Association of amount of physical activity with cortical bone size and trabecular volumetric BMD in young adult men: the GOOD study.

In this population-based study, amount of PA was associated with cortical bone size (increased thickness and periosteal circumference) and trabecular vBMD, but not with cortical vBMD or length of the long bones in young men. The lowest effective amount of PA was > or = 4 h/week. INTRODUCTION: Physical activity (PA) is believed to have positive effects on the skeleton and possibly help in preventing the occurrence of osteoporosis. Neither the lowest effective amount of PA needed to induce an osteogenic response nor its effect on the BMD and size of the different bone compartments (i.e., trabecular and cortical bone) has yet been clarified. MATERIALS AND METHODS: In this population-based study, we investigated the amount of all types of PA in relation to areal BMD (aBMD), trabecular and cortical volumetric BMD (vBMD), and cortical bone size in 1068 men (age, 18.9 +/- 0.02 years), included in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study. aBMD was measured by DXA, whereas cortical and trabecular vBMD and bone size were measured by pQCT. RESULTS AND CONCLUSIONS: The amount of PA was associated with aBMD of the total body, radius, femoral neck, and lumbar spine, as well as with cortical bone size (increased thickness and periosteal circumference) and trabecular vBMD, but not with cortical vBMD or length of the long bones. The lowest effective amount of PA was > or = 4 h/week. aBMD, cortical bone size, and trabecular vBMD were higher in subjects who started their training before age 13 than in subjects who started their training later in life. Our data indicate that > or = 4 h/week of PA is required to increase bone mass in young men and that exercise before and during the pubertal growth is of importance. These findings suggest that PA is imperative for the augmentation of cortical bone size and trabecular vBMD but does not affect the cortical vBMD in young men.     

Free testosterone is a positive, whereas free estradiol is a negative, predictor of cortical bone size in young Swedish men: the GOOD study.

In this study, we evaluated the predictive roles of sex steroids for skeletal parameters in young men (n = 1068) at the age of peak bone mass. Serum free estradiol was a negative predictor, whereas free testosterone and SHBG were positive predictors of cortical bone size. INTRODUCTION: Previous studies have shown that free estradiol in serum is an independent predictor of areal BMD (aBMD) in elderly men. The aim of this study was to determine whether sex steroids are predictors of volumetric BMD (vBMD) and/or size of the trabecular and cortical bone compartments in young men at the age of peak bone mass. MATERIALS AND METHODS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men, 18.9 +/- 0.6 years of age. Serum levels of testosterone, estradiol, and sex hormone binding globulin (SHBG) were measured, and free levels of testosterone and estradiol were calculated. The size of the cortical bone and the cortical and trabecular vBMDs were measured by pQCT. RESULTS: Regression models including age, height, weight, free estradiol, and free testosterone showed that free estradiol was an independent negative predictor of cortical cross-sectional area (tibia beta = -0.111, p < 0.001; radius beta = -0.125, p < 0.001), periosteal circumference, and endosteal circumference, whereas it was a positive independent predictor of cortical vBMD (tibia beta = 0.100, p < 0.003; radius beta = 0.115, p = 0.001) in both the tibia and radius. Free testosterone was an independent positive predictor of cortical cross-sectional area (tibia beta = 0.071, p = 0.013; radius beta = 0.064, p = 0.039), periosteal circumference, and endosteal circumference in both the tibia and radius. Neither cortical nor trabecular vBMD was associated with free testosterone. SHBG was an independent positive predictor of parameters reflecting the size of the cortical bone, including cross-sectional area (beta = 0.078, p = 0.009), periosteal circumference, and endosteal circumference. CONCLUSIONS: Free estradiol is a negative, whereas free testosterone is a positive, predictor of cortical bone size in young men at the age of peak bone mass. These findings support the notion that estrogens reduce, whereas androgens increase, cortical bone size, resulting in the well-known sexual dimorphism of cortical bone geometry.     

Polymorphisms in the aromatase gene predict areal BMD as a result of affected cortical bone size: the GOOD study.

The association between aromatase gene polymorphisms, bone parameters, and sex steroid levels was studied in 1068 men (18.9 +/- 0.6 years of age). Several aromatase gene polymorphisms were found to be associated with serum testosterone levels and cortical bone size but not with trabecular volumetric BMD. INTRODUCTION: Both testosterone and estrogens are important for the male skeleton. Aromatase, the product of the CYP19 gene, is the key enzyme in the conversion of testosterone to estradiol. A functional aromatase enzyme has been shown to be crucial for the normal development of the male skeleton. The role of genetic polymorphisms in the aromatase gene for trabecular volumetric BMD (vBMD) and cortical bone size has not previously been studied in men. MATERIALS AND METHODS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men (18.9 +/- 0.6 years of age). The TTTA repeat polymorphism (TTTAn) and three single nucleotide polymorphisms (SNPs), including the Val80 SNP, in the CYP19 gene, were analyzed. Serum levels of testosterone and estradiol were measured. Areal BMD (aBMD) was measured by DXA, whereas cortical and trabecular vBMD and cortical bone size were measured by pQCT. RESULTS: The TTTAn and the Val80 genotypes were independent predictors of aBMD of the radius, lumbar spine, total body, and cortical bone size (cortical cross-sectional area and thickness) of both the radius and tibia. In contrast, trabecular vBMD was not associated with CYP19 polymorphisms. Homozygosity for the long allele (>9 repeats) of the TTTAn and for the G allele of the Val80 SNP was associated with the highest aBMD and testosterone levels as well as with the greatest cortical bone size. Regression analyses indicated that the association with aBMD was mediated through affected cortical bone size. CONCLUSIONS: We showed, in a large well-characterized cohort of men at the age of peak bone mass, that several common aromatase polymorphisms are associated with cortical bone size but not with trabecular vBMD. One may speculate that affected CYP19 activity, resulting in altered testosterone levels during pubertal development, might contribute to the association between CYP19 polymorphisms and cortical bone size.     

Association between physical activity and BMD in young men is modulated by catechol-O-methyltransferase (COMT) genotype: the GOOD study.

In this large population-based study in young men, we show that the COMT val158met polymorphism modulates the association between physical activity, aBMD (DXA), and trabecular vBMD (pQCT). INTRODUCTION: Peak BMD is an important predictor of future risk of osteoporosis and is largely determined by genetic factors but also by environmental factors, among which physical activity (PA) is a strong contributor. Estrogens are believed to influence the mechanical strain signal generated by bones subjected to mechanical loading. Catechol-O-methyltransferase (COMT) is involved in the degradation of estrogens. A functional polymorphism in the COMT gene (val158met), results in a 60-75% difference in enzyme activity between the val (high activity = H) and met (low activity = L) variants. The aim of this study was to determine if the COMT val158met polymorphism modulates the association between PA and BMD in young men. MATERIALS AND METHODS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men (age, 18.9 +/- 0.6 yr). Areal BMD (aBMD) was measured by DXA, whereas cortical and trabecular volumetric BMD (vBMD) were measured by pQCT. Study subjects were genotyped and classified as COMT(LL), COMT(HL), or COMT(HH). The amount (h/wk) of PA was determined through questionnaires. RESULTS: Using a linear regression model (including age, height, weight, smoking, and calcium intake as covariates), significant interactions between the COMT genotype and PA were seen for aBMD at all sites and for trabecular vBMD in both the radius and the tibia. The difference in adjusted aBMD and trabecular vBMD between high (>or=4 h/wk) and low PA (<4 h/wk) was greater in COMT(LL) subjects than in subjects homozygous for the COMT(HH) (total body aBMD: COMT(LL) 4.2% versus COMT(HH) 1.5%, p = 0.02; lumbar spine aBMD: COMT(LL) 7.8% versus COMT(HH) 3.9%, p = 0.04; tibia trabecular vBMD: COMT(LL) 7.1% versus COMT(HH) 1.0%, p < 0.01). The COMT polymorphism was associated with aBMD, at all sites and with trabecular vBMD in the low-PA subjects, but not in their high-PA counterparts. CONCLUSIONS: We show that the COMT val158met polymorphism modulates the association between PA, aBMD, and trabecular vBMD, suggesting that this polymorphism is of importance for BMD in subjects with a low level of PA.     

The COMT val158met polymorphism is associated with peak BMD in men.

The associations between the functional val158met polymorphism of the estrogen-degrading COMT enzyme and skeletal properties in young men were investigated. BMD was associated with COMT genotype. INTRODUCTION: Peak BMD is an important predictor of future risk of osteoporosis, and it is to a large extent determined by genetic factors. Estrogens are involved in the accretion of bone mass during puberty. Catechol-O-methyltransferase (COMT) is involved in the degradation of estrogens. There is a functional polymorphism in the COMT gene (val158met), resulting in a 60-75% difference in enzyme activity between the val (high activity [H]) and met (low activity [L]) variants. The aim of this cross-sectional study was to investigate the associations between this polymorphism and peak BMD in young men. MATERIALS AND METHODS: A total of 458 healthy men (mean age, 19 +/- 0.6 years) were genotyped and classified as COMT(LL), COMT(HL), or COMT(HH). Areal BMD (aBMD) was measured by DXA. Cortical and trabecular volumetric BMD (vBMD) were measured by pQCT. The associations between COMT genotype and skeletal phenotypes were determined. RESULTS AND CONCLUSIONS: Regression models using physical activity, height, weight, age, and COMT genotype as covariates showed that COMT genotype was an independent predictor of aBMD in the total body and in all femur locations investigated, but not in the spine. The values for COMT(HL) and COMT(HH) were very similar, and therefore, they were pooled into one group. aBMD at Ward's triangle, trochanter, and total femur were 4.9%, 4.5%, and 3.7% lower, respectively, in the COMT(LL) than in the COMT(HL/HH) group (p < 0.01). pQCT analyses showed that COMT genotype was an independent predictor of trabecular vBMD of the tibia, radius, and fibula. Trabecular vBMD of the radius and fibula in COMT(LL) was 5.3% and 7.4% lower, respectively, than that of the combined COMT(HL/HH) group. COMT genotype was associated with cortical vBMD but not with cortical cross-sectional area in the tibia. These findings show that the COMT polymorphism is associated with BMD in young adult men.     

Trabecular volumetric bone mineral density is associated with previous fracture during childhood and adolescence in males: The GOOD study

Areal bone mineral density (aBMD) measured with dual‐energy X‐ray absorptiometry (DXA) has been associated with fracture risk in children and adolescents, but it remains unclear whether this association is due to volumetric BMD (vBMD) of the cortical and/or trabecular bone compartments or bone size. The aim of this study was to determine whether vBMD or bone size was associated with X‐ray‐verified fractures in men during growth. In total, 1068 men (aged 18.9 ± 0.6 years) were included in the population‐based Gothenburg Osteoporosis and Obesity Determinants (GOOD) Study. Areal BMD was measured by DXA, whereas cortical and trabecular vBMD and bone size were measured by peripheral quantitative computerized tomography (pQCT). X‐ray records were searched for fractures. Self‐reported fractures in 77 men could not be confirmed in these records. These men were excluded, resulting in 991 included men, of which 304 men had an X‐ray‐verified fracture and 687 were nonfracture subjects. Growth charts were used to establish the age of peak height velocity (PHV, n = 600). Men with prevalent fractures had lower aBMD (lumbar spine 2.3%, p = .005; total femur 2.6%, p = .004, radius 2.1%, p < .001) at all measured sites than men without fracture. Using pQCT measurements, we found that men with a prevalent fracture had markedly lower trabecular vBMD (radius 6.6%, p = 7.5 × 10^?8; tibia 4.5%, p = 1.7 × 10^?7) as well as a slightly lower cortical vBMD (radius 0.4%, p = .0012; tibia 0.3%, p = .015) but not reduced cortical cross‐sectional area than men without fracture. Every SD decrease in trabecular vBMD of the radius and tibia was associated with 1.46 [radius 95% confidence interval (CI) 1.26–1.69; tibia 95% CI 1.26–1.68] times increased fracture prevalence. The peak fracture incidence coincided with the timing of PHV (±1 year). In conclusion, trabecular vBMD but not aBMD was independently associated with prevalent X‐ray‐verified fractures in young men. Further studies are needed to determine if assessment of trabecular vBMD could enhance prediction of fractures during growth in males. © 2010 American Society for Bone and Mineral Research     

Bone density,geometry, microstructure,and stiffness: Relationships between peripheral and central skeletal sites assessed by DXA,HR‐pQCT,and cQCT in premenopausal women

High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a new in vivo imaging technique for assessing 3D microstructure of cortical and trabecular bone at the distal radius and tibia. No studies have investigated the extent to which measurements of the peripheral skeleton by HR‐pQCT reflect those of the spine and hip, where the most serious fractures occur. To address this research question, we performed dual‐energy X‐ray absorptiometry (DXA), central QCT (cQCT), HR‐pQCT, and image‐based finite‐element analyses on 69 premenopausal women to evaluate relationships among cortical and trabecular bone density, geometry, microstructure, and stiffness of the lumbar spine, proximal femur, distal radius, and distal tibia. Significant correlations were found between the stiffness of the two peripheral sites (r = 0.86), two central sites (r = 0.49), and between the peripheral and central skeletal sites (r = 0.56–0.70). These associations were explained in part by significant correlations in areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), and cross‐sectional area (CSA) between the multiple skeletal sites. For the prediction of proximal femoral stiffness, vBMD (r = 0.75) and stiffness (r = 0.69) of the distal tibia by HR‐pQCT were comparable with direct measurements of the proximal femur: aBMD of the hip by DXA (r = 0.70) and vBMD of the hip by cQCT (r = 0.64). For the prediction of vertebral stiffness, trabecular vBMD (r = 0.58) and stiffness (r = 0.70) of distal radius by HR‐pQCT were comparable with direct measurements of lumbar spine: aBMD by DXA (r = 0.78) and vBMD by cQCT (r = 0.67). Our results suggest that bone density and microstructural and mechanical properties measured by HR‐pQCT of the distal radius and tibia reflect the mechanical competence of the central skeleton. © 2010 American Society for Bone and Mineral Research.     

Bone Density,Microstructure and Strength in Obese and Normal Weight Men and Women in Younger and Older Adulthood

Obesity is associated with greater areal BMD (aBMD) and is considered protective against hip and vertebral fracture. Despite this, there is a higher prevalence of lower leg and proximal humerus fracture in obesity. We aimed to determine if there are site‐specific differences in BMD, bone structure, or bone strength between obese and normal‐weight adults. We studied 100 individually‐matched pairs of normal (body mass index [BMI] 18.5 to 24.9 kg/m²) and obese (BMI >30 kg/m²) men and women, aged 25 to 40 years or 55 to 75 years. We assessed aBMD at the whole body (WB), hip (TH), and lumbar spine (LS) with dual‐energy X‐ray absorptiometry (DXA), LS trabecular volumetric BMD (Tb.vBMD) by quantitative computed tomography (QCT), and vBMD and microarchitecture and strength at the distal radius and tibia with high‐resolution peripheral QCT (HR‐pQCT) and micro–finite element analysis. Serum type 1 procollagen N‐terminal peptide (P1NP) and collagen type 1 C‐telopeptide (CTX) were measured by automated electrochemiluminescent immunoassay (ECLIA). Obese adults had greater WB, LS, and TH aBMD than normal adults. The effect of obesity on LS and WB aBMD was greater in older than younger adults (p < 0.01). Obese adults had greater vBMD than normal adults at the tibia (p < 0.001 both ages) and radius (p < 0.001 older group), thicker cortices, higher cortical BMD and tissue mineral density, lower cortical porosity, higher trabecular BMD, and higher trabecular number than normal adults. There was no difference in bone size between obese and normal adults. Obese adults had greater estimated failure load at the radius (p < 0.05) and tibia (p < 0.01). Differences in HR‐pQCT measurements between obese and normal adults were seen more consistently in the older than the younger group. Bone turnover markers were lower in obese than in normal adults. Greater BMD in obesity is not an artifact of DXA measurement. Obese adults have higher BMD, thicker and denser cortices, and higher trabecular number than normal adults. Greater differences between obese and normal adults in the older group suggest that obesity may protect against age‐related bone loss and may increase peak bone mass. © 2014 American Society for Bone and Mineral Research.     

Heritability and Genetic Correlations for Bone Microarchitecture: The Framingham Study Families

High‐resolution peripheral quantitative computed tomography (HR‐pQCT) measures bone microarchitecture and volumetric bone mineral density (vBMD), important risk factors for osteoporotic fractures. We estimated the heritability (h²) of bone microstructure indices and vBMD, measured by HR‐pQCT, and genetic correlations (ρ_G) among them and between them and regional aBMD measured by dual‐energy X‐ray absorptiometry (DXA), in adult relatives from the Framingham Heart Study. Cortical (Ct) and trabecular (Tb) traits were measured at the distal radius and tibia in up to 1047 participants, and ultradistal radius (UD) aBMD was obtained by DXA. Heritability estimates, adjusted for age, sex, and estrogenic status (in women), ranged from 19.3% (trabecular number) to 82.8% (p < 0.01, Ct.vBMD) in the radius and from 51.9% (trabecular thickness) to 98.3% (cortical cross‐sectional area fraction) in the tibia. Additional adjustments for height, weight, and radial aBMD had no major effect on h² estimates. In bivariate analyses, moderate to high genetic correlations were found between radial total vBMD and microarchitecture traits (ρ_G from 0.227 to 0.913), except for cortical porosity. At the tibia, a similar pattern of genetic correlations was observed (ρ_G from 0.274 to 0.948), except for cortical porosity. Environmental correlations between the microarchitecture traits were also substantial. There were high genetic correlations between UD aBMD and multivariable‐adjusted total and trabecular vBMD at the radius (ρ_G = 0.811 and 0.917, respectively). In summary, in related men and women from a population‐based cohort, cortical and trabecular microarchitecture and vBMD at the radius and tibia were heritable and shared some h² with regional aBMD measured by DXA. These findings of high heritability of HR‐pQCT traits, with a slight attenuation when adjusting for aBMD, supports further work to identify the specific variants underlying volumetric bone density and fine structure of long bones. Knowledge that some of these traits are genetically correlated can serve to reduce the number of traits for genetic association studies. © 2016 American Society for Bone and Mineral Research.     

Alterations of Bone Density,Microstructure, and Strength of the Distal Radius in Male Patients With Rheumatoid Arthritis: A Case‐Control Study With HR‐pQCT

In this cross‐sectional study, we investigated volumetric bone mineral density (vBMD), bone microstructure, and biomechanical competence of the distal radius in male patients with rheumatoid arthritis (RA). The study cohort comprised 50 male RA patients of average age of 61.1 years and 50 age‐matched healthy males. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual‐energy X‐ray absorptiometry. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) of the distal radius provided measures of cortical and trabecular vBMD, microstructure, and biomechanical indices. aBMD of the hip but not the lumbar spine or ultradistal radius was significantly lower in RA patients than controls after adjustment for body weight. Total, cortical, and trabecular vBMD at the distal radius were, on average, –3.9% to –23.2% significantly lower in RA patients, and these differences were not affected by adjustment for body weight, testosterone level, or aBMD at the ultradistal radius. Trabecular microstructure indices were, on average, –8.1% (trabecular number) to 28.7% (trabecular network inhomogeneity) significantly inferior, whereas cortical pore volume and cortical porosity index were, on average, 80.3% and 63.9%, respectively, significantly higher in RA patients. RA patients also had significantly lower whole‐bone stiffness, modulus, and failure load, with lower and more unevenly distributed cortical and trabecular stress. Density and microstructure indices significantly correlated with disease activity, severity, and levels of pro‐inflammatory cytokines (interleukin [IL] 12p70, tumor necrosis factor, IL‐6 and IL‐1β). Ten RA patients had focal periosteal bone apposition most prominent at the ulnovolar aspect of the distal radius. These patients had shorter disease duration and significantly higher cortical porosity. In conclusion, HR‐pQCT reveals significant alterations of bone density, microstructure, and strength of the distal radius in male RA patients and provides new insight into the microstructural basis of bone fragility accompanying chronic inflammation. © 2014 American Society for Bone and Mineral Research.     

Effects of Odanacatib on the Radius and Tibia of Postmenopausal Women: Improvements in Bone Geometry,Microarchitecture, and Estimated Bone Strength

The cathepsin K inhibitor odanacatib (ODN), currently in phase 3 development for postmenopausal osteoporosis, has a novel mechanism of action that reduces bone resorption while maintaining bone formation. In phase 2 studies, odanacatib increased areal bone mineral density (aBMD) at the lumbar spine and total hip progressively over 5 years. To determine the effects of ODN on cortical and trabecular bone and estimate changes in bone strength, we conducted a randomized, double‐blind, placebo‐controlled trial, using both quantitative computed tomography (QCT) and high‐resolution peripheral (HR‐p)QCT. In previously published results, odanacatib was superior to placebo with respect to increases in trabecular volumetric BMD (vBMD) and estimated compressive strength at the spine, and integral and trabecular vBMD and estimated strength at the hip. Here, we report the results of HR‐pQCT assessment. A total of 214 postmenopausal women (mean age 64.0 ± 6.8 years and baseline lumbar spine T‐score –1.81 ± 0.83) were randomized to oral ODN 50 mg or placebo, weekly for 2 years. With ODN, significant increases from baseline in total vBMD occurred at the distal radius and tibia. Treatment differences from placebo were also significant (3.84% and 2.63% for radius and tibia, respectively). At both sites, significant differences from placebo were also found in trabecular vBMD, cortical vBMD, cortical thickness, cortical area, and strength (failure load) estimated using finite element analysis of HR‐pQCT scans (treatment differences at radius and tibia = 2.64% and 2.66%). At the distal radius, odanacatib significantly improved trabecular thickness and bone volume/total volume (BV/TV) versus placebo. At a more proximal radial site, odanacatib attenuated the increase in cortical porosity found with placebo (treatment difference = –7.7%, p = 0.066). At the distal tibia, odanacatib significantly improved trabecular number, separation, and BV/TV versus placebo. Safety and tolerability were similar between treatment groups. In conclusion, odanacatib increased cortical and trabecular density, cortical thickness, aspects of trabecular microarchitecture, and estimated strength at the distal radius and distal tibia compared with placebo. © 2014 American Society for Bone and Mineral Research     

Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight.

We measured cortical and trabecular bone loss using QCT of the spine and hip in 14 crewmembers making 4- to 6-month flights on the International Space Station. There was no compartment-specific loss of bone in the spine. Cortical bone mineral loss in the hip occurred primarily by endocortical thinning. INTRODUCTION: In an earlier study, areal BMD (aBMD) measurements by DXA showed that cosmonauts making flights of 4- to 12-month duration on the Soviet/Russian MIR spacecraft lost bone at an average rate of 1%/month from the spine and 1.5%/month from the hip. However, because DXA measurements represent the sum of the cortical and trabecular compartments, there is no direct information on how these bone envelopes are affected by spaceflight. MATERIALS AND METHODS: To address this, we performed a study of crewmembers (13 males and 1 female; age range, 40-55 years) on long-duration missions (4-6 months) on the International Space Station (ISS). We used DXA to obtain aBMD of the hip and spine and volumetric QCT (vQCT) to assess integral, cortical, and trabecular volumetric BMD (vBMD) in the hip and spine. In the heel, DXA was used to measure aBMD, and quantitative ultrasound (QUS) was used to measure speed of sound (SOS) and broadband ultrasound attenuation (BUA). RESULTS AND CONCLUSIONS: aBMD was lost at rates of 0.9%/month at the spine (p < 0.001) and 1.4-1.5%/month at the hip (p < 0.001). Spinal integral vBMD was lost at a rate of 0.9%/month (p < 0.001), and trabecular vBMD was lost at 0.7%/month (p < 0.05). In contrast to earlier reports, these changes were generalized across the vertebrae and not focused in the posterior elements. In the hip, integral, cortical, and trabecular vBMD was lost at rates of 1.2-1.5%/month (p < 0.0001), 0.4-0.5%/month (p < 0.01), and 2.2-2.7%/month (p < 0.001), respectively. The cortical bone loss in the hip occurred primarily by cortical thinning. Calcaneal aBMD measurements by DXA showed smaller mean losses (0.4%/month) than hip or spine measurements, with SOS and BUA showing no change. In summary, our results show that ISS crewmembers, on average, experience substantial loss of both trabecular and cortical bone in the hip and somewhat smaller losses in the spine. These results do not support the use of calcaneal aBMD or QUS measurements as surrogate measures to estimate changes in the central skeleton.     

Effects of genes, sex, age, and activity on BMC, bone size, and areal and volumetric BMD.

Quantitative genetic analyses of bone data for 710 inter-related individuals 8-85 yr of age found high heritability estimates for BMC, bone area, and areal and volumetric BMD that varied across bone sites. Activity levels, especially time in moderate plus vigorous activity, had notable effects on bone. In some cases, these effects were age and sex specific. INTRODUCTION: Genetic and environmental factors play a complex role in determining BMC, bone size, and BMD. This study assessed the heritability of bone measures; characterized the effects of age, sex, and physical activity on bone; and tested for age- and sex-specific bone effects of activity. MATERIALS AND METHODS: Measures of bone size and areal and volumetric density (aBMD and vBMD, respectively) were obtained by DXA and pQCT on 710 related individuals (466 women) 8-85 yr of age. Measures of activity included percent time in moderate + vigorous activity (%ModVig), stair flights climbed per day, and miles walked per day. Quantitative genetic analyses were conducted to model the effects of activity and covariates on bone outcomes. RESULTS: Accounting for effects of age, sex, and activity levels, genes explained 40-62% of the residual variation in BMC and BMD and 27-75% in bone size (all p<0.001). Decline in femoral neck (FN), hip, and spine aBMD with advancing age was greater among women than men (age-by-sex interaction; all p 相似文献   

Correlates of bone microarchitectural parameters and serum sclerostin levels in men: The STRAMBO study

Sclerostin is predominantly expressed by osteocytes. Serum sclerostin levels are positively correlated with areal bone mineral density (aBMD) measured by dual‐energy X‐ray absorptiometry (DXA) and bone microarchitecture assessed by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) in small studies. We assessed the relation of serum sclerostin levels with aBMD and microarchitectural parameters based on HR‐pQCT in 1134 men aged 20 to 87 years using multivariable models adjusted for confounders (age, body size, lifestyle, comorbidities, hormones regulating bone metabolism, muscle mass and strength). The apparent age‐related increase in serum sclerostin levels was faster before the age of 63 years than afterward (0.43 SD versus 0.20 SD per decade). In 446 men aged ≤63 years, aBMD (spine, hip, whole body), trabecular volumetric BMD (Tb.vBMD), and trabecular number (Tb.N) at the distal radius and tibia were higher in the highest sclerostin quartile versus the three lower quartiles combined. After adjustment for aBMD, men in the highest sclerostin quartile had higher Tb.vBMD (mainly in the central compartment) and Tb.N at both skeletal sites (p < 0.05 to 0.001). In 688 men aged >63 years, aBMD was positively associated with serum sclerostin levels at all skeletal sites. Cortical vBMD (Ct.vBMD) and cortical thickness (Ct.Th) were lower in the first sclerostin quartile versus the three higher quartiles combined. Tb.vBMD increased across the sclerostin quartiles, and was associated with lower Tb.N and more heterogeneous trabecular distribution (higher Tb.Sp.SD) in men in the lowest sclerostin quartile. After adjustment for aBMD, men in the lowest sclerostin quartile had lower Tb.vBMD and Tb.N, but higher Tb.Sp.SD (p < 0.05 to 0.001) at both the skeletal sites. In conclusion, serum sclerostin levels in men are strongly positively associated with better bone microarchitectural parameters, mainly trabecular architecture, regardless of the potential confounders.     

Characterization of low bone mass in young patients with thalassemia by DXA, pQCT and markers of bone turnover

Previous reports using dual x-ray absorptiometry (DXA) suggest that up to 70% of adults with thalassemia major (Thal) have low bone mass. However, few studies have controlled for body size and pubertal delay, variables known to affect bone mass in this population. In this study, bone mineral content and areal density (BMC, aBMD) of the spine and whole body were assessed by DXA, and volumetric BMD and cortical geometries of the distal tibia by peripheral quantitative computed tomography (pQCT) in subjects with Thal (n = 25, 11 male, 10 to 30 years) and local controls (n=34, 15 male, 7 to 30 years). Z-scores for bone outcomes were calculated from reference data from a large sample of healthy children and young adults. Fasting blood and urine were collected, pubertal status determined by self-assessment and dietary intake and physical activity assessed by written questionnaires. Subjects with Thal were similar in age, but had lower height, weight and lean mass index Z-scores (all p < 0.001) compared to controls. DXA aBMD was significantly lower in Thal compared to controls at all sites. Adult Thal subjects (> 18 years, n = 11) had lower tibial trabecular vBMD (p = 0.03), cortical area, cortical BMC, cortical thickness, periosteal circumference and section modulus Z-scores (all p < 0.01) compared to controls. Cortical area, cortical BMC, cortical thickness, and periosteal circumference Z-scores (p = 0.02) were significantly lower in young Thal (≤ 18 years, n = 14) compared to controls. In separate multivariate models, tibial cortical area, BMC, and thickness and spine aBMD and whole body BMC Z-scores remained lower in Thal compared to controls after adjustment for gender, lean mass and/or growth deficits (all p < 0.01). Tanner stage was not predictive in these models. Osteocalcin, a marker of bone formation, was significantly reduced in Thal compared to controls after adjusting for age, puberty and whole body BMC (p=0.029). In summary, we have found evidence of skeletal deficits that cannot be dismissed as an artifact of small bone size or delayed maturity alone. Given that reduced bone density and strength are associated with increased risk of fracture, therapies focused on increasing bone formation and bone size in younger patients are worthy of further evaluation.     

Longitudinal Change in Bone Density,Geometry, and Estimated Bone Strength in Older Men and Women From The Gambia: Findings From the Gambian Bone and Muscle Aging Study (GamBAS)

Musculoskeletal aging in the most resource-limited countries has not been quantified, and longitudinal data are urgently needed to inform policy. The aim of this prospective study was to describe musculoskeletal aging in Gambian adults. A total of 488 participants were recruited stratified by sex and 5-year age band (aged 40 years and older); 386 attended follow-up 1.7 years later. Outcomes were dual-energy X-ray absorptiometry (DXA) (n = 383) total hip areal bone mineral density (aBMD), bone mineral content (BMC), bone area (BA); peripheral quantitative computed tomography (pQCT) diaphyseal and epiphyseal radius and tibia (n = 313) total volumetric BMD (vBMD), trabecular vBMD, estimated bone strength indices (BSIc), cross-sectional area (CSA), BMC, and cortical vBMD. Mean annualized percentage change in bone outcomes was assessed in 10-year age bands and linear trends for age assessed. Bone turnover markers, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25(OH)D) were explored as predictors of change in bone. Bone loss was observed at all sites, with an annual loss of total hip aBMD of 1.2% in women after age 50 years and in men at age 70 years plus. Greater loss in vBMD and BSIc was found at the radius in both men and women; strength was reduced by 4% per year in women and 3% per year in men (p trend 0.02, 0.03, respectively). At cortical sites, reductions in BMC, CSA, and vBMD were observed, being greatest in BMC in women, between 1.4% and 2.0% per annum. Higher CTX and PINP predicted greater loss of trabecular vBMD in women and BMC in men at the radius, and higher 25(OH)D with less loss of tibial trabecular vBMD and CSA in women. The magnitude of bone loss was like those reported in countries where fragility fracture rates are much higher. Given the predicted rise in fracture rates in resource-poor countries such as The Gambia, these data provide important insights into musculoskeletal health in this population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Longitudinal changes in lean mass predict pQCT measures of tibial geometry and mineralisation at 6–7 years

BackgroundStudies in childhood suggest that both body composition and early postnatal growth are associated with bone mineral density (BMD). However, little is known of the relationships between longitudinal changes in fat (FM) and lean mass (LM) and bone development in pre-pubertal children. We therefore investigated these associations in a population-based mother-offspring cohort, the Southampton Women's Survey.MethodsTotal FM and LM were assessed at birth and 6–7 years of age by dual-energy x-ray absorptiometry (DXA). At 6–7 years, total cross-sectional area (CSA) and trabecular volumetric BMD (vBMD) at the 4% site (metaphysis) of the tibia was assessed using peripheral quantitative computed tomography [pQCT (Stratec XCT-2000)]. Total CSA, cortical CSA, cortical vBMD and strength–strain index (SSI) were measured at the 38% site (diaphysis). FM, LM and bone parameters were adjusted for age and sex and standardised to create within-cohort z-scores. Change in LM (ΔLM) or FM (ΔFM) was represented by change in z-score from birth to 7 years old and conditioned on the birth measurement. Linear regression was used to explore the associations between ΔLM or ΔFM and standardised pQCT outcomes, before and after mutual adjustment and for linear growth. The β-coefficient represents SD change in outcome per unit SD change in predictor.ResultsDXA at birth, in addition to both DXA and pQCT scans at 6–7 years, were available for 200 children (48.5% male). ΔLM adjusted for ΔFM was positively associated with tibial total CSA at both the 4% (β = 0.57SD/SD, p < 0.001) and 38% sites (β = 0.53SD/SD, p < 0.001), cortical CSA (β = 0.48SD/SD, p < 0.001) and trabecular vBMD (β = 0.30SD/SD, p < 0.001), but not with cortical vBMD. These relationships persisted after adjustment for linear growth. In contrast, ΔFM adjusted for ΔLM was only associated with 38% total and cortical CSA, which became non-significant after adjustment for linear growth.ConclusionIn this study, gain in childhood LM was positively associated with bone size and trabecular vBMD at 6–7 years of age. In contrast, no relationships between change in FM and bone were observed, suggesting that muscle growth, rather than accrual of fat mass, may be a more important determinant of childhood bone development.     

Abnormal microarchitecture and reduced stiffness at the radius and tibia in postmenopausal women with fractures

Measurement of areal bone mineral density (aBMD) by dual‐energy x‐ray absorptiometry (DXA) has been shown to predict fracture risk. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) yields additional information about volumetric BMD (vBMD), microarchitecture, and strength that may increase understanding of fracture susceptibility. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA and trabecular and cortical vBMD and trabecular microarchitecture of the radius and tibia measured by HR‐pQCT. Finite‐element analysis (FEA) of HR‐pQCT scans was performed to estimate bone stiffness. DXA T‐scores were similar in women with and without fracture at the spine, hip, and one‐third radius but lower in patients with fracture at the ultradistal radius (p < .01). At the radius fracture, patients had lower total density, cortical thickness, trabecular density, number, thickness, higher trabecular separation and network heterogeneity (p < .0001 to .04). At the tibia, total, cortical, and trabecular density and cortical and trabecular thickness were lower in fracture patients (p < .0001 to .03). The differences between groups were greater at the radius than at the tibia for inner trabecular density, number, trabecular separation, and network heterogeneity (p < .01 to .05). Stiffness was reduced in fracture patients, more markedly at the radius (41% to 44%) than at the tibia (15% to 20%). Women with fractures had reduced vBMD, microarchitectural deterioration, and decreased strength. These differences were more prominent at the radius than at the tibia. HR‐pQCT and FEA measurements of peripheral sites are associated with fracture prevalence and may increase understanding of the role of microarchitectural deterioration in fracture susceptibility. © 2010 American Society for Bone and Mineral Research.     

Predictors of Bone Mass by Peripheral Quantitative Computed Tomography in Early Adolescent Girls

This cross-sectional study used peripheral quantitative computed tomography (pQCT) to evaluate the influences of age, body size, puberty, calcium intake, and physical activity on bone acquisition in healthy early adolescent girls. The pQCT technique provides analyses of volumetric bone mineral density (vBMD) (mg/cm(3)) for total as well as cortical and trabecular bone compartments and bone strength expressed as polar strength strain index (mm(2)). Bone mass of the nondominant distal and midshaft tibia by pQCT and lumbar spine and hip by dual X-ray absorptiometry (DXA) were measured in 84 girls ages 11-14 yr. Pubertal stage, menarche status, anthropometrics, and 3-d food intake and physical activity records were collected. Total and cortical bone mineral content and vBMD measurements by pQCT were significantly related to lumbar spine and femoral neck BMD measurements by DXA. We did not note any significant determinants or predictors for trabecular bone mass. Body weight was the most important predictor and determinant of total and cortical bone density and strength in healthy adolescent girls. Menarche, calcium intake, height, body mass index, and weight-bearing physical activity level age were also identified as minor but significant predictors and determinants of bone density and strength. Bone measurements by the pQCT technique provide information on bone acquisition, architecture, and strength during rapid periods of growth and development. Broader cross-sectional studies using the pQCT technique to evaluate the influence of age, gender, ethnicity, puberty, body size, and lifestyle factors on bone acquisition and strength are needed.     

Catch up in bone acquisition in young adult men with late normal puberty

The aim of this study was to investigate the development of bone mineral density (BMD) and bone mineral content (BMC) in relation to peak height velocity (PHV), and to investigate whether late normal puberty was associated with remaining low BMD and BMC in early adulthood in men. In total, 501 men (mean ± SD, 18.9 ± 0.5 years of age at baseline) were included in this 5‐year longitudinal study. Areal BMD (aBMD) and BMC, volumetric BMD (vBMD) and cortical bone size were measured using dual‐energy X‐ray absorptiometry (DXA) and pQCT. Detailed growth and weight charts were used to calculate age at PHV, an objective assessment of pubertal timing. Age at PHV was a strong positive predictor of the increase in aBMD and BMC of the total body (R² aBMD 11.7%; BMC 4.3%), radius (R² aBMD 23.5%; BMC 22.3%), and lumbar spine (R² aBMD 11.9%; BMC 10.5%) between 19 and 24 years (p < 0.001). Subjects were divided into three groups according to age at PHV (early, middle, and late). Men with late puberty gained markedly more in aBMD and BMC at the total body, radius, and lumbar spine, and lost less at the femoral neck (p < 0.001) than men with early puberty. At age 24 years, no significant differences in aBMD or BMC of the lumbar spine, femoral neck, or total body were observed, whereas a deficit of 4.2% in radius aBMD, but not in BMC, was seen for men with late versus early puberty (p < 0.001). pQCT measurements of the radius at follow‐up demonstrated no significant differences in bone size, whereas cortical and trabecular vBMD were 0.7% (p < 0.001) and 4.8% (p < 0.05) lower in men with late versus early puberty. In conclusion, our results demonstrate that late puberty in males was associated with a substantial catch up in aBMD and BMC in young adulthood, leaving no deficits of the lumbar spine, femoral neck, or total body at age 24 years. © 2012 American Society for Bone and Mineral Research.