BADERC-Anne Klibanski

Anne Klibanski, M.D.

Growth Hormone and IGF-1 Actions on Bone Metabolism and Cardiovascular Risk

A major research focus in the Neuroendocrine Unit is the role of growth hormone (GH) and IGF-1 on bone metabolism. We have identified severe osteopenia in patients with GH deficiency as well as in patients with acquired GH resistance and IGF-1 deficiency due to undernutrition. The effects of GH action on osteoblast function in such groups is under investigation as is the use of rhIGF-1 to reverse these effects. Short-term studies have identified a specific stimulatory effect on osteoblast function during rhIGF-1 administration. Studies are underway to determine the chronic effects of rhIGF-l administration on bone mass and its relationship to gonadal steroids. A second area focuses on the investigation of the effects of GH deficiency and rhGH administration on cardiovascular risk, specifically effects on inflammatory markers. CRP levels are markedly elevated in patients with acquired GH deficiency and we have shown that they improve markedly following physiologic GH administration. Growth hormone deficiency is associated with abnormalities in insulin action and effects of GH administration on these parameters is also under investigation.

References:

1. Grinspoon S, Baum H, Peterson S, Klibanski A. Effects of rhIGF-I administration on bone turnover during short-term fasting. J Clin Invest. 1995; 96:900-6.

2. Baum HBA, Biller BMK, Katznelson L, Oppenheim DS, Clemmons DR, Cannistraro KB, Schoenfeld DA, Best SA, Klibanski A. Assessment of growth hormone (GH) secretion in men with adult-onset GH deficiency compared with normal men. J Clin Endocrinol Metab. 1996; 81:84-92.

3. Grinspoon S, Baum H, Lee K, Anderson E, Herzog D, Klibanski A. Effects of short-term recombinant human insulin-like growth factor administration on bone turnover in osteopenic women with anorexia nervosa. J Clin Endocrinol Metab. 1996; 81:3864-70.

4. Grinspoon S, Gulick T, Askari H, Landt M, Lee K, Anderson E, Ma Z, Vignati L, Bowsher R, Herzog D, Klibanski A. Serum leptin levels in women with anorexia nervosa. J Clin Endocrinol Metab. 1996; 81: 3861-3.

5. Baum HBA, Biller BMK, Finkelstein JS, Cannistraro KB, Oppenheim DS, Schoenfeld DA, Michel TH, Wittink H, Klibanski A. Effects of physiologic growth hormone on bone density and body composition in patients with adult-onset growth hormone deficiency: A randomized controlled trial. Ann Int Med. 1996;125-883-90.

6. Miller KK, Parulekar MS, Schoenfeld E, Anderson E, Hubbard J, Klibanski A, Grinspoon SK. Decreased leptin levels in normal weight women with hypothalamic amenorrhea: The effects of body composition and nutritional intake. J Clin Endocrinol Metab. 1998; 83:2309-12.

7. Soyka LA, Grinspoon S, Levitsky LL, Herzog DB, Klibanski A. The effects of anorexia nervosa on bone metabolism in female adolescents. J Clin Endocrinol Metab. 1999; 84: 4489-96.

8. Biller BMK, Sesmilo G, Baum HBA, Hayden D, Schoenfeld D, Klibanski A. Withdrawal of long-term physiologic growth hormone (GH) administration: Differential effects on bone density and body composition in men with adult-onset GH deficiency. J Clin Endocrinol Metab. 2000; 85:970-6.

9. Trainer PJ, Drake WM, Katznelson L, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. New Engl J Med. 2000; 342:1171-7.

10. Sesmilo G, Biller BMK, Llevadot J, Rifai N, Hanson G, Hayden D, Klibanski A. Effects of growth hormone (GH) administration on inflammatory and other cardiovascular risk markers in men with GH deficiency. Ann Intern Med. 2000; 133:111-22.

11. Miller KK, Grinspoon S, Klibanski A. The effects of estrogen-deficiency on cardiovascular risk factors in hypothalamic amenorrhea. Clin Endo. 2000; 53:359-6

12. Grinspoon S, Thomas E, Pitts S, Gross E, Mickley D, Miller K, Herzog D, Klibanski A. Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa. Ann Int Med. 2000; 133:790-4.

13. Sesmilo G, Biller BMK, Llevadot J, Hayden D, Hanson G, Rifai N, Klibanski A. Effects of growth hormone (GH) administration on homocyst(e)ine levels in men with GH deficiency. A randomized controlled trial. J Clin Endocrinol Metab. 2001; 86:1518-24.

14. Sesmilo G, Miller KK, Hayden D, Klibanski A. Inflammatory cardiovascular risk markers in women with hypopituitarism. J Clin Endocrinol Metab. 2001; 86:5774-81.

15. Sesmilo G, Fairfield W, Katznelson L, Pulaski K, Freda PU, Bonert V, Dimarki E, Stavrou S, Vance ML, Hayden D, and Klibanski A. Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant. J Clin Endocrinol Metab. 2002; 87:1692-9.

16. Grinspoon S, Thomas L, Miller K, Herzog D, Klibanski A. Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J Clin Endocrinol Metab. 2002; 87(6): 2883-9.

17. Soyka LA, Misra M, Frenchman A, Miller KK, Grinspoon S, Schoenfeld DA, Klibanski A. Abnormal bone mineral accrual in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab. 2002; 87:4177-85.

18. Misra M, Miller KK, Bjornson J, Hackman A, Aggarwal A, Chung J, Ott M, Herzog DB, Johnson ML, Klibanski A. Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. 2003. (In Press).






			Anne Klibanski, M.D. Growth Hormone and IGF-1 Actions on Bone Metabolism and Cardiovascular Risk A major research focus in the Neuroendocrine Unit is the role of growth hormone (GH) and IGF-1 on bone metabolism. We have identified severe osteopenia in patients with GH deficiency as well as in patients with acquired GH resistance and IGF-1 deficiency due to undernutrition. The effects of GH action on osteoblast function in such groups is under investigation as is the use of rhIGF-1 to reverse these effects. Short-term studies have identified a specific stimulatory effect on osteoblast function during rhIGF-1 administration. Studies are underway to determine the chronic effects of rhIGF-l administration on bone mass and its relationship to gonadal steroids. A second area focuses on the investigation of the effects of GH deficiency and rhGH administration on cardiovascular risk, specifically effects on inflammatory markers. CRP levels are markedly elevated in patients with acquired GH deficiency and we have shown that they improve markedly following physiologic GH administration. Growth hormone deficiency is associated with abnormalities in insulin action and effects of GH administration on these parameters is also under investigation. References: 1. Grinspoon S, Baum H, Peterson S, Klibanski A. Effects of rhIGF-I administration on bone turnover during short-term fasting. J Clin Invest. 1995; 96:900-6. 2. Baum HBA, Biller BMK, Katznelson L, Oppenheim DS, Clemmons DR, Cannistraro KB, Schoenfeld DA, Best SA, Klibanski A. Assessment of growth hormone (GH) secretion in men with adult-onset GH deficiency compared with normal men. J Clin Endocrinol Metab. 1996; 81:84-92. 3. Grinspoon S, Baum H, Lee K, Anderson E, Herzog D, Klibanski A. Effects of short-term recombinant human insulin-like growth factor administration on bone turnover in osteopenic women with anorexia nervosa. J Clin Endocrinol Metab. 1996; 81:3864-70. 4. Grinspoon S, Gulick T, Askari H, Landt M, Lee K, Anderson E, Ma Z, Vignati L, Bowsher R, Herzog D, Klibanski A. Serum leptin levels in women with anorexia nervosa. J Clin Endocrinol Metab. 1996; 81: 3861-3. 5. Baum HBA, Biller BMK, Finkelstein JS, Cannistraro KB, Oppenheim DS, Schoenfeld DA, Michel TH, Wittink H, Klibanski A. Effects of physiologic growth hormone on bone density and body composition in patients with adult-onset growth hormone deficiency: A randomized controlled trial. Ann Int Med. 1996;125-883-90. 6. Miller KK, Parulekar MS, Schoenfeld E, Anderson E, Hubbard J, Klibanski A, Grinspoon SK. Decreased leptin levels in normal weight women with hypothalamic amenorrhea: The effects of body composition and nutritional intake. J Clin Endocrinol Metab. 1998; 83:2309-12. 7. Soyka LA, Grinspoon S, Levitsky LL, Herzog DB, Klibanski A. The effects of anorexia nervosa on bone metabolism in female adolescents. J Clin Endocrinol Metab. 1999; 84: 4489-96. 8. Biller BMK, Sesmilo G, Baum HBA, Hayden D, Schoenfeld D, Klibanski A. Withdrawal of long-term physiologic growth hormone (GH) administration: Differential effects on bone density and body composition in men with adult-onset GH deficiency. J Clin Endocrinol Metab. 2000; 85:970-6. 9. Trainer PJ, Drake WM, Katznelson L, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. New Engl J Med. 2000; 342:1171-7. 10. Sesmilo G, Biller BMK, Llevadot J, Rifai N, Hanson G, Hayden D, Klibanski A. Effects of growth hormone (GH) administration on inflammatory and other cardiovascular risk markers in men with GH deficiency. Ann Intern Med. 2000; 133:111-22. 11. Miller KK, Grinspoon S, Klibanski A. The effects of estrogen-deficiency on cardiovascular risk factors in hypothalamic amenorrhea. Clin Endo. 2000; 53:359-6 12. Grinspoon S, Thomas E, Pitts S, Gross E, Mickley D, Miller K, Herzog D, Klibanski A. Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa. Ann Int Med. 2000; 133:790-4. 13. Sesmilo G, Biller BMK, Llevadot J, Hayden D, Hanson G, Rifai N, Klibanski A. Effects of growth hormone (GH) administration on homocyst(e)ine levels in men with GH deficiency. A randomized controlled trial. J Clin Endocrinol Metab. 2001; 86:1518-24. 14. Sesmilo G, Miller KK, Hayden D, Klibanski A. Inflammatory cardiovascular risk markers in women with hypopituitarism. J Clin Endocrinol Metab. 2001; 86:5774-81. 15. Sesmilo G, Fairfield W, Katznelson L, Pulaski K, Freda PU, Bonert V, Dimarki E, Stavrou S, Vance ML, Hayden D, and Klibanski A. Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant. J Clin Endocrinol Metab. 2002; 87:1692-9. 16. Grinspoon S, Thomas L, Miller K, Herzog D, Klibanski A. Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J Clin Endocrinol Metab. 2002; 87(6): 2883-9. 17. Soyka LA, Misra M, Frenchman A, Miller KK, Grinspoon S, Schoenfeld DA, Klibanski A. Abnormal bone mineral accrual in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab. 2002; 87:4177-85. 18. Misra M, Miller KK, Bjornson J, Hackman A, Aggarwal A, Chung J, Ott M, Herzog DB, Johnson ML, Klibanski A. Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism. 2003. (In Press).