BONE-MINERAL METABOLISM IN GIRLS WITH PRECOCIOUS PUBERTY DURING GONADOTROPIN-RELEASING-HORMONE AGONIST TREATMENT

Bone mineral metabolism and mineralization before and during treatment were studied in 10 girls aged 6.9-8.4 years affected by central preco cious puberty and treated with gonadotrophin-releasing hormone agonist (GnRHa) leuprolide acetate depot, in order to understand better the c onsequences of oestrogen deficiency and the reduction of growth hormon e (GH)-insulin-like growth factor I (IGF-I) axis activity. Before and after 12 months of therapy, the patients underwent a clonidine stimula tion 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 sa mples. Trabecular and cortical bone mass variations, measured by dual X-ray absorptiometry in the lumbar spine and by dual photon absorptiom etry in the radius, respectively were evaluated before the start and a fter 12 months of therapy. During treatment, a decrease of serum oestr adiol 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 ch ange significantly after calcitrol load, either before or after GnRHa therapy. Urinary hydroxyproline decreased significantly after 12 month s. Before therapy, lumbar spine and radius bone mass were high for chr onological age but appropriate for bone age; after 12 months of treatm ent, bone mass in the lumbar spine, but not in the radius, had decreas ed significantly. In our patients, regression of pubertal development was associated with a reduction of trabecular bone mass, which appears to be the primary consequence of GnRHa therapy and possibly related t o decreased GH secretion.