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.
F Antoniazzi, G Zamboni, F Bertoldo, S Lauriola and L Tato
T Arrigo, F De Luca, F Antoniazzi, F Galluzzi, M Segni, M Rosano, MF Messina and F Lombardo
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.
T Arrigo, M Cisternino, F Galluzzi, S Bertelloni, AM Pasquino, F Antoniazzi, P Borrelli, G Crisafulli, M Wasniewska and F De Luca
The aim of this retrospective study was to analyze the factors which affected the auxological response to GnRH agonist treatment and the final height (FH) outcome in 71 girls with idiopathic and truly precocious (onset before 8 years) central puberty (CTPP) who had been treated with the same therapy protocol (Decapeptyl Depot, 60 microg/kg i.m. every 28 days) for at least 2 years (since 7.0+/-1. 3 (S.D.) years of age) and followed until puberty was completed and FH was reached. During the entire treatment period we observed: (a) a decrease of height standard deviation scores (SDS) (from 1.5+/-1.7 to 0.9+/-1.3 SDS, P<0.01); (b) a striking deceleration of bone age (BA), revealed by the subnormal DeltaBA:Deltachronological age (CA) ratio (0.2+/-0.1); (c) an increase of predicted adult height (from 155.6+/-7.0 to 160.7+/-6.7 cm, P<0.0005). Treatment interruption was followed by an important catch-down growth, with an FH (158.4+/-5.8 cm) lower (P<0.025) than that predicted at the end of therapy. However, FH fell within the population norm and the target range in respectively 87.3 and 90% of the patients. The tallest FH was recorded in the patients who started therapy at less than 6 years of age and in those who discontinued treatment at a BA of 12.0--12.5 years. At stepwise regression analysis, FH in the whole study population was positively affected by the following independent factors: (a) height at the end of therapy (F=45.45, P<0.0001); (b) pretreatment height (F=13.91, P<0.0005); (c) treatment duration (F=8. 51, P<0.005); (d) target height (TH) (F=7.70, P<0.01). We conclude that: (i) most girls with idiopathic CTPP treated by GnRH agonists may achieve an adult height within the population norm and/or their target range; (ii) the height gain from therapy onset until FH attainment, however, is generally rather limited (on average 2.9 cm) and only few patients are able to reach their target percentile; (iii) the most favorable height prognosis with respect to TH is generally observed in the subjects with the tallest height at the end of treatment and the lowest BA2:CA2 ratio, due to the important deterioration of height prognosis which frequently follows therapy interruption; (iv) FH is also significantly conditioned by both TH and treatment duration; (v) in order to strengthen the weak therapeutic effect of GnRH agonists in CTPP this treatment should be started as early as possible and discontinued at a BA of 12.0--12.5 years.