Early recognition of osteoporosis in children and adolescents is important in order to establish an appropriate diagnosis of the underlying condition and to initiate treatment if necessary. In this review, we present the diagnostic work-up, and its pitfalls, of pediatric patients suspected of osteoporosis including a careful collection of the medical and personal history, a complete physical examination, biochemical data, molecular genetics, and imaging techniques. The most recent and relevant literature has been reviewed to offer a broad overview on the topic. Genetic and acquired pediatric bone disorders are relatively common and cause substantial morbidity. In recent years, there has been significant progress in the understanding of the genetic and molecular mechanistic basis of bone fragility and in the identification of acquired causes of osteoporosis in children. Specifically, drugs that can negatively impact bone health (e.g. steroids) and immobilization related to acute and chronic diseases (e.g. Duchenne muscular dystrophy) represent major risk factors for the development of secondary osteoporosis and therefore an indication to screen for bone mineral density and vertebral fractures. Long-term studies in children chronically treated with steroids have resulted in the development of systematic approaches to diagnose and manage pediatric osteoporosis.Conclusions: Osteoporosis in children requires consultation with and/or referral to a pediatric bone specialist. This is particularly relevant since children possess the unique ability for spontaneous and medication-assisted recovery, including reshaping of vertebral fractures. As such, pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children. What is Known:• Both genetic and acquired pediatric disorders can compromise bone health and predispose to fractures early in life.• The identification of children at risk of osteoporosis is essential to make a timely diagnosis and start the treatment, if necessary. What is New:• Pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children and children at risk of osteoporosis.• We offer an extensive but concise overview about the risk factors for osteoporosis and the diagnostic work-up (and its pitfalls) of pediatric patients suspected of osteoporosis.

Type 1 diabetes (T1D) is the most common chronic metabolic disease in children and adolescents. The etiology of T1D is not fully understood but it seems multifactorial. The genetic background determines the predisposition to develop T1D, while the autoimmune process against β-cells seems to be also determined by environmental triggers, such as endocrine disrupting chemicals (EDCs). Environmental EDCs may act throughout different temporal windows as single chemical agent or as chemical mixtures. They could affect the development and the function of the immune system or of the β-cells function, promoting autoimmunity and increasing the susceptibility to autoimmune attack. Human studies evaluating the potential role of exposure to EDCs on the pathogenesis of T1D are few and demonstrated contradictory results. The aim of this narrative review is to summarize experimental and epidemiological studies on the potential role of exposure to EDCs in the development of T1D. We highlight what we know by animals about EDCs’ effects on mechanisms leading to T1D development and progression. Studies evaluating the EDC levels in patients with T1D were also reported. Moreover, we discussed why further studies are needed and how they should be designed to better understand the causal mechanisms and the next prevention interventions.

Background: Early puberty suppression (ePS; Tanner stages 2 and 3) through gonadotropin-releasing hormone agonists (GnRHas) and gender-affirming hormones (GAHs) interferes with growth and may impact final height (FH).Aim: To investigate the impact of ePS and GAH on FH in trans boys and trans girls.Methods: Retrospective study, including 10 trans boys and 22 trans girls at FH. Bone age (BA) was determined at the start of ePS and at the start of GAH according to Greulich and Pyle; predicted adult height (PAH) was calculated according to Bayley and Pinneau's tables; target height (TH) was calculated as adjusted mean of maternal and paternal height. Target height, PAH, and BA were determined according to sex registered at birth (SRAB) and experienced gender (EG).Results: The age at the start of PS was 12.37 ± 0.74 years in trans boys and 13.10 ± 1.12 years in trans girls. Total height gain since the start of ePS in trans boys was 14.62 ± 4.08 cm, with 70% achieved before the start of GAH. In trans girls, it was 20.68 ± 7.66 cm, with 61% achieved before GAH. Target height for SRAB was the most accurate predictor for FH in both trans boys and girls: the difference with FH was 1.57 cm ± 3.1 (P = .168) and −0.98 cm ± 4.17 (P = .319), respectively. Also the difference between FH and PAH at the start of PS for SRAB was nonsignificant in both trans boys and girls (2.62 cm ± 3.79, P = .056 and −2.35 cm ± 5.2, P = .051, respectively).Conclusion: Early puberty suppression and GAH do not impact FH, supporting the safety of the treatment; however, trans adolescents achieve a FH in line with SRAB, rather than EG.

The effects of puberty suppression for more than 2 years before the start of gender-affirming hormones (GAH) on bone mass acquisition and body composition are understudied. Retrospective study on 46 transgender adolescents (20 trans boys and 26 trans girls) receiving a gonadotropin-releasing hormone analogue (GnRHa) from Tanner stage 2-3, followed by GAH around the age of 16 years. At start of GnRHa and at start of GAH, dual-energy X-ray absorptiometry (DXA) at lumbar spine (LS), femoral neck (FN) and total body (TB), handgrip strength test and fasting blood sampling were performed. Z-scores were calculated using reference values for both cis girls and cis boys. GnRHa were administered for a median of 3.2 years (± 0.69) in trans boys and 2.7 years (± 1.05) in trans girls. Bone mineral apparent density (BMAD)-LS Z-scores decreased significantly in both trans boys and trans girls, while BMAD-FN Z-scores decreased only in trans boys. Fat% and Fat Mass Index Z-scores significantly increased in both groups, while Lean Mass Index Z-scores significantly decreased. Handgrip strength Z-scores for the sex registered at birth (SRAB) remained stable in trans boys while they decreased in trans girls. There was no significant influence of the treatment on either insulin sensitivity or lipid profile. GnRHa administration for more than two years during the physiological time of puberty decreases bone mass acquisition, mainly at the lumbar spine and induces a general increase in fat mass. Although lean mass acquisition is undermined in both groups, handgrip strength is affected mainly in trans girls compared with age-matched peers for the SRAB.