RESUMEN
Ginsenosides are active compounds that are beneficial to bone metabolism and have anti-osteoporosis properties. However, very few clinical investigations have investigated the effect of ginseng extract (GE) on bone metabolism. This study aims to determine the effect of GE on improving bone metabolism and arthritis symptoms in postmenopausal women with osteopenia. A 12-week randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 90 subjects were randomly divided into a placebo group, GE 1 g group, and GE 3 g group for 12 weeks based on the random 1:1:1 assignment to these three groups. The primary outcome is represented by bone metabolism indices consisting of serum osteocalcin (OC), urine deoxypyridinoline (DPD), and DPD/OC measurements. Secondary outcomes were serum CTX, NTX, Ca, P, BsALP, P1NP, OC/CTX ratio, and WOMAC index. The GE 3 g group had a significantly increased serum OC concentration. Similarly, the GE 3 g group showed a significant decrease in the DPD/OC ratio, representing bone resorption and bone formation. Moreover, among all the groups, the GE 3 g group demonstrated appreciable improvements in the WOMAC index scores. In women with osteopenia, intake of 3 g of GE per day over 12 weeks notably improved the knee arthritis symptoms with improvements in the OC concentration and ratios of bone formation indices like DPD/OC.
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Artritis/tratamiento farmacológico , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Panax/química , Extractos Vegetales/uso terapéutico , Artritis/sangre , Artritis/complicaciones , Artritis/fisiopatología , Biomarcadores/sangre , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/complicaciones , Enfermedades Óseas Metabólicas/fisiopatología , Remodelación Ósea , Método Doble Ciego , Ingestión de Alimentos , Ejercicio Físico , Femenino , Humanos , Persona de Mediana Edad , Osteocalcina/sangre , Fenilendiaminas/sangre , Placebos , Extractos Vegetales/efectos adversos , Extractos Vegetales/farmacología , Resultado del TratamientoRESUMEN
Rosiglitazone is an effective insulin-sensitizer, however associated with bone loss mainly due to increased bone resorption and bone marrow adiposity. We investigated the effect of the co-administration of fish oil rich in omega-3 fatty acids (FAs) on rosiglitazone-induced bone loss in C57BL/6 mice and the mechanisms underlying potential preventive effect. Mice fed the iso-caloric diet supplemented with fish oil exhibited significantly higher levels of bone density in different regions compared to the other groups. In the same cohort of mice, reduced activity of COX-2, enhanced activity of alkaline phosphatase, lower levels of cathepsin k, PPAR-γ, and pro-inflammatory cytokines, and a higher level of anti-inflammatory cytokines were observed. Moreover, fish oil restored rosiglitazone-induced down-regulation of osteoblast differentiation and up-regulation of adipocyte differentiation in C3H10T1/2 cells and inhibited the up-regulation of osteoclast differentiation of RANKL-treated RAW264.7 cells. We finally tested our hypothesis on human Mesenchymal Stromal Cells differentiated to osteocytes and adipocytes confirming the beneficial effect of docosahexaenoic acid (DHA) omega-3 FA during treatment with rosiglitazone, through the down-regulation of adipogenic genes, such as adipsin and FABP4 along the PPARγ/FABP4 axis, and reducing the capability of osteocytes to switch toward adipogenesis. Fish oil may prevent rosiglitazone-induced bone loss by inhibiting inflammation, osteoclastogenesis, and adipogenesis and by enhancing osteogenesis in the bone microenvironment.
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Enfermedades Óseas Metabólicas/prevención & control , Suplementos Dietéticos , Ácidos Grasos Omega-3/administración & dosificación , Rosiglitazona/efectos adversos , Adipogénesis/efectos de los fármacos , Envejecimiento/fisiología , Animales , Enfermedades Óseas Metabólicas/inducido químicamente , Enfermedades Óseas Metabólicas/fisiopatología , Diferenciación Celular/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Modelos Animales de Enfermedad , Femenino , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/fisiología , Ratones , Ratones Endogámicos C57BL , Osteoblastos/efectos de los fármacos , Osteoblastos/fisiología , Osteoclastos/efectos de los fármacos , Osteoclastos/fisiología , Osteogénesis/efectos de los fármacos , Cultivo Primario de Células , Células RAW 264.7RESUMEN
Spaceflight is a unique environment that includes at least two factors which can negatively impact skeletal health: microgravity and ionizing radiation. We have previously shown that a diet supplemented with dried plum powder (DP) prevented radiation-induced bone loss in mice. In this study, we investigated the capacity of the DP diet to prevent bone loss in mice following exposure to simulated spaceflight, combining microgravity (by hindlimb unloading) and radiation exposure. The DP diet was effective at preventing most decrements in bone micro-architectural and mechanical properties due to hindlimb unloading alone and simulated spaceflight. Furthermore, we show that the DP diet can protect osteoprogenitors from impairments resulting from simulated microgravity. Based on our findings, a dietary supplementation with DP could be an effective countermeasure against the skeletal deficits observed in astronauts during spaceflight.
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Enfermedades Óseas Metabólicas/prevención & control , Radiación Cósmica/efectos adversos , Suspensión Trasera/efectos adversos , Prunus domestica , Vuelo Espacial , Animales , Densidad Ósea/fisiología , Densidad Ósea/efectos de la radiación , Enfermedades Óseas Metabólicas/diagnóstico , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/fisiopatología , Modelos Animales de Enfermedad , Alimentos en Conserva , Suspensión Trasera/fisiología , Humanos , Masculino , Ratones , Esqueleto/diagnóstico por imagen , Esqueleto/fisiopatología , Esqueleto/efectos de la radiación , Microtomografía por Rayos XRESUMEN
PURPOSE OF REVIEW: Osteosarcopenia is commonly accepted as the presence of low muscle mass and function (sarcopenia) and low bone mineral density (osteopenia and osteoporosis). Osteosarcopenia remains a topic of controversy as researchers worldwide seek to elucidate whether osteosarcopenia is associated with greater risk of negative outcomes than its component parts. This review examines the latest research and controversies, and charts a path forward. RECENT FINDINGS: Osteosarcopenia may occur in 5-37% of community-dwelling adults over the age of 65. This wide range is driven by variation in population, setting, and definitions applied. These differences in study design have resulted in mixed findings in associations with adverse outcomes for older adults living with osteosarcopenia. Research into interventions to prevent or treat osteosarcopenia, such as exercise, protein supplementation, and pharmacotherapy, is in its infancy but examined herein. The absence of a consensus operational definition of sarcopenia, and inaccurate measures of muscle mass, has hampered global progress in the field. We present a case for the path forward by reflecting on our recent history.
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Osteoporosis/fisiopatología , Sarcopenia/fisiopatología , Accidentes por Caídas/prevención & control , Accidentes por Caídas/estadística & datos numéricos , Conservadores de la Densidad Ósea/uso terapéutico , Enfermedades Óseas Metabólicas/complicaciones , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Enfermedades Óseas Metabólicas/epidemiología , Enfermedades Óseas Metabólicas/fisiopatología , Denosumab/uso terapéutico , Difosfonatos/uso terapéutico , Humanos , Mortalidad , Osteoporosis/complicaciones , Osteoporosis/tratamiento farmacológico , Osteoporosis/epidemiología , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/prevención & control , Prevalencia , Factores de Riesgo , Sarcopenia/complicaciones , Sarcopenia/tratamiento farmacológico , Sarcopenia/epidemiologíaRESUMEN
BACKGROUND: Cnidii Rhizoma is the dried root stem of Cnidium officinale Makino. Cnidii Rhizoma (CR) has been used to treat menstrual irregularity, menstrual pain, and menopause in Korea. However, the effects and mechanisms of CR on RANKL-induced osteoclastogenesis pathway remain to be elucidated. In this study, we investigated the effects of CR on the inhibition of bone resorption of osteoclast and its mechanism RANK signaling pathway. METHODS: The anti-osteoclastogenesis of water extract of CR was measured using RAW 264.7 cell. Tartrate-resistant acid phosphatase (TRAP) assay, pit assay, reverse transcription polymerase chain reaction (RT-PCR) and western blot were performed. Moreover, the effects of CR were determined with an in vivo model using ovariectomized (OVX) rats. RESULTS: CR extract suppressed osteoclastogenesis, its activity and bone resorption activity through decreasing gene of osteoclast-related such as nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), c-Fos, etc. Moreover, CR extract prevented the bone loss in OVX rats. CONCLUSION: These results show that CR has a positive effect on menopausal osteoporosis by suppressing osteoclastogenesis.
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Enfermedades Óseas Metabólicas/prevención & control , Cnidium/química , Factores de Transcripción NFATC/metabolismo , Osteogénesis/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ligando RANK/metabolismo , Animales , Enfermedades Óseas Metabólicas/genética , Enfermedades Óseas Metabólicas/metabolismo , Enfermedades Óseas Metabólicas/fisiopatología , Femenino , Humanos , Ratones , Factores de Transcripción NFATC/genética , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Ovariectomía , Proteínas Proto-Oncogénicas c-fos/genética , Ligando RANK/genética , Células RAW 264.7 , Ratas , República de Corea , Rizoma/química , Transducción de Señal/efectos de los fármacosRESUMEN
The diurnal rhythm of bone remodeling suggests nocturnal dietary intervention to be most effective. This study investigated the effect of bedtime ingestion of a calcium-fortified, milk-derived protein matrix (MBPM) or maltodextrin (CON) on acute (0-4 h) blood and 24-h urinary change in biomarkers of bone remodeling in postmenopausal women with osteopenia. In CON, participants received 804 ± 52 mg calcium, 8.2 ± 3.2 µg vitamin D and 1.3 ± 0.2 g/kg BM protein per day. MBPM increased calcium intake to 1679 ± 196 mg, vitamin D to 9.2 ± 3.1 µg and protein to 1.6 ± 0.2 g/kg BM. Serum C-terminal cross-linked telopeptide of type I collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), and urinary N-telopeptide cross-links of type I collagen (NTX), pyridinoline (PYD) and deoxypyridinoline (DPD) was measured. Analyzed by AUC and compared to CON, a -32% lower CTX (p = 0.011, d = 0.83) and 24% (p = 0.52, d = 0.2) increase in P1NP was observed for MBPM. Mean total 24 h NTX excreted in MBPM was -10% (p = 0.035) lower than CON. Urinary PYD and DPD were unaffected by treatment. This study demonstrates the acute effects of bedtime ingestion of a calcium-fortified, milk-based protein matrix on bone remodeling.
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Enfermedades Óseas Metabólicas/dietoterapia , Remodelación Ósea , Calcio de la Dieta/administración & dosificación , Ritmo Circadiano , Suplementos Dietéticos , Alimentos Fortificados , Proteínas de la Leche/administración & dosificación , Posmenopausia/sangre , Anciano , Biomarcadores/sangre , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/diagnóstico , Enfermedades Óseas Metabólicas/fisiopatología , Calcio de la Dieta/efectos adversos , Colágeno Tipo I/sangre , Suplementos Dietéticos/efectos adversos , Femenino , Alimentos Fortificados/efectos adversos , Humanos , Irlanda , Persona de Mediana Edad , Proteínas de la Leche/efectos adversos , Hormona Paratiroidea/sangre , Fragmentos de Péptidos/sangre , Péptidos/sangre , Procolágeno/sangre , Factores de Tiempo , Resultado del Tratamiento , Vitamina D/administración & dosificaciónRESUMEN
PURPOSE: To determine whether posterior implant removal prevents stress-shielding-induced vertebral osteopenia within the posterior fusion area in surgically treated patients with adolescent idiopathic scoliosis (AIS). METHODS: Eighteen patients with major thoracic AIS (mean age, 43.3 years; range, 32-56 years; mean follow-up, 28.8 years, range, 20-39 years) who underwent posterior spinal fusion (PSF) alone between 1973 and 1994 were included. Participants were divided into implant removal (group R, n = 10, mean interval until implant removal, 50 months) and implant non-removal groups (group NR, n = 8). Bone mineral density was evaluated using the Hounsfield units (HU) of the computed tomography image of the full spine. The HU values of the UIV-1 (one level below the uppermost instrumented vertebra), apex, LIV+1 (one level above the lowermost instrumented vertebra), and LIV-1 (one level below the lowermost instrumented vertebra; as a standard value) were obtained. Stress-shielding-induced osteopenia was assessed as the UIV-1/LIV-1, apex/LIV-1, and LIV+1/LIV-1 HU ratios (× 100). RESULTS: Overall (median, 25th-75th percentile), the apex (144.7, 108.6-176.0) and LIV+1 (159.4, 129.7-172.3) demonstrated lower HU values than LIV-1 (180.3, 149.2-200.2) (both comparisons, p < .05). Comparison of groups R and NR showed no significant differences in the scoliosis correction rate, bone mineral density of the proximal femur, the HU absolute values of all investigated vertebrae, or in the HU ratios of the investigated vertebrae to LIV-1. CONCLUSION: Instrumented PSF causes stress-shielding-induced osteopenia of the vertebral body within the fusion area in adulthood, which cannot be prevented by posterior implant removal, probably due to firm fusion mass formation. These slides can be retrieved under Electronic Supplementary Material.
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Enfermedades Óseas Metabólicas/etiología , Tornillos Óseos/efectos adversos , Escoliosis/cirugía , Fusión Vertebral/efectos adversos , Adolescente , Adulto , Densidad Ósea , Enfermedades Óseas Metabólicas/fisiopatología , Enfermedades Óseas Metabólicas/prevención & control , Remoción de Dispositivos , Femenino , Fémur/fisiopatología , Estudios de Seguimiento , Humanos , Cifosis/diagnóstico por imagen , Cifosis/cirugía , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Radiografía , Estudios Retrospectivos , Escoliosis/diagnóstico por imagen , Fusión Vertebral/instrumentación , Fusión Vertebral/métodos , Vértebras Torácicas/cirugía , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Bone disease is a frequent event in cancer patients, both due to cancer spread to bone and to cancer therapies. Bone is the organ most frequently affected by metastatic disease when considering the two most frequent cancers in the Western world (breast and prostate cancers). Bone metastases can have a substantial detrimental effect on patients' quality of life, as well as significant morbidity due to complications collectively known as skeletal-related events (SREs), which include hypercalcaemia, pathological fractures, spinal cord compression, and need of radiotherapy or surgery to the bone. These have been successfully mitigated with the development of bone-targeted agents (BTAs; bisphosphonates and denosumab), focused on inhibiting osteoclast activity. The potential direct antitumour effect of bisphosphonates, as well as the impact of osteoclast inhibition with subsequent decrease in bone metabolism, have also propelled investigation on the role of BTAs in preventing cancer relapse in bone. In this review, the authors aimed to discuss the role of BTAs in the treatment and prevention of bone metastases, as well as their potential value in preventing cancer treatment-induced bone loss (CTIBL). The review will focus on breast and prostate cancers, with the aim of providing the most relevant clinical data emerging from bench to bedside translational research in the field of cancer-induced bone disease.
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Antineoplásicos/efectos adversos , Conservadores de la Densidad Ósea/uso terapéutico , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Neoplasias Óseas/tratamiento farmacológico , Remodelación Ósea/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Animales , Conservadores de la Densidad Ósea/efectos adversos , Enfermedades Óseas Metabólicas/inducido químicamente , Enfermedades Óseas Metabólicas/patología , Enfermedades Óseas Metabólicas/fisiopatología , Neoplasias Óseas/fisiopatología , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Cuidados Paliativos , Neoplasias de la Próstata/patología , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Animal studies provide strong evidence that the CNS directly regulates bone remodeling through the actions of the hypothalamus via two distinct pathways, the neural (mediated by leptin) arm and neurohumoral (mediated by neurohormones and growth factors) arm. The impact of AD on central regulatory mechanisms of bone mass is not known. OBJECTIVES: To test a model that assesses the relationship between hypothalamic atrophy and bone loss in Alzheimer's disease (AD) and potential mediation through neural (leptin) and neurohumoral (insulin-like growth factor -1, IGF-1) mechanisms. HYPOTHESES: AD-related hypothalamic structural change alters neural and neurohumoral regulatory systems of bone remodeling and contributes to bone loss in early AD. DESIGN: A secondary data analysis of data obtained in a two-year longitudinal study with path analysis and longitudinal mediation modeling. PARTICIPANTS: The data were collected as a part of the University of Kansas Brain Aging Project, a two-year observational study of 71 older adults with early stage AD and 69 non-demented controls. MEASUREMENTS: Demographic characteristics and measures of bone density, body composition, and hypothalamic volume, serum levels of leptin, growth hormone, and IGF-1 were collected. RESULTS: Hypothalamic atrophy and bone loss were observed in AD group and were associated. Data modeling suggests that bone loss may precede measurable changes in the brain. Leptin increased over two years in AD and the increase in leptin was associated with hypothalamic atrophy. However, changes in leptin or IGF-1 levels did not mediate the relationship between hypothalamic atrophy and bone loss. CONCLUSIONS: This study extends previous findings by suggesting that bone loss in AD may be related to neurodegenerative changes (atrophy) in the hypothalamus. Further studies are needed to explore the role of brain atrophy and mediating mechanisms in bone loss. Further exploring temporal relationship between bone loss and AD may have an important diagnostic value.
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Enfermedad de Alzheimer/fisiopatología , Enfermedades Óseas Metabólicas/fisiopatología , Anciano , Anciano de 80 o más Años , Envejecimiento , Enfermedad de Alzheimer/complicaciones , Animales , Atrofia , Composición Corporal , Densidad Ósea , Enfermedades Óseas Metabólicas/complicaciones , Encéfalo , Estudios de Casos y Controles , Sistema Nervioso Central/fisiología , Femenino , Hormona de Crecimiento Humana/sangre , Humanos , Hipotálamo/fisiopatología , Factor I del Crecimiento Similar a la Insulina/análisis , Leptina/sangre , Estilo de Vida , Estudios Longitudinales , Masculino , Modelos EstadísticosRESUMEN
OBJECTIVE: To investigate the impact of Qing'e Pill (, QEP) on the cancellous bone microstructure and its effect on the level of ß-catenin in a mouse model of postmenopausal osteoporosis. METHODS: Ninety-six 8-week-old specific pathogen free C57BL/6 mice were randomly divided into 4 groups (24/group): sham, ovariectomised osteoporosis model, oestradiol-treated, and QEP-treated groups. Three months after surgery, the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography (micro-CT) to acquire three-dimensional (3D) parameters of their cancellous bone microstructure. The impact of ovariectomy, the effect of oestradiol and QEP intervention on cancellous bone microstructure, and the expression of ß-catenin were evaluated. RESULTS: The oestradioland the QEP-treated groups exhibited a significant increase in the bone volume fraction, trabecular number, trabecular thickneßs, bone surface to bone volume ratio (BS/BV), and ß-catenin expression compared with those of the model group (P <0.05). In contrast, the structure model index, trabecular separation, and BS/BV were significantly decreased compared with those of the ovariectomised osteoporosis model group (P <0.05). No differences were observed in the above parameters between animals of the QEP- and oestradiol-treated groups. CONCLUSIONS: The increased ß-catenin expression may be the mechanism underlying QEP's improvement of the cancellous bone microstructure in ovariectomised mice. Our findings provide a scientific rationale for using QEP as a dietary supplement to prevent bone loss in postmenopausal women.
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Enfermedades Óseas Metabólicas/patología , Enfermedades Óseas Metabólicas/fisiopatología , Hueso Esponjoso/patología , Hueso Esponjoso/fisiopatología , Medicamentos Herbarios Chinos/farmacología , Animales , Fenómenos Biomecánicos/efectos de los fármacos , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/efectos de los fármacos , Fémur/diagnóstico por imagen , Fémur/efectos de los fármacos , Fémur/patología , Fémur/fisiopatología , Imagenología Tridimensional , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/patología , Vértebras Lumbares/fisiopatología , Ratones Endogámicos C57BL , Ovariectomía , Análisis de Supervivencia , Microtomografía por Rayos X , beta Catenina/metabolismoRESUMEN
Bone fragility, despite relatively high BMD values, is an important complication related to insulin resistance and oxidative stress in diabetes mellitus type 1. The present study aimed to compare the effects of soy milk (SM), soy milk containing Lactobacillus casei (PSM), and soy milk enriched with Lactobacillus casei and omega-3 (OPSM) on the stereology of the tibia and vertebra, and antioxidant activity in type 1 diabetic rats. Sixty-five male Sprague Dawley rats were randomly assigned into 5 groups of 13 animals each. Diabetes was induced by a single injection of STZ (60 mg/kg); two control groups (non-diabetic: CN and diabetic: CD) were selected and then fed with 1 mL of distilled water. Three treatment groups were fed 1 ml of SM, PSM, and OPSM via intragastric gavage for 60 days. Treatment with SM, PSM, and OPSM significantly decreased (P < 0.05) the number of the osteoclasts in both tibia and L5 vertebra, and plasma alkaline phosphatase level. Also, the osteoblast number, calcium level, catalase activity, and total antioxidant capacity were increased in the SM, PSM, and OPSM groups compared to the STZ group. OPSM had the greatest effects on the stereological and biochemical parameters compared to the SM and PSM groups. Soy milk combination with Lactobacillus casei and omega-3 can ameliorate the stereological changes in the tibia and vertebra. In addition, this combination increased the antioxidant activity and improved the redox homeostasis in diabetic rats. These results suggest the potential role of soy milk containing Lactobacillus casei enriched with omega-3 in preventing and delaying osteoporosis in diabetic patients.
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Enfermedades Óseas Metabólicas/tratamiento farmacológico , Diabetes Mellitus Tipo 1/complicaciones , Ácidos Grasos Omega-3/metabolismo , Probióticos/administración & dosificación , Leche de Soja/metabolismo , Tibia/metabolismo , Fosfatasa Alcalina/sangre , Animales , Densidad Ósea/efectos de los fármacos , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/fisiopatología , Calcio/sangre , Aditivos Alimentarios/análisis , Aditivos Alimentarios/metabolismo , Humanos , Lacticaseibacillus casei/fisiología , Vértebras Lumbares/química , Vértebras Lumbares/efectos de los fármacos , Masculino , Probióticos/análisis , Ratas , Ratas Sprague-Dawley , Leche de Soja/química , Tibia/químicaRESUMEN
The relationship involving acid-base imbalance, mineral metabolism and bone health status has previously been reported but the efficacy of the alkalizing supplementation in targeting acid overload and preventing bone loss has not yet been fully elucidated. In this randomized, double-blind, placebo-controlled study, the hypothesis that potassium citrate (K citrate) modifies bone turnover in women with postmenopausal osteopenia was tested. Three hundred and ten women were screened; 40 women met the inclusion criteria and were randomly assigned to the treatment or the placebo group. They were treated with K citrate (30 mEq day-1) or a placebo in addition to calcium carbonate (500 mg day-1) and vitamin D (400 IU day-1). At baseline and time points of 3 and 6 months, serum indicators of renal function, electrolytes, calciotropic hormones, serum bone turnover markers (BTMs), tartrate-resistant acid phosphatase 5b (TRACP5b), carboxy-terminal telopeptide of type I collagen (CTX), bone alkaline phosphatase (BAP), procollagen type 1 N terminal propeptide (PINP)), and urine pH, electrolytes, and citrate were measured. The follow-up was completed by 17/20 patients in the "K citrate" group and 18/20 patients in the "placebo" group. At baseline, 90% of the patients exhibited low potassium excretion in 24 h urine samples, and 85% of cases had at least one urine parameter associated with low-grade acidosis (low pH, low citrate excretion). After treatment, CTX and BAP decreased significantly in both groups, but subjects with evidence of low-grade acidosis gained significant benefits from the treatment compared to the placebo. In patients with low 24h-citrate excretion at baseline, a 30% mean decrease in BAP and CTX was observed at 6 months. A significant reduction was also evident when low citrate (BAP: -25%; CTX: -35%) and a low pH (BAP: -25%; CTX: -30%) were found in fasting-morning urine. In conclusion, our results suggested that K citrate supplementation improved the beneficial effects of calcium and vitamin D in osteopenic women with a documented potassium and citrate deficit, and a metabolic profile consistent with low-grade acidosis.
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Conservadores de la Densidad Ósea/administración & dosificación , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Remodelación Ósea/efectos de los fármacos , Suplementos Dietéticos , Citrato de Potasio/administración & dosificación , Equilibrio Ácido-Base/efectos de los fármacos , Anciano , Biomarcadores/sangre , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/diagnóstico , Enfermedades Óseas Metabólicas/fisiopatología , Método Doble Ciego , Femenino , Humanos , Italia , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
The effects of exogenous pulsed electromagnetic field (PEMF) stimulation on T1DM-associated osteopathy were investigated in alloxan-treated rabbits. We found that PEMF improved bone architecture, mechanical properties, and porous titanium (pTi) osseointegration by promoting bone anabolism through a canonical Wnt/ß-catenin signaling-associated mechanism, and revealed the clinical potential of PEMF stimulation for the treatment of T1DM-associated bone complications. INTRODUCTION: Type 1 diabetes mellitus (T1DM) is associated with deteriorated bone architecture and impaired osseous healing potential; nonetheless, effective methods for resisting T1DM-associated osteopenia/osteoporosis and promoting bone defect/fracture healing are still lacking. PEMF, as a safe and noninvasive method, have proven to be effective for promoting osteogenesis, whereas the potential effects of PEMF on T1DM osteopathy remain poorly understood. METHODS: We herein investigated the effects of PEMF stimulation on bone architecture, mechanical properties, bone turnover, and its potential molecular mechanisms in alloxan-treated diabetic rabbits. We also developed novel nontoxic Ti2448 pTi implants with closer elastic modulus with natural bone and investigated the impacts of PEMF on pTi osseointegration for T1DM bone-defect repair. RESULTS: The deteriorations of cancellous and cortical bone architecture and tissue-level mechanical strength were attenuated by 8-week PEMF stimulation. PEMF also promoted osseointegration and stimulated more adequate bone ingrowths into the pore spaces of pTi in T1DM long-bone defects. Moreover, T1DM-associated reduction of bone formation was significantly attenuated by PEMF, whereas PEMF exerted no impacts on bone resorption. We also found PEMF-induced activation of osteoblastogenesis-related Wnt/ß-catenin signaling in T1DM skeletons, but PEMF did not alter osteoclastogenesis-associated RANKL/RANK signaling gene expression. CONCLUSION: We reveal that PEMF improved bone architecture, mechanical properties, and pTi osseointegration by promoting bone anabolism through a canonical Wnt/ß-catenin signaling-associated mechanism. This study enriches our basic knowledge for understanding skeletal sensitivity in response to external electromagnetic signals, and also opens new treatment alternatives for T1DM-associated osteopenia/osteoporosis and osseous defects in an easy and highly efficient manner.
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Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/prevención & control , Diabetes Mellitus Tipo 1/complicaciones , Magnetoterapia/métodos , Oseointegración/fisiología , Animales , Fenómenos Biomecánicos/fisiología , Enfermedades Óseas Metabólicas/fisiopatología , Remodelación Ósea/fisiología , Huesos/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatología , Implantes Experimentales , Masculino , Porosidad , Conejos , Titanio , Vía de Señalización Wnt/fisiología , Microtomografía por Rayos XRESUMEN
Osteoporosis is a serious medical and socioeconomic problem of the 21st century. Mechanical load is a key regulator which controls bone formation and remodelling, with participation of osteocytes. Sclerostin is produced and released by mature osteocytes into bone surface, where it inhibits the conveyance of osteoblast proliferation and differentiation activating signals from mesenchymal cells, thus suppressing new bone formation. The goal of the study was an evaluation of the effects of a 12-week physical training programme on the levels of bone turnover markers [Sclerostin, Osteocalcin (OC), C-terminal telopeptide of type I collagen (ß-CTX)] in blood serum of women with osteopenia. MATERIALS & METHODS: The study included 50 women of the Regional Menopause and Osteoporosis Centre of the WAM Teaching Hospital, at the age of 50-75 years with the diagnosis of osteopenia, obtained on the basis of hip and/or lumbar spine densitometry (T-score from -1.0 to -2.5 SD). During the initial 12 weeks (between point 1 and 2), the patients maintained their previous, normal level of physical activity. During subsequent 12 weeks (between point 2 and 3), a programme of exercise was implemented. The programme included the interval training on a bicycle ergometer, three times a week for 36 minutes. During the entire study duration, all the patients received a supplementation of calcium (500 mg) and vit. D3 (1800 IU) once daily. Serum levels of OC, alkaline phosphatase (ALP), ß-CTX and sclerostin were assayed at 3 time points. RESULTS: After the course of the exercise cycle, the OC concentration was increased, sclerostin levels decreased, while no statistical differences were observed in ß-CTX levels vs. the period of physical inactivity. No correlations were found between sclerostin level changes and osteocalcin level changes during the training time, because of too small groups. Neither statistically significant were the differences in alkaline phosphatase, calcium and phosphorus levels. CONCLUSIONS: The obtained results emphasise the role of physical training as an effective stimulation method of bone formation processes in women with osteopenia. Sclerostin can be a marker of physical activity. < /p > < p >.
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Enfermedades Óseas Metabólicas/sangre , Proteínas Morfogenéticas Óseas/sangre , Ejercicio Físico , Proteínas Adaptadoras Transductoras de Señales , Anciano , Biomarcadores/sangre , Enfermedades Óseas Metabólicas/fisiopatología , Colágeno Tipo I/sangre , Femenino , Marcadores Genéticos , Humanos , Persona de Mediana Edad , Osteocalcina/sangreRESUMEN
A growing body of evidence has revealed that microRNAs (miRNAs) play crucial roles in regulating osteoblasts and bone metabolism. However, the effects of miRNAs in osteoblast mechanotransduction remain to be defined. In this study, we investigated the regulatory effect of miR-33-5p in osteoblasts and tested its anti-osteopenia effect when delivered by an osteoblast-targeting delivery system in vivo. First, we demonstrated that miR-33-5p could promote the activity and mineralization of osteoblasts without influencing their proliferation in vitro. Then our data showed that supplementing miR-33-5p in osteoblasts by a targeted delivery system partially recovered the osteopenia induced by mechanical unloading at the biochemical, microstructural, and biomechanical levels. In summary, our findings demonstrate that miR-33-5p is a key factor in the occurrence and development of the osteopenia induced by mechanical unloading. In addition, targeted delivery of the mimics of miR-33-5p is a promising new strategy for the treatment of pathological osteopenia.
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Enfermedades Óseas Metabólicas/patología , Enfermedades Óseas Metabólicas/fisiopatología , Técnicas de Transferencia de Gen , Suspensión Trasera , MicroARNs/administración & dosificación , Osteoblastos/metabolismo , Animales , Biomarcadores/metabolismo , Fenómenos Biomecánicos , Calcificación Fisiológica , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/patología , Diferenciación Celular , Línea Celular , Proliferación Celular , Masculino , Ratones Endogámicos C57BL , Osteogénesis , Sustancias Protectoras/metabolismoRESUMEN
Tocotrienols have shown bone-protective effect in animals. This study showed that a 12-week tocotrienol supplementation decreased concentrations of bone resorption biomarker and bone remodeling regulators via suppressing oxidative stress in postmenopausal osteopenic women. INTRODUCTION: Tocotrienols (TT) have been shown to benefit bone health in ovariectomized animals, a model of postmenopausal women. The purpose of this study was to evaluate the effect of 12-week TT supplementation on bone markers (serum bone-specific alkaline phosphatase (BALP), urine N-terminal telopeptide (NTX), serum soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), and serum osteoprotegerin (OPG)), urine calcium, and an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine (8-OHdG)) in postmenopausal women with osteopenia. METHODS: Eighty-nine postmenopausal osteopenic women (59.7 ± 6.8 year, BMI 28.7 ± 5.7 kg/m2) were randomly assigned to three groups: (1) placebo (430 mg olive oil/day), (2) low TT (430 mg TT/day, 70% purity), and (3) high TT (860 mg TT/day, 70% purity). TT, an extract from annatto seed with 70% purity, consisted of 90% delta-TT and 10% gamma-TT. Overnight fasting blood and urine samples were collected at baseline, 6, and 12 weeks for biomarker analyses. Eighty-seven subjects completed the 12-week study. RESULTS: Relative to the placebo group, there were marginal decreases in serum BALP level in the TT-supplemented groups over the 12-week study period. Significant decreases in urine NTX levels, serum sRANKL, sRANKL/OPG ratio, and urine 8-OHdG concentrations and a significant increase in BALP/NTX ratio due to TT supplementation were observed. TT supplementation did not affect serum OPG concentrations or urine calcium levels throughout the study period. There were no significant differences in NTX level, BALP/NTX ratio, sRANKL level, and sRANKL/OPG ratio between low TT and high TT groups. CONCLUSIONS: Twelve-week annatto-extracted TT supplementation decreased bone resorption and improved bone turnover rate via suppressing bone remodeling regulators in postmenopausal women with osteopenia. Such osteoprotective TT's effects may be, in part, mediated by an inhibition of oxidative stress. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02058420. TITLE: Tocotrienols and bone health of postmenopausal women.
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Antioxidantes/uso terapéutico , Resorción Ósea/prevención & control , Suplementos Dietéticos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Tocotrienoles/uso terapéutico , Anciano , Antioxidantes/farmacología , Biomarcadores/metabolismo , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Enfermedades Óseas Metabólicas/fisiopatología , Remodelación Ósea/efectos de los fármacos , Calcio/orina , Método Doble Ciego , Femenino , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/fisiopatología , Tocotrienoles/farmacologíaRESUMEN
BACKGROUND: Breastfeeding leads to bone calcium loss for milk production, resulting in progressive maternal osteopenia. Calcium supplement from natural sources has been postulated to be more beneficial to bone health than purified CaCO3 because natural sources also contain other nutrients such as certain amino acids that might enhance calcium metabolism. Herein, we examined the effect of calcium supplementation from tuna bone powder and CaCO3 on bones of dams and the offspring. RESULTS: Both forms of calcium supplement, i.e. tuna bone powder and CaCO3 , increased maternal bone mineral density (BMD). However, bone histomorphometry revealed that only tuna bone had beneficial effect on maternal bone microstructure, i.e. increased bone formation, decreased bone resorption and increased in bone volume. Regarding the mechanical properties, the decreased ultimate load in non-supplement lactating mothers was restored to the load seen in nulliparous animals by calcium supplementation. Moreover, both tuna bone and CaCO3 supplementation in mothers led to increased milk calcium concentration and consequently increased BMD in the growing offspring. CONCLUSION: Calcium supplement from tuna bone powder was effective in preventing maternal osteopenia. Tuna bone, which is a readily available fishing industrial waste, is a good alternative source of calcium supplement that increases BMD in both lactating mothers and the neonates. © 2017 Society of Chemical Industry.
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Densidad Ósea , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Enfermedades Óseas Metabólicas/metabolismo , Huesos/química , Calcio/metabolismo , Suplementos Dietéticos/análisis , Alimentos Fortificados/análisis , Animales , Enfermedades Óseas Metabólicas/fisiopatología , Huesos/metabolismo , Femenino , Humanos , Lactancia , Masculino , Ratas , AtúnRESUMEN
PURPOSE OF REVIEW: This review assembles recent understanding of the profound loss of muscle and bone in spinal cord injury (SCI). It is important to try to understand these changes, and the context in which they occur, because of their impact on the wellbeing of SC-injured individuals, and the urgent need for viable preventative therapies. RECENT FINDINGS: Recent research provides new understanding of the effects of age and systemic factors on the response of bone to loading, of relevance to attempts to provide load therapy for bone in SCI. The rapidly growing dataset describing the biochemical crosstalk between bone and muscle, and the cell and molecular biology of myokines signalling to bone and osteokines regulating muscle metabolism and mass, is reviewed. The ways in which this crosstalk may be altered in SCI is summarised. Therapeutic approaches to the catabolic changes in muscle and bone in SCI require a holistic understanding of their unique mechanical and biochemical context.
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Huesos/fisiopatología , Músculo Esquelético/fisiopatología , Osteoporosis/fisiopatología , Sarcopenia/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Densidad Ósea , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/metabolismo , Enfermedades Óseas Metabólicas/fisiopatología , Huesos/irrigación sanguínea , Huesos/metabolismo , Fibronectinas/metabolismo , Humanos , Interleucina-6/metabolismo , Mecanotransducción Celular , Músculo Esquelético/metabolismo , Enfermedades Musculoesqueléticas/etiología , Enfermedades Musculoesqueléticas/metabolismo , Enfermedades Musculoesqueléticas/fisiopatología , Miostatina/metabolismo , Osteocitos , Osteoporosis/etiología , Osteoporosis/metabolismo , Sarcopenia/etiología , Sarcopenia/metabolismo , Transducción de Señal , Traumatismos de la Médula Espinal/complicaciones , Soporte de PesoRESUMEN
The characteristics of patients with dermatitis herpetiformis (DH) in France is poorly documented. Furthermore, the risk of fractures and bone mineral density (BMD) in DH remain under-described, and recommendations for systematic screening for osteoporosis in DH are lacking. To describe the characteristics of DH in a large French cohort and evaluate the association between BMD and features of osteoporosis. Patients were recruited from the French Association of Gluten Intolerants (AFDIAG) and a single university dermatology department. A telephone questionnaire was used to record features of DH, history of fractures, calcium intake, treatment, and the gluten-free diet (GFD). Serum calcium and 25(OH) vitamin D3+D2 levels, as well as BMD, were measured. We included 53 patients (27 men) with a median age of 49 years (range: 23-86). Median disease duration before inclusion was 14 years (range: 2-55); 51 patients (96%) were adherent to a GFD and had no digestive symptoms. Overall, 18 (34%) had a history of fractures; 16 high-velocity (traumatic) and two low-velocity (non-traumatic). Mean BMD, measured in 48 patients, was normal (femoral neck: 0.956 ± 0.210 g/cm2; lumbar spine: 1.091 ± 1.199 g/cm2). In all, 18 patients (38%) had osteopenia and one (2%) osteoporosis. T-score for bone density did not differ with and without fractures. Calcium intake and serum calcium level were normal in all patients. Screening for osteoporosis does not appear to be mandatory for DH patients with good adherence to a GFD and without digestive symptoms or additional risk factors of osteoporosis.
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Densidad Ósea , Enfermedades Óseas Metabólicas/etiología , Dermatitis Herpetiforme/complicaciones , Dermatitis Herpetiforme/fisiopatología , Enfermedades Gastrointestinales/etiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Óseas Metabólicas/fisiopatología , Calcio/sangre , Calcio de la Dieta , Dapsona/uso terapéutico , Dermatitis Herpetiforme/terapia , Dieta Sin Gluten , Femenino , Antagonistas del Ácido Fólico/uso terapéutico , Fracturas Óseas/etiología , Francia , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/etiología , Osteoporosis/fisiopatología , Fósforo/sangre , Estudios Retrospectivos , Adulto JovenRESUMEN
Osteopenia is a condition in which bone mineral density (BMD) is lower than normal. Exercise increases BMD in both the young and adults. This study aimed to compare the radial apparent BMD (aBMD) in Japanese females who are Kendo practitioners (KPs) and those with no regular exercise habits (no-REH). The analysis participants consisted of 45 KPs (mean age: 49.4 years old) and 110 no-REH (mean age: 48.8 years old). Radial aBMD was measured using an ultrasonic bone densitometry system. Radial aBMD in KPs was 196.1 ± 33.9 mg/cm3, and was 182.9 ± 45.3 mg/cm3 in no-REH participants. KPs had significantly higher BMD than no-REH participants. In KPs, left radial aBMD was 196.1 ± 33.9 mg/cm3, and right radial aBMD was 184.5 ± 37.7 mg/cm3. The left radius was also significantly higher than the right radius with respect to aBMD in KPs. After adjusting for age, body mass index, menstrual status, parous women and frequency of milk and dairy intake, the odds ratio (OR) of osteopenia associated with no-REH was 6.58 (95% confidence interval (CI): 1.72-25.1) and the prevalence ratio (PR) of osteopenia associated with no-REH was 4.12 (95% CI: 1.23-13.7). Therefore, the Kendo practice may have a protective efficacy for osteopenia in women.