Leiting Xu

Bone and muscle development during puberty in girls: a seven-year longitudinal study.

The growth of lean mass precedes that of bone mass, suggesting that muscle plays an important role in the growth of bone. However, to date, no study has directly followed the growth of bone and muscle size through puberty and into adulthood. This study aimed to test the hypothesis that the growth of muscle size precedes that of bone size (width and length) and mass during puberty. Bone and muscle properties were measured using pQCT and DXA in 258 healthy girls at baseline (mean age, 11.2 yr) and 1‐, 2‐, 3–4‐ and 7‐yr follow‐up. Growth trends as a function of time relative to menarche were determined from prepuberty to early adulthood for tibial length (TL), total cross‐sectional area (tCSA), cortical CSA (cCSA), total BMC (tBMC), cortical volumetric BMD (cBMD), and muscle CSA (mCSA) in hierarchical models. The timings of the peak growth velocities for these variables were calculated. Seventy premenopausal adults, comprising a subset of the girls mothers (mean age, 41.5 yr), were included for comparative purposes. In contrast to our hypothesis, the growth velocity of mCSA peaked 1 yr later than that of tibial outer dimensions (TL and tCSA) and slightly earlier than tBMC. Whereas TL ceased to increase 2 yr after menarche, tCSA, cCSA, tBMC, and mCSA continued to increase and were still significantly lower than adult values at the age of 18 yr (all p < 0.01). The results do not support the view that muscle force drives the growth of bone size during puberty.

Women With and Without Metabolic Disorder Differ in Their Gut Microbiota Composition

The aim of this study was to investigate whether overweight/obese women in metabolic disorder group (MDG, n = 27) differ in their gut microbiota composition from overweight/obese women in non‐metabolic disorder group (NMDG, n = 47) and normal weight women group (NWG, n = 11). Gut microbiota was profiled from fecal samples by 16S rRNA fluorescence in situ hybridization and flow cytometry in 85 premenopausal women. Body composition was measured by bioimpedance, and dietary intakes were collected via food diaries. Standard procedures were used to assess plasma glucose, serum insulin, lipids, and inflammatory status. We found that the proportion of bacteria belonging to Eubacterium rectale‐Clostridium coccoides group, indicating efficient energy harvest from nutrients in gut, was higher in MDG compared to NMDG and NWG, while no difference was found between NMDG and NWG. The proportion of Eubacterium rectale‐Clostridium coccoides group correlated positively with weight, BMI, total fat, fat mass percentage (FM%), visceral fat area, and serum triglycerides, and negatively with high‐density lipoprotein (HDL). Our results indicate that certain members of Eubacterium rectale‐Clostridium coccoides group are associated with obesity‐related MDs not obesity per se.

Low volumetric BMD is linked to upper-limb fracture in pubertal girls and persists into adulthood: a seven-year cohort study.

The aetiology of increased incidence of fracture during puberty is unclear. This study aimed to determine whether low volumetric bone mineral density (vBMD) in the distal radius is associated with upper-limb fractures in growing girls, and whether any such vBMD deficit persists into adulthood. Fracture history from birth to 20 years was obtained and verified by medical records in 1034 Finnish girls aged 10-13 years. Bone density and geometry at distal radius, biomarkers and lifestyle/behavioural factors were assessed in a subset of 396 girls with a 7.5-year follow-up. We found that fracture incidence peaked during puberty (relative risk 3.1 at age of 8-14 years compared to outside this age window), and 38% of fractures were in the upper-limb. Compared to the non-fracture cohort, girls who sustained upper-limb fracture at ages 8-14 years had lower distal radial vBMD at baseline (258.9+/-37.5 vs. 287.5+/-34.1 mg/cm(3), p=0.001), 1-year (252.0+/-29.3 vs. 282.6+/-33.5 mg/cm(3), p=0.001), 2-year (258.9+/-32.2 vs. 289.9+/-40.1 mg/cm(3), p=0.003), and 7-year follow-ups (early adulthood, 307.6+/-35.9 vs. 343.6+/-40.9 mg/cm(3), p=0.002). There was a consistent trend towards larger bone cross-sectional area in the fracture cohort compared to non-fracture. In a logistic regression model, lower vBMD (p=0.001) was the only significant predictor of upper-limb fracture during the period of 8-14 years. Our results indicate that low BMD is an important factor underlying elevated upper-limb fracture risk during puberty, and that low BMD in pubertal girls with fracture persists into adulthood. Hence low vBMD during childhood is not a transient deficit. Methods to monitor vBMD and to maximise bone mineral accrual and reduce risks of falling in childhood should be developed.

Prolonged breast-feeding protects mothers from later-life obesity and related cardio-metabolic disorders

OBJECTIVE To investigate the long-term effects of duration of postpartum lactation on maternal body composition and risk for cardio-metabolic disorders in later life. DESIGN Retrospective study. Body composition was measured using dual-energy X-ray absorptiometry and serum glucose, insulin and lipids were analysed using enzymatic photometric methods 16-20 years after the last pregnancy. Medical history and lifestyle factors were collected via a self-administered questionnaire. Detailed information regarding weight change patterns during each pregnancy was obtained from personal maternity tracking records. SETTING City of Jyväskylä and surroundings in Central Finland. SUBJECTS Two hundred and twelve women (mean age 48, range 36-60 years). RESULTS At 16-20 years after their last pregnancy, women who had breast-fed for less than 6 months had higher total body fat mass and fat mass percentage, particularly in the android region (46·5 (sd 8·2) %) than mothers who had breast-fed for longer than 6 months (39·0 (sd 10·2) %) or for longer than 10 months (38·4 (sd 10·9) %, P < 0·01). These differences were independent of pre-pregnancy weight and BMI, menopausal status, smoking status, level of education, participation in past and present leisure-time physical activity, and current dietary energy intake. Higher body fat mass was also associated with higher fasting serum glucose concentration and insulin resistance, TAG, LDL cholesterol and total cholesterol concentrations, as well as higher systolic and diastolic blood pressure (P < 0·05 for all). CONCLUSIONS Short duration of breast-feeding may induce weight retention and fat mass accumulation, resulting in increased risk of cardio-metabolic disorders in later life.

Serum Osteocalcin Is Not Associated with Glucose but Is Inversely Associated with Leptin across Generations of Nondiabetic Women

CONTEXT The skeleton is recognized as an important player in energy metabolism through its interactions with other tissues. Whether the association of osteocalcin with glucose metabolism is age dependent has not been fully addressed. OBJECTIVE The objective of the study was to examine the age-specific association between different forms of osteocalcin and glucose and adipokines. DESIGN This was a family-based study across three generations. SETTING The study was conducted at a university laboratory. PARTICIPANTS Sixty-four daughter-premenopausal mother-maternal grandmother trios participated in the study. METHODS Fasting plasma glucose and insulin concentrations, serum total (tOC), carboxylated (cOC), and uncarboxylated (ucOC = tOC - cOC) osteocalcin, leptin, and adiponectin levels, and fat masses were assessed. Generalized estimating equations (GEE) model was used to assess the associations of bone biomarkers with glucose metabolism variables and adipokines. RESULTS No significant difference in insulin was found between generations, whereas glucose and leptin increased with age. Levels of tOC, cOC, and ucOC were highest in girls and lowest in mothers (P < 0.01). Grandmothers had higher leptin and adiponectin than mothers and girls. Despite the differences in insulin and glucose between the low and high homeostasis model assessment insulin resistance index (HOMA-IR) groups within generations, no significant differences in tOC, cOC, and ucOC were found. Compared with their low HOMA-IR counterparts, the high HOMA-IR group had significantly higher leptin and lower adiponectin in mothers and grandmothers. The tOC, cOC, and ucOC levels did not correlate with HOMA-IR, leptin, or adiponectin when the three generations were evaluated together, but when separated by generation, leptin was inversely correlated with tOC (P = 0.003) and cOC (P = 0.047) in mothers and with ucOC in grandmothers (P = 0.042). CONCLUSIONS Osteocalcin, glucose, and adipokines change with age but in a noncommensurate manner. We infer that the association between osteocalcin and glucose metabolism is minor and age specific in nondiabetic women. Leptin, however, strongly correlated with insulin resistance independently of fat masses, suggesting that obesity, as a metabolic disorder risk factor, affects glucose metabolism, partly through the role of leptin.

Concerted actions of insulin-like growth factor 1, testosterone, and estradiol on peripubertal bone growth: a 7-year longitudinal study.

A better understanding of how bone growth is regulated during peripuberty is important for optimizing the attainment of peak bone mass and for the prevention of osteoporosis in later life. In this report we used hierarchical models to evaluate the associations of insulin‐like growth factor 1 (IGF‐1), estradiol (E2), and testosterone (T) with peripubertal bone growth in a 7‐year longitudinal study. Two‐hundred and fifty‐eight healthy girls were assessed at baseline (mean age 11.2 years) and at 1, 2, 3.5, and 7 years. Serum concentrations of IGF‐1, E2, and T were determined. Musculoskeletal properties in the left lower leg were measured using peripheral quantitative computed tomography (pQCT). Serum levels of IGF‐1, E2, and T increased dramatically before menarche, whereas they decreased, plateaued, or increased at a lower rate, respectively, after menarche. IGF‐1 level was positively associated with periosteal circumference (PC) and total bone mineral content (tBMC) throughout peripuberty but not after adjustment for muscle cross‐sectional area (mCSA). On the other hand, IGF‐1 was associated with tibial length (TL) independently of mCSA before menarche. T was positively associated with TL, PC, tBMC, and cortical volumetric bone mineral density, independent of mCSA, before menarche but not after. E2 was associated with TL positively before menarche but negatively after menarche. These findings suggest that during puberty, circulating IGF‐1 promotes bone periosteal apposition and mass accrual indirectly, probably through stimulating muscle growth, whereas the effects of sex steroids on bone growth differ before and after menarche, presenting a biphasic pattern. Hence the concerted actions of these hormones are essential for optimal bone development in peripuberty.

Adipose Tissue Dysfunction and Altered Systemic Amino Acid Metabolism Are Associated with Non-Alcoholic Fatty Liver Disease

Background Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49) and women (n = 52) with and without NAFLD. Methods Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS). Serum samples were analyzed using a nuclear magnetic resonance (NMR) metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot. Results Increased branched-chain amino acid (BCAA), aromatic amino acid (AAA) and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all). Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all), whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all). Conclusions Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.

Fat Mass Accumulation Compromises Bone Adaptation to Load in Finnish Women: A Cross-Sectional Study Spanning Three Generations

Body weight and lean mass correlate with bone mass, but the relationship between fat mass and bone remains elusive. The study population consisted of 396 girls and 138 premenopausal mothers and 114 postmenopausal grandmothers of these girls. Body composition and tibial length were assessed using dual‐energy X‐ray absorptiometry (DXA), and bone traits were determined at the tibia using peripheral quantitative computed tomography (pQCT) in the girls at the ages of 11.2 ± 0.8, 13.2 ± 0.9, and 18.3 ± 1.0 years and in the mothers (44.7 ± 4.1 years) and grandmothers (70.7 ± 6.3 years). The values of relative bone strength index (RBSI), an index reflecting the ratio of bone strength to the load applied on the tibia, were correlated among family members (all p < .05). The mean values of RBSI were similar among 11‐ and 18‐year‐old girls and premenopausal women but significantly lower in 13‐year‐old girls and postmenopausal women. However, in each age group, subjects in the highest BMI tertiles had the lowest RBSI values (all p < .01). RBSI was inversely associated with body weight (all p < .01), indicating a deficit in bone strength relative to the applied load from greater body weight. RBSI was inversely associated with fat mass (all p < .001) across age groups and generations but remained relatively constant with increasing lean mass in girls and premenopausal women (all p > .05), indicating that the bone‐strength deficit was attributable to increased fat mass, not lean mass. Moreover, the adverse effect of fat mass was age‐dependent, with every unit increase in fat mass associated with a greater decrease in RBSI in pre‐ and postmenopausal women than in girls (all p < .001). This is largely due to the different capacity of young and adult bones to increase diaphyseal width by periosteal apposition in response to increased load. In summary, increasing body weight with fat accumulation is accompanied by an age‐dependent relative bone‐strength deficit in women because the beneficial effects of increased fat mass on bone, if any, do not compensate for the mechanical burden that it imposes.

Effect of long-term leisure time physical activity on lean mass and fat mass in girls during adolescence

The purpose of this 7-yr prospective longitudinal study was to examine if the level and consistency of leisure-time physical activity (LTPA) during adolescence affected the quantity and distribution of lean mass (LM) and fat mass (FM) at early adulthood. The study subjects were 202 Finnish girls who were 10-13 yr old at baseline. LM and FM of the total body (TB), arms, legs, and trunk were assessed by dual-energy X-ray absorptiometry. Muscle cross-sectional area (mCSA) of the left leg was assessed by peripheral quantitative computed tomography. Scores of LTPA were obtained by questionnaire. Girls were divided into four groups comprising those with consistently low (G(LL)) or consistently high (G(HH)) physical activity, or those whose physical activity changed from low to high (G(LH)), or from high to low (G(HL)), over the 7 yr of follow-up. At baseline, no differences were found in LM, FM, and FM% among the groups in any of the body segments. By the end of the study G(HH) and G(LH) had higher values of LM of the TB, arms, legs, and trunk than that of the G(HL) and G(LL) groups (P < 0.05, respectively). High FM% of the TB was associated with low level of LTPA, but no significant differences were found in the absolute amount of FM and mCSA among the LTPA groups. Our results suggest that a consistently high level of LTPA during the transition from prepuberty to early adulthood has a positive effect on lean mass gain in girls. Participating in 5 h of LTPA per week had a significant effect on FM% but not on the absolute amount of fat mass.

Is bone loss the reversal of bone accrual? Evidence from a cross-sectional study in daughter-mother-grandmother trios.

Bone adapts to mechanical loads applied on it. During aging, loads decrease to a greater extent at those skeletal sites where loads increase most in earlier life. Thus, the loss of bone may occur preferentially at sites where most bone has been deposited previously; ie, bone loss could be the directional reversal of accrual. To test this hypothesis, we compared the bone mass distribution at weight‐bearing (tibia) and non‐weight‐bearing (radius) bones among 18‐year‐old girls, their premenopausal mothers, and their postmenopausal maternal grandmothers. Bone and muscle properties were measured by pQCT, and polar distribution of bone mass was obtained in 55 girl‐mother–maternal grandmother trios. Site‐matched differences in bone mass were compared among three generations. The differences between girls and mothers and between mothers and grandmothers were used to represent the patterns of bone mass accrual from early adulthood to middle age and bone loss from middle to old age, respectively. Compared to the mothers, 18‐year old girls had less bone mass in the anterior and medial‐posterior regions of the tibial shaft, while the grandmothers had less bone in the anterior and posterior regions. In contrast, the bone mass differences in the radial shaft between girls and mothers and mothers and grandmothers were relatively uniform. We conclude that both bone accrual and loss are direction‐specific in weight‐bearing bones but relatively uniform in non‐weight‐bearing bones. Bone loss in old age is largely, but not completely, a reversal of the preferential deposition of bone in the most highly loaded regions during early life.