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1.
Life Sci ; 258: 118164, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739467

RESUMO

High mobility group box-1 (HMGB1) protein is a diverse, single polypeptide moiety, present in mammalian eukaryotic cells. In response to stimuli, this nuclear protein is actively secreted in to the extracellular compartment or passively released by the necrotic cells, in order to mediate inflammatory responses, by forming complexes with IL-1α, IL-1ß, LPS and other moieties, and binding to RAGE, TLR and other receptor ligands, initiating downstream, signaling processes. This molecule acts as a proinflammatory cytokine and contributes to the progression of diseases like, acute lung injury, autoimmune liver damage, graft rejection immune response and arthritis. Small concentrations of HMGB1 are released during apoptosis, which facilitates oxidative regulation on Cys106, and propagates immune inactivating tolerogenic signals in the body. The review portrays the role of HMGB1 in rheumatoid arthritis, evidently supported by pre-clinical and clinical investigations, demonstrating extensive HMGB1 expression in synovial tissue and fluid as well as serum, excessive expression of transduction receptor signaling molecules, bone remodeling and uncontrolled expression of bone destroying osteoclastogenesis, resulting in destruction of articular cartilage, bone deformation and synovial proliferation, alleviating the pathogenesis in RA disease. Moreover, the review highlights the therapeutic regime targeting HMGB1, facilitating inhibition of its actions and release into the extracellular compartment, to ameliorate the destructive events that prevail in rheumatoid arthritis.


Assuntos
Artrite Reumatoide/patologia , Proteína HMGB1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/fisiopatologia , Remodelação Óssea/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Cartilagem Articular/fisiopatologia , Proteína HMGB1/análise , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Terapia de Alvo Molecular , Osteogênese/efeitos dos fármacos
3.
Scand J Rheumatol ; 49(4): 312-322, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32484386

RESUMO

OBJECTIVE: This is the first randomized double-blinded, placebo-controlled pilot trial to investigate the efficacy of pamidronate in reducing radiological and clinical disease activity in chronic non-bacterial osteomyelitis (CNO). METHOD: Patients received pamidronate or placebo at baseline and weeks 12 and 24. Whole-body magnetic resonance imaging was performed at baseline and weeks 12 and 36, and computed tomography of the anterior chest wall (ACW) at baseline and week 36. Radiological disease activity was systematically scored in the ACW and spine. Patient-reported outcomes [visual analogue scale (VAS) pain, VAS global health, Health Assessment Questionnaire (HAQ), EuroQol-5 Dimensions (EQ-5D), and 36-item Short-Form Health Survey (SF-36)] and biomarkers of bone turnover and inflammation were assessed at baseline and weeks 1, 4, 12, 24, and 36. Data are expressed as median [interquartile range]. RESULTS: Fourteen patients were randomized and 12 were analysed. From baseline to week 36, the radiological disease activity score in the ACW decreased from 5 [4-7] to 2.5 [1-3] in the pamidronate group, but did not change in the placebo group (p = 0.04). From baseline to week 36, VAS pain and VAS global health tended to decrease more in the pamidronate than in the placebo group (p = 0.11, p = 0.08). Physical functioning (HAQ) and health-related quality of life (EQ-5D, SF-36) did not change. Biomarkers of bone turnover decreased only in the pamidronate group (p ≤ 0.02). CONCLUSION: Pamidronate may improve radiological and clinical disease activity in CNO. Methods to score radiological disease activity in adult CNO were suggested. Clinical Trials: NCT02594878.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteomielite/tratamento farmacológico , Pamidronato/uso terapêutico , Coluna Vertebral/efeitos dos fármacos , Parede Torácica/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteomielite/sangue , Osteomielite/diagnóstico por imagem , Pamidronato/farmacologia , Medidas de Resultados Relatados pelo Paciente , Projetos Piloto , Coluna Vertebral/diagnóstico por imagem , Parede Torácica/diagnóstico por imagem , Imagem Corporal Total , Adulto Jovem
4.
Ann Agric Environ Med ; 27(2): 219-224, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32588596

RESUMO

INTRODUCTION: Osteoporosis, the "quiet epidemic", is one of the most serious threats to public health. It is known that estrogen plays a significant role in the regulation of bone turnover, and its loss at menopause causes osteoporosis. Added to this, insufficient calcium intake accelerates bone mass loss, increasing the risk of fractures. OBJECTIVE: The study aimed to answer the question whether a fructan-enriched diet could be helpful in preventing from disturbances in bone turnover caused by calcium restriction combined with ovariectomy-induced estrogen deficiency. The differences related to the kind of fructan and 'matrix effect' of fructan action (form of addition) were also evaluated. MATERIAL AND METHODS: The study was conducted using sham-operated (control groups) or ovariectomized (OVX) rats fed a calcium restricted diet. The treatment diets contained one of three fructan sources - Jerusalem artichoke, yacon and Beneo Orafti Synergy1 - added alone or as an ingredient of strawberry sorbet, all in the amount providing 8% fructans. Analyses of biological material included: serum Ca, Mg and P concentrations, alkaline phosphatase activity (ALP), osteocalcin (OC) and C-telopeptide degradation products from type I collagen (CTX). Densitometric parameters of femora were also assayed. RESULTS: Among markers of bone turnover, the ALP activity depended both on the kind of fructan and the form of addition. The highest value was shown in the OVX group fed a low-calcium diet, whereas administration of diet enriched with Jerusalem artichoke led to an almost 50% decrease in the value of this parameter. Dietary fructans also lowered the OC level. Feeding rats with diet containing sorbet enriched in yacon or Jerusalem artichoke resulted in a decrease of CTX, compared to the diet containing yacon alone or fructan formulation in both forms No significant differences were observed in densitometric parameters between treatment groups. CONCLUSIONS: The obtained findings suggest that fructan administration with a calcium-restricted diet might exert a positive effect on bone turnover parameters. Regarding the form of their addition, it is possible that other constituents of sorbets contributed to the fructan action. It remains open whether this impact would be significant over a longer period of time.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Cálcio/deficiência , Fêmur/efeitos dos fármacos , Frutanos/metabolismo , Osteoporose/prevenção & controle , Ovariectomia , Ração Animal/análise , Animais , Cálcio/administração & dosagem , Cálcio na Dieta/administração & dosagem , Dieta , Suplementos Nutricionais/análise , Feminino , Frutanos/administração & dosagem , Ratos , Ratos Wistar
5.
Eur J Endocrinol ; 183(2): 181-189, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32454455

RESUMO

Objective: Long-term androgen deprivation therapy (ADT) negatively influences bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover. Design: Prospective cohort study. Methods: Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied. Results: Of 26 screened patients, 17 were included. The median age was 44 (range 20-75) years. The median time interval between baseline and first follow-up was 13 (6-27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4-12.2); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01-0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7-35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered. Conclusions: In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.


Assuntos
Antagonistas de Androgênios/farmacologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiologia , Calcificação Fisiológica/efeitos dos fármacos , Acetato de Ciproterona/farmacologia , Adulto , Idoso , Bélgica , Remodelação Óssea/efeitos dos fármacos , Cálcio/sangue , Estudos de Coortes , Homeostase/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Estudos Prospectivos , Delitos Sexuais , Testosterona/sangue
6.
Med. clín (Ed. impr.) ; 154(9): 358-365, mayo 2020. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-193217

RESUMO

La artritis reumatoide (AR) es una enfermedad inflamatoria crónica que puede ocasionar destrucción articular y marcada discapacidad. El tratamiento precoz con fármacos modificadores de la enfermedad, incluyendo la terapia biológica, constituye el principal tratamiento para prevenir el daño estructural asociado a esta entidad. Algunos estudios han indicado que el tratamiento concomitante con antirresortivos, como los bisfosfonatos o el denosumab, podría prevenir el desarrollo de lesiones erosivas en este proceso, e incluso se ha sugerido que el tratamiento con un osteoformador, como la teriparatida, podría revertir las lesiones erosivas previamente establecidas. En este artículo se revisa la evidencia disponible sobre la eficacia del tratamiento antirresortivo y osteoformador en la prevención o tratamiento de las erosiones óseas asociadas a la AR


Rheumatoid arthritis (RA) is a chronic inflammatory disease that can cause joint destruction and marked disability. Early treatment with disease-modifying drugs, including biological therapy, is the principal treatment to prevent the structural damage associated with this entity. Some studies have indicated that concomitant treatment with antiresorptives, such as bisphosphonates or denosumab, could prevent erosive lesions in this process, and it has even been suggested that treatment with a bone forming agent, such as teriparatide, could revert previously established erosive lesions. In this article we review the evidence available on the efficacy of treatment with antiresorptives and bone forming agents in the prevention and/or treatment of bone erosions associated with RA


Assuntos
Humanos , Artrite Reumatoide/terapia , Antirreumáticos/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Denosumab/uso terapêutico , Articulações/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Autoimunidade , Articulações/fisiopatologia
7.
J Bone Miner Metab ; 38(5): 730-736, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32405760

RESUMO

INTRODUCTION: Aromatase inhibitors are known to accelerate bone loss in patients with breast cancer. However, how much AIs affect the efficacy of antiresorptive agents has not been studied. The study aimed to compare the effect of alendronate on bone mineral density (BMD) between patients with and without AI treatment. MATERIALS AND METHODS: In this retrospective study, 90 postmenopausal women with early breast cancer who were being treated with both AI and alendronate 70 mg weekly (ALN + AI), and 90 age- and body mass index (BMI)-matched patients who were only taking alendronate (ALN-only) were analyzed. BMD and bone turnover markers (BTMs) were assessed at the baseline and 12 months. RESULTS: The mean age was 63 years. At baseline, the ALN-only group had lower lumbar spine (LS), femur neck (FN), and total hip (TH) BMD than ALN + AI group. After 1-year of alendronate treatment, the LS and FN BMD were improved more in the ALN-only group than those in the ALN + AI group after adjustments for age, BMI, baseline BMD, diabetes, hypertension, renal function, and previous fracture history [LS BMD: 6.2% (3.1%; 9.2%) in ALN-only, 3.5% (-0.5%; 6.5%) in ALN + AI, p = 0.001; FN BMD: 2.5% (0.3%; 5.7%) in ALN-only, 0.9% (- 1.8%; 3.6%) in ALD + AI, p = 0.032]. BTMs were significantly decreased in both groups, but the changes between groups were similar. CONCLUSION: The effect of alendronate on the LS and FN BMD was attenuated in postmenopausal women who were taking AI compared to those who were not on AI.


Assuntos
Alendronato/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Alendronato/farmacologia , Inibidores da Aromatase/farmacologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Neoplasias da Mama/fisiopatologia , Feminino , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Lancet Diabetes Endocrinol ; 8(5): 407-417, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32333877

RESUMO

BACKGROUND: Medical treatment options for primary hyperparathyroidism are scarce. We aimed to assess the efficacy of denosumab and combined with cinacalcet in patients with primary hyperparathyroidism. METHODS: In this randomised, single-centre, proof-of-concept, double-blind trial, patients aged at least 18 years with primary hyperparathyroidism were recruited from the Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. Key eligibility criteria were a T-score between -1·0 and -3·5 at the lumbar spine, femoral neck, or total hip. Patients were assigned (1:1:1) via permuted block randomisation to receive 30 mg cinacalcet per day plus 60 mg denosumab subcutaneously every 6 months (n=14; combination group) for 1 year, denosumab plus placebo (n=16; denosumab group) for 1 year, or placebo plus placebo injection (n=15; placebo group) for 1 year. Primary outcomes were changes in bone mineral density (BMD) measured by dual x-ray absorptiometry at the lumbar spine, total hip, femoral neck, and distal forearm after 1 year. Additionally, effects on bone-metabolic biochemistry were explored. Patients and investigators were masked. All enrolled patients were included in efficacy analyses. The trial was done in an outpatient setting and is registered at ClinicalTrials.gov, NCT03027557, and has been completed. FINDINGS: Between March 14, 2017, and March 16, 2018 we recruited 285 participants. 16 patients were randomly allocated to the denosumab group, 15 to the combination group, and 15 to the placebo group. Dropout was limited to one patient in the combination group. Compared with placebo, BMD improved in groups receiving denosumab: lumbar spine (combination group 5·4% [95% CI 2·7-8·1], denosumab group 6·9% [95% CI 4·2-9·6]; p<0·0001), total hip (combination group 5·0% [3·0-6·9], denosumab group 4·1% [2·5-5·8]; p<0·0001), and femoral neck (combination group 4·5% [1·9-7·9]; p=0·0008, denosumab group 3·8% [1·4-6·3]; p=0·0022]). Changes in BMD at the third distal forearm were borderline significant. Six non-fatal serious adverse events occurred (combination group [n=2], denosumab group [n=1], placebo group [n=3]). The overall prevalence of adverse events did not differ between treatment groups, and no fatal adverse events occurred. INTERPRETATION: Evidence suggested denosumab was effective in improving BMD and lowering bone turnover in patients with primary hyperparathyroidism irrespective of cinacalcet treatment and might be a valid option for patients in which surgery is undesirable. FUNDING: Aalborg University Hospital and Aalborg University, Denmark.


Assuntos
Cinacalcete/uso terapêutico , Denosumab/uso terapêutico , Hiperparatireoidismo Primário/tratamento farmacológico , Idoso , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Cinacalcete/efeitos adversos , Denosumab/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Toxicology ; 436: 152412, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32145347

RESUMO

We investigated the effects of Kalach 360 SL (KL), Glyphosate (G)-based herbicide, on bone tissue in different groups of female Wistar rats. Group 1 (n = 6) received a standard diet and served as a control, groups 2 and 3 (n = 6 each) received 0.07 ml (D1: 126 mg/Kg) and 0.175 ml (D2: 315 mg/Kg) of KL dissolved in the water for 60 days. The plasma was used to examine the metabolic balance markers (calcium, phosphorus, phosphatase alkaline (PAL), and vitamin D (vit D) and hormonal status (oestrogen and thyroid hormones). As a result, sub-chronic exposure to KL induced a perturbation of bone metabolism (calcium and phosphorus) and hormonal status disturbance. The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Moreover, the KL disrupting eff ;ect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in female rats breast-fed from rats treated with D and D2 of KL. This eff ;ect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). Thus, that KL leads to hypothyroidism. Decrease in levels of oestrogen and thyroid dysfunction led to a disruption in the skeletal bone. The histological study and SEM in bone results allowed us to observe, in rats exposed to KL, the thinning and discontinuity of bone trabecular with a significant decrease in the number of nodes (intertrabecular links).In conclusion, KL sub-chronic exposure caused an aspect of osteoporosis.


Assuntos
Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Animais , Biomarcadores/sangue , Estrogênios/sangue , Feminino , Fêmur/metabolismo , Fêmur/ultraestrutura , Glicina/toxicidade , Hipotireoidismo/sangue , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/patologia , Osteoporose/sangue , Osteoporose/induzido quimicamente , Osteoporose/patologia , Ratos Wistar , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Hormônios Tireóideos/sangue
10.
J Bone Miner Metab ; 38(4): 522-532, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32140784

RESUMO

INTRODUCTION: Eldecalcitol increases bone mineral density (BMD) and reduces vertebral fracture in patients with primary osteoporosis. However, the effect of eldecalcitol on BMD and fracture in glucocorticoid-induced osteoporosis (GIO) patients is unknown. This study was undertaken to compare the effect of eldecalcitol on BMD and fracture with that of alfacalcidol in GIO patients. MATERIALS AND METHODS: A randomized, open-label, parallel group study was conducted to identify the effectiveness and safety of monotherapy with 0.75 µg eldecalcitol compared with 1.0 µg alfacalcidol in GIO patients. RESULTS: Lumbar spine BMD increased with eldecalcitol, but decreased with alfacalcidol at 12 and 24 months (between group difference 1.29%, p < 0.01, and 1.10%, p < 0.05, respectively). Total hip and femoral neck BMD were maintained until 24 months by eldecalcitol, but decreased by alfacalcidol (between group difference 0.97%, p < 0.05 and 1.22%, p < 0.05, respectively). Both bone formation and resorption markers were more strongly suppressed by eldecalcitol than by alfacalcidol. Eldecalcitol showed better effect on BMD than alfacalcidol in patients with no prevalent fracture and BMD > 70% of the young adult mean, and with ≤ 3 months of previous glucocorticoid treatment. No significant difference in the incidence of vertebral fracture was found, and the incidence of adverse events was similar between the two groups. CONCLUSIONS: Eldecalcitol was more effective than alfacalcidol in maintaining BMD in GIO patients. Because eldecalcitol was effective in patients with no or short-term previous glucocorticoid treatment, as well as those without prevalent fracture or low BMD, eldecalcitol can be a good candidate for primary prevention of GIO. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000011700.


Assuntos
Densidade Óssea , Glucocorticoides/efeitos adversos , Hidroxicolecalciferóis/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia , Vitamina D/análogos & derivados , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Feminino , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiopatologia , Quadril/fisiopatologia , Humanos , Hidroxicolecalciferóis/efeitos adversos , Hidroxicolecalciferóis/farmacologia , Estimativa de Kaplan-Meier , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fraturas da Coluna Vertebral/epidemiologia , Vitamina D/efeitos adversos , Vitamina D/farmacologia , Vitamina D/uso terapêutico
11.
J Bone Miner Metab ; 38(4): 501-510, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32140785

RESUMO

INTRODUCTION: High-turnover bone disease is a major consequence of SHPT and may explain the high risk for fracture in patients with advanced chronic kidney disease (CKD). Bisphosphonates suppress bone turnover and improve bone strength, but their effects have not been fully characterized in advanced CKD with severe SHPT. Bisphosphonates also increase 1,25-dihydroxyvitamin D levels in normal and uremic rats, but the underlying mechanism remains to be determined. MATERIALS AND METHODS: We investigated the skeletal and mineral metabolic effects of RIS, a pyridinyl bisphosphonate, in rats with severe SHPT induced by 5/6 nephrectomy plus a high phosphate diet. RESULTS: Nephrectomized rats developed severe SHPT, along with hyperphosphatemia, low 1,25-dihydroxyvitamin D, and markedly increased FGF23. Moreover, these rats exhibited characteristic features of high-turnover renal osteodystrophy, including increased indices of trabecular bone turnover, decreased cortical bone thickness, inferior cortical biomechanical properties, and a prominent increase in peritrabecular fibrosis. RIS treatment increased bone volume and partially attenuated trabecular bone remodeling, cortical bone loss, and mechanical properties, whereas it produced a marked improvement in peritrabecular fibrosis along with a corresponding decrease in osteogenic gene markers. RIS treatment also suppressed the elevation of FGF23, which was associated with increased 1,25-dihydroxyvitamin D. CONCLUSIONS: In a rat model of severe SHPT, treatment with RIS partially attenuated histological manifestations of high-turnover bone disease. RIS treatment also suppressed the elevation of FGF23, which may explain the increased 1,25-dihydroxyvitamin D production during the treatment.


Assuntos
Remodelação Óssea , Osso e Ossos/patologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Minerais/metabolismo , Ácido Risedrônico/uso terapêutico , Animais , Fenômenos Biomecânicos , Nitrogênio da Ureia Sanguínea , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Creatinina/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Nefrectomia , Fragmentos de Peptídeos/sangue , Fósforo/sangue , Pró-Colágeno/sangue , Ratos Sprague-Dawley , Ácido Risedrônico/farmacologia
12.
Rev. osteoporos. metab. miner. (Internet) ; 12(1): 20-27, ene.-mar. 2020. graf
Artigo em Espanhol | IBECS | ID: ibc-192306

RESUMO

OBJETIVO: El bazedoxifeno es un SERM de 3ª generación con efectos agonistas sobre el hueso y sobre el útero y el tejido mamario. Nuestro objetivo ha sido estudiar los efectos del bazedoxifeno sobre la calidad ósea en un modelo experimental de ratas ovariectomizadas. MATERIAL Y MÉTODOS: Se utilizaron 3 grupos de 15 ratas Wistar hembras de 6 meses de edad: uno control; otro de ratas ovariectomizadas; y un tercer grupo de ratas ovariectomizadas tratadas con bazedoxifeno (0,33 mg/kg/día). Tras 8 meses se estudiaron la densitometría ósea lumbar y femoral, los parámetros microtomográficos, los marcadores bioquímicos de remodelado y los parámetros biomecánicos del hueso. RESULTADOS: La ovariectomía descendió la densidad ósea femoral y lumbar. La última se recuperó parcialmente con bazedoxifeno. El remodelado óseo aumentó, recuperando el bazedoxifeno los niveles de formación. El bazedoxifeno recuperó la fracción volumétrica ósea (BV/TV), la densidad de superficie ósea (BS/TV), el aumento en la separación trabecular (Tb. Sp), la disminución en el número de trabéculas (Tb. N), el aumento del factor de patrón trabecular (Tb. Pf) y el índice de modelo estructural (SMI). La superficie relativa cortical aumentó tras la ovariectomía, normalizándose con bazedoxifeno. También recuperó la deformación máxima antes de la rotura producida por la ovariectomía, y amortiguó parcialmente la ganancia de peso de las ratas ovariectomizadas. CONCLUSIONES: Nuestro estudio muestra resultados positivos del bazedoxifeno sobre la calidad ósea. Este fármaco podría estar especialmente indicado para mujeres jóvenes postmenopáusicas con osteoporosis o en riesgo de padecerla


OBJETIVE: Bazedoxifene is a 3rdgeneration SERM with agonistic effects on the bones, uterus and breast tissue. Our goalhas been to study the effects of bazedoxifene on bone quality of an experimental group of ovariectomized rats. MATERIAL AND METHODS:3 groups of 15 6‐month‐old Wistar female rats were used: a control group, a group of untreatedovariectomized rats and a group of ovariectomized rats treated with bazedoxifene (0.33 mg/kg/day). After 8 monthswe studied the lumbar and femur bone densitometry, the microtomographic parameters, the biochemical markers forbone remodelling and the bone biomechanical parameters. RESULTS:The ovariectomy depleted the femur and lumbar bone density. After receiving bazedoxifene, the lumbar bonedensity showed partial healing. Bone remodelling increased recovering bazedoxifene formation levels. Bazedoxifenepromoted the recovery of the bone volume fraction (BV/TV), the bone surface density (BS/BV), the trabecular number(Tb. N), the trabecular spacing (Tb. Sp), the trabecular pattern factor (Tb. Pf) and the structural model index (SMI). Thecortical surface increased after the ovariectomy and returned to normal levels with the administration of bazedoxifene. The maximum deformation showed before the ovariectomy was also restored, partially cushioning the ovariectomizedrats' weight gain. CONCLUSIONS:Our study has shown bazedoxifene positive results on bone quality. This specific drug could be particularlysuitable for young postmenopausal women suffering or at risk of suffering osteoporosis


Assuntos
Animais , Feminino , Ratos , Conservadores da Densidade Óssea/administração & dosagem , Remodelação Óssea/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Microtomografia por Raio-X , Fatores de Tempo , Ovariectomia , Ratos Wistar
13.
Niger J Clin Pract ; 23(2): 154-158, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32031088

RESUMO

Background: There are a lot study confirmed the relationship of bone serum markers changes and skeletal irregularities. But there is no sufficient case control studies about the role of these markers on bisphosphonate induced osteonecrosis of jaws (BRONJ). Aims: The aim of this study is to find out if there is any derangement of bone markers in bisphosphonate-treated patients with ONJ. Methods: We obtained serum bone markers and other relevant endocrine assays on 20 patients with osteonecrosis of the jaw (ONJ) and 20 randomized healthy volunteers. All of the ONJ group treated with zoledronic acid and had been withdrawn from bisphosphonate for at least 6 months. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons. Serum levels of several indices of bone remodeling were evaluated using commercial enzyme-linked immunosorbent assays. The biochemical assays were performed on N-Telopeptides of type I collagen (NTX), bone-specific alkaline phosphatase (ALP), calcitonin, osteocalcin, intact parathyroid hormone (PTH), T3, T4, TSH, and Vitamin D 25 hydroxy (Vit-D). Results: In ONJ group, PTH level is statistically higher and TSH, Vit-D, osteocalcin and NTX levels statistically lower compared to control group. Conclusion: We conclude that these changes in PTH, Vit-D, TSH, osteocalcin and NTX levels maybe have a role in the pathophysiology of BRONJ. But the data need to be confirmed by future studies.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/sangue , Conservadores da Densidade Óssea/efeitos adversos , Remodelação Óssea/efeitos dos fármacos , Colágeno Tipo I/sangue , Difosfonatos/efeitos adversos , Hormônio Paratireóideo/sangue , Vitamina D/sangue , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Conservadores da Densidade Óssea/administração & dosagem , Estudos de Casos e Controles , Difosfonatos/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteocalcina , Peptídeos , Ácido Zoledrônico/uso terapêutico
14.
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
15.
J Bone Miner Metab ; 38(4): 544-554, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31983034

RESUMO

INTRODUCTION: The purpose of this study was to compare bone mineral density (BMD) and bone turnover markers between combined oral contraceptive (COC) and non-COC users over 12 months. MATERIALS AND METHODS: COC users (n = 34, age = 19.2 ± 0.5) and non-COC users (n = 28, age = 19.3 ± 0.6) provided serum at baseline, 6 months, and 12 months. C-terminal telopepetides (CTX) and pro-collagen type 1 N-terminal propeptides (P1NP) were determined using ELISA. BMD was measured at the three time points using dual-energy x-ray absorptiometry (DXA). RESULTS: COC users had greater CTX than non-COC users at baseline (18.6 ± 8.2 vs. 13.8 ± 5.3 ng/mL, P = 0.021) and 6 months (20.4 ± 10.3 vs. 14.2 ± 8.5 ng/mL, P = 0.018). Controlling for lean mass, groups were similar in BMD. Over 12 months, non-COC users maintained BMD at the spine, while the COC users declined 2.2% in lateral spine BMD (0.773 ± 0.014 to 0.756 ± 0.014 g/cm2, P = 0.03) and 0.7% in anterior-posterior spine BMD (1.005 ± 0.015 to 0.998 ± 0.015 g/cm2, P = 0.069). Non-COC users increased in BMD of the whole body over 12 months (P < 0.001) while COC users had no change. Women who began COCs within 4 years after menarche had lower BMD at the hip and whole body. Women taking very low dose COCs (20 mcg ethinyl estradiol, EE) significantly declined in CTX, P1NP, and lateral spine BMD in comparison to participants using low dose COCs (30/35 mcg EE). CONCLUSION: College-aged women who did not use COCs increased BMD of the whole body, while COC users had elevated bone turnover, declines in spinal BMD, and lack of bone acquisition of the whole body over 12 months. Young females who initiate COC use early after menarche may experience skeletal detriments.


Assuntos
Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Anticoncepcionais Orais Combinados/farmacologia , Absorciometria de Fóton , Biomarcadores/metabolismo , Etinilestradiol/farmacologia , Feminino , Humanos , Coluna Vertebral/efeitos dos fármacos , Adulto Jovem
16.
Arch Osteoporos ; 15(1): 7, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898803

RESUMO

Here, we report the case of a 69-year-old female who discontinued denosumab to undergo dental treatment. She subsequently suffered rebound-associated vertebral fractures (RVFs) twice. Denosumab is approved in several countries for osteoporosis treatment. Its discontinuation can result in bone turnover rebound increase and rapid bone mineral density loss. Rebound-associated vertebral fractures (RVFs) after discontinuing denosumab have been widely reported. We previously reported the case of a patient who suffered RVFs after discontinuing denosumab to undergo dental treatment. A 69-year-old female suffered five acute VFs 10 months after the last denosumab injection. The current report identifies the risks associated with denosumab discontinuation to undergo dental treatment. The patient described in this report also underwent an additional clinical course after the first RVFs. Next month after the first RVFs, she developed severe back pain when she changed her posture. Magnetic resonance imaging showed new RVFs at T9 and T12 levels. This case indicates that RVFs may occur more than once. In addition, it suggests that additional denosumab injections do not completely eliminate the risk of RVFs.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Denosumab/efeitos adversos , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas da Coluna Vertebral/induzido quimicamente , Síndrome de Abstinência a Substâncias/complicações , Idoso , Densidade Óssea , Remodelação Óssea/efeitos dos fármacos , Feminino , Humanos , Imagem por Ressonância Magnética , Osteoporose Pós-Menopausa/diagnóstico por imagem , Suspensão de Tratamento
17.
Int J Mol Sci ; 21(3)2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31979046

RESUMO

Osteoporosis is a common skeletal disorder, occurring as a result of an imbalance between bone resorption and bone formation, with bone breakdown exceeding bone building. Bone resorption inhibitors, e.g., bisphosphonates, have been designed to treat osteoporosis, while anabolic agents such as teriparatide stimulate bone formation and correct the characteristic changes in the trabecular microarchitecture. However, all of these drugs are associated with significant side effects. It is therefore crucial that we continue to research the pathogenesis of osteoporosis and seek novel modes of therapy. This editorial summarizes and discusses the themes of the fifteen articles published in the Special Issue, Osteoporosis: From Molecular Mechanisms to Therapies 2019, as part of the global picture of the current understanding of osteoporosis.


Assuntos
Osteoporose/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Humanos , Osteogênese/efeitos dos fármacos
18.
Clin Oral Investig ; 24(3): 1239-1247, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31317257

RESUMO

OBJECTIVES: Metoprolol is a cardioselective competitive beta-1 adrenergic receptor antagonist with antihypertensive properties, devoid of intrinsic sympathomimetic activity. Various studies have suggested the effect of beta-blockers on bone remodeling. We aimed to investigate whether metoprolol affects bone remodeling by altering anti-inflammatory and pro-inflammatory cytokines. MATERIALS AND METHODS: Surgical defects of 3 mm diameter were created in tibiae of 72 Sprague-Dawley rats. Rats were randomly assigned to a control group without metoprolol treatment (n = 36), and a test group treated with 0.1 mg/kg/day metoprolol (n = 36). Six rats from each group were sacrificed at days 0, 1, 3, 5, 7, and 14. The percentages of cells, which showed positive immunohistochemical staining for IL-1ß, IL-6, IL-10, and RANKL, were assessed in the defect area. Differences in percentages of stained cells within each of the test and control groups over various time intervals were tested using one-way ANOVA test. A P value of < 0.05 was considered statistically significant. RESULTS: No significant differences in IL-1ß, IL-10, IL-6, and RANKL expressions were found between test and control groups at the same interval. Significant reduction was observed at different time intervals in the same group (P < 0.05). CONCLUSION: Metoprolol did not reduce bone-active cytokine: IL-1ß, IL-6, and RANKL. It also did not elevate IL-10 expression levels. Thus, it does not appear to decrease osteoclastogenesis. CLINICAL RELEVANCE: Results from this animal model help us understand any effect of metoprolol on bone healing by potential contribution to different real-world clinical research.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Remodelação Óssea/efeitos dos fármacos , Metoprolol/administração & dosagem , Tíbia/efeitos dos fármacos , Animais , Injeções Intraperitoneais , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Projetos Piloto , Ligante RANK/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Tíbia/patologia
19.
J Bone Miner Metab ; 38(1): 117-125, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31471646

RESUMO

Pathogenic mutations in the melanocortin-4 receptor (MC4R) are associated with obesity, increased linear growth, and higher bone mass in children, and rodent studies have indicated an effect of the MC4R on bone turnover. Furthermore, GLP-1 receptor agonists (GLP-1 RAs) may influence bone metabolism. However, these associations have not been assessed in adults with pathogenic MC4R mutations. Thus, we wished to assess the impact of the MC4R on bone mass and metabolism. Secondly, we wished to investigate the impact of the GLP-1 RA liraglutide on bone mass in adults with pathogenic MC4R mutations. 17 patients with obesity-causing MC4R mutations (BMI: 35.5 ± 7.6) and 35 matched control participants with common obesity (BMI: 34.3 ± 7.1) underwent a DEXA scan for assessment of bone mineral density (BMD), bone mineral apparent density [BMAD = (BMD/√(bone area)], and bone turnover markers (BTMs). Individuals with a BMI above 28 (14 MC4R mutation carriers and 28 matched control participants) underwent 16 weeks treatment with liraglutide 3.0 mg. The MC4R group had higher BMD [mean difference: 0.065 g/m2 (- 0.008 to 0.138), p = 0.03], but BMAD and BTMS were not different compared to the control group. In response to liraglutide, BMAD increased in the control group, compared to no change in the MC4R group [mean group difference: 0.0007 (0.0001-0.001), p = 0.04]. In conclusion, BMD is increased in MC4R causal obesity compared to common obesity, but when corrected for body size (BMAD), bone mass was not increased, and no evidence of an influence of the MC4R on bone metabolism in adults was found. Liraglutide treatment did not change bone metabolism in MC4R causal obesity, but increased bone mass as measured by BMAD in common obesity.


Assuntos
Estatura/genética , Osso e Ossos/patologia , Mutação/genética , Receptor Tipo 4 de Melanocortina/genética , Absorciometria de Fóton , Adulto , Composição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Liraglutida/farmacologia , Masculino , Tamanho do Órgão/efeitos dos fármacos
20.
J Bone Miner Metab ; 38(1): 86-98, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31420748

RESUMO

Absorption of oral immediate-release (IR) risedronate tablets is reduced by food intake, thus a delayed-release (DR) tablet has been developed to overcome the necessity of taking IR tablets under fasting conditions. This randomized, double-blind, phase II/III study compared efficacy and safety of risedronate IR once-daily (QD) and DR once-monthly (QM) tablets in Japanese patients with involutional osteoporosis. Patients received 2.5 mg IR on awakening QD, or 25 or 37.5 mg DR on awakening, following breakfast, or 30 min after breakfast, QM for 12 months. Primary endpoint was non-inferiority in mean percent change from baseline to end of study (month 12, last observation carried forward [M12, LOCF]) in mean lumbar spine (L2-L4) bone mineral density (BMD) between risedronate IR on awakening and DR following breakfast. Mean percent changes in (L2-L4) BMD at M12, LOCF were 5.07% (IR at awakening, n = 190), 3.36% (25 mg DR following breakfast, n = 194), and 4.11% (37.5 mg DR following breakfast, n = 181). Mean percent change in (L2-L4) BMD was numerically lower in the DR following breakfast groups versus the respective on awakening and 30 min after breakfast DR groups. Overall incidences of treatment-emergent adverse events (TEAEs) were comparable between groups. In the DR groups, 1.5-4.0% of patients reported TEAEs potentially associated with acute-phase reactions versus 0% in the IR group. In this study, non-inferiority could not be declared for 37.5 or 25 mg DR following breakfast QM (p = 0.1346 or p = 0.6711, respectively) versus 2.5 mg IR on awakening QD.


Assuntos
Grupo com Ancestrais do Continente Asiático , Osteoporose/tratamento farmacológico , Ácido Risedrônico/uso terapêutico , Idoso , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Osteoporose/complicações , Cooperação do Paciente , Ácido Risedrônico/efeitos adversos , Ácido Risedrônico/farmacologia , Fraturas da Coluna Vertebral/complicações , Resultado do Tratamento
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