Age, sex, and grip strength determine architectural bone parameters assessed by peripheral quantitative computed tomography (pQCT) at the human radius

The purpose of this study was to estimate the relation of some noninvasively derived mechanical characteristics of radial bone including architectural parameters for bone strength to grip strength and muscle cross-section. Sixty-three males between 21 and 78yr of age and 101 females between 18 and 80yr of age were measured at the nondominant forearm using peripheral quantitative computed tomography (pQCT). We assessed the integral bone mineral density (BMD(I)) and content (BMC(I)) by pQCT at the distal and at the mid-shaft radius. Integral bone area (Area(I)), cortical thickness (C-th), and a newly proposed index for bone strength; the stress-strain index (SSI) were also calculated. The dynamometrically measured maximum grip strength was taken as a mechanical loading parameter and muscle cross-section as a substitute for it. Sex, grip strength, BMC(I) and BMD(I) (distal radius) were identified in a multiple regression analysis to significantly predict bone strength as expressed by SSI, after adjusting for all other independent variables, including age and sex (p<0.0001). Grip strength was closest related to age, sex, BMD(I) and SSI(p) of the distal radius. The cross-sectional area of muscle was not significantly determining the grip strength within the analysis model. In conclusion, our results suggested that architectural parameters at the distal radius were better related to grip strength than to cross-sectional muscle area in both males and females. Maximum muscle strength as estimated by grip strength might be a stronger determinant of mechanical characteristics of bones as compared with cross-sectional muscle area.     

Analysis of the independent power of age-related,anthropometric and mechanical factors as determinants of the structure of radius and tibia in normal adults. A pQCT study

To compare the independent influence of mechanical and non-mechanical factors on bone features, multiple regression analyses were performed between pQCT indicators of radius and tibia bone mass, mineralization, design and strength as determined variables, and age or time since menopause (TMP), body mass, bone length and regional muscles’ areas as selected determinant factors, in Caucasian, physically active, untrained healthy men and pre- and post-menopausal women. In men and pre-menopausal women, the strongest influences were exerted by muscle area on radial features and by both muscle area and bone length on the tibia. Only for women, was body mass a significant factor for tibia traits. In men and pre-menopausal women, mass/design/strength indicators depended more strongly on the selected determinants than the cortical vBMD did (p<0.01-0.001 vs n.s.), regardless of age. However, TMP was an additional factor for both bones (p<0.01-0.001). The selected mechanical factors (muscle size, bone lengths) were more relevant than age/TMP or body weight to the development of allometrically-related bone properties (mass/design/strength), yet not to bone tissue “quality” (cortical vBMD), suggesting a determinant, rather than determined role for cortical stiffness. While the mechanical impacts of muscles and bone levers on bone structure were comparable in men and pre-menopausal women, TMP exerted a stronger impact than allometric or mechanical factors on bone properties, including cortical vBMD.     

Increased osteogenic response to exercise in metaphyseal versus diaphyseal cortical bone

Recent experimental data suggest that the anabolic response of bone to changes in physical activity and mechanical loading may vary among different skeletal elements, and even within different regions of the same bone. In order to better understand site-specific variation in bone modeling we used an experimental protocol in which locomotor activity was increased in laboratory mice with regular treadmill exercise for only 30 min/day. We predicted that the regular muscle contractions that occur during exercise would significantly increase cortical bone formation in these animals, and that the increase in cortical bone mass would vary between metaphyseal and diaphyseal regions. Cortical bone mass, density, and bone geometry were compared between these two regions using pQCT technology. Results indicate that exercise increases bone mineral content (BMC) in the mid-diaphysis by approximately 20%, whereas bone mass in the metaphyseal region is increased by approximately 35%. Endosteal and periosteal circumference at the midshaft are increased with exercise, whereas increased periosteal circumference is accompanied by marked endosteal contraction at the metaphysis, resulting in an increase in cortical area of more than 50%. These findings suggest that the osteogenic response of cortical bone to exercise varies significantly along the length of a bone, and more distal regions appear most likely to exhibit morphologic changes when loading conditions are altered.     

The Associations of Serum Serotonin with Bone Traits Are Age- and Gender-Specific

Context

Serotonin plays a potential role in bone metabolism, but the nature and extent of this relationship is unclear and human studies directly addressing the skeletal effect of circulating serotonin are rare.

Objective

The study aimed to investigate the associations between serum serotonin and bone traits at multiple skeletal sites in women and men.

Subjects and Methods

Subjects were part of the CALEX-family study and comprised 235 young women, 121 premenopausal women, 124 postmenopausal women, and 168 men. Body composition was assessed using DXA, as was areal bone mineral density (aBMD) of spine, femur and whole body. In addition, pQCT was used to determine bone properties at tibial midshaft and distal radius. Fasting serum serotonin concentration was assessed using a competitive enzyme-linked immunosorbent assay.

Results

Serum serotonin declined with advancing age both in females and males (all p<0.01). Serotonin was negatively correlated with weight, BMI, lean and fat mass in women (r = −0.22 to −0.39, all p<0.001), but positively with height and lean mass in men (all p<0.01). In the premenopausal women, serotonin was negatively correlated with lumbar spine aBMD (r = −0.23, p<0.05) but the statistical significance disappeared after adjustment for weight. Conversely, in postmenopausal women, serotonin was positively correlated with whole body and femur aBMD, as well as with distal radius bone mineral content and volumetric BMD (r = 0.20 to 0.30, all p<0.05), and these associations remained significant after adjustment for weight. In men, no significant associations were found between serotonin and bone traits.

Conclusion

Serum serotonin is positively associated with bone traits in postmenopausal women, but not in premenopausal women or men. This partially supports the idea of circulating serotonin playing a role in the regulation of bone metabolism, but also indicates the importance of gender and age specific factors.     

Hormone replacement therapy improves distal radius bone structure by endocortical mineral deposition

Hormone replacement therapy (HRT) produces a small increase in bone mineral density (BMD) when measured by dual energy X-ray absorptiometry (DXA). The corresponding decrease in fracture risk is more impressive, implying that other factors that contribute to bone strength are favourably modified by HRT. We investigated, using peripheral quantitated computed tomography (pQCT), the changes produced by HRT in both the distribution of mineral between cortical and trabecular bone and the changes produced by HRT in the apparent structure of trabecular bone, expressed as average hole area and apparent connectivity. Twenty-one postmenopausal women starting HRT and 32 control women were followed for 2 years, with distal radius pQCT measurements every 6 months. HRT prevented the loss of total bone mass seen in controls (p < 0.02). HRT also produced an apparent rapid loss of trabecular bone mass within the first 6 months of the study (p < 0.02), with an associated rapid loss in the apparent connectivity (p = 0.034). Average hole area also increased but not to a statistically significant extent. Exogenous estrogen apparently fills small marrow pores close to the endocortical surface, such that the pQCT-defined boundary between trabecular and cortical bone is shifted in favour of cortical bone. Trabecular bone structure indices are adversely affected, as the central, poorly interconnected trabecular bone with greater than average marrow spaces constitutes a greater fraction of the remaining trabecular bone. This study suggests that the improvements in fracture risk resulting from HRT are explained by a reversal of net endocortical resorption of bone.     

Estimation of bone mineral density and architectural parameters of the distal radius in hemodialysis patients using peripheral quantitative computed tomography

We analyzed bone changes in a series of hemodialysis patients followed up for a maximum of 299 months by assessing bone mineral density (BMD) and architectural parameters of the distal radius using peripheral quantitative computed tomography (pQCT), and determined the predictors of skeletal changes in these patients. No significant differences in trabecular BMD (BMD(T)) were found compared with BMD(T) of the normal control. In contrast, cortical BMD (BMD(C)) was significantly decreased compared with BMD(C) of the normal controls. Hemodialysis patients had significantly lower values for cortical bone area, cortical thickness, moment of inertia, and polar moment of inertia than the age-matched controls. From single and multiple regression analysis, the most significant predictor of metabolic bone disease in these cases was found to be duration of hemodialysis. In addition, increases in serum alkaline phosphatase and intact parathyroid hormone in secondary hyperparathyroidism were found to correlate with a decrease in pQCT values in cortical bone; as such, these increases were also found to be a predictive. The present study confirms that the reduction in both BMD(C) and architectural parameters in hemodialysis patients occurs partly because of prolonged hemodialysis and secondary hyperparathyroidism. In addition, immobilization, dietary factors, daily intake of calcium or vitamin D, and so on must be taken into account when clarifying the causes of skeletal complications resulting from hemodialysis.     

Muscle-bone relationships in the lower leg of healthy pre-pubertal females and males

Muscle-bone relationships in healthy pre-pubertal children were investigated using four muscle measures as predictors of tibial strength: 66% tibia cross-sectional muscle area (CSMA) by pQCT; leg lean mass (LLM) by DXA; and muscle power (Power) and force (Force) measured during a two-footed jump. Polar strength strain index (pSSI), a calculated surrogate for bone strength at the 20% distal tibia, was obtained on 105 (54 male) self-assessed pre-pubertal children. The amount of muscle (CSMA, LLM) may influence bone strength more than muscle strength (Power, Force) during periods of rapid growth. Correlations and multiple regression partial-R values from models controlling for age, sex, height and weight were obtained for each muscle predictor. CSMA, LLM, Power and Force were positively correlated with pSSI (R=0.84, 0.92, 0.85; 0.66, respectively, all p<0.01). Partial-R values were highest for LLM (partial-R=0.21), similar for CSMA and Power (0.14, 0.15, respectively) and lowest for Force (0.04) in predicting pSSI. Muscle predictors were associated with total and cortical area (R=0.59 to 0.90; p<0.01 for all), but not cortical vBMD at the 20% distal tibia site. These data support relationships between muscle predictors and bone parameters measured by pQCT in healthy pre-pubertal children.     

Peripheral quantitative computed tomography at the distal radius: cross-calibration between two scanners

Peripheral quantitative computed tomography (pQCT) is an important technique to study the interaction between the muscle and bone systems. We have recently established pQCT reference ranges for children, adolescents and young adults using a recent version (XCT 2000) of the Stratec scanners (Stratec Inc., Pforzheim, Germany). However, the previous version of this type of scanner (XCT 900) is still widely used and cross-calibration is needed to use these reference data. Therefore, both distal radii of 19 healthy subjects (age 21 to 59 years; 11 women) were analyzed at the "4% site" using both the XCT 900 and the XCT 2000. Cross-sectional area, total and trabecular bone mineral density (BMD), total bone mineral content (BMC) and polar Strength-Strain Index (SSI) results from the two scanners were compared using linear regression analysis. To achieve scanner calibration we used the intercept and slope of the correlations. The correlation coefficients between the two devices were 0.82 for the cross-sectional area, 0.81 for total BMD, 0.97 for trabecular BMD, 0.99 for total BMC and 0.86 for polar SSI. In conclusion, these data allow for the conversion of XCT 900 results at the distal radius to XCT 2000 values and vice versa.     

Bone mineral density and microarchitecture in participants of a 105-day experiment in isolated environment

A study on the bone system state in healthy volunteers has been performed before and after 105-day experiment in hermetically isolated environment (the Mars-105 experiment) using dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). The values of bone mineral density (BMD), volumetric bone mineral density (VBMD), and bone structural characteristics of distal segments in radius and tibia have been evaluated. No significant DXA changes have been revealed in segments of skeleton critically important in terms of biomechanics. Microarchitectural deterioration (a decrease in the trabecula number and increase in the bone tissue heterogeneity) has been found using the pQCT technique in the radius of the majority of subjects. A VBMD decrease has been revealed for both cortical and trabecular bones in tibia, along with an unexpected trabecular bone improvement in the form of an increase in the trabecula quantity and decrease in bone tissue heterogeneity. Comprehensive studies, including estimation of projective and volumetric bone mineral densities (the bone mineral content) and bone structural characteristics (bone quality) are required to have a clear view on the changes in the bone system under the conditions of a simulation experiment.     

湖南、湖北、贵州土家族成人的体成分比较

体成分指的是身体脂肪、蛋白质、肌肉、水等含量在体质量中所占的百分比.各成分之间的合理比例,对于维持机体的正常运行,十分重要.因此身体成分的研究一直是国内外研究的热点.体成分存在着人种和民族差异,因此它也是人类学研究的重要课题.目前的研究主要集中在中国青少年、大学生的体成分及体成分与其他身体指标的关系,而对于土家族的研究...     

Shape and size of the body vs. musculoskeletal stress markers

The objective of this paper is to assess the relationship between the degree of development of muscle attachment sites (musculoskeletal stress markers - MSM1) and the length and circumference measurements of long bones and the body build expressed with the reconstructed values of body height (BH) and body mass (BM). The bone material (102 male and 99 female skeletons) used in the study was collected in the medieval burial ground in Cedynia, Poland. The authors analyzed 10 musculoskeletal stress markers located on the scapula (2), humerus (2), radius (2), femur (2) and tibia (2). The frequency and the degree of expression of muscle attachment size was carried out using the scale prepared by Myszka (2007). The scale encompassed three degrees of expression of muscle attachment size. Only changes of robusticity type (nonpathological changes) were taken into account. The assessment of body build of individuals was carried out according to the method proposed by Vancata & Charvátová (2001). Body height was reconstructed from the length of the humerus and femur using eight equations. Body mass was reconstructed from the measurements of the breadth of the proximal and distal sections of the femur and tibia (mechanical method) using twenty one equations. The equations were developed for different reference populations. The same equations were used for men and women. The correlation between the MSM and the length and circumference measurements of the bones was analyzed using the principal components analysis and the Gamma correlation coefficient. The strength of the correlation between the reconstructed body build traits (BH, BM) and the moderate degree of musculoskeletal stress markers expression was studied based on the principal components method and the Pearson correlation coefficient. A linear correlation was found between musculoskeletal stress markers and the circumference measurements and the reconstructed body mass, but no relationship with body height and the length measurements of long bones was revealed. From previous research it is evident that the relationship between the MSM and metric skeletal traits does not occur in every population. Divergent findings necessitate further corroboration of results on diverse skeletal material.     

Regionalized adaptations and muscle fiber proliferation in stretch-induced enlargement

The relative contribution of increases in fiber area to stretch-induced muscle enlargement was evaluated in the slow tonic fibers of the anterior latissimus dorsi of adult Japanese quails. A weight corresponding to 10% of the bird's body mass was attached to one wing. Thirty days of stretch in 34 birds averaged 171.8 +/- 13.5% increase in muscle mass and 23.5 +/- 0.8% increase in muscle fiber length. The volume density of noncontractile tissue increased in middle and distal regions of stretch-enlarged muscles. Mean fiber cross-sectional area increased 56.7 +/- 12.3% in the midregion of stretched muscles. Further analysis indicated slow beta-fiber hypertrophy occurred in proximal, middle, and distal regions; however, fast alpha-type fiber hypertrophy was limited to middle regions of stretched muscles. Stretched muscles had a significant increase in the frequency of slow beta-fibers that were less than 500 microns 2 in all regions and fast alpha-type fibers in middle and distal regions. Total fiber number was determined after nitric acid digestion of connective tissue in 10 birds. Fiber number increased 51.8 +/- 19.4% in stretched muscle. These results are the first to clearly show that muscle fiber proliferation contributes substantially to adult skeletal muscle stretch-induced enlargement, although we do not know whether the responses of the slow tonic anterior latissimus dorsi might be similar or different from mammalian twitch muscle.     

Changes in bone mineral density and microarchitecture in cosmonauts after a six-month space flight

The effect of microgravity on the bone tissue of cosmonauts has been studied after a six-month space flight. The volumetric bone mineral density (VBMD) and the bone structural characteristics of distal segments in the radius and tibia have been studied by means of peripheral quantitative computed tomography (pQCT). The changes in VBMD were found to correlate with the position of the bone relative to the vector of gravity. In the radius, reversible hypermineralization, together with thickening of the compact bone were recorded. In the tibia, reversible osteopenia was characterized by significant losses in both compact and trabecular bones. Irrespective of the position relative to the vector of gravity, there was a trend towards microarchitectural deterioration, such as a decrease in the trabecula number and increase in the bone tissue heterogeneity. Postflight dynamics of structural parameters showed an integrative character with nonlinear time dependence.     

Experimental and finite element analysis of the rat ulnar loading model-correlations between strain and bone formation following fatigue loading

The rat forelimb compression model has been used widely to study bone response to mechanical loading. We used strain gages to assess load sharing between the ulna and radius in the forelimb of adult Fisher rats. We used histology and peripheral quantitative computed tomography (pQCT) to quantify ulnar bone formation 12 days after in vivo fatigue loading. Lastly, we developed a finite element model of the ulna to predict the pattern of surface strains during compression. Our findings indicate that at the mid-shaft the ulna carries 65% of the applied compressive force on the forelimb. We observed large variations in fatigue-induced bone formation over the circumference and length of the ulna. Bone formation was greatest 1-2 mm distal to the mid-shaft. At the mid-shaft, we observed woven bone formation that was greatest medially. Finite element analysis indicated a strain pattern consistent with a compression-bending loading mode, with the greatest strains occurring in compression on the medial surface and lesser tensile strains occurring laterally. A peak strain of -5190 microepsilon (for 13.3N forelimb compression) occurred 1-2 mm distal to the mid-shaft. The pattern of bone formation in the longitudinal direction was highly correlated to the predicted peak compressive axial strains at seven cross-sections (r2 = 0.89, p = 0.014). The in-plane pattern of bone formation was poorly correlated to the predicted magnitude of axial strain at 51 periosteal locations (r2 = 0.21, p < 0.001), because the least bone formation was observed where tensile strains were highest. These findings indicate that the magnitude of bone formation after fatigue loading is greatest in regions of high compressive strain.     

Differences in skeletal and muscle mass with aging in black and white women

Previous cross-sectional studies using delayed gamma neutron activation analysis and whole body counting suggested that the relationship of total body calcium (TBCa) to total body potassium (TBK) (muscle mass, body cell mass) remained constant with age. This led to the hypothesis that the muscle mass and skeletal mass compartments are integrated in their response to aging. It had also been hypothesized that loss of skeletal and muscle mass was similar between races. In the current study, delayed gamma neutron activation analysis and whole body counting were performed on 90 black and 143 white women 20-69 yr of age. Black women had higher TBCa and TBK values than white women, even when the data were adjusted for age, height, and weight. TBCa was correlated with height and TBK with weight. The estimated decline of skeletal mass (TBCa) from 20 to 70 yr was 18% in black women and 19% in white women. However, the lifetime decline of TBK was only 8% for black women, compared with 22% for white women. Black women may lose TBK more slowly than TBCa with aging, compared with white women. In particular, correlation of TBCa and age was similar for blacks and whites (r = -0.44 and r = -0.54, respectively). However, for TBK these correlations were r = -0.14 and r = -0.42. These data confirm a higher musculoskeletal mass in black women and suggest that the loss of muscle mass with age may be lower in black than in white women. These ethnic differences do not support the hypothesis of an integrated musculoskeletal system, so that these two components should be considered separately. A prospective study is needed to confirm these findings.     

Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats.

This study was designed to determine the effects of 28 days of hindlimb unloading (HU) on the mature female rat skeleton. In vivo proximal tibia bone mineral density and geometry of HU and cage control (CC) rats were measured with peripheral quantitative computed tomography (pQCT) on days 0 and 28. Postmortem pQCT, histomorphometry, and mechanical testing were performed on tibiae and femora. After 28 days, HU animals had significantly higher daily food consumption (+39%) and lower serum estradiol levels (-49%, P = 0.079) compared with CC. Proximal tibia bone mineral content and cortical bone area significantly declined over 28 days in HU animals (-4.0 and 4.8%, respectively), whereas total and cancellous bone mineral densities were unchanged. HU animals had lower cortical bone formation rates and mineralizing surface at tibial midshaft, whereas differences in similar properties were not detected in cancellous bone of the distal femur. These results suggest that cortical bone, rather than cancellous bone, is more prominently affected by unloading in skeletally mature retired breeder female rats.     

Hormonal aspects of the muscle-bone unit

Osteoporotic fractures are the result of low density and especially inferior bone quality (microarchitecture) caused by both internal (genes, hormones) and external (life style) influences. Bone mechanosensors are extremely important for the overall integrity of the skeleton, because in response to mechanical load they activate its modeling, resulting in an increase in bone density and strength. The largest physiological loads are caused by muscle contractions. Bone mass in adult men has a closer relationship to muscle mass than is case in women. The sexual differences in the relationship between bone and muscle mass are also apparent in children. Based on the mechanostatic theory, the muscle-bone unit has been defined as a functional system whose components are under the common control of the hormones of the somatotropin-IGF-I axis, sexual steroids, certain adipose tissue hormones and vitamin D. The osteogenic effects of somatotropin-IGF-I system are based on the stimulation of bone formation, as well as increase in muscle mass. Moreover, somatotropin decreases the bone mechanostat threshold and reinforces the effect of physical stress on bone formation. The system, via the muscle-bone unit, plays a significant role in the development of the childhood skeleton as well as in its stability during adulthood. The muscle and bone are also the targets of androgens, which increase bone formation and the growth of muscle mass in men and women, independently of IGF-I. The role of further above-mentioned hormones in regulation of this unified functional complex is also discussed.     

Bone mineral density in Addison's disease: evidence for an effect of adrenal androgens on bone mass.

It is unknown whether replacement doses of cortisone acetate and the absence of the small amounts of androgens secreted by the adrenal cortex may cause osteoporosis. This was studied in 35 patients (12 men and 23 women) suffering from primary adrenocortical failure and taking cortisone acetate 25-37.5 mg and fludrocortisone 50-100 micrograms daily. Bone mineral density was measured by single photon absorptiometry at the midshaft of the radius, representing cortical bone, and at the distal part of the radius, a site with a significant trabecular component. The bone mineral density was normal in premenopausal female patients as well as in male patients, showing that replacement doses of cortisone acetate do not affect bone mass. By contrast, in postmenopausal patients there was a dramatic bone loss in addition to the physiological postmenopausal decrease in bone mass. This loss, combined with the low plasma concentrations of androstenedione, dehydroepiandrosterone, and testosterone (and low concentrations of oestrone of adrenal origin), indicates that adrenal androgens may be essential for the maintenance of bone mass in postmenopausal women with Addison''s disease. In addition, these data indicate that the small amounts of androgens secreted by the adrenal cortex have a role in the maintenance of bone mass in normal postmenopausal women.     

Functional assessment of the muscle-bone unit in the lower leg

Based on the mechanostat theory and the muscle-bone hypothesis, a methodological assessment of the musculoskeletal status in health and disease should relate maximum muscle force in relation to bone mass and geometry. While useful (i.e. three-dimensional) measures of tibial bone parameters can be obtained by peripheral quantitative computed tomography (pQCT), intrinsic plantarflexor muscle force cannot be directly measured under in vivo condition in humans. Instead, tissue size, torque and ground reaction force have been used as proxy markers of intrinsic muscle force. However, most of these proxy markers are not or insufficiently representative of maximum force. Based on our recent research, we describe a novel approach for the assessment of the lower leg muscle-bone unit in health and disease. It incorporates multiple one-legged hopping (m1LH) to assess maximum voluntary ground reaction force acting on the forefoot (F(m1LH)) and bone mineral content at the 14%-site of tibia length (vBMC(14%)) as assessed by pQCT. Using the quantitative relationship between these two variables in conjunction with F(m1LH) per body weight, we present a two-step quantitative diagnostic algorithm to discriminate between primary and secondary bone disorders in children and adults.