Low bone mass is known to be associated with an increased risk of fractures. Osteoporosis prevention by maximizing bone mass will be crucial and requires a better knowledge of bone mass acquisition during adolescence. Bone mass was assessed in 574 healthy volunteer females aged 10-24 years. Spine bone mineral density (BMD) in anteroposterior (AP L2-4) and lateral (LAT L3) views was measured using dual-energy X-ray absorptiometry (DXA) and AP bone mineral content (BMC) was calculated. At the same time, spine AP-BMD (L2-4) was evaluated in 333 normal menstruating women, aged 27-47 years. Bone values, osteocalcin and IGF-1 serum concentrations were correlated with chronological age, skeletal age, pubertal stages and time after menarche. In this cross-sectional study, AP- and LAT-BMD and BMC increased dramatically between skeletal ages 10 and 14 or until the first year after menarche. Between 14 and 17 skeletal years of age, AP-BMD and BMC increased moderately, whereas LAT-BMD remained unchanged. After skeletal age 17, or the fourth year after menarche, there was no significant increase in BMD or BMC, and their values did not differ from those of menstruating women. A serum osteocalcin peak was observed at skeletal ages 11-12 or at stage P3, whereas IGF-1 peaked at 13-14 skeletal years of age or at P4 and the first year after menarche. Eighty-six per cent of the adult bone mass of the spine is acquired before skeletal age 14 or the second year after menarche; therefore osteoporosis prevention programs will be particularly effective before that age.

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.

In a longitudinal study of 395 normal 10- to 24-year-old female volunteers, 105 of whom were initially premenarcheal, lumbar bone mineral density (BMD) and content (BMC) were measured by dual-energy X-ray absorptiometry (DXA) at inclusion and after a 2-year interval. The mean age of menarche was 13.1 +/- 1.1 years (n = 395). In a multiple regression analysis the BMD and BMC relative gains were highly correlated with the height and weight relative gains and with the time since menarche (r = 0.91 and r = 0.93, respectively). The mean relative annual increments in body height, in L2-4 vertebral height, in BMD and in BMC peaked respectively at 1.5, 1.0, 0.6 and 0.7 years before menarche. The four perimenarcheal years, beginning with the first pubertal clinical signs, are essential for bone acquisition, since 46.7% of adult BMC is acquired during this period. Two years after menarche, BMC is 85% of the adult value. Seven years after menarche no further significant variation in BMC is observed. In 206 menstruating women 27-47 years old, a DXA lumbar measurement was also performed after a 4-year interval. There was a small but significant increase of 0.3%/year in BMD and 0.7%/year in BMC, contrasting with the results in the young population. This could be explained by a volumetric expansion with aging, which is supported by a small increase in L2-4 area (0.4%/year). In conclusion, this longitudinal study on the lumbar site emphasizes the importance of the pre- and perimenarcheal period, when half of lumbar adult BMC is acquired. This suggests that greater attention must be paid to this period regarding nutrition and physical activity.

Milk consumption, preferably to other calcium sources, is associated with lumbar BMC and BMD in postmenarcheal girls. Aside from being a major source of calcium, milk provides phosphates, magnesium, proteins, and as yet unidentified nutrients likely to favor bone health.

These observations highlight infliximab as a potentially useful and safe salvage treatment for patients with refractory SNV.