Our data suggest that bone metabolism markers are good predictors of bone mass in boys and of bone mass increase in both sexes. In early puberty, sex steroids stimulate the pubertal growth spurt in conjunction with GH and IGF-1. The fast increase in height gives rise to an increase in bone turnover and bone mineral apposition. It is known that at the end of puberty high levels of oestradiol inhibit chondrocyte proliferation. This leads to a decline in height velocity and bone turnover. Bone mass still increases under the influence of sex steroids and IGF-1. The data in our study confirm previous reports that markers of bone turnover relate positively to height velocity.

In humans, foetal and early postnatal growth failure may have persistent consequences for growth and pubertal development in later life. During this period, the developing organs are still plastic to change their function, which may have long-lasting effects. At the time of onset of puberty, acute factors may also interfere with pubertal development. Malnutrition, as seen in anorexic patients, and chronic diseases with malabsorption or diseases with systemic effects result in a delayed onset of puberty. We have observed an earlier onset of puberty in girls with low birth weight; menarcheal age also tended to be earlier. In boys, a low birth weight tended to be associated with a later development. Two rat models with growth failure based on perinatal malnutrition have been examined, one with intrauterine growth retardation (IUGR) by ligation of the uterine arteries and one with postnatal food restriction (FR) by increasing the litter size postnatally. In both models, the rats had a persistent postnatal growth failure. The onset of puberty in female rats, defined by vaginal opening, was delayed only in the IUGR group. Despite a significantly lower weight, there was no difference in the timing of puberty onset in the FR group. In IUGR rats, the ovaries had fewer follicles, while FR rats had a normal number of follicles but an abnormal maturation pattern. In male rats, both models showed a delayed onset of puberty, defined by the balano-preputial separation, as well as impaired testicular function, shown by decreased testosterone levels. These data indicate that early malnutrition during a critical developmental time window may have long-lasting effects on pubertal development, including gonadal maturation in both humans and rats.

In adult bone, vitamin K contributes to bone health, probably through its role as co-factor in the carboxylation of osteocalcin. In children, the significance of vitamin K in bone-mass acquisition is less well known. The objective of this longitudinal study was to determine whether biochemical indicators of vitamin K status are related to (gains in) bone mineral content (BMC) and markers of bone metabolism in peripubertal children. In 307 healthy children (mean age 11·2 years), BMC of the total body, lumbar spine and femoral neck was determined at baseline and 2 years later. Vitamin K status (ratio of undercarboxylated (ucOC) to carboxylated (cOC) fractions of osteocalcin; UCR) was also measured at both time points. Markers of bone metabolism, sex steroids, vitamin D status and growth hormones were measured at baseline only. Large variations in the levels of the UCR were found at both time-points, indicating a substantial interindividual difference in vitamin K status. Improvement of vitamin K status over 2 years (n 281 children) was associated with a marked increase in total body BMC (r 249·1, P,0·001). The UCR was associated with pubertal stage, markers of bone metabolism, sex hormones and vitamin D status. A better vitamin K status was associated with more pronounced increase in bone mass in healthy peripubertal children. In order to determine the significance of these findings for childhood bone health, additional paediatric studies are needed.