Relationships of cardiorespiratory fitness with metabolic risk factors, inflammation, and liver transaminases in overweight youths.

The aim of this study was to assess the relationships of fatness and fitness with metabolic risk factors, including liver transaminases and inflammation in obese youth, taking in account gender, age, and pubertal stage. 241 children were studied (135 girls), age 11.9 +/- 2.2 years (x +/- SD), Body Mass Index z score 5.4 +/- 2.7. For girls, VO(2max) was significantly associated with insulin (P = .001), Insulin resistance (HOMA-IR) (P = .005), and ALT (P = .012); a relationship was displayed between fibrinogen and age and % fat mass (FM) (P = .008); for boys, relationships were found between VO(2max) and diastolic blood pressure and triglycerides; independent associations were also found between age and insulin, HOMA-IR and HDL cholesterol; fibrinogen and sedimentation rate were related (P

Adverse interaction of low-calcium diet and low 25(OH)D levels on lumbar spine mineralization in late-pubertal girls.

No consensus has been reached on the serum 25-hydroxyvitamin D [25(OH)D] levels required to ensure optimal bone health around menarche. We searched for a possible interaction of 25(OH)D levels and calcium intake on lumbar spine mineralization and on biologic features of bone metabolism in healthy late-pubertal girls. Lumbar spine parameters (ie, area, mineral content, and density) and calcium intake were evaluated in 211 healthy white adolescent girls at pubertal stages IV-V (11 to 16.9 years), together with biologic markers of calcium and bone metabolism and with International External Quality Assessment Scheme for Vitamin D Metabolite (DEQAS)-validated serum 25(OH)D levels. A high prevalence of 25(OH)D levels ≤ 30 nmol/L (41%), ≤ 40 nmol/L (61%), and ≤ 50 nmol/L (70%) was found during winter-spring. Parathyroid hormone (PTH) levels were inversely associated with 25(OH)D levels (p = .0021). In contrast, lumbar spine mineral content and density were not associated with 25(OH)D, excepted when calcium intake was below 600 mg/day (p = .0081). Girls with such low calcium intake and 25(OH)D levels of 40 nmol/L or less (9% of the cohort) had a 0.4 to 0.7 SD lower mean areal bone mineral density Z-score than girls with higher calcium intake and/or higher 25(OH)D status. The adverse association between lumbar spine mineralization and combined calcium deficiency-low 25(OH)D levels remained significant in the 91 girls who could be followed over 4 years after their initial evaluation. We conclude that low 25(OH)D levels (≤40 nmol/L) are observed frequently during winter-spring in late-pubertal European girls, which may exacerbate the negative impact of calcium deficiency on lumbar spine mineralization.

Higher milk requirements for bone mineral accrual in adolescent girls bearing specific caucasian genotypes in the VDR promoter.

Low milk intakes hamper bone mineral acquisition during adolescence, especially in European girls. We hypothesized that ethnic-specific polymorphisms of the vitamin D receptor gene promoter (VDRp) influence this milk/bone association. We evaluated lumbar spine BMC and BMD, milk/dairy products and calcium intakes, markers of P-Ca metabolism, and VDRp polymorphisms at the Cdx-2 binding (rs11568820) and -1012 (rs4516035) loci in 117 healthy European peri- and postmenarcheal girls (14.9 +/- 1.6 yr) during a 4-yr follow-up. Calcium intakes from milk, nonmilk dairy products, and nondairy products averaged 199, 243, and 443 mg/d at the initiation of the study. Results show no association between milk intakes and bone mass accrual in girls bearing an A/A genotype at the -1012 VDRp locus (30% of the cohort). In contrast, A/G or G/G girls had lower spine BMC (-13%, p = 0.031), BMD (-10%, p = 0.004), and BMD Z-score (-0.84 SD, p = 0.0003) when their milk intakes were <260 ml/d compared with genotype-matched girls with higher milk intakes and with girls with an A/A genotype. The negative impact of low milk intake persisted up to 19.0 +/- 1.7 yr. These findings suggest that European girls bearing a -1012 A/G or G/G VDRp genotype should have higher milk/calcium intakes for optimal vertebral mass accrual during adolescence than girls bearing an A/A genotype, a genotype found in 30% of European and 98% of Asian and Sub-Saharan African populations. VDRp genotype diversity may contribute to the ethnic differences observed in milk requirements for bone health during adolescence.

Medical management of patients over 50 years admitted to orthopedic surgery for low-energy fracture.

OBJECTIVE: To develop a cost-effective strategy for improving osteoporosis management in patients admitted to an orthopedic surgery department for low-energy fractures. METHODS: From November 2003 to July 2004, all patients over 50 years admitted to the orthopedics department of the Caen Teaching Hospital (France) for low-energy fractures were identified and evaluated by rheumatology department physicians in the same hospital. RESULTS: During the study period, 313 patients were identified, 257 women (mean age, 79.5+/-10.2 years) and 56 men (mean age, 74.6+/-10.8 years), each with one fracture (proximal femur, 58.9%; wrist, 13%). Among them, 91 (29%) had a previous history of osteoporotic fractures. Mean bone mineral density (BMD) values were lower at the femoral neck than at the total hip or lumbar spine (e.g. in women, -2.3+/-0.9 versus -1.8+/-1.0 and -1.4+/-1.7, respectively). Osteoporosis treatment was given to 88 (28%) patients and consisted of calcium and vitamin D supplements, combined with alendronate in 32 patients. Complete loss of self-sufficiency occurred in 73 patients. Thus, 161 patients (88 with osteoporosis treatment and 73 with loss of self-sufficiency) received optimal treatment. CONCLUSION: Cooperation between the orthopedics and rheumatology departments improved the management of osteoporosis in patients with low-energy fractures. However, appropriate investigation and treatment of osteoporosis proved difficult in the oldest old and in patients with cognitive impairments.

Comparison of bone loss induced in female rats by hindlimb unloading, ovariectomy, or both.

INTRODUCTION: Clinical and experimental evidence supports a link between the effects of mechanical loading and those of estrogens on bone. The objective of this study was to compare bone loss induced in female rats by hindlimb unloading, ovariectomy, or both. MATERIALS AND METHODS: Thirty-six female Wistar rats aged 12 weeks were randomized to bilateral surgical ovariectomy without tail suspension (OV) or with tail suspension for 30 days (OV-TS) or to sham surgery without tail suspension (control group, C) or with tail suspension for 30 days (TS). Bone mineral density (BMD) of the distal femoral metaphysis was measured in g/cm2 by dual X-ray absorptiometry in all 12 animals on days 0, 7, 14, and 30. RESULTS: On D14 and D30, BMD (mean+/-S.D.) was significantly lower in the OV, TS, and OV-TS groups than in the control group (D14: 0.239+/-0.014, 0.243+/-0.016, and 0.227+/-0.018, respectively, vs. 0.258+/-0.005 in the controls; P<0.05; and D30: 0.241+/-0.011, 0.227+/-0.015, and 0.200+/-0.018, respectively, vs. 0.279+/-0.009 in the controls; P<0.001). On D30, the percentage BMD change versus baseline (mean+/-S.D.) differed significantly between the combination (OV-TS) group (-14.26+/-8.14) and the single-intervention groups (OV: +0.99+/-6.44, P<0.001; and TS: -6.36+/-4.56, P<0.05). As early as D7, bone loss was significantly greater in the combination (OV + TS) group than in the OV group (-1.79%+/-7.17 vs. +4.29%+/-9.55; P<0.05). CONCLUSION: In female rats, the rate and severity of bone loss were greater when estrogen deprivation was combined with mechanical unloading than when either intervention was used alone. Mechanical unloading induced a greater degree of bone loss than did estrogen deprivation. In this model of high-rate bone loss, mechanical unloading may predominate over estrogen deprivation in the genesis of bone loss.

Two single-nucleotide polymorphisms in the human vitamin D receptor promoter change protein-DNA complex formation and are associated with height and vitamin D status in adolescent girls.

Numerous association studies have dealt with single-nucleotide polymorphisms (SNPs) in coding and intronic regions of the human vitamin D receptor (hVDR) gene. We have hypothesized that phenotypic traits may also be associated with variations in VDR expression due to the presence of SNPs in promoter regions. In this work, we have studied two SNPs located 1521 bp (G/C) and 1012 bp (A/G) upstream of the transcriptional start site of the main human VDR gene promoter. One base-change in any of the two variant sites led to a dramatic change in protein-DNA complex formation using nuclear extracts from HEK293, Caco-2 and COS-7 cells. Genetic analysis of 185 healthy adolescent girls evidenced two major haplotypes: 1521G/1012A and 1521C/1012G and three main genotypes: homozygous for 1521G/1012A (21.1%), homozygous for 1521C/1012G (17.3%) and heterozygous 1521CG/1012GA (57.3%). On the basis of transfection data, promoter activity was nearly 2-fold higher with the 1521G/1012A haplotype, when compared with the 1521C/1012G haplotype. Clinical and biological association study in the adolescent cohort showed that girls with a CC/GG genotype had (i) lower circulating levels of 25-dihydroxyvitamin D, with no detectable consequence on calcium metabolism, (ii) lower serum IGF-1 levels and (iii) smaller height from 11 years of age up to adult height.

Recommendations for monitoring antiresorptive therapies in postmenopausal osteoporosis.

Antiresorptive agents are effective in preventing and treating postmenopausal osteoporosis, provided they are taken as directed. Regular physical examinations including height measurements may fail to ensure optimal compliance. Bone mineral density (BMD) measurement is indispensable for determining whether treatment is warranted. The measurement can be repeated after 2 years at least, provided quality-control procedures are adequate. BMD changes over time should be compared to the least significant change calculated from the in vivo BMD reproducibility at the measurement center. However, BMD changes are not correlated with the fracture risk reduction induced by antiresorptive treatment. Biochemical markers for bone turnover can be monitored after only 3-6 months provided steps are taken to control for intraindividual variability. They are useful when patient compliance is poor or the treatment response inadequate.

Labyrinthectomy decreases bone mineral density in the femoral metaphysis in rats.

To determine whether the vestibular system could influence bone remodeling in rats, we measured bone mineral density with dual energy X-rays absorptiometry before and 30 days after bilateral labyrinthectomy. Comparatively to intact control rats, labyrinthectomized animals showed a reduced bone mineral density in distal femoral metaphysis (p = 0.007): the variations between D0 and D30 were +3.0% for controls and -13.9% for labyrinthectomized rats. No significant difference between the 2 groups was observed in the whole body mineral density. These results suggest that the peripheral vestibular apparatus is a modulator of bone mass and more specifically in weight bearing bone. We discuss possible mechanisms of this vestibular influence probably mediated by the sympathetic nervous system.

Zinc status and bone mineralisation in adolescent girls.

The aim of the project was to assess the relationship between zinc status and bone mineralisation in pre-menarcheal adolescent girls. One hundred and thirty-nine healthy pre-menarcheal girls (Tanner pubic hair stage < or = 4), aged 12.4 +/- 1.0 years, had two visits at an interval of 2 years. Serum and urine zinc concentrations (Zn S; Zn U; Zn U/ creatinine), insulin-like growth factor 1 (IGF-I), and markers of bone turn-over, i.e. osteocalcin and parathormone (PTH), concentrations were measured at the first visit. Lumbar (L2-L4) bone mineral content and density (BMC, BMD) were measured at both visits. BMC and BMD and their increase at the follow-up after 2 years were compared with biochemical data by multiple regression. The stage of puberty was added as a covariable in the analysis. At the first visit, a significant correlation was found between sexual maturity and initial BMC, BMD, height, weight, and IGF-I. Zn S was negatively correlated with osteocalcin. Zn U showed a positive correlation with BMC, BMD, IGF-I, height, weight, and PTH. At the second visit, sexual maturity showed a positive correlation with BMD and weight increments and a negative one with BMC and height gains. Zn S was significantly related with BMD increase. These correlations suggest that zinc plays a role in normal growth and bone mineralisation during puberty onset.

[Physiopathology of osteoporosis]. / Physiopathologie de l'ostéoporose.

PURPOSE: The pathophysiology of osteoporosis has seen many recent progress especially with the use of genetically modified animal models. CURRENT KNOWLEDGE AND KEY POINTS: Among many discoveries, one can notice the crucial role of LRP5, GH, IGF-1 and the sex hormones receptors in the acquisition of the peak bone mass, the control of bone remodeling by the sympathetic nervous system and his implication as a transmitter of mechanical loading in bone. Also, the role of estrogen and androgen receptors as well as the aromatase is specified according to sexes. The role of growth plate's chondrocytes in the installation of the trabecular bone network is better and better demonstrated. The greater periosteal apposition in men, mediated by androgens receptor, seems to explain the greatest radial growth and so the greatest bone resistance to mechanical strains like a lower fracture rate in men compared to women. The bone microarchitecture and quality explain an important part of the mechanical properties of bones and why considering the same bone mass one bone is breaking and another one not. FUTURE PROSPECTS AND PROJECTS: Many therapeutic applications should finalize the discovery of these new bone cells signalisation pathways.

The absorptiometry T-score: influence of selection of the reference population and related considerations for everyday practice.

OBJECTIVES: The WHO definition of osteoporosis is based on T-scores, which are calculated from mean bone mineral density values in reference populations composed of young adults. The definition of this reference population is a key-point. METHODS: We compared lumbar spine T-scores in three reference populations of young adults, one from the US and two from France. RESULTS: Reference values were higher in the American population than in the two French populations. As a result, the prevalence of a T-score indicating osteoporosis in a population of 2887 patients aged 20-87 years (mean age, 62.4 +/- 9.5 years) was 32% with the American reference population and 22% and 24% with the two French populations. Thus, about 25% and 32% of patients classified as having osteoporosis with the American reference population did not have osteoporosis with the two French reference populations, respectively. There was no significant difference between the prevalences obtained with the two French populations. CONCLUSIONS: Reference populations of young adults should be representative of the population of each country, for each measurement site, gender, and ethnic group. When evaluating individuals, in addition to the clinical setting and T-score, age should be taken into account. The Z-score remains useful.