Muscular development and physical activity as major determinants of femoral bone mass acquisition during growth

[EN] OBJECTIVES: To investigate to what extent bone mass accrual is determined by physical activity and changes in lean, fat, and total body mass during growth. METHODS: Twenty six physically active and 16 age matched control boys were followed up for three years. All subjects were prepubertal at the start of the survey (mean (SEM) age 9.4 (0.3) years). The weekly physical activity of the active boys included compulsory physical education sessions (80-90 minutes a week), three hours a week of extracurricular sports participation, and occasional sports competitions at weekends. The physical activity of the control group was limited to the compulsory physical education curriculum. Bone mineral content (BMC) and areal density (BMD), lean mass, and fat mass were measured by dual energy x ray absorptiometry. RESULTS: The effect of sports participation on femoral bone mass accrual was remarkable. Femoral BMC and BMD increased twice as much in the active group as in the controls over the three year period (p < 0.05). The greatest correlation was found between the increment in femoral bone mass and the increment in lean mass (BMC r = 0.67 and BMD r = 0.69, both p < 0.001). Multiple regression analysis revealed enhancement in lean mass as the best predictor of the increment in femoral bone BMC (R = 0.65) and BMD (R = 0.69). CONCLUSIONS: Long term sports participation during early adolescence results in greater accrual of bone mass. Enhancement of lean mass seems to be the best predictor of this bone mass accumulation. However, for a given muscle mass, a greater level of physical activity is associated with greater bone mass and density in peripubertal boys.

Overweight children have a greater proportion of fat mass relative to muscle mass in the upper limbs than in the lower limbs: implications for bone strength at the distal forearm

BACKGROUND: The influence of adiposity on upper-limb bone strength has rarely been studied in children, despite the high incidence of forearm fractures in this population. OBJECTIVE: The objective was to compare the influence of muscle and fat tissues on bone strength between the upper and lower limbs in prepubertal children. DESIGN: Bone mineral content, total bone cross-sectional area, cortical bone area (CoA), cortical thickness (CoTh) at the radius and tibia (4% and 66%, respectively), trabecular density (TrD), bone strength index (4% sites), cortical density (CoD), stress-strain index, and muscle and fat areas (66% sites) were measured by using peripheral quantitative computed tomography in 427 children (206 boys) aged 7-10 y. RESULTS: Overweight children (n = 93) had greater values for bone variables (0.3-1.3 SD; P < 0.0001) than did their normal-weight peers, except for CoD 66% and CoTh 4%. The between-group differences were 21-87% greater at the tibia than at the radius. After adjustment for muscle cross-sectional area, TrD 4%, bone mineral content, CoA, and CoTh 66% at the tibia remained greater in overweight children, whereas at the distal radius total bone cross-sectional area and CoTh were smaller in overweight children (P < 0.05). Overweight children had a greater fat-muscle ratio than did normal-weight children, particularly in the forearm (92 +/- 28% compared with 57 +/- 17%). Fat-muscle ratio correlated negatively with all bone variables, except for TrD and CoD, after adjustment for body weight (r = -0.17 to -0.54; P < 0.0001). CONCLUSIONS: Overweight children had stronger bones than did their normal-weight peers, largely because of greater muscle size. However, the overweight children had a high proportion of fat relative to muscle in the forearm, which is associated with reduced bone strength.

Reduced bone breakage and increased bone strength in free range laying hens fed omega-3 polyunsaturated fatty acid supplemented diets

INTRODUCTION The omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are the immediate precursors to a number of important mediators of immunity, inflammation and bone function, with products of omega-6 generally thought to promote inflammation and favour bone resorption. Western diets generally provide a 10 to 20-fold deficit in omega-3 PUFAs compared with omega-6, and this is thought to have contributed to the marked rise in incidence of disorders of modern human societies, such as heart disease, colitis and perhaps osteoporosis. Many of our food production animals, fed on grains rich in omega-6, are also exposed to a dietary deficit in omega-3, with perhaps similar health consequences. Bone fragility due to osteoporotic changes in laying hens is a major economic and welfare problem, with our recent estimates of breakage rates indicating up to 95% of free range hens suffer breaks during lay. METHODS Free range hens housed in full scale commercial systems were provided diets supplemented with omega-3 alpha linolenic acid, and the skeletal benefits were investigated by comparison to standard diets rich in omega-6. RESULTS There was a significant 40-60% reduction in keel bone breakage rate, and a corresponding reduction in breakage severity in the omega-3 supplemented hens. There was significantly greater bone density and bone mineral content, alongside increases in total bone and trabecular volumes. The mechanical properties of the omega-3 supplemented hens were improved, with strength, energy to break and stiffness demonstrating significant increases. Alkaline phosphatase (an osteoblast marker) and tartrate-resistant acid phosphatase (an osteoclast marker) both showed significant increases with the omega-3 diets, indicating enhanced bone turnover. This was corroborated by the significantly lower levels of the mature collagen crosslinks, hydroxylysyl pyridinoline, lysyl pyridinoline and histidinohydroxy-lysinonorleucine, with a corresponding significant shift in the mature:immature crosslink ratio. CONCLUSIONS The improved skeletal health in laying hens corresponds to as many as 68million fewer hens suffering keel fractures in the EU each year. The biomechanical and biochemical evidence suggests that increased bone turnover has enhanced the bone mechanical properties, and that this may suggest potential benefits for human osteoporosis.

The 'muscle-bone unit' during the pubertal growth spurt

Mechanostat theory postulates that developmental changes in bone strength are secondary to the increasing loads imposed by larger muscle forces. Therefore, the increase in muscle strength should precede the increase in bone strength. We tested this prediction using densitometric surrogate measures of muscle force (lean body mass, LBM) and bone strength (bone mineral content, BMC) in a study on 70 boys and 68 girls who were longitudinally examined during pubertal development. On the level of the total body, the peak in LBM accrual preceded the peak in BMC accretion by an average of 0.51 years in girls and by 0.36 years in boys. In the arms, the maximal increase in LBM was followed by arm peak BMC accrual after an interval of 0.71 years in girls and 0.63 years in boys. In the lower extremities, the maximal increase in LBM was followed by peak BMC accrual after an interval of 0.22 years in girls and 0.48 years in boys. A multiple regression model revealed that total body peak LBM velocity, but not peak height velocity and sex, was independently associated with total body peak BMC velocity (r(2) = 0.50; P < 0.001). Similarly, arm and leg peak LBM velocity, but not peak height velocity and sex, were independently associated with arm and leg peak BMC velocity, respectively (r(2) = 0.61 for arms, r(2) = 0.41 for legs; P < 0.001 in both cases). These results are compatible with the view that bone development is driven by muscle development, although the data do not exclude the hypothesis that the two processes are independently determined by genetic mechanisms. (C) 2004 Elsevier Inc. All rights reserved.

Mechanical vibration preserves bone structure in rats treated with glucocorticoids

Glucocorticoids are an important cause of secondary osteoporosis in humans, which decreases bone quality and leads to fractures. Mechanical stimulation in the form of low-intensity and high-frequency vibration seems to be able to prevent bone loss and to stimulate bone formation. The objective of this study was to evaluate the effects of mechanical vibration on bone structure in rats treated with glucocorticoids. Thirty 3-month-old adult male Wistar rats were randomized to three groups: control (C), glucocorticoid (G), and glucocorticoid with vibration (CV). The G and GV groups received 3.5 mg/kg/day of methylprednisolone 5 days/week for a duration of 9 weeks, and the C group received vehicle (saline solution) during the same period. The CV group was vibrated on a special platform for 30 min per day, 5 days per week during the experiment. The platform was set to provide a vertical acceleration of 1 G and a frequency of 60 Hz. Skeletal bone mass was evaluated by total body densitometry (DXA). Fracture load threshold, undecalcified bone histomorphometry, and bone volume were measured in tibias. Glucocorticoids induced a significantly lower weight gain (-9.7%) and reduced the bone mineral content (-9.2%) and trabecular number (-41.8%) and increased the trabecular spacing (+98.0%) in the G group, when compared to the control (C). Vibration (CV) was able to significantly preserve (29.2%) of the trabecular number and decrease the trabecular spacing (+ 26.6%) compared to the G group, although these parameters did not reach C group values. The fracture load threshold was not different between groups, but vibration significantly augmented the bone volume of the tibia by 21.4% in the CV group compared to the C group. Our study demonstrated that low-intensity and high-frequency mechanical vibration was able to partially inhibit the deleterious consequences of glucocorticoids on bone structure in rats. (C) 2010 Elsevier Inc. All rights reserved.

Coronary Calcification Is Associated With Lower Bone Formation Rate in CKD Patients Not Yet in Dialysis Treatment

Vascular calcification is a strong prognostic marker of mortality in hemodialysis patients and has been associated with bone metabolism disorders in this population. In earlier stages of chronic kidney disease (CKD), vascular calcification also has been documented. This study evaluated the association between coronary artery calcification (CAC) and bone histomorphometric parameters in CKD predialysis patients assessed by multislice coronary tomography and by undecalcified bone biopsy. CAC was detected in 33 (66%) patients, and their median calcium score was 89.7 (0.4-2299.3 AU). The most frequent bone histologic alterations observed included low trabecular bone volume, increased eroded and osteoclast surfaces, and low bone-formation rate (BFR/BS). Multiple logistic regression analysis, adjusted for age, sex, and diabetes, showed that BFR/BS was independently associated with the presence of coronary calcification [p=.009; odd ratio (OR) = 0.15; 95% confidence interval (Cl) 0.036-0.619] This study showed a high prevalence of CAC in asymptomatic predialysis CKD patients. Also, there was an independent association of low bone formation and CAC in this population. In conclusion, our results provide evidence that low bone-formation rate constitutes another nontraditional risk factor for cardiovascular disease in CKD patients. 2010 American Society for Bone and Mineral Research.

EVALUATION OF CENTRIFUGED OSTEOGENIC BONE MARROW IN FRACTURE CONSOLIDATION IN RABBITS

Objective The purpose of this study was to evaluate the efficacy of a centrifuged osteogenic bone marrow aspirate to stimulate healing in rabbit fibular osteotomies Methods Ten white New Zealand rabbits were used A transverse medial diaphyseal fibular osteotomy was performed on the right fibula where an absorbable collagen sponge embedded in osteogenic centrifuged bone marrow aspirate obtained from the ipsilateral iliac bone was inserted The left fibula was used as the control group where the collagen absorbable sponge was inserted without the osteogenic centrifuged aspirate The rabbits were sacrificed four weeks after surgery to evaluate bone callus formation Analyses of results were performed with DEXA bone densitometry to evaluate callus mineral mass multislice computed tomography to evaluate callus volume and histomorphometry to evaluate the relative rate of tissue formation Results The employment of centrifuged osteogenic bone marrow aspirate resulted in a 40 3% increase of callus bone mineral mass and increased relative quantity of bone tissue formation by 9 4% without a significant increase in the relative quantities of cartilage fibrous tissue or in callus volume Conclusions This study shows that the centrifuged osteogenic bone marrow aspirate was able to improve the healing of experimental fibular osteotomies in rabbits

Bril: A novel bone-specific modulator of mineralization

In the course of attempting to define the bone ""secretome"" using a signal-trap screening approach, we identified a gene encoding a small membrane protein novel to osteoblasts. Although previously identified in silico as ifitm5, no localization or functional studies had been undertaken on this gene. We characterized the expression patterns and localization of this gene in vitro and in vivo and assessed its role in matrix mineralization in vitro. The bone specificity and shown role in mineralization led us to rename the gene bone restricted ifitm-like protein (Bril). Bril encodes a 14.8-kDa 1.34 arnino acid protein with two transmembrane domains. Northern blot analysis showed bone-specific expression with no expression in other embryonic or adult tissues. In situ hybridization and immunohistochemistry in mouse embryos showed expression localized on the developing bone. Screening of cell lines showed Bril expression to be highest in osteoblasts, associated with the onset of matrix maturation/mineralization, suggesting a role in bone formation. Functional evidence of a role in mineralization was shown by adenovirus-mediated Brit overexpression and lentivirus-mediated Bril shRNA knockdown in vitro. Elevated Bril resulted in dose-dependent increases in mineralization in UMR106 and rat primary osteoblasts. Conversely, knockdown of Bril in MC3T3 osteoblasts resulted in reduced mineralization. Thus, we identified Bril as a novel osteoblast protein and showed a role in mineralization, possibly identifying a new regulatory pathway in bone formation.

Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures

We recently demonstrated that suppressed bone remodeling allows microdamage to accumulate and causes reductions in some mechanical properties. However, in our previous study, I year treatment with high-dose etidronate (EHDP) did not increase microdamage accumulation in most skeletal sites of dogs in spite of complete remodeling suppression and the occurrence of spontaneous fractures of ribs and/or thoracic spinous processes. This study evaluates the effects of EHDP on microdamage accumulation and biomechanical properties before fractures occur. Thirty-six female beagles, 1-2 years old, were treated daily for 7 months with subcutaneous injections of saline vehicle (CNT) or EHDP at 0.5 (E-low) or 5 mg/kg per day (E-high). After killing, bone mineral measurement, histomorphometry, microdamage analysis, and biomechanical testing were performed. EHDP treatment suppressed intracortical and trabecular remodeling by 60%-75% at the lower dose, and by 100% at the higher dose. Osteoid accumulation caused by a mineralization deficit occurred only in the E-high group, and this led to a reduction of mineralized bone mass. Microdamage accumulation increased significantly by two- to fivefold in the rib, lumbar vertebra, ilium, and thoracic spinous process in E-low, and by twofold in the lumbar vertebra and ilium in E-high. However, no significant increase in damage accumulation was observed in ribs or thoracic spinous processes in E-high where fractures occur following 12 months of treatment. Mechanical properties of lumbar vertebrae and thoracic spinous processes were reduced significantly in both E-low and E-high. These findings suggest that suppression of bone remodeling by EHDP allows microdamage accumulation, but that osteoid accumulation reduces production of microdamage. (Bone 29:271-278; 2001) (C) 2001 by Elsevier Science Inc. All rights reserved.

Age does not influence the bone response to treadmill exercise in female rats

Purpose: Because it is believed that bone may respond to exercise differently at different ages, we compared bone responses in immature and mature rats after 12 wk of treadmill running. Methods: Twenty-two immature (5-wk-old) and 21 mature (17-wk-old) female Sprague Dawley rats were randomized into a running (trained, N = 10 immature, 9 mature) or a control group (controls, N 12 immature, 12 mature) before sacrifice 12 wk later. Rats ran on a treadmill five times per week for 60-70 min at speeds up to 26 m.min(-1). Both at baseline and after intervention, we measured total body, lumbar spine, and proximal femoral bone mineral, as well as total body soft tissue composition using dual-energy x-ray absorptiometry (DXA) in vivo. After sacrificing the animals, we measured dynamic and static histomorphometry and three-point bending strength of the tibia. Results: Running training was associated with greater differences in tibial subperiosteal area, cortical cross-sectional area, peak load, stiffness, and moment of inertia in immature and mature rats (P < 0.05). The trained rats had greater periosteal bone formation rates (P < 0.01) than controls, but there was no difference in tibial trabecular bone histomorphometry. Similar running-related gains were seen in DXA lumbar spine area (P = 0.04) and bone mineral content (BMC; P = 0.03) at both ages. For total body bone area and BMC, the immature trained group increased significantly compared with controls (P < 0.05), whereas the mature trained group gained less than did controls (P < 0.01). Conclusion: In this in vivo model, where a similar physical training program was performed by immature and mature female rats, we demonstrated that both age groups were sensitive to loading and that bone strength gains appeared to result more from changes in bone geometry than from improved material properties.

The predictive value of trabecular bone score (TBS) on whole lumbar vertebrae mechanics: an ex vivo study.

We investigated the association of trabecular bone score (TBS) with microarchitecture and mechanical behavior of human lumbar vertebrae. We found that TBS reflects vertebral trabecular microarchitecture and is an independent predictor of vertebral mechanics. However, the addition of TBS to areal BMD (aBMD) did not significantly improve prediction of vertebral strength. INTRODUCTION: The trabecular bone score (TBS) is a gray-level measure of texture using a modified experimental variogram which can be extracted from dual-energy X-ray absorptiometry (DXA) images. The current study aimed to confirm whether TBS is associated with trabecular microarchitecture and mechanics of human lumbar vertebrae, and if its combination with BMD improves prediction of fracture risk. METHODS: Lumbar vertebrae (L3) were harvested fresh from 16 donors. The anteroposterior and lateral bone mineral content (BMC) and areal BMD (aBMD) of the vertebral body were measured using DXA; then, the TBS was extracted using TBS iNsight software (Medimaps SA, France). The trabecular bone volume (Tb.BV/tissue volume, TV), trabecular thickness (Tb.Th), degree of anisotropy, and structure model index (SMI) were measured using microcomputed tomography. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies to assess failure load and stiffness. RESULTS: The TBS was significantly correlated to Tb.BV/TV and SMI (râeuro0/00=âeuro0/000.58 and -0.62; pâeuro0/00=âeuro0/000.02, 0.01), but not related to BMC and BMD. TBS was significantly correlated with stiffness (râeuro0/00=âeuro0/000.64; pâeuro0/00=âeuro0/000.007), independently of bone mass. Using stepwise multiple regression models, we failed to demonstrate that the combination of BMD and TBS was better at explaining mechanical behavior than either variable alone. However, the combination TBS, Tb.Th, and BMC did perform better than each parameter alone, explaining 79 % of the variability in stiffness. CONCLUSIONS: In our study, TBS was associated with microarchitecture parameters and with vertebral mechanical behavior, but TBS did not improve prediction of vertebral biomechanical properties in addition to aBMD.

Weight-bearing bones are more sensitive to physical exercise in boys than in girls during pre- and early puberty: a cross-sectional study.

We carried out a cross-section study of the sex-specific relationship between bone mineral content and physical activity at sites with different loading in pre- and early pubertal girls and boys. There was significant sensitivity of bone mineral content of the hip to physical exercise in boys, but not in girls. BACKGROUND: Since little is known whether there are sex differences in sensitivity of bone to loading, we investigated sex differences in the cross-sectional association between measures of physical activity (PA) and bone mass and size in pre- and early pubertal children of both sexes. METHODS: We measured bone mineral content/density (BMC/BMD) and fat-free mass (FFM) in 269 6- to 13-year-old children from randomly selected schools by dual-energy X-ray absorptiometry. Physical activity (PA) was measured by accelerometers and lower extremity strength by a jump-and-reach test. RESULTS: Boys (n = 128) had higher hip and total body BMC and BMD, higher FFM, higher muscle strength and were more physically active than girls (n = 141). Total hip BMC was positively associated with time spent in total and vigorous PA in boys (r = 0.20-0.33, p < 0.01), but not in girls (r = 0.02-0.04, p = ns), even after adjusting for FFM and strength. While boys and girls in the lowest tertile of vigorous PA (22 min/day) did not differ in hip BMC (15.62 vs 15.52 g), boys in the highest tertile (72 min/day) had significantly higher values than the corresponding girls (16.84 vs 15.71 g, p < 0.05). CONCLUSIONS: Sex differences in BMC during pre- and early puberty may be related to a different sensitivity of bone to physical loading, irrespective of muscle mass.

Does Bracing affect Bone Health in Females with adolescent Idiopathic Scoliosis?

This study examined the bone mineral content (BMC) in young women with Adolescent Idiopathic Scoliosis (AIS), treated with a brace (27.9 ±21.6 months, for 18.0±5.4 h/d) during adolescence (AIS-B, n = 15, 25.6 ±5.8 yrs), versus women with AIS but no treatment (AIS-NB, n = 15, 24.0 ±4.0 yrs), and women without AIS (C, n = 19, 23.5 ±3.8 yrs). After controlling for lean body mass, calcium and vitamin D daily intake, and strenuous physical activity, femoral neck BMC was lower in the AIS-B compared with AIS-NB and C (all p’s < .05). In summary, women with AIS, braced during their growing years are characterized by low lower limb BMC. However, the lack of a relationship between brace treatment duration and BMC, suggests that bracing was not the likely mechanism.

The effect of impaired thyroid function during development on the mechanical properties of avian bone

Thyroid hormones show fluctuating levels during the post-hatching development of birds. In this paper we report the results of the first mechanical tests to quantify the effect of hypothyroidism, during post-natal development, on the skeletal properties of a precocial bird, the barnacle goose, as determined by microhardness testing. The effect of hypothyroidism is tissue-specific; bone from the femora of birds is not significantly affected by induced hypothyroidism, however, there is a strong positive relationship between the levels of circulating thyroid hormones and the mechanical properties of bone from humeri. In the barnacle goose the development of the wing skeleton and musculature depends on an increase in circulating thyroid hormones and our analysis shows that, in its absence, the mechanical competence of the bone mineral itself is reduced in addition to the decreased bone length and muscle development previously reported in the literature. (C) 2004 Wiley-Liss, Inc.