Cortical Volumetric Bone Mineral Density Research Articles

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.

Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, Improves Trabecular Bone Mineral Density and Microstructure in Obese, Insulin-Resistant, Pre-diabetic Rats.

Obese insulin resistance and type 2 diabetes mellitus profoundly impair bone mechanical properties and bone quality. However, because several antidiabetes drugs, especially thiazolidinediones, further aggravate bone loss in individuals with diabetes, diabetic osteopathy should not be treated by using simply any glucose-lowering agents. Recently, incretins have been reported to affect osteoblast function positively. The present study aimed to investigate the effects of vildagliptin, an inhibitor of dipeptidyl peptidase-4, on bone of rats with high-fat-diet-induced prediabetes. Male rats were fed a high-fat diet for 12 weeks to induce obese insulin resistance and then treated with vildagliptin for 4 weeks. The effects of the drug on bone were determined by microcomputed tomography and bone histomorphometry. Vildagliptin markedly improved insulin resistance in these obese insulin-resistant rats. It also significantly increased volumetric bone mineral density. Specifically, vildagliptin-treated obese insulin-resistant rats exhibited higher trabecular volumetric bone mineral density than vehicle-treated obese insulin-resistant rats, whereas cortical volumetric bone mineral density, cortical thickness and area were not changed. Bone histomorphometric analysis in a trabecular-rich area (i.e. tibial metaphysis) revealed greater trabecular bone volume and number and less trabecular separation without change in trabecular thickness, osteocyte lacunar area or cortical thickness in the vildagliptin-treated group. Vildagliptin had a beneficial effect on the bone of obese insulin-resistant rats with prediabetes, particularly at the trabecular site. Such benefit probably results from enhanced bone formation rather than from suppressed bone resorption.

Familial resemblance in trabecular and cortical volumetric bone mineral density and bone microarchitecture as measured by HRpQCT.

To estimate the heritability of bone geometry, volumetric bone mineral density (vBMD) and microarchitecture of trabecular (Tb) and cortical (Ct) bone measured by high resolution peripheral quantitative computerised tomography (HRpQCT) at the distal radius and tibia and to investigate the genetic correlations of these measures. Participants were 177 mother-offspring pairs from 162 families (mothers, mean age (SD) = 52.1 (4.7) years; offspring, 25.6 (0.73) years). Trabecular and cortical bone measures were obtained by HRpQCT. Multivariable linear regression was used to analyse the association of bone measures between mother and offspring. Sequential Oligogenic Linkage Analysis Routines (SOLAR) software was utilised to conduct quantitative genetic analyses. All maternal bone measures were independently associated with the corresponding bone measures in the offspring before and after adjustment for age, sex, weight and height. Heritability estimates ranged from 24% to 67% at the radius and from 42% to 74% at the tibia. The relationship for most bone geometry measures was significantly stronger in mother-son pairs (n = 107) compared with mother-daughter pairs (n = 70) (p < 0.05). In contrast, the heritability for most vBMD and microarchitecture measures were higher in mother-daughter pairs. Bivariate analyses found moderate to strong genetic correlations across all measures between radius and tibia (Rg = 0.49 to 0.93). Genetic factors have an important role in the development of bone geometry, vBMD and microarchitecture. These factors are strongly shared for the radius and tibia but vary by sex implying a role for imprinting.

HR-pQCT detects alterations in bone microstructure in men with CKD stages 3 and 4, which are influenced by hormonal changes and body composition .

Factors associated with osteodystrophy in predialysis patients are poorly understood. In the present study, we attempted to evaluate the impact of body composition and hormonal regulatory factors on the bone microstructure in a group of men with chronic kidney disease (CKD) stages 3 and 4. 46 men, aged 50-75 years, with previously unrecognized CKD were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT), and dual-energy X-ray absorptiometry (DXA). HR-pQCT parameters were correlated with estimated glomerular filtration rate (eGFR), age, body mass index (BMI), muscle mass index (MMI), and biochemistry. As compared to patients in stage 3 CKD, those with stage 4 CKD showed lower serum 25-hydroxyvitamin D (25(OH)D) and bicarbonate levels, and higher serum fibroblast growth factor 23 (FGF-23) and parathyroid hormone (PTH) levels. They also exhibited lower total, trabecular, and cortical volumetric bone mineral density, lower trabecular bone volume/tissue volume, trabecular number, trabecular and cortical thickness, and increased heterogeneity of the trabecular network. In the whole cohort, cortical bone density and thickness were negatively associated with age, PTH, and FGF-23, and positively with BMI. Trabecular bone parameters were positively associated with MMI and 25(OH)D. After simultaneously adjusting for age and eGFR, BMI, and MMI remained significantly associated with bone microstructural variables. HR-pQCT showed significant differences in bone microstructure in stage 4 vs. stage 3 CKD patients. Increased BMI, probably due to increased muscle mass, may favorably affect bone architecture in predialysis CKD patients. .

Bone turnover marker determinants in young women: results from the Safe-D study.

Background Bone turnover markers (BTMs) may provide insight into bone health in young women, but have been little studied in this demographic. We aimed to explore the association between body composition, hormonal contraception, bone mineral density and biochemical parameters and BTMs in young women. Methods Participants were community-dwelling females aged 16-25 years, living in Victoria, Australia. Carboxy-terminal cross-linking telopeptide of type 1 collagen (CTX) and total procollagen type 1 N-propeptide (P1NP) were analysed on the Roche Elecsys automated analyzer. A total of 305 were evaluated, after excluding participants with medical conditions or medications (except hormonal contraceptives), which may affect bone metabolism. Results Median (Q1, Q3) BTM values were 540 (410, 690) ng/L for CTX and 61.7 (46.2, 83.7) µg/L for P1NP. Serum CTX and P1NP were inversely associated with chronological age ( P < 0.001), transferrin ( P < 0.020) and serum dehydroepiandrosterone sulphate concentration ( P < 0.001). BTM values were up to 22% lower in combined oral contraceptive (COC) pill users ( P < 0.001). Serum CTX was inversely associated with per cent body fat ( P = 0.009) and tibial cortical volumetric bone mineral density (vBMD; P = 0.003). Serum P1NP concentrations were 23 µg/L higher in participants who reported using an osteopath in the previous year ( P = 0.007). Conclusions These data suggest that BTMs are influenced by age, COC use, body composition, iron status and hormonal profiles. Higher CTX values were associated with lower tibial cortical vBMD. Examining BTMs in relation to interventions aimed at improving bone health in young women is warranted.

Associations of components of sarcopenic obesity with bone health and balance in older adults

ObjectivesTo determine characteristics of sarcopenic obesity that are independently associated with bone health and balance in older adults. Study designCross-sectional study of 168 community-dwelling older adults (mean age 67.7 ± 8.4 years; 55% women). Main outcome measuresAppendicular lean mass (ALM), whole-body areal BMD (aBMD) and body fat percentage were assessed by dual-energy X-ray absorptiometry. Peripheral quantitative computed tomography assessed muscle density and cortical volumetric BMD (vBMD), area, thickness, and strength-strain index (SSI) at 66% tibial length. Hand grip strength (dynamometry) and balance path length (computerised posturography) were assessed. Obesity was defined as high body fat percentage. ResultsGreater lower-leg muscle density was associated with lower balance path length in men (r = −0.36; P < .01) and women (r = −0.40; P = < .01). Obese participants by body fat percentage did not differ to non-obese on bone indices, although a trend towards lower cortical vBMD was observed in obese compared with non-obese men (1041.4 ± 39.8 vs 1058.8 ± 36.1 mg/cm3; P = .051). In multivariable models, ALM was positively associated with all bone parameters in obese women, and with whole-body aBMD, proximal tibial cortical area and SSI in non-obese women, and both non-obese and obese men (all P < .05). Lower-leg muscle density was also positively associated with cortical vBMD (B = 2.91; 95% CI 0.02, 5.80) and area (2.70; 0.06, 5.33) in obese women. ConclusionsAmongst components of sarcopenic obesity, higher ALM is a consistent independent predictor of better bone health. Low muscle density may also compromise bone health and balance. Interventions which improve muscle mass and composition may lower fracture risk in sarcopenic obesity.

Analysis of the evolution of cortical and trabecular bone compartments in the proximal femur after spinal cord injury by 3D-DXA.

SCI is associated with a marked increase in bone loss and risk of osteoporosis development short-term after injury. 3D-DXA is a new imaging analysis technique providing 3D analysis of the cortical and trabecular bone from DXA scans. The aim of this study was to assess the evolution of trabecular macrostructure and cortical bone using 3D-DXA in patients with recent SCI followed over 12months. Sixteen males with recent SCI (<3months since injury) and without antiosteoporotic treatment were included. Clinical assessment, bone mineral density (BMD) measurements by DXA, and 3D-DXA evaluation at proximal femur (analyzing the integral, trabecular and cortical volumetric BMD [vBMD] and cortical thickness) were performed at baseline and at 6 and 12months of follow-up. vBMD significantly decreased at integral, trabecular, and cortical compartments at 6months (-8.8, -11.6, and -2.4%), with a further decrease at 12months, resulting in an overall decrease of -16.6, -21.9, and -5.0%, respectively. Cortical thickness also decreased at 6 and 12months (-8.0 and -11.4%), with the maximal decrease being observed during the first 6months. The mean BMD losses by DXA at femoral neck and total femur were -17.7 and -21.1%, at 12months, respectively. Marked trabecular and cortical bone loss was observed at the proximal femur short-term after SCI. 3D-DXA measured vBMD evolution at both femoral compartments and cortical thinning, providing better knowledge of their differential contributory role to bone strength and probably of the effect of therapy in these patients.

Evaluation of Radius Microstructure and Areal Bone Mineral Density Improves Fracture Prediction in Postmenopausal Women.

A majority of low-trauma fractures occur in subjects with only moderate decrease of areal bone mineral density (aBMD), ie, osteopenia, assessed by dual-energy X-ray absorptiometry (DXA) or low fracture probability assessed by FRAX. We investigated whether peripheral bone microstructure and estimated strength improve the prediction of incident fractures beyond central DXA and FRAX. In this population-based study of 740 postmenopausal women (aged 65.0 ± 1.4 years) from the Geneva Retirees Cohort (ISRCTN registry 11865958), we assessed at baseline cortical (Ct) and trabecular (Tb) volumetric bone mineral density (vBMD) and microstructure by peripheral quantitative computed tomography (HR-pQCT); bone strength by micro-finite element analysis; aBMD and trabecular bone score (TBS) by DXA; and FRAX fracture probability. Eighty-five low-trauma fractures occurred in 68 women over a follow-up of 5.0 ± 1.8 years. Tb and Ct vBMD and microstructure predicted incident fractures, independently of each other and of femoral neck (FN) aBMD and FRAX (with BMD ± TBS). However, the associations were markedly attenuated after adjustment for ultra-distal radius aBMD (same bone site). The best discrimination between women with and without fracture was obtained at the radius with total vBMD, the combination of a Tb with a Ct parameter, or with failure load, which improved the area under the curve (AUC) for major osteoporotic fracture when added to FN aBMD (0.760 versus 0.695, p = 0.022) or to FRAX-BMD (0.759 versus 0.714, p = 0.015). The replacement of failure load by ultra-distal aBMD did not significantly decrease the AUC (0.753, p = 0.747 and 0.750, p = 0.509, respectively). In conclusion, peripheral bone microstructure and strength improve the prediction of fractures beyond central DXA and FRAX but are partially captured in aBMD measured by DXA at the radius. Because HR-pQCT is not widely available for clinical purposes, assessment of ultra-distal radius aBMD by DXA may meanwhile improve fracture risk estimation. © 2017 American Society for Bone and Mineral Research.

Diabetes and Deficits in Cortical Bone Density, Microarchitecture, and Bone Size: Framingham HR-pQCT Study.

Older adults with type 2 diabetes (T2D) tend to have normal or greater areal bone mineral density (aBMD), as measured by DXA, than those who do not have diabetes (non-T2D). Yet risk of fracture is higher in T2D, including 40% to 50% increased hip fracture risk. We used HR-pQCT to investigate structural mechanisms underlying skeletal fragility in T2D. We compared cortical and trabecular bone microarchitecture, density, bone area, and strength in T2D and non-T2D. In secondary analyses we evaluated whether associations between T2D and bone measures differed according to prior fracture, sex, and obesity. Participants included 1069 members of the Framingham Study, who attended examinations in 2005 to 2008 and underwent HR-pQCT scanning in 2012 to 2015. Mean age was 64 ± 8 years (range, 40 to 87 years), and 12% (n = 129) had T2D. After adjustment for age, sex, weight, and height, T2D had lower cortical volumetric BMD (vBMD) (p < 0.01), higher cortical porosity (p = 0.02), and smaller cross-sectional area (p = 0.04) at the tibia, but not radius. Trabecular indices were similar or more favorable in T2D than non-T2D. Associations between T2D and bone measures did not differ according to sex or obesity status (all interaction p > 0.05); however, associations did differ in those with a prior fracture and those with no history of fracture. Specifically, cortical vBMD at the tibia and cortical thickness at the radius were lower in T2D than non-T2D, but only among those individuals with a prior fracture. Cortical porosity at the radius was higher in T2D than non-T2D, but only among those who did not have a prior fracture. Findings from this large, community-based study of older adults suggest that modest deterioration in cortical bone and reductions in bone area may characterize diabetic bone disease in older adults. Evaluation of these deficits as predictors of fracture in T2D is needed to develop prevention strategies in this rapidly increasing population of older adults. © 2017 American Society for Bone and Mineral Research.

Effects of a Randomized Weight Loss Intervention Trial in Obese Adolescents on Tibia and Radius Bone Geometry and Volumetric Density.

Obese adolescents have increased fracture risk, but effects of alterations in adiposity on bone accrual and strength in obese adolescents are not understood. We evaluated 12-month changes in trabecular and cortical volumetric bone mineral density (vBMD) and cortical geometry in obese adolescents undergoing a randomized weight management program, and investigated the effect of body composition changes on bone outcomes. Peripheral quantitative computed tomography (pQCT) of the radius and tibia, and whole-body dual-energy X-ray absorptiometry (DXA) scans were obtained at baseline, 6 months, and 12 months in 91 obese adolescents randomized to standard care versus behavioral intervention for weight loss. Longitudinal models assessed effects of body composition changes on bone outcomes, adjusted for age, bone length, and African-American ancestry, and stratified by sex. Secondary analyses included adjustment for physical activity, maturation, vitamin D, and inflammatory biomarkers. Baseline body mass index (BMI) was similar between intervention groups. Twelve-month change in BMI in the standard care group was 1.0 kg/m2 versus -0.4 kg/m2 in the behavioral intervention group (p < 0.01). Intervention groups were similar in bone outcomes, so they were combined for subsequent analyses. For the tibia, BMI change was not associated with change in vBMD or structure. Greater baseline lean body mass index (LBMI) associated with higher cortical vBMD in males, trabecular vBMD in females, and polar section modulus (pZ) and periosteal circumference (Peri-C) in both sexes. In females, change in LBMI positively associated with gains in pZ and Peri-C. Baseline visceral adipose tissue (VFAT) was inversely associated with pZ in males and cortical vBMD in females. Change in VFAT did not affect bone outcomes. For the radius, BMI and LBMI changes positively associated with pZ in males. Thus, in obese adolescents, weight loss intervention with modest changes in BMI was not detrimental to radius or tibia bone strength, and changes in lean, but not adiposity, measures were beneficial to bone development. © 2017 American Society for Bone and Mineral Research.

The Effect of Depression, Generalized Anxiety, and Selective Serotonin Reuptake Inhibitors on Change in Bone Metabolism in Adolescents and Emerging Adults.

The purpose of this study was to prospectively examine the independent contribution of major depressive disorder (MDD), generalized anxiety disorder (GAD), and selective serotonin reuptake inhibitors (SSRIs) use to changes in bone metabolism in older adolescents and emerging adults. Medically healthy 15- to 20-year-olds who were unmedicated or within 1 month of starting an SSRI were prospectively followed. Psychiatric functioning and medication treatment were assessed monthly. Every 4 months, trabecular and cortical volumetric bone mineral density (vBMD) at the radius and markers of bone metabolism were evaluated. Every 8 months, total body less head areal bone mineral content and lumbar spine (LS) areal BMD (aBMD) were determined. Linear mixed-effects regression analysis examined associations between bone measures on the one hand and MDD, GAD, and SSRI indices on the other. A total of 264 participants were followed for 1.51 ± 0.76 years. After adjusting for age, sex, vitamin D concentration, physical activity, lean mass or grip strength, and time in the study, MDD severity was associated with increasing LS aBMD. Similarly, SSRI use was associated with increasing LS aBMD and bone formation in female participants. In contrast, SSRI use was associated with decreasing LS aBMD in males. After accounting for depression, GAD was independently, albeit weakly, associated with increased bone mineralization. In older adolescents and emerging adults, MDD and GAD are associated with increasing bone mass, particularly in the lumbar spine and in females, whereas SSRIs are associated with increasing bone mass in females but decreasing bone mass in males. © 2017 American Society for Bone and Mineral Research.

Cortical and Trabecular Bone Analysis of Patients With High Bone Mass From the Barcelona Osteoporosis Cohort Using 3-Dimensional Dual-Energy X-ray Absorptiometry: A Case-Control Study

High bone mass (HBM), a rare phenotype, can be detected by dual-energy X-ray absorptiometry (DXA) scanning. Measurements with peripheral quantitative computed tomography at the tibia have found increased trabecular bone mineral density and changes in cortical bone density and structure, all of which lead to increased bone strength. However, no studies on cortical and trabecular bone have been performed at the femur. The recently developed 3-dimensional (3D)-DXA software algorithm quantifies the trabecular and cortical volumetric bone mineral density (vBMD) and the anatomical distribution of cortical thickness using routine hip DXA scans. We analyzed the femurs of 15 women with HBM and 15 controls from the Barcelona Osteoporosis (BARCOS) cohort using the 3D-DXA technique. The mean vBMD of proximal femur was 29.7% higher in HBM cases than in controls for the integral bone, 41.3% higher for the trabecular bone, and 7.3% higher for the cortical bone (p < 0.001). No differences in bone size were detected between cases and controls. Patients with HBM had a thicker cortex and higher trabecular and cortical vBMDs, as measured by 3D-DXA at the femur and compared to controls; bone size was similar in both groups. To the best of our knowledge, this is the first description of trabecular and cortical characteristics of the hip in patients with HBM.

Effects of Denosumab and Teriparatide Transitions on Bone Microarchitecture and Estimated Strength: the DATA-Switch HR-pQCT study.

In postmenopausal osteoporosis, switching from teriparatide to denosumab results in continued bone mineral density (BMD) gains whereas switching from denosumab to teriparatide results in BMD loss. To assess the effects of these transitions on bone microarchitecture and strength, we performed high-resolution peripheral QCT (HR-pQCT) at the distal tibia and radius in postmenopausal osteoporotic women who received 24 months of teriparatide 20 μg daily followed by 24 months of denosumab 60 mg every 6 months, 24 months of denosumab followed by 24 months of teriparatide, or 24 months of both medications followed by 24 months of denosumab. The 77 women who completed at least one post-switch visit are included in this analysis. Tibial cortical volumetric BMD (vBMD) increased between months 24 and 48 in the teriparatide-to-denosumab (net 48-month change -0.8% ± 2.4%) and combination-to-denosumab groups (net 48-month changes +2.4% ± 4.1%) but decreased in the denosumab-to-teriparatide group (net 48-month change -3.4% ± 3.2%, p < 0.001 for all between-group comparisons). Changes in total vBMD, cortical thickness, and estimated stiffness (by micro-finite element analysis [µFEA]) followed a similar pattern, as did changes at the radius. Conversely, tibial cortical porosity remained stable between months 24 and 48 in the teriparatide-to-denosumab and combination-to-denosumab groups (net 48-month changes +7.2% ± 14.8% and -3.4% ± 12.1%, respectively) but increased in the denosumab-to-teriparatide group (net 48-month change +16.2% ± 11.5%, p < 0.05 versus other groups). Trabecular vBMD changes did not differ among groups. Together, these findings demonstrate that in women treated with denosumab, switching to teriparatide is associated with a reduction in total and cortical vBMD, cortical thickness, and estimated strength, whereas switching to denosumab from teriparatide or combination therapy results in improvements in these parameters with the greatest improvements observed in women treated with combined therapy followed by denosumab. These findings strongly suggest that the use of teriparatide after denosumab should be avoided and that the use of combined teriparatide/denosumab followed by denosumab alone may be a useful treatment strategy in those with severe osteoporosis. © 2017 American Society for Bone and Mineral Research.

Relationship between Vitamin D Levels and Bone Tissue in Adolescents with and without Down Syndrome

Vitamin D (vitD) deficiency is a worldwide problem. Therefore, the main aims of this study were to compare 25-hydroxivitamin D levels (25(OH)D) in adolescents with and without Down syndrome (DS) and to study the relationship between 25(OH)D and bone. Eleven adolescents with DS (6 females) aged 15.5 ± 2.8 years and sixteen healthy controls (non-DS) (6 females) aged 14.3 ± 2.2 years were evaluated by bone imaging techniques. Blood samples were collected to determine vitD levels. Independent t-tests and analyses of covariance controlling for age, height, sex, sexual maturation, calcium intake and body mass index were performed to evaluate differences in 25(OH)D levels between groups. Pearson’s correlation test and multiple linear regression analyses were performed to examine the association between 25(OH)D and bone mass. Adolescents with DS had lower 25(OH)D (22.8 ± 8.0 vs. 36.0 ± 6.5 ng/ml) than non-DS (d = 1.81; p 0.05) but linear regression analyses suggested that 25(OH)D influenced positively femoral neck bone mineral density (β = 0.477, p = 0.038) and content at the 4% of the length of the tibia (β = 0.453, p = 0.008) in the non-DS and cortical volumetric bone mineral density at the 38% (β = 0.841, p = 0.034) in the DS. Adolescents with DS had lower levels of 25(OH)D and higher prevalence of vitD deficiency compared with non-DS. Associations between 25(OH)D and bone parameters were not observed for adolescents with DS but medium and positive correlations were observed in the non-DS group.

Progressive skeletal benefits of physical activity when young as assessed at the midshaft humerus in male baseball players.

The current study explored physical activity-induced bone adaptation at different stages of somatic maturity by comparing side-to-side differences in midshaft humerus properties between male throwing athletes and controls. Throwers present an internally controlled model, while inclusion of control subjects removes normal arm dominance influences. Throwing athletes (n=90) and controls (n=51) were categorized into maturity groups (pre, peri, post-early, post-mid, and post-late) based on estimated years from peak height velocity (<-2, -2 to 2, 2 to 4, 4 to 10, and >10years). Side-to-side percent differences in midshaft humerus cortical volumetric bone mineral density (Ct.vBMD) and bone mineral content (Ct.BMC); total (Tt.Ar), medullary (Me.Ar), and cortical (Ct.Ar) areas; average cortical thickness (Ct.Th); and polar Strength Strain Index (SSIP) were assessed. Significant interactions between physical activity and maturity on side-to-side differences in Ct.BMC, Tt.Ar, Ct.Ar, Me.Ar, Ct.Th, and SSIP resulted from the following: (1) greater throwing-to-nonthrowing arm differences than dominant-to-nondominant arm differences in controls (all p<0.05) and (2) throwing-to-nonthrowing arm differences in throwers being progressively greater across maturity groups (all p<0.05). Regional analyses revealed greatest adaptation in medial and lateral sectors, particularly in the three post-maturity groups. Years throwing predicted 59% of the variance of the variance in throwing-to-nonthrowing arm difference in SSIP (p<0.001). These data suggest that physical activity has skeletal benefits beginning prior to and continuing beyond somatic maturation and that a longer duration of exposure to physical activity has cumulative skeletal benefits. Thus, physical activity should be encouraged at the earliest age possible and be continued into early adulthood to optimize skeletal benefits.

The relationship of bone properties using high resolution peripheral quantitative computed tomography to radiographic components of hip osteoarthritis.

Positive associations between radiographic osteoarthritis (OA) and areal bone mineral density (BMD) have been demonstrated and appear strongest when bony features of OA are considered. To date, these associations have not been assessed using HRpQCT. A total of 318 participants (170 men and 148 women), aged 72.1-81.4 years from a non-selected cohort, underwent HRpQCT of the distal radius and tibia along with hip radiography. Differences in bone microarchitecture were assessed between those with and without osteophytes, sclerosis or joint space narrowing (JSN) in either hip. Men with osteophytes alone had significantly higher radial trabecular volumetric BMD (Tb.vBMD) and radial and tibial trabecular thickness (Tb.Th). Men with both sclerosis and osteophytes had significantly higher cortical volumetric BMD (Ct.vBMD) and cortical thickness (Ct.Th) at the distal tibia than those with osteophytes alone (P<0.05). These relationships were maintained after adjustment for age and Body Mass Index (BMI), and were not replicated in women. Bone microarchitecture did not differ significantly in those with JSN from those without it in men or women. Our findings suggest higher Tb.vBMD and Tb.Th in men with osteophytosis but higher tibial Ct.vBMD and Ct.Th in men with hip joint sclerosis. These results do however require replication in other cohorts.

Proximal Femur Volumetric Bone Mineral Density and Mortality: 13 Years of Follow-Up of the AGES-Reykjavik Study.

Bone mineral density (BMD) has been linked to mortality, but little is known about the independent contribution of each endosteal bone compartment and also the rate of bone loss to risk of mortality. We examined the relationships between (1) baseline trabecular and cortical volumetric BMD (vBMD) at the proximal femur, and (2) the rate of trabecular and cortical bone loss and all-cause mortality in older adults from the AGES-Reykjavik study. The analysis of trabecular and cortical vBMD and mortality was based on the baseline cohort of 4654 participants (aged ≥66 years) with a median follow-up of 9.4 years; the association between rate of bone loss and mortality was based on 2653 participants with bone loss data (median follow-up of 5.6 years). Analyses employed multivariable Cox-proportional models to estimate hazard ratios (HRs) with time-varying fracture status; trabecular and cortical variables were included together in all models. Adjusted for important confounders, Cox models showed that participants in the lowest quartile of trabecular vBMD had an increased risk of mortality compared to participants in other quartiles (HR = 1.12; 95% confidence interval (CI), 1.01 to 1.25); baseline cortical vBMD was not related to mortality (HR = 1.08; 95% CI, 0.97 to 1.20). After adjustment for time-dependent fracture status, results were attenuated and not statistically significant. A faster loss (quartile 1 versus quartiles 2-4) in both trabecular and cortical bone was associated with higher mortality risk (HR = 1.37 and 1.33, respectively); these associations were independent of major potential confounders including time-dependent incident fractures (HR = 1.32 and 1.34, respectively). Overall, data suggest that faster bone losses over time in both the trabecular and cortical bone compartments are associated with mortality risk and that measurements of change in bone health may be more informative than single-point measurements in explaining mortality differences in older adults. © 2017 American Society for Bone and Mineral Research.

Monoclonal gammopathy of undetermined significance and bone health outcomes: a systematic review and exploratory meta-analysis.

Monoclonal gammopathy of undetermined significance (MGUS) is a common condition in the elderly. A number of studies have investigated the relationship between MGUS and bone health outcomes including bone mineral density (BMD), osteoporosis and fractures, but no meta-analysis exists. We conducted a systematic review and exploratory meta-analysis comparing bone health outcomes in patients with MGUS. Two independent authors searched PubMed and Scopus from inception until 19 October 2016. A meta-analysis of cross-sectional and longitudinal studies investigating fractures and BMD was conducted. Standardised mean differences (SMD)±95% confidence intervals (CIs) were calculated for BMD, and risk ratios (RRs) were calculated for prevalent and incident fractures. Of 174 initial hits, 10 studies of moderate methodological quality were eligible, including 8711 individuals with MGUS vs. 52,865 controls. Compared to controls, subjects with MGUS showed significantly lower values for radial cortical volumetric BMD (1 study; SMD=-5.45, 95% CI: -7.24 to -3.66), but not at the lumbar spine, femoral neck or hip. The incidence of fractures was higher in people with MGUS (n=7466) vs. controls (n=52,304) (RR=1.36, 95% CI 1.28-1.44, I 2=0%) over a median of 12.5-year follow-up. The incidence of vertebral fractures was particularly elevated (RR=2.50, 95% CI 1.53-4.06) although limited to two studies. In conclusion, although with limitations, our preliminary meta-analysis suggests that patients with MGUS are at higher risk of fractures despite evidence for differences in BMD being equivocal. Future longitudinal research is required to confirm our findings and determine if fracture prevention interventions are warranted in people with MGUS.

Bone Structure and Geometric Properties at the Radius and Tibia in Adolescent Endurance-Trained Cyclists.

To describe cortical and trabecular volumetric bone mineral density (vBMD), bone mineral content (BMC), cross-sectional area (CSA), and bone strength indexes (BSIs) in adolescent endurance-trained cyclists (CYC) and compare them with controls (CON). Descriptive cohort study. Twenty-five male adolescent CYC and 17 CON. Peripheral quantitative computed tomography was used to evaluate proximal and distal sites of the radius and tibia. Total, trabecular, and cortical BMC, vBMD, and CSA were measured. Also, cortical thickness, endosteal and periosteal circumferences, and different BSIs were calculated. Unadjusted analysis of variance and body weight-adjusted analysis of covariance tests were applied between cyclist and control groups. Cyclists were almost 12% lighter than CON (P < 0.05). Unadjusted data showed lower distal total vBMD and proximal cortical BMC and vBMD in cyclists compared with CON at the radius (P < 0.05) and lower distal total and trabecular BMC, vBMD and bone area, proximal total and cortical BMC and vBMD, and cortical bone area at the tibia (P < 0.05). Body weight-adjusted data showed the same differences for distal total vBMD at the radius and total and trabecular BMC and vBMD at the tibia, diaphyseal radius cortical vBMD and tibia total vBMD, cortical BMC and area, and also for tibia cortical thickness and BSI. The rest of differences were no longer detectable and bone area at the distal radius become significantly higher in cyclist compared with CON (P < 0.05). Adolescent CYC in this study showed lower values of BMC and vBMD at determined sites of the radius and tibia than CON, some of these differences were explained in part by their lower body weight. However, even further adjustment, some differences remained, which indicates that further longitudinal studies are needed to better understand if cycling influences these differences.

Type 2 Diabetes Mellitus Is Associated With Better Bone Microarchitecture But Lower Bone Material Strength and Poorer Physical Function in Elderly Women: A Population-Based Study.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of fractures according to several studies. The underlying mechanisms remain unclear, although small case-control studies indicate poor quality of the cortical bone. We have studied a population-based sample of women aged 75 to 80 years in Gothenburg, randomly invited from the population register. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (Hologic Discovery A), bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT; ExtremeCT from Scanco Medical AG), and reference point indentation was performed with Osteoprobe (Active Life Scientific). Women with T2DM (n = 99) had higher aBMD compared to controls (n = 954). Ultradistal tibial and radial trabecular bone volume fraction (+11% and +15%, respectively), distal cortical volumetric BMD (+1.6% and +1.7%), cortical area (+11.5% and +9.3%), and failure load (+7.7% and +12.9%) were higher in diabetics than in controls. Cortical porosity was lower (mean ± SD: 1.5% ± 1.1% versus 2.0% ± 1.7%, p = 0.001) in T2DM in the distal radius but not in the ultradistal radius or the tibia. Adjustment for covariates (age, body mass index, glucocorticoid treatment, smoking, physical activity, calcium intake, bone-active drugs) eliminated the differences in aBMD but not in HR-pQCT bone variables. However, bone material strength index (BMSi) by reference point indentation was lower in T2DM (74.6 ± 7.6 versus 78.2 ± 7.5, p < 0.01), also after adjustment, and women with T2DM performed clearly worse in measures of physical function (one leg standing: -26%, 30-s chair-stand test: -7%, timed up and go: +12%, walking speed: +8%; p < 0.05-0.001) compared to controls. In conclusion, we observed a more favorable bone microarchitecture but no difference in adjusted aBMD in elderly women with T2DM in the population compared to nondiabetics. Reduced BMSi and impaired physical function may explain the increased fracture risk in T2DM. © 2016 American Society for Bone and Mineral Research.