To determine the timing of peak bone mass and density, we conducted a cross-sectional study of bone mass measurements in 265 premenopausal Caucasian females, aged 8-50 yr. Bone mass and bone mineral density were measured using dual X-ray absorptiometry and single-photon absorptiometry at the spine (anteroposterior, lateral), proximal femur, radius shaft, distal forearm, and the whole body. Bone mass parameters were analyzed using a quadratic regression model and segmented regression models with quadratic-quadratic or quadratic-linear form. The results show that most of the bone mass at multiple skeletal locations will be accumulated by late adolescence. This is particularly notable for bone mineral density of the proximal femur and the vertebral body. Bone mass of the other regions of interest is either no different in women between the age of 18 yr and the menopause or it is maximal in 50-yr-old women, indicating slow but permanent bone accumulation continuing at some sites up to the time of menopause. This gain in bone mass in premenopausal adult women is probably the result ofcontinuous periosteal expansion with age. Since rapid skeletal mineral acquisition at all sites occurs relatively early in life, the exogenous factors which might optimize peak bone mass need to be more precisely identified and characterized. (J. Clin. Invest.

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A statistical investigation of the fatigue crack propagation process was conducted. Sixty-eight replicate constant amplitude crack propagation tests were conducted on 2024-T3 aluminum alloy. From the experimental data, the distribution of N was found to be represented best by the 3-parameter log-normal distribution. Six growth rate calculation methods were investigated and a modified secant method was found to introduce the least amount of error into the growth rate data. No one single distribution was found to describe the distribution of da/dN. A prediction scheme using the distribution parameters of da/dN was partially successful.

We study non-trivial firing patterns in small assemblies of pulse-coupled oscillatory maps. We find conditions for the existence of waves in rings of coupled maps that are coupled bi-directionally. We also find conditions for stable synchrony in general all-to-all coupled oscillators. Surprisingly, we find that for maps that are derived from physiological data, the stability of synchrony depends on the number of oscillators. We describe rotating waves in two-dimensional lattices of maps and reduce their existence to a reduced system of algebraic equations which are solved numerically.

We suggested that calcium may be an important determinant of peak bone mass. For further elucidation, calcium balances in adolescent females with different calcium intakes (270-1637 mg/d), and a 2-y intervention study of calcium supplementation were performed. Hereditary influences on bone status were also evaluated by comparing subjects' and parents' bone mass. The main determinant of calcium balance was calcium intake; net calcium absorption increased with intake and urinary calcium did not change. Adolescent females retained 200-500 mg Ca/d, suggesting that inadequate calcium intake may translate into inadequate calcium retention and a reduction in peak bone mass. There was a more pronounced increase in bone mass over time in the calcium-supplemented group (1640 mg Ca/d) than in the control group (750 mg Ca/d), but the differences between bone mass measurements were not statistically significant, possibly because of a type II error. By the age of 16 y daughters had accumulated 90-97% of the bone mass of their premenopausal mothers.

Calcium supplementation significantly influenced bone accretion in young females during the pubertal growth spurt. By young adulthood, significant effects remained at metacarpals and at the forearm of tall persons, which indicated that the calcium requirement for growth is associated with skeletal size. These results may be important for both primary prevention of osteoporosis and prevention of bone fragility fractures during growth.

NEDD4-2 (also known as NEDD4L, neural precursor cell expressed developmentally down-regulated 4-like) is a ubiquitin protein ligase of the Nedd4 family which is known to bind and regulate a number of membrane proteins to aid in their internalization and turnover. Several of the NEDD4-2 substrates include ion channels, such as the epithelial and voltage-gated sodium channels. Given the critical function of NEDD4-2 in regulating membrane proteins, this ligase is essential for the maintenance of cellular homeostasis. In this article we review the biology and function of this important ubiquitin-protein ligase and discuss its pathophysiological significance.

Calcium is an important determinant of peak bone mass in young adults because of its influence on skeletal development during growth. Attainment of maximum peak bone mass requires optimal positive balance between calcium intake and obligatory losses of calcium, primarily in urine and feces. Urinary excretion is an important determinant of calcium retention in the body. Accordingly, the purpose of this study was to evaluate the influence of various nutrients on urinary calcium excretion, and to assess their impact on bone mass of young females, aged 8-13 y, during early puberty. The study was conducted in 381 healthy white females in pubertal stage 2. From each participant we collected basic anthropometric measurements, a 3-d food record, blood, a 24-h urine sample, and bone mass measurements of the total body and forearm by dual X-ray absorptiometry. Urinary sodium was found to be one of the most important determinants of urinary calcium excretion: [urinary calcium (mmol/d) = 0.01154 x urinary sodium (mmol/d) + 0.823], whereas calcium intake had relatively little impact: [urinary calcium (mmol/d) = 0.02252 x calcium intake (mmol/d) + 1.5261]. Urinary calcium was much higher at a calcium intake of approximately 37.5 mmol/d (1500 mg/d), supporting the notion that calcium is a threshold nutrient. Calcium intake had a significant positive influence on the bone mineral content and density of the whole body and radius shaft whereas urinary calcium had a negative influence, presumably by reducing calcium accretion into the skeleton.(ABSTRACT TRUNCATED AT 250 WORDS)