Exploration of bone metabolism status in the distal femur of mice at different growth stages.

The mouse femur, particularly the distal femur, is commonly utilized in orthopedic research. Despite its significance, little is known about the key events involved in the postnatal development of the distal femur. Therefore, investigating the development process of the mouse distal femur is of great importance. In this study, distal femurs of CD-1 mice aged 1, 2, 4, 6, and 8 weeks were examined. We found that the width and height of the distal femur continued to increase till the 4th week, followed with stabilization. Notably, the width to height ratio remained relatively consistent with age. Micro computed tomography analysis demonstrated gradual increases in bone volume/tissue volume, trabecular number, and trabecular thickness from 1 to 6 weeks, alongside a gradual decrease in trabecular separation. Histological analysis further indicated the appearance of the secondary ossification center at approximately 2 weeks, with ossification mostly completed by 4 weeks, leading to the formation of a prototype epiphyseal plate. Subsequently, the epiphyseal plate gradually narrowed at 6 and 8 weeks. Moreover, the thickness and maturity of the bone cortex surrounding the epiphyseal plate increased over time, reaching peak cortical bone density at 8 weeks. In conclusion, to enhance model stability and operational ease, we recommend constructing conventional mouse models of the distal femur between 4 and 8 weeks old.

[NFIX gene mutation causes Marshall-Smith syndrome in a pair of identical twins and literature review]. / NFIXåŸºå› å˜å¼‚å¯¼è‡´ä¸€å¯¹åŒåµåŒèƒžèƒŽMarshall-Smithç»¼åˆå¾å¹¶æ–‡çŒ®å¤ä¹ .

This article reports on the clinical and genetic characteristics of monozygotic twins with Marshall-Smith syndrome (MRSHSS) due to a mutation in the NFIX gene, along with a review of related literature. Both patients presented with global developmental delays, a prominent forehead, shallow eye sockets, and pectus excavatum. Genetic testing revealed a heterozygous splicing site mutation c.697+1G>A in both children, with parents showing wild-type at this locus. According to the guidelines of the American College of Medical Genetics and Genomics, this mutation is considered likely pathogenic and has not been previously reported in the literature. A review of the literature identified 32 MRSHSS patients with splicing/frameshift mutations. Accelerated bone maturation and moderate to severe global developmental delay/intellectual disability are the primary clinical manifestations of patients with MRSHSS. Genetic testing results are crucial for the diagnosis of this condition.

Growth pattern of lumbar maturity stage at L1 to L5 during adolescent growth spurt.

PURPOSE: This study aimed to clarify the order of the lumbar maturity stage, each at L1 to L5, and the relationships between age at peak height velocity (APHV) and the lumbar maturity stage. METHODS: A total of 120 male first-grade junior high school soccer players were enrolled and followed for two years, and measurements were performed five times (T1 to T5). The lumbar maturity stage was assessed according to the degree of lesion of the epiphyseal from L1 to L5 using magnetic resonance imaging and classified into three stages: cartilaginous stage, apophyseal stage, and epiphyseal stage. The relationships between T1 and T5 temporal changes and developmental stages divided by 0.5 year increments based on APHV and the lumbar maturity stage at L1 to L5 were examined. For the apophyseal stage, developmental age calculated based on the difference between APHV and chronological age between each lumbar vertebra was compared. RESULTS: We found that part of the cartilaginous stages decreased as time progressed, while that of the apophyseal and epiphyseal stages increased at L1 to L5 (chi-square test, p < 0.01). L5 matured earlier with the apophyseal stage than L1 to L4 (p < 0.05). The lumbar maturity stage was attained toward L1 from L5, comparing different lumbar levels. CONCLUSION: The lumbar maturity stage progresses from L5 toward L1, and the apophyseal and epiphyseal stages would replace the cartilaginous stage at approximately 14 years of age or after APHV.

Factors affecting bone maturation in Chinese girls aged 4-8 years with isolated premature thelarche.

BACKGROUND: In isolated premature thelarche (IPT) girls, bone age (BA) is considered consistent with chronological age. However, some IPT girls confirmed by gonadotropin-releasing hormone (GnRH) stimulation test could show another trend. We analysed BA and possible potentiating factors in a selected group of girls aged 4-8 years with IPT. METHODS: IPT girls confirmed by GnRH stimulation test aged 4-8 years hospitalized from January 2015 to April 2018 at Shenzhen Children's Hospital were included in this retrospective study. They were divided into two groups with advanced BA of 2 years as the cut-off. Body mass index (BMI) and hormone levels were the main outcome measures, and regression analysis was used to identify independent risk factors. IPT girls were divided into subgroups according to the levels of BMI standard deviation score (SDS), insulin-like growth factor-1 (IGF-1) SDS and dehydroepiandrosterone sulfate (DHEAS) SDS for comparisons of advanced BA. RESULTS: Overall, 423 subjects were included and classified into the advanced BA group (48.7%, n = 206) and control group (51.3%, n = 217). The advanced BA group had significantly higher BMI SDS, serum DHEAS SDS, IGF-1 SDS, androstenedione and fasting insulin and significantly lower sex hormone binding globulin (all p < 0.001). Serum IGF-1 SDS (OR = 1.926, p<0.001), BMI SDS (OR = 1.427, p = 0.001) and DHEAS SDS (OR = 1.131, p = 0.005) were independent risk factors for significantly advanced BA. In the multiple linear regression model, serum IGF-1 SDS, BMI SDS and DHEAS SDS were the strongest predictors of advanced BA, accounting for 19.3% of the variance. According to BMI, 423 patients were classified into three groups: normal weight (56.03%, n = 237), overweight (19.15%, n = 81) and obesity (24.82%, n = 105). The proportion of advanced BA in obesity group was significantly higher than those of normal weight and overweight groups (χ2 = 18.088, p<0.001). In the subgroup with normal weight, higher serum IGF-1 SDS (p = 0.009) and DHEAS SDS (p = 0.003) affected BA advancement independent of BMI SDS. CONCLUSIONS: Girls with IPT confirmed by GnRH stimulation test aged 4-8 years might have significantly advanced BA. Obesity was highly associated with advanced BA. Age-specific serum IGF-1 SDS and DHEAS SDS were risk factors for BA advancement independent of BMI.

Automated radiogrammetry is a feasible method for measuring bone quality and bone maturation in severely disabled children.

BACKGROUND: Children with severe neurological impairment and intellectual disability are prone to low bone quality and fractures. OBJECTIVE: We studied the feasibility of automated radiogrammetry in assessing bone quality in this specific group of children. We measured outcome of bone quality and, because these children tend to have altered skeletal maturation, we also studied bone age. MATERIALS AND METHODS: We used hand radiographs obtained in 95 children (mean age 11.4 years) presenting at outpatient paediatric clinics. We used BoneXpert software to determine bone quality, expressed as paediatric bone index and bone age. RESULTS: Regarding feasibility, we successfully obtained a paediatric bone index in 60 children (63.2%). The results on bone quality showed a mean paediatric bone index standard deviation score of -1.85, significantly lower than that of healthy peers (P < 0.0001). Almost 50% of the children had severely diminished bone quality. In 64% of the children bone age diverged more than 1 year from chronological age. This mostly concerned delayed bone maturation. CONCLUSION: Automated radiogrammetry is feasible for evaluating bone quality in children who have disabilities but not severe contractures. Bone quality in these children is severely diminished. Because bone maturation frequently deviated from chronological age, we recommend comparison to bone-age-related reference values.

Effect of rhBMP-2 dose on bone formation/maturation in a rat critical-size calvarial defect model.

BACKGROUND: Application of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been associated with significant adverse events in craniofacial settings, including swelling and seroma formation. Recent work has demonstrated an inverse relationship between bone formation/maturation and rhBMP-2 dose, frequency/severity of adverse events increasing with rising dose. OBJECTIVE: The objective of this study was to determine the most effective dose for rhBMP-2 soak-loaded onto an absorbable collagen sponge (ACS) carrier for bone formation/maturation using an established defect model. METHODS: One hundred sixty-eight outbred male Sprague-Dawley rats, age 11-13 weeks, weight 325-375 g randomized into seven groups of 24 subdivided into groups of eight, were used to provide radiographic and light microscopy observations of bone formation/maturation and aberrant healing events at 2, 4 and 8 weeks following application of rhBMP-2/ACS into critical-size, ø8-mm, through-through, calvarial osteotomy defects for a dose of 1.25, 2.5, 5.0, 10.0 and 20.0 µg rhBMP-2/defect, or serve as ACS or sham-surgery controls. RESULTS: rhBMP-2 dosages ≥ 2.5 µg/defect showed histological defect closure >90% within 2 weeks, and complete resolution within 4 weeks. Adverse healing events including swelling, excessive bone formation or seroma formation could not be determined with certainty in this defect model. Notably ACS control sites showed complete defect closure at the 8-week healing interval. CONCLUSIONS: rhBMP-2/ACS accelerates local bone formation in the rat critical-size through-through calvarial defect model once reaching an osteoinductive dose threshold. This threshold may already be reached at a 1.25-/2.5-µg dose in this model. No further enhancement to bone formation/maturation may be observed adding rhBMP-2 above the 2.5-µg dose. The 1.25-20.0 µg dose range did not invoke appreciable aberrant healing events.

Chronology of fusion of the primary and secondary ossification centers in the human sacrum and age estimation in child and adolescent skeletons.

Little is known about fusion times of the primary and secondary centers of ossification in the sacrum, particularly from dry bone observations. In this study, the timing of union of these centers was studied in a sample of modern Portuguese skeletons (90 females and 101 males) between the ages of 0 and 30 years, taken from the Lisbon documented skeletal collection. A three-stage scheme was used to assess fusion status between ossification centers as unfused, partially fused and completely fused. Posterior probability tables of age, given a certain stage of fusion, were calculated for most anatomical locations studied using both reference and uniform priors. Partial union of primary centers of ossification was observed from 1 to 8 years of age and partial union of secondary centers of ossification was observed from 15 to 21 years of age. The first primary centers of ossification to complete fusion are the neural arch with the centrum of the fifth sacral vertebrae and the last are the costal element with the centrum of the first sacral vertebra. The annular and sacroiliac epiphyses are the first, among the secondary centers of ossification observed, to complete fusion, after which the lateral margin fuses. This study offers information on timing of fusion of diverse locations in the developing sacrum useful for age estimation of complete or fragmented immature human skeletal remains and fills an important gap in the literature, by adding to previously published times of fusion of primary and secondary ossification centers in this sample.

Case Report: Anastrozole as a monotherapy for pre-pubertal children with non-classic congenital adrenal hyperplasia.

Most children with non-classic congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency are asymptomatic and do not require cortisol replacement therapy unless they develop symptoms of hyperandrogenemia. The current practice is to treat symptomatic children with hydrocortisone aimed at suppressing excess adrenal androgen production irrespective of the child's level of endogenous cortisol production. Once on hydrocortisone therapy, even children with normal cortisol production require stress dosing. Some children with NC-CAH may present with premature adrenarche, growth acceleration, and advanced bone age, but with no signs of genital virilization and normal endogenous cortisol production. In these cases, an alternative therapy to hydrocortisone treatment that does not impact the hypothalamic-pituitary-adrenal axis, but targets increased estrogen production and its effects on bone maturation, could be considered. Aromatase inhibitors (AIs), which block the aromatization of androgen to estrogen, have been used off-label in men with short stature to delay bone maturation and as an adjunct therapy in children with classic CAH. The use of AI as a monotherapy for children with NC-CAH has never been reported. We present three pre-pubertal female children with a diagnosis of NC-CAH treated with anastrozole monotherapy after presenting with advanced bone age, early adrenarche, no signs of genital virilization, and normal peak cortisol in response to ACTH stimulation testing. Bone age z-scores normalized, and all three reached or exceeded their target heights. Monotherapy with anastrozole can be an effective alternative in slowing down bone maturation and improving height outcomes in children with NC-CAH and normal adrenal cortisol production.

Effects of half-dose spiomet treatment in girls with early puberty and accelerated bone maturation: a multicenter, randomized, placebo-controlled study protocol.

BACKGROUND: A "mismatch" sequence of less prenatal weight gain and more postnatal weight gain may lead to ectopic lipid accumulation, and trigger the development of early adrenarche/pubarche and the activation of the gonadotropic axis resulting in early puberty and ending up in full-blown adolescent polycystic ovary syndrome (PCOS). In the present study, we assess whether a low-dose combination of generics that collectively reduce ectopic fat through different pathways can slow down the accelerated maturation in "mismatch" girls with early puberty. METHODS: Randomized, placebo-controlled, multicenter, phase 2a, study in 64 girls [age, 8.0-9.3 years; birthweight (BW) for gestational age in lower tertile (-1.96< Z-score <-0.44), body mass index (BMI) in upper tertile (+0.44< Z-score < +1.96) and early progressive puberty (Tanner B2 at 7.7-9.0 years)]. Pharmacological intervention will be with a half-dose version of SPIOMET (mini-spiomet), a combination that reverts the PCOS phenotype in "mismatch" adolescents; mini-spiomet will contain spironolactone (25 mg/day, to raise brown adipose tissue activity), pioglitazone (3.75 mg/day, to raise adiponectin and insulin sensitivity), and metformin (425 mg/day, to raise AMPK activity and GDF15). Recruitment: 1 year; double-blind treatment: 1 year; open follow-up: 1 year; analyses and reporting: 1 year. INTERVENTIONS: randomization (1:1) for placebo vs mini-spiomet. PRIMARY OUTCOME: annualized bone age advancement (0-1 year) by BoneXpert; secondary outcomes: insulin, IGF-I, high-molecular-weight adiponectin (HMW-adip), sex hormone binding globulin (SHBG), ultra-sensitive C-reactive protein (usCRP), androgens, luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol, growth-and-differentiation factor 15 (GDF15), C-X-C motif chemokine ligand-14 (CXCL14), safety parameters, and quantification of hepato-visceral fat. DISCUSSION: The present study, if successful, may provide a first proof of the concept that the rapid maturation of girls with an upward mismatch between pre- and post-natal weight gain can be slowed down with a fixed low-dose combination of old and safe generics jointly targeting a reduction of ectopic fat without necessarily lowering body weight. TRIAL REGISTRATION: EudraCT 2021-006766-21. Registered on May 30, 2022.

Leptin receptor in osteocytes promotes cortical bone consolidation in female mice.

Bone strength is partially determined during cortical bone consolidation, a process comprising coalescence of peripheral trabecular bone and its progressive mineralisation. Mice with genetic deletion of suppressor of cytokine signalling 3 (Socs3), an inhibitor of STAT3 signalling, exhibit delayed cortical bone consolidation, indicated by high cortical porosity, low mineral content, and low bone strength. Since leptin receptor (LepR) is expressed in the osteoblast lineage and is suppressed by SOCS3, we evaluated whether LepR deletion in osteocytes would rectify the Dmp1cre.Socs3fl/fl bone defect. First, we tested LepR deletion in osteocytes by generating Dmp1cre.LepRfl/fl mice and detected no significant bone phenotype. We then generated Dmp1cre.Socs3fl/fl.LepRfl/fl mice and compared them to Dmp1cre.Socs3fl/fl controls. Between 6 and 12 weeks of age, both Dmp1cre.Socs3fl/fl.LepRfl/fl and control (Dmp1cre.Socs3fl/fl) mice showed an increasing proportion of more heavily mineralised bone, indicating some cortical consolidation with time. However, at 12 weeks of age, rather than resolving the phenotype, delayed consolidation was extended in female Dmp1cre.Socs3fl/fl.LepRfl/fl mice. This was indicated in both metaphysis and diaphysis by greater proportions of low-density bone, lower proportions of high-density bone, and greater cortical porosity than Dmp1cre.Socs3fl/fl controls. There was also no change in the proportion of osteocytes staining positive for phospho-STAT3, suggesting the effect of LepR deletion in Dmp1cre.Socs3fl/fl mice is STAT3-independent. This identifies a new role for leptin signalling in bone which opposes our original hypothesis. Although LepR in osteocytes has no irreplaceable physiological role in normal bone maturation, when STAT3 is hyperactive, LepR in Dmp1Cre-expressing cells supports cortical consolidation.

Estimating Cervical Vertebral Maturation with a Lateral Cephalogram Using the Convolutional Neural Network.

Recently, the estimation of bone maturation using deep learning has been actively conducted. However, many studies have considered hand-wrist radiographs, while a few studies have focused on estimating cervical vertebral maturation (CVM) using lateral cephalograms. This study proposes the use of deep learning models for estimating CVM from lateral cephalograms. As the second, third, and fourth cervical vertebral regions (denoted as C2, C3, and C4, respectively) are considerably smaller than the whole image, we propose a stepwise segmentation-based model that focuses on the C2-C4 regions. We propose three convolutional neural network-based classification models: a one-step model with only CVM classification, a two-step model with region of interest (ROI) detection and CVM classification, and a three-step model with ROI detection, cervical segmentation, and CVM classification. Our dataset contains 600 lateral cephalogram images, comprising six classes with 100 images each. The three-step segmentation-based model produced the best accuracy (62.5%) compared to the models that were not segmentation-based.

Bone Maturation as a Predictive Factor of Catch-Up Growth During the First Year of Life in Born Small for Gestational Age Infants: A Prospective Study.

Background: About 85-90% of children born small for gestational age (SGA) experience a catch-up growth that occurs mostly during the first year of life and results in a full stature recovery by the age of 2. Objective: To investigate the relation between bone maturation (BM) and catch-up growth during the first year of life in SGA infants. Method: Newborns whose weight and/or length was <-2 SD for gestational age were classified as SGA (group A). The study included a group of 32 SGA, 21 of which are full term [37-41 gestation weeks (GW), subgroup A1] and 11 preterm (30-36 GW, subgroup A2). Control group (B) consisted of 19 full-term and adequate-for-gestational-age (AGA) newborns. All the participants were born in the same hospital and period (January-December 2017). Chromosomal disorders, congenital defects, and maternal chronic diseases were criteria of exclusion. The study population underwent longitudinal evaluation of growth parameters and BM at 0, 3, 6, and 12 months. Assessment of BM was performed by an ultrasonographic (US) study of Béclard's nucleus (NB) (<3 mm at birth, meaning intrauterine delay of BM). Results: Significantly higher height velocity (HV) was observed in subgroup A2 vs. A1 (32.4 ± 8.0 vs. 25.6 ± 2.9 cm, p = 0.01); nevertheless, more subjects in subgroup A2 had height <-2 SD at year 1 than had subgroup A1 (27.3 vs. 0%, p = 0.01). Intrauterine delay of BM was more common in group A vs. B (59.4 vs. 21.2%, p = 0.0078) and in subgroup A2 vs. A1 (90.9 vs. 42.9%, p = 0.0086). In group A, HV over the first year of life negatively correlates with NB diameter assessed at birth (r = -0.6, p < 0.001) but positively correlates with NB growth (r = 0.52, p < 0.01). Moreover, SGA babies with intrauterine delay of BM showed higher HV and better height gain at 12 months' evaluation than did SGA with adequate BM (29.75 ± 3.1 vs. 23.8 ± 2.7 cm, p = 0.003). Conclusion: Neonatal BM should be regarded as a predictive factor of SGA height gain during the first year of life. US evaluation of NB is a useful noninvasive technique to identify intrauterine delay of BM, which positively correlates with early postnatal catch-up growth of SGA infants.

Long-term follow-up of children with classic congenital adrenal hyperplasia: suggestions for age dependent treatment in childhood and puberty.

Background In congenital adrenal hyperplasia (CAH), achieving the balance between overtreatment and undertreatment remains challenging. Final height (FH) can serve as a long-term outcome measure. We aimed to identify age-dependent factors that influence FH in CAH patients, resulting in age-specific treatment goals. Methods We retrospectively evaluated longitudinal data of 39 pediatric CAH patients born between 1980 and 1997 from the Radboudumc CAH database. We analyzed height and bone age (BA) at diagnosis or 4 years of age, at the start of puberty and at FH. Height data were corrected for parental height and secular trend. Hydrocortisone (HC) use and salivary steroid concentrations were studied longitudinally throughout childhood and puberty. Results Median FH standard deviation scores (SDSs) corrected for target height SDSs (THSDSs) was -1.63. Median height SDS corrected for THSDS (HSDS-THSDS) decreased from diagnosis/age 4 years to FH in both salt wasting (SW) CAH and simple virilizing (SV) CAH, and in both male and female patients. However, when height was corrected for BA, no height loss occurred from diagnosis/age 4 years to FH in any of the subgroups, while a height gain was seen in SV males. In the combined model analyzing both HC dose and salivary steroid concentrations, in childhood the androstenedione (A) concentration was negatively associated with FH, while in puberty the HC dose was negatively associated with FH. Conclusions In CAH, loss of growth potential already occurs in early childhood. In prepubertal children, exposure to elevated androgens is associated with decreased FH. In puberty, the growth suppressing effects of HC outweigh the negative effects of elevated androgens. Therefore, we suggest different treatment approaches in prepubertal and pubertal patients.

Typical characteristics of children with congenital adrenal hyperplasia due to 11ß-hydroxylase deficiency: a single-centre experience and review of the literature.

Background 11ß-hydroxylase deficiency (11ßOHD) is a rare disease representing the second most common cause of congenital adrenal hyperplasia (CAH) (5-8%) with an incidence of about 1:100,000. In contrast to 21-hydroxylase deficiency (21OHD), 11ßOHD is not included in neonatal screening programmes. The objective of this study was to demonstrate the typical features of male patients with 11ßOHD. Methods Clinical, biochemical and radiological data of patients with 11ßOHD were analysed in this retrospective single-centre analysis. Results Six male patients of four unrelated families with 11ßOHD were identified (0.1-13.5 years of chronological age [CA] at diagnosis). The predominant symptoms were arterial hypertension, tall stature and precocious pseudopuberty. Bone ages (BAs) were remarkably advanced at diagnosis in four index patients (median difference BA-CA: 5.5 years, range 1.5-9.2 years). Homozygous mutations were identified in exon 7 (c.1179_1180dupGA [p.Asn394Argfs*37]) and exon 8 (c.1398+2T>C) of the CYP11B1 gene leading both to a complete loss of function. The latter mutation has not yet been described in databases. 11ßOHD was identified by the measurement of 11-deoxycortisol in a newborn screening card of one patient retrospectively. Testicular adrenal rest tumours (TARTs) were detected in three patients at 3.7 years, 11 years and 14.4 years. Conclusion The diagnosis of CAH due to 11ßOHD is delayed and should be suspected in children with arterial hypertension, tall stature and precocious pseudopuberty. Patients may develop TARTs as early as infancy. 11ßOHD should be included in newborn screening programmes, at least in newborns of index families, to allow early diagnosis and the start of treatment to reduce morbidity.

Suprascapular notch morphology in the pediatric population: a computed tomography study.

Suprascapular notch is characterized by variable morphology. However, its development is not well studied. We hypothesize that it proceeds postnatally. Thus, the aim of this research was to characterize the morphology of the suprascapular notch in a pediatric population based on computed tomography. A retrospective analysis was performed of 291 chest computed tomography examinations of patients under 18 years old taken following other clinical indications. The inclusion criteria were as follows: both scapulae encompassed in a field of view; no artifacts; no pathologies concerning the scapulae. Based on visual assessment and measurements, the suprascapular notch was classified according to a fivefold classification (type I, deeper than wider; type II, equally deep and wide; type III, wider than deeper; type IV, bony foramen; type V, discreet notch). In all, 173 examinations were included (60 females and 113 males). The most common suprascapular notch types were discreet notch (type V, 225 scapulae; 65.0 %) and type III (114 scapulae; 32.9 %). Children with type V suprascapular notch were significantly younger than children with other types (26.1 ± 42.4 months vs. 111.2 ± 66.7 months; p < 0.05). In types I-III, a positive correlation was found between age and dimensions of the suprascapular notch (p < 0.05). This study provides the first description of the suprascapular notch in a pediatric population based on computed tomography. It confirms that morphology of the suprascapular notch undergoes postnatal development.

Metformin for Rapidly Maturing Girls with Central Adiposity: Less Liver Fat and Slower Bone Maturation.

BACKGROUND/AIMS: Girls with low-birth weight (LBW) and postnatal weight catch-up tend to develop visceral and hepatic fat excess, which may be accompanied by an upregulated adrenarche with precocious pubarche (PP) and by a rapidly progressive puberty with early menarche and shorter stature. A pilot study suggested that metformin treatment for 4 years reduces central adiposity in LBW-PP girls and normalizes puberty and adult height. In this cohort, we studied the relationship between metformin treatment, bone maturation, and body composition. METHODS: Longitudinal hand X-rays (0-4 years, analyzed by BoneXpert) were available from 34 LBW-PP girls (89% of the original cohort; n = 17 untreated, n = 17 metformin-treated; age at the start of treatment 8 years) along with body composition (0-4 years, by DXA), hepatic fat, and abdominally subcutaneous and visceral fat (posttreatment, by MRI). RESULTS: The tempo of bone aging was accelerated in untreated girls (≈16% faster vs. chronological aging) and normal in metformin-treated girls (≈20% slower vs. untreated girls). Metformin-treated girls gained more height per bone-age year and had less visceral and hepatic fat. The tempo of bone maturation was associated (R = 0.55; p < 0.001) with hepatic fat. CONCLUSION: Metformin treatment in rapidly maturing girls with central adiposity normalized bone maturation. This normalization was accompanied by less central fat and was related closely to hepatic fat.

Bony Maturity of the Tibial Tuberosity With Regard to Age and Sex and Its Relationship to Pathogenesis of Osgood-Schlatter Disease: An Ultrasonographic Study.

BACKGROUND: Although tensile force on an immature tibial tuberosity is considered the main cause of Osgood-Schlatter disease (OSD), the relationship between bony maturity and the pathogenesis of OSD remains obscure. PURPOSE: To survey the bone maturation process of the tibial tuberosity by age and sex and clarify its relationship to OSD. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 731 Japanese basketball players aged 6 to 14 years were enrolled in this study. Ultrasonographic examination was performed in all participants (1462 knees) to evaluate the bony maturity of the tibial tuberosity by use of the Ehrenborg classification. The age- and sex-specific prevalence of each stage was investigated, and the prevalence of symptomatic OSD and its relationship with bony maturity were also assessed. RESULTS: The process of bone maturation occurred 1 to 2 years earlier in female participants compared with male participants. Among female participants, 59.2% were already at the epiphyseal stage (stage E) by 10 years of age, and 47.4% were skeletally mature by 14 years. Among male participants, conversely, only 8.0% were at stage E by 10 years of age, and only 13.8% were skeletally mature by 14 years. The overall prevalence of symptomatic OSD was 6.8% (males, 6.4%; females, 7.2%), and the onset was 1 year earlier in the female participants. The prevalence of symptomatic OSD tended to increase with age and bony maturity, significantly increasing from the cartilaginous stage (stage C) to the apophyseal stage (stage A) (odds ratio, 9.48) and from stage A to stage E (odds ratio, 2.22). CONCLUSION: The tibial tuberosity matures earlier in female participants. The risk of OSD is greater in stage A than stage C and in stage E than stage A. The risk of OSD increases with age in males but not in females.

Predictors of bone maturation, growth rate and adult height in children with central precocious puberty treated with depot leuprolide acetate.

BACKGROUND: Children with central precocious puberty (CPP) are treated with gonadotropin-releasing hormone agonists (GnRHa) to suppress puberty. Optimizing treatment outcomes continues to be studied. The relationships between growth, rate of bone maturation (bone age/chronological age [ΔBA/ΔCA]), luteinizing hormone (LH), predicted adult stature (PAS), as well as variables influencing these outcomes, were studied in children treated with depot leuprolide (LA Depot) Methods: Subjects (64 girls, seven boys) with CPP received LA Depot every 3 months for up to 42 months. Multivariate regression analyses were conducted to examine the predictors affecting ΔBA/ΔCA, PAS and growth rate. RESULTS: Ninety percent of subjects (18 of 20) were suppressed (LH levels <4 IU/L) at 42 months. Over 42 months, the mean growth rate declined 2 cm/year, the mean BA/CA ratio decreased 0.21 and PAS increased 8.90 cm for girls (n=64). PAS improved to mid-parental height (MPH) in 46.2% of children by 30 months of treatment. Regression analysis showed that only the Body Mass Index Standardized Score (BMI SDS) was significantly associated (ß+0.378 and +0.367, p≤0.05) with growth rate. For PAS, significant correlations were with MPH (ß+0.808 and +0.791, p<0.001) and ΔBA/ΔCA (ß+0.808 and +0.791, p<0.001). For ΔBA/ΔCA, a significant association was found only with BA at onset of treatment (ß-0.098 and -0.103, p≤0.05). Peak-stimulated or basal LH showed no significant influence on growth rate, ΔBA/ΔCA or PAS. CONCLUSIONS: Growth rate and bone maturation rate normalized on treatment with LA Depot. LH levels were not significantly correlated with growth rate, ΔBA/ΔCA or PAS, suggesting that suppression was adequate and variations in gonadotropin levels were below the threshold affecting outcomes.

Estudio de la edad biológica en atletas del sexo masculino de la categoría escolar / Estudo da idade biológica em atletas do sexo masculino da categoria escolar / Study of the biological age in male athletes of the school category

RESUMEN Se realizó un estudio de la edad biológica de los deportistas escolares del sexo masculino. Como objetivo de este trabajo se declaró caracterizar el comportamiento de la edad biológica de los atletas escolares del sexo masculino, de 13 y 14 años de los deportes de tenis, balonmano, atletismo, judo y levantamiento de pesas en la Eide (Escuela de Iniciación Deportiva) "Julio Díaz González" de la provincia Artemisa, Cuba. En este diseño no experimental, se emplearon métodos de investigación, tanto de carácter teórico como del nivel empírico. Entre los empíricos, se encuentran la revisión de documentos, la observación, la entrevista y la medición. Estos permitieron constatar información relacionada con la edad biológica de los atletas y su integración a la planificación del proceso de entrenamiento deportivo que se desarrolla a largo plazo. Fue esencial en este estudio la aplicación del método de Tanner y Whitehouse, ajustado por Jordán, de la radiografía de la mano izquierda (mano total). Como resultado se identifica el comportamiento de la maduración ósea de los atletas escolares participantes en la investigación.

RESUMO Foi realizado um estudo sobre a idade biológica dos atletas da escola masculina. O objectivo deste trabalho era caracterizar o comportamento da idade biológica dos atletas escolares masculinos, de 13 e 14 anos, nos desportos de ténis, handebol, atletismo, judô e halterofilismo, na Eide (Escola de Iniciação ao Desporto) "Julio Díaz González", na província de Artemisa, Cuba. Neste desenho não experimental, foram utilizados métodos de investigação tanto teóricos como empíricos. Entre os empíricos, há a revisão de documentos, observação, entrevista e medição. Estes permitiram apurar informações relacionadas com a idade biológica dos atletas e a sua integração no planeamento do processo de treino desportivo que é desenvolvido a longo prazo. Foi essencial neste estudo a aplicação do método de Tanner e Whitehouse, ajustado por Jordán, da radiografia da mão esquerda (mão total). Como resultado, é identificado o comportamento da maturação óssea dos atletas escolares que participam na investigação.

ABSTRACT A study of the biological age of male school athletes was carried out. It was declared as an objective to characterize the behavior of the biological age of male school athletes, 13-14 years of age in tennis, handball, athletics, judo and weightlifting sports, at the EIDE (Sports Initiation School) Julio Diaz Gonzalez from Artemisa. In this non-experimental design some methods of investigation were used as well Empiric and Theoretical methods. The Empiric ones are: document review, observation, interview and measurement which allowed verifying information related to the biological age of the athletes and their integration to the planning of the sport training process that is developed to long term. The application of the method of Tanner Whitehouse, adjusted by Jordan of the radiograph of the left hand, total hand, was essential in this study. As a result is identified the athletes `bone maturation behavior that participated in this investigation.