共查询到20条相似文献,搜索用时 31 毫秒
1.
K. Kananen L. Volin K. Laitinen T. Ruutu M. J. Välimäki 《Osteoporosis international》2006,17(5):724-730
Purpose: Osteoporosis is a long-term complication of allogeneic stem cell transplantation (SCT). Receptor activator of nuclear factor-κB
ligand (RANKL) increases osteoclast activity, while osteoprotegerin (OPG) neutralizes RANKL. A deficiency of OPG or an excess
of RANKL may contribute to post-SCT bone loss. Methods: Serum OPG and soluble RANKL (sRANKL) concentrations were determined in 30 patients who received calcium, vitamin D and sex
steroids – with or without pamidronate – prior to SCT and 1, 3, 6, and 12 months post-SCT and compared to those in healthy
controls. Results: Despite all treatments patients lost bone at the hip. At baseline, serum OPG was similar in patients and controls; in the
two patient groups it increased by 26–27% at 6 months post-SCT (p=0.002–0.028) and over the control level (p=0.002). Serum sRANKL concentrations were also similar in patients and controls at baseline. In those patients receiving pamidronate
sRANKL concentrations decreased by 42% (p=0.0007) at 3 months post-SCT. The findings on the effect of SCT on OPG and sRANKL serum levels were ascertained in 28 additional
patients who did not receive pamidronate, at a median of 122 days after SCT. In this latter group, OPG but not sRANKL concentrations
were clearly elevated (p<0.001) in comparison to healthy controls. In conclusion, the present study fails to support the view that an excess of sRANKL
or a deficiency of OPG would have a substantial impact on bone loss in SCT-recipients. Conclusion: Serum sRANKL concentrations may be modulated by bisphosphonates. 相似文献
2.
Liu JM Zhao HY Ning G Zhao YJ Chen Y Zhang Zh Sun LH Xu MY Chen JL 《Calcified tissue international》2005,76(1):1-6
The correlations between the serum levels of OPG, RANKL with age, menopause, bone markers, and bone mineral densities (BMDs) at the lumbar spine and proximal femur were studied in 504 pre- and postmenopausal Chinese women aged 20–75 years. We found that age was positively and negatively correlated with serum concentrations of OPG (r = 0.442, P < 0.001) and RANKL (r = –0.263, P < 0.001), respectively. Compared with premenopausal women, postmenopausal women showed higher serum OPG levels (107.6 ± 3.0 vs 72.0 ± 1.8 pg/ml, P < 0.001), lower serum RANKL concentrations (4.7 ± 0.4 vs. 5.8 ± 0.3 pg/ml, P < 0.001) and RANKL/OPG ratios (0.045 ± 0. 004 vs. 0.099 ± 0.008, P < 0.001). Neither serum levels of OPG nor RANKL or RANKL/OPG ratio correlated with BMDs after adjustment of age and menopause. They also showed no differences among normal, osteopenic and osteoporotic postmenopausal women. Serum levels of OPG were positively correlated with urinary excretion of NTx (r = 0.1453, P = 0.006). Serum levels of RANKL (r = –0.1928, P < 0.001) and RANKL/OPG ratio (r = –0.1303, P = 0.013) were inversely correlated with serum concentrations of OC. In multiple regression analysis, up to 20% variance (R2 = 0.106–0.224) of the OPG-RANKL system in peripheral circulation can be explained by age, menopause and bone markers.These results suggest that although serum OPG and RANKL concentrations were unrelated with BMDs, the age– and menopause– dependent changes of serum OPG and RANKL might be a protective mechanism against the accelerated bone loss in postmenopausal women. 相似文献
3.
《BONE》2013,57(2):474-481
PurposeThe osteoprotogerin/receptor activator of NF-kappa β/receptor activator of NF-kappa β ligand (OPG/RANK/RANKL) pathway plays a critical role in bone remodeling. This study investigated associations between serum levels of OPG, soluble RANKL (sRANKL), and the ratio of OPG/sRANKL to risk of incident hip fracture.MethodsA nested case–control study was conducted among postmenopausal, Caucasian women aged 50–79 at baseline (1993–1998), followed for hip fracture through March 2005 in the Women's Health Initiative Observational Study. 400 incident hip fracture cases were selected and individually matched to 400 controls with no prior fracture or incident hip fracture. Matching factors were baseline age, enrollment date and hormone therapy (HT) exposure. Baseline serum OPG and sRANKL levels were measured using high sensitivity ELISA. Odds ratios were computed for quartiles of each biomarker adjusting for matching factors and hip fracture risk factors.ResultsSerum OPG was significantly associated with older age, low physical activity and poorer physical function in control women. sRANKL was inversely associated with total calcium intake in control women, but not associated with age or other fracture risk factors. The odds ratio for hip fracture comparing the highest to lowest quartiles of OPG was 2.28 (95% confidence interval (CI), 1.45–3.61) after adjusting for the matching variables (p-value for linear trend < 0.001), and 1.87 (95% CI, 1.15–3.04; p for linear trend = 0.02) after adjusting for self-rated health status, physical activity and physical functioning. No significant associations between sRANKL or the ratio of OPG/sRANKL and hip fracture risk were observed.ConclusionSerum OPG levels were independently associated with a nearly twofold increased risk of hip fracture in postmenopausal women. 相似文献
4.
Pedro Mezquita-Raya Magdalena de la Higuera Diego Fernández García Guillermo Alonso María Estrella Ruiz-Requena Juan de Dios Luna Fernando Escobar-Jiménez Manuel Muñoz-Torres 《Osteoporosis international》2005,16(11):1368-1374
Regulation of osteoclastic activity is critical for understanding bone loss associated with the postmenopausal period. In vitro and animal studies have revealed the role of OPG as a decoy receptor that neutralizes the effect of RANKL on the differentiation and activation of osteoclasts. However, the role of the OPG-RANKL system in postmenopausal osteoporosis is controversial. Thus, the aim of this study was to investigate the relationship among circulating levels of OPG, RANKL, bone turnover markers (BTM), bone mineral density (BMD) and vertebral fractures in postmenopausal women. We determined anthropometric parameters, circulating OPG and RANKL, BTM, estradiol, BMD by dual X-ray absorptiometry at the lumbar spine (LS) and femoral neck (FN), and pre-existing vertebral fractures in 206 ambulatory postmenopausal women of a mean age of 62 years (SD 7). Circulating OPG was significantly related to age ( r =0.158; P =0.023), years since menopause ( r =0.167; P =0.016) and BMD (LS Z-score: r =0.240; P =0.001, FN Z-score: r =0.156; P =0.025). Over half of the women had undetectable RANKL ( n =113; 54.9%). There were no significant differences in clinical variables, BTM or BMD among women with detectable vs. undetectable RANKL. OPG was found to be independently associated with osteoporosis (OR: 2.9, 1.4–5.9) and prevalent vertebral fractures (OR: 2.5, 1.2–5.4). We conclude that serum OPG levels are independently associated with bone mass and prevalent vertebral fractures in postmenopausal women. 相似文献
5.
Hassan Afzali Amir Hosein Jafari Kashi Mansooreh Momen‐Heravi Reza Razzaghi Elaheh Amirani Fereshteh Bahmani Hamid Reza Gilasi Zatollah Asemi 《Wound repair and regeneration》2019,27(3):277-284
This study was carried out to determine the effects of magnesium and vitamin E co‐supplementation on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). The current randomized, double‐blind, placebo‐controlled trial was conducted among 57 patients with grade 3 DFU. Participants were randomly divided into two groups to take either 250 mg magnesium oxide plus 400 IU vitamin E (n = 29) or placebo per day (n = 28) for 12 weeks. Compared with the placebo, taking magnesium plus vitamin E supplements reduced ulcer length (β [difference in the mean of outcomes measures between treatment groups] ?0.56 cm; 95% CI, ?0.92, ?0.20; p = 0.003), width (β ?0.35 cm; 95% CI, ?0.64, ?0.05; p = 0.02) and depth (β ?0.18 cm; 95% CI, ?0.33, ?0.02; p = 0.02). In addition, co‐supplementation led to a significant reduction in fasting plasma glucose (β ?13.41 mg/dL; 95% CI, ?20.96, ?5.86; p = 0.001), insulin (β ?1.45 μIU/ml; 95% CI, ?2.37, ?0.52; p = 0.003), insulin resistance (β ?0.60; 95% CI, ?0.99, ?0.20; p = 0.003) and HbA1c (β ?0.32%; 95% CI, ?0.48, ?0.16; p < 0.003), and a significant elevation in insulin sensitivity (β 0.007; 95% CI, 0.003, 0.01; p < 0.001) compared with the placebo. Additionally, compared with the placebo, taking magnesium plus vitamin E supplements decreased triglycerides (β ?10.08 mg/dL; 95% CI, ?19.70, ?0.46; p = 0.04), LDL‐cholesterol (β ?5.88 mg/dL; 95% CI, ?11.42, ?0.34; p = 0.03), high sensitivity C‐reactive protein (hs‐CRP) (β ?3.42 mg/L; 95% CI, ?4.44, ?2.41; p < 0.001) and malondialdehyde (MDA) (β ?0.30 μmol/L; 95% CI, ?0.45, ?0.15; p < 0.001), and increased HDL‐cholesterol (β 2.62 mg/dL; 95% CI, 0.60, 4.63; p = 0.01) and total antioxidant capacity (TAC) levels (β 53.61 mmol/L; 95% CI, 4.65, 102.57; p = 0.03). Overall, magnesium and vitamin E co‐supplementation for 12 weeks to patients with DFU had beneficial effects on ulcer size, glycemic control, triglycerides, LDL‐ and HDL‐cholesterol, hs‐CRP, TAC, and MDA levels. 相似文献
6.
H.-Y. Zhao J.-M. Liu G. Ning Y.-J. Zhao Y. Chen L.-H. Sun L.-Z. Zhang M.-Y. Xu J.-L. Chen 《Osteoporosis international》2008,19(2):221-226
Summary Serum IGF-I level was negatively correlated with OPG and OPG/RANKL ratio, but positively correlated with RANKL. Serum OPG
level in the highest quintile of IGF-I was significantly lower than that in the lowest. We conclude that the effect of IGF-I
on bone remodeling may be mediated by the OPG/RANKL system.
Introduction Insulin-like growth factor I (IGF-I) is an important factor in coupling bone remodeling, activating both formation and resorption.
Compared with the many studies on the role of IGF-I in bone formation, the information regarding its effects on bone resorption
is limited and conflicting. The balance of the two peptides produced by osteoblasts, osteoprotegerin (OPG) and receptor activator
of nuclear factor-κB ligand (RANKL), is critical for the bone resorption process. Our study was designed to analyze the relationships
of serum concentrations of IGF-I with OPG, RANKL, OPG/RANKL ratio as well as BMDs in healthy Chinese women.
Methods BMDs at lumbar spine and proximal femur in 504 pre- and postmenopausal women were measured by DXA. Serum levels of IGF-I,
OPG and RANKL were also measured. Pearson’s correlation and partial correlation analysis, ANOVA, covariance analysis and stepwise
multiple regression analysis were used as appropriate.
Results Age was negatively correlated with serum levels of IGF-I (r = −0.702, p < 0.001). IGF-I was negatively correlated with OPG and OPG/RANKL ratio, but positively correlated with RANKL. The relationship
between IGF-I and BMDs disappeared after adjustment for age. In postmenopausal women, IGF-I was lower in women with osteoporosis
than in those with normal BMD (p = 0.056), but no differences were found among OPG, RANKL and OPG/RANKL ratio. Serum levels of OPG in the highest quintile
of IGF-I were significantly lower than those in the lowest quintile of IGF-I, while no difference was found in RANKL. In the
multiple regression analysis model, serum levels of IGF-I were the main determinants of the bone mass in Chinese women.
Conclusions In conclusion, the relationship between decreasing IGF-I and BMDs in healthy Chinese women influenced by age, whereas the
effect of IGF-I on bone remodeling (bone resorption) may be mediated by the OPG/RANKL system. 相似文献
7.
H. Dobnig L. C. Hofbauer V. Viereck B. Obermayer-Pietsch A. Fahrleitner-Pammer 《Osteoporosis international》2006,17(5):693-703
Introduction Since the soluble receptor activator of the NF-κB ligand (sRANKL) as well as the endogenous anti-resorptive cytokine osteoprotegerin
(OPG) are produced by osteoblasts and given that these cells undergo significant changes during antiresorptive treatment,
we hypothesized that treatment with bisphosphonates (BP) would be accompanied by changes in serum OPG and sRANKL levels.
Methods In a prospective, randomized controlled trial of previously untreated postmenopausal women with osteoporosis, oral BP therapy
(daily doses of either 10 mg alendronate or 5 mg risedronate) in combination with calcium/vitamin D was compared to calcium/vitamin D
treatment alone (control group). Follow-up at 2, 6 and 12 months was completed for 56 patients. Standardized spinal X-rays
were performed at baseline, and DEXA measurements at the femoral neck and trochanter were made at baseline and after 1 year.
Serum OPG and sRANKL levels were measured with a polyclonal antibody-based ELISA system.
Results After 1 year, there was a non-significant loss in neck and trochanteric bone mineral density (BMD) in the CTR group and a
mean increase of 3.3% and 4.6% in the combined BP group (both p<0.0001), respectively. Serum levels of C-terminal telopeptides of type I collagen (sCTX) and osteocalcin decreased by 12%
and 10% at 12 months in the CTR group and by 43% and 23% in the combined BP group, respectively (all significant). OPG serum
levels in the CTR group decreased significantly by 9% at 2 months (p<0.005) and remained below pre-treatment levels at later time points. Both the alendronate- and risedronate-treated patient
groups showed unaltered OPG levels after 2 months, but they had significantly increased serum levels at 6 and 12 months. Levels
of sRANKL were unchanged throughout the treatment period. Univariate regression analysis demonstrated that changes in serum
OPG levels after 12 months of BP treatment were positively and better correlated to BMD changes (trochanter: r= 0.59, p<0.0001; neck: r= 0.50, p<0.001) than those of sCTX, which showed the expected negative correlation to BMD change (trochanter: r= –0.35, p=0.03; neck: r= –0.23, p=0.16). With multiple regression analyses at 12 months, R2 values for 1-year changes in trochanteric BMD of 0.33 (OPG alone) and 0.23 (sCTX alone) were significantly improved to the
0.57 when OPG and sCTX changes were combined (p<0.001). Results for the femoral neck were also statistically significant R2=0.35, p<0.001). BMD and OPG changes in the CTR group were not correlated with each other.
Conclusions We conclude that with BP treatment, changes in serum OPG levels, unlike changes in sCTX levels, are positively correlated to changes in BMD response. The BP-related changes in serum OPG levels during treatment could result from effects
on osteoclastogenesis and osteoclast apoptosis as well as from a direct stimulatory effect on osteoblastic OPG production.
These changes in OPG levels may be used to predict the individual response of patients to BP treatment. 相似文献
8.
Julia Köttstorfer Anita Thomas Markus Gregori Mathias Kecht Georg Kaiser Stefan Eipeldauer Kambiz Sarahrudi 《Journal of orthopaedic research》2014,32(12):1557-1561
Human fracture healing is a complex interaction of several cytokines that regulate osteoblast and osteoclast activity. By monitoring OPG (osteoprotegerin) and sRANKL we aimed to possibly predict normal or impaired fracture healing. In 64 patients with a fracture of a long bone serum level of sRANKL and OPG were evaluated with respect to bony union (n = 57) or pseudarthrosis (n = 7). Measurements were carried out at admission and at 1, 2, 4, 6, 8, 12, 24, and 48 weeks after the injury. Patients' serum levels were compared to 33 healthy controls. Fracture hematoma contained significantly higher sRANKL and OPG concentrations compared to patients serum (p = 0.005, p = 0.028). OPG level in fracture hematoma was higher compared to the unions serum level (p = 0.028). sRANKL was decreased in unions during the observation period. In non‐unions sRANKL and OPG levels showed a variable course, with no statistical significance. This is the first study to document the course of OPG and sRANKL in normal and delayed human fracture healing emphasizing its local and systemic involvement. We provide evidence of strongly enhanced OPG levels in patients with a long bone fracture compared to healthy controls. Further, levels of free sRANKL were decreased during regular fracture repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1557–1561, 2014. 相似文献
9.
Alice Chin Yanqi Yang Lei Chai Ricky W. K. Wong Abou‐Bakr M. Rabie 《Journal of orthopaedic research》2011,29(7):1059-1063
Sufficient osteoinduction is essential for the success and effectiveness of bone grafting. It was previously found that Salvia Miltiorrhiza (SM), a commonly used Chinese herb increased osteogenesis in vivo. The aim of this study is to investigate the effects of SM on bone cells in vitro, in an attempt to get a better understanding on how SM can promote bone remodeling. MC3T3‐E1, an osteoblastic cell line, was cultured with SM for different time intervals (24, 48, and 72 h), whereas the control group consisted of cells cultured without any intervention. The mRNA expression of alkaline phosphatase (ALP), osteocalcin (OCN), osteoprotegerin (OPG), and the receptor activator of nuclear factor kappa B ligand (RANKL) were examined by real‐time polymerase chain reaction (qPCR). The expression of ALP showed an early increase at 24 h by 50% (p < 0.001) and at 48 h by 13% (p < 0.001). OCN was decreased by 22% at 24 h (p < 0.001) but increased by 50% and 88% at 48 and 72 h, respectively (p < 0.001). RANKL showed an early increase at the first two time points of 24 and 48 h by 45% (p < 0.001) and 36% (p < 0.01), respectively, while OPG was up‐regulated at the latter two time points by 10% at 48 h (p < 0.01) and 68% at 72 h (p < 0.001). Thus, OPG/RANKL was down‐regulated first, and then up‐regulated. SM enhances bone remodeling by regulating the gene expression of ALP, OCN, OPG, and RANKL. It is a potential medicinal herb to be utilized in the application that requires stimulation in bone cell activities. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1059–1063, 2011 相似文献
10.
Ostrowska Z Ziora K Oświęcimska J Swiętochowska E Szapska B Wołkowska-Pokrywa K Dyduch A 《BONE》2012,50(1):156-160
Minimal data exist concerning the relationship between osteokines of the RANKL/RANK/OPG system, especially RANKL, and bone status in females with anorexia nervosa (AN). For this reason we investigated the relationship between bone metabolism (as assessed based on serum levels of OC and CTx), and OPG and sRANKL concentrations in females with AN. Ninety-one female patients with AN and 29 healthy female subjects aged 13 to 18 years of age participated in the study. Serum OC, CTx, OPG and sRANKL were measured by ELISA. The female patients with AN demonstrated an essential suppression of OC and CTx, increased OPG and sRANKL levels, and a reduced OPG/sRANKL ratio. OC, CTx and the OPG/sRANKL ratio correlated positively with body mass and BMI in these patients, whereas in the case of OPG and sRANKL the relationship was negative. A significant positive correlation was observed between OPG and sRANKL and also between bone markers and the OPG/sRANKL ratio, and negative between CTx and sRANKL. In female patients with AN, the OPG/RANKL ratio was a significant and independent predictor of osteocalcin, a bone formation marker — OC (R2 = 0.065, p = 0.012) whereas the OPG/sRANKL ratio and BMI were significant and independent predictors of a bone resorption marker — CTx (R2 = 0.095; p = 0.012). In conclusion, the body mass, BMI values, and bone markers suppression observed in female patients with AN might be associated with an increase in OPG and sRANKL levels and a significant decrease of the OPG/sRANKL ratio. Although higher OPG levels may compensate for excessive bone resorption in female patients with AN, the lower OPG/sRANKL ratio seems to indicate that some inadequacies exist regarding this compensation effect, which might contribute to low bone density in these patients. The OPG/sRANKL ratio might prove a more relevant marker to predict bone metabolism in female patients with AN than sRANKL and/or OPG alone. 相似文献
11.
Anna Wasilewska Agnieszka Rybi-Szuminska Walentyna Zoch-Zwierz 《Pediatric nephrology (Berlin, Germany)》2010,25(10):2067-2075
Receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) play key roles in the pathogenesis of glucocorticoid-induced
osteoporosis (GIO). The aim of our study was to determine whether the cumulative glucocorticoid dose (CGCS) in children with
idiopathic nephrotic syndrome (INS) has any effect on the concentration of serum RANKL and OPG and the RANKL/OPG ratio. The
study population consisted of 90 children with INS, aged 3–20 years, who were treated with GCS. These children were divided
into two groups according to the CGCS: low (L) <1 g/kg body weight (BW) and high (H) ≥1 g/kg BW, respectively. The control
group (C) consisted of 70 healthy children. RANKL concentration was observed to be significantly higher and OPG significantly
lower in INS children than in the reference group: 0.21 (range 0.01–1.36) versus 0.15 (0–1.42) pmol/l (p < 0.05), respectively, and 3.76 (1.01–7.25) versus 3.92 (2.39–10.23) pmol/l (p < 0.05), respectively. The RANKL/OPG ratio was significantly higher in INS children (p < 0.01). The concentration of RANKL, similar to the RANKL/OPG ratio, was significantly higher in Group H children than in
Group L children: 0.46 (0.02–1.36 ) versus 0.19 (0.01–1.25) (p < 0.01) and 0.14 (0.01–0.71) versus 0.05 (0.002–0.37) (p < 0.01), respectively. The concentration of OPG was similar in both groups. There was a positive correlation between CGCS
and the concentration of sRANKL as well as the RANKL/OPG ratio (in both cases r = 0.33, p < 0.05). Based on these results, we suggest that long-term exposure to GCS results in a dose-dependent increase in serum
RANKL concentration and the RANKL/OPG ratio, but not in the level of serum OPG. 相似文献
12.
Franklin Joseph MBBS MRCP Aftab M Ahmad Mazhar Ul‐Haq Brian H Durham Pauline Whittingham William D Fraser Jiten P Vora 《Journal of bone and mineral research》2008,23(5):721-729
Introduction : Growth hormone (GH) replacement improves target organ sensitivity to PTH, PTH circadian rhythm, calcium and phosphate metabolism, bone turnover, and BMD in adult GH‐deficient (AGHD) patients. In postmenopausal women with established osteoporosis, GH and insulin like growth factor‐1 (IGF‐1) concentrations are low, and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear. We studied the effects of GH administration on PTH sensitivity, PTH circadian rhythm, and bone mineral metabolism in postmenopausal women with established osteoporosis. Materials and Methods : Fourteen postmenopausal women with osteoporosis were compared with 14 healthy premenopausal controls at baseline that then received GH for a period of 12 mo. Patients were hospitalized for 24 h before and 1, 3, 6, and 12 mo after GH administration and half‐hourly blood and 3‐h urine samples were collected. PTH, calcium (Ca), phosphate (PO4), nephrogenous cyclic AMP (NcAMP), β C‐telopeptide of type 1 collagen (βCTX), procollagen type I amino‐terminal propeptide (PINP), and 1,25‐dihydroxyvitamin D [1,25(OH)2D] were measured. Circadian rhythm analysis was performed using Chronolab 3.0 and Student's t‐test and general linear model ANOVAs for repeated measures were used where appropriate. Results : IGF‐1 concentration was significantly lower in the women with established osteoporosis compared with controls (101.5 ± 8.9 versus 140.9 ± 10.8 μg/liter; p < 0.05) and increased significantly after 1, 3, 6, and 12 mo of GH administration (p < 0.001). Twenty‐four‐hour mean PTH concentration was higher in the osteoporotic women (5.4 ± 0.1 pM) than in healthy controls (4.4 ± 0.1 pM, p < 0.001) and decreased after 1 (5.2 ± 0.1 pM, p < 0.001), 3 (5.0 ± 0.1 pM, p < 0.001), 6 (4.7 ± 0.1 pM, p < 0.001), and 12 mo (4.9 ± 0.1 pM, p < 0.05) of GH administration compared with baseline. NcAMP was significantly lower in osteoporotic women (17.2 ± 1.2 nM glomerular filtration rate [GFR]) compared with controls (21.4 ± 1.4 nM GFR, p < 0.05) and increased after 1 (24.2 ± 2.5 nM GFR, p < 0.05), 3 (27.3 ± 1.5 nM GFR, p < 0.001), and 6 mo (32.4 ± 2.5 nM GFR, p < 0.001) compared with baseline. PTH secretion was characterized by two peaks in premenopausal women and was altered in postmenopausal women with a sustained increase in PTH concentration. GH administration also restored a normal PTH secretory pattern in the osteoporotic women. The 24‐h mean adjusted serum calcium (ACa) concentration increased at 1 and 3 mo (p < 0.001) and PO4 at 1, 3, 6, and 12 mo (p < 0.001). 1,25(OH)2D concentration increased after 3, 6, and 12 mo of GH (p < 0.05). An increase in urine Ca excretion was observed at 3 and 6 mo (p < 0.05), and the renal threshold for maximum tubular phosphate reabsorption rate (TmPO4/GFR) increased after 1, 3, 6, and 12 mo (p < 0.05). βCTX concentration increased progressively from 0.74 ± 0.07 μg/liter at baseline to 0.83 ± 0.07 μg/liter (p < 0.05) at 1 mo and 1.07 ± 0.09 μg/liter (p < 0.01) at 3 mo, with no further increase at 6 or 12 mo. PINP concentration increased progressively from baseline (60 ± 5 μg/liter) to 6 mo (126 ± 11 μg/liter, p < 0.001), with no further increase at 12 mo. The percentage increase in PINP concentration was significantly higher than βCTX (p < 0.05). Conclusions : Our study shows that GH has a regulatory role in bone mineral metabolism. GH administration to postmenopausal osteoporotic women improves target organ sensitivity to PTH and bone mineral metabolism and alters PTH secretory pattern with greater increases in bone formation than resorption. These changes, resulting in a net positive bone balance, may partly explain the mechanism causing the increase in BMD after long‐term administration of GH in postmenopausal women with osteoporosis shown in previous studies and proposes a further component in the development of age‐related postmenopausal osteoporosis. 相似文献
13.
Serum osteoprotegerin, RANKL and fibroblast growth factor-23 in children with chronic kidney disease
Siomou E Challa A Printza N Giapros V Petropoulou F Mitsioni A Papachristou F Stefanidis CJ 《Pediatric nephrology (Berlin, Germany)》2011,26(7):1105-1114
Osteoprotegerin (OPG), receptor activator of the nuclear factor κB ligand (RANKL) and fibroblast growth factor-23 (FGF-23)
play a central role in renal osteodystrophy. We evaluated OPG/RANKL and FGF-23 levels in 51 children with chronic kidney disease
(CKD) [n = 26 stage 3 or 4 (CKD3–4) and n = 25 stage 5 (CKD5)] and 61 controls. Any possible association with intact parathyroid hormone (iPTH) and bone turnover markers
was also investigated. The OPG levels were lower in the CKD3–4 group (p < 0.001) and higher in the CKD5 group (p < 0.01) than in the controls, while RANKL levels did not differ. The FGF-23 levels were higher in both patient groups (p < 0.0001), while the levels of phosphate and iPTH were higher only in the CKD5 group (p < 0.0001). There were independent positive correlations between OPG and RANKL (β = 0.297, p < 0.01) and FGF-23 (β = 0.352, p < 0.05) and a negative correlation with the bone resorption marker TRAP5b (β = −0.519, p < 0.001). OPG was positively correlated with iPTH (R = 0.391, p < 0.01). An independent positive correlation between FGF-23 and phosphate (β = 0.368, p < 0.05) or iPTH (β = 0.812, p < 0.0001) was noted. In conclusion, we found that higher OPG levels in patients with CKD stage 5 correlated with the levels
of RANKL, FGF-23, iPTH, and TRAP5b. These findings may reflect a compensatory mechanism to the negative balance of bone turnover.
High FGF-23 levels in early CKD stages may indicate the need for intervention to manage serum phosphate (Pi) levels. 相似文献
14.
Correlates of Osteoprotegerin Levels in Women and Men 总被引:18,自引:0,他引:18
S. Khosla H. M. Arrighi L. J. Melton III E. J. Atkinson W. M. O’Fallon C. Dunstan B. L. Riggs 《Osteoporosis international》2002,13(5):394-399
Osteoprotegerin (OPG) is a potent antiresorptive molecule that binds the final effector for osteoclastogenesis, receptor
activator of NF-kB ligand (RANK-L). OPG production is regulated by a number of cytokines and hormones, including sex steroids,
but there are few data on age and gender effects on circulating serum OPG levels, as well as possible relationships between
OPG levels and bone turnover markers or bone mineral density (BMD). Thus, we measured serum OPG levels in an age-stratified,
random sample of men (n= 346 age range, 23–90 years) and women (n= 304; age range 21–93 years) and related them to sex steroid levels, bone turnover markers and BMD. Serum OPG levels increased
with age in both men (R= 0.39, p<0.001) and women (R= 0.18, p<0.01). Premenopausal women had higher OPG levels than men under age 50 years (171 ± 6 pg/ml vs 134 ± 6 pg/ml, respectively,
p<0.001), whereas serum OPG levels were no different in postmenopausal women compared with men = 50 years (195 ± 7 pg/ml vs
188 ± 7 pg/ml, respectively, p= 0.179). OPG levels correlated inversely with serum bioavailable testosterone levels in men = 50 years (R=–0.27, p<0.001), but no associations were present with either estrogen or testosterone levels in the women. In the men, there was
a trend for OPG levels to be associated positively with bone resorption markers and inversely with BMD. Collectively, the
gender difference in OPG levels suggests that sex steroids may regulate OPG production in vivo, as has been found in vitro.
Moreover, OPG production may also rise with increases in bone turnover, probably as a homeostatic mechanism to limit bone
loss. Further studies directly testing these hypotheses should provide additional insights into the potential role of OPG
in bone loss related to aging and sex steroid deficiency.
Received: 14 August 2001 / Accepted: 20 November 2001 相似文献
15.
Morena M Terrier N Jaussent I Leray-Moragues H Chalabi L Rivory JP Maurice F Delcourt C Cristol JP Canaud B Dupuy AM 《Journal of the American Society of Nephrology : JASN》2006,17(1):262-270
Expression of bone proteins resulting from transdifferentiation of vascular smooth muscle cells into osteoblasts suggests that vascular calcifications are a bioactive process. Regulating molecules such as osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) could play a key role in bone-vascular calcification imbalance. This study investigated the contribution of these proteins as well as mineral metabolism disorders in hemodialysis (HD) patient outcome. A total of 185 HD patients were followed up prospectively for 2 yr. In addition to clinical characteristics, mineral metabolism markers as well as OPG and soluble RANKL (sRANKL) were measured at baseline. After 2 yr, survival rates were described with Kaplan-Meier and compared with Cox regression analyses; 50 patients died (27 from cardiovascular diseases). Calcium, phosphate, and calcium x phosphate product were not associated with mortality. Both hyperparathyroidism (parathyroid hormone > or =300 pg/ml) and hypoparathyroidism (parathyroid hormone <150 pg/ml) were poorly associated with all-cause and cardiovascular mortality. By contrast, elevated OPG levels predicted all-cause (relative risk [RR] 2.67; 95% confidence interval [CI] 1.32 to 5.41; P = 0.006) and cardiovascular mortality (RR 3.15; 95% CI 1.14 to 8.69; P = 0.03). Low levels of sRANKL were associated with a protective effect for all-cause mortality (RR 0.45; 95% CI 0.21 to 0.94; P = 0.03). The association of OPG with all-cause mortality was stronger in patients with C-reactive protein > or =12.52 mg/L. In this condition, both highest (RR 5.68; 95% CI 1.48 to 22.73; P = 0.01) and lowest tertiles (RR 5.37; 95% CI 147 to 1968; P = 0.01) significantly predicted poor outcome. These results show that regulating-bone molecules, especially OPG, are strong predictors of mortality in HD patients, suggesting that OPG is a vascular risk factor, in particular in patients who have high C-reactive protein levels. OPG determination therefore should be added to the biologic follow-up of these patients. 相似文献
16.
Laura van Dussen Jurgen H Runge Michael W Tanck Erik Endert Annemieke C Heijboer Eric Fliers Carla E Hollak Erik M Akkerman Peter H Bisschop 《Journal of bone and mineral research》2015,30(11):2058-2066
Bone marrow fat, an unique component of the bone marrow cavity increases with aging and menopause and is inversely related to bone mass. Sex steroids may be involved in the regulation of bone marrow fat, because men have higher bone marrow fat than women and clinical observations have suggested that the variation in bone marrow fat fraction is greater in premenopausal compared to postmenopausal women and men. We hypothesized that the menstrual cycle and/or estrogen affects the bone marrow fat fraction. First, we measured vertebral bone marrow fat fraction with Dixon Quantitative Chemical Shift MRI (QCSI) twice a week during 1 month in 10 regularly ovulating women. The vertebral bone marrow fat fraction increased 0.02 (95% CI, 0.00 to 0.03) during the follicular phase (p = 0.033), and showed a nonsignificant decrease of 0.02 (95% CI, –0.01 to 0.04) during the luteal phase (p = 0.091). To determine the effect of estrogen on bone marrow fat, we measured vertebral bone marrow fat fraction every week for 6 consecutive weeks in 6 postmenopausal women before, during, and after 2 weeks of oral 17‐β estradiol treatment (2 mg/day). Bone marrow fat fraction decreased by 0.05 (95% CI, 0.01 to 0.09) from 0.48 (95% CI, 0.42 to 0.53) to 0.43 (95% CI, 0.34 to 0.51) during 17‐β estradiol administration (p < 0.001) and increased again after cessation. During 17‐β estradiol administration the bone formation marker procollagen type I N propeptide (P1NP) increased (p = 0.034) and the bone resorption marker C‐terminal crosslinking telopeptides of collagen type I (CTx) decreased (p < 0.001). In conclusion, we described the variation in vertebral bone marrow fat fraction among ovulating premenopausal women. And among postmenopausal women, we demonstrated that 17‐β estradiol rapidly reduces the marrow fat fraction, suggesting that 17‐β estradiol regulates bone marrow fat independent of bone mass. © 2015 American Society for Bone and Mineral Research. 相似文献
17.
Bone Mineral Density Increases in Trans Persons After 1 Year of Hormonal Treatment: A Multicenter Prospective Observational Study
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Chantal M Wiepjes Mariska C Vlot Maartje Klaver Nienke M Nota Christel JM de Blok Renate T de Jongh Paul Lips Annemieke C Heijboer Alessandra D Fisher Thomas Schreiner Guy T'Sjoen Martin den Heijer 《Journal of bone and mineral research》2017,32(6):1252-1260
Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross‐sex hormonal treatment (CHT) in transgender persons can affect bone mineral density (BMD). The aim of this study was to investigate in a prospective observational multicenter study the first‐year effects of CHT on BMD in transgender persons. A total of 231 transwomen and 199 transmen were included who completed the first year of CHT. Transwomen were treated with cyproterone acetate and oral or transdermal estradiol; transmen received transdermal or intramuscular testosterone. A dual‐energy X‐ray absorptiometry (DXA) was performed to measure lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD before and after 1 year of CHT. In transwomen, an increase in LS (+3.67%, 95% confidence interval [CI] 3.20 to 4.13%, p < 0.001), TH (+0.97%, 95% CI 0.62 to 1.31%, p < 0.001), and FN (+1.86%, 95% CI 1.41 to 2.31%, p < 0.001) BMD was found. In transmen, TH BMD increased after 1 year of CHT (+1.04%, 95% CI 0.64 to 1.44%, p < 0.001). No changes were observed in FN BMD (–0.46%, 95% CI –1.07 to 0.16%, p = 0.144). The increase in LS BMD was larger in transmen aged ≥50 years (+4.32%, 95% CI 2.28 to 6.36%, p = 0.001) compared with transmen aged <50 years (+0.68%, 95% CI 0.19 to 1.17%, p = 0.007). In conclusion, BMD increased in transgender persons after 1 year of CHT. In transmen of postmenopausal age, the LS BMD increased more than in younger transmen, which may lead to the hypothesis that the increase in BMD in transmen is the result of the aromatization of testosterone to estradiol. © 2017 American Society for Bone and Mineral Research. 相似文献
18.
Jacques P Brown Richard L Prince Chad Deal Robert R Recker Douglas P Kiel Luiz H de Gregorio Peyman Hadji Lorenz C Hofbauer Jose M Álvaro‐Gracia Huei Wang Matthew Austin Rachel B Wagman Richard Newmark Cesar Libanati Javier San Martin Henry G Bone 《Journal of bone and mineral research》2009,24(1):153-161
Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, double‐blind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty‐nine postmenopausal women with a T‐score ≤ ?2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one‐third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p < 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12‐mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one‐third radius; p ≤ 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab‐ and alendronate‐treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments. 相似文献
19.
Low magnitude high frequency vibration (LMHFV) has been shown to improve anabolic and osteogenic responses in osteoporotic intact bones and during osteoporotic fracture healing; however, the molecular response of LMHFV during osteoporotic fracture healing has not been investigated. It was hypothesized that LMHFV could enhance osteoporotic fracture healing by regulating the expression of genes related to chondrogenesis (Col‐2), osteogenesis (Col‐1) and remodeling (receptor activator for nuclear factor‐ κ B ligand (RANKL) and osteoproteger (OPG)). In this study, the effects of LMHFV on both osteoporotic and normal bone fracture healing were assessed by endpoint gene expressions, weekly radiographs, and histomorphometry at weeks 2, 4 and 8 post‐treatment. LMHFV enhanced osteoporotic fracture healing by up‐regulating the expression of chondrogenesis‐, osteogenesis‐ and remodeling‐related genes (Col‐2 at week 4 (p = 0.008), Col‐1 at week 2 and 8 (p < 0.001and p = 0.008) and RANKL/OPG at week 8 (p = 0.045)). Osteoporotic bone had a higher response to LMHFV than normal bone and showed significantly better results as reflected by increased expression of Col‐2 and Col‐1 at week 2 (p < 0.001 for all), larger callus width at week 2 (p = 0.001), callus area at week 1 and 5(p < 0.05 for all) and greater relative area of osseous tissue (p = 0.002) at week 8. This study helps to understand how LMHFV regulates gene expression of callus formation, mineralization and remodeling during osteoporotic fracture healing. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1572–1579, 2014. 相似文献
20.
L. Jørgensen A. Vik N. Emaus J. Brox J.-B. Hansen E. Mathiesen P. Vestergaard 《Osteoporosis international》2010,21(6):931-938