Higher Areal Bone Mineral Density Research Articles

Deciphering the complex relationship between type 2 diabetes and fracture risk with both genetic and observational evidence.

The 'diabetic bone paradox' suggested that type 2 diabetes (T2D) patients would have higher areal bone mineral density (BMD) but higher fracture risk than individuals without T2D. In this study, we found that the genetically predicted T2D was associated with higher BMD and lower risk of fracture in both weighted genetic risk score (wGRS) and two-sample Mendelian randomization (MR) analyses. We also identified ten genomic loci shared between T2D and fracture, with the top signal at SNP rs4580892 in the intron of gene RSPO3. And the higher expression in adipose subcutaneous and higher protein level in plasma of RSPO3 were associated with increased risk of T2D, but decreased risk of fracture. In the prospective study, T2D was observed to be associated with higher risk of fracture, but BMI mediated 30.2% of the protective effect. However, when stratified by the T2D-related risk factors for fracture, we observed that the effect of T2D on the risk of fracture decreased when the number of T2D-related risk factors decreased, and the association became non-significant if the T2D patients carried none of the risk factors. In conclusion, the genetically determined T2D might not be associated with higher risk of fracture. And the shared genetic architecture between T2D and fracture suggested a top signal around RSPO3 gene. The observed effect size of T2D on fracture risk decreased if the T2D-related risk factors could be eliminated. Therefore, it is important to manage the complications of T2D to prevent the risk of fracture.

Deciphering the complex relationship between type 2 diabetes and fracture risk with both genetic and observational evidence

The ‘diabetic bone paradox’ suggested that type 2 diabetes (T2D) patients would have higher areal bone mineral density (BMD) but higher fracture risk than individuals without T2D. In this study, we found that the genetically predicted T2D was associated with higher BMD and lower risk of fracture in both weighted genetic risk score (wGRS) and two-sample Mendelian randomization (MR) analyses. We also identified ten genomic loci shared between T2D and fracture, with the top signal at SNP rs4580892 in the intron of gene RSPO3. And the higher expression in adipose subcutaneous and higher protein level in plasma of RSPO3 were associated with increased risk of T2D, but decreased risk of fracture. In the prospective study, T2D was observed to be associated with higher risk of fracture, but BMI mediated 30.2% of the protective effect. However, when stratified by the T2D-related risk factors for fracture, we observed that the effect of T2D on the risk of fracture decreased when the number of T2D-related risk factors decreased, and the association became non-significant if the T2D patients carried none of the risk factors. In conclusion, the genetically determined T2D might not be associated with higher risk of fracture. And the shared genetic architecture between T2D and fracture suggested a top signal around RSPO3 gene. The observed effect size of T2D on fracture risk decreased if the T2D-related risk factors could be eliminated. Therefore, it is important to manage the complications of T2D to prevent the risk of fracture.

Dairy food intake is not associated with spinal trabecular bone score in men and women: the Framingham Osteoporosis Study

BackgroundPrevious studies reported that dairy foods are associated with higher areal bone mineral density (BMD) in older adults. However, data on bone texture are lacking. We determined the association of dairy food intake (milk, yogurt, cheese, milk + yogurt and milk + yogurt + cheese) with spinal trabecular bone score (TBS).MethodsIn this cross-sectional study, a validated semi-quantitative food frequency questionnaire was used to assess dairy food intake (servings/wk). TBS, an analysis of bone texture, was calculated from dual energy X-ray absorptiometry (DXA) scans. Sex-specific multivariable linear regression was used to estimate the association of dairy food intake (energy adjusted via residual methods) with each bone measure adjusting for covariates.ResultsMean age of 4,740 participants was 49 (SD: 13) years and mean milk + yogurt + cheese intake was 10.1 (SD: 8.4) servings/week in men and 10.9 (SD: 8.0) servings/week in women. There were no associations between dairy food intake and spinal TBS in adjusted models.ConclusionsIn this cohort of primarily healthy adults, dairy intake was not associated with bone texture.

Hyperglycemia Is Not Associated With Higher Volumetric BMD in a Chinese Health Check-up Cohort.

Background and PurposeType 2 diabetes mellitus patients have an increased fracture risk despite having higher areal bone mineral density (aBMD) measured by DXA. This apparent paradox might be explained by the overestimation of BMD by DXA due to the higher fat mass in type 2 diabetes mellitus patients. Volumetric BMD (vBMD) as assessed by quantitative CT (QCT) is not influenced by fat mass. We assessed the association of vBMD and fasting plasma glucose in a large cohort of Chinese subjects and compared the vBMD in healthy and diabetic subjects. In addition, we compared the relation between aBMD, vBMD, glucose and fat mass in a subset of this cohort.Materials and Methods10309 participants from the China Biobank project underwent QCT based on chest low dose CT to compute vBMD of L1 and L2 vertebrae and FPG measurements between 2018 and 2019. Among them, 1037 subjects also had spine DXA scans. Data was analyzed using linear regression models.ResultsIn the total cohort (5889 men and 4420 women, mean age 53 years, range 30-96), there was no significant association between vBMD and FPG after adjustment for age (women: p=0.774; men: p=0.149). 291 women and 606 men fitted the diagnostic criteria of diabetes. Both women and men with diabetes had lower vBMD compared to non-diabetic subjects, but this became non-significant after adjusting for age in the total cohort (women: p=0.817; men: p=0.288) and after propensity score matching based on age (women: p=0.678; men: p=0.135). In the DXA subcohort, aBMD was significantly higher in men with diabetes after adjusting for age and this difference disappeared after further adjusting for total fat area (p=0.064).ConclusionWe did not find any effect of fasting plasma glucose or diabetes on the volumetric BMD measured with QCT after adjustment for age. Therefore, vBMD measured with QCT might be a more reliable measurement to diagnose osteoporosis and assess fracture risk than aBMD measured with DXA in diabetic patients.

Is it important to achieve physical activity recommendations at early stages of life to improve bone health?

SummaryResearch in bone health during childhood is limited and important to prevent future diseases, particularly, osteoporosis. Bone parameters using DXA and pQCT in 295 Spanish children were evaluated and we found a benefit of meeting the World Health Organization physical activity recommendations in bone composition in childhood.PurposeTo investigate the association between physical activity (PA) and bone health in a Spanish paediatric cohort, considering the influence of meeting/not meeting the current World Health Organization (WHO) PA recommendations and to elucidate if there are differences between boys and girls.MethodsIn a cohort of children born in the region of Aragon (Spain) in 2009, followed until the age of 7 years, bone parameters were assessed using dual-energy X-ray absorptiometry (DXA) (whole body scan) and peripheral quantitative computed tomography (pQCT) (tibia scanned at the 8% (distal) and 38% (diaphyseal) of the total tibia length) in 295 7-year-old children (154 boys) in the last evaluation performed between 2016 and 2017. PA was assessed using GT3X Actigraph accelerometers.ResultsBoys had significantly higher areal bone mineral density (aBMD), higher total bone mineral content (BMC) at the diaphyseal site and higher trabecular BMC and vBMD, and higher total bone area at the distal site than girls (p<0.01 for all of them). Both boys and girls complying with the WHO PA recommendations had significantly higher trabecular BMC than their inactive counterparts.ConclusionsMeeting WHO PA recommendations has a beneficial effect in bone composition in childhood both in boys and in girls.

Dairy Food Intake Is Not Associated with Measures of Bone Microarchitecture in Men and Women: The Framingham Osteoporosis Study.

Previous studies reported that dairy foods are associated with higher areal bone mineral density (BMD) in older adults. However, data on bone strength and bone microarchitecture are lacking. We determined the association of dairy food intake (milk, yogurt, cheese, milk + yogurt, and milk + yogurt + cheese, servings/week) with high resolution peripheral quantitative computed tomography (HR-pQCT) measures of bone (failure load, cortical BMD, cortical thickness, trabecular BMD, and trabecular number). This cross-sectional study included participants with diet from a food frequency questionnaire (in 2005–2008 and/or 1998–2001) and measurements of cortical and trabecular BMD and microarchitecture at the distal tibia and radius (from HR-pQCT in 2012–2015). Sex-specific multivariable linear regression estimated the association of dairy food intake (energy adjusted) with each bone measure adjusting for covariates. Mean age was 64 (SD 8) years and total milk + yogurt + cheese intake was 10.0 (SD 6.6) and 10.6 (6.4) servings/week in men and women, respectively. No significant associations were observed for any of the dairy foods and bone microarchitecture measures except for cheese intake, which was inversely associated with cortical BMD at the radius (p = 0.001) and tibia (p = 0.002) in women alone. In this cohort of primarily healthy older men and women, dairy intake was not associated with bone microarchitecture. The findings related to cheese intake and bone microarchitecture in women warrant further investigation.

Relationship Between Serum Estradiol Concentrations and Clinical Outcomes in Transgender Individuals Undergoing Feminizing Hormone Therapy: A Narrative Review.

Transgender, including gender diverse and nonbinary, individuals are treated with estradiol with or without antiandrogen to align their physical appearance with their gender identity, improve mental health and quality of life. Consensus guidelines give target ranges for serum estradiol concentration based on premenopausal female reference ranges. However, limited studies have evaluated the relationship between serum estradiol concentrations and clinical outcomes in transgender individuals undergoing feminizing hormone therapy. The available evidence has not found that higher serum estradiol concentrations, together with suppressed testosterone, enhance breast development, or produce more feminine changes to body composition. However, ensuring testosterone suppression appears to be an important factor to maximize these physical changes. Higher serum estradiol concentrations have been associated with higher areal bone mineral density. Although the resultant long-term clinical implications are yet to be determined, this could be a consideration for individuals with low bone mass. The precise serum estradiol concentration that results in adequate feminization without increasing the risk of complications (thromboembolic disease, cholelithiasis) remains unknown. Further prospective trials are required.

Oxytocin and bone quality in the femoral neck of rats in periestropause

The objective of this study is to identify whether oxytocin (OT) contributes to the reduction of osteopenia in the femoral neck of rats in periestropause. Animals in irregular estrous cycles received two NaCl injections (0.15 mol/L) or OT (134 μg/kg) over a 12-h interval, and after thirty-five days without treatments, the biological sample collection was performed. The oxytocin group (Ot) demonstrated the highest enzymatic activity of alkaline phosphatase (p = 0.0138), lowest enzymatic activity of tartrate-resistant acid phosphatase (p = 0.0045), higher percentage of compact bone (p = 0.0359), cortical expression of runt-related transcription factor 2 (p = 0.0101), osterix (p = 0.0101), bone morphogenetic protein-2/4 (p = 0.0101) and periostin (p = 0.0455). Furthermore, the mineral-to-matrix ratio (ν1PO4/Proline) was higher and type-B carbonate substitution (CO3/ν1PO4) was lower (p = 0.0008 and 0.0303) in Ot group. The Ot showed higher areal bone mineral density (p = 0.0050), cortical bone area (p = 0.0416), polar moment of inertia, maximum, minimum (p = 0.0480, 0.0480, 0.0035), bone volume fraction (p = 0.0166), connectivity density (p < 0.0001), maximal load (p = 0.0003) and bone stiffness (p = 0.0145). In Ot percentage of cortical pores (p = 0.0102) and trabecular number (p = 0.0088) was lower. The results evidence action of OT in the reduction of osteopenia, suggesting that it is a promising anabolic strategy for the prevention of primary osteoporosis during the periestropause period.

Examining Bone, Muscle and Fat in Middle-Aged Long-Term Endurance Runners: A Cross-Sectional Study.

Aerobic exercise training has many known cardiovascular benefits that may promote healthy aging. It is not known if long-term aerobic exercise training is also associated with structural benefits (e.g., lower fat mass, higher areal bone mineral density (BMD) and greater muscle mass). We evaluated these parameters in middle-aged long-term endurance runners compared to sex-, age-, height-, and weight-matched non-running controls. Total and regional lean and fat mass and areal BMD were assessed by dual-energy X-ray absorptiometry. Sagittal magnetic resonance images captured the cross-sectional area and thickness of the lumbar multifidus. Runners (n = 10; all male) had a mean (standard deviation; SD) age of 49 (4) years, height of 178.9 (4.9) cm, weight of 67.8 (5.8) kg, body mass index (BMI) of 21.4 (1.4) kg/m2 and had been running 82.6 (27.9) km/week for 23 (13) years. Controls (n = 9) had a mean (SD) age of 51 (5) years, height of 176.0 (5.1) cm, weight of 72.8 (7.1) kg, and BMI of 23.7 (2.1) kg/m2. BMI was greater in controls (p = 0.010). When compared to controls on average, runners had a 10 percentage-point greater total body lean mass than controls (p = 0.001) and 14% greater trunk lean mass (p = 0.010), as well as less total body (8.6 kg; p < 0.001), arm (58%; p = 0.002), leg (52%; p < 0.001), trunk (73%; p < 0.001), android (91%; p < 0.001), and gynoid fat mass (64%; p < 0.001). No differences were observed between groups for BMD outcomes or multifidus size. These results underscore the benefits of endurance running to body composition that carry over to middle-age.

Association of Dairy Food Intake with Measures of Bone Microarchitecture in Men and Women from the Framingham Study (OR18-08-19)

ObjectivesPrevious studies reported that dairy foods are associated with higher areal bone mineral density (BMD) in older adults. However, data on bone strength and bone microarchitecture are lacking. The objective of this study was to determine the association of milk, yogurt, cheese, cream, milk + yogurt and milk + yogurt + cheese intakes with high resolution peripheral quantitative computed tomography (HR-pQCT) measures of bone in older adults from the Framingham Offspring study. MethodsThis cross-sectional study included 532 men and 694 women (aged 32–81y, mean 64y) with measures of dairy food intake (servings/wk.) from a food frequency questionnaire. Cortical and trabecular BMD and microarchitecture at the distal tibia and radius were measured using HR-pQCT. We focused on five bone parameters: 1) Bone strength assessed via failure load from micro–finite element analysis, 2) Two cortical bone measures: cortical BMD and cortical thickness; and 3) Two trabecular bone measures: trabecular bone density and trabecular number. Sex-combined and sex-specific multivariable linear regression was used to estimate the association of dairy food intake (energy adjusted) with each bone measure adjusting for covariates (sex, age, height, weight, current smoking, energy intake, calcium supplement use, vitamin D supplement use, physical activity and multivitamin use). ResultsOver 90% of the participants consumed the recommended ≥ 3 servings of dairy per day. Mean milk intake ± SD was 5.5 servings/week in both men and women. In sex combined analyses, only cheese intake was associated with cortical BMD at the radius and tibia (Table). None of the other dairy foods were significantly associated with any of the bone measures. In sex-stratified analysis higher cheese intake was associated with lower cortical BMD at the radius and tibia in women alone (radius: β = –9.61 ± 2.73, P = 0.001, tibia: β = –9.41 ± 3.10, P = 0.001). In men, higher cream intake was associated with higher trabecular number (radius: β = 0.021 ± 0.011, P = 0.02, tibia: β = 0.024 ± 0.012, P = 0.05). Higher yogurt intake was also associated with higher trabecular volumetric BMD at the tibia in men alone (tibia: β = 4.86 ± 2.00, P = 0.02). ConclusionsIn this cohort of primarily healthy older men and women with high dairy food consumption, specific dairy foods seem to be more beneficial in men than women. Negative associations for cheese intake and cortical BMD in women should be further confirmed in longitudinal studies. Funding SourcesNIH AR # 053205; FHS N01-HC-25195 R01 AR/AG 41398 and unrestricted institutional research grant from Dairy Management Inc. Supporting Tables, Images and/or Graphs▪

SAT-273 Suboptimal Bone Adaptation to Increasing Body Weight in Adolescents across the Nutritional Spectrum of Anorexia Nervosa, Normal Weight, and Obesity

Despite their higher areal bone mineral density (aBMD), adolescents with obesity (OB) have an increase in fracture risk, particularly of the extremities, compared with normal-weight controls (C). Whereas bone parameters that increase fracture risk are well characterized at the other end of nutritional spectrum in anorexia nervosa (AN), these data are lacking in adolescents with obesity. Our objective was to compare bone geometry, microarchitecture, density and strength estimates in adolescents across the nutritional spectrum, to determine whether suboptimal bone adaptation to increased body weight may explain the increased fracture risk in OB. We assessed bone endpoints in 153 adolescents 14-21 years old: 50 OB, 48 C and 55 AN. We used DXA to assess aBMD at the lumbar spine, proximal femur and whole body, high resolution peripheral quantitative CT (HRpQCT) to assess bone geometry, microarchitecture and volumetric BMD (vBMD), and finite element analysis to assess failure load (a strength estimate) at the distal radius and tibia. All HRpQCT and FEA analyses were controlled for age. Groups did not differ for age or height. Per design, weight and BMI were highest in OB and lowest in AN. Areal BMD Z-scores at all sites were highest in OB, intermediate in C and lowest in AN (p<0.03 for all comparisons). At the radius, cortical area and thickness increased progressively from AN to C to OB (p<0.03) while trabecular area did not differ across groups. Compared to C and AN, OB had higher cortical porosity (p<0.03), trabecular number and thickness (p<0.01). Cortical vBMD did not differ in OB vs. C but was lower in AN (p<0.0001). Trabecular and total vBMD increased progressively from AN to C to OB (p<0.04). Of note, plate BV/TV did not differ in OB vs. C, but was lower in AN (p<0.0001); rod BV/TV was higher in OB vs. C and AN (p <0.002). At the tibia, cortical area and thickness increased progressively from AN to C to OB (p<0.002), while trabecular area was higher in OB vs. AN and C (p<0.004). Compared to C and AN, OB had higher cortical porosity (p<0.007) and lower trabecular thickness (p<0.02). Trabecular number increased progressively from AN to C to OB (p<0.02). Cortical vBMD did not differ in OB vs. C but was lower in AN (p<0.02). Trabecular and total vBMD were higher in OB vs. AN and C (p<0.002). Plate BV/TV was comparable in the three groups but rod BV/TV was higher in OB vs. C and AN (p<0.0001). Finally, failure load (a strength estimate) increased from AN to C to OB for the radius and tibia (p<0.04 for all). However, after adjusting for weight, failure load was lower in OB vs. C at both sites (p<0.05), and did not differ from AN. These data demonstrate that not all bone parameters appropriately adapt to an increase in body weight, with cortical porosity, cortical vBMD, and plate BV/TV at the radius and tibia, and tibial trabecular thickness being particularly at risk. These changes may explain the higher risk for fracture in OB than controls.

Higher Dairy Food Intake Is Associated With Higher Spine Quantitative Computed Tomography (QCT) Bone Measures in the Framingham Study for Men But Not Women.

Previous studies found that dairy foods were associated with higher areal bone mineral density (BMD). However, data on bone geometry or compartment-specific bone density is lacking. In this cross-sectional study, the association of milk, yogurt, cheese, cream, milk+yogurt, and milk+yogurt+cheese intakes with quantitative computed tomography (QCT) measures of bone were examined, and we determined if associations were modified by serum vitamin D (25-OH D, tertiles) or age (<50 versus ≥50 years). Participants were 1522 men and 1104 women (aged 32 to 81 years, mean 50 years [men]; 55 years [women]) from the Framingham Heart Study with measures of dairy food intake (servings/wk) from a food-frequency questionnaire, volumetric BMD (vBMD, integral and trabecular, g/cm3 ), cross-sectional area (CSA, cm2 ), and estimated vertebral compressive strength (VCS, N) and 25-OH D (radioimmunoassay). Sex-specific multivariable linear regression was used to calculate the association of dairy food intake (energy adjusted) with each QCT measure, adjusting for covariates. Mean milk intake ±SD was 6 ± 7 servings/week in both men and women. In men, higher intake of milk, milk+yogurt, and milk+yogurt+cheese was associated with higher integral (p = 0.001 to 0.006) and trabecular vBMD (p = 0.006 to 0.057) and VCS (p = 0.001 to 0.010). Further, a higher cheese intake was related with higher CSA (p = 0.049). In women, no significant results were observed for the dairy foods, except for a positive association of cream intake with CSA (p = 0.016). The associations appeared to be stronger in older men. Across 25-OH D tertiles, dairy was positively associated with bone health. In summary, men with higher intakes of milk, milk+yogurt, and milk+yogurt+cheese had higher trabecular and integral vBMD and VCS but not CSA. Dairy intake seems to be most beneficial for older men, and dairy continued to have positive associations among all 25-OH D levels. © 2018 American Society for Bone and Mineral Research.

Longitudinal Growth and pQCT Measures in Hutterite Children and Grandchildren Are Associated With Prevalence of Hip or Knee Replacement Resulting From Osteoarthritis in Parents and Grandparents.

BackgroundOsteoarthritis (OA) is one of the leading causes of disability in the world. Several genes are associated with the development of OA, and previous studies have shown adult children of individuals with OA have higher areal bone mineral density (BMD). Because childhood is an important period of growth and bone development, and body composition is known to be associated with BMD, we speculated that there may be differences in growth and bone measures among young children with a genetic predisposition to OA.Questions/purposes(1) Do differences exist at baseline in anthropometric and peripheral quantitative CT (pQCT) measurements between children and grandchildren of individuals with OA and controls? (2) Do children and grandchildren of individuals with OA accrue bone longitudinally at a different rate than controls?MethodsLongitudinal anthropometric (height, weight) and bone (cortical and trabecular volumetric BMD and cross-sectional area) measurements by pQCT were obtained at baseline and 18 and 36 months on children (n = 178) and grandchildren (n = 230) of 23 individuals with hip or knee arthroplasty resulting from OA and 23 sex-matched controls (16 females each). Grandchildren (age, 8–30 years) were further categorized as growing (premenarcheal or male < 14 years, n = 99) or mature (≥ 2 years postmenarchal or males ≥ 18 years, n = 96). The remaining 35 grandchildren could not be categorized and were excluded.ResultsMature granddaughters and grandsons of individuals with OA had greater trabecular volumetric BMD than controls (236 ± 24 and 222 ± 26 mg/cm3, respectively, for granddaughters, difference of 14 [95% confidence interval {CI}, 1-28] mg/cm3, p = 0.041 and 270 ± 22 and 248 ± 30 mg/cm3, respectively, for grandsons, difference of 22 [95% CI, 1-42] mg/cm3, p = 0.040). Greater trabecular volumetric BMD was observed in daughters of individuals with OA compared with daughters of controls (228 ± 28 and 212 ± 33 mg/cm3, respectively, difference of 18 [95% CI, 3-30] mg/cm3, respectively [p = 0.021]). Growing granddaughters and grandsons of controls had greater decreases in cortical volumetric BMD than grandchildren of individuals with OA (time-by-group [T*G] based on mixed model [± standard error] -9.7 ± 4.3 versus -0.8 ± 4.4 mg/cm3/year, respectively, for granddaughters, difference of 9.0 [95% CI, 2.4-15.5] mg/cm3/year, p = 0.007 and -6.8 ± 3.3 versus 4.5 ± 3.4 mg/cm3/year, respectively, for grandsons, difference of 11.3 [95% CI, 4.3-18.3] mg/cm3/year, p = 0.002). Cortical volumetric BMD was maintained in sons of individuals with OA, but decreased in sons of controls (-0.0 ± 1.5 versus -4.3 ± 1.0 mg/cm3/year, respectively, difference of 4.3 [95% CI, 0.7-7.8] mg/cm3/year, p = 0.019 [T*G]). There was a greater apparent decrease in cross-sectional area among daughters of individuals with OA than in controls (-4.6 ± 0.9 versus -1.7 ± 0.9 mm2/year, respectively, difference of -2.9 [95% CI, -5.3 to -0.6] mm2/year, p = 0.015 [T*G]).ConclusionsSeveral anthropometric and bone differences exist between children and grandchildren of individuals with OA and controls. If these differences are confirmed in additional studies, it would be important to identify the mechanism so that preventive measures could be developed and implemented to slow or reduce OA development.Clinical RelevanceDifferences in growth and bone development may lead to increased loads on cartilage that may predispose offspring to the development of OA. If these differences are confirmed in additional studies, it would be important to identify the mechanism so that preventive measures could be developed and implemented to slow or reduce OA development.

Bone mineral density at the hip and its relation to fat mass and lean mass in adolescents: the Troms\xf8 Study, Fit Futures

BackgroundPositive association between body weight and bone mass is well established, and the concept of body mass index (BMI) is associated with higher areal bone mineral density (aBMD) and reduced fracture risk. BMI, that comprises both fat mass (FM) and lean mass (LM) may contribute to peak bone mass achievement in different ways. This study explored the influence of body composition in terms of total body LM and FM on hip aBMD-values in adolescence.MethodsIn 2010/2011, 93% of the region’s first-year upper-secondary school students (15–17 years old) in Tromsø, Norway attended the Tromsø Study, Fit Futures. Areal BMD at femoral neck (aBMDFN) and total hip (aBMDTH) (g/cm2), total body LM and FM (g) were measured by dual energy X-ray absorptiometry (DXA). Height and weight were measured, and BMI calculated. Lifestyle variables were collected by self-administered questionnaires and interviews, including questions on time spent on leisure time physical activity. Stratified analyses of covariance and regression models included 395 girls and 363 boys. Crude results were adjusted for age, height, sexual maturation, physical activity levels, vitamin D levels, calcium intake, alcohol consumption and smoking habits.ResultsUnadjusted distribution indicated higher aBMD-levels at higher LM-levels in both genders (p < 0.001), but higher aBMD at higher FM-levels were found only in girls (p < 0.018). After multiple adjustments, aBMDFN-levels in girls were associated by 0.053 g/cm2 and 0.032 g/cm2 per standard deviation (SD) change in LM and FM (p < 0.001). Corresponding values in boys were 0.072 and 0.025 (p < 0.001). The high LM groups accounted for the highest aBMD-levels, while aBMD-levels at the LM/FM-combinations indicated different patterns in girls compared to boys. The adjusted odds ratio (95% CI) for low levels of aBMDFN was 6.6 (3.4,13.0) in boys, compared to 2.8 (1.6,4.9) in girls per SD lower LM.ConclusionsLM and FM should be regarded as strong predictors for bone mass and hence bone strength in adolescents. A gender specific difference indicated that high lean mass is of crucial importance prominently in boys. In adolescents with low lean mass, especially in girls, high fat mass may partially ameliorate the effect of deficient lean mass levels.

Hyperglycemia is associated with increased bone mineral density and decreased trabecular bone score in elderly Japanese men: The Fujiwara-kyo osteoporosis risk in men (FORMEN) study

PurposePatients with type 2 diabetes mellitus (T2DM) have an increased fracture risk despite having higher areal bone mineral density (aBMD). This study aimed to clarify the association between glycemic and insulin resistance status and bone microarchitecture, and whether pentosidine and bone turnover markers play any roles in the association. MethodsA total of 2012 community-dwelling men aged ≥65years completed baseline measurements of spine aBMD, fasting plasma glucose (FPG) and serum insulin, hemoglobin A1c (HbA1c), osteocalcin, type I procollagen N-terminal propeptide, type I collagen C-terminal crosslinking telopeptide, tartrate-resistant acid phosphatase isoenzyme 5b, pentosidine, height and weight and an interview regarding past disease history. Homeostasis model assessment-insulin resistance (HOMA-IR) was also calculated. T2DM was defined as physician-diagnosed middle age or elderly-onset diabetes mellitus, or according to biochemical test results. To evaluate bone microarchitecture, trabecular bone score (TBS) was calculated at the same vertebrae as those used for aBMD measurement. ResultsAfter excluding participants who had a disease history and/or were taking medications affecting bone metabolism, 1683 men (age, 72.9±5.2years) were analyzed. Men with T2DM had significantly higher aBMD compared to those without T2DM. There was no significant difference in TBS. However, FPG, HbA1c and HOMA-IR levels were significantly inversely correlated with TBS after adjusting for age, BMI and aBMD. Multivariate linear regression analyses revealed that glycemic indices (FPG and HbA1c) were significantly associated with increased aBMD and decreased TBS, and that HOMA-IR was associated only with TBS. These associations did not change after further adjusting for bone turnover makers and pentosidine levels. ConclusionsHyperglycemia and elevated insulin-resistance were associated with low TBS independently of bone turnover and pentosidine levels.

Subregional DXA-Derived Vertebral Bone Mineral Measures are Stronger Predictors of Failure Load in Specimens with Lower Areal Bone Mineral Density, Compared to Those with Higher Areal Bone Mineral Density

Measurement of areal bone mineral density (aBMD) in intravertebral subregions may increase the diagnostic sensitivity of dual-energy X-ray absorptiometry (DXA)-derived parameters for vertebral fragility. This study investigated whether DXA-derived bone parameters in vertebral subregions were better predictors of vertebral bone strength in specimens with low aBMD, compared to those with higher aBMD. Twenty-five lumbar vertebrae (15 embalmed and 10 fresh-frozen) were scanned with posteroanterior- (PA) and lateral-projection DXA, and then mechanically tested in compression to ultimate failure. Whole-vertebral aBMD and bone mineral content (BMC) were measured from the PA- and lateral-projection scans and within 6 intravertebral subregions. Multivariate regression was used to predict ultimate failure load by BMC, adjusted for vertebral size and specimen fixation status across the whole specimen set, and when subgrouped into specimens with low aBMD and high aBMD. Adjusted BMC explained a substantial proportion of variance in ultimate vertebral load, when measured over the whole vertebral area in lateral projection (adjusted R (2) 0.84) and across the six subregions (ROIs 2-7) (adjusted R (2) range 0.58-0.78). The association between adjusted BMC, either measured subregionally or across the whole vertebral area, and vertebral failure load, was increased for the subgroup of specimens with identified 'low aBMD', compared to those with 'high aBMD', particularly in the anterior subregion where the adjusted R (2) differed by 0.44. The relative contribution of BMC measured in vertebral subregions to ultimate failure load is greater among specimens with lower aBMD, compared to those with higher aBMD, particularly in the anterior subregion of the vertebral body.

Sport-specific association between exercise loading and the density, geometry, and microstructure of weight-bearing bone in young adult men

SummaryIn this population-based study of 24-year-old men, we have investigated the association between sport-specific exercise loading and different bone parameters. We reveal that the association between exercise loading and bone parameters is sport-specific, indicating that nonspecific resistance exercise does not impact bone density, geometry, or microstructure in young men.IntroductionIn this cross-sectional study, the association between nonspecific resistive exercise and areal and volumetric bone density, bone geometry, or bone microstructure was investigated in young adult men.MethodsA total of 184 male athletes, 24.0 ± 0.6 years of age (mean ± SD), representing nonspecific resistive exercise and soccer (proportion of recreational athletes, 93.4 and 7.7 %, respectively), and 177 nonathletic age-matched controls were measured with dual-energy X-ray absorptiometry. Radius and tibia were measured by peripheral quantitative computed tomography (pQCT) at the diaphysis and by three-dimensional pQCT at the metaphysis.ResultsMen in the nonspecific resistive exercise group had higher grip strength(9.1 % or 0.4 SD) and higher lean mass(5.6 % or 0.5 SD) than those in the nonathletic group(p < 0.01 and p < 0.001, respectively). However, men who participated in nonspecific resistive exercise did not have higher bone density or a more favorable bone microstructure or geometry than their nonathletic referents. In contrast, men playing soccer had higher areal bone mineral density (aBMD) at the femoral neck (19.5 % or 1.2 SD) and lumbar spine (12.6 % or 1.0 SD), as well as larger cortical cross-sectional area (16.4 % or 1.1 SD) and higher trabecular bone volume fraction (14.5 % or 0.9 SD), as a result of increased trabecular number (8.7 % or 0.6 SD) and thickness (5.7 % or 0.4 SD) at the tibia than men in the nonathletic group(p < 0.001).ConclusionsWeight-bearing exercise with impacts from varying directions (playing soccer) is associated with aBMD and volumetric BMD, cortical bone geometry, as well as trabecular microstructure of weight-bearing bone. Nonspecific recreational resistance exercise does not appear to be a strong determinant of bone density, geometry, or microstructure in young adult men.

Bone turnover markers, glucose and lipid metabolism in relation to atherosclerosis in type-2 diabetic patients: a longitudinal study

Background: Bone metabolism is affected by risk factors of atherosclerosis and hyperglycemia induced low bone turnover with osteoblastic dysfunction. Limited information is available on the relationship between bone turnover markers (BTMs) and atherosclerosis or its related risk factors in patients with Type-2 diabetes mellitus (T2DM). Methods: A total of 135 patients (men=62; women=73) (age≥50 years) with poorly controlled T2DM [indicated by haemoglobin-A1c (HbA1c)] were followed-up over 12 months during glycemic control evaluation. Each patient (at baseline and visits on 3, 6, 9 and 12 months) provided fasting blood sample and second-void morning urine samples for the measurements of BTMs [serum osteocalcin (s-OC), bone alkaline phosphatase (s-bone ALP), procollagen type 1 Nterminal propeptide (s-PINP), crosslinked C-terminal telopeptide of type 1 collagen (sCTX), tartarate-resistance acid phosphatase isoform 5b (s-TRACP-5b) and urinary Ntelopeptide of type 1 collagen (u-NTX)]. Various hormones, HbA1c; lipids, glucose and creatinine were measured. Bone mineral density was determined at baseline visit and at 12-month visit. Also, the plaque score (PS) was calculated. Results: Multiple regression analysis showed that changes in s-OC were negatively correlated with HbA1c (r=-0.46, Pb0.001). Baseline s-OC levels were negatively correlated with changes in triglyceride levels (r=-0.37, Pb0.001) and positively with high-density lipoprotein-cholesterol (HDL-c) (r=0.44, Pb0.001). Changes in s-OC correlated positively with baseline PS (r=0.49, Pb0.001) and negatively with changes in PS (r=-0.41, Pb0.001) independent of other potential atherosclerosis risk factors. Conclusions: Association between s-OC with glucose, lipid metabolic indicators and PS independently of other atherosclerosis-related risk factors in patients with T2DM. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None Declared. doi:10.1016/j.bone.2012.02.442 PP254 Volumetric bone mineral density (vbmd) at tibia site and vitamin d status in premenopausal south asian and caucasian women O.A. Hakim⁎, A. Darling, K. Hart, J.L. Berry, S. Lanham-New Nutrition, University of Surrey, Guildford, UK Vitamin D Research Group, University of Manchester, Manchester, UK Abstract: Recent studies indicate thatwomenof European origin have higher areal bone mineral density (BMD) than South Asianwomen. However this has been explained by ethnic variation in bone size [1]. Few data exist on true volumetric BMD in premenopausal South Asianwomen and nodata is available at the tibia site. As part of theD-FINES (VitaminD, Food Intake,Nutrition andExposure to Sunlight in SouthernEngland) study,which investigates the interaction betweendiet and sunlight exposure and vitaminD status,we aimed to investigate differences in volumetric bone mineral density (vBMD) between South Asian (SA) and Caucasian (C)womenat the tibia and determine if there is an association betweenvBMDand serum 25(OH)D. Thirty five healthy premenopausal women (21 C and 14 SA), age ranges 1855 yrs, were scanned by peripheral Quantitative Computed Tomography (pQCT) at the tibia (non-dominant) using a Stratec XCT 2000 pQCT machine. Fasted blood samples were Recent studies indicate thatwomenof European origin have higher areal bone mineral density (BMD) than South Asianwomen. However this has been explained by ethnic variation in bone size [1]. Few data exist on true volumetric BMD in premenopausal South Asianwomen and nodata is available at the tibia site. As part of theD-FINES (VitaminD, Food Intake,Nutrition andExposure to Sunlight in SouthernEngland) study,which investigates the interaction betweendiet and sunlight exposure and vitaminD status,we aimed to investigate differences in volumetric bone mineral density (vBMD) between South Asian (SA) and Caucasian (C)womenat the tibia and determine if there is an association betweenvBMDand serum 25(OH)D. Thirty five healthy premenopausal women (21 C and 14 SA), age ranges 1855 yrs, were scanned by peripheral Quantitative Computed Tomography (pQCT) at the tibia (non-dominant) using a Stratec XCT 2000 pQCT machine. Fasted blood samples were collected for vitamin D analysis. SA women were significantly shorter (pb0.001), and slightly heavier than C women; Therefore SA had significantly higher BMI (pb0.05) than C women. SA women had significantly lower 25(OH)D concentration than C women (pb0.001) with mean values of 31.53[16.32] and 80.91[20.08] (nmol/l) respectively. SA women had significantly smaller bone size and higher vBMD than C women (pb0.05) for total, trabecular, and cortical bone at the 4% site. SA women had significantly lower total vBMD at 14% site (pb0.05) and the 38% site (pb0.01) than Caucasians. SA had significantly lower cortical density at site 14% than Caucasians (pb0.05).This was also lower at the 38% site but this was not statistically significant. There was a trend for a negative association between 25(OH)D and total area, trabecular area, and cortical area at the 4% site in the Asian group only (p=0.06). There was no correlation between 25(OH)D and vBMD at any site in either ethnic group. Our finding of differences in vBMD at the tibia for SA and C premenopausal women is novel and now requires further investigation. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None Declared.

Relationships of dietary fat, body composition, and bone mineral density in inbred mouse strain panels

Laboratory inbred mouse strains show a broad range of variation in phenotypes, such as body composition, bone mineral density (BMD), plasma leptin, and insulin-like growth factor I (IGF-I), and thus provide a basis for the study of associations among them. We analyzed these phenotypes in male and female mice from 43 inbred strains fed on a high-fat (30% caloric content) diet and from 30 inbred strains fed on a low-fat (6%) diet. Structural equation modeling of these data reveals that the relationship of body fat content and areal BMD is altered by dietary factors and genotypes. Sex has no net effect on areal BMD, but after accounting for body mass difference females have higher areal BMD. Leptin is affected by relative fat mass and has no net effect on areal BMD. IGF-I has a direct effect on areal BMD.

Former college artistic gymnasts maintain higher BMD: a nine-year follow-up

If higher bone gains acquired from weight-bearing sports during growth persist into old age, the residual benefits could delay or even prevent osteoporotic fractures. The purpose of this study was to determine if the higher areal bone mineral density (aBMD) observed 15 years after competitive training and competition in former female college artistic gymnasts (GYM) compared with controls (CON) is maintained nine years later in this same cohort approaching menopause. In this 9-year follow-up, aBMD changes were also compared between GYM (n=16; aged 45.3+/-3.3 years) and CON (n=13; aged 45.4+/-3.8 years). Total body, lumbar spine, proximal femur, femoral neck, leg, and arm aBMD were assessed at baseline and follow-up using dual-energy X-ray absorptiometry (DXA), (Hologic QDR-1000W). GYM had higher aBMD at all sites at follow-up (P<0.05; eta (2)>0.14). While there were no significant differences between groups for percent changes in aBMD at the total body, lumbar spine, total proximal femur, femoral neck, and arm, the change in leg aBMD was significantly different between GYM and CON (P=0.05; eta (2)=0.14). Former female college artistic gymnasts maintained significantly higher aBMD than controls 24 years after retirement from gymnastics training and competition. This study provides greater insight into the effects of past athletic participation on skeletal health in women approaching menopause.