Roberto Franceschi

GH in combination with bisphosphonate treatment in osteogenesis imperfecta

OBJECTIVE To verify the effects of bisphosphonates (Bps) in combination with recombinant human GH (rGH) in pediatric osteogenesis imperfecta (OI) patients; we focused on possible improvement of bone mineral density (BMD), projected bone areas, growth velocity, and fractures risk. DESIGN A randomized controlled 1-year clinical trial on 30 prepubertal children (M:F=14:16) affected by OI (type I, IV, and III) being treated with neridronate. METHODS Following an observational period of 12 months during ongoing neridronate treatment, the patients were randomly divided into two groups: 15 were treated for 12 months with rGH and neridronate (group Bp+rGH) and 15 continued neridronate alone (group Bp). We evaluated auxological parameters, number of fractures, bone age (BA), bone metabolic parameters, and bone mass measurements (at lumbar spine and radius by dual-energy X-ray absorptiometry). RESULTS The mean variation in percentage of BMD (Delta%BMD)--at lumbar spine (L2-L4), at distal and ultradistal radius--and the projected area of lumbar spine increased significantly in group Bp+rGH (P<0.05). Growth velocity was significantly higher during rGH treatment in group Bp+rGH versus group Bp and versus pretreatment (P<0.05), with no difference in increase in BA or fracture risk rate. Patients with quantitative (-qt) collagen synthesis defects had a higher, although not significant, response to rGH in terms of growth velocity and BMD. CONCLUSIONS In OI patients, the combined rGH-Bp treatment may give better results than Bp treatment alone, in terms of BMD, lumbar spine projected area and growth velocity, particularly in patients with quantitative defects.

Thyrotropin receptor gene mutations and TSH resistance: variable expressivity in the heterozygotes

Objective  TSH resistance ranges from overt nonautoimmune hypothyroidism to subclinical hypothyroidism, defined as mild hyperthyrotrophinaemia but a euthyroid state clinically. To date, 23 inactivating mutations of the TSH receptor (TSHR) gene have been proven responsible for the clinical condition, but an absence of mutations in the TSHR gene has been reported for several cases of TSH resistance as well. In this paper, we aimed to investigate the actual role of the TSHR gene in the development of both subclinical and congenital hypothyroidism.

Prevalence of polycystic ovary syndrome in young women who had idiopathic central precocious puberty

OBJECTIVE To assess the prevalence of polycystic ovary syndrome (PCOS) in a cohort of young women with previous idiopathic central precocious puberty (ICPP) at least 3 years after menarche, and to look for any predictive factors of PCOS at the time ICPP was diagnosed. DESIGN Longitudinal study. SETTING Pediatrics unit, Verona, Italy. PATIENT(S) Forty-six young women (18.1 +/- 3.0 years) who had been treated with GnRH analogues during childhood, observed at gynecologic age of 6.23 +/- 3.3 years. INTERVENTION(S) Semistructured interview concerning cycles, physical exam, blood sampling, and transabdominal pelvic ultrasound. MAIN OUTCOME MEASURE(S) Oligomenorrhea, LH, FSH, E(2), T, DHEAS, free T, delta4-androstenedione, 17-OHP, P, polycystic ovary morphology (PCOM). RESULT(S) Fifteen percent of the young women had oligomenorrhea, 28% clinical hyperandrogenism, 48% biochemical hyperandrogenism, and 37% PCOM. A total of 32% of the patients had PCOS according to the Rotterdam definition and 30% had PCOS according to the Androgen Exess Society. The prevalent phenotype of PCOS was characterized by clinical and/or biochemical hyperandrogenism and PCOM. We did not find any predictive factors for PCOS at the time ICPP was diagnosed. CONCLUSION(S) Patients with ICCP are prone to developing PCOS. The prominent phenotype in this cohort was PCOM associated with clinical and/or biochemical hyperandrogenism. Further follow-ups of these young adult patients will clarify whether this phenotype persists and if it will have important long-term implications regarding increased risk of infertility or metabolic complications.

Idiopathic Juvenile Osteoporosis: Clinical Experience from a Single Centre and Screening of LRP5 and LRP6 Genes

We report clinical findings, bone mineral density (BMD) and bone biopsy data in ten children with features of classic idiopathic juvenile osteoporosis (IJO). We also screened the patients for mutations in LRP5 and LRP6. We found low BMD in the lumbar spine, the hip and distal radius. In the spine and distal radius, the reduction in BMD was more marked in the trabecular compartment. Biopsy confirmed that the trabecular compartment is more severely involved with reduction in bone formation and increase in bone resorption. No mutations in LRP5 and LRP6 could be identified. IJO is likely to be a heterogeneous bone disorder, and next-generation genomic sequencing studies may help reveal causative genes.

Bone Geometry, Quality, and Bone Markers in Children with Type 1 Diabetes Mellitus

Adults with Type 1 diabetes mellitus show a high risk of bone fracture, probably as a consequence of a decreased bone mass and microarchitectural bone alterations. The aim of the study was to investigate the potential negative effects of type 1 diabetes on bone geometry, quality, and bone markers in a group of children and adolescents. 96 children, mean age 10.5 ± 3.1 years, agreed to participate to the study. Bone geometry was evaluated on digitalized X-rays at the level of the 2nd metacarpal bone. The following parameters were investigated and expressed as SDS: outer diameter (D), inner diameter (d), cortical area (CA), and medullary area (MA). Bone strength was evaluated as Bending Breaking Resistance Index (BBRI) from the geometric data. Bone turnover markers (PINP, CTX-I, and BAP), sclerostin, Dkk-1, PTH, and 25OH-Vitamin D were also assessed. A group of healthy 40 subjects of normal body weight and height served as controls for the bone markers. D (− 0.99 ± 0.98), d (− 0.41 ± 0.88), CA (− 0.85 ± 0.78), and MA (− 0.46 ± 0.78) were all significantly smaller than in controls (p < 0.01). BBRI was significantly lower (− 2.61 ± 2.18; p < 0.0001). PTH, PINP, and BAP were higher in the diabetic children. Multiple regression analysis showed that CA and D were influenced by insulin/Kg/day and by BMI, while d was influenced by PINP only. Type 1 diabetic children show smaller and weaker bones. The increased bone turnover could play a key role since it might amplify the deficit in bone strength associated with the inadequate osteoblastic activity caused by the disease itself.

Possible andrologic markers in elevated neonatal 17-hydroxyprogesterone.

In this prospective study, we analyzed 30 male infants with increased neonatal 17-hydroxyprogesterone (17OH-P) (patients) and for comparison 52 age-matched healthy babies (control subjects) with the aim of investigating the hypothalamic-pituitary-testis axis in the first 6 months of life. Although T, FSH, and LH levels were not significantly different in patients and control subjects, inhibin B was higher in patients than in control subjects. Therefore we suggest a clinical follow-up of these babies during childhood and puberty to verify the evolution of their condition.