osteoprotegerin and Hip-Fractures

Osteoporosis and atherosclerosis share common risk factors. Aim of this study was to test if FRAX (which is an algorithm that can identify subjects at risk of fracture), without or with BMD values, also adjusted for trabecular bone score (TBS) was able to identify subclinical atherosclerosis, evaluated by measurement of carotid intima media thickness (cIMT ≥ 0.9 mm) as compared to DXA values.. Ninety postmenopausal women underwent DXA measurement and cIMT evaluation. For each patient, the FRAX algorithm for major osteoporotic fracture (M) and for hip fracture (H) without BMD was computed, together with FRAX with BMD and TBS-adjusted FRAX. Serum levels of osteoprotegerin, sRANKL, and interleukin-6 were also measured.. There were no differences in anthropometric parameters and cardiovascular risk factors between subjects with cIMT ≥ 0.9 mm (35% of subjects, group A) compared to those with cIMT < 0.9 mm (group B). The prevalence of osteoporosis and FRAX BMD, TBS-adjusted FRAX both for M and H were higher in group A compared to group B. The best ROC curves to identify subjects with a cIMT ≥ 0.9 mm were: lumbar spine T-score, with a threshold of - 2.5 SD (area under the curve, AUC 0.64; p = 0.02) with a sensibility of 50% and a specificity of 76%; TBS-adjusted FRAX H with a sensibility of 50% and a specificity of 72% (AUC 0.64; p = 0.01 with a threshold of 3%). Interleukin-6 positively correlated with FRAX BMD H and M.. FRAX without BMD does not identify subclinical carotid atherosclerosis, while lumbar spine T-score and TBS-adjusted FRAX H similarly detected it with higher specificity for T-score.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Bone Density; Carotid Artery Diseases; Carotid Intima-Media Thickness; Female; Hip Fractures; Humans; Lumbar Vertebrae; Middle Aged; Osteoporotic Fractures; Osteoprotegerin; Postmenopause; Prevalence; RANK Ligand; Risk Assessment; ROC Curve; Spinal Fractures; Trabecular Meshwork

Bone diseases represent an increasing health burden worldwide, and basic research remains necessary to better understand the complexity of these pathologies and to improve and expand existing prevention and treatment approaches. In the present study, 216 bone samples from the caput femoris and collum femoris of 108 patients with degenerative or dysplastic coxarthrosis, hip fracture, or osteonecrosis were evaluated for the proportion of trabecular bone (TB) and expression of parathyroid hormone (PTH) type 1 receptor (PTH1R), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL). Serum levels of PTH, OPG, soluble RANKL (sRANKL), alkaline phosphatase (AP), osteocalcin, total procollagen type-1 intact N-terminal propeptide (TP1NP), tartrate-resistant acid phosphatase type 5b (TRAP5b), sclerostin, and C-telopeptide of type-1 collagen (ICTP) were also determined. Age was positively correlated with serum levels of PTH, OPG, and sclerostin but negatively associated with TB and sRANKL. Women exhibited less TB, lower sclerostin and ICTP, and higher TRAP5b. Impaired kidney function was associated with shorter bone decalcification time, less TB, lower sRANKL, and higher serum PTH, OPG, and sclerostin. Furthermore, correlations were observed between bone PTH1R and OPG expression and between serum PTH, OPG, and AP. There were also positive correlations between serum OPG and TP1NP; serum OPG and sclerostin; serum AP, osteocalcin, and TRAP5b; and serum sclerostin and ICTP. Serum OPG was negatively associated with sRANKL. In summary, clear relationships between specific bone metabolism markers were observed, and distinct influences of age, sex, and kidney function, thus underscoring their suitability as diagnostic or prognostic markers.

Topics: Adult; Aged; Aged, 80 and over; Cancellous Bone; Female; Hip Fractures; Humans; Male; Middle Aged; Osteoarthritis, Hip; Osteocalcin; Osteonecrosis; Osteoprotegerin; Parathyroid Hormone; RANK Ligand

The lack of a univocal definition of frailty, a condition frequently found in the elderly population which is correlated with an increased risk of mortality, has prompted the search for clinical and laboratory parameters associated with this condition. Whereas OPG is a protein involved in different pathophysiological conditions including bone, vascular, immune and tumor disease and studies found a positive linear correlation between OPG and age we hypothesized that it may represent a frailty marker in the elderly.We conducted an observational study of 172 elderly subjects, with and without hip fracture, including a multidimensional geriatric evaluation and a laboratory evaluation, aimed to evaluate the association between OPG and frailty.Frailty Score was associated with FT3 and osteoprotegerin (OPG), regardless of fracture event. Excluding subjects with hip fracture, in whom the acute event had a direct effect on bone production of OPG, the Frailty Score showed a linear correlation with circulating levels of osteoprotegerin.In the elderly, an increase in osteoprotegerin levels may reflect a progressive accumulation of organ damage leading to the development of frailty. The correlation between OPG and Frailty Score found in our study points to its potential use as a biomarker for geriatric frailty syndrome.

Topics: Aged; Aged, 80 and over; Biomarkers; Female; Frailty; Hip Fractures; Humans; Male; Osteoprotegerin

Identification of risk factors may help us to understand the pathogenesis of osteoporotic hip fracture as well as to formulate development of better diagnostic, prevention and treatment strategies. The present study was designed to determine the impact of multiple metabolic risk factors such as markers of systemic inflammation (C-reactive protein), immune responses-acute phase reactants (ferritin), insulin resistance (HOMA-IR) and bone remodeling (osteoprotegerin), for the prediction of hip fractures in postmenopausal osteoporotic women. The study group consisted of 115 postmenopausal women divided into two groups: Group 1 consisted of 49 women hospitalized in the Orthopedic Department, Wolfson Medical Center for the diagnosis of non-traumatic hip fracture and Group 2 contained 66 postmenopausal osteoporotic women without a history of hip fracture. Metabolic parameters were determined. Circulating OPG was significantly higher in Group 1 than in Group 2 (205.2 ± 177.1 vs 60.0 =/-22.3, p < 0.0001). While levels of hemoglobin (Hbg) as well as MCV and MCH did not differ between groups, circulating ferritin was significantly increased in Group 1 compared to the control Group 2 (217.9 ± 195.1 vs 49.7 ± 31.3, p < 0.0001). In multiple linear regression analysis, which explains about 40 % of the variability in CRP, 42 % in OPG, and 28 % in ferritin, significant by-group differences in terms of these parameters persisted even after adjustment. Elevated serum ferritin concentrations and bone remodeling marker, osteoprotegerin, are independent predictors of hip fracture in postmenopausal women hospitalized for fragility fracture.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Female; Ferritins; Hip Fractures; Humans; Insulin Resistance; Mass Screening; Middle Aged; Osteoprotegerin; Postmenopause; Vitamin D

Bone turnover markers have a potential clinical use in describing bone remodeling and in predicting fractures.. In an elderly population ≥75 years with a fresh hip fracture, and in healthy controls, investigate bone turnover markers and their relation to each other, to vitamin D status and to bone mineral density (BMD).. In a cross-sectional study serum levels of dickkopf-1 (DKK-1), sclerostin (SOST), osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, 25-hydroxyvitamin D (25(OH)D) were analyzed in 89 Swedish patients with a fresh hip fracture and in 82 healthy volunteers. Serum levels of bone markers were determined by Luminex technique.. S-25-hydroxyvitamin D (S-25(OH)D) was decreased in patients compared to controls (48 ± 21 vs. 76 ± 25 nmol/L, p < 0.001). SOST, but none of the other bone turnover markers correlated with BMD (r = 0.50, p < 0.001). Compared with controls, higher levels of OPG (488 ± 1.4 vs. 191 ± 1.4 ng/L, p < 0.001), OPN (69 ± 1.7 vs. 19 ± 1.4 µg/L, p < 0.001), DKK-1 (273 ± 1.7 vs. 168 ± 1.7 ng/L, p < 0.001), and lower levels of osteocalcin (5.8 ± 3.5 vs. 9.5 ± 3.6 µg/L, p < 0.001), were found in the fracture group. Levels of OPG, DKK-1 and SOST in both groups were positively associated. S-25(OH)D concentration was not found to be strongly associated with any of the bone markers.. In contrast to findings in other studies, we found no strong correlation between 25(OH)D and the investigated bone markers. Both in patients with a fresh hip fracture and in healthy elderly, DKK-1, SOST and OPG appear to be associated. This suggests a relevance in these relationships meriting further investigation.

Topics: Adaptor Proteins, Signal Transducing; Aged; Aged, 80 and over; Biomarkers; Bone Density; Bone Morphogenetic Proteins; Bone Remodeling; Case-Control Studies; Cross-Sectional Studies; Female; Genetic Markers; Hip Fractures; Humans; Immunoassay; Intercellular Signaling Peptides and Proteins; Male; Osteocalcin; Osteopontin; Osteoprotegerin; Sweden; Vitamin D

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fracture. Several factors have been identified as being potentially responsible for this risk, such as alterations in bone remodelling that may have been induced by changes in circulating glucose or/and by the presence of non-oxidative end products of glycosylation (AGEs). The aim of this study is to assess whether such variations generate a change in the gene expression related to the differentiation and osteoblast activity (OPG, RANKL, RUNX2, OSTERIX, and AGE receptor) in primary cultures of human osteoblast-like cells (hOB).. We recruited 32 patients; 10 patients had osteoporotic hip fractures (OP group), 12 patients had osteoporotic hip fractures with T2DM (T2DM group), and 10 patients had hip osteoarthritis (OA group) with no osteoporotic fractures and no T2DM. The gene expression was analyzed in hOB cultures treated with physiological glucose concentration (4.5 mM) as control, high glucose (25 mM), and high glucose plus AGEs (2 μg/ml) for 24 h.. The hOB cultures from patients with hip fractures presented slower proliferation. Additionally, the hOB cultures from the T2DM group were the most negatively affected with respect to RUNX2 and OSX gene expression when treated solely with high glucose or with high glucose plus AGEs. Moreover, high levels of glucose induced a major decrease in the RANKL/OPG ratio when comparing the OP and the T2DM groups to the OA group.. Our data indicates an altered bone remodelling rate in the T2DM group, which may, at least partially, explain the reduced bone strength and increased incidence of non-traumatic fractures in diabetic patients.

Topics: Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Bone Remodeling; Core Binding Factor Alpha 1 Subunit; Diabetes Mellitus, Type 2; Female; Gene Expression; Glucose; Glycation End Products, Advanced; Hip Fractures; Humans; Male; Osteoarthritis, Hip; Osteoblasts; Osteoporotic Fractures; Osteoprotegerin; Primary Cell Culture; RANK Ligand; Sp7 Transcription Factor

Patients with rheumatoid arthritis (RA) have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies. The purpose of this study was to identify genetic variants associated with the occurrence of hip fracture in Japanese patients with RA.. DNA samples from 2,282 Japanese patients with RA were obtained from the DNA collection of the Institute of Rheumatology Rheumatoid Arthritis cohort (IORRA) study. Six single nucleotide polymorphisms (SNPs) that have been reported to be associated with fractures in recent studies were selected and genotyped. Forty hip fractures were identified with a maximum follow-up of 10 years. The genetic risk for hip fracture was examined using a multivariate Cox proportional hazards regression model.. The risk analyses revealed that patients who are homozygous for the major allele of SNP rs6993813, in the OPG locus, have a higher risk for hip fracture (hazard ratio [95% CI] = 2.53 [1.29-4.95], P = 0.0067). No association was found for the other SNPs.. Our results indicate that an OPG allele is associated with increased risk for hip fracture in Japanese patients with RA.

Topics: Aged; Arthritis, Rheumatoid; Asian People; Cohort Studies; Female; Genome-Wide Association Study; Hip Fractures; Humans; Japan; Male; Middle Aged; Osteoprotegerin; Polymorphism, Single Nucleotide; Proportional Hazards Models; Risk

Intertrochanteric fractures occur most commonly in elderly patients. Osteoblasts and osteoclasts have been reported to be regulated by the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), during bone modeling and remodeling, respectively. Based on these observations, we hypothesized that the serum levels of RANKL, OPG and the RANKL/OPG ratio are important in the healing of intertrochanteric fractures in elderly patients. Enzyme-linked immunosorbent assays were used to measure the serum concentrations of RANKL and OPG in 36 elderly patients with intertrochanteric fractures and 30 age-matched healthy control subjects, at baseline and 4, 8 and 12 weeks following injury. The RANKL/OPG ratio in the two groups was also evaluated. Similar trends in RANKL and OPG levels were detected during the fracture healing process. The serum levels of RANKL and OPG were higher in the fracture group than in the controls, and were significantly higher at baseline and 4 weeks following injury (P<0.05). Notably, although the RANKL/OPG ratio gradually increased during healing, it was lower in the fracture group than in the control group. The RANKL/OPG ratio was significantly lower immediately after and 4 weeks after injury in the fracture group (P<0.05). Our data suggest a close correlation between higher serum levels of RANKL and OPG and the fracture healing process, indicating that RANKL and OPG are involved in fracture healing. The serum RANKL/OPG ratio also appears to be significant in the healing of intertrochanteric fractures in elderly patients.

Topics: Aged; Aged, 80 and over; Female; Fracture Healing; Hip Fractures; Humans; Interleukin-6; Male; Middle Aged; Osteoblasts; Osteoclasts; Osteoprotegerin; RANK Ligand

The 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.. A 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.. Serum 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.. Serum OPG levels were independently associated with a nearly twofold increased risk of hip fracture in postmenopausal women.

Topics: Aged; Case-Control Studies; Female; Hip Fractures; Humans; Middle Aged; Osteoprotegerin; Postmenopause; RANK Ligand

Osteoprotegerin (OPG) is a cytokine essential for the regulation of bone resorption, but large longitudinal studies on its relationship to fracture risk in humans are lacking. In this population-based study of 2740 men and 2857 post-menopausal women, it was examined whether serum OPG was associated with hip fracture incidence. The participants were followed for 15 years.. Baseline measurements included height, weight and serum OPG, and information about lifestyle, prevalent diseases and use of medication.. Men with OPG in the highest quartile were 2.79-fold [95% confidence interval (CI) 1.34-5.82] more likely to have a hip fracture during follow-up, compared with those with OPG in the lowest quartile (P-trend over OPG quartiles ≤ 0.001, after adjustments for age and other confounders). In women not using post-menopausal hormone therapy (HT), the risk of hip fracture was 1.64-fold higher (95% CI 0.94-2.86) in the highest quartile compared with the lowest OPG quartile (P-trend over OPG quartiles = 0.05). No relationship was found in post-menopausal women using HT (P-trend over OPG quartiles = 0.23).. In men, OPG was positively associated with the incidence of hip fracture. In post-menopausal women not using HT a similar, but weaker, relationship was found.

Topics: Aged; Aged, 80 and over; Bone Density; Enzyme-Linked Immunosorbent Assay; Female; Health Surveys; Hip Fractures; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Norway; Osteoprotegerin; Proportional Hazards Models; Risk Factors; Sex Factors

To identify the susceptibility genes for osteoporotic fracture in postmenopausal Chinese women, a two-stage case-control association study using joint analysis was conducted in 1046 patients with nontraumatic vertebra, hip, or distal radius fractures and 2303 healthy controls. First, 113 single-nucleotide polymorphisms (SNPs) in 16 potential osteoporosis candidate genes reported in recent genomewide association studies, meta-analyses studies, large-scale association studies, and functional studies were genotyped in a small-sample-size subgroup consisting of 541 patients with osteoporotic fractures and 554 healthy controls. Variants and haplotypes in SPTBN1, TNFRSF11B, CNR2, LRP4, and ESR1 that have been identified as being associated with osteoporotic fractures were further reanalyzed in the entire case-control group. We identified one SNP in TNFRSF11B (rs3102734), three SNPs in ESR1 (rs9397448, rs2234693, and rs1643821), two SNPs in LRP4 (rs17790156 and rs898604), and four SNPs in SPTBN1 (rs2971886, rs2941583, rs2941584, and rs12475342) were associated with all of the broadly defined osteoporotic fractures. The most significant polymorphism was rs3102734, with increased risk of osteoporotic fractures (odds ratio, 1.35; 95% confidence interval [CI], 1.17-1.55, Bonferroni p = 2.6 × 10(-4) ). Furthermore, rs3102734, rs2941584, rs12475342, rs9397448, rs2234693, and rs898604 exhibited significant allelic, genotypic, and/or haplotypic associations with vertebral fractures. SNPs rs12475342, rs9397448, and rs2234693 showed significant genotypic associations with hip fractures, whereas rs3102734, rs2073617, rs1643821, rs12475342, and rs2971886 exhibited significant genotypic and/or haplotypic associations with distal radius fractures. Accordingly, we suggest that in addition to the clinical risk factors, the variants in TNFRSF11B, SPTBN1, ESR1, and LRP4 are susceptibility genetic loci for osteoporotic fracture in postmenopausal Chinese women.

Topics: Aged; Asian People; Bone Density; Case-Control Studies; Estrogen Receptor alpha; Female; Genetic Predisposition to Disease; Haplotypes; Hip Fractures; Humans; LDL-Receptor Related Proteins; Middle Aged; Osteoporotic Fractures; Osteoprotegerin; Polymorphism, Single Nucleotide; Postmenopause; Spectrin

An elevated annual incidence rate of hip fracture has been reported among elderly Taiwanese. Moreover, bone mineral density (BMD) is the single most reliable predictor of fragility fractures. We aimed to identify the association between gene sequence variants and hip BMD in postmenopausal Taiwanese women.. We prospectively analyzed data from 163 postmenopausal Taiwanese women to test an association between rs7524102, rs6696981, or rs6993813 single-nucleotide polymorphisms (SNPs) and hip BMD.. Our study showed that rs6993813 (osteoprotegerin gene) and rs6696981 (ZBTB40 gene) SNPs have an opposite association with hip BMD. For rs6993813 genotypic frequencies, the adjusted odds ratio for hip osteoporosis was 9.53 for individuals with T/T minor allele homozygotes, compared with that of participants with C/C wild-type homozygotes. Hip BMD also had an association with rs6993813 SNPs, especially in T/T minor allele homozygotes. For rs6696981 SNPs, hip BMD in G/T heterozygotes and at least one mutated T allele was higher than that in wild-type G/G homozygotes.. The gene sequence variant rs6993813 reduced hip BMD and increased the risk of hip osteoporosis, whereas rs6696981 increased hip BMD in postmenopausal Taiwanese women. This indicated that the two SNPs may provide some explanation for the high risk of hip fracture in this population.

Topics: Aged; Bone Density; DNA-Binding Proteins; Female; Genotype; Hip; Hip Fractures; Humans; Middle Aged; Osteoprotegerin; Polymorphism, Single Nucleotide; Postmenopause; Retrospective Studies; Zinc Fingers

Topics: Female; Hip Fractures; Humans; Male; Osteoprotegerin

Fracture healing is orchestrated by a specific set of events that culminates in the repair of bone and reachievement of its biomechanical properties. The aim of our work was to study the sequence of gene expression events involved in inflammation and bone remodeling occurring in the early phases of callus formation in osteoporotic patients.. Fifty-six patients submitted to hip replacement surgery after a low-energy hip fracture were enrolled in this study. The patients were grouped according to the time interval between fracture and surgery: bone collected within 3 days after fracture (n = 13); between the 4(th) and 7(th) day (n = 33); and after one week from the fracture (n = 10). Inflammation- and bone metabolism-related genes were assessed at the fracture site. The expression of pro-inflammatory cytokines was increased in the first days after fracture. The genes responsible for bone formation and resorption were upregulated one week after fracture. The increase in RANKL expression occurred just before that, between the 4(th)-7(th) days after fracture. Sclerostin expression diminished during the first days after fracture.. The expression of inflammation-related genes, especially IL-6, is highest at the very first days after fracture but from day 4 onwards there is a shift towards bone remodeling genes, suggesting that the inflammatory phase triggers bone healing. We propose that an initial inflammatory stimulus and a decrease in sclerostin-related effects are the key components in fracture healing. In osteoporotic patients, cellular machinery seems to adequately react to the inflammatory stimulus, therefore local promotion of these events might constitute a promising medical intervention to accelerate fracture healing.

Topics: Adaptor Proteins, Signal Transducing; Aged, 80 and over; Bone Morphogenetic Proteins; Bone Remodeling; Bony Callus; Down-Regulation; Female; Fracture Healing; Genetic Markers; Hip Fractures; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Male; Osteocytes; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Up-Regulation

The OPG/RANKL/RANK system is important in the balance between bone formation and resorption. We used primary human osteoblasts (hOBs) cells to examine the impact of 17-beta-estradiol (E2) or/and 1,25-dihydroxyvitamin D (1,25D) in OPG/RANKL system in 28 post-menopausal (PM) women; (a) with hip fracture (OP) or (b) with osteoarthritis (OA). The hOB from OP patients proliferated slower during the first stage, than the OA women (31.5+/-2.6 and 21.4+/-1.3 days, respectively, p<0.05). The OP group secreted significantly higher OPG protein levels than the OA women (10.1+/-2.6 and 4.4+/-0.8pmol/L, respectively, p<0.05). The 1,25D and 1,25D+E2 induce an increase in RANKL and RANKL/OPG mRNA expression in OP patients above 200% (p<0.05). HOBs from the osteoporotic hip initially proliferate slower but after reaching the first cellular confluence, the proliferation rate is equal in both groups. Furthermore, hOBs from hips with OP present a higher protein secretion of OPG, and higher RANKL and RANKL/OPG expression ratio in response to 1,25D and 1,25D+E2, than hOBs from OA women. All this could suggest that the greater bone loss that characterizes OP patients can be mediated due to differences in the secretion and expression of the RANKL/OPG system in response to different stimuli.

Topics: Aged; Aged, 80 and over; Cells, Cultured; Estradiol; Female; Gene Expression Regulation; Hip Fractures; Humans; Osteoarthritis; Osteoblasts; Osteoporosis; Osteoprotegerin; Postmenopause; RANK Ligand; RNA, Messenger; Vitamin D

In the estrogen-regulated RANK ligand (RANKL)/RANK/osteoprotegerin (OPG) pathway, estrogen deficiency favors osteoclast maturation, leading to increased bone resorption compared with bone formation. Treatment of low bone mineral density (BMD) should be based on fracture risk, assessed using the WHO Fracture Risk Algorithm (FRAX(R)). Criteria for treatment are 10-year overall fracture risk ≥ 20% or 10-year hip fracture risk ≥ 3%. Vitamin D supplementation at levels higher than those traditionally recommended may be appropriate for healthy menopausal women. Multiple strategies are needed to effectively manage osteoporosis in postmenopausal women.

Topics: Absorptiometry, Photon; Accidental Falls; Aged; Algorithms; Biomarkers; Bone Density; Bone Density Conservation Agents; Calcium; Congresses as Topic; Diphosphonates; Drug Interactions; Drug Therapy, Combination; Estrogen Replacement Therapy; Female; Food-Drug Interactions; Hip Fractures; Humans; Life Style; Mass Screening; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Osteoprotegerin; Practice Guidelines as Topic; RANK Ligand; Risk Assessment; Risk Factors; Treatment Outcome; Vitamin D

We aimed to discuss the risk assessments for both patients with hip fractures due to fall-related, low energy traumas and non-fractured control patients by examining bone mineral density and genetic data, two features associated with femoral strength and hip fracture risk.. Twenty-one osteoporotic patients with proximal femur fractures and non-fractured, osteoporotic, age- and gender-matched controls were included in the study. Bone mineral density measurements were performed with a Lunar DXA. The COL1A1, ESR, VDR, IL-6, and OPG genes were amplified, and labeling of specific gene sequences was performed in a multiplex polymerase chain reaction using the osteo/check PCR kit from the whole blood of all subjects.. The bone mineral density (trochanteric and total bone mineral density values) of the fracture group was significantly decreased relative to the control group. We were not able to conduct statistical tests for the polymorphisms of the COL1A1, ESR, and VDR genes because our results were expressed in terms of frequency. Although they were not significant, we did examine differences in the IL-6 and OPG genes polymorphisms between the two groups. We concluded that increasing the number of cases will allow us to evaluate racial differences in femoral hip fracture risk by genotypes.

Topics: Absorptiometry, Photon; Accidental Falls; Aged; Bone Density; Case-Control Studies; Collagen Type I; Collagen Type I, alpha 1 Chain; Estrogen Receptor alpha; Female; Genetic Predisposition to Disease; Genotype; Hip Fractures; Humans; Interleukin-6; Male; Osteoporosis; Osteoprotegerin; Polymerase Chain Reaction; Polymorphism, Genetic; Risk Assessment; Turkey

Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator nuclear factor kappa-beta that blocks osteoclastic bone resorption.. We investigated the association between a Lys3Asn polymorphism in the OPG gene and bone mineral density (BMD), and the risk of fracture in 6695 women aged 65 yr and older participating in the Study of Osteoporotic Fractures.. BMD was measured using either single-photon absorptiometry (Osteon Osteoanalyzer; Dove Medical Group, Los Angeles, CA) or dual-energy x-ray absorptiometry (Hologic QDR 1000; Hologic, Inc., Bedford, MA). Incident fractures were confirmed by physician adjudication of radiology reports. Genotyping was performed using an immobilized probe-based assay.. Women who were homozygous for the minor G (Lys) allele had significantly lower BMD at the intertrochanter, distal radius, lumbar spine, and calcaneus than those with the C (Asn) allele. There were 701 incident hip fractures during 13.6-yr follow-up (91,249 person-years), including 362 femoral neck and 333 intertrochanteric hip fractures. Women with the C/C (Asn-Asn) genotype had a 51% higher risk of femoral neck fracture (95% confidence interval, 1.13-2.02) and 26% higher risk of hip fracture (95% confidence interval, 1.02-1.54) than those with the G/G (Lys-Lys) genotype. These associations were independent of BMD. Intertrochanteric fractures were not associated with the Lys3Asn polymorphism.. These results require confirmation but suggest a role for the OPG Lys3Asn polymorphism in the genetic susceptibility to hip fractures among older white women.

Topics: Aged; Bone Density; Female; Genetic Predisposition to Disease; Genotype; Hip Fractures; Humans; Osteoprotegerin; Polymorphism, Genetic; Prospective Studies; Risk Factors

Osteoporosis (OP) is a systemic metabolic lesion of the skeleton involving a reduced osseous tissue weight and an impaired microarchitectonics, which worsens the bone strength and contributes to a higher risk of bone fractures. An essential spread of OP and of osteoporotic fractures among populations in various countries, including Russia, a high-severity outcome, and big economic expenses related with treatment and rehabilitation are indicative of a high social OP significance. OP is a multi-factor pathology provoked by impaired processes in osseous remodeling with a higher resorption of osseous tissue and a reduced osteogenesis. A study of molecular mechanisms of intercellular interaction in OP resulted in discovering new elements in the family of tumor necrosis factor (TNF) and their ligands and receptors (RANKL-RANK-OPG), which are of primary importance in osteoclastogenesis and which are molecular mediators in many regulatory effects. The key drugs applicable to prevention and treatment of OP are also described in the article. The current methods of OP prevention and treatment improve the bone quality and reduce the incidence rate of fracture in an essential share of patients.

Topics: Adult; Age Factors; Aged; Bone Density; Diphosphonates; Female; Glycoproteins; Hip Fractures; Humans; Male; Middle Aged; Moscow; Multicenter Studies as Topic; Osteoporosis; Osteoporosis, Postmenopausal; Osteoprotegerin; Placebos; Prospective Studies; Randomized Controlled Trials as Topic; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Risk Factors; Russia; Sex Factors; Spinal Fractures; United States