóis/uso terapêutico , Pessoa de Meia-Idade , Dor Musculoesquelética/fisiopatologia , Osteoporose Pós-Menopausa/metabolismo , Projetos Piloto , Estudos Prospectivos , Vitamina D/farmacologia , Vitaminas/farmacologia , Ácido Zoledrônico
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