DOI QR코드

DOI QR Code

성조숙증 혹은 조기 사춘기가 있는 여아에서 단기간의 성선자극호르몬 방출호르몬 효능약제 사용이 골밀도에 미치는 영향

Effect of GnRH analogue on the bone mineral density of precocious or early pubertal girls

  • 임정숙 (충북대학교 의과대학 소아과학교실) ;
  • 한헌석 (충북대학교 의과대학 소아과학교실)
  • Lim, Jeong Sook (Department of Pediatrics, Chungbuk National University, College of Medicine) ;
  • Han, Heon-Seok (Department of Pediatrics, Chungbuk National University, College of Medicine)
  • 투고 : 2009.07.14
  • 심사 : 2009.11.03
  • 발행 : 2009.12.15

초록

목 적:성선자극호르몬 효능약제로 성조숙증을 치료하는 동안에 성선자극호르몬이 억제되고 성선 스테로이드가 감소되면 사춘기 발달동안의 골량에 좋지 않은 영향을 미칠 수가 있어, 성조숙증 혹은 조기 성성숙이 있는 여아에서 성선자극호르몬 효능약제 단독 혹은 성장호르몬과 같이 사용하여 치료하는 경우에 단기간 동안의 골밀도의 변화가 어떠한지를 알아보고자 하였다. 방 법:성장클리닉을 방문한 여아들 중 특발성 성조숙증 혹은 조기 성성숙을 보이며 역연령에 비하여 골연령이 증가되어 있는 여아 40명(역연령 $9.0{\pm}1.5$세, 골연령 $11.6{\pm}1.3$년)을 대상으로, 26명은 성선자극호르몬 효능약제 단독으로 치료하였고(Group I), 14명은 성장호르몬과 병합요법(Group II)으로 치료하였다. 치료 전후에 골연령과 골밀도를 구하고, 역연령과 골연령에 대한 골밀도를 비교하였다. 결 과:전체 환아에서 치료 전후에 역연령으로 비교한 골밀도는 정상범위에 있었으나, 골연령으로 비교해 보면 정상범위에 비하여 감소되어 있었다(P<0.05). 치료기간 동안의 골밀도의 표준편차점수는 역연령 기준으로는 변화가 없었으나, 골연령 기준으로는 의미 있는 증가를 보였다(P<0.05). 치료 전후에 성선자극호르몬 효능약제 단독 치료군의 골밀도 표준편차점수는 역연령 혹은 골연령 기준으로 변화가 없었으나, 성장호르몬 병합 치료군의 골밀도 표준편차점수는 역연령 기준에는 변화가 없었으나 골연령 기준으로는 의미 있는 증가를 보였다(P<0.05). 결 론:성선자극호르몬 방출호르몬 효능약제를 사용하는 동안 역연령에 따른 골밀도의 저하는 관찰되지 않았으나, 골연령에 따른 골밀도의 저하는 관찰되어, 투약 중단 후 성선 기능이 회복되면 골밀도의 정상화의 가능성에 대한 추적 관찰이 필요하겠다. 한편으로는 성장호르몬을 같이 치료한 경우에는 치료 경과 중 골밀도의 의미 있는 증가를 볼 수 있어 성선자극호르몬 효능약제를 사용할 때 고려해야 할 사항으로 보인다.

Purpose:Treatment of precocity with gonadotropin releasing hormone analogue (GnRHa) might theoretically exert a detrimental effect on the bone mass during pubertal development. We investigated the short-term changes in bone mineral density (BMD) during GnRHa treatment and the enhancement in the changes with the co-administration of GnRHa and human growth hormone (hGH). Methods:Forty girls with precocious or early puberty who were using GnRHa for more than 1 year were enrolled. Of them, 14 concurrently received hGH. Lumbar bone mineral density was measured before and after the treatment, and bone mineral density-standard deviation scores (BMD-SDSs) were compared according to chronologic age (CA) and bone age (BA), as well as according to the administration of GnRHa alone (Group I) or the co-administration of hGH and GnRHa (Group II). Results:BMDs before and after treatment were in the normal range according to CA but were significantly lower according to BA (P<0.05). During treatment, BMD-SDSs did not change according to CA but significantly increased according to BA (P<0.05). BMD-SDSs in group I did not change during treatment according to CA or BA, while those in group II increased significantly according to BA (P<0.05), but not according to CA. Conclusion:Lumbar BMD was adequate according to CA at initial manifestation of precocity but was lower if compared to BA, that is, BMD did not increase with BA. Because co-treatment with hGH significantly increased BMD-SDSs according to BA, hGH co-treatment could be considered during GnRHa therapy.

키워드

과제정보

연구 과제 주관 기관 : Chungbuk National University

참고문헌

  1. Crowley WF Jr, Comite F, Vale W, Rivier J, Loriaux DL, Cutler GB Jr. Therapeutic use of pituitary desensitization with a long-acting LHRH agonist : a potential new treatment for idiopathic precocious puberty. J Clin Endocrinol Metab 1981; 52:370-2 https://doi.org/10.1210/jcem-52-2-370
  2. Conn PM, Crowley WF Jr. Gonadotropin-releasing hormone and its analogs. Annu Rev Med 1994;45:391-405 https://doi.org/10.1146/annurev.med.45.1.391
  3. Carrel AL, Allen DB. Effects of growth hormone on body composition and bone metabolism. Endocrine 2000;12:163- 72 https://doi.org/10.1385/ENDO:12:2:163
  4. Saggese G, Bertelloni S, Baroncelli GI, Battini R, Franchi G. Reduction of bone mineral density: an effect of gonadotropin releasing hormone analogue treatment in central precocious puberty. Eur J Pediatr 1993;152:712-20 https://doi.org/10.1007/BF01953981
  5. Bertelloni S, Baroncelli GI, Sorrentino MC, Perri G, Saggese G. Effect of central precocious puberty and gonadotropin-releasing hormone analogue treatment on peak bone mass and final height in females. Eur J Pediatr 1998;157:363-7 https://doi.org/10.1007/s004310050831
  6. Antoniazzi F, Zamboni G, Bertoldo F, Lauriola S, Tato L. Bone development during GH and GnRH analog treatment. Eur J Endocrinol 2004;151:S47-S54 https://doi.org/10.1530/eje.0.151S047
  7. Gleulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist. 2nd ed. California : Stanford University Press, 1971
  8. Barden HS, Wacker WK, Faulkner KG, GE Healthcare. Pediatric DXA enhancements: variable standard deviations, total body skull exclusion. Annual meeting of International Society for Clinical Densitometry; 2005 Feb; New Orleans. Available from: URL://http://www.iscd.org/Visitors/conferences/index 05.cfm
  9. Lim JS, Hwang JS, Park KD, Lee JA, Kim DH, Cheon GJ, et al. Bone mineral density according to age, bone age, and pubertal stages in Korean children and adolescents. J Clin Densitom 2009; in press https://doi.org/10.1016/j.jocd.2009.09.006
  10. Gordon CL, Holton JM, Atkinson SA, Webber CE. The contributions of growth and puberty to peak bone mass. Growth Dev Aging 1991;55:257-62
  11. Lu PW, Briody JN, Ogle GD, Morley K, Humphries IR, Allen J, et al. Bone mineral density of total body, spine and femoral neck in children and young adults: a cross sectional and longitudinal study. J Bone Miner Res 1994;9:1451-8 https://doi.org/10.1002/jbmr.5650090918
  12. Finkelstein JS, Neer RM, Biller BM, Crawford JD, Klibanski A. Osteopenia in men with a history of delayed puberty. N Engl J Med 1992;326:600-4 https://doi.org/10.1056/NEJM199202273260904
  13. Constantini NW, Warren MP. Special problems of the female athlete. Baillieres Clin Rheumatol 1994;8:199-19 https://doi.org/10.1016/S0950-3579(05)80232-8
  14. Parfitt AM. The two faces of growth: benefits and risks to bone integrity. Osteoporos Int 1994;4:382-98 https://doi.org/10.1007/BF01622201
  15. Antoniazzi F, Bertoldo F, Zamboni G, Valentini R, Sirpresi S, Cavallo L, et al. Bone mineral metabolism in girls with precocious puberty during gonadotropin releasing hormone agonist treatment. Eur J Endocrinol 1995;133:412-7 https://doi.org/10.1530/eje.0.1330412
  16. Ruiz JC, Mandel C, Garabedian M. Influence of spontaneous calcium intake and physical exercise on the vertebral and femoral bone mineral density of children and adolescents. J Bone Miner Res 1995;10:675-82 https://doi.org/10.1002/jbmr.5650100502
  17. Johnston CC Jr, Miller JZ, Siemenda CW, Rester TK, Hui S, Christian JC, Peacock M. Calcium supplementation and increase in bone mineral density in children. N Engl J Med 1992;327:82-7 https://doi.org/10.1056/NEJM199207093270204
  18. Antoniazzi F, Zamboni G, Bertoldo F, Lauriola S, Mengarda F, Pietrobelli A, et al. Bone mass at final height in precocious puberty after gonadotropin-releasing hormone agonist with and without calcium supplementation. J Clin Endocrinol Metab 2003;88:1096-101 https://doi.org/10.1210/jc.2002-021154
  19. Pasquino AM, Pucarelli I, Accardo F, Demiraj V, Segni M, Di Nardo R. Long-term observation of 87 girls with idiopathic central precocious puberty treated with gonadotropin-releasing hormone analogs: Impact on adult height, body mass index, bone mineral content and reproductive function. J Clin Endocrinol Metab 2008;93:190-5 https://doi.org/10.1210/jc.2007-1216
  20. Saggese G, Federico G, Barsanti S, Cerri S. Is there a place for combined therapy with GnRH agonist plus growth hormone in improving final height in short statured children? J Pediatr Endocrinol Metab 2000;13 Suppl 1:821-6
  21. Saggese G, Federico G, Barsanti S, Fiore L. The effect of administering gonadotropin-releasing hormone agonist with recombinant-human growth hormone (GH) on the final height of girls with isolated GH deficiency: results from a controlled study. J Clin Endocrinol Metab 2001;86:1900-4 https://doi.org/10.1210/jc.86.5.1900
  22. Lanes R. Growth velocity, final height and bone mineral metabolism of short children treated long term with growth hormone. Curr Pharm Biotechnol 2000;1:33-46 https://doi.org/10.2174/1389201003378997
  23. Lanes R, Gunczler P, Esaa S, Weisinger JR. The effect of short- and long-term growth hormone treatment on bone mineral density and bone metabolism of prepubertal children with idiopathic short stature: a 3-year study. Clin Endocrinol 2002;57:725-30 https://doi.org/10.1046/j.1365-2265.2002.01614.x
  24. Bertelloni S, Baroncelli GI, Ferdeghini M, Menchini-Fabris F, Saggese G. Final height, gonadal function and bone mineral density of adolescent males with central precocious puberty after therapy with gonadotropin-releasing hormone analogues. Eur J Pediatr 2000;159:369-74 https://doi.org/10.1007/s004310051289