Gender differences in plasma ghrelin and its relations to body composition and bone – an opposite-sex twin study

Backgrond Ghrelin, a peptide hormone that plays a role in the regulation of appetite and body adiposity, may also play a role in bone metabolism. Objectives We used the opposite-sex twin model to study associations of plasma ghrelin levels with measures of bone mass and body composition, and determine how such associations were influenced by gender and age. Patients and measurements We measured total plasma ghrelin by radioimmunoassay (RIA) and bone mass/body composition parameters by dual energy X-ray absorptiometry in 79 pairs of opposite sex twins (n = 158 subjects). To examine the effect of age, the study population was divided by median age into two groups: under 51.2 years (38 pairs) and over 51.2 years (41 pairs). Results Women had higher plasma ghrelin levels than men (median 1063 vs. 869 ng/l, P 30) no significant gender differences in plasma ghrelin were found. Plasma ghrelin levels were not significantly associated with bone mineral density (BMD) generally, except for hip BMD in younger women (r = -0.39). Conclusion Plasma ghrelin levels are associated with age, gender, alcohol intake and fat mass measures but only weakly to bone mass measures

Association between serum cholesterol and bone mineral density

Background: Hypercholesterolaemia has been associated with low bone mineral density (BMD) in some but not all studies. Objectives: To examine the influence of age, menopausal status and hormone replacement therapy (HRT) on the relationship between serum cholesterol and BMD in women. Patients and measurements: 497 female participants (age range 20-81) comprising 224 premenopausal and 273 postmenopausal women (156 on HRT and 117 no HRT) underwent measurements of bone mineral density (BMD) and serum lipid profile. Results: Total serum cholesterol (TC) and low density lipoprotein (LDL) levels were higher and lumbar spine BMD was lower in postmenopausal women not taking HRT compared to those taking HRT. TC and LDL were negatively associated with BMD at all measured sites among postmenopausal women not taking HRT in univariate regression analysis (all p<0.05). High density lipoprotein (HDL) had inverse relationships with BMD at all sites in pre-menopausal women and those who were exposed to HRT (p<0.05). In fully adjusted regression models the relationships between TC and BMD remained significant at the lumbar spine and whole body (p<0.05) and between LDL and lumbar spine BMD only (p<0.05). For subjects in the other groups, no significant associations between TC or LDL and BMD were found. Significant interactions between total cholesterol and LDL levels with HRT were detected among post-menopausal women in the regression analyses (all p<0.05). No such interactions were found between HDL levels and HRT. Conclusion: There is a modest inverse relationship between lumbar spine and whole body BMD and serum TC and LDL levels and in post-menopausal women and HDL in pre-menopausal women. HRT use appears to modify these relationships. The mechanisms of this relationship require further study. (C) 2008 Elsevier Inc. All rights reserved

Genetic Effects on Bone Loss in Peri- and Postmenopausal Women: A Longitudinal Twin Study

This longitudinal twin study was designed to assess the heritability of bone loss in peri- and postmenopausal women. A sample of 724 female twins was studied. Baseline and repeat BMD measurements were performed. Results of genetic model-fitting analysis indicated genetic effects on bone loss account for similar to 40% of the between-individual variation in bone loss at the lumbar spine, forearm, and whole body. Introduction: BMD and bone loss are important predictors of fracture risk. Although the heritability of peak BMD is well documented, it is not clear whether bone loss is also under genetic regulation. This study was designed to assess the heritability of bone loss in peri- and postmenopausal women. Materials and Methods: A sample of 724 female twins (177 monozygotic [MZ] and 185 dizygotic [DZ] pairs), 45-82 yr of age, was studied. Each individual had baseline BMD measurements at the lumbar spine, hip, forearm, and total body by DXA and at least one repeat measure, on average 4.9 yr later. Change in BMD (Delta BMD) was expressed as percent of gain or loss per year. Intraclass correlation coefficients for ABMD were calculated for MZ and DZ pairs. Genetic model-fitting analysis was conducted to partition the total variance of ABMD into three components: genetic (G), common environment (C), and specific environment, including measurement error (E). The index of heritability was estimated as the ratio of genetic variance over total variance. Results: The mean annual Delta BMD was -0.37 +/- 1.43% (SD) per year at the lumbar spine, -0.27 +/- 1.32% at the total hip, -0.77 +/- 1.66% at the total forearm, -0.36 +/- 56% at the femoral neck, and -0.16 +/- 0.81% at the whole body. Intraclass correlation coefficients were significantly higher in MZ than in DZ twins for all studied parameters, except at the hip sites. Results of genetic model-fitting analysis indicated that the indices of heritability for ABMD were 0.38, 0.49, and 0.44 for the lumbar spine, total forearm, and whole body, respectively. However, the genetic effect on ABMD at all hip sites was not significant. Conclusions: These data suggest that, although genetic effects on bone loss with aging are less pronounced than on peak bone mass, they still account for similar to 40% of the between-individual variation in bone loss for the lumbar spine, total forearm, and whole body in peri- and postmenopausal women. These findings are relevant for studies aimed at identification of genes that are involved in the regulation of bone loss

High osteoporotic fracture risk and CVD risk co-exist in postmenopausal women

Introduction: Osteoporosis related risk factors such as BMD have been associated with cardiovascular endpoints in previous studies but there have been no studies of integrated risk using risk factor algorithms. Methods: A sample of 358 peri- and postmenopausal women, mean age 59.3 (range 45-74) years were studied. Each individual had bone mineral density (BMD) measurements by dual energy X-ray absorptiometiy. Fracture risk was assessed using the WHO FRAX algorithm and cardiovascular disease (CVD) risk using the Framingham Risk Tool. Results: Women with higher 10 year risk of major osteoporotic had significantly higher cardiovascular risk (4.634% vs 8.36%, p=0.001). In multiple regression analysis, 5-year CVD risk was significantly associated with the 10-year risk of having major osteoporotic (beta=0.095, p=0.001) and hip (beta=0.055, p=0.001) fracture. Women with the highest CVD risk were 5.4 times more likely to have higher risk of major osteoporotic fracture. Conclusions: Fracture risk, determined by using a multiple risk factor algorithm such as FRAX, was positively associated with higher cardiovascular risk determined by using the Framingham Risk Tool. Awareness regarding these concurrent risk factors needs to be raised so that appropriate risk reduction can be implemented. (C) 2012 Elsevier Inc. All rights reserved

Serum uric acid plays a protective role for bone loss in peri- and postmenopausal women: A longitudinal study

Objective: Oxidative stress has been linked to osteoporosis. Serum uric acid (UA), a strong endogenous antioxidant, has been associated with higher bone mineral density (BMD), lower bone turnover and lower prevalence of fractures in a large cross-sectional study of men. Whether this relationship is present in women and how UA relates to changes in BMD longitudinally has not been examined. Methods: A sample of 356 peri- and postmenopausal women, mean age 60.5 years was studied. Each individual had baseline BMD and body composition measurements by dual energy x-ray absorptiometry (DXA) and at least one repeat measure, on average 9.7 years later. Annual rate of change in BMD (A%Delta BMD) was calculated. UA was measured at each DXA visit. Calciotropic hormones and bone turnover markers were measured at the final visit only. Results: Cross-sectional data analyses revealed that women with higher UA levels had significantly higher absolute BMD measures at all skeletal sites. These women also had higher measures of body weight and its components such as lean mass (LM) and fat mass (FM). Results of multiple regression analyses showed a positive association between UA and BMD that remained significant even after accounting for possible confounders including LM and FM. Regression analyses of the longitudinal BMD data demonstrated significant associations between serum UA levels and annual rates of change in BMD at all skeletal sites. After adjustment associations remained significant for lumbar spine, forearm and whole body BMD but not for hip BMD. Conclusion: Higher serum UA levels appear to be protective for bone loss in peri- and postmenopausal women and this relationship is not affected by changes in body composition measures

How is symptom flare defined in musculoskeletal conditions: a systematic review

To systematically review the definitions for "flare" in musculoskeletal conditions, the derivation processes, and validation of definitions for the 12 most burdensome musculoskeletal conditions.A literature search was conducted in MEDLINE, EMBASE, CINAHL, AMED, PsycInfo and Lilacs to identify studies that investigated derivation or validation of a flare definition, which we considered as a phrase or group of domains.Reports of derivation of flare definitions were identified for 9/12 musculoskeletal conditions. Validation of flare definitions was initiated for 4/12. For each condition, different derivation and validation methods have been used, with variable levels of consumer involvement, and in some cases different groups have worked on the process in parallel. Although some flare definitions began simply as "symptom worsening" or "change in treatment", most evolved into multidimensional definitions that include: pain, impact on function, joint symptoms, and emotional elements. Frequently initial attempts to create phrase to define the term flare evolved into consensus on the breadth of domains involved. Validation has compared flare definitions/domains against measures of disease activity, clinicians' diagnosis, response to drug therapy, or a combination.This review suggests that greater characterisation and definition of flares in musculoskeletal conditions are linked to the inclusion of multiple perspectives, multifaceted domains and compound comparators for their validation. Further work is required to optimise and test the derived definitions for most musculoskeletal conditions. As some elements are disease-specific, flare definitions cannot be extrapolated to other conditions. Research regarding flare in back pain (most burdensome disease) is limited

Genetic Effects on Bone Loss in Peri- and Postmenopausal Women: A Longitudinal Twin Study

This longitudinal twin study was designed to assess the heritability of bone loss in peri- and postmenopausal women. A sample of 724 female twins was studied. Baseline and repeat BMD measurements were performed. Results of genetic model-fitting analysis indicated genetic effects on bone loss account for similar to 40% of the between-individual variation in bone loss at the lumbar spine, forearm, and whole body. Introduction: BMD and bone loss are important predictors of fracture risk. Although the heritability of peak BMD is well documented, it is not clear whether bone loss is also under genetic regulation. This study was designed to assess the heritability of bone loss in peri- and postmenopausal women. Materials and Methods: A sample of 724 female twins (177 monozygotic [MZ] and 185 dizygotic [DZ] pairs), 45-82 yr of age, was studied. Each individual had baseline BMD measurements at the lumbar spine, hip, forearm, and total body by DXA and at least one repeat measure, on average 4.9 yr later. Change in BMD (Delta BMD) was expressed as percent of gain or loss per year. Intraclass correlation coefficients for ABMD were calculated for MZ and DZ pairs. Genetic model-fitting analysis was conducted to partition the total variance of ABMD into three components: genetic (G), common environment (C), and specific environment, including measurement error (E). The index of heritability was estimated as the ratio of genetic variance over total variance. Results: The mean annual Delta BMD was -0.37 +/- 1.43% (SD) per year at the lumbar spine, -0.27 +/- 1.32% at the total hip, -0.77 +/- 1.66% at the total forearm, -0.36 +/- 56% at the femoral neck, and -0.16 +/- 0.81% at the whole body. Intraclass correlation coefficients were significantly higher in MZ than in DZ twins for all studied parameters, except at the hip sites. Results of genetic model-fitting analysis indicated that the indices of heritability for ABMD were 0.38, 0.49, and 0.44 for the lumbar spine, total forearm, and whole body, respectively. However, the genetic effect on ABMD at all hip sites was not significant. Conclusions: These data suggest that, although genetic effects on bone loss with aging are less pronounced than on peak bone mass, they still account for similar to 40% of the between-individual variation in bone loss for the lumbar spine, total forearm, and whole body in peri- and postmenopausal women. These findings are relevant for studies aimed at identification of genes that are involved in the regulation of bone loss

A definition of flare in low back pain (LBP): A multiphase process involving perspectives of individuals with LBP and expert consensus

Low back pain (LBP) varies over time. Consumers, clinicians and researchers use various terms to describe fluctuations of LBP symptoms. Although "flare" is commonly used to describe symptom fluctuation, there is no consensus on how it is defined. This study aimed to obtain consensus for a LBP flare definition using a mixed-method approach. Step 1 involved derivation of a preliminary candidate flare definition based on thematic analysis of consumers' views in consultation with an expert consumer writer. In Step 2, a workshop was conducted to incorporate perspectives of LBP experts into the preliminary flare definition, which resulted in two alternative LBP flare definitions. Step 3 refined the definition using a two-round Delphi consensus process with experts in musculoskeletal conditions. The definition favoured by experts was further tested with individuals with LBP in Step 4, using the definition in three scenarios. This multiphase study produced a LBP flare definition that distinguishes it from other LBP fluctuations, represents views of consumers, involves expert consensus, and is understandable by consumers in clinical and research contexts: "A flare-up is a worsening of your condition that lasts from hours to weeks that is difficult to tolerate and generally impacts your usual activities and/or emotions". Perspective: A multiphase processes produced a low back pain (LBP) flare definition that distinguishes it from other LBP fluctuations, involves expert consensus and represents consumers' views

Genome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55–85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or −4.0 to −1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD–associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies

Gender differences in relationships between body composition components, their distribution and bone mineral density: a cross-sectional opposite sex twin study

Numerous studies indicate that bone mineral density (BMD) is closely related to body mass and its components. Most studies have examined these relationships in women with little attention given to how these relationships differ by gender. The aims of the present study were to use the opposite sex twin model to determine if there were gender differences in the relationship between body composition and its relation to BMD and how any such differences were influenced by age. We measured body composition and bone mass by dual energy X-ray absorptiometry in 93 pairs of opposite sex twins. To examine the effect of age, they were divided into two age groups: under 50 years old (45 pairs) and over 50 years old (48 pairs). Lean mass (LM) had stronger positive relationships with the most bone variables than fat mass in both genders at all ages. Fat mass (FM) had positive relationships with total body and hip BMD in women under age 50, but not over 50. There was no significant relationship between FM and total or regional BMD in men under age 50, but men over 50 showed positive relationships between FM measures and total and some regional BMD measures. Central adiposity showed a positive relationship with BMD in men over 50 and women under 50. Fat mass (FM) and lean mass (LM) and their distribution in the body have different relationships with regional BMD in men and women that differ by age