Between a Rock and a Short Place-The Impact of Nephrolithiasis on Skeletal Growth and Development Across the Lifespan.

PURPOSE OF REVIEW: The impact of nephrolithiasis on skeletal growth and bone health across the life span of kidney stone formers is reviewed. MAIN FINDINGS: Bone disease is an early event among kidney stone formers (SF), with distinct phenotypes according to each age, sex, menopausal status, dietary, hormonal and genetic factors. Nephrolithiasis-associated bone disorder is characterized by reduced bone mineral density (BMD) and histologically discloses low bone formation, high bone resorption and abnormal mineralization. Although hypercalciuria has been presumed to be pathogenic for bone loss in SF, the association of BMD with urinary calcium is not uniform in all studies. Hypocitraturia, metabolic disturbances, cytokines and receptors, growth factors and acid-base status may all influence skeletal outcomes. The potential link of bone disease with vascular calcification and cardiovascular disease among SF is discussed. The unique vulnerability of the younger skeleton to the effects of nephrolithiasis on attainment of peak bone mass and strength is highlighted and the association of bone loss with kidney stone formation early in life indicate the opportunity for intervention to reduce the risk of future bone fractures.

Radiographic evaluation of the forelimb bone development in maned wolves (Chrysocyon brachyurus).

This study aimed to assess the fusion of growth plates and the development of secondary ossification centres in the forelimb bones of maned wolves (Chrysocyon brachyurus), contrasting the findings with established data from domestic dogs. Three maned wolves, comprising one male and two females, initially aged between 3 and 4 months, were subjected to monthly radiographic evaluations until 10-11 months of age, followed by bimonthly assessments until 18-19 months of age, encompassing both forelimbs. The closure times of growth plates were observed as follows: supraglenoid tubercle (7-8 months), proximal humerus (17-19 months), distal humerus (8-9 months), medial epicondyle of the humerus (8-9 months), proximal ulna (9-10 months), proximal radius (13-15 months), distal ulna (13-15 months) and distal radius (17-19 months). Statistical analysis revealed significant differences in the areas of secondary ossification centres in the proximal epiphyses of the humerus and radius, respectively, observed from the initial evaluation at 8-9 months and 6-7 months. Conversely, the epiphyses of the supraglenoid tubercle, distal humerus, proximal ulna, distal ulna, medial epicondyle of the humerus and distal radius did not exhibit significant area differences between 3-4 months and 4-5 months, yet notable distinctions emerged at 5-6 months. In summary, while the radiographic appearance of epiphyseal growth plates and secondary ossification centres in maned wolves resembles that of domestic dogs, closure times vary. These findings contribute to understanding the dynamics of epiphyseal growth plates in this species.

Bone development in fetuses with intrauterine growth restriction caused by maternal endocrine-metabolic dysfunctions.

Intrauterine growth restriction (IUGR) affects a large proportion of infants, particularly in underdeveloped countries. Among the main causes of IUGR, maternal endocrine-metabolic dysfunction is highlighted, either due to its high incidence or due to the severity of the immediate and mediated changes that these dysfunctions cause in the fetus and the mother. Although the effects of endocrine and metabolic disorders have been widely researched, there are still no reviews that bring together and summarize the effects of these conditions on bone development in cases of IUGR. Therefore, the present literature review was conducted with the aim of discussing bone changes observed in fetuses with IUGR caused by maternal endocrine-metabolic dysfunction. The main endocrine dysfunctions that occur with IUGR include maternal hyperthyroidism, hypothyroidism, and hypoparathyroidism. Diabetes mellitus, hypertensive disorders, and obesity are the most important maternal metabolic dysfunctions that compromise fetal growth. The bone changes reported in the fetus are, for the most part, due to damage to cell proliferation and differentiation, as well as failures in the synthesis and mineralization of the extracellular matrix, which results in shortening and fragility of the bones. Some maternal dysfunctions, such as hyperthyroidism, have been widely studied, whereas conditions such as hypoparathyroidism and gestational hypertensive disorders require further study regarding the mechanisms underlying the development of bone changes. Similarly, there is a gap in the literature regarding changes related to intramembranous ossification, as most published articles only describe changes in endochondral bone formation associated with IUGR. Furthermore, there is a need for more research aimed at elucidating the late postnatal changes that occur in the skeletons of individuals affected by IUGR and their possible relationships with adult diseases, such as osteoarthritis and osteoporosis.

Osteocondroma en una localización atípica. Reporte de Caso / Osteochondroma in an atypical location. Case report

INTRODUCCIÓN. Los osteocondromas son considerados como el tumor benigno más común entre los de origen óseo, se denomina también exostosis, y se lo define por la Organización Mundial de la Salud como una proyección ósea cubierta de una capa cartilaginosa en la superficie externa. Representa el 20-50% de todos los tumores benignos óseos. Se diagnostica en su mayoría en pacientes pediátricos. RESULTADOS. Presentamos el caso de una paciente de 8 años con osteocondroma único en escápula de aparición espontánea, sin otras lesiones en el cuerpo. DISCUSIÓN. Los lugares comunes de aparición de osteocondromas son los huesos largos con placa de crecimiento o metáfisis, localizaciones raras como la escapula comprenden menos del 1%. El tratamiento es expectante y al momento de producirse síntomas, está indicado la excision quirúrgica. CONCLUSIÓN. La enfermedad tiene un curso benigno sin complicaciones cuando se trata de un tumor esporádico, en los síndormes de exostosis, las recurrencias y riesgo de malignidad hacen necesario un seguimiento más cercano.

INTRODUCTION. Osteochondromas are considered the most common benign tumor among those of bone origin, it is also called exostosis, and is considered by the World Health Organization as a bone projection covered with a cartilaginous layer on the external surface), it represents 20­50% of all benign tumors and is mostly diagnosed in pediatric patients. RESULTS. We present the case of an 8-year-old female with a single osteochondroma in the scapula of spontaneous appearance, without other lesions in the body. DISCUSSION: The common places of appearance are long bones with a growth plate or metaphysis, rare locations such as the scapula comprise less than 1%. The treatment is expectant, and when symptoms occur, surgical excision is indicated. CONCLUSION: The disease has a benign course without complications when it is a sporadic tumor, in exostosis syndromes the recurrences and risk of malignancy make closer follow-up necessary.

Resistance training presents beneficial effects on bone development of adolescents engaged in swimming but not in impact sports: ABCD Growth Study.

BACKGROUND: Sports practice during adolescence is important to enhance bone development, although it may provide different effects depending on the mechanical impact present in the sport. Besides, resistance training (RT) may also induce bone changes directly (via muscle contractions) and indirectly (via myokines). However, there have been no studies analyzing the longitudinal influence of engaging in sport with and without added mechanical load. Thus, this study aims to analyze the combined effects of sports participation and resistance training on areal bone mineral density (aBMD) accrual in adolescent athletes participating in swimming and impact sports for 12-months. METHODS: This was a 12-month longitudinal study. The sample comprised 91 adolescents (21 females) aged 10 to 18 years, engaged in impact sports (basketball, tennis, track & field, baseball and gymnastics, n = 66) and non-impact sport (swimming, n = 25). The sample was divided according to resistance training participation: impact sports only (n = 45), impact sports + resistance training (n = 21), swimming-only (n = 17) and swimming + resistance training (n = 8). aBMD and soft tissues were measured using dual-energy X-ray absorptiometry. Generalized linear models analysis was used for the resistance training (RT) x type of sport interaction in predicting aBMD changes overtime, adjusting for maturation, sex and baseline aBMD. RESULTS: After 12-months, all groups showed a significant increase in aBMD, except for the swimming groups (regardless of resistant training), which showed a significant loss in spine aBMD (-0.045 [-0.085 to -0.004] g/cm2 in swimming-only and - 0.047 [-0.073 to -0.021] g/cm2 in swimming + RT). In comparisons between groups, only swimming + RT group, compared with swimming-only group presented higher upper limbs aBMD (0.096 g/cm2 [0.074 to 0.118] in swimming + RT vs. 0.046 [0.032 to 0.060] g/cm2 in swimming only; p < 0.05) and whole body less head (WBLH) aBMD (0.039 [0.024 to 0.054] g/cm2 in swimming + RT vs. 0.017 [0.007 to 0.027] g/cm2 swimming-only; p < 0.05). CONCLUSION: Despite the significant gain in aBMD in all groups and body sites after 12-months, except for the spine site of swimmers, the results indicate that participation in RT seems to improve aBMD accrual in swimmers at the upper limbs and WBLH.

Noncoding RNAs in skeletal development and disorders.

Protein-encoding genes only constitute less than 2% of total human genomic sequences, and 98% of genetic information was previously referred to as "junk DNA". Meanwhile, non-coding RNAs (ncRNAs) consist of approximately 60% of the transcriptional output of human cells. Thousands of ncRNAs have been identified in recent decades, and their essential roles in the regulation of gene expression in diverse cellular pathways associated with fundamental cell processes, including proliferation, differentiation, apoptosis, and metabolism, have been extensively investigated. Furthermore, the gene regulation networks they form modulate gene expression in normal development and under pathological conditions. In this review, we integrate current information about the classification, biogenesis, and function of ncRNAs and how these ncRNAs support skeletal development through their regulation of critical genes and signaling pathways in vivo. We also summarize the updated knowledge of ncRNAs involved in common skeletal diseases and disorders, including but not limited to osteoporosis, osteoarthritis, rheumatoid arthritis, scoliosis, and intervertebral disc degeneration, by highlighting their roles established from in vivo, in vitro, and ex vivo studies.

Use of F18 bioglass putty for induced membrane technique in segmental bone defect of the radius in rabbits

Purpose: To evaluate the inductive capacity of F18 bioglass putty on the induced membrane technique in a segmental bone defect of the rabbit's radius. Methods: Ten female Norfolk at 24 months of age were used. The animals were randomly separated based on postoperative time points: five rabbits at 21 and four at 42 days. A 1-cm segmental bone defect was created in both radii. The bone defects were filled with an F18 bioglass putty. Results: Immediate postoperative radiographic examination revealed the biomaterial occupying the segmental bone defect as a well-defined radiopaque structure with a density close to bone tissue. At 21 and 42 days after surgery, a reduction in radiopacity and volume of the biomaterial was observed, with particle dispersion in the bone defect region. Histologically, the induced membrane was verified in all animals, predominantly composed of fibrocollagenous tissue. In addition, chondroid and osteoid matrices undergoing regeneration, a densely vascularized tissue, and a foreign body type reaction composed of macrophages and multinucleated giant cells were seen. Conclusions: the F18 bioglass putty caused a foreign body-type inflammatory response with the development of an induced membrane without expansion capacity to perform the second stage of the Masquelet technique.

Analysis of the Mutational Landscape of Osteosarcomas Identifies Genes Related to Metastasis and Prognosis and Disrupted Biological Pathways of Immune Response and Bone Development.

Osteosarcoma (OS) is the most prevalent type of bone tumor, but slow progress has been achieved in disentangling the full set of genomic events involved in its initiation and progression. We assessed by NGS the mutational spectrum of 28 primary OSs from Brazilian patients, and identified 445 potentially deleterious SNVs/indels and 1176 copy number alterations (CNAs). TP53 was the most recurrently mutated gene, with an overall rate of ~60%, considering SNVs/indels and CNAs. The most frequent CNAs (~60%) were gains at 1q21.2q21.3, 6p21.1, and 8q13.3q24.22, and losses at 10q26 and 13q14.3q21.1. Seven cases presented CNA patterns reminiscent of complex events (chromothripsis and chromoanasynthesis). Putative RB1 and TP53 germline variants were found in five samples associated with metastasis at diagnosis along with complex genomic patterns of CNAs. PTPRQ, KNL1, ZFHX4, and DMD alterations were prevalent in metastatic or deceased patients, being potentially indicative of poor prognosis. TNFRSF11B, involved in skeletal system development and maintenance, emerged as a candidate for osteosarcomagenesis due to its biological function and a high frequency of copy number gains. A protein-protein network enrichment highlighted biological pathways involved in immunity and bone development. Our findings reinforced the high genomic OS instability and heterogeneity, and led to the identification of novel disrupted genes deserving further evaluation as biomarkers due to their association with poor outcomes.

Genomic association using principal components of morphometric traits in horses: identification of genes related to bone growth.

The measurement of morphometric traits in horses is important for determining breed qualification and is one of the main selection criteria for the species. The development of an index (HPC) that consists of principal components weighted by additive genetic values allows to explore the most relevant relationships using a reduced number of variables that explain the greatest amount of variation in the data. Genome-wide association studies (GWAS) using HPC are a relatively new approach that permits to identify regions related to a set of traits. The aim of this study was to perform GWAS using HPC for 15 linear measurements as the explanatory variable in order to identify associated genomic regions and to elucidate the biological mechanisms linked to this index in Campolina horses. For GWAS, weighted single-step GBLUP was applied to HPC. The eight genomic windows that explained the highest proportion of additive genetic variance were identified. The sum of the additive variance explained by the eight windows was 95.89%. Genes involved in bone and cartilage development were identified (SPRY2, COL9A2, MIR30C, HEYL, BMP8B, LTBP1, FAM98A, and CRIM1). They represent potential positional candidates for the HPC of the linear measurements evaluated. The HPC is an efficient alternative to reduce the 15 usually measured traits in Campolina horses. Moreover, candidate genes inserted in region that explained high additive variance of the HPC were identified and might be fine-mapped for searching putative mutation/markers.

Influence of age and sex on bone development and athletic career longevity of Thoroughbred racehorses in Brazil - preliminary study / Influência do gênero e da idade no estágio de desenvolvimento ósseo e longevidade atlética de equinos da Raça Puro Sangue Inglês de corridas no Brasil - estudo preliminar

The impact of high-speed exercise on the musculoskeletal system of young racehorses has been extensively discussed because of concerns regarding animal health and welfare. This study investigated the correlation between age, degree of ossification of the distal radial epiphysis, sex, and career longevity of Thoroughbred racehorses in Brazil from 2012 to 2015. We performed a retrospective evaluation of 286 dorsopalmar radiographs of the left radiocarpal region of young horses and their racing performance. Distal radial epiphyseal closure was classified into three degrees: A, B, or C. Performance data included the number of races raced, athletic career length, and the number of races per month. The variables were subjected to regression analysis. At the time of radiographic examination, male horses were significantly older than females, and horses with epiphyseal closure degrees differed with age. Age at first race was 33.08±3.81 months, the average of races raced was 18.32±15.14 races, athletic career duration was 20.37±13.82 months, and the number of races raced per month was 0.93±0.46 races. Age influenced (P>0.001) the distal radial epiphyseal closure on racehorses, but sex did not (P=0.218 for males and P=0.275 for females). An inverse association was observed between age at the first race, the number of races raced per month, and athletic career duration. The frequency of race and the age at the first race influenced athletic career duration.

O impacto do exercício de alta velocidade no sistema musculoesquelético de cavalos de corrida jovens tem sido amplamente discutido devido a preocupações com a saúde e o bem-estar animal. Este estudo investigou a correlação entre idade, grau de ossificação da epífise radial distal, sexo e longevidade da carreira de cavalos Puro Sangue Inglês de corrida no Brasil de 2012 a 2015. Realizamos uma avaliação retrospectiva de 286 radiografias dorsopalmar da região radiocarpica esquerda de cavalos jovens e seu desempenho de corrida. O fechamento epifisário radial distal foi classificado em três graus decrescentes: A, B ou C. Os dados de desempenho incluíram o número de corridas disputadas, duração da carreira atlética e o número de corridas por mês. As variáveis foram submetidas à análise de regressão. No momento do exame radiográfico, os cavalos machos eram significativamente mais velhos que as fêmeas, e os cavalos com diferentes graus de fechamento epifisário diferiram com a idade. A idade na primeira corrida foi de 33,08±3,81 meses, a média de corridas disputadas foi de 18,32±15,14 corridas, a duração da carreira atlética foi de 20,37±13,82 meses e o número de corridas realizadas por mês foi de 0,93±0,46 corridas. A idade influenciou (P>0,001) o fechamento da epífise radial distal em cavalos de corrida, mas o sexo não (P=0,218 para machos e P=0,275 para fêmeas). Uma associação inversa foi observada entre a idade na primeira corrida, o número de corridas disputadas por mês e a duração da carreira atlética. A frequência de corrida e a idade na primeira corrida influenciaram a duração da carreira atlética.

Bone Growth and Meat Quality of Quails Submitted to Different Lighting Programs

The present study was executed to evaluate the effect of lighting programs for meat quails on their bone growth and development. A total of 1500 sexed European quails (Coturnix coturnix coturnix) were distributed using a completely randomized design in a 2 × 3 factorial arrangement, with two sexes and three lighting programs (natural, intermittent, and continuous) with five replicates of 50 quails. The lighting programs were applied in the period from 7 to 49 d of age. Weekly slaughterings were performed to remove the tibiotarsus and femur and subsequently determine weight, length, dry and mineral matter content. The growth and deposition curves of dry and mineral matter in the bones were obtained using the Gompertz model. There was no significant interaction between lighting programs and sex for the estimates of the Gompertz curve parameters of all variables studied. There was an effect of the lighting programs only on the time needed to reach the maximum deposition rate of the growth curve and dry and mineral matter deposition. Females showed higher weight and deposition of mineral matter at maturity, and took longer to reach the maximum deposition rate value for these variables. There was influence of the lighting programs on resistance and bone deformity of the tibiotarsus. For quails raised in the tropical region, a natural or intermittent lighting program must be used, as it does not compromise the development of bones and assures bone quality.(AU)

Comparison of the reproducibility of two cervical vertebrae maturation methods

Aim: Facial orthopaedic treatments based on the stimulation or restrictions of craniofacial bone growth are more effective when carried out during the pubertal growth spurt. The aim of this cross-sectional study was to evaluate the reproducibility of two cervical vertebrae methods (CVM) with manual tracing and direct visual inspection. Methods: A sample of 60 lateral cephalometric radiographs (10 of each of the 6 CVM stages) was randomly selected from 171 records. 5 orthodontists classified these radiographs according to the skeletal maturation stage in 2002 and 2005, and the application of both methods was conducted by direct visual inspection and evaluation through manual tracing. Results: The average reliability of the two methods determination and the two forms of evaluation was substantial. The direct visual inspection evaluation showed the highest reliability and agreement interexaminer values for both methods, as well as the intraexaminers evaluation. Conclusion: The reproducibility of CVM method was substantial, indicating its clinical use to determine the skeletal maturity and the ideal moment for treatment execution

Desordens hiperostóticas em American Bully / Hiperostotic disorders in american bully

O complexo de desordens hiperostóticas é uma condição rara e autolimitante, que tem as mesmas características histopatológicas, que cursa com proliferação óssea de caráter não neoplásico. Acomete cães jovens de raças distintas, com variabilidade quanto ao tipo de proliferação óssea e quanto aos ossos acometidos. O complexo é composto pela osteopatia craniomandibular, hiperostose da calota craniana e osteodistrofia hipertrófica. Podendo estar presente nos ossos da calota craniana, mandíbulas, coluna cervical e esqueleto apendicular. O presente relato, descreveu o quadro de uma cadela, da raça American Bully, não castrada, três meses de idade, que foi atendida com queixa de aumento de volume doloroso das mandíbulas, hiporexia e sialorreia há 15 dias, apresentando ao exame físico, amplitude de movimento diminuída e sensibilidade dolorosa da articulação temporomandibular, espessamento firme bilateral do crânio em região de fossa temporal, espessamento palpável de consistência firme das mandíbulas e crepitação respiratória. Após avaliação clínica e realização de exames complementares, chegou-se ao diagnóstico presuntivo, de complexo de desordens hiperostóticas. Foi instituído como conduta terapêutica o suporte analgésico, sendo eficaz para a manutenção das necessidades fisiológicas até a paciente alcançar a fase adulta. O prognóstico para esta paciente foi considerado bom, uma vez que não havia indícios de anquilose da articulação temporomandibular e/ou manifestações neurológicas.

The complex of hyperostotic disorders is a rare and self-limiting condition, which has the same histophatological characteristics, which courses with non-neoplastic bone proliferations. It affects young dogs of different breeds, with variability the bones affected. The complex is composed of craniomandibular osteopathy, calvarial hyperostotic syndrome and hypertrophic osteodystrophy. It may be present in the bones of the skullcap, jaws, cervical spine and appendicular skeleton. The present report describes the condition of a female dog, American Bully breed, entire, three months old, with a complaint of painful swelling of the jaws, hyporexia and drooling for 15 days, presenting on physical examination, reduced amplitude and pain of the temporomandibular joint, bilateral firm thickening of the skull in the temporal fossa region, palpable firm-consistent thickening of the mandibles and respiratory crackle. After clinical evaluation and complementary tests, a presumptive diagnosis of hyperostotic disorders complex was reached. It was instituted pain management as a treatment, being effective for the maintenance of physiological needs until the patient reaches the adulthood. The prognosis for this patient was considered good, since there was no evidence of temporomandibular joint ankylosis and/or neurological manifestations.

Ultrasound evaluation of fetal bone development in the collared (Pecari tajacu) and white-lipped peccary (Tayassu pecari).

The study of fetal development allows for evaluating the different strategies adopted by mammal species to maximize neonatal survival. Autonomous locomotion is fundamental for newborns to perform foraging activities and increases newborn survival from predation. In this study, we assess the gestational bone development of 53 collared (CP, Pecari tajacu) and 61 white-lipped (WLP, Tayassu pecari) peccaries, collected through the collaboration of subsistence hunters in the Amazon. The bone mineralization and biometry of the axial and appendicular skeleton were assessed by ultrasound examinations, and the timing of the main bone developmental events was calculated in relation to the total dorsal length (TDL) and the percentage of the total gestational period (GP). The first US signs of mineralization of the axial skeleton in CP and WLP were observed in fetuses with 3.4 cm (42 gestation days, 30% GPCP ) and 5.1 cm (51 gestation days, 32% GPWLP ). The early development of the appendicular skeleton was observed by the synchronic appearance of the mineralized scapula, humerus, radius, ulna, ilium, ischium, femur, tibia, and fibula at 36% GPCP (50 gestation days), and 35% GPWLP (56 gestation days). The pubis was mineralized in fetuses at 55% GPCP (75 gestation days) and 59% GPWLP (94 gestation days). The mineralization was observed in all autopod bones at 79% GPCP (109 gestation days) and 67% GPWLP (106 gestation days). All primary ossification centers in long bones of thoracic and pelvic limbs were mineralized in advanced fetuses (GPCP and GPWLP ≥75%). The mineralized patella was not observed in advanced fetuses in either species. Secondary ossification centers first appeared at the distal epiphysis of the femur in the CP (99 gestation days, 72% GPCP ) and the distal epiphysis of the radius, femur, and tibia in the WLP (106 gestation days, 67% GPWLP ). Advanced fetuses of CP and WLP presented 60% (15/25) and 68% (17/25) of the total secondary ossification centers observed present in the adult domestic pig, while newborns from the domestic pig presented 52% (13/25). The early intrauterine development of the skeletal system in both peccary species suggests a precocial development strategy, which likely correlates with neonatal ability to escape predators and reduces the dependence on parental care.

How do bones grow? A mathematical description of the mechanobiological behavior of the epiphyseal plate.

Growth modulation is an emerging method for the treatment of skeletal deformities originating in the long bones or the vertebral bodies. It requires the controlled application of mechanical loads to the affected bone, causing an alteration of the growth and ossification process occurring in a cartilaginous region called epiphyseal growth plate or physis. In order to avoid the possibility of under- or over-correction, quantification of the applied forces is necessary. Pursuing this goal, here we propose a phenomenological model of mechanobiological effects on the epiphyseal growth plate, based on the observed similarity between the mechanobiologically induced growth and viscoelastic material behavior. The model incorporates mechanical loading effects on growth direction, growth rate and ossification speed; it also allows to evaluate the occurrence of transient effects. Model consistency was tested against a rather large set of experiments existing in the literature. A generic simplified geometrical model of bones was established for this. Analytical solutions for growth and ossification evolution were obtained for different loading conditions, allowing to test the ability of the model to describe bone growth under various kinds of mechanical loading conditions. Model-predicted changes regarding epiphyseal growth plate thickness as well as longitudinal growth speed are consistent with experiments in which static tension or compression were applied to long bones. Results suggest that when the mechanical load is sinusoidally variable, conflicting data existing in the literature could be explained by a previously unconsidered effect of the the applied load initial phase. The model can accurately fit data regarding torsional loads effects on growth. Mechanobiological data for humans is very scarce. For this reason, when possible, the model parameters values were estimated, for the proposed generic geometry, after growth measurements in animal models available in the literature. Although it is not possible to assert their validity for humans, the proposed model along with the obtained parameters values give a rational foundation to be used in more advanced computational studies.

[What is the best method for estimating final height in patients with precocious puberty?] / ¿Cuál es el mejor método de estimación de talla final en pacientes con pubertad precoz?

Central precocious puberty is the premature activation of the hypothalamic-pituitary-gonadal axis, leading to an early epiphyseal fusion and, in many cases, heights below the genetic target. Therefore, a proper adult stature prediction is essential for the treatment decision. OBJECTIVE: To compare the concordance of final height using height prediction made by two validated methods versus the ge netic target height in girls who consulted due to central precocious puberty. PATIENTS AND METHOD: Retrospective, non-concurrent cohort study including 93 girls with central precocious puberty, who were not treated with LHRH analogs and had reached their final adult height. The data was obtained from the clinical records. To predict height, the Bayley-Pinneau method and the Roche-Wainer- Thissen method were applied, and the results were compared with the genetic target height. The concordance between the estimated final height and the final height obtained was evaluated using the Bland-Altman method. RESULTS: When comparing the final height obtained with that predicted by the Bayley-Pinneau method, there was a mean difference of 1.01 cm, and using the Rocke-Wainer- Thissen method, there was a difference of +0.96 cm. The calculation of the genetic target height showed a difference of +0.05 cm with respect to the final height. CONCLUSION: The prediction of height made by the Bayley-Pinneau and Roche-Wainer-Thissen methods was adequate and, contrary to expectations, it was similar to the calculation of the genetic target height that does not use the age of bone maturation. This also presented better concordance and less dispersion of the results with respect to the final height obtained.

Growth of teeth and bones in adult subjects with congenital untreated isolated growth hormone deficiency.

OBJECTIVE: To understand the growth of teeth and mandibular and maxillary bones in subjects with isolated growth hormone deficiency (IGHD). MATERIAL AND METHODS: Mesiodistal tooth width of 28 maxillary and mandibular dental models of 14 adult IGHD subjects (9 men) were digitalized and compared to 40 models of 20 normal-statured controls (11 men). The mean SDS of the maxillary and mandibular teeth were compared with height, cephalic perimeter, total anterior facial height, total maxillary and mandibular length, and maxillary and mandibular arches. RESULTS: All average mesiodistal dimensions in absolute values of the 14 dental pairs were reduced in the IGHD group. Eight of 28 (28.6%) mesiodistal dimensions in IGHD subjects of both sexes had an average SDS below -2, thirteen of them (46.4%) had mean SDS between -1 and - 2, and seven of them (25.0%) had SDS above -1. The highest SDS values were the upper lateral incisor (-0.32 in women), and the upper canine (-0.91 in men). The lowest SDS values were the 2nd upper molar (-3.51 in men), and the 2nd upper premolar (-2.64 in women). The ascending order of the mean SDS was height, total maxillary length, total mandibular length, total anterior height of the face, cephalic perimeter, the maxillary arches width, the mesiodistal width of the mandibular teeth, the mesiodistal width of the maxillary teeth and the mandibular arches width. CONCLUSIONS: Reduction in mesiodistal width is present in untreated IGHD adults with magnitude of tooth size reduction being lower than height, cephalic perimeter, total anterior facial height, and most jaw measurements. IGHD abolishes the sexual dimorphism in mesiodistal dental measures.

Radial shockwave treatment promotes chondrogenesis in human growth plate and longitudinal bone growth in rabbits.

OBJECTIVE: The process of longitudinal bone growth occurs at the growth plate where the chondrocytes undergo apparent structural and molecular changes to promote growth. Recent reports suggest that radial shockwave treatment (rSWT) stimulates bone length in cultured fetal rat metatarsals. Therefore, we investigated if rSWT has similar growth promoting effects on cultured human growth plate fragments and addressed the same in a preclinical in vivo rabbit model by subjecting their growth plates to rSWT. METHODS: Short-term effects of high-energy rSWT were evaluated in a unique model of cultured human growth plate cartilage (n = 5) wherein samples exposed to rSWT were assessed for chondrogenic markers at 24 h in comparison to unexposed samples obtained from the same limb. Local in vivo effects were studied in six-week-old rabbits who had their distal femurs exposed to four weekly sessions of rSWT at low- and high-energy levels (n = 4 each). At sacrifice, histomorphometric and immunohistochemistry analyses were performed. For effect on longitudinal growth, proximal tibiae of 22-week-old rabbits (n = 12) were asymmetrically exposed to rSWT; the contralateral side served as untreated controls. At sacrifice, the final bone length was measured. RESULTS: In the ex vivo model of cultured human growth plate cartilage, rSWT exposure upregulated SOX9 and COL2A1 compared to control. In the immature rabbit model, an increased number of proliferative chondrocytes and column density was seen for both the energy levels. In the adolescent rabbits, an increase in tibial length was observed after the fourth session of high-energy rSWT and until six-weeks after rSWT compared to the untreated limb. CONCLUSIONS: Our preliminary experimental results suggest that rSWT may serve as a non-invasive treatment and possibly a safe strategy to stimulate longitudinal bone growth. However, further studies are needed to assess the in vivo effects of rSWT in models of disturbed bone growth.

Postembryonic development and aging of the appendicular skeleton in Ambystoma mexicanum.

BACKGROUND: The axolotl is a key model to study appendicular regeneration. The limb complexity resembles that of humans in structure and tissue components; however, axolotl limbs develop postembryonically. In this work, we evaluated the postembryonic development of the appendicular skeleton and its changes with aging. RESULTS: The juvenile limb skeleton is formed mostly by Sox9/Col1a2 cartilage cells. Ossification of the appendicular skeleton starts when animals reach a length of 10 cm, and cartilage cells are replaced by a primary ossification center, consisting of cortical bone and an adipocyte-filled marrow cavity. Vascularization is associated with the ossification center and the marrow cavity formation. We identified the contribution of Col1a2-descendants to bone and adipocytes. Moreover, ossification progresses with age toward the epiphyses of long bones. Axolotls are neotenic salamanders, and still ossification remains responsive to l-thyroxine, increasing the rate of bone formation. CONCLUSIONS: In axolotls, bone maturation is a continuous process that extends throughout their life. Ossification of the appendicular bones is slow and continues until the complete element is ossified. The cellular components of the appendicular skeleton change accordingly during ossification, creating a heterogenous landscape in each element. The continuous maturation of the bone is accompanied by a continuous body growth.