Delayed puberty and peak bone mass.

The accrual of bone mass during childhood and adolescence is a major determinant of peak bone mass (PBM), and thereby of the risk of osteoporotic fractures occurring in advanced age (1). The development of noninvasive techniques, such as dual-energy X-ray absorptiometry (DXA), has made it possible to determine with precision and very low radiation exposure the pattern of bone mineral mass accumulation at various sites of the axial and appendicular skeleton during infancy, childhood and adolescence. At the end of the growth period, a wide variance in areal bone mineral density (aBMD, in g/cm) or content (BMC, in g) in either the axial or the appendicular skeleton is observed both in healthy females and males (1). This broad variance is barely reduced after correction for standing height. It is already present before puberty, but at certain skeletal sites, such as lumbar (L) spine and proximal femur, this height-independent variance in aBMD/BMC still tends to become broader (1). The mechanical resistance of bone depends upon several factors among which the size of the bone, the amount of bony tissue within the periostal envelope (i.e. the volumetric density) and its space distribution (i.e. the microand macroarchitecture) appear to be the most important determinants. The aBMD variable as measured by DXA is directly related both to the volumetric mineral density (vBMD) and to the size of the bone in the axis of the beam generated by the energy source. The integration of these two important components of mechanical resistance can explain why it is not surprising that inverse relationships have repeatedly been found between aBMD and the incidence of osteoporotic fractures (2). During development the increase in aBMD at several skeletal sites is essentially due to an augmentation in bone size with an increase in cortical thickness which mainly results from the process of periosteal apposition. In contrast, in the parts of the skeleton with both compact and spongious bony tissue as, for instance, in vertebral bodies, the volumetric trabecular density appears to increase very little from birth to the age at which peak bone mass is attained (1). The gender difference in either aBMD or BMC observed at the level of the radial or femoral diaphysis in young adults is essentially generated during pubertal maturation, with a greater gain in bone size in males than in females (1). Likewise in the lumbar spine, where the gender difference in BMC observed at PBM (2) appears to result essentially from a greater increase in the size of the male vertebral bodies during pubertal maturation (3). In both clinical practice and trials in human subjects the measurement of aBMD provides important information on the factors that can affect bone mineral mass accrual and loss (4). The operational definition of osteoporosis as endorsed by the World Health Organisation is based on the measurement of aBMD, the risk of fragility fractures being inversely related to the value of aBMD (4). Puberty is a crucial time in bone mineral mass development. Thus, at the lumbar spine level the mass of bone mineral more than doubles from 9 to 15 years and from 11 to 17 years in females and males respectively (1, 3). Epidemiological studies have provided suggestive evidence that late menarche is a risk factor of osteoporosis. Osteopenia has been reported in a cohort of men with a history of delayed puberty (5). Delayed puberty or adolescence has been defined as the absence of any sign of puberty in a subject who has attained the upper normal limit of chronological age for the onset of puberty. This means an absence of increase in testicular volume at 14 years in a boy or an absence of any breast development in a girl at 13 years of age (6). The causes of delayed adolescence have been classified in permanent and temporary disorders. The permanent ones can be due to either hypothalamo– pituitary or gonadal failure (6). Among the temporary disorders, some can be explained by the presence of chronic systemic diseases, nutritional disorders, psychological stress, intensive competitive training, or hormonal disturbances such as hyposecretion of thyroid hormones or growth hormone, or hypercortisolism (6). However, the most common cause of delayed adolescence is the so-called ‘constitutional delay of growth and puberty’ (CDGP). It is a transient disorder with, in some cases, a familial history of late menarcheal age of the mother or sisters, or a delayed growth spurt in the father (6). This condition has been considered so far as an extreme form of the physiological variations of the timing of the onset of puberty of which the ‘normal’ range is about 8–12 and 9–13 years of age in girls and boys respectively (7). The onset of puberty is a complex process involving the activation of the hypothalamic– pituitary–gonadal axis and other endocrine systems such as the growth hormone–insulin-like growth factor (IGF) axis (6, 7) of which the targets include factors European Journal of Endocrinology (1998) 139 257–259 ISSN 0804-4643