Bone mineral metabolism in girls with precocious puberty during gonadotrophin-releasing hormone agonist treatment

Abstract

Bone mineral metabolism and mineralization before and during treatment were studied in 10 girls aged 6.9-8.4 years affected by central precocious puberty and treated with gonadotrophin-releasing hormone agonist (GnRHa) leuprolide acetate depot, in order to understand better the consequences of oestrogen deficiency and the reduction of growth hormone (GH)-insulin-like growth factor I (IGF-I) axis activity. Before and after 12 months of therapy, the patients underwent a clonidine stimulation test and a 4-day calcitriol osteoblast stimulation test. On day 0, day 5 and at 3-month intervals thereafter, serum calcium, phosphate, alkaline phosphatase, IGF-I, IGF binding protein 3 (IGFBP-3), GH, GH binding protein and osteocalcin levels were measured; urinary calcium, phosphate and hydroxyproline levels were evaluated in fasting spot samples. Trabecular and cortical bone mass variations, measured by dual X-ray absorptiometry in the lumbar spine and by dual photon absorptiometry in the radius, respectively were evaluated before the start and after 12 months of therapy. During treatment, a decrease of serum oestradiol levels from pubertal to prepubertal levels was observed. The GH peak following clonidine diminished significantly after 1 year. Growth hormone binding protein showed a slight increase, and IGF-I and IGFBP-3 decreased, although not significantly. Osteocalcin levels decreased significantly after 9 and 12 months of treatment, but they did not change significantly after calcitriol load, either before or after GnRHa therapy. Urinary hydroxyproline decreased significantly after 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues

“…Some studies showed BMD values not different between GnRHa-treated and GnRHa-untreated patients [27, 53]. Otherwise, lower BMD and bone strength before and during GnRHa therapy were demonstrated in CPP patients [25, 54, 55], with a completely restored bone mineral content during the first year of therapy [25] or some years after GnRHa withdrawal [10-12]. Moreover, Antoniazzi et al [56] demonstrated that the BMD reduction observed during GnRHa therapy was reversible and preventable by providing calcium supplementation from the beginning of treatment.…”

Sex Steroids and the Acquisition of Bone Mass

“…Most of the studies demonstrated a significant increase in radial and/or lum bar BMD compared with prepubertal girls of a similar age [8][9][10][11], while BMD was not significantly different from control girls with a similar bone age [8,9,12], Only Arisaka et al [13] did not find the gain of lumbar BMD in girls with central precocious puberty.…”

“…1) [8], Recently, the BMD decrease during GnRH analogue treatment has been con firmed at radial and lumbar levels [9,10], However, other authors [12] did not confirm the decrease in lumbar area BMD during 2 years of GnRH analogue therapy.…”

Bone development during GH and GnRH analog treatment

“…Treatment of precocious puberty with GnRHa, by suppressing gonadotropin secretion and reducing sex steroid levels, leads to hypoestrogenism, which may be accompanied by delayed skeletal maturation and deficient bone mineralization (25,26). This estrogen deprivation may theoretically have a detrimental effect on bone mass during pubertal development.…”

“…To test this hypothesis, we studied some years ago (26) bone mineral metabolism and mineralization by dualenergy X-ray absorptiometry (DEXA) before and during treatment in 10 girls aged 6.9-8.4 years affected by CPP and treated with GnRHa, in order to clarify the consequences of estrogen deficiency and of the reduction of GH -IGF-I axis activity.…”