Jean‐Philippe Bonjour

Maximizing peak bone mass is advocated as a way to prevent osteoporosis. As a prerequisite to the elaboration of any preventive program aimed at maximizing peak bone mass, it is important to determine how the rate of skeletal growth at clinically relevant sites, such as lumbar spine and femoral neck, proceeds in relation to age and pubertal stages in both sexes. Bone mass was assessed in 207 healthy caucasian boys and girls, aged 9-18 yr. Bone mineral density (BMD; grams per cm2) and content (BMC; grams) were determined in lumbar spine (L2-L4), femoral neck (FN), and midfemoral shaft (FS), using dual energy x-ray absorptiometry. Bone variables were correlated with both chronological age and pubertal stage, and compared with young adult (20-35 yr) reference values. The main results are: 1) in males, compared to females, there was a marked age-related delay in L2-L4 BMD or BMC increase, but no delay was observed in relation to pubertal stages; 2) at the end of the rapid growth spurt, trends for higher mean values in males were observed for L2-L4 BMC, FN BMD, and particularly FS BMD, but no sex difference was observed for L2-L4 BMD; 3) in females, but not in males, a dramatic reduction in bone mass growth was observed after 15 yr of age, particularly for L2-L4 BMD/BMC and FN BMD. This sharp reduction occurred between the second and fourth years after menarche. In the 14- to 15-yr-old female group, BMD in L2-L4, FN, and FS corresponded to 99.2%, 105.1%, and 94.1%, respectively, and BMC in L2-L4 to 97.6% of the mean values recorded in 20- to 35-yr-old women. In conclusion, this cross-sectional study indicates that during pubertal development, major differences are observed in bone mass growth according to sex and skeletal site. Whereas in males bone mass at different skeletal sites continues to increase substantially between 15-18 yr, skeletal mass growth appears to dramatically slow down at the levels of both lumbar spine and FN at 15-16 yr of age in female adolescents. This suggests that the generally accepted notion that in both males and females bone mass continues to substantially accumulate at all skeletal sites until the fourth decade may not be a constant in human physiology.

The amount of skeletal mass acquired during adolescence is one of the most important determinants for the risk of postmenopausal and involutional osteoporosis. In both sexes, a large variance in bone mineral density (BMD) and content (BMC) is observed among healthy individuals at the beginning of the third decade. To determine the crucial pubertal years during which bone mass accumulation mainly occurs, we longitudinally monitored the gain in BMD/BMC at clinically important sites, such as lumbar spine and femoral neck, with respect to osteoporotic fracture risk. The changes in BMD (grams per cm2) and BMC (grams) were determined at 1-yr intervals at the level of lumbar spine vertebrae (L2-L4), femoral neck, and midfemoral shaft, using dual energy x-ray absorptiometry (Hologic QDR 1000), in 198 healthy adolescents (98 females and 100 males), aged 9-19 yr. Mean daily energy and calcium intakes, height, weight, and body mass index of the studied cohort were within the normal range for age. In females, the increment rate in BMD/BMC was particularly pronounced over a 3-yr period, i.e. from 11-14 yr of age. This increment dramatically fell after 16 yr and/or 2 yr after menarche. The mean gains in lumbar, femoral neck, and midfemoral shaft BMD were not statistically significant between 17-20 yr. In males, the gain in BMD/BMC was particularly high over a 4-yr period, i.e. from 13-17 yr. Then the increment rate markedly declined, but remained significant between 17-20 yr for L2-L4 BMD/BMC and midfemoral shaft BMD. In contrast, no significant increase was observed for femoral neck BMD. An impressive interindividual variation was observed between the yearly height increment and the bone mass accumulation. The bone mass-height gains relationship during puberty evolved according to a loop pattern, with maximal variance at Tanner stages P3-P4. This longitudinal study delineates the crucial pubertal years during which the skeletal mass accumulates at high, but various, rates at skeletal sites where the consequences of the osteoporosis are particularly dramatic. Furthermore, the results indicate that in a cohort of healthy females with apparently adequate intakes of energy and calcium, bone mass accumulation is drastically reduced by 16 yr of age in both lumbar spine and femoral neck.

The renal handling of inorganic phosphate (Pi) is controlled not only by PTH, but also by hitherto undetermined mechanisms dependent on phosphate intake. Recently, fibroblast growth factor (FGF)-23 was identified as a novel phosphaturic factor in tumor-induced osteomalacia and autosomal-dominant hypophosphatemic rickets. We hypothesized that phosphate intake could influence FGF-23 concomitantly to the changes in renal Pi handling. Twenty-nine healthy males were subjected to a 5-d low-phosphate diet and a phosphate binder, followed by a high-phosphate diet including supplements. Concomitant modifications in calcium intake allowed minimizing PTH changes in response to dietary phosphate. Serum FGF-23 levels significantly decreased on the low-phosphate diet, then increased with the oral phosphate load. Changes in FGF-23 were positively correlated with changes in 24-h urinary Pi excretion and negatively correlated with changes in the maximal tubular reabsorption of Pi and 1,25(OH)(2)D(3) (calcitriol), whereas PTH was not. In multivariate analysis, changes in FGF-23 remained the most significantly correlated to changes in 1,25(OH)(2)D(3) and maximal tubular reabsorption of Pi. Moreover, FGF-23 was positively correlated to serum osteocalcin, a marker of osteoblastic activity. In summary, FGF-23 was inversely related to renal Pi transport and serum calcitriol levels in healthy young men. These data suggest that FGF-23 may be implicated in the physiological regulation of Pi homeostasis in response to dietary phosphate changes, independent of PTH.