Bertelloni S, Baroncelli G I, Sorrentino M C, Perri G, Saggese G
Department of Paediatrics, University of Pisa, Santa Chiara Hospital, Italy.
Eur J Pediatr. 1998 May;157(5):363-7. doi: 10.1007/s004310050831.
To evaluate the effect of central precocious puberty (CPP) and its treatment with gonadotropin-releasing hormone (GnRH) analogues on final height and peak bone mass (PBM), we measured lumbar bone mineral density (BMD) in 23 girls at final height. Patients were distributed in two groups. Group 1: 14 patients with progressive CPP were treated with GnRH analogues; seven patients received buserelin (1600 microg/daily), subsequently switched to depot triptorelin (60 microg/kg/26-28 days); seven patients were treated with depot triptorelin (60 microg/kg/26-28 days); mean age of treatment was 6.2 years (range 2.7-7.8 years); the treatment was discontinued at the mean age of 10.1 years (range 8.7-11.3 years); final height was reached at the mean age 13.4 years (range 12.0-14.9 years). Group 2: 9 patients (mean age 6.5 years, range 4.8-7.7 years) with a slowly progressing variant of CPP were followed without treatment; final height was reached at the mean age 13.6 years (range 12.5-14.8 years). Lumbar BMD (L2-L4 by dual energy X-ray absorptiometry) was measured in all patients at final height. In group 1, final height (158.9+/-5.4 cm) was significantly greater than the pre-treatment predicted height (153.5+/-7.2 cm, P < 0.001), but significantly lower than mid-parental height (163.2+/-6.2 cm, P < 0.005). Subdividing the girls of group 1 according to the bone age at discontinuation of therapy (i.e. < or =11.5 years, n=5, or > or =12.0 years, n=9), the former patients had a final height significantly higher than the latter (163.7+/-3.9 cm vs 156.5+/-4.6 cm, P < 0.02). In group 2, final height (161.8+/-4.6 cm) was similar to the pre-treatment predicted height (163.1+/-6.2 cm, P=NS) and was not significantly different from mid-parental height (161.0+/-5.9 cm). BMD values (group 1: 1.11+/-0.14 g/cm2, group 2: 1.22+/-0.08 g/cm2) were not significantly different from those of a control group (1.18+/-0.10 g/cm; n=20, age 16.3-20.5 years) and the patients' mothers (group 1: 1.16+/-0.07 g/cm2, n=11, age 32.9-45.1 years; group 2: 1.20+/-0.08 g/cm2, n=7, age 33.5-46.5 years). In group 1, the girls who stopped therapy at a bone age < or =11.5 years had significantly higher BMD (1.22+/-0.10 g/cm2) compared to those who discontinued therapy at a bone age > or =12.0 years (1.04+/-0.12 g/ cm2, P < 0.05).
In girls with progressive CPP, long-term treatment with GnRH analogues improves final height. A subset of patients with CPP does not require treatment because good statural outcome (slowly progressing variant). In CPP, the abnormal onset of puberty and the long-term GnRH analogue treatment do not impair the achievement of PBM. In GnRH treated patients, the discontinuation of therapy at an appropriate bone age for pubertal onset may improve both final height and PBM.
为评估中枢性性早熟（CPP）及其用促性腺激素释放激素（GnRH）类似物治疗对最终身高和峰值骨量（PBM）的影响，我们在23名女孩达到最终身高时测量了腰椎骨密度（BMD）。患者分为两组。第1组：14例进展性CPP患者接受GnRH类似物治疗；7例患者接受布舍瑞林（1600微克/天）治疗，随后改用长效曲普瑞林（60微克/千克/26 - 28天）；7例患者接受长效曲普瑞林（60微克/千克/26 - 28天）治疗；平均治疗年龄为6.2岁（范围2.7 - 7.8岁）；治疗在平均10.1岁（范围8.7 - 11.3岁）时停止；最终身高在平均13.4岁（范围12.0 - 14.9岁）时达到。第2组：9例（平均年龄6.5岁，范围4.8 - 7.7岁）进展缓慢型CPP患者未接受治疗进行随访；最终身高在平均13.6岁（范围12.5 - 14.8岁）时达到。在所有患者达到最终身高时测量腰椎BMD（采用双能X线吸收法测量L2 - L4）。在第1组中，最终身高（158.9±5.4厘米）显著高于治疗前预测身高（153.5±7.2厘米，P < 0.001），但显著低于父母身高中位数（163.2±6.2厘米，P < 0.005）。根据治疗停止时的骨龄（即≤11.5岁，n = 5，或≥12.0岁，n = 9）对第1组女孩进行细分，前一组患者的最终身高显著高于后一组（163.7±3.9厘米对156.5±4.6厘米，P < 0.02）。在第2组中，最终身高（161.8±4.6厘米）与治疗前预测身高（163.1±6.2厘米，P = 无显著性差异）相似，且与父母身高中位数（161.0±5.9厘米）无显著差异。BMD值（第1组：1.11±0.14克/平方厘米，第2组：1.22±0.08克/平方厘米）与对照组（1.·18±0.10克/平方厘米；n = 20，年龄16.3 - 20.5岁）及患者母亲（第·1组：1.16±0.07克/平方厘米，n = 11，年龄32.9 - 45.1岁；第2组：1.20±0.08克/平方厘米，n = 7，年龄33.5 - 46.5岁）无显著差异。在第1组中，骨龄≤11.5岁时停止治疗的女孩的BMD（1.22±0.10克/平方厘米）显著高于骨龄≥12.0岁时停止治疗的女孩（1.04±0.12克/平方厘米，P < 0.05）。
在进展性CPP女孩中，用GnRH类似物长期治疗可提高最终身高。一部分CPP患者不需要治疗，因为身材发育良好（进展缓慢型）。在CPP中，青春期异常启动及长期GnRH类似物治疗不会损害峰值骨量的获得。在接受GnRH治疗的患者中，在适合青春期启动的骨龄时停止治疗可能会同时改善最终身高和峰值骨量。
