70 Yaş ve Üzeri Erkek Cinsiyette Kemik Mineral Dansitesinin İnsülin Benzeri Büyüme Faktörü 1 ve Estradiol Düzeyleri ile İlişkisi

Abstract

Amaç: Osteoporoz düşük kemik kütlesi ve kemiğin mikromimarisinin bozulması ile karakterize bir hastalıktır. Kadınlarda osteoporozun daha sıklıkla görülmesi, erkeklerde göz ardı edilmesine yol açmıştır. Bu çalışmanın amacı, 70 yaş ve üzeri erkek cinsiyette kemik mineral dansitesinin insülin benzeri büyüme faktörü 1 (IGF-1) ve Estradiol düzeyleri ile ilişkisini değerlendirmektir. Gereç ve Yöntem: Çalışma, 2014-2015 arasında 28 hasta (osteoporoz ve osteopeni) ve 23 kontrol grubu olarak 51 kişi ile yapıldı. Vakaların diyette 3 günlük ortalama kalsiyum alımları ve fiziksel aktivite durumları kaydedildi. Kemik mineral yoğunluğu (KMY), albumine göre düzeltilmiş serum kalsiyum düzeyi (Alb-sCa), fosfor (P), paratiroid hormon (PTH), 25 (OH) D3 vitamini, total testesteron, estradiol (E2), IGF-1 ve 24 saatlik idrar Ca düzeyleri ölçüldü. Bulgular: Hasta ve kontrol grubu arasında yaş, vücut kitle indeksi (BMI), fiziksel aktivite ile Alb-sCa, P, PTH ve 24 saatlik idrar Ca düzeyleri yönünden fark bulunmazken (p>0.05); kontrol grubunun boy, kilo, 3 günlük ortalama kalsiyum alımları ile 25 (OH) D3 vitamini düzeyi anlamlı olarak yüksekti (p<0.05). Hasta grubunun Femur boyun ve Lomber total T skorları ile KMY kontrol grubuna göre daha düşüktü (p<0,05). Kontrol grubunun IGF-1 düzeyi 113,41±36,50 ng/ml iken hasta grubunun 99,62±35,20 ng/ml ölçüldü ancak fark istatistiksel olarak anlamlı bulunmadı (p=0.17). E2 düzeyi hasta grubunda 26,14±18,07 pmol/L, kontrol grubunda 35,83±15,49 pmol/L olup hasta grubunda anlamlı düşük görüldü (p=0,04). E2 düzeyinin Lomber total T skoru ile arasında anlamlı pozitif yönlü ilişki bulundu (p=0.02). Sonuç: Çalışmamızda gruplar arasında IGF-1 düzeyleri arasında anlamlı fark saptanmazken, E2’nin KMY üzerine etkisi aşikar bulunmuştur. Herhangi bir nedenle E2 düzeyi düşük erkeklerde KMY’nin azalacağı unutulmamalıdır. Anahtar kelimeler: Erkek, Osteoporoz, İnsülin benzeri büyüme faktörü 1, Estradiol.

Keywords

• Erkek
• Osteoporoz
• İnsülin benzeri büyüme faktörü 1
• Estradiol.

The Relationship of Bone Mineral Density with Insulin-like Growth Factor 1 and Estradiol Levels in Males Aged 70 and Over

Abstract

Aim: Osteoporosis is a disease characterized by low bone mass and deterioration of bone microarchitecture. The higher incidence of osteoporosis in women has led to its being overlooked in men. The aim of this study was to evaluate the relationship between bone mineral density and insulin-like growth factor 1 (IGF-1) and Estradiol levels in men aged 70 years and over. Material-Method: The study was conducted between 2014-2015 with 28 patients (osteoporosis and osteopenia) and 51 people as 23 control groups. The 3-day average dietary calcium intake and physical activity status of the cases were recorded. Bone mineral density (BMD), albumin-corrected serum calcium level (Alb-sCa), phosphorus (P), parathyroid hormone (PTH), vitamin 25 (OH) D3, total testosterone, estradiol (E2), IGF-1 and 24 hourly urinary Ca levels were measured. Results: While there was no difference between the patient and control groups in terms of age, body mass index (BMI), physical activity, Alb-sCa, P, PTH and 24-hour urinary Ca levels (p>0.05); Height, weight, 3-day average calcium intake and 25 (OH) D3 vitamin levels of the control group were significantly higher (p<0.05). Femur neck and Lumbar total T scores and BMD of the patient group were lower than the control group (p<0.05). While the IGF-1 level of the control group was 113.41±36.50 ng/ml, it was 99.62±35.20 ng/ml in the patient group, but the difference was not statistically significant (p=0.17). E2 level was 26.14±18.07 pmol/L in the patient group and 35.83±15.49 pmol/L in the control group, which was significantly lower in the patient group (p=0.04). A significant positive correlation was found between E2 level and Lumbar total T score (p=0.02). Conclusion: While no significant difference was found between the groups in IGF-1 levels in our study, the effect of E2 on BMD was found to be obvious. It should be noted that BMD will decrease in men with a low E2 level for any reason. Keywords: Male, Osteoporosis, Insulin-like growth factor 1, Estradiol.

Keywords

• Male
• Osteoporosis
• Insulin-like growth factor 1
• Estradiol.

References

1. 1. Aibar-Almazán A, Voltes-Martínez A, Castellote-Caballero Y, Afanador-Restrepo DF, Carcelén-Fraile MDC, López-Ruiz E. Current Status of the Diagnosis and Management of Osteoporosis. Int J Mol Sci. 2022;23(16):9465. Published 2022 Aug 21. doi:10.3390/ijms23169465.
2. 2. Tuzun S, Eskiyurt N, Akarirmak U, Saridogan M, Senocak M, Johansson H, et al. Turkish Osteoporosis Society. Incidence of hip fracture and prevalence of osteoporosis in Turkey: the FRACTURK study. Osteoporos Int. 2012; 23(3):949-955. doi: 10.1007/s00198-011-1655-5. PMID: 21594756.
3. 3. Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 2009; 301(5):513-521. doi: 10.1001/jama.2009.50. PMID: 19190316.
4. 4. Kelepouris N, Harper KD, Gannon F, Kaplan FS, Haddad JG. Severe osteoporosis in men. Ann Intern Med. 1995; 123(6):452-60. doi: 10.7326/0003-4819-123-6-199509150-00010. PMID: 7639446.
5. 5. Seeman E, Melton LJ 3rd, O'Fallon WM, Riggs BL. Risk factors for spinal osteoporosis in men. Am J Med. 1983 Dec;75(6):977-83. doi: 10.1016/0002-9343(83)90878-1. PMID: 6650552.
6. 6. Callewaert F, Boonen S, Vanderschueren D. Sex steroids and the male skeleton: a tale of two hormones. Trends Endocrinol Metab. 2010;21(2):89-95.
7. 7. LeBlanc ES, Nielson CM, Marshall LM, Lapidus JA, BarrettConnor E, Ensrud KE, et al. The effects of serum testosterone, estradiol, and sex hormone binding globulin levels on fracture risk in older men. J Clin Endocrinol Metab. 2009;94(9):3337-46.
8. 8. Szulc P, Munoz F, Claustrat B, Garnero P, Marchand F, Duboeuf F, et al. Bioavailable estradiol may be an important determinant of osteoporosis in men: the MINOS study. J Clin Endocrinol Metab. 2001 Jan;86(1):192-199. doi: 10.1210/jcem.86.1.7126. PMID: 11232000.

9. 9. Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995; 16(1):3-34. doi: 10.1210/edrv-16-1-3. PMID: 7758431.
10. 10. Rosen CJ, Donahue LR, Hunter SJ. Insulin-like growth factors and bone: the osteoporosis connection. Proc Soc Exp Biol Med. 1994; 206(2):83-102. doi: 10.3181/00379727-206-43726. PMID: 8208742.
11. 11. Kurland ES, Rosen CJ, Cosman F, McMahon D, Chan F, Shane E, et al. Insulin-like growth factor-I in men with idiopathic osteoporosis. J Clin Endocrinol Metab. 1997; 82(9):2799-2805. doi: 10.1210/jcem.82.9.4253. PMID: 9284699.
12. 12. Duman AE, Güven GS, Gürlek A. Erkek osteoporozu. Hacettepe Tıp Dergisi. 2005; 36(3):175-183.
13. 13. Riggs BL, Melton LJ 3rd. Involutional osteoporosis. N Engl J Med. 1986; 314(26):1676-1686. doi: 10.1056/NEJM198606263142605. PMID: 3520321.
14. 14. Gennari L, Bilezikian JP. Idiopathic osteoporosis in men. Curr Osteoporos Rep. 2013; 11(4):286-98. doi: 10.1007/s11914-013-0164-1. PMID: 24052235.
15. 15. Arıoğul S. Yaşlıda Osteoporoz ve Tedavisi. Klinik Gelişim Dergisi. 2012; 25:38-40.
16. 16. Giusti A, Bianchi G. Male osteoporosis. Reumatismo. 2014; 66(2):136-143. doi: 10.4081/reumatismo.2014.786. PMID: 25069495.
17. 17. Gennari L, Bilezikian JP. Osteoporosis in men. Endocrinol Metab Clin North Am. 2007; 36(2):399-419. doi: 10.1016/j.ecl.2007.03.008. PMID: 17543726.
18. 18. Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, et al. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest. 2002; 110(6):771-781. doi: 10.1172/JCI15463. PMID: 12235108; PMCID: PMC151128.
19. 19. Ohlsson C, Mellström D, Carlzon D, Orwoll E, Ljunggren O, Karlsson MK, et al. Older men with low serum IGF-1 have an increased risk of incident fractures: the MrOS Sweden study. J Bone Miner Res. 2011; 26(4):865-872. doi: 10.1002/jbmr.281. PMID: 21433071.
20. 20. Giustina A, Mazziotti G, Canalis E. Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev. 2008; 29(5):535-559. doi: 10.1210/er.2007-0036. Epub 2008 Apr 24. PMID: 18436706; PMCID: PMC2726838.
21. 21. Kawai M, Rosen CJ. Insulin-like growth factor-I and bone: lessons from mice and men. Pediatr Nephrol. 2009; 24(7):1277-1285. doi: 10.1007/s00467-008-1040-6. Epub 2008 Nov 15. PMID: 19011906.
22. 22. Ohlsson C, Mohan S, Sjögren K, Tivesten A, Isgaard J, Isaksson O, et al. The role of liver-derived insulin-like growth factor-I. Endocr Rev. 2009; 30(5):494-535. doi: 10.1210/er.2009-0010. Epub 2009 Jul 9. PMID: 19589948; PMCID: PMC2759708.
23. 23. Sjögren K, Sheng M, Movérare S, Liu JL, Wallenius K, Törnell J, et al. Effects of liver-derived insulin-like growth factor I on bone metabolism in mice. J Bone Miner Res. 2002; 17(11):1977-1987. doi: 10.1359/jbmr.2002.17.11.1977. PMID: 12412805.
24. 24. Reed BY, Zerwekh JE, Sakhaee K, Breslau NA, Gottschalk F, Pak CY. Serum IGF 1 is low and correlated with osteoblastic surface in idiopathic osteoporosis. J Bone Miner Res. 1995; 10(8):1218-1224. doi: 10.1002/jbmr.5650100812. PMID: 8585426.
25. 25. Ljunghall S, Johansson AG, Burman P, Kämpe O, Lindh E, Karlsson FA. Low plasma levels of insulin-like growth factor 1 (IGF-1) in male patients with idiopathic osteoporosis. J Intern Med. 1992; 232(1):59-64. doi: 10.1111/j.1365-2796.1992.tb00550.x. PMID: 1640193.
26. 26. Arasıl T. Osteoporozda Temel Fizyopatoloji Osteoporozda Tanı ve Tedavi Edt: Meray J, Peker O. İstanbul 2012 8-22.
27. 27. Lian JB, Stein G. Osteoblast biology. In: Marcus R, Feldman DD, Kelsey J (Eds): Osteoporosis, San Diego, Academic Press, 2001:(1)21-71.
28. 28. Khosla S, Melton LJ 3rd, Achenbach SJ, Oberg AL, Riggs BL. Hormonal and biochemical determinants of trabecular microstructure at the ultradistal radius in women and men. J Clin Endocrinol Metab. 2006; 91(3):885-891. doi: 10.1210/jc.2005-2065. Epub 2005 Dec 20. PMID: 16368747.
29. 29. Khosla S, Melton LJ 3rd, Atkinson EJ, O'Fallon WM. Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. J Clin Endocrinol Metab. 2001; 86(8):3555-3561. doi: 10.1210/jcem.86.8.7736. PMID: 11502778.
30. 30. Orwoll E, Lambert LC, Marshall LM, Phipps K, Blank J, Barrett-Connor E, et al. Testosterone and estradiol among older men. J Clin Endocrinol Metab. 2006; 91(4):1336-1344. doi: 10.1210/jc.2005-1830. Epub 2005 Dec 20. PMID: 16368750.
31. 31. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev. 2001; 22(4):477-501. doi: 10.1210/edrv.22.4.0437. PMID: 11493580.
32. 32. Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab. 1996; 81(12):4358-4365. doi: 10.1210/jcem.81.12.8954042. PMID: 8954042.
33. 33. Drinka PJ, Olson J, Bawens S, Voeks SK, Carlson I, Wilson M. Lack of association between free testosterone and bone density separate from age in elderly males. Calcif Tissue Int. 1993; 52:67–69.
34. 34. Rapado A, Hawkins F, Sobrinho L, Díaz-Curiel M, Galvao-Telles A, Arver S, et al. Bone mineral density and androgen levels in elderly males. Calcif Tissue Int. 1999; 65(6):417-421. doi: 10.1007/s002239900726. PMID: 10594158.
35. 35. Sezgin M, Çimen B, Ankaralı HÇ, As İ, Erçetin N, Çimen ÖB, et al. Are Bioactive and Free Sex Steroids Associated with Bone Mineral Density and Bone Turnover Markers in Middle Aged Men? From the World Osteoporosis 2009;15:59-65.
36. 36. Grumbach MM, Auchus RJ. Estrogen: consequences and implications of human mutations in synthesis and action. J Clin Endocrinol Metab. 1999; 84(12):4677-4694. doi: 10.1210/jcem.84.12.6290. PMID: 10599737.
37. 37. Riggs BL, Khosla S, Melton LJ 3rd. A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res. 1998; 13(5):763-773. doi: 10.1359/jbmr.1998.13.5.763. PMID: 9610739.
38. 38. Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab. 1995; 80(12):3689-3698. doi: 10.1210/jcem.80.12.8530621. PMID: 8530621.
39. 39. Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, et al. Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med. 1997; 337(2):91-95. doi: 10.1056/NEJM199707103370204. PMID: 9211678.
40. 40. Van Pottelbergh I, Goemaere S, Zmierczak H, Kaufman JM. Perturbed sex steroid status in men with idiopathic osteoporosis and their sons. J Clin Endocrinol Metab. 2004; 89(10):4949-4953. doi: 10.1210/jc.2003-032081. PMID: 15472190.
41. 41. Slemenda CW, Longcope C, Zhou L, Hui SL, Peacock M, Johnston CC. Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens. J Clin Invest. 1997; 100(7):1755-1759. doi: 10.1172/JCI119701. PMID: 9312174; PMCID: PMC508359.
42. 42. Amin S, Zhang Y, Sawin CT, Evans SR, Hannan MT, Kiel DP, Wilson PW, Felson DT. Association of hypogonadism and estradiol levels with bone mineral density in elderly men from the Framingham study. Ann Intern Med. 2000; 133(12):951-963. doi: 10.7326/0003-4819-133-12-200012190-00010. PMID: 11119396.
43. 43. Gillberg P, Johansson AG, Ljunghall S. Decreased estradiol levels and free androgen index and elevated sex hormone-binding globulin levels in male idiopathic osteoporosis. Calcif Tissue Int. 1999; 64(3):209-213. doi: 10.1007/s002239900604. PMID: 10024377.
44. 44. Khosla S, Melton LJ 3rd, Atkinson EJ, O'Fallon WM, Klee GG, Riggs BL. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab. 1998; 83(7):2266-2274. doi: 10.1210/jcem.83.7.4924. PMID: 9661593.
45. 45. Evans SF, Davie MW. Low body size and elevated sex-hormone binding globulin distinguish men with idiopathic vertebral fracture. Calcif Tissue Int. 2002; 70(1):9–15.
46. 46. Khosla S, Melton LJ 3rd, Riggs BL. Clinical review 144: Estrogen and the male skeleton. J Clin Endocrinol Metab. 2002; 87(4):1443-1450. doi: 10.1210/jcem.87.4.8417. PMID: 11932262.
47. 47. Mellström D, Vandenput L, Mallmin H, Holmberg AH, Lorentzon M, Odén A, et al. Older men with low serum estradiol and high serum SHBG have an increased risk of fractures. J Bone Miner Res. 2008; 23(10):1552-1560. doi: 10.1359/jbmr.080518. PMID: 18518773.
48. 48. Gürlek A, Gedik O. Endogenous sex steroid, GH and IGF-I levels in normal elderly men: relationships with bone mineral density and markers of bone turnover. J Endocrinol Invest. 2001; 24(6):408-414. doi: 10.1007/BF03351040. PMID: 11434664.
49. 49. Keleş I, Aydin G, Başar MM, Hayran M, Atalar E, Orkun S, et al. Endogenous sex steroids and bone mineral density in healthy men. Joint Bone Spine. 2006; 73(1):80-85. doi: 10.1016/j.jbspin.2005.04.003. Epub 2005 Jul 1. PMID: 16087380.