Menstrual cycle pattern during the first gynaecological years in girls with precocious puberty following gonadotropin-releasing hormone analogue treatment.
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Child↗
Biomedical subjects
Franco Antoniazzi
Publications and source records attributed to Franco Antoniazzi.
Early bisphosphonate treatment in infants with severe osteogenesis imperfecta.
OBJECTIVE: To evaluate prospectively the efficacy of bisphosphonate treatment in infants with severe forms of osteogenesis imperfecta (OI). STUDY DESIGN: Of 10 children (6 females) with OI type III, 5 (group A) started treatment (2 mg/kg neridronate administered intravenously for 2 consecutive days, every 3 months) just after diagnosis at birth and 5 (group B) after 6 months. Ten untreated children, matched for sex, age, and clinical severity of OI, constituted a historical control group (group C). We measured weight, length, and number of fractures every 3 months and serum and urinary levels of calcium, phosphorus, creatinine, serum alkaline phosphatase, 25-hydroxyvitamin D, insulin-like growth factor I, parathyroid hormone, and osteocalcin, urinary type I collagen N-terminal telopeptide, and lateral radiography of vertebral column every 6 months. RESULTS: Group A had better growth and a lower incidence of fractures than groups B and C in the first 6 months of treatment. In the second 6 months, both groups A and B had lower fracture rates than group C. After 12 months of therapy, osteocalcin and insulin-like growth factor I levels significantly increased only in group A. The urinary Ca/Cr ratio and N-terminal telopeptide/Cr ratio significantly declined only in treated patients. Vertebral body area and the structure of vertebral bodies improved in all treated patients, but especially in group A. CONCLUSIONS: Cyclical neridronate treatment, started just after diagnosis at birth, had positive effects on growth and fracture rate.
Absorptiometry, Photon↗
Osteogenesis imperfecta and its molecular diagnosis by determination of mutations of type I collagen genes.
Osteogenesis Imperfecta is a genetic disorder of increased bone fragility and low bone mass. Most cases are caused by a mutation in one of the two genes coding for the type I collagen protein. The correct clinical diagnosis of OI can be difficult sometimes, because of the wide phenotypic range. Therefore collagen I genes mutation identification can be helpful. We screened 23 patients by direct sequencing of the exons encoding the collagen protein. We identified 18 different mutations, while 5 cases were negative because of an uncertain clinical diagnosis or an atypical form of OI not related to collagen I genes. The current medical and pharmaceutical treatments are only symptomatic and do not alter the course of collagen mutations. Cells and gene therapies as potential treatments for OI have therefore to be actively investigated.
Collagen Type I↗
Intravenous neridronate in children with osteogenesis imperfecta: a randomized controlled study.
UNLABELLED: In a randomized controlled study, we investigated the effect of treatment with intravenous neridronate in prepubertal children with OI. Our study suggests that quarterly intravenous infusions of the bisphosphonate significantly raise the rate of increase in BMD at both the spine and hip, the projected area of the lumbar vertebrae, and height. These results are associated with a significant decrease in the risk of clinical fractures. INTRODUCTION: Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seem to be the most promising therapy, but randomized, controlled studies are scarce and have never been carried out in prepubertal children. MATERIALS AND METHODS: This was a randomized, controlled 3-year clinical trial. The Italian Patients' Society of OI (AsItOI) sent their members affected by any type of OI to two centers at the University of Verona (Italy) to participate in the study. Sixty-four children, 6-11 years of age for boys and 6-9 years of age for girls, with no signs of puberty and who were never treated with bisphosphonates, were randomized to either intravenous neridronate (2 mg/kg infused IV in 30 minutes every 3 months) or no treatment, with a ratio of 2:1. Control patients were given the same bisphosphonate therapy at the end of the first year. BMD and projected bone areas, as measured by DXA, at spine and hip, height, and peripheral fracture incidence, both prospective and retrospective (2 years preceding randomization), were the main outcomes of the study. RESULTS: At the end of the first year, spine and hip BMD rose by 3.5-5.7% in control patients and by 18-25% (p < 0.001 versus controls) in the active group, respectively. During the following 2 years, the treatment in all patients was associated with BMD increases of 10-25% per year. Height and the DXA-derived projected area of lumbar spine rose during the first year of observation significantly more in the active group than in the control group (<0.01 and <0.05, respectively). Both height and spine projected area continued to rise in the treated patients toward levels found in healthy individuals. During the first year of treatment, 45% of the control patients and 27% of the active group had a nonvertebral fracture, but this difference was not statistically significant (p = 0.2). The total number of fractures was 18 in the 22 control patients and 13 in the active group (relative risk, 0.36; 95% CI, 0.15-0.87; p < 0.05). CONCLUSION: Intravenous neridronate infusions, administered quarterly, significantly increase BMD and lower the risk of clinical fracture in prepubertal children with OI.
Alkaline Phosphatase↗
Graves' ophthalmopathy evolution studied by MRI during childhood and adolescence.
Pediatric patients with Graves' disease (n=26) were studied longitudinally by magnetic resonance imaging of the orbits, allowing an assessment of the enlargement of the extraocular muscles and orbital volume variations. The positive outcome of Graves' ophthalmopathy correlated with low TRAb (autoantibodies to thyroid-stimulating hormone receptor) titers at diagnosis and during follow-up and with prepubertal condition at diagnosis.
Adolescent↗
Reduction of baseline body mass index under gonadotropin-suppressive therapy in girls with idiopathic precocious puberty.
OBJECTIVE: To investigate longitudinally body mass index (BMI) evolution and obesity prevalence in a large and very homogeneous study population consisting only of girls with non-organic central precocious puberty (CPP) who were treated with gonadotropin-releasing hormone agonists (GnRHa) for at least two years. PATIENTS AND DESIGN: The 101 girls with idiopathic CPP who were selected for this study fulfilled the following inclusion criteria: (a) suppression of gonadotropin and gonadal sex steroid secretion during the overall GnRHa treatment period; (b) adequate compliance with the therapy regimen. All the girls were treated for 44+/-14 months and were followed-up for 15.7+/-7.8 months after therapy withdrawal. RESULTS: At the start of therapy, 23.8% of the girls had a BMI exceeding 2 standard deviation scores (SDS) and were therefore classified as obese; both average BMI-SDS and obesity prevalence significantly decreased during the treatment period (chi(2)=16.6, P<0.0005) and only 4% of the patients, all with pre-existing obesity, were still obese at the end of therapy; during the therapy period, BMI-SDS increased in none of the patients. Both average BMI-SDS and obesity prevalence (from 4 to 0%; chi(2)=4.0, P<0.05) further decreased during the period that followed therapy withdrawal. CONCLUSIONS: (a) girls with idiopathic CPP are frequently obese at the onset of GnRHa therapy (23.8%), probably due to the hormonal changes which accompany the start of puberty; (b) their obesity is neither long-lasting nor related to GnRHa administration; (c) on the contrary, GnRHa therapy may have a favourable effect on BMI decrease, provided that treatment is performed for at least two years and is accompanied by a complete suppression of gonadotropin secretion; (d) this unexpected effect, which has never been reported hitherto, might represent a further indication for GnRHa administration in idiopathic CPP.
Antineoplastic Agents, Hormonal↗
Bone development during GH and GnRH analog treatment.
Estrogens, GH and IGFs are essential in the development and growth of the skeleton and for the maintenance of bone mass and density. Treatment of precocious puberty with GnRH analogs (GnRHa), by reducing sex steroid levels, leads to a situation of hypoestrogenism that may theoretically have a detrimental effect on bone mass during pubertal development. A reduction in bone mineral density (BMD) during GnRHa treatment has been demonstrated, but GnRHa treatment in patients with central precocious puberty (CPP) does not seem to impair the achievement of normal peak bone mass (PBM) at final height. However, calcium supplementation is effective in improving bone densitometric levels and may promote better PBM achievement. In children and adolescents with GH deficiency (GHD), BMD assessed by dual-energy X-ray absorptiometry (DEXA) and bone turnover are significantly reduced, but they are stimulated by GH treatment. GH treatment leads to improved bone density, function of the dose and duration of treatment, and patients may require prolonged GH treatment beyond the time of growth to improve PBM. After the discontinuation of GH therapy, the more active population had higher bone mineral content (BMC) levels than patients with low physical activity. In our experience, the therapeutic association of GH and calcium also represents a valuable tool in pursuing a proper BMC in GHD patients. We concluded that nonhormonal factors, such as physical activity and nutritional factors, are important in determining bone metabolism and bone mass.
Adolescent↗
Central precocious puberty: current treatment options.
Central precocious puberty (CPP) is characterized by early pubertal changes, acceleration of growth velocity, and rapid bone maturation that often result in reduced adult height. An onset of pubertal signs before the age of 8 years in girls and 9 years in boys should always be evaluated. A combination of clinical signs, bone age, pelvic echography in girls, and hormonal data are required to diagnose CPP and make a judgment concerning progression and prognosis. Not all children with apparently true CPP require medical intervention. The main reasons for treatment are to prevent compromised adult height and to avoid psychosocial or behavioral problems. The need for treatment for auxologic reasons is based on estimation of predicted adult height, with the finding of a reduced height potential, which may require a follow-up. Indication for treatment on the basis of psychologic and behavioral anomalies has to be determined on an individual basis. The main short-term aims of therapy are to stop the progression of secondary sex characteristics and menses (in girls) and to treat the underlying cause, when known. Long-term goals are to increase final adult height and to promote psychosocial well-being. Once it has been decided that treatment is appropriate, it should be initiated immediately with depot gonadotropin-releasing hormone (GnRH) agonists. The effective suppression of pituitary gonadal function is achieved with these compounds in practically all CPP patients. Long-term data are now available from 2 decades of GnRH agonist treatment for patients with CPP. Treatment preserves height potential in the majority of patients (especially in younger patients) and improves the final adult height of children with rapidly progressing CPP, with a complete recovery of the hypothalamic-pituitary-gonadal axis after treatment. GnRH agonist treatment using depot preparations is useful and has a good safety profile, with minimal adverse effects and no severe long-term consequences. Although further data are need, there may be a role in the future for combining somatropin (growth hormone) and GnRH agonist treatment for some patients with significantly impaired growth velocity. The introduction of GnRH antagonists is likely to improve the treatment options for CPP.
Body Height↗
Bone mass at final height in precocious puberty after gonadotropin-releasing hormone agonist with and without calcium supplementation.
The aim of our longitudinal study was to evaluate bone mass in girls affected by central precocious puberty (CPP) that have reached final height, treated with GnRH agonist triptorelin (GnRHa), with or without calcium supplementation. We studied 48 Caucasian females affected by CPP (age at diagnosis, 7.19 +/- 0.96 yr), randomly assigned to two groups: group A (n = 21) treated with GnRHa and group B (n = 27) treated with GnRHa plus calcium gluconolactate and carbonate (1 g calcium/day in two doses) for at least 2 yr. Auxological parameters (standing height, weight, body mass index) and bone mineral density (BMD) at the lumbar spine [L2-L4, anteroposterior (AP)-BMD; lateral BMD; volumetric (v)BMD)] by dual-energy x-ray absorptiometry were evaluated at the beginning [chronological age (CA), 7.29 +/- 0.91 yr; bone age (BA), 8.80 +/- 1.24 yr] and end of treatment (CA, 11.27 +/- 0.97 yr; BA, 12.35 +/- 0.43 yr) and at final height (CA, 16.17 +/- 1.9 yr; BA, 16.93 +/- 0.98 yr, in each case >15 yr). Total bone mineral content, total BMD, and fat percentage were evaluated at the end of the study period using dual-energy x-ray absorptiometry. Final height was significantly higher than predicted height at diagnosis (159.9 +/- 6.3 cm vs. 152.9 +/- 9.6 cm; P < 0.05). Body mass index and fat percentage were not statistically different from control values. Densitometric values at final evaluation in groups A and B together were lower than in controls, but the differences were not statistically significant. The vBMD was significantly higher in group B than in group A at the end of treatment period (0.213 +/- 0.022 g/cm(3) vs. 0.192 +/- 0.021 g/cm(3); P < 0.01) and at final evaluation (0.246 +/- 0.023 g/cm(3) vs. 0.227 +/- 0.024 g/cm(3); P < 0.05). The percentage change (Delta%) between the start and end of treatment period in AP-BMD and vBMD was significantly higher in group B than in group A (Delta% AP-BMD: 20.36% +/- 1.10% vs. 16.16% +/- 1.90%, P < 0.01; Delta% vBMD: 19.08% +/- 3.52% vs. 9.26% +/- 5.15%; P < 0.01) and also between the start of treatment and final evaluation (Delta% AP-BMD: 61.23% +/- 1.61% vs. 56.97% +/- 1.45%, P < 0.01; Delta% vBMD: 36.69% +/- 5.01% vs. 28.01% +/- 5.76%, P < 0.01). In all our females with CPP treated with GnRHa, bone densitometric parameters were in the normal range for age and sex. However, bone mass achievement seemed to be better preserved in the group of patients supplemented with calcium.
Body Height↗
The volumetric bone density and cortical thickness in adult patients affected by osteogenesis imperfecta.
In patients with osteogenesis imperfecta (OI), a disease characterized by abnormal bone fragility, bone mineral density (BMD) was found to be relatively preserved. Quantitative computed tomography (QCT) is the only available method for directly measuring in vivo both volumetric density and the cross-sectional area. Here we report the data from dual-energy X-ray absorptiometry DXA (spine and hip) and peripheral (pQCT) (ultradistal and proximal radius) measurement of 27 adult patients affected by OI, mostly of type I, compared with a group of healthy persons. In the patients with OI, areal BMD values at both femoral neck and lumbar spine were considerably lower than in control subjects (-32 and -36%, respectively; p<0.001 for body weight and height adjusted values). pQCT volumetric density at the ultradistal radius was 19% lower than in control subjects and this difference rose to 32% for purely cancellous bone tissue. The whole bone cross-sectional area of ultradistal radius, as measured by pQCT, was superimposable to normal. At the proximal radius, both cross-sectional area and cortical area, together with Bending Breaking Resistance Index (BBRI), were significantly lower in OI (-23; -22; -32% respectively; p<0.001 for body weight and height adjusted values), but cortical volumetric density was even slightly higher in the OI group than in control subjects. In conclusion, it appears that the most obvious defect in adults with OI is the inability to acquire an adequate thickness of the cortices of long bone and to achieve or maintain normal trabecular density.
Absorptiometry, Photon↗