The association of serum 25-hydroxyvitamin D with indicators of bone quality in men of Caucasian and African ancestry.

UNLABELLED: We examined the association of serum 25-hydroxyvitamin D [25(OH)D] with indices of bone quality in older men. Positive associations for 25(OH)D and bone mineral density, content, cortical thickness, and axial and polar strength strain indices were observed among Caucasians; however, among men of African descent findings were either null or negative. INTRODUCTION: There are limited data on serum 25(OH)D and bone measures in men of African ancestry. To better understand racial differences in vitamin D status and bone health, a cross-sectional study among 446 Caucasian men in the US and 496 men of African ancestry in Tobago (age ≥ 65 years) was conducted. METHODS: Serum 25(OH)D (liquid chromatography and tandem mass spectrometry) was measured, and peripheral quantitative computed tomography scans were administered. Bone measures estimated included trabecular and cortical volumetric bone mineral density (vBMD), bone mineral content (BMC), bone geometry (cross-sectional area and cortical thickness), and polar and axial strength strain indices (SSIp and SSIx). RESULTS: Men of African ancestry had higher 25(OH)D than Caucasians (34.7 vs. 27.6 ng/ml, p < 0.01). Among Caucasians, 25(OH)D was positively (p trend < 0.05) associated with cortical vBMD, total BMC, cortical thickness, SSIp, and SSIx at the distal radius after adjustment for potential confounders. Similar patterns were observed at the distal tibia. In contrast, in men of African ancestry, there was an inverse association (p trend < 0.05) between 25(OH)D and the cross-sectional area, and SSIx. Race modified (p for interaction < 0.05) the association between 25(OH)D and total BMC, cross-sectional area, SSIp, SSIx, and trabecular vBMD of the radius. In men of African ancestry, there was evidence of a threshold effect (at approximately 18 ng/ml) for 25(OH)D on tibial total BMC and cortical thickness. CONCLUSIONS: More studies are needed to better comprehend these race differences for 25(OH)D and bone density, geometry, and indices of bone strength.

Peripubertal estrogen levels and physical activity affect femur geometry in young adult women.

UNLABELLED: The growing skeleton is particularly responsive to exercise around the time of puberty, suggesting a possible role for estrogen in mechanical adaptation in young women. We assessed femoral neck strength index at age 17 in young women with varying adolescent physical activity levels and E2 levels in the first 3 years after menarche. The results indicate that both E2 levels in the first year after menarche and adolescent physical activity are positively associated with bone strength in young adulthood, such that hormone levels may modify human osteogenic responses to exercise. INTRODUCTION: It is well established that physical activity contributes to bone strength in young females, but less is known about how peripubertal estrogen affects skeletal responses to exercise. METHODS: We used data from 84 participants in the Penn State Young Women's Health Study to test the prediction that young women who (1) had higher E2 levels during the first year after menarche or (2) were more physically active in adolescence will have greater bone strength at the end of adolescence. Subjects were divided into tertiles of physical activity and of E2 level in the first, second, and third postmenarchal years, and femoral strength was calculated from dual-energy X-ray absorptiometry scans of the proximal femur using hip structure analysis. RESULTS: At age 17, subjects with the highest E2 levels in year 1 after menarche had 5-14% greater strength in the narrow neck and intertrochanteric region, and the most active subjects had 10-11% greater strength in the femoral narrow neck vs. less active girls. CONCLUSIONS: This study suggests that both physical activity and peripubertal estrogen have important influences on young adult bone strength and that hormone levels may be mediators of human osteogenic responses to exercise.

Biological underpinnings of Frost's mechanostat thresholds: the important role of osteocytes.

Harold Frost first proposed the existence of several mechanical thresholds in bone, two of which determine whether bone is added to, or lost from, the skeleton. Recent evidence from bone biology helps elucidate the role of osteocytes in determining these mechanical thresholds. Specifically, when mechanical stimuli fall below the resorption threshold, osteocyte apoptosis occurs, followed by bone resorption. Conversely, mechanical loading maintains osteocytes viability, and consequently, no bone is lost. With a greater than customary mechanical stimulus, osteocytes perturbation from pulsatile fluid flow results in release of anabolic factors and subsequent bone formation. Osteocytes also play a pivotal role in bone remodeling in response to alterations in the mechanical environment. In particular, osteocyte apoptosis results in bone turnover in disuse as well as in response to greater than customary mechanical stimuli due to microdamage accumulation. Given the important role of osteocytes in bone modeling and remodeling, these cells provide an ideal target for both drug therapies and exercise to prevent bone fragility.

New insights into intestinal phages.

The intestinal microbiota plays important roles in human health. This last decade, the viral fraction of the intestinal microbiota, composed essentially of phages that infect bacteria, received increasing attention. Numerous novel phage families have been discovered in parallel with the development of viral metagenomics. However, since the discovery of intestinal phages by d'Hérelle in 1917, our understanding of the impact of phages on gut microbiota structure remains scarce. Changes in viral community composition have been observed in several diseases. However, whether these changes reflect a direct involvement of phages in diseases etiology or simply result from modifications in bacterial composition is currently unknown. Here we present an overview of the current knowledge in intestinal phages, their identity, lifestyles, and their possible effects on the gut microbiota. We also gather the main data on phage interactions with the immune system, with a particular emphasis on recent findings.

Correction: New insights into intestinal phages.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Does a novel school-based physical activity model benefit femoral neck bone strength in pre- and early pubertal children?

UNLABELLED: The effects of physical activity on bone strength acquisition during growth are not well understood. In our cluster randomized trial, we found that participation in a novel school-based physical activity program enhanced bone strength acquisition and bone mass accrual by 2-5% at the femoral neck in girls; however, these benefits depended on teacher compliance with intervention delivery. Our intervention also enhanced bone mass accrual by 2-4% at the lumbar spine and total body in boys. INTRODUCTION: We investigated the effects of a novel school-based physical activity program on femoral neck (FN) bone strength and mass in children aged 9-11 yrs. METHODS: We used hip structure analysis to compare 16-month changes in FN bone strength, geometry and bone mineral content (BMC) between 293 children who participated in Action Schools! BC (AS! BC) and 117 controls. We assessed proximal femur (PF), lumbar spine (LS) and total body (TB) BMC using DXA. We compared change in bone outcomes between groups using linear regression accounting for the random school effect and select covariates. RESULTS: Change in FN strength (section modulus, Z), cross-sectional area (CSA), subperiosteal width and BMC was similar between control and intervention boys, but intervention boys had greater gains in BMC at the LS (+2.7%, p = 0.05) and TB (+1.7%, p = 0.03) than controls. For girls, change in FN-Z tended to be greater (+3.5%, p = 0.1) for intervention girls than controls. The difference in change increased to 5.4% (p = 0.05) in a per-protocol analysis that included girls whose teachers reported 80% compliance. CONCLUSION: AS! BC benefits bone strength and mass in school-aged children; however, our findings highlight the importance of accounting for teacher compliance in classroom-based physical activity interventions.

The NAD-dependent ligase encoded by yerG is an essential gene of Bacillus subtilis.

DNA ligases are grouped into two families, ATP-dependent and NAD-dependent, according to the cofactor required for their activity. A surprising capability of both kinds of ligases to complement for one another in vivo has been observed. Bacillus subtilis harbours one NAD-dependent ligase, YerG, and two ATP-dependent ligases, YkoU and YoqV, this last one being encoded by the 134 kb lysogenic bacteriophage SPss and consisting of a single adenylation domain typical of ATP-dependent ligases. Because the genetics of ligases in B.subtilis had not been studied previously, the genes encoding for one ligase of each kind, yerG and yoqV, were investigated. We found that the yerG gene was essential in B.subtilis. This suggests that none of the ATP-dependent ligases was able to complement the yerG defect. In addition, the ATP-dependent ligase encoded by yoqV, when cloned on a plasmid under appropriate expression signals, was unable to rescue a yerG mutant strain. The two B.subtilis ligase genes yerG and yoqV were also introduced in an Escherichia coli strain encoding a thermosensitive ligase (ligts), and whereas yoqV did not complement the ligts defects, yerG fully complemented the growth and UV sensitivity defects of the lig mutant. We propose to rename the yerG and yoqV genes of B.subtilis ligA and ligB respectively.

Systematic determination of the mosaic structure of bacterial genomes: species backbone versus strain-specific loops.

BACKGROUND: Public databases now contain multitude of complete bacterial genomes, including several genomes of the same species. The available data offers new opportunities to address questions about bacterial genome evolution, a task that requires reliable fine comparison data of closely related genomes. Recent analyses have shown, using pairwise whole genome alignments, that it is possible to segment bacterial genomes into a common conserved backbone and strain-specific sequences called loops. RESULTS: Here, we generalize this approach and propose a strategy that allows systematic and non-biased genome segmentation based on multiple genome alignments. Segmentation analyses, as applied to 13 different bacterial species, confirmed the feasibility of our approach to discern the 'mosaic' organization of bacterial genomes. Segmentation results are available through a Web interface permitting functional analysis, extraction and visualization of the backbone/loops structure of documented genomes. To illustrate the potential of this approach, we performed a precise analysis of the mosaic organization of three E. coli strains and functional characterization of the loops. CONCLUSION: The segmentation results including the backbone/loops structure of 13 bacterial species genomes are new and available for use by the scientific community at the URL: http://genome.jouy.inra.fr/mosaic.

Plasmid replication stimulates DNA recombination in Bacillus subtilis.

The effects of plasmid replication on the frequency of homologous recombination have been investigated. For that purpose Bacillus subtilis strains that carry in their chromosome directly repeated DNA sequences, and an integrated copy of plasmid pE194 either proximal or distal to the repeats, were constructed. The repeat consists either of 3.9 X 10(3) base pBR322 sequences or 2.1 X 10(3) base B. subtilis chromosomal sequences. As plasmid pE194 is naturally thermosensitive for replication, the activity of the replicon could be regulated. Recombination between the repeated sequences was infrequent (about 10(-4) per generation) when the integrated plasmid did not replicate. It was 20 to 450 times higher when the plasmid was allowed to replicate, provided that the repeats were in the proximity of the plasmid. These results show that plasmid replication stimulates DNA recombination.

Control of large chromosomal duplications in Escherichia coli by the mismatch repair system.

Excessive recombination between repeated, interspersed, and diverged DNA sequences is a potential source of genomic instability. We have investigated the possibility that a mechanism exists to suppress genetic exchange between these quasi-homologous (homeologous) sequences. We examined the role of the general mismatch repair system of Escherichia coli because previous work has shown that the mismatch repair pathway functions as a barrier to interspecies recombination between E. coli and Salmonella typhimurium. The formation of large duplications by homeologous recombination in E. coli was increased some tenfold by mutations in the mutL and mutS genes that encode the mismatch recognition proteins. These findings indicate that the mismatch recognition proteins act to prevent excessive intrachromosomal exchanges. We conclude that mismatch repair proteins serve as general controllers of the fidelity of genetic inheritance, acting to suppress chromosomal rearrangements as well as point mutations.

Examining the developing bone: What do we measure and how do we do it?

The clinical tools available to evaluate bone development in children are often ambiguous, and difficult to interpret. Unfortunately bone densitometry methods (i.e., dual energy X-ray absorptiometry, DXA) which have a relatively straightforward application in adult osteoporosis, are far more difficult to evaluate in the growing skeleton. Even with adequate "adjustment" for bone size or maturity, bone "density" (areal or volumetric) alone often gives an inaccurate assessment of bone strength--especially in children. Ideally, we would like to measure both material and geometric properties of bone to accurately estimate "strength". Mechanically meaningful measures of bone geometry (bone cross-sectional area, cortical thickness) and estimates of bending strength (section modulus, or SSI) are available with non-invasive techniques such as (p)QCT and some DXA software. With new technology it might be possible to also measure bone material properties, which will be especially important in some pediatric disorders. In children, we also need to know something about the loads imposed on a child's bone and consider not only absolute bone strength, but also the strength of bone relative to the physiologic loads. Interpreting bone strength in light of the loads imposed (particularly muscle force) is critical for an accurate diagnosis of the developing bone.

Immunochemical structure of the hepatitis B surface antigen vaccine--I. Treatment of immobilized HBsAg by dissociation agents with or without enzymatic digestion and identification of polypeptides by protein blotting.

Since the immunosorbent techniques and the cycles of isopycnic and rate zonal velocity ultracentrifugations were shown to be unsuitable for the purification of hepatitis B surface antigen (HBsAg) particles from human sera because HBsAg was still largely contaminated by serum proteins, we applied a drastic dissociating treatment of HBsAg stabilized by adsorption on silica gel which appeared essential to remove extraneous components initially present in the HBsAg particles. Only albumin and sometimes IgG were recovered with the purified antigen. The polypeptide composition of our purified HBsAg preparations was analyzed by SDS-PAGE with subsequent transfer to a nitrocellulose sheet by blotting, incubation with 125I-anti-HBs and exposure to X-ray film. Samples from HBsAg-positive sera containing the hepatitis B virus e antigen (HBeAg) displayed three proteins: P 24.5 and GP 28 as major components and GP 36 as a minor component. Dimers of these polypeptides were also immunologically detected. When a supplementary step of trypsin or pepsin digestion was included in our purification procedure after adsorption to silica and acid dissociation of HBsAg, proteolytic cleavage fragments of HBsAg with mol. wts lower than 10,000 were obtained on SDS-PAGE after reduction. This finding shows that arginine and lysine residues inaccessible to tryptic digestion in the intact HBsAg lipoprotein particle were exposed to enzymatic hydrolysis by our treatment. However, HBsAg kept the antigenic and immunogenic properties of the native antigen. Therefore such a HBsAg preparation appeared as a new candidate for the vaccination against HBV and a useful material for the analysis of the HBs antigenic structure.

A monoclonal antibody specific for the hepatocyte receptor binding site on hepatitis B virus.

The sequence of the preS1 region of the hepatitis B virus (HBV) envelope (env) proteins contains a dominant binding site for hepatocytes between residues preS21 and preS47. Purified HBV particles (subtype ad) were used as the immunogen to produce specific monoclonal antibodies (McAbs) against three antigenic regions (S, preS2 and preS1) of the HBV env protein. One McAb, F35.25, was found to be specific for the region 32-53 of the preS1 sequence of HBV, which largely overlapped the hepatocyte receptor binding site. The preS1-specific McAb F35.25 reacted with both HBV subtypes, ad and ay, in radioimmunoassays (RIA) and with the large surface proteins, P39 and GP42, as well as with tryptic fragments preS(1-99/103) and preS(1-113) in Western blotting experiments. This McAb F35.25 preferentially recognized, however, the homologous (ad) preS1 sequence in RIA. The ad/ay amino acid substitution within the hepatocyte receptor binding site at position 35 (Gly-Arg) may explain the relative subtype-specificity of F35.25. Finally, the F35.25 epitope was detected in all HBV particles purified from HBeAg-positive human sera, confirming that this preS1 region 32-53 is exposed at the surface of complete virions. Thus, we developed a RIA system allowing us to assess the infectivity of HBV particles by the detection of preS1 sequences associated with the viral hepatocyte receptor. Moreover, it is expected that F35.25 may be a virus-neutralizing antibody by blockage of the attachment of HBV to liver cells.

Demonstration of a firm association between hepatitis B surface antigen proteins bearing polymerized human albumin binding sites and core-specific determinants in serum hepatitis B viral particles.

Hepatitis B viral particles (HB-VP) were purified from sera of chronic hepatitis B surface antigen (HBsAg) positive carriers by consecutive isopycnic and rate-zonal sedimentation in sucrose gradients. Their immunological properties [HBsAg, hepatitis B core antigen (HBcAg) and hepatitis B e-antigen (HBeAg) activities] were examined by a radioimmunoassay based upon the classical "sandwich principle". A double antibody specificity radioimmunoassay (DAS-RIA) was then developed to determine whether envelope proteins (HBsAg) with binding activity for polymerized human serum albumin (pHSA-BA) were associated with core-specific antigenicities (HBc/HBeAg). An e-antigen activity cosedimenting with intact HB-VP (negative for HBcAg reactivity) was detected in association with HBsAg and receptors for pHSA. The presence of HBcAg-specific determinant(s) on HBeAg molecules was also indicated by DAS-RIA. So, we postulated that such hepatitis B virion (HBV) specific molecules are involved in immune complexes with anti-HBc as antibodies in sera of patients with chronic HBV infection. To define the significance of these molecular forms in HB-VP morphogenesis, we studied the effects of a mild treatment with a chaotropic salt, NaSCN, on HB-VP-rich fractions (DNA polymerase positive). A small mol. wt HBeAg derived from HB-VP by dissociating treatment was detected. We found that core-specific determinants (HBe/HBcAg) were bound to large surface proteins (HBsAg) with pHSA-BA and therefore probably contained the pre-S sequence. The selective release from HB-VP of such molecular forms, which could be a product of the major S-region transcript, suggests that they may be components of complete virions.

Immunochemical structure of the hepatitis B surface antigen vaccine--II. Analysis of antibody responses in human sera against the envelope proteins.

Antibody responses to the three envelope (env) proteins of hepatitis B viral particles (HB-VP): the S-encoded P25 polypeptide; the pre-S(2)- and S-encoded GP33/GP36 polypeptide; and the large entire env gene (pre-S + S) product, P39/GP42, were investigated using a Western immunoblotting assay (WIBA). HB-VP proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose by electroblotting were used as antigenic probes to determine the polypeptide specificity of these antibodies present in immune individuals. Antisera from human subjects either after a natural HBV infection or after active immunization with the hepatitis B vaccine licensed in France were selected on the basis of a positive serological RIA test for antibodies against hepatitis B surface antigen (HBsAg). In all studied cases, the lack of reactivity of the anti-HBs/P25 antibodies in blots from reduced SDS gels confirms that the S-related-determinants have a conformation sensitive to denaturing agents. In contrast, the anti-pre-S(2)/GP33-GP36 antibodies and the anti-pre-S(1)/P39-GP42 antibodies can be easily detected in WIBA, providing these antibodies recognize the disulfide-bond independent pre-S determinants on the denatured env proteins. However, antisera raised in guinea-pigs against individual HBsAg polypeptides contain antibodies reacting with denatured S-proteins, suggesting that the sequential S-determinants are lost during HBV morphogenesis. Antibody responses in HBV convalescing patients or vaccinated healthy donors are shown to be characterized by: an early transient polypeptide specific-antibody response to pre-S(2)-sequences (detected in WIBA); a persistent antibody response to conformation-dependent S-determinants (detected in RIA). This implies that effective long-term protection against HBV infection requires antibodies directed to native env proteins.

Inhibitory activity of monoclonal antibody F35.25 on the interaction between hepatocytes (HepG2 cells) and preS1-specific ligands.

The capacity of a preS1-specific monoclonal antibody (McAb) F35.25 to block the attachment of preS1-specific ligands to human hepatoma HepG2 cells was studied. In order to define more precisely the fine epitope specificity of McAb F35.25, its reaction with synthetic peptides derived from the preS1 sequence (12-53) was investigated. McAb F35.25 was found to recognize better synthetic peptide preS(21-47) from the adw 2 and ayw sequences than the synthetic peptide preS(32-53) adw 2. The shortest sequence recognized by McAb F35.25 among the peptide sequence studied was preS(32-47). The corresponding amino acid sequence (for HBV subtype adw 2) is PAFGANSNNPDWDFNP. As expected, it was found that McAb F35.25 inhibited the attachment of HepG2 cells to HBsAg-cellulose, as well as to preS(21-47)-cellulose, corresponding to two HBV subtypes adw 2 and ayw. Finally, the inhibitory effect of different peptides on the interaction of McAb F35.25 with HBsAg particles containing the preS1 sequence was also studied. The peptide preS(12-47) appeared to be the most effective inhibitor. Therefore, the McAb F35.25 is specific for the sequence preS1(X to 47), where (12 less than or equal to X less than 32). These results indicate that McAb F35.25 is probably virus-neutralizing and represents a reagent of great value to study the interaction between HBV and hepatocytes independently of d/y subtype changes.

Immunological cross-reactivity between preS2 sequences of the hepatitis B virus envelope proteins corresponding to serological subtypes adw2 and ayw.

An immune response to epitopes localized on the preS region of the hepatitis B virus (HBV) envelope (env) is elicited during recovery from HBV infection and appears to play a role in virus clearance. Anti-preS antibodies (Ab) are expected to be protective against HBV infection as indicated by the virus-neutralizing capacity of Ab to a preS2-specific synthetic peptide preS(120-145). However, there is considerable amino acid variability between preS regions corresponding to distinct serological subtypes of HBV, raising the question whether the preS sequences are sufficiently related immunologically to have the potential of inducing cross-protective immunity. To answer this question concerning the preS2 region, antisera to synthetic peptides preS(120-153) and preS(128-153) corresponding to subtypes adw2 and ayw, as well as to the native env [ayw] protein were raised. Using the resulting polyclonal Ab, an immunological relatedness between preS2 sequences of subtypes adw2 and ayw was demonstrated. On the other hand, Ab selected by affinity chromatography or by cloning hybridoma cells may recognize with strong preference subtype-specific determinants within the preS2 region when the compared antigens are in solution rather than on the solid phase. These findings have implication for the design of: (1) preS2-specific immunogens and (2) immunoassays for quantitation of preS2 sequences in HBV env proteins.

Antibodies to synthetic peptides from the pre-S1 and pre-S2 regions of one subtype of the hepatitis B virus (HBV) envelope protein recognize all HBV subtypes.

Immunodominant B and T cell epitopes have been demonstrated recently on the preS1 and PreS2 regions of the hepatitis B virus (HBV) envelope protein. Synthetic peptide analogs corresponding to the preS2 region elicit virus-neutralizing antibodies and protect chimpanzees against HBV infection. Antibodies raised by immunization with peptides derived from the preS1 sequence block the site involved in HBV attachment to cell receptors, and are expected to be virus-neutralizing. Results presented here show that antisera raised against synthetic peptide analogs carrying the immunodominant epitope of the preS1 and preS2 sequence, respectively, and corresponding to two HBV subtypes, adw2 and ayw, each recognized preS1 and preS2 specific epitopes on all serological subtypes of the HBV envelope protein. Thus, the sequence variability within the preS1 and preS2 regions does not represent an impediment to the development of synthetic peptide or genetically engineered hepatitis B preS immunogens for worldwide immunization.

Characterization of monoclonal antibodies specific for the pre-S2 region of the hepatitis B virus envelope protein.

Monoclonal antibodies (McAb) specific for the pre-S region of the hepatitis B virus (HBV) envelope protein were prepared using HBV particles of hepatitis B surface antigens (HBsAg) as immunogens. The antibodies reacted in Western blot analyses and in ELISA with pre-S2 sequences of the HBV envelope protein. Pepsin or protease V8 treatment of the antigen abolished reactivity. The fine specificity of one of the McAb (F376) was established by immunoassays using synthetic peptides and a pre-S2-beta-galactosidase fusion protein expressed in E. coli. The shortest peptide recognized by F376 is demarcated by residues pre-S(132) at the N-terminal and pre-S(140)-pre-S(145) at the C-terminal. The corresponding amino acid sequence (for HBV subtype adw2) is: QDPRVRGLY(LPAGG). Additional amino acid residues at the N-terminal, and possibly at the C-terminal ends contribute to the binding of McAb, probably due to conformational influences. The McAb was applied to immunoassays of pre-S2 sequences in purified HBsAg and in human sera containing HBsAg.

Bone mineral response to a 7-month randomized controlled, school-based jumping intervention in 121 prepubertal boys: associations with ethnicity and body mass index.

We examined the effects of a 7-month jumping intervention (10 minutes, 3 times per week) on bone mineral gain in prepubertal Asian and white boys (10.3+/-0.6 years, 36.0+/-9.2 kg) at 14 schools randomized to control (n = 60) and intervention (n = 61) groups. Intervention and control groups had similar mean baseline and change in height, weight, lean mass and fat mass, baseline areal bone mineral density (aBMD; g/cm2), bone mineral content (BMC; g; dual-energy X-ray absorptiometry [DXA], QDR 4500W), and similar average physical activity and calcium intakes. Over 7 months, the intervention group gained more total body (TB) BMC (1.6%,p < 0.01) and proximal femur (PF) aBMD (1%, p < 0.05) than the control group after adjusting for age, baseline weight, change in height, and loaded physical activity. We also investigated the 41 Asian and 50 white boys (10.2+/-0.6 years and 31.9+/-4.4 kg) who were below the 75th percentile (19.4 kg/m2) of the cohort mean for baseline body mass index (BMI). Boys in the intervention group gained significantly more TB and lumbar spine (LS) BMC, PF aBMD, and trochanteric (TR) aBMD (+ approximately2%) than boys in the control group (adjusted for baseline weight, final Tanner stage, change in height, and loaded physical activity). Bone changes were similar between Asians and whites. Finally, we compared the boys in the control group (n = 16) and the boys in the intervention group (n = 14) whose baseline BMI fell in the highest quartile (10.5+/-0.6 years and 49.1+/-8.2 kg). Seven-month bone changes (adjusted as aforementioned) were similar in the control and intervention groups. In summary, jumping exercise augmented bone mineral accrual at several regions equally in prepubertal Asian and white boys of average or low BMI, and intervention effects on bone mineral were undetectable in high BMI prepubertal boys.