BONE MINERAL METABOLISM IN PRECOCIOUS PUBERTY DURING TREATMENT

Abstract

Gonadal steroids are known to play an important role in the control of GH-IGF-I axis and in bone mineral increase that occur during puberty. To better know the importance of estrogens on bone mineral metabolism during growth and puberty we studied ten girls (age range 6-7.2 yrs.) with true precocious puberty, before and after 1 year of LHRH analogs treatment. In these patients, before starting treatment with Leuprolide acetate (Enantone depot-Takeda), 0.2 mg/kg administered i.m. every 28 days, we performed: a clonidin stimulation test for GH; a 1, 25dihydroxyvitaminD3 llad (Rocaltrol-Roche) giving a dose of 2 μg/day for four consecutive days with the dosage before and after of serum Ca, P, IGF-I and Osteocalcin; a densitometric evaluation (dual photon absorptiometry) of BMC and BD (BMC/BW) in the distal and ultradistal region of the nondominant radius, After 1 year of therapy we repeated the same evaluations. During therapy serum estradiol levels decreased from pubertal (35.7 ± 3.5 pg/ml) (M± DS) to prepubertal levels (<20 pg/ml in each patient) as expected. GH peak after clonidin stimulation test after treatment was significantly lower than before (18.7 ± 2.2 vs 6.8 ± 3.5 ng/ml; p=0.005). IGF-I levels decreased not significantly at 12 months (from 278 ± 38 to 223 ± 53 ng/ml) and were not influenced by 1, 25(OH)2D3 load, while Osteocalcin levels were in the pubertal range before therapy (35, 8 ± 6, 2 ng/ml), decreased not significantly after therapy, and showed a slight increase after 1, 25(OH)2D3 load both before and after LHRHa therapy. Before therapy, BMC and BD were increased for chronological age, but appropriate for bone age. After 12 months of LHRH analogs treatment, BMC and BD showed a significant decrease (−4, 9 ± 1, 0 and −5, 1 ± 0, 9 %; p<0.05) in the ultradistal region (measuring trabecular bone), while there was a not significant difference in the distal region (measuring cortical bone). These results indicate that contemporary decrease in estrogen and GH-IGF-I levels may reduce osteoblastic activity and produce a decrease in bone mass.