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1.
Eslami B Zhou S Van Eekeren I LeBoff MS Glowacki J 《Calcified tissue international》2011,88(4):272-280
Alendronate (AL) is commonly used for the prevention and treatment of osteoporotic fractures. Little is known about the effects
of AL administration on osteoclast differentiation from human marrow progenitor cells. We used marrow discarded during orthopedic
surgery to test the hypothesis that cultures of bone marrow-derived stem cells (BMCs) from subjects receiving AL (+AL) may
differ from control subjects with respect to in vitro osteoclast differentiation and regulatory factors. The number of osteoclasts
generated in BMC cultures from control subjects was 4.7-fold greater than that from +AL subjects (P = 0.015). RANKL expression in +AL BMCs was 57% of that in controls (P = 0.001), and OPG expression in +AL BMCs was greater than in controls (153%, P = 0.01). The mean RANKL/OPG ratio in BMCs was 0.65 ± 0.35 for +AL specimens and 1.28 ± 0.53 for controls (P = 0.031). In addition, we assessed the direct effect of AL on expression of RANKL and OPG in marrow stromal cells isolated
from nine control women. Treatment with AL downregulated RANKL expression and upregulated OPG expression, with an average
50% decrease in RANKL/OPG ratio at 10−7 M (P = 0.004). These results show that osteoclast differentiation is dysregulated in marrow isolated from +AL subjects. Furthermore,
AL may inhibit human osteoclastogenesis by affecting the key regulatory genes in marrow cells. 相似文献
2.
Bergström I Parini P Gustafsson SA Andersson G Brinck J 《Journal of bone and mineral metabolism》2012,30(2):202-207
The purpose of this study was to explore whether mechanical loading by exercise over a 1–year period in postmenopausal women
had an effect on the receptor activator for nuclear factor kappa B ligand/osteoprotegerin (RANKL/OPG) system or the levels
of the Wnt-signaling antagonist sclerostin. A total of 112 postmenopausal were randomized to either sedentary life (controls)
or physical activity (training group). Ninety-two women fulfilled the study protocol. The training program consisted of three
fast 30-min walks and one or two 1-h aerobic training sessions per week. The effect on the bone mineral density of the hip
assessed with dual X-ray absorptiometry was positive as reported earlier. Blood samples were taken from participants at baseline
and after 1 year and serum levels of OPG, RANKL and sclerostin were quantified together with the bone metabolism markers C-terminal
telopeptide of collagen type I (CTX) and bone-specific alkaline phosphatase (BALP). The results were analyzed using an analysis
of covariance model using baseline values as the covariate. The training group displayed a clear mean increase of OPG +7.55 pg/ml
compared to controls (p = 0.007). The mean changes for RANKL +0.19 pg/ml (square-root transformed data) and sclerostin +0.62 pmol/l were non-significant
(p = 0.13 and p = 0.34). The changes in bone turnover markers CTX and BALP showed a tendency to decrease in the training group versus controls
but the changes were small and non-significant. Although our study is limited in number of participating women, we have been
able to show an OPG-associated, and RANKL- and sclerostin-independent, training-induced inhibition of postmenopausal bone
loss. 相似文献
3.
Lee JS Ryu CH Moon NH Kim SJ Park SY Suh KT 《Archives of orthopaedic and trauma surgery》2009,129(5):711-718
Introduction Several reports indicated that interleukin-6 (IL-6) and tumor necrosis factor α (TNF- α) play important regulatory roles in
bone remodeling and homeostasis. In addition, receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG)
have been shown to be important regulators of osteoclastogenesis during bone remodeling, and their expressions were examined
during fracture healing in a mouse model of tibial fracture. However, studies linking RANKL, OPG, IL-6 and TNF-α in patients
with head injury and fracture are lacking.
Patients and methods Within the first few hours of admission to hospital and at 4, 8, and 12 weeks after the injury, we evaluated changes in serum
levels of RANKL, OPG, IL-6 and TNF-α in 24 male patients with a concomitant head injury and fracture and in 26 male patients
with fracture only. These levels were compared with those found in 36 healthy controls.
Results The RANKL/OPG ratios were found to significantly lower in patients with a concomitant head injury and fracture than in the
controls immediately after admission and at 4, 8, and 12 weeks after the injury. In addition, RANKL/OPG ratios were significantly
lower in patients with a concomitant head injury and fracture than in those with fracture at 8 and 12 weeks after the injury.
The serum IL-6 levels were significantly higher in patients with a concomitant head injury and fracture than in the controls
upon admission, and at 4, 8, and 12 weeks after the injury. Moreover, the serum IL-6 levels were significantly higher in patients
with a head injury and fracture than in those with just a fracture at 4, 8, and 12 weeks after the injury.
Conclusions Based on these changes in the profiles of RANKL, OPG, and IL-6 and the RANKL/OPG ratio, altered repair of a fracture can occur
in patients with a concomitant head injury and fracture.
J. S. Lee and C. H. Ryu contributed equally to this study. 相似文献
4.
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
5.
Núria Guañabens Anna Enjuanes Luisa Alvarez Pilar Peris Llorenç Caballería M. Jesús Martínez de Osaba Dacia Cerdá Anna Monegal Francesca Pons Albert Parés 《Journal of bone and mineral metabolism》2009,27(3):347-354
The influence of osteoprotegerin and RANKL as regulators of osteoclastogenesis and bone remodeling in liver disease and in
the development of osteoporosis in primary biliary cirrhosis (PBC) is uncertain. Therefore, 68 women with PBC and 20 healthy
females were studied by assessing circulating osteoprotegerin and RANKL. Bone mineral density and markers of bone turnover
were measured as well. Osteoprotegerin-mRNA expression was also assessed in liver tissue from 16 patients and 5 controls.
Osteoprotegerin was higher in PBC than in controls (5.4 ± 0.2 vs. 2.9 ± 0.2 pM/l, P < 0.0001), whilst RANKL was lower in patients than in controls (0.39 ± 0.06 vs. 1.40 ± 0.16 pM/l, P < 0.0001). Osteoprotegerin was more elevated in patients with more advanced disease, as defined by bilirubin above 1.2 mg/dl
(6.6 ± 0.6 vs. 5.2 ± 0.2 pM/l, P = 0.02) or by Mayo over 4 (5.9 ± 0.3 vs. 4.8 ± 0.2 pM/l, P = 0.02). Osteoprotegerin and RANKL were unrelated with osteoporosis, and no associations were found with markers of bone
remodeling, except for RANKL, which was particularly decreased in patients with low osteocalcin. This marker of bone formation
was also higher in patients with elevated circulating osteoprotegerin. Liver osteoprotegerin gene expression was similar in
patients and controls, and no correlation was found between liver osteoprotegerin-mRNA and patients’ respective circulating
levels. In conclusion, osteoprotegerin and RANKL are abnormal in patients with PBC, regardless of osteoporosis. The elevated
circulating osteoprotegerin is associated with the severity of disease, but not with gene expression in the liver. 相似文献
6.
Kim YD Song WW Kim SS Kim GC Hwang DS Shin SH Kim UK Kim JR Chung IK 《Lasers in medical science》2009,24(4):577-584
The aim of this study was to investigate by immunohistochemistry the effects of low-level laser (LLL) irradiation on the expression
of the receptor activator of nuclear factor -κB ligand (RANKL), osteoprotegerin (OPG), and the receptor activator of nuclear
factor -κB (RANK) in deproteinized bovine bone grafts in rats. Twenty-four male Sprague-Dawley rats aged 15 weeks were allocated
to either an experimental group that underwent LLL irradiation during bone healing at the bone graft sites of the rats’ calvarial
bone defects or a control group. In the experimental group, gallium–aluminum–arsenide (Ga-Al-As) diode LLL (wavelength 808 nm;
output 96 mW) was used to irradiate three areas on and around bone defects. The radiation was administered by the contact
method for 10 s at 8.3 J/cm2, once a day for 7 days. The total dose over the complete schedule was 40.32 J. The animals were killed on days 7, 14 or 21.
The results of immunohistochemical analysis showed that the expression of RANKL (P = 0.199), OPG (P = 0.035), and RANK (P = 0.020) in the experimental group significantly increased from day 7, with a more even distribution than in the control
group, and that this difference prevailed until the end of the experiment. Bone density of the experimental group after trichrome
staining was also higher than in the control group. These results suggest that LLL irradiation facilitates bone metabolism
during bone healing at the sites of deproteinized bovine bone grafts in rats. 相似文献
7.
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
8.
Summary.
We report two cases of nonunion of subtrochanteric fractures associated with failure of fixation with a dynamic condylar
screw (DCS) due to plate fracture. In both cases the nonunion was successfully treated by insertion of a reconstruction femoral
nail. This implant allowed early weightbearing despite the patients’ advanced age and poor bone quality. We did not perform
direct bone grafting and the fractures healed without complication.
Accepted: 6 June 1995 相似文献
Résumé. Les auteurs rapportent deux cas de pseudarthrose après fracture sous-trochantérienne du fémur associée à une rupture du matériel d’ostéosynthèse. Il s’agissait de plaques vissées à vissage épiphysaire dynamique (dynamic condylar screw: DCS) qui se sont rompues au niveau de la plaque. Dans les deux cas, la consolidation a été obtenue par la mise en place d’un clou fémoral de reconstruction. Ce type d’ostéosynthèse autorise un appui complet précoce malgré l’age avancé des patients et la mauvaise qualité de l’os. Une greffe osseuse n’a pas été nécessaire et les fractures ont consolidé sans complication.
Accepted: 6 June 1995 相似文献
9.
Association between osteoprotegerin gene polymorphism and bone mineral density in patients with adolescent idiopathic scoliosis 总被引:1,自引:0,他引:1
Il-Soo Eun Weon Wook Park Kuen Tak Suh Jeung Il Kim Jung Sub Lee 《European spine journal》2009,18(12):1936-1940
Generalized low bone mass and osteopenia have been reported in the axial and peripheral skeleton of adolescent idiopathic
scoliosis (AIS) patients. Recently, many studies have shown that gene polymorphisms are related to osteoporosis. However,
no studies have linked the association between gene polymorphisms and bone mass of AIS. Therefore, this study examined the
association between the bone mass and RANKL, RANK, and OPG gene polymorphisms in 198 girls diagnosed with AIS. OPG 163 A → G,
209 G → A, 245 T → G, and 1181 G → C polymorphisms; RANK 421 C → T and 575 C → T polymorphisms; and RANKL rs12721445 and rs2277438
polymorphisms, as well as the bone mineral density at the lumbar spine (LSBMD) and femoral neck (FNBMD) were analyzed. The
163 A → G, 209 G → A, and 245 T → G polymorphisms in the OPG gene were in complete linkage. No RANK 421 C → T and 575 C → T
polymorphisms or RANKL rs12711445 polymorphism were observed. There was a significant association between the OPG gene 1181
G → C polymorphism and LSBMD. LSBMD in AIS with the CC genotype was found to be significantly higher than in AIS with the
GC (P < 0.05) or GG (P < 0.01) genotype. However, there was no significant association between LSBMD or FNBMD and the OPG gene 245 T → G polymorphism
or the RANKL rs2277438 polymorphism. These results suggest that the OPG gene 1181 G → C polymorphism is associated with LSBMD
in girls with AIS. 相似文献
10.
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
11.
Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels. 总被引:17,自引:3,他引:14
Patients with vascular calcifications often have low bone mineral density (BMD), but it is still uncertain if osteoporosis and peripheral vascular disease (VD) are interrelated and linked by a common pathomechanism. Moreover, data on bone turnover in patients with advanced atherosclerosis are lacking. We measured BMD by dual-energy X-ray absorptiometry (DXA) and quantitative bone ultrasound (QUS), as well as the serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), osteoprotegerin (OPG) and its ligand RANKL, and the urinary concentration of the C-terminal telopeptides of type I collagen (CrossLaps), in 36 patient (20 male and 16 female) with serious atherosclerotic involvement of the carotid and/or femoral artery to investigate the underlying mechanism of vascular and osseous disorders. Thirty age-matched and gender matched healthy individuals served as controls. After adjustment for age, BMD was significantly reduced at the lumbar spine in 23/36 (63%) patients (mean T score –1.71±1.42) and at the proximal femur in 34/36 (93%) patients (neck mean T score –2.5±0.88). Ten patients (27%) had abnormal QUS parameters. Gender and diabetes had no effect on the relationship between vascular calcification and bone density at any site measured. VD subjects had OC and BAP serum levels lower than controls (13.3±3.1 vs 27.7±3.3 ng/ml, P<0.01, and 8.4±2.3 vs 12.5±1.4 g/l, P<0.01, respectively). Urinary CrossLaps excretion was not significantly different in patients with VD and in controls (257.9±138.9 vs 272.2±79.4 µg/mmol Cr, respectively). Serum OPG and RANKL levels were similar in patients and in controls (3.5±1.07 vs 3.4±1.05 pmol/l, and 0.37±0.07 vs 0.36±0.06 pmol/l, respectively). We proved high occurrence of osteoporosis in VD, with evidence of age and gender independence. Negative bone remodelling balance would be a consequence of reduced bone formation, with no apparent increased activation of the OPG–RANKL system. 相似文献
12.
Ivica Avbersek-Luznik Breda Pecovnik Balon Igor Rus Janja Marc 《Nephrology, dialysis, transplantation》2005,20(3):566-570
BACKGROUND: The receptor activator of nuclear factor kappaB ligand (RANKL), produced by osteoblasts/stromal cells, is a member of the RANK/RANKL/OPG system, which regulates bone resorption by osteoclasts. Since RANKL and osteoprotegerin (OPG) production in bone is influenced by parathyroid hormone (PTH), we measured serum RANKL and OPG concentrations in haemodialysis (HD) patients, who commonly hypersecrete PTH. We aimed to determine if clinically demonstrated PTH-enhanced bone resorption is a consequence of increased RANKL synthesis. METHODS: RANKL, OPG, osteocalcin, intact PTH, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase 5b and beta-CrossLaps (CTx) were measured in blood samples from 80 HD patients and 50 age-matched controls. HD patients were stratified to tertiles according to their serum PTH levels: 29.3-103.0, 109.7-263.0 and 262.0-1700.0 pg/ml in the first, second and third tertiles, respectively. RESULTS: Mean serum RANKL levels were 1.6 times higher in HD patients than in age-matched controls (1.36+/-0.39 vs 0.83+/-0.70 pmol/l; P<0.001). All the measured bone markers significantly differed between patients and controls (P<0.001). Spearman's tests of correlation showed a statistically significant association of RANKL with PTH, osteocalcin and CTx (r=0.322, P=0.004; r=0.231, P=0.039; and r=0.230, P=0.040, respectively). Mean serum RANKL levels were significantly different between PTH tertiles (P = 0.003), but serum OPG levels were not (P=0.144). The highest RANKL levels were measured in the upper PTH tertile (1.54+/-0.39 pmol/l) and were significantly higher than in the middle or lower tertiles (1.27+/-0.42 and 1.23+/-0.26 pmol/l, respectively; P=0.003). Both of the measured bone-resorption markers, tartarate-resistant acid phosphatase 5b and CTx, as well as both bone formation markers, osteocalcin and bone-specific alkaline phosphatase were also significantly higher in the upper tertile, indicating that whole-bone remodelling is activated at high PTH and RANKL levels. CONCLUSIONS: Serum RANKL levels were significantly higher in HD patients than in healthy age-matched controls. Moreover, RANKL levels were significantly higher in the upper PTH tertile, indicating enhanced RANKL synthesis in a PTH-dependent fashion. Thus, our clinical findings clearly support published in vitro studies that demonstrated a stimulating effect of PTH on RANKL synthesis. Therefore, the hypothesis that PTH increases bone resorption in HD patients through RANKL appears valid. 相似文献
13.
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
14.
《BONE》2006,38(6):751-758
Osteoprotegerin (OPG) is a naturally occurring protein, which prevents bone resorption by inhibition of osteoclastogenesis, function, and survival. Therefore, recombinant OPG may be an attractive drug in the treatment of chronic bone resorptive diseases such as osteoporosis. Gene therapy has the potential to achieve long-term treatment by delivering genes of anti-resorptive proteins to the recipient. The effects of OPG gene therapy on fracture healing have not been described previously.The influence of OPG gene therapy on callus formation, callus tissue structural strength, apparent material properties, and histology of tibia fractures in rats was investigated after 3 weeks and 8 weeks of healing. Intramuscular administration of adeno-associated virus (AAV) vector-mediated OPG resulted in increased levels of OPG in serum of approximately 100 ng/ml throughout the study period. Control animals with fractures received transduction with an AAV reporter gene construct (AAV-enhanced green fluorescent protein (eGFP)), and in this group serum OPG levels remained at baseline (<10 ng/ml). After 3 weeks of healing, AAV-OPG treatment reduced the number of osteoclasts in the callus tissue (33%, P < 0.001). However, AAV-OPG treatment did not influence callus dimensions, callus bone mineral content (BMC), fracture structural strength, or apparent callus tissue material properties. After 8 weeks of healing, AAV-OPG treatment reduced the number of osteoclasts in the callus tissue (31%, P < 0.001) compared with AAV-eGFP fractures. Furthermore, deposition of new woven bone at the fracture line of the original cortical bone was hampered (new woven bone present: in all AAV-eGFP animals, in 41% of AAV-OPG-treated animals, P < 0.001). AAV-OPG treatment also increased callus BMC (18%, P = 0.023) compared with AAV-eGFP fractures. AAV-OPG did not influence callus dimensions, structural strength of the fractures, or ultimate stress, whereas elastic modulus was reduced in the AAV-OPG groups (37%, P = 0.039). The experiment demonstrates that AAV-OPG gene therapy decreases the fracture remodeling, but this does not influence the structural strength of healing fractures. 相似文献
15.
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
16.
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
17.
Angelopoulos NG Goula A Katounda E Rombopoulos G Kaltzidou V Kaltsas D Malaktari S Athanasiou V Tolis G 《Journal of bone and mineral metabolism》2007,25(1):60-67
Osteoporosis represents an important cause of morbidity in patients with β-thalassemia major, and its etiology is multifactorial.
Thus, the aim of this study was to characterize the possible role of the osteoprotegerin (OPG) and receptor activator of the
NF-κB ligand (RANKL) system in thalassemia-related bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers
of bone turnover, and lumbar spine bone mineral density (BMD) were measured in random samples of males (n = 29; mean age ± SEM, 24.26 ± 1.29 years; range, 13–41 years) and females (n = 31; age, 24.59 ± 0.95 years; range, 12–34 years) with β-thalassemia major and in 30 healthy age-, height-, and weight-matched
subjects. Thalassemic patients had significantly lower levels of OPG compared with controls (2.54 ± 0.12 vs. 3.25 ± 0.122,
respectively; P < 0.05) and higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 ± 0.03 vs. 0.295 ± 0.046, respectively;
P < 0.05). s-RANKL correlated negatively with age (r = −0.3, P < 0.05), and OPG correlated positively with the duration of the interval between the onset of transfusions and chelation
therapy (r = 0.52, P < 0.001). Regarding markers of bone metabolism, plasma values of osteocalcin correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s-RANKL ratio (r = −0.55, P < 0.01). In multiple regression analysis only cross-linked N-teleopeptide of type I collagen (NTX) significantly accounted
for BMD. Although the OPG/RANKL system may have some clinical usefulness as a marker of bone turnover in β-thalassemia, conventional
markers of bone turnover more accurately represent changes in the BMD of these patients. 相似文献
18.
The aim of this study was to evaluate the immunohistochemical expression of molecules involved in osteoclastogenesis, including
the receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) in odontogenic keratocysts
(OKCs), which has been named as a keratocystic odontogenic tumour by the WHO, and compare their expression with radicular
cysts and ameloblastomas. RANK is a member of tumour necrosis factor receptor family and it is activated by RANK ligand. OPG
binds to RANKL and inactivates it. The imbalance of these factors could cause the differential bone resorption activity in
some diseases and tumours. The expression of these molecules was evaluated in ameloblastomas (n = 20), OKCs (n = 20), and radicular cysts (n = 20) by immunohistochemistry. Immunohistochemical reactivity for RANK, RANKL, and OPG was detected in neoplastic and nonneoplastic
epithelium and connective tissue cells. RANK showed the greatest expression in OKCs followed by ameloblastomas, with the lowest
expression seen in radicular cysts. Expression of RANKL was detected in all lesions and no significant differences were observed
between groups. OPG was expressed very low in all groups. In the stroma, the number of RANK positive cells was higher in OKCs
when compared with ameloblastomas and radicular cysts but radicular cyst had higher numbers of RANKL positive cells in the
stroma than ameloblastomas. The molecular system of RANK/RANKL/OPG is variably expressed in OKCs, radicular cysts, and ameloblastomas
and this system may be involved in the osteoclastogenic mechanisms in OKCs and ameloblastomas. Advanced studies could further
clarify the role of RANK, RANKL, and OPG in mediating tumour associated bone osteolysis. 相似文献
19.
Abdallah BM Stilgren LS Nissen N Kassem M Jørgensen HR Abrahamsen B 《Calcified tissue international》2005,76(2):90-97
RANKL (receptor activator of NF-B) is a potent physiological inducer of osteoclastogenesis. Its actions are blocked by the decoy receptor osteoprotegerin (OPG), and treatment with OPG blocks bone resorption in postmenopausal women. Both positive and negative associations between serum OPG and bone mineral density (BMD) have been reported in the literature. We hypothesized that decreased OPG production relative to RANKL within bone itself could lead to increased risk of osteoporotic fracture. We included ten women with hip fracture (age 76.3 ± 8.0 years, N.S, hip BMD 0.686 ± 1.3 g/cm2, P < 0.05) and 24 women with osteoarthrosis of the hip (age 72.8 ± 7.2 years, hip BMD 0.832 ± 1.1 g/cm2). Transiliac biopsies were obtained at the time of surgery. Total RNA was extracted from biopsies and reverse-transcribed. Real-time quantification of mRNA was performed with a SYBR Green I real time PCR assay, calculating relative gene expession with normalization of results for actin mRNA. Actin normalized mRNA levels for OPG and interleukin (IL)-6 were significantly lower in fracture patients, with a significantly higher RANKL/OPG ratio in patients with fractures. There was no significant difference in tumor necrosis factor (TNF), IL-1, IL-1ra, or IL-7 expression. IL-6 mRNA levels were lower in fracture patients (P < 0.05). The effect of increased RANKL/OPG ratio (Z = 2.08, P < 0.05) on fracture risk was additive to that of hip BMD T score (Z = –1.95, P < 0.05) when assessed using logistic regression. Elderly women with hip fractures exhibit an increased RANKL/OPG mRNA content of iliac bone. This is associated with increased fracture susceptibility, which is not in itself explained by low BMD. 相似文献
20.
F. M. Ulivieri L. P. Piodi G. Marotta D. Marchelli C. Commadini L. Parravicini C. Verdoia P. Gerundini 《Journal of orthopaedics and traumatology》2006,7(4):192-194
Osteoprotegerin (OPG) is a protein that inhibits of osteoclastogenesis. The aim this study was to evaluate the response of
serum OPG levels to neridronate treatment in patients with Paget's disease of bone resistant to previous therapy. Nine patients
(4 men) affected by active Paget’s disease of bone (6 polyostotic, 3 monostotic) not responsive to clodronate were studied.
Serum OPG, osteocalcin, total and bone isoenzyme of alkaline phosphatase (AP and BAP, respectively), and urinary deoxypyridinoline
(DPD) were measured before and 5 months after neridronate treatment (100 mg/day, i.v. for two days). A scintigraphic activity
index (SAI) was also calculated before treatment. Mean baseline OPG levels were within normal values and were not significantly
different 5 months after neridronate treatment. In contrast, there were significant reductions in AP (41.9%, p<0.02) and BAP (38.8%, p<0.04). Serum OPG levels correlated with DPD (r=0.925) and SAI (r=0.689). Although OPG is an important regulator of bone metabolism,
in our series of already treated patients it was not a sensitive marker for diagnosing Paget's disease and for monitoring
the response to pharmacological treatment, whereas AP and BAP confirmed their clinical usefulness. This preliminary study
requires confirmation by a study with a larger population. 相似文献