Age at voice break in Danish boys: effects of pre-pubertal body mass index and secular trend

Voice break is a late, but characteristic event in male puberty. Assessment of age at voice break may be a relevant marker for epidemiological studies of male pubertal development. We investigated the timing of voice break and its association with explanatory variables [calendar year of admission in the boys choir and pre-pubertal body mass index (BMI)] by survival analysis techniques based on retrospective analyses of age at voice break in 463 Danish choir boys who were studied over a 10-year period. We found an overall median age at voice break of 14.0 [13.9-14.6] years, and a statistically significant downwards trend in age at voice break in the 10-year period (1994-2003) (log-rank test p = 0.0146). There was a statistically significant difference in age at voice break between boys in the different BMI quartiles in pre-puberty (p = 0.00822) with a tendency towards early voice break with increasing BMI standard deviation scores. Thus boys in the heaviest quartile at 8 years of age had an increased risk of early voice break (RR of 1.74 [1.14-2.65]) approximately 6 years later, compared with boys in the thinnest quartile. The earlier voice break seen during the 10-year observation period could however not exclusively be explained by a general increase in BMI in that period. Our findings indicate that puberty, as assessed by age at voice break in boys, may be starting earlier in Denmark as it has been observed in the USA, and suggest a relationship between pre-pubertal BMI and the timing of puberty.     

Influence of Age,Sex, and Growth Variables on Phalangeal Quantitative Ultrasound Measures: A Study in Healthy Children and Adolescents

Skeletal status by phalangeal quantitative osteosonography (DBM Sonic BP - IGEA) was examined in 1227 healthy children (641 boys and 586 girls) aged 3–16 years. Aims of the study were to evaluate some physical parameters pertaining to the ultrasound transmission crossing the phalanx in a school-age population and to relate these values to age, sex, and growth variables. A correlation was found between AD-SoS (amplitude-dependent speed of sound) and BTT (bone transmission time) and, age, height, weight, and pubertal stage, respectively. No correlation existed between FWA (fast wave amplitude) and SDy (dynamics of the ultrasound signal) and age, height, weight, pubertal stage, and BMI, respectively. AD-SoS increased in boys until 7–8 years of age. Thereafter a plateau was reached up to age 12–13 years, when a rapid increase was observed corresponding to pubertal growth rate acceleration. In girls, AD-SoS increased with age up to 10–11 years with a steeper increase at the time of puberty starting about 2 years earlier than in boys. BTT presented a similar trend. Mean AD-SoS values increased from Tanner pubertal stages 1 to 2 and from stage 3 to 4 in both sexes. Significantly higher mean AD-SoS values in stages 2, 3, and 4 were observed in girls as compared to boys. Mean BTT values increased significantly from stage 1 to 5 in girls and from 1 to 4 in boys. QUS technology showed the ability to assess bone changes in the growing bone.     

Timing of pubertal maturation according to the age at first conscious ejaculation

The first conscious ejaculation (ejacularche) is an important event in the somatic and psychic development of boys. The aim of this study was to reveal the age at first ejaculation in Bulgarian boys and to observe the secular trend of this marker for puberty. A total of 1582 (901 from urban and 681 from rural origin respectively) gave a positive answer admitting the age in years at the first ejaculation. The mean age ± standard deviation (SD) of ejacularche was 13.27 ± 1.08 years, and the median was 13.0. It was found a significant difference between the urban (13.34 ± 1.07) and rural (13.18 ± 1.08) inhabitants in relation to the age of their remembered first ejaculation (P = 0.003). A secular trend in appearance of ejacularche was revealed when our results were compared with those from the previous studies in Bulgaria. We can suggest that in the presence of testicular volume ≥6 ml asking about ejaculation is reasonable and not superfluous. Self-reported spontaneous ejaculation can be used as an index of male pubertal timing.     

Pubertal maturation characteristics and the rate of bone mass development longitudinally toward menarche.

To assess risks for osteoporosis and to compare bone mass in different groups of healthy children or children with diseases, it is important to have knowledge of their sexual maturation status during puberty. The aim of our study was to evaluate bone mass formation longitudinally in relation to pubertal maturation characteristics in healthy white girls. We investigated the bone mineral content (BMC) and the bone mineral density (BMD) at different skeletal sites in 151 girls with increasing pubertal stages in relation with their chronological age and with an early or late onset of puberty or menarche and with a slow or fast maturation. Bone mass was measured at the onset of puberty, during puberty, and at menarche. We conclude the following: (1) from midpuberty to menarche, the increase in bone mass formation is highest at all skeletal sites in white girls; (2) early mature girls at the onset of puberty have slightly but definitely lower bone masses at all skeletal sites and at all pubertal stages than late mature girls, whereas the average bone mass formation from the onset of puberty to menarche is similar in both groups; (3) girls with a slow rate of pubertal maturation have lower bone mass values 2 years after the onset of puberty, but at menarche bone mass is similar compared with fast maturers; and (4) it cannot be confirmed that there is an effect of menarcheal age on bone mass values at menarche.     

Pubertal timing and body mass index gain from birth to maturity in relation with femoral neck BMD and distal tibia microstructure in healthy female subjects

Summary  

Childhood body mass index (BMI) gain is linked to hip fracture risk in elderly. In healthy girls, menarcheal age is inversely related to BMI gain during childhood and to femoral neck areal bone mass density (aBMD) and distal tibia structural components at maturity. This study underscores the importance of pubertal timing in age-related fragility fracture risk.     

Pubertal timing is an independent predictor of central adiposity in young adult males: the Gothenburg osteoporosis and obesity determinants study

The role of puberty and normal variations in pubertal timing for the development of obesity in men is unclear. The aim of the current study was to investigate the impact of pubertal timing and prepubertal BMI (kg/m(2)) for young adult BMI and fat mass distribution. Detailed growth charts from birth to age 18-20 years were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants study. Age at peak height velocity (PHV) and BMI at age 10 years were estimated for 579 subjects, and PHV was used as an assessment of pubertal timing. The fat mass characterization and distribution were analyzed using dual X-ray absorptiometry and peripheral as well as abdominal computed tomography at age 18.9 +/- 0.5 years. We demonstrate that age at PHV is an independent negative predictor of young adult BMI and whole-body fat mass. Interestingly, age at PHV is an independent negative predictor of central, but not peripheral, fat mass. In contrast, BMI at 10 years of age predicts both central and peripheral subcutaneous fat mass. In conclusion, we demonstrate that early pubertal onset specifically predicts a central fat mass distribution, while a predominantly subcutaneous obese phenotype is strongly predicted by a high prepubertal BMI.     

Bone mineral density in girls and boys at different pubertal stages: relation with gonadal steroids, bone formation markers, and growth parameters

Puberty has a key role in bone development. During puberty, several nutritional and hormonal factors play a major role in this process. The aim of this study was to determine the changes in areal bone mineral density (BMD), gonadal steroids, bone formation markers, and growth parameters in healthy Turkish pubertal girls and boys at different pubertal stages. In additional, we aimed to detect the relationship between BMD, sex steroids, and growth parameters, and to reveal the most important determinant of BMD in the pubertal period. BMD of the lumbar spine and total body was performed by dual-energy X-ray absorptiometry (Lunar DPX series) in 174 healthy pubertal children (91 girls, 83 boys), aged 11–15 years. Height and weight were measured. Pubertal stages were assesed. Bone formation markers and gonadal steroids were measured. BMD values significantly increased until stage IV in girls. In boys, BMD values also increased during puberty (P < 0.05), but it was significantly higher in stage IV compared with that in other pubertal stages (P < 0.01). Testosterone levels increased until stage IV in both sexes, particularly in boys. Estrogen levels significantly increased during puberty in girls, whereas it was significantly higher at stage IV in boys (P < 0.001). Bone-specific alkaline phosphatase (BAP) level was higher in early and midpuberty, and decreased in late puberty in girls (P < 0.001). BAP level was higher in stage IV in boys. Osteocalcin level was shown not to change significantly in pubertal stages. There was a modest correlation between BMD values and estrogen and testosterone levels in boys. In girls, there was a correlation between BMD values and estrogen levels only (P < 0.05). Weight was significantly associated with BMD in both sexes (P < 0.05). Estrogen had a significant influence on BMD in boys and girls. In conclusion, bone mass increased throughout puberty in both sexes. Peak bone mass was not achieved in girls, but was obtained at stage IV in boys. Bone formation markers were good predictors of bone mass in girls, but not in boys. Estrogen level made the greatest contribution to bone mineral acquisition in boys and girls. The achievement of peak bone mass was sustained by estrogen in boys. The major independent determinant of BMD in both sexes was weight.     

Effect of renal transplantation in childhood on longitudinal growth and adult height

BACKGROUND: Severe growth failure is frequently observed in children suffering from end-stage renal disease (ESRD). METHODS: We analyzed the effect of renal transplantation (RTx) on longitudinal growth and final height in 37 children (19 girls) with ESRD with a mean follow-up of 8.5 years. The mean age at RTx was 11.3 years. RESULTS: In children transplanted before start of puberty, mean height velocity increased significantly from 4.9 to 8.0 cm/year (P < 0.01), resulting in an increase in standardized height of 0.6 SD within two years post RTx. Although peak height velocity during puberty was significantly increased compared with healthy children, total pubertal height gain was reduced by 20% because of its shortened duration. Mean standardized height significantly increased from the time of RTx until final height by 1.3 SD and 0.7 SD in children transplanted before and after start of puberty, respectively. Mean adult height (boys 170 cm; girls 151 cm) was normal (> -2 SD) in 68% of patients. Change in standardized height from RTx until adult height was associated with initial degree of stunting and glomerular filtration rate (GFR; cumulative r2 0.49). Total pubertal height gain was associated with the age at start of puberty, GFR, and age at RTx (cumulative r2 0.57). CONCLUSION: RTx in children with ESRD induces moderate catch-up growth during the prepubertal growth period. However, final height is reduced in about one third of patients due to the reduced pubertal height gain and preexisting height deficit at the time of RTx.     

Growth and pubertal development following pediatric heart transplantation: a 15-year experience at Ste-Justine Hospital.

BACKGROUND: Thirty-one children and adolescents have undergone allograft heart transplantation at Ste-Justine Hospital from July 1984 to August 1996. Twenty-five patients were followed prospectively more than 3 years to document their growth and pubertal development. METHODS: Parameters surveyed were clinical (height, weight, pubertal staging, and bone age) and biochemical (luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, dehydroepiandrosterone sulphate (DHEAS), IGF-1, and fasting insulin). RESULTS: At surgery, there were 18 boys and 7 girls aged 11 months to 17 years (median 13 years); 14 had congenital heart defects (CHDs) and 11 had a cardiomyopathy (CM). Immunosuppressive therapy included cyclosporine, azathioprine, and prednisone. Eighteen patients were still growing (15 boys, 3 girls): 8 had a retarded bone age and 6 with CHD had severe growth failure. Following surgery, most patients maintained their height within one sodium dodecyl sulfate (SDS) score of that initially observed. Patients reaching their target heights do so mainly in the lower range. Three patients not reaching target height had a CHD. Weight was greatest 1 year postoperatively (113 +/- 27% ideal body weight) with normalization at 2 years (100 +/- 18%). Of the 13 prepubertal patients, menarche occurred at age 12 in 1 girl, while 3 boys began puberty at age 12 years. In both sexes, serum levels of gonadotropins and IGF-1 increased during puberty, moderate hyperinsulinism was observed, and DHEAS levels decreased. CONCLUSIONS: Our results indicate that children and adolescents grow normally following cardiac transplantation and that they attain their target height despite a lack of catch-up growth. They gain weight significantly in the first postoperative year with normalization of their weight at 2 years. Furthermore, the clinical and biochemical indices of puberty are overall within the norms. However, the severity of growth delay at the time of transplantation inherent to the cardiac pathology has a major impact on adult height.     

Insulin resistance during puberty: results from clamp studies in 357 children.

Insulin resistance may be an important cause of a constellation of cardiovascular risk factors in adults, and onset of this syndrome may occur in childhood. However, children normally experience transient insulin resistance at puberty. There were 357 normal children (159 girls, 198 boys) age 10-14 years who underwent euglycemic clamp studies to assess the effects of Tanner stage (T), sex, ethnicity, and BMI on insulin resistance. Insulin resistance increased immediately at the onset of puberty (T2), but returned to near prepubertal levels by the end of puberty (T5). Its peak occurred at T3 in both sexes, and girls were more insulin resistant than boys at all T stages. White boys appeared to be more insulin resistant than black boys; no difference was seen between white and black girls. Insulin resistance was strongly related to BMI, triceps skinfold thickness, and waist circumference, and this relationship was independent of Tanner stage or sex. Differences in BMI and adiposity did not, however, entirely explain the insulin resistance of puberty. These results demonstrate that 1) significant differences in insulin resistance are present between boys and girls; 2) insulin resistance increases significantly at T2, T3, and T4, but decreases to near prepubertal levels at T5; and 3) while insulin resistance is related to BMI and anthropometric measures of fatness, these factors do not completely explain the insulin resistance that occurs during the Tanner stages of puberty.     

Differential effect of age,gender and puberty on bone formation rate assessed by measurement of bone-specific alkaline phosphatase in healthy Italian children and adolescents

Bones undergo intensive modeling during growth, a process involving both formation and resorption processes. Bone formation can be accurately monitored by measurements of bone-specific alkaline phosphatase (BAP) in serum. The lack of appropriate reference values has hampered the use of BAP in pediatric subjects. The purposes of the present study were to verify the effect of age, gender, and puberty on BAP concentration in healthy children, and to generate reference curves. Morning blood samples were collected from 239 healthy children and adolescents (113 boys), aged 4.5–20.9 years. Anthropometric measurements and pubertal stage were recorded. Blood samples were also obtained from 37 healthy young adults (13 men), aged 21.5–30.2 years. BAP concentration varied significantly with age, showing a peak at age 10–12 years in girls and 12–14 years in boys. Prepubertal concentration of BAP was six- to sevenfold higher than in healthy adults. We observed significantly higher BAP values at the beginning of puberty (stage II) compared to prepubertal stage in both sexes. The effect of puberty was independent from age and gender. We demonstrated that BAP serum concentration varies with age in children and adolescents, and we provided equations to calculate reference values. Because BAP concentrations vary markedly according to the pubertal stage, the values of BAP obtained in single patients should be compared to reference considering not only age and sex, but also the stage of pubertal development.     

High urinary phthalate concentration associated with delayed pubarche in girls

Phthalates are a group of chemicals present in numerous consumer products. They have anti-androgenic properties in experimental studies and are suspected to be involved in human male reproductive health problems. A few studies have shown associations between phthalate exposure and changes in pubertal timing among girls, although controversies exist. We determined the concentration of 12 phthalate metabolites in first morning urine samples from 725 healthy Danish girls (aged 5.6-19.1 years) in relation to age, pubertal development (breast and pubic hair stage) and reproductive hormone levels (luteinizing hormone, oestradiol and testosterone). Furthermore, urinary phthalates were determined in 25 girls with precocious puberty (PP). In general, the youngest girls with less advanced pubertal development had the highest first morning urinary concentration of the monobutyl phthalate isoforms (∑MBP((i+n))), monobenzyl phthalate (MBzP), metabolites of di-(2-ethylhexyl) phthalate (∑DEHPm) and of di-iso-nonyl phthalate (∑DINPm). After stratification of the urinary phthalate excretion into quartiles, we found that the age at pubarche was increasing with increasing phthalate metabolite quartiles (except for MEP). This trend was statistically significant when all phthalate metabolites (except MEP) were summarized and expressed as quartiles. No association between phthalates and breast development was observed. In addition, there were no differences in urinary phthalate metabolite levels between girls with PP and controls. We demonstrated that delayed pubarche, but not thelarche, was associated with high phthalate excretion in urine samples from 725 healthy school girls, which may suggest anti-androgenic actions of phthalates in our study group of girls.     

Do Secular Trends in Skeletal Maturity Occur Equally in Both Sexes?

Background

Skeletal maturity assessment provides information on a child’s physical development and expectations based on chronological age. Given recently recognized trends for earlier maturity in a variety of systems, most notably puberty, examination of sex-specific secular trends in skeletal maturation is important. For the orthopaedist, recent trends and changes in developmental timing can affect clinical management (eg, treatment timing) if they are currently based on outdated sources.

Questions/purposes

(1) Has the male or female pediatric skeleton experienced a secular trend for earlier maturation over the past 80 years? (2) Do all indicators of maturity trend in the same direction (earlier versus later)?

Methods

In this retrospective study, a total of 1240 children were examined longitudinally through hand-wrist radiographs for skeletal maturity based on the Fels method. All subjects participate in the Fels Longitudinal Study based in Ohio and were born between 1930 and 1964 for the “early” cohort and between 1965 and 2001 for the “recent” cohort. Sex-specific secular trends were estimated for (1) mean relative skeletal maturity through linear mixed models; and (2) median age of maturation for individual maturity indicators through logistic regression and generalized estimating equations.

Results

Overall relative skeletal maturity was significantly advanced in the recent cohort (maximum difference of 5 months at age 13 years for girls, 4 months at age 15 years for boys). For individual maturity indicators, the direction and magnitude of secular trends varied by indicator type and sex. The following statistically significant secular trends were found: (1) earlier maturation of indicators of fusion in both sexes (4 months for girls, 3 months for boys); (2) later maturation of indicators of projection in long bones in both sexes (3 months for girls, 2 months for boys); (3) earlier maturation of indicators of density (4 months) and projection (3 months) in carpals and density in long bones (6 months), for girls only; and (4) later maturation of indicators of long bone shape (3 months) for boys only.

Conclusions

A secular trend has occurred in the tempo of maturation of individual components of the pediatric skeleton, and it has occurred in a sex-specific manner. The mosaic nature of this trend, with both earlier and later maturation of individual components of the skeletal age phenotype, calls for greater attention to specific aspects of maturation in addition to the overall skeletal age estimate. The Fels method is currently the most robust method for capturing these components, and future work by our group will deliver an updated, user-friendly version of the Fels assessment tool.

Clinical Relevance

Appreciation of sex-specific secular changes in maturation is important for clinical management, including treatment timing, of orthopaedic patients, because children today exhibit a different pattern of maturation than children on whom original maturity assessments were based (including Fels and Greulich-Pyle).

Electronic supplementary material

The online version of this article (doi:10.1007/s11999-015-4213-1) contains supplementary material, which is available to authorized users.     

Lower-limb growth: how predictable are predictions?

Purpose  The purpose of this review is to clarify the different methods of predictions for growth of the lower limb and to propose a simplified method to calculate the final limb deficit and the correct timing of epiphysiodesis. Background  Lower-limb growth is characterized by four different periods: antenatal growth (exponential); birth to 5 years (rapid growth); 5 years to puberty (stable growth); and puberty, which is the final growth spurt characterized by a rapid acceleration phase lasting 1 year followed by a more gradual deceleration phase lasting 1.5 years. The younger the child, the less precise is the prediction. Repeating measurements can increase the accuracy of predictions and those calculated at the beginning of puberty are the most accurate. The challenge is to reduce the margin of uncertainty. Confrontation of the different parameters—bone age, Tanner signs, annual growth velocity of the standing height, sub-ischial length and sitting height—is the most accurate method. Charts and diagrams are only models and templates. There are many mathematical equations in the literature; we must be able to step back from these rigid calculations because they are a false guarantee. The dynamic of growth needs a flexible approach. There are, however, some rules of thumb that may be helpful for different clinical scenarios. Calculation of limb length discrepancy  For congenital malformations, at birth the limb length discrepancy must be multiplied by 5 to give the final limb length discrepancy. Multiple by 3 at 1 year of age; by 2 at 3 years in girls and 4 years in boys; by 1.5 at 7 years in girls and boys, by 1.2 at 9 years in girls and 11 years in boys and by 1.1 at the onset of puberty (11 years bone age for girls and 13 years bone age for boys). Timing of epiphysiodesis  For the timing of epiphysiodesis, several simple principles must be observed to reduce the margin of error; strict and repeated measurements, rigorous analysis of the data obtained, perfect evaluation of bone age with elbow plus hand radiographs and confirmation with Tanner signs. The decision should always be taken at the beginning of puberty. A simple rule is that, at the beginning of puberty, there is an average of 5 cm growth remaining at the knee. There are four common different scenarios: (1) A 5-cm discrepancy—epiphysiodesis of both femur and tibia at the beginning of puberty (11 years bone age girls and 13 years in boys). (2) A 4-cm discrepancy—epiphysiodesis of femur and tibia 6 months after the onset of puberty (11 years 6 months bone age girls, 13 years 6 months bone age boys, tri-radiate cartilage open). (3) A 3-cm discrepancy—epiphysiodesis of femur only at the start of puberty, (skeletal age of 11 years in girls and 13 years in boys). (4) A 2-cm discrepancy—epiphysiodesis of femur only, 1 year after the start of puberty (12 years bone age girls and 14 years in boys).     

Development of fat tissue and body mass index from infancy to adulthood

This paper gives a short overview of our recent research on changes in the body mass index (BMI) or in body fat for children studied longitudinally from birth to adulthood. The BMI shows characteristic changes in childhood and adolescence which are different from those known for skeletal growth. A period of loss of BMI from 1 to 6 years is followed by a pubertal spurt which is larger in females than in males. Fat shows a dramatic increase in the 1st year, and velocity is higher for girls than for boys after 3 years of age. At puberty there is a pre-pubertal and a post-pubertal spurt in total body fat or in arm fat and a dip in between. Those heavy or fat as adults have a qualitatively similar pattern of developmental changes, but much more accentuated fluctuations. The analysis relies on new statistical techniques.     

Cortical porosity is higher in boys compared with girls at the distal radius and distal tibia during pubertal growth: an HR-pQCT study

The aim of this study was to determine the sex- and maturity-related differences in bone microstructure and estimated bone strength at the distal radius and distal tibia in children and adolescents. We used high-resolution pQCT to measure standard morphological parameters in addition to cortical porosity (Ct.Po) and estimated bone strength by finite element analysis. Participants ranged in age from 9 to 22 years (n = 212 girls and n = 186 boys) who were scanned annually for either one (11%) or two (89%) years at the radius and for one (15%), two (39%), or three (46%) years at the tibia. Participants were grouped by the method of Tanner into prepubertal, early pubertal, peripubertal, and postpubertal groups. At the radius, peri- and postpubertal girls had higher cortical density (Ct.BMD; 9.4% and 7.4%, respectively) and lower Ct.Po (-118% and -56%, respectively) compared with peri- and postpubertal boys (all p < 0.001). Peri- and postpubertal boys had higher trabecular bone volume ratios (p < 0.001) and larger cortical cross-sectional areas (p < 0.05, p < 0.001) when compared with girls. Based upon the load-to-strength ratio (failure load/estimated fall force), boys had lower risk of fracture than girls at every stage except during early puberty. Trends at the tibia were similar to the radius with differences between boys and girls in Ct.Po (p < 0.01) and failure load (p < 0.01) at early puberty. Across pubertal groups, within sex, the most mature girls and boys had higher Ct.BMD and lower Ct.Po than their less mature peers (prepuberty) at both the radius and tibia. Girls in early, peri-, and postpubertal groups and boys in peri- and postpubertal groups had higher estimates of bone strength compared with their same-sex prepubertal peers (p < 0.001). These results provide insight into the sex- and maturity-related differences in bone microstructure and estimated bone strength.     

Staging puberty in slipped capital femoral epiphysis: importance of the triradiate cartilage

In 83 children with slipped capital femoral epiphysis, puberty was staged at the time of diagnosis using bone age, closure of triradiate cartilage, Risser index, and the pubertal diagram of Dimeglio. In boys 95% and in girls 83% of slips occurred during the accelerating phase of puberty (stage 1 and 2), in which mainly the limbs grow. In boys (54%) and in girls (66%), most slips occurred in stage 1. The triradiate cartilage was still open at the time of diagnosis in 65% of boys and 64% of girls. Staging puberty is useful to differentiate the risk for slipped capital femoral epiphysis and to evaluate the risk for a contralateral slip. Closure of the triradiate cartilage is a simple measure to identify this risk. Once the triradiate cartilage is closed, there is a 4% chance of a contralateral slip.     

The relationships between pubertal development, IGF-1 axis, and bone formation in healthy adolescents

As IGF-1 is the major factor that affects bone growth, and both osteocalcin and bone-specific alkaline phosphatase are important markers of bone formation during puberty, there must be a relationship between these markers that does not change according to sex. The aim of this study was to investigate the relationships between pubertal development, the IGF-1 axis, and bone formation in healthy adolescents. Two hundred and five healthy children and adolescents were included in this cross-sectional study. Tanners classification was used to determine the pubertal developmental stage. Serum IGF-1 levels and IGF-1/IGFBP-3 ratios increased with advancing pubertal stages, and maximum mean values were found at stages III–IV in girls and at stage IV in boys. Serum IGF-1 and IGFBP-3 levels were significantly correlated with osteocalcin and bone-specific alkaline phosphatase levels in boys, but not in girls. This difference between the sexes, and the relation of the IGF-1 axis to increased bone formation during puberty in both sexes, can be explained by the rate of increase of the IGF-1/IGFBP-3 ratio. We conclude that the timing of the increased bone formation rate during puberty; that is, the timing of the pubertal growth spurt, is determined by the maximum increase rate of the IGF-1/IGFBP-3 ratio. But this new hypothesis needs to be supported by longitudinal studies.     

Effect of gender, puberty, and vitamin D status on biochemical markers of bone remodedeling

Peak bone mass, a determinant of osteoporosis at older ages, is affected by genetic, nutritional, lifestyle, and hormonal factors. Adolescence is a critical time for peak bone mass accrual, and boys achieve a higher peak bone mass than girls. We have reported vitamin D insufficiency in adolescents in our population, but its impact on bone remodeling is unclear. We systematically evaluated the impact of puberty, gender, and vitamin D status on biochemical markers of bone remodeling. Serum osteocalcin (OC), bone alkaline phosphatase (BAP), C-terminal telopeptide of type I collagen crosslinks (S-CTX), and 25 OH vitamin D were measured in 172 healthy students from private schools in the fall of 1999: There were 92 girls and 80 boys, age 10-17 years. In girls, all markers of bone turnover changed significantly with pubertal stage, were maximal at midpuberty, and decreased toward adult levels by Tanner stage V. Conversely in boys, these markers increased during early pubertal stages but had not normalized by Tanner stage V. Levels of all biochemical markers were significantly higher in boys compared to girls even after adjustment for age, body weight, and Tanner stage, P < 0.0001. In the subgroup of girls, those with vitamin D insufficiency, serum levels of BAP and S-CTX were highest. However, in multiple regression analyses, gender was the only consistent correlate of all three markers of bone remodeling. In conclusion, after adjusting for age, weight, and Tanner stages, changes in bone remodeling markers were most powerfully affected by gender. The latter may have important implications on gender differences in peak bone mass.