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BACKGROUND Long-term clinical practice has suggested a possible association between ossification of cervical ligament (OCL) and primary osteoporosis (POP). However, there is a lack of relevant research data. This study aimed to clarify the potential relationship between OCL and POP, and propose new strategies for preventing the onset of POP. MATERIAL AND METHODS The study involved 107 patients. The patients' diagnosis included OCL (ossification of the posterior longitudinal ligament, ossification of the ligamentum flavum, and ossification of the nuchal ligament) and POP. Bone mineral density (BMD), types of OCL, types of ossification of posterior longitudinal ligament, age, sex, serum calcium, serum phosphorus, alkaline phosphatase, type I collagen amino-terminal extension peptide, type I collagen degradation products, osteocalcin N-terminal molecular fragments, 25-hydroxyvitamin D, and history of taking steroid drugs were collected. SPSS24.0 and GraphPad Prism 8 were used to obtain the risk factors for POP. RESULTS One-way analysis of variance found that OCL, ossification of posterior longitudinal ligament, alkaline phosphatase, and osteocalcin N-terminal molecular fragments had statistical significance on BMD of the femoral neck (P<0.05). The independent sample t test showed that patient sex had statistical significant effect on BMD (femoral neck) (P=0.036). Incorporating the above factors into multiple linear regression analysis, it was found that OCL, alkaline phosphatase, and osteocalcin N-terminal molecular fragments were risk factors affecting BMD of femoral neck (P<0.05). CONCLUSIONS OCL, osteocalcin N-terminal molecular fragments, and alkaline phosphatase are risk factors for POP.
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Fosfatasa Alcalina , Densidad Ósea , Osificación del Ligamento Longitudinal Posterior , Osteocalcina , Osteoporosis , Humanos , Femenino , Masculino , Factores de Riesgo , Persona de Mediana Edad , Fosfatasa Alcalina/sangre , Fosfatasa Alcalina/metabolismo , Anciano , Osteocalcina/metabolismo , Osteocalcina/sangre , Adulto , Osificación Heterotópica , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Vitamina D/sangre , Ligamentos , Cuello Femoral/metabolismo , Vértebras CervicalesRESUMEN
BACKGROUND: Numerous studies have shown that various cytokines are important factors affecting bone mineral density (BMD), but the causality between the two remains uncertain. METHODS: Genetic variants associated with 41 circulating cytokines from a genome-wide association study (GWAS) in 8,293 Finns were used as instrumental variables (IVs) for a two-sample Mendelian randomization (MR) analysis. Inverse variance weighting (IVW) was employed as the primary method to investigate whether the 41 cytokines were causally associated with BMD at five different sites [total body bone mineral density (TB-BMD), heel bone mineral density (HE-BMD), forearm bone mineral density (FA-BMD), femoral neck bone mineral density (FN-BMD), and lumbar spine bone mineral density (LS-BMD)]. Weighted median and MR-Egger were chosen to further confirm the robustness of the results. We performed MR pleiotropy residual sum and outlier test (MR-PRESSO), MR-Egger regression, and Cochran's Q test to detect pleiotropy and sensitivity testing. RESULTS: After Bonferroni correction, two circulating cytokines had a strong causality with BMD at corresponding sites. Genetically predicted circulating hepatocyte growth factor (HGF) levels and HE-BMD were negatively correlated [ß (95 % CI) -0.035(-0.055, -0.016), P=0.00038]. Circulating macrophage inflammatory protein-1α (MIP-1α) levels and TB-BMD were negatively correlated [ß(95 %CI): -0.058(-0.092, -0.024), P=0.00074]. Weighted median and MR-Egger results were in line with the IVW results. We also found suggestive causal relationship (IVW P<0.05) between seven circulating cytokines and BMD at corresponding sites. No significant pleiotropy or heterogeneity was observed in our study. CONCLUSION: Our MR analyses indicated a causal effect between two circulating cytokines and BMD at corresponding sites (HGF and HE-BMD, MIP-1α and TB-BMD), along with suggestive evidence of a potential causality between seven cytokines and BMD at the corresponding sites. These findings would provide insights into the prevention and treatment of osteoporosis, especially immunoporosis.
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Densidad Ósea , Citocinas , Estudio de Asociación del Genoma Completo , Factor de Crecimiento de Hepatocito , Análisis de la Aleatorización Mendeliana , Humanos , Densidad Ósea/genética , Citocinas/sangre , Masculino , Femenino , Factor de Crecimiento de Hepatocito/sangre , Factor de Crecimiento de Hepatocito/genética , Polimorfismo de Nucleótido Simple/genética , Persona de Mediana Edad , Cuello Femoral/metabolismo , Quimiocina CCL3/sangre , Quimiocina CCL3/genéticaRESUMEN
Despite numerous investigations on the influence of fibroblast growth factor 23 (FGF23), α-Klotho and FGF receptor-1 (FGFR1) on osteoporosis (OP), there is no clear consensus. Mendelian randomization (MR) analysis was conducted on genome-wide association studies (GWASs)-based datasets to evaluate the causal relationship between FGF23, α-Klotho, FGFR1 and OP. The primary endpoint was the odds ratio (OR) of the inverse-variance weighted (IVW) approach. Furthermore, we stably transfected FGF23-mimic or siRNA-FGF23 into human bone marrow mesenchymal stem cells (hBMSCs) in culture and determined its cell proliferation and the effects on osteogenic differentiation. Using MR analysis, we demonstrated a strong correlation between serum FGF23 levels and Heel- and femoral neck-BMDs, with subsequent ORs of 0.919 (95% CI: 0.860-0.983, p = 0.014) and 0.751 (95% CI: 0.587-0.962; p = 0.023), respectively. The expression levels of FGF23 were significantly increased in femoral neck of patients with OP than in the control cohort (p < 0.0001). Based on our in vitro investigation, after overexpression of FGF23, compared to the control group, the BMSC's proliferation ability decreased, the expression level of key osteogenic differentiation genes (RUNX2, OCN and OSX) significantly reduced, mineralized nodules and ALP activity significantly decreased. After silencing FGF23, it showed a completely opposite trend. Augmented FGF23 levels are causally associated with increased risk of OP. Similarly, FGF23 overexpression strongly inhibits the osteogenic differentiation of hBMSCs, thereby potentially aggravating the pathological process of OP.
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Diferenciación Celular , Proliferación Celular , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Células Madre Mesenquimatosas , Osteogénesis , Osteoporosis , Humanos , Factor-23 de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/genética , Osteoporosis/genética , Osteoporosis/metabolismo , Osteoporosis/patología , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/genética , Proliferación Celular/genética , Diferenciación Celular/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Proteínas Klotho/metabolismo , Femenino , Glucuronidasa/genética , Glucuronidasa/metabolismo , Densidad Ósea/genética , Masculino , Persona de Mediana Edad , Cuello Femoral/metabolismo , Cuello Femoral/patologíaRESUMEN
Preclinical studies demonstrated that bone plays a central role in energy metabolism. However, how bone metabolism is related to the risk of diabetes in humans is unknown. We investigated the association of bone health (bone mineral density [BMD] and bone turnover markers) with incident type-2 diabetes mellitus (T2DM) based on the Hong Kong Osteoporosis Study (HKOS). A total of 993 and 7160 participants from the HKOS were studied for the cross-sectional and prospective analyses, respectively. The cross-sectional study evaluated the association of BMD and bone biomarkers with fasting glucose and glycated hemoglobin (HbA1c ) levels, whereas the prospective study examined the associations between BMD at study sites and the risk of T2DM by following subjects a median of 16.8 years. Body mass index (BMI) was adjusted in all full models. Mendelian randomization (MR) was conducted for causal inference. In the cross-sectional analysis, lower levels of circulating bone turnover markers and higher BMD were significantly associated with increased fasting glucose and HbA1c levels. In the prospective analysis, higher BMD (0.1 g/cm2 ) at the femoral neck and total hip was associated with increased risk of T2DM with hazard ratios (HRs) of 1.10 (95% confidence interval [CI], 1.03 to 1.18) and 1.14 (95% CI, 1.08 to 1.21), respectively. The presence of osteoporosis was associated with a 30% reduction in risk of T2DM compared to those with normal BMD (HR = 0.70; 95% CI, 0.55 to 0.90). The MR results indicate a robust genetic causal association of estimated BMD (eBMD) with 2-h glucose level after an oral glucose challenge test (estimate = 0.043; 95% CI, 0.007 to 0.079) and T2DM (odds ratio = 1.064; 95% CI, 1.036 to 1.093). Higher BMD and lower levels of circulating bone biomarkers were cross-sectionally associated with poor glycemic control. Moreover, higher BMD was associated with a higher risk of incident T2DM and the association is probably causal. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Diabetes Mellitus Tipo 2 , Osteoporosis , Humanos , Densidad Ósea/genética , Estudios Transversales , Hong Kong/epidemiología , Hemoglobina Glucada , Análisis de la Aleatorización Mendeliana , Estudios Prospectivos , Osteoporosis/epidemiología , Osteoporosis/genética , Osteoporosis/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Glucosa/metabolismo , Cuello Femoral/metabolismo , Biomarcadores/metabolismo , Remodelación Ósea/genética , Minerales/metabolismoRESUMEN
Introducción y objetivo: la calcificación aórtica abdominal (CAA) es predictora de eventos cardiovasculares. El objetivo de este trabajo fue valorar la asociación de la gamma glutamil transferasa (GGT) con presencia y progresión de CAA y los cambios en densidad mineral ósea (DMO) en columna lumbar y cuello femoral. Material y métodos: se seleccionaron 326 hombres y mujeres mayores de 50 años que realizaron un cuestionario, dos radiografías laterales dorso-lumbares y DMO, repitiendo a los 4 años las mismas pruebas y un estudio analítico. Resultados: la presencia y progresión de CAA (nuevas o mayor severidad) fue inferior en el cuartil 1 (Q1) de GGT respecto a los otros cuartiles (40 % vs. 58 %, p = 0,021; 24 % vs. 44 %, p = 0,022). Comparado con Q1, el análisis de regresión logística ajustado por confusores mostró que los Q2 y Q4 se asociaron con aumentos en la presencia de CAA [odds ratio (OR) = 2,53, intervalo de confianza del 95 % (IC 96 %) = (1,22-5,25) y OR = 3,04, IC 95 % = (1,36-6,77)] y Q2, Q3 y Q4 se asociaron con aumentos en progresión de CAA [OR = 2,24, IC 95 % = (1,07-4,67); OR = 2,35, IC 95 % = (1,09-5,07) y OR = 3,47, IC 95 % = (1,56-7,70)]. El análisis multivariante por sexos mostró que tanto en hombres como mujeres el Q4 de GGT se asoció con progresión de CAA [OR = 3,27, IC 95 % = (1,14-9,36) y OR = 3,26, IC 95 % = (1,03-10,29) respectivamente] y en mujeres con mayores pérdidas de DMO a nivel lumbar. No hubo efecto con respecto a la prevalencia de CAA. Conclusiones: valores elevados de GGT podrían ser un indicador de presencia y progresión de CAA en población mayor de 50 años. De forma separada por sexo, los mayores niveles de GGT se asociaron con progresión de CAA, siendo un marcador pronóstico de daño cardiovascular.(AU)
Introduction and objective: abdominal aortic calcification (AAC) is a predictor of cardiovascular events. This study aimedto assess the association of gamma glutamyl transferase (GGT) in the presence and progression of AAC, as well as changesto bone mineral density (BMD) in the lumbar spine and femoral neck.Materials and methods: a total of 326 men and women over 50 years of age were selected for this study. They completeda questionnaire, underwent two lateral dorso-lumbar spine X-rays, and BMD measurements. The same tests and 1 analyticalassessment were repeated after 4 years.Results: the presence and progression of AAC (new occurrences or increased severity) were lower in GGT quartile 1 (Q1)compared with the other quartiles (40 % vs 58 %; p = 0.021; 24 % vs 44 %; p = 0.022). Compared with Q1, the confound -ers-adjusted logistic regression analysis showed that Q2 and Q4 were associated with more presence of AAC [odds ratio(OR), 2.53; 95 % confidence interval (95 % CI), 1.22-5.25 and OR, 3.04; 95 % CI, 1.36-6.77]. Additionally, Q2, Q3, and Q4were associated with more AAC progression [OR, 2.24; 95 % CI, 1.07-4.67; OR, 2.35; 95 % CI, 1.09-5.07; and OR, 3.47;95 % CI, 1.56-7.70]. The gender-stratified multivariate analysis revealed that in both men and women, the Q4 of GGT wasassociated with AAC progression [OR, 3.27; 95 % CI, 1.14-9.36, and OR, 3.26; 95 % CI, 1.03-10.29, respectively], and inwomen alone, with greater lumbar BMD losses. There were no effects regarding the prevalence of AAC.Conclusions: elevated GGT levels could serve as an indicator of the presence and progression of AAC in individuals olderthan 50 years. When analyzed separately by gender, higher GGT levels were associated with AAC progression, which actedas a prognostic marker for cardiovascular disease.(AU)
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Humanos , Masculino , Femenino , Persona de Mediana Edad , gamma-Glutamiltransferasa , Densidad Ósea , Columna Vertebral , Cuello Femoral/metabolismo , Densitometría , Metabolismo , Osteoporosis , Encuestas y Cuestionarios , Factores de RiesgoRESUMEN
Childhood and adolescence are critical periods for optimizing skeletal growth. Dairy products are valuable sources of bone-beneficial nutrients, particularly calcium and protein. A random-effects meta-analysis of published randomized controlled trials was performed to quantitatively assess the effects of dairy supplementation on bone health indices in children and adolescents. The PubMed and Web of Science databases were searched. Dairy supplementation increased whole-body bone mineral content (BMC) (+25.37 g) and areal bone mineral density (aBMD) (+0.016 g/cm2), total hip BMC (+0.49 g) and aBMD (+0.013 g/cm2), femoral neck BMC (+0.06 g) and aBMD (+0.030 g/cm2), lumbar spine BMC (+0.85 g) and aBMD (+0.019 g/cm2), and height (0.21 cm). When expressed as a percentage difference, whole-body BMC was increased by 3.0%, total hip BMC by 3.3%, femoral neck BMC by 4.0%, lumbar spine BMC by 4.1%, whole-body aBMD by 1.8%, total hip aBMD by 1.2%, femoral neck aBMD by 1.5%, and lumbar spine aBMD by 2.6%. Dairy supplementation increased serum insulin-like growth factor I concentrations (19.89 nmol/L) and reduced concentrations of urinary deoxypyridinoline (-1.78 nmol/mmol creatinine) and serum parathyroid hormone (-10.46 pg/mL) but did not significantly affect the serum concentrations of osteocalcin, bone alkaline phosphatase, and C-terminal telopeptide of type 1 collagen. Serum 25-hydroxyvitamin D concentrations (+4.98 ng/mL) increased with vitamin D-fortified dairy supplementation. The positive effects on bone mineral mass parameters and height were generally consistent across subgroups defined by sex, geographical region, baseline calcium intake, calcium from the supplementation, trial duration, and Tanner stages. In summary, dairy supplementation during growth leads to a small but significant increase in bone mineral mass parameters, and these findings are generally supported by the changes in several biochemical parameters related to bone health.
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Densidad Ósea , Calcio , Adolescente , Niño , Humanos , Calcio de la Dieta/farmacología , Productos Lácteos , Suplementos Dietéticos , Cuello Femoral/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , PreescolarRESUMEN
Cystic fibrosis (CF) is a multi-system disease that is characterized by lung disease due to recurrent airway infection and inflammation. Endocrine complications, such as CF bone disease (CFBD), are increasingly identified as patients are living longer. The cause of CFBD is multifactorial with chronic systemic inflammation theorized to be a contributing factor. Thus, we attempted to identify inflammatory biomarkers that are associated with CFBD. We conducted a retrospective observational study of 56 adult patients with CF with an average percentage predictive forced expiratory volume in one second (ppFEV1) of 73.7% (standard deviation: 30.0) who underwent baseline serum analysis for osteoprotegerin (OPG) and pro-inflammatory biomarkers (IL-1ß, IL-6, IL-8 and TNF-α), and had repeated dual-energy x-ray absorptiometry (DXA) scans separated by at least 2 years to examine correlations between serum biomarkers and bone mineral density (BMD) measurements. Univariate linear regression model analysis demonstrated that serum IL-1ß and IL-8, but not other pro-inflammatory markers, were negatively correlated with baseline BMD results. However, after accounting for confounding variables, only the relationship between IL-8 and left femoral neck BMD remained statistically significant. Additionally, IL-8 level was associated with BMD decline over time. These results suggest that IL-8 might play a unique role in the pathophysiology of CFBD relative to other pro-inflammatory cytokines but further study is warranted before firm conclusions can be made.
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Densidad Ósea/genética , Fibrosis Quística/sangre , Cuello Femoral/metabolismo , Interleucina-1beta/sangre , Interleucina-8/sangre , Adolescente , Adulto , Remodelación Ósea/genética , Fibrosis Quística/genética , Fibrosis Quística/patología , Cuello Femoral/patología , Humanos , Inflamación/sangre , Inflamación/genética , Inflamación/patología , Masculino , Persona de Mediana Edad , Osteoporosis/sangre , Osteoporosis/genética , Osteoporosis/patología , Factor de Necrosis Tumoral alfa/sangre , Adulto JovenRESUMEN
INTRODUCTION: The relationship between the gut and skeleton is increasingly recognized as a component of the regulation of carbohydrate metabolism. The aim of our study was to assess the relationship between bone mineral density (BMD), incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), intestinotrophic peptide glucagon-like peptide-2 (GLP-2) and osteocalcin isoforms in patients with long-term type 1 diabetes (T1D) when compared to healthy controls. METHODS: Eighty two patients with long term T1D, treated in the Department of Metabolic Diseases and 53 healthy controls were recruited to the study. Long term disease duration was defined as lasting for more than 10 years. The control group was selected among age- and sex-matched healthy people. Fasting blood samples were collected to measure levels of incretin hormones (GLP-1, GLP-2, GIP), two forms of osteocalcin (uncarboxylated (ucOC), and carboxylated (cOC)), and additional biochemical parameters associated with glucose and bone metabolism (HbA1c, calcium, phosphorus, 25(OH)D3, PTH). RESULTS: Patients with T1D had higher BMI than in controls (p = 0.02). There was no difference in BMD at the lumbar spine and the femoral neck between patients with long-term T1D and healthy ones. Z-score values in both groups were within normal ranges. The level of GIP was significantly higher in T1D patients (p = 0.0002) in comparison to the healthy ones. The levels of GLP-1 and GLP-2 did not differ between T1D patients and controls. In the T1D group, strong, positive associations were found between serum levels of GLP-1 and cOC (r = 0.546, p < 0.001) and between GLP-1 and total OC (r = 0.51, p < 0.001), also after adjusting for BMI (p < 0.001 and p < 0.001, respectively). Significant positive associations were also found between serum levels of GLP-2 and cOC (r = 0.27, p = 0.013) and between GLP-2 and total OC (r = 0.25, p = 0.018), also in a multivariate regression (p = 0.009, p = 0,175, respectively). Moreover, in T1D patients, GLP-1 correlated positively with the femoral neck BMD (g/cm2) (r = 0.265, p = 0.016) and this association was statistically significant after adjusting for BMI (p = 0.011). These correlations were not present in the control group. The only significant correlation observed in the control group was between OC and BMD of the neck (p = 0.049 for neck BMD g/cm2, and p = 0.041 for neck Z-score). CONCLUSIONS: Our data suggests an effect of gut hormones on bone in long-term T1D, which could be associated with OC activity, however we did not find a direct connection with glucose metabolism. GLP-1 could have a possible, protective role on bone mineral density in patients with T1D. The data from our study suggests that gut hormones could be considered as a new link in the skeleton - pancreatic endocrine loop in patients with T1D.
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Diabetes Mellitus Tipo 1 , Glucemia , Cuello Femoral/metabolismo , Polipéptido Inhibidor Gástrico , Péptido 1 Similar al Glucagón , Humanos , Insulina/metabolismo , OsteocalcinaRESUMEN
Nucleoside/nucleotide analogs such as tenofovir, have been used as long-term therapy for the treatment of hepatitis B and side effects such as the reduction in bone mineral density have been associated with their use. To determine the relationships between bone, hormonal, biochemical, and mineral parameters in patients with hepatitis B treated with nucleoside/nucleotide antiviral. A cross-sectional study was conducted with 81 adult patients with chronic hepatitis B infection. Dual-energy X-ray absorptiometry (DXA) was performed to assess bone mineral density. Biochemical analyses were performed for osteocalcin, deoxypyridinoline, parathyroid hormone, vitamin D, IGF-1, TSH, testosterone, estradiol, FSH, transaminases, urea, creatinine, calcium, serum and urinary phosphorus, magnesium, and FGF-23, body composition was performed by DXA. Participants, both gender, were divided according to the use of antiretrovirals: Group1: 27 inactive virus carriers without medication; Group2: 27 patients using tenofovir; and Group3: 27 patients using lamivudine or entecavir. DXA readings diagnosed osteopenia in the lumbar spine for 7.4% of individuals in Group1, 15% in Group2, and 3.7% in Group3. For all groups, we observed normal values in bone formation markers, osteocalcin levels as well as parathyroid hormone, insulin growth factor 1, and FGF-23. In all groups, we found increased levels of urinary deoxypyridinoline, a bone resorption marker. Increased levels in the bone resorption markers indicated a high resorptive activity of bone tissue. These data suggested high resorption activity of bone tissue in hepatitis B virus-infected patients independent of the use of antiretrovirals.
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Antirretrovirales/uso terapéutico , Resorción Ósea/complicaciones , Resorción Ósea/metabolismo , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Osteoclastos/metabolismo , Absorciometría de Fotón , Adulto , Composición Corporal/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/virología , Estudios Transversales , Femenino , Cuello Femoral/diagnóstico por imagen , Cuello Femoral/metabolismo , Cuello Femoral/virología , Factor-23 de Crecimiento de Fibroblastos , Guanina/análogos & derivados , Guanina/uso terapéutico , Virus de la Hepatitis B/efectos de los fármacos , Cadera/diagnóstico por imagen , Cadera/virología , Humanos , Lamivudine/uso terapéutico , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/metabolismo , Vértebras Lumbares/virología , Masculino , Persona de Mediana Edad , Osteoclastos/efectos de los fármacos , Osteoclastos/virología , Tenofovir/uso terapéuticoRESUMEN
The aim of this study was to provide definitive reference values for bone mineral density (BMD) and bone turnover markers in the general elderly population. Registered citizens of 50 to 89 years old were targeted for this survey. After random sampling from the resident registry of Obuse town, we established eight groups based on age (50 s, 60 s, 70 s, and 80 s) and gender. A total of 411 people were enrolled. We used a dual-energy x-ray absorptiometry device to measure and evaluate BMD. The bone formation marker bone alkaline phosphatase (BAP) was measured as a bone turnover marker. Bone quality marker pentosidine, and bone resorption markers including urinary total deoxypyridinoline (DPD), tartrate-resistant acid phosphatase 5b (TRACP-5b), 25-hydroxyvitamin D (25[OH]D), and whole parathyroid hormone (PTH) were also measured as bone turnover markers. Sixty-three people (15.3%) were diagnosed as osteoporosis. BMD decreased with age in the femoral neck and total hip. On the other hand, there was no characteristic change with age in the lumber spine. As for bone markers, pentosidine and DPD increased with aging, although 25(OH)D, whole PTH, and BAP showed no characteristic associations with gender and aging. In terms of the relationship between low BMD and bone markers, there was a significant independent association between low BMD and TRACP-5b in females. In conclusions, hip BMD decreased with aging in men and women. However, there was no characteristic decline with aging in the lumbar spine. All bone markers showed no significant independent characteristics associated with age or gender in a multivariate analysis model, except for a significant association between low BMD and TRACP-5b in females. TRACP-5b was a potentially useful marker for the detection of low BMD.
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Envejecimiento/metabolismo , Densidad Ósea , Resorción Ósea/metabolismo , Cuello Femoral/metabolismo , Osteoporosis/diagnóstico , Osteoporosis/metabolismo , Sistema de Registros , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/metabolismo , Arginina/análogos & derivados , Arginina/metabolismo , Biomarcadores/metabolismo , Estudios de Cohortes , Femenino , Cadera , Humanos , Japón/epidemiología , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , Persona de Mediana Edad , Osteoporosis/epidemiología , Valores de Referencia , Fosfatasa Ácida Tartratorresistente/metabolismo , Vitamina D/análogos & derivados , Vitamina D/metabolismoRESUMEN
Recently, coupled musculoskeletal-finite element modelling approaches have emerged as a way to investigate femoral neck loading during various daily activities. Combining personalised gait data with finite element models will not only allow us to study changes in motion/movement, but also their effects on critical internal structures, such as the femur. However, previous studies have been hampered by the small sample size and the lack of fully personalised data in order to construct the coupled model. Therefore, the aim of this study was to build a pipeline for a fully personalised multiscale (body-organ level) model to investigate the strain levels at the femoral neck during a normal gait cycle. Five postmenopausal women were included in this study. The CT and MRI scans of the lower limb, and gait data were collected for all participants. Muscle forces derived from the body level musculoskeletal models were used as boundary constraints on the finite element femur models. Principal strains were estimated at the femoral neck region during a full gait cycle. Considerable variation was found in the predicted peak strain among individuals with mean peak first principal strain of 0.24% ± 0.11% and mean third principal strain of -0.29% ± 0.24%. For four individuals, two overall peaks of the maximum strains were found to occur when both feet were in contact with the floor, while one individual had one peak at the toe-off phase. Both the joint contact forces and the muscular forces were found to substantially influence the loading at the femoral neck. A higher correlation was found between the predicted peak strains and the gluteus medius (R2 ranged between 0.95 and 0.99) than the hip joint contact forces (R2 ranged between 0.63 and 0.96). Therefore, the current findings suggest that personal variations are substantial, and hence it is important to consider multiple subjects before deriving general conclusions for a target population.
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Cuello Femoral/metabolismo , Predicción/métodos , Esguinces y Distensiones/etiología , Anciano , Fenómenos Biomecánicos , Simulación por Computador , Femenino , Fémur/fisiología , Cuello Femoral/fisiología , Análisis de Elementos Finitos , Marcha/fisiología , Articulación de la Cadera/fisiología , Humanos , Extremidad Inferior , Imagen por Resonancia Magnética , Persona de Mediana Edad , Modelos Biológicos , Músculo Esquelético/fisiología , Esguinces y Distensiones/fisiopatología , Estrés Mecánico , Tomografía Computarizada por Rayos X , Caminata/fisiología , Soporte de Peso/fisiologíaRESUMEN
This study is aimed at establishing the prevalence of osteoporosis and osteopenia in kidney transplant recipients (KTRs) and determining the risk factors for bone mass loss. We invited KTRs who were under regular follow-up at Jiangxi Provincial People's Hospital Affiliated with Nanchang University to attend an assessment of osteoporotic risk assessed by questionnaire, biochemical profile, and dual-energy X-ray absorptiometry (DXA) scanning of the lumbar spine, total hip, and femoral neck. Binary logistic regression models were used to investigate the relationship between the different variables and bone mass density (BMD). A total of 216 patients satisfied the inclusion criteria. The group consisted of 156 men (72.22%) and 60 women (27.78%), and the mean age was 41.50 ± 9.98 years. There were 81 patients with normal bone mass (37.50%) and 135 patients with bone mass loss (62.50%). Logistic regression analysis showed that a higher phosphorus value and higher alkaline phosphatase concentration and a longer use of glucocorticoids were risk factors for bone mass loss in KTRs, and maintaining an appropriate weight and exercising an appropriate number of times per week helped to maintain bone mass.
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Huesos/metabolismo , Trasplante de Riñón , Receptores de Trasplantes , Absorciometría de Fotón , Adulto , Densidad Ósea , Enfermedades Óseas Metabólicas/complicaciones , Estudios Transversales , Femenino , Cuello Femoral/metabolismo , Humanos , Inmunosupresores/uso terapéutico , Vértebras Lumbares/metabolismo , Masculino , Persona de Mediana Edad , Osteoporosis/complicaciones , Análisis de RegresiónRESUMEN
The parathyroid hormone 1 receptor (PTHR1) plays a crucial role in calcium homeostasis and bone metabolism. However, its genetic role in regulating bone turnover markers (BTMs) in postmenopausal osteoporosis (PMO) remains unclear. Herein, we explored parathyroid hormone (PTH) and PTHR gene variant susceptibility to osteoporosis and their association with various circulating BTM and inflammatory markers in postmenopausal women of Arab ethnicity. In total, 600 postmenopausal Arab women (300-PMO and 300-control) were genotyped for selected SNPs in PTH (rs1459015, rs307253, rs6054, rs307247, rs10500783 and rs10500784), PTHR1 (rs6442037, rs1138518, and rs724449 SNPs) and PTHR2 (rs9288393, rs10497900, and rs897083). Anthropometrics, BTMs, and inflammatory markers were measured. Bone mineral density (BMD) was measured at the lumbar spine L1-L4 and the femoral neck using dual-energy X-ray absorptiometry (DXA). PTHR1 rs1138518 genotype C/T was found to be a significant risk factor for PMO (OR = 1.49, 95% CI 1.0-2.1, P = 0.03). The genotypes C/T and T/T of PTHR1 rs1138518 were associated with 25-hydroxy-vitamin D (25(OH)D) regulation. In the PMO group, carriers of the C/T genotype had significantly lower 25(OH)D levels than carriers of the same genotypes in the control group (59.9 (36.7-92.4) nmol/l and 66.4 (43.5-87.8) nmol/l, respectively; P = 0.048]. Our study concludes that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and 25(OH)D regulation in Arab women with PMO.
Asunto(s)
Osteoporosis Posmenopáusica/genética , Polimorfismo Genético/genética , Posmenopausia/genética , Receptor de Hormona Paratiroídea Tipo 1/genética , Árabes , Biomarcadores/metabolismo , Densidad Ósea/genética , Remodelación Ósea/genética , Calcifediol/metabolismo , Estudios de Casos y Controles , Femenino , Cuello Femoral/metabolismo , Humanos , Vértebras Lumbares/metabolismo , Persona de Mediana Edad , Vitamina D/análogos & derivados , Vitamina D/genética , Deficiencia de Vitamina D/genéticaRESUMEN
Both bone mineral density (BMD) and lean body mass (LBM) are important physiological measures with strong genetic determination. Besides, BMD and LBM might have common genetic factors. Aiming to identify pleiotropic genomic loci underlying BMD and LBM, we performed bivariate genome-wide association study meta-analyses of femoral neck bone mineral density and LBM at arms and legs, and replicated in the large-scale UK Biobank cohort sample. Combining the results from discovery meta-analysis and replication sample, we identified three genomic loci at the genome-wide significance level (p < 5.0 × 10-8): 2p23.2 (lead SNP rs4477866, discovery p = 3.47 × 10-8, replication p = 1.03 × 10-4), 16q12.2 (rs1421085, discovery p = 2.04 × 10-9, replication p = 6.47 × 10-14) and 18q21.32 (rs11152213, discovery p = 3.47 × 10-8, replication p = 6.69 × 10-6). Our findings not only provide useful insights into lean mass and bone mass development, but also enhance our understanding of the potential genetic correlation between BMD and LBM.
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Cuello Femoral/metabolismo , Sitios Genéticos , Pleiotropía Genética , Predisposición Genética a la Enfermedad , Osteoporosis/genética , Sarcopenia/genética , Pueblo Asiatico , Población Negra , Índice de Masa Corporal , Densidad Ósea , Femenino , Cuello Femoral/patología , Genoma Humano , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/etnología , Osteoporosis/metabolismo , Osteoporosis/patología , Polimorfismo de Nucleótido Simple , Sarcopenia/etnología , Sarcopenia/metabolismo , Sarcopenia/patología , Delgadez/genética , Delgadez/metabolismo , Población BlancaRESUMEN
Bone becomes more fragile with ageing. Among many structural changes, a thin layer of highly mineralized and brittle tissue covers part of the external surface of the thin femoral neck cortex in older people and has been proposed to increase hip fragility. However, there have been very limited reports on this hypermineralized tissue in the femoral neck, especially on its ultrastructure. Such information is critical to understanding both the mineralization process and its contributions to hip fracture. Here, we use multiple advanced techniques to characterize the ultrastructure of the hypermineralized tissue in the neck across various length scales. Synchrotron radiation micro-CT found larger but less densely distributed cellular lacunae in hypermineralized tissue than in lamellar bone. When examined under FIB-SEM, the hypermineralized tissue was mainly composed of mineral globules with sizes varying from submicron to a few microns. Nano-sized channels were present within the mineral globules and oriented with the surrounding organic matrix. Transmission electron microscopy showed the apatite inside globules were poorly crystalline, while those at the boundaries between the globules had well-defined lattice structure with crystallinity similar to the apatite mineral in lamellar bone. No preferred mineral orientation was observed both inside each globule and at the boundaries. Collectively, we conclude based on these new observations that the hypermineralized tissue is non-lamellar and has less organized mineral, which may contribute to the high brittleness of the tissue.
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Calcificación Fisiológica/fisiología , Cuello Femoral/metabolismo , Cuello Femoral/fisiología , Minerales/metabolismo , Anciano de 80 o más Años , Envejecimiento/metabolismo , Envejecimiento/fisiología , Densidad Ósea/fisiología , Femenino , Humanos , Sincrotrones , Microtomografía por Rayos X/métodosRESUMEN
BACKGROUND: Osteoporosis is a metabolic bone disease. Bisphosphonate (BP) and eldecalcitol (ELD) are two clinical first-line drugs for osteoporosis patients. However, the effect of ELD + BP vs. BP alone on osteoporosis treatment is still unclear. The present meta-analysis was conducted to evaluate the different therapeutic effect of BP + ELD vs. BP alone in osteoporosis treatment. METHODS: Eligible documents that selected from online databases including PubMed, Embase, and Cochrane Library were included in this study (updated to March 3, 2020). The quality assessment of the included studies was based on the guidelines of Cochrane. Meta-analysis was performed according to criteria such as intervention plan and outcome. The indicators including bone mineral density (BMD) in all enrolled studies were included in the current analysis. Pooled odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Then, heterogeneity analysis was performed based on Cochran's Q test and I2 statistics. RESULTS: A total of 4 studies (456 cases) with high quality were enrolled in this study. The effect of ELD + BP was superior to BP alone based on indicators including femoral neck BMD (FN-BMD) and total hip BMD (TH-BMD) in patients with followed up ≤ 6 months. Moreover, the effect of ELD + BP was superior to BP alone based on lumbar spine BMD (LS-BMD) in patients with 12 months followed up. CONCLUSION: Therapeutic effect of ELD + BP was superior to BP alone in osteoporotic patients based on the influence of BMD.
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Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Osteoporosis/tratamiento farmacológico , Vitamina D/análogos & derivados , Anciano , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/farmacología , Difosfonatos/farmacología , Quimioterapia Combinada , Femenino , Cuello Femoral/metabolismo , Estudios de Seguimiento , Humanos , Vértebras Lumbares/metabolismo , Masculino , Osteoporosis/metabolismo , Huesos Pélvicos/metabolismo , Factores de Tiempo , Resultado del Tratamiento , Vitamina D/administración & dosificación , Vitamina D/farmacologíaRESUMEN
Saliva was proposed as a diagnostic tool for systemic diseases. Here we determined the correlation of bone turnover markers in saliva, bone turnover markers in serum and bone mineral density in postmenopausal osteoporotic and healthy women. Forty postmenopausal osteoporotic and 40 age-matched healthy non-osteoporotic females were recruited for this case-control study. Serum and stimulated saliva levels of osteocalcin, N-terminal propeptide of type I collagen, bone-specific alkaline phosphatase and cross-linked-C-telopeptide of type I collagen were determined. Bone mineral density of the lumbar spine, proximal femur, and total hip were obtained. We show that osteocalcin and cross-linked-C-telopeptide of type I collagen (CTX) reached detectable levels in saliva while N-terminal propeptide of type I collagen and alkaline phosphatase were close or below the detection limit. Serum levels of bone turnover markers were significantly higher than saliva levels. Correlation analysis revealed a strong correlation of serum osteocalcin and, to a lesser extent, also serum CTX values with bone mineral density in lumbar spine, femoral neck, or total hip, respectively. There was, however, no significant correlation of bone mineral density with the respective bone turnover markers in saliva. There was a trend that saliva osteocalcin correlates with femoral neck (p = 0.16) or total hip (p = 0.06). There was also no association between serum and saliva bone turnover markers. This study reveals that saliva cannot replace the withdrawal of serum to evaluate bone metabolism.
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Densidad Ósea , Remodelación Ósea , Huesos/fisiología , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/metabolismo , Saliva/metabolismo , Anciano , Biomarcadores/metabolismo , Estudios de Casos y Controles , Colágeno Tipo I/metabolismo , Estudios Transversales , Femenino , Cuello Femoral/metabolismo , Humanos , Cinética , Vértebras Lumbares/metabolismo , Persona de Mediana Edad , Osteocalcina/sangre , Osteocalcina/metabolismo , Pacientes Ambulatorios , Péptidos/metabolismo , PronósticoRESUMEN
BACKGROUND: Osteoporosis is highly prevalent in postmenopausal women and may result in fractures and disabilities. Total thyroidectomy has also been associated with loss of bone mass. The aim of this cross-sectional study was to evaluate associations among nutritional status, skeletal muscle index and markers of bone turnover to bone mineral density in postmenopausal women who had undergone total thyroidectomy. METHODS: Fifty postmenopausal women who had undergone total thyroidectomy were included. Body composition was measured using dual-energy X-ray absorptiometry (DXA). The Geriatric Nutritional Risk Index (GNRI) was calculated using baseline body weight and serum albumin level. Skeletal muscle mass index was calculated as the appendicular skeletal muscle mass (ASM) divided by the height squared and assessed using DXA. RESULTS: Multivariate stepwise linear regression analysis showed that a low GNRI was significantly associated with low lumbar spine bone mineral density (BMD) and T-score, and that a low ASM/height2 was significantly associated with low femoral neck BMD and T-score. A low vitamin D level was significantly associated with low femoral neck BMD and T-score and low total hip BMD and T-score. A high bone alkaline phosphatase (ALP) level was significantly associated with low femoral neck T-score and low total hip BMD and T-score. A low insulin-like growth factor-1 (IGF-1) was significantly associated with low total hip BMD and T-score. CONCLUSION: In the postmenopausal women who had undergone total thyroidectomy in this study, BMD was positively associated with GNRI, skeletal muscle mass index, and levels of vitamin D and serum IGF-1, and inversely associated with bone ALP level. Nutritional status, skeletal muscle mass index and bone turnover biomarkers can be used to early identify patients with a high risk of osteoporosis in this high-risk group.
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Constitución Corporal , Densidad Ósea , Evaluación Geriátrica , Músculo Esquelético/metabolismo , Evaluación Nutricional , Fenómenos Fisiológicos de la Nutrición/fisiología , Estado Nutricional , Osteoporosis Posmenopáusica/etiología , Osteoporosis Posmenopáusica/metabolismo , Posmenopausia , Tiroidectomía/efectos adversos , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/fisiología , Composición Corporal , Estudios Transversales , Femenino , Cuello Femoral/metabolismo , Humanos , Vértebras Lumbares/metabolismo , Persona de Mediana Edad , Osteoporosis Posmenopáusica/prevención & control , RiesgoRESUMEN
OBJECTIVES: To investigate changes in bone mineral density (BMD) in patients with early rheumatoid arthritis (RA) over a 10-year period. METHODS: Consecutive patients with early RA (symptom duration <12 months) were followed according to a structured programme and examined with dual-energy X-ray absorptiometry (DXA) at inclusion and after 2, 5 and 10 years. Mean Z-scores over the study period were estimated using mixed linear effect models. Changes in Z-scores between follow-up visits were analysed using paired T-tests. RESULTS: At inclusion, 220 patients were examined with DXA. At the femoral neck, the mean Z-score over 10 years was -0.33 (95 % CI -0.57 to -0.08) in men and -0.07 (-0.22 to 0.08) in women. Men had significantly lower BMD at the femoral neck than expected by age at inclusion (intercept Z-score value -0.35; 95 % CI -0.61 to -0.09), whereas there was no such difference in women. At the lumbar spine, the mean Z-score over the study period for men was -0.05 (-0.29 to 0.19) and for women 0.06 (-0.10 to 0.21). In paired comparisons of BMD at different follow-up visits, femoral neck Z-scores for men decreased significantly from inclusion to the 5-year follow-up. After 5 years, no further reduction was seen. CONCLUSIONS: In this observational study of a limited sample, men with early RA had reduced femoral neck BMD at diagnosis, with a further significant but marginal decline during the first 5 years. Lumbar spine BMD Z-scores were not reduced in men or women with early RA. Data on 10-year follow-up were limited.
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Artritis Reumatoide/complicaciones , Densidad Ósea/fisiología , Enfermedades Óseas Metabólicas/etiología , Osteoporosis/etiología , Absorciometría de Fotón/métodos , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/metabolismo , Densidad Ósea/efectos de los fármacos , Enfermedades Óseas Metabólicas/diagnóstico , Femenino , Cuello Femoral/diagnóstico por imagen , Cuello Femoral/metabolismo , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/metabolismo , Masculino , Persona de Mediana Edad , Osteoporosis/inducido químicamente , Osteoporosis/metabolismo , Suecia/epidemiologíaRESUMEN
The objective of this study is to identify whether oxytocin (OT) contributes to the reduction of osteopenia in the femoral neck of rats in periestropause. Animals in irregular estrous cycles received two NaCl injections (0.15 mol/L) or OT (134 µg/kg) over a 12-h interval, and after thirty-five days without treatments, the biological sample collection was performed. The oxytocin group (Ot) demonstrated the highest enzymatic activity of alkaline phosphatase (p = 0.0138), lowest enzymatic activity of tartrate-resistant acid phosphatase (p = 0.0045), higher percentage of compact bone (p = 0.0359), cortical expression of runt-related transcription factor 2 (p = 0.0101), osterix (p = 0.0101), bone morphogenetic protein-2/4 (p = 0.0101) and periostin (p = 0.0455). Furthermore, the mineral-to-matrix ratio (ν1PO4/Proline) was higher and type-B carbonate substitution (CO3/ν1PO4) was lower (p = 0.0008 and 0.0303) in Ot group. The Ot showed higher areal bone mineral density (p = 0.0050), cortical bone area (p = 0.0416), polar moment of inertia, maximum, minimum (p = 0.0480, 0.0480, 0.0035), bone volume fraction (p = 0.0166), connectivity density (p < 0.0001), maximal load (p = 0.0003) and bone stiffness (p = 0.0145). In Ot percentage of cortical pores (p = 0.0102) and trabecular number (p = 0.0088) was lower. The results evidence action of OT in the reduction of osteopenia, suggesting that it is a promising anabolic strategy for the prevention of primary osteoporosis during the periestropause period.