Growth hormone deficiency, its influence on bone mineral density and incidence of osteoporotic fractures
Authors:
Martin Kužma; Juraj Payer
Authors place of work:
Univerzita Komenského v Bratislave, Lekárska fakulta, V. interná klinika FNsP, Slovenská republika
Published in the journal:
Čas. Lék. čes. 2010; 149: 211-216
Category:
Review Article
Summary
Growth hormone (GH) is the most abundant hormone from all pituitary hormones. Linear bone growth increases as a result of complex hormonal reactions, in particular as an effect of insulin-like growth factor I (IGF I). GH has a key role in longitudinal bone growth and in reaching peak bone mass (PBM) during childhood and adolescence. PBM is a important risk predictor of osteoporotic fractures. Despite closure of epiphyseal growth plates, effect of GH/IGF on bone turnover, bone mass, bone density and strength lasts by regulation of bone remodelation. Many authors have observed low BMD in hypopituitarismus, especially in growth hormone deficient (GHD) patients. Initially reduction of BMD has been described after 6–12 months of therapy with growth hormone. When therapy continued, BMD has normalized or was even higher in comparison with the beginning of the therapy. Reduction in BMD results from increased remodelation space after enhanced activation of bone turnover during GH therapy. Decrease in bone growth and PBM also influences incidence of fractures in elderly patients. It has been shown, that 18–24 months of GH therapy slightly increased BMD in a group of adult men with adult onset of GHD (AO-GHD), whereas in women it has not significantly changed. Three previous studies have proved increased fracture risk in patients with GHD. Not only high number of patients, but also an applicable control group, confirmation of potential risk factors such as BMI, smoking, sex, calcium intake and physical activity are needed to estimate the risk of fractures. Holmer et al. have analysed fracture incidence in GHD patients on replacement therapy compared to normal population. No increase of fracture risk in AO GHD women has been observed, but GHD was associated with higher fracture risk in women with childhood onset of GHD (CO GHD). Men have even lower incidence of fractures matched with control group. There are also sexual differences in effects of GH on bone. Women have in general higher levels of GH secretion, but the normal range for serum IGF-I is similar in men and women. In a placebo controlled double blind study, where men and women with GHD received the same dose of GH on m2/body, the increase of serum IGF-I levels was higher in men. Possible explanation for sexual differences in response to GH therapy is that sexual hormones affect GH secretion.
Key words:
growth hormone, IGF-I, bone density, peak bone mass, fractures.
Zdroje
1. Mohsen S, Eledrisi, MD. FACP, FACE, Consultant, Department of Internal Medicine, Division of Endocrinology and Metabolism. King Abdulaziz National Guard Medical Center, Saudi Arabia 2009
2. Kužma M, Payer J. Deficit rastového hormónu v dospelosti. Slovenský lekár, 2009; 19(33): 131–138.
3. Rizzoli R, Bonjour JP. Determinants of peak bone mass and mechanisms of bone loss. Osteoporos Int 1999; 9 (Suppl. 2): S17–S23.
4. Ohlsson C, Bengtsson BA, Isaksson OG, Andreassen TT, Slootweg MC. Growth hormone and bone. Endocr Rev 1998; 19(1): 55–79.
5. Bouillon R. Growth hormone and bone. Horm Res 1991; 36 (Suppl. 1): 49–55.
6. de Boer H, Blok GJ, van der Veen, EA. Clinical aspects of growth hormone deficiency in adults. Department of Endocrinology, Free University Hospital, Amsterdam, The Netherlands. Endocr Rev 1995; 16(1): 63–86.
7. Johansson AG, Burman P, Westermark K, Ljunghall S. The bone mineral density in acquired growth hormone deficiency correlates with circulating levels of insulin-like growth factor I. J Intern Med 1992; 232(5): 447–452.
8. Holmes SJ, Economou G, Whitehouse RW, Adams JE, Shalet SM. Reduced bone mineral density in patients with adult onset growth hormone deficiency. J Clin Endocrinol Metab 1994; 78(3): 669–674.
9. Kaufman JM, Taelman P, Vermeulen A, Vandeweghe M. Bone mineral status in growth hormone-deficient males with isolated and multiple pituitary deficiencies of childhood onset. J Clin Endocrinol Metab 1992; 74(1): 118–123.
10. Attanasio AF, Lamberts SW, Matranga AM, Birkett MA, Bates PC, Valk NK, Hilsted J, Bengtsson BA, Strasburger CJ. Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. Adult Growth Hormone Deficiency Study Group. J Clin Endocrinol Metab 1997; 82(1): 82–88.
11. Rosén T, Hansson T, Granhed H, Szucs J, Bengtsson BA. Reduced bone mineral content in adult patients with growth hormone deficiency. Acta Endocrinol (Copenh) 1993; 129(3): 201–206.
12. Whitehead HM, Boreham C, McIlrath EM, Sheridan B, Kennedy L, Atkinson AB, Hadden DR. Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled cross-over study. Clin Endocrinol (Oxf) 1992; 36(1): 45–52.
13. Binnerts A, Swart GR, Wilson JH, Hoogerbrugge N, Pols HA, Birkenhager JC, Lamberts SW. The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition. Clin Endocrinol (Oxf) 1992; 37(1): 79–87.
14. Vandeweghe M, Taelman P, Kaufman JM. Short and long-term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone-deficient males. Clin Endocrinol (Oxf) 1993; 39(4): 409–415.
15. Johansson AG, Engström BE, Ljunghall S, Karlsson FA, Burman P. Gender differences in the effects of long term growth hormone (GH) treatment on bone in adults with GH deficiency. J Clin Endocrinol Metab 1999; 84(6): 2002–2007.
16. Johansson G, Rosen T, Bosaeus I, Sjostrom L, Bengtsson B‑A. Two zears of growth hormone treatment increases bone mineral content and density in hypopituitary patients with adult-onset GH deficiency. J Clin endocrinol Metab 1996; 81: 2865–2873.
17. Baum HBA, Biller BMK, Finkelstein JS, Baker CK, Oppenhein DS, Schoenfeld DA, Hoskins MT, Wittink H, Klibanski A. Effects of physiologic growth hormone therapy on bone density and body composition in patients with adult onset growth hormone deficiency. A randomized, placebo-controlled trial. Ann Intern Med 1996; 125: 883–890.
18. Välimäki MJ, Salmela PI, Salmi J, Viikari J, Kataja M, Turunen H, Soppi E. Effects of 42 months of GH treatment on bone mineral density and bone turnover in GH-deficient adults. Eur J Endocrinol 1999; 140(6): 545–554.
19. Janssen YJ, Hamdy NA, Frölich M, Roelfsema F. Skeletal effects of two years of treatment with low physiological doses of recombinant human growth hormone (GH) in patients with adult-onset GH deficiency. J Clin Endocrinol Metab 1998; 83(6): 2143–2418.
20. Longobardi S, Di Rella F, Pivonello R, Di Somma C, Klain M, Maurelli L, Scarpa R, Colao A, Merola B, Lombardi G. Effects of two years of growth hormone (GH) replacement therapy on bone metabolism and mineral density in childhood and adulthood onset GH deficient patients. J Endocrinol Invest 1999; 22(5): 333–339.
21. Kann P, Piepkorn B, Schehler B, Andreas J, Lotz J, Prellwitz W, Beyer J. Effect of long-term treatment with GH on bone metabolism, bone mineral density and bone elasticity in GH‑deficient adults. Clin Endocrinol (Oxf) 1998; 48(5): 561–568.
22. Holmes SJ, Whitehouse RW, Economou G, O’Halloran DJ, Adams JE, Shalet SM. Further increase in forearm cortical bone mineral content after discontinuation of growth hormone replacement. Clin Endocrinol (Oxf) 1995; 42(1): 3–7.
23. Rahim A, Holmes SJ, Adams JE, Shalet SM. Long-term change in the bone mineral density of adults with adult onset growth hormone (GH) deficiency in response to short or long-term GH replacement therapy. Clin Endocrinol (Oxf) 1998; 48(4): 463–469.
24. Seeman E, Hopper JL, Bach LA, Cooper ME, Parkinson E, McKay J, Jerums G. Reduced bone mass in daughters of women with osteoporosis. N Engl J Med 1989; 320(9): 554–558.
25. Wüster C, Slenczka E, Ziegler R. Increased prevalence of osteoporosis and arteriosclerosis in conventionally substituted anterior pituitary insufficiency: Is there a need for additional growth hormone substitution? (In German). Klin Wochenschr 1991; 69: 769–773.
26. Rosén T, Wilhelmsen L, Landin-Whilhelmsen K, Lappas G, Bengtsson BA. Increased fracture frequency in adult patients with hypopituitarism and GH deficiency. Eur J Endocrinol 1997; 137: 240–245.
27. Wüster C, Abs R, Bengtsson BĀ, Bennmarker H, Feldt-Rasmussen U, Hernberg-StĆhl E, Monson JP, Westberg B, Wilton P on behalf of the KIMS study group the KIMS international board. The influence of growth hormone deficiency, growth hormone replacement therapy and other aspects of hypopituitarism on fracture rate and bone mineral density. J Bone Miner Res 2001; 2: 398–405.
28. Wang MC, Bachrach LK, Van Loan M, Hudes M, Flegal KM, Crawford PB. The relative contribution of lean tissue mass and fat mass to bone density in young women. Bone 2005; 37: 474–481.
29. De Laet C, Kanis JA, Odén A, Johanson H, Johnell O, Delmas P, Eisman JA, Kroger H, Fujiwara S, Garnero P, McCloskey EV, Mellstrom D, Melton LJ III, Meunier PJ, Pols HAP, Reeve J, Silman A, Tenenhouse A. Body mass index as a predictor of fracture risk: A meta-analysis. Osteoporos Int 2005; 16: 1330–1338.
30. Kiel DP, Zhang Y, Hannan MT, Anderson JJ, Baron JA, Felson DT. The effect of smoking at different life stages on bone mineral density in elderly men and women. Osteoporos Int 1996; 6: 240–248.
31. Becker W, Pearson M. Riksmaten 1997–1998, National Food Administration 1998.
32. Slemenda CW, Miller JZ, Hui SL, Reister TK, Johnston CC Jr. Role of physical activity in the development of skeletal mass in children. J Bone Miner Res 1991; 6: 1227–1233.
33. Davee AM, Rosen CJ, Adler RA. Exercise patterns and trabecular bone density in college women. J Bone Miner Res 1990; 5: 245–250.
34. Margulies JY, Simkin A, Leichter I, Bivas A, Steinberg R, Giladi M, Stein M, Kashtan H, Milgrom C. Effect of intense physical activity on the bone-mineral content in the lower limbs of young adults. J Bone Joint Surg Am 1986; 68: 1090–1093.
35. Holmer H, Svensson J, Rylander L, Johannsson G, Rosén T, Bengtsson BA, Thorén M, Höybye C, Degerblad M, Bramnert M, Hägg E, Engström BE, Ekman B, Thorngren KG, Hagmar L, Erfurth EM. Fracture incidence in GH-deficient patients on complete hormone replacement including GH. J Bone Miner Res 2007; 22(12): 1842–1850.
36. Holmer H, Svensson J, Rylander L, Johannsson G, Rosén T, Bengtsson BA, Thorén M, Höybye C, Degerblad M, Bramnert M, Hägg E, Engström BE, Ekman B, Thorngren KG, Hagmar L, Erfurth EM. Fracture incidence in GH-deficient patients on complete hormone replacement including GH. J Bone Miner Res 2007; 22(12): 1842–1850.
37. Brixen K, Nielsen HK, Mosekilde L, Flyvbjerg A. A short course of recombinant human growth hormone treatment stimulates osteoblasts and activates bone remodeling in normal human volunteers.J Bone Miner Res 1990; 5(6): 609–618.
38. Johansson AG, Lindh E, Blum WF, Kollerup G, SŅrensen OH, Ljunghall S. Effects of growth hormone and insulin-like growth factor I in men with idiopathic osteoporosis. J Clin Endocrinol Metab 1996; 81(1): 44–48.
39. Nielsen HK, JŅrgensen JO, Brixen K, Christiansen JS. Serum osteocalcin and bone isoenzyme alkaline phosphatase in growth hormone-deficient patients: dose-response studies with biosynthetic human GH. Calcif Tissue Int 1991; 48(2): 82–87.
40. Jensen LT, Jorgenssen JOL, Risteli J, Christiansen JS, Lorenzen I. Type I and III procolagen propeptides in growth hormone-deficient patients: Effects of increasing doses of GH. Acta Endocrinol (Copenh) 1991; 124: 278–282.
41. Eden EB, Karlsson FA, Wide L. Marked gender differences in ambulatory morning growth hormone values in young adults. Clin Chem 1998; 44: 1289–1295.
42. Jansson JO, Edén S, Isaksson O. Sexual dimorphism in the control of growth hormone secretion. Endocr Rev 1985; 6(2): 128–150.
43. Juul A, Bang P, Hertel NT, Main K, Dalgaard P, JŅrgensen K, Müller J, Hall K, Skakkebaek NE. Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab 1994; 78(3): 744–752.
44. Burman P, Johansson AG, Siegbahn A, Vessby B, Karlsson FA. Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. J Clin Endocrinol Metab 1997; 82(2): 550–555.
45. Cook DM, Ludlam WH, Cook MB. Route of estrogen administration helps to determine growth hormone (GH) replacement dose in GH-deficient adults. J Clin Endocrinol Metab 1999; 84(11): 3956–3960.
Štítky
Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management Dental HygienistČlánok vyšiel v časopise
Journal of Czech Physicians
- Metamizole at a Glance and in Practice – Effective Non-Opioid Analgesic for All Ages
- Advances in the Treatment of Myasthenia Gravis on the Horizon
- Metamizole vs. Tramadol in Postoperative Analgesia
- Spasmolytic Effect of Metamizole
- What Effect Can Be Expected from Limosilactobacillus reuteri in Mucositis and Peri-Implantitis?
Najčítanejšie v tomto čísle
- Shy-Drager syndrome
- Means of early diagnostics and subsequent care for critically ill patient
- Buchvald D. Contact dermatitis and atopic dermatitis – rare comorbidity?
- Growth hormone deficiency, its influence on bone mineral density and incidence of osteoporotic fractures