Kırık iyileşmesinde büyüme hormonu somatomedin-C aksının etkisi

Yıl 2019, , 672 - 675, 01.09.2019

Özgür Kaya , Özgür Doğan Emrah Çalışkan , Batuhan Gencer , Hakan Kocaoğlu Ali Biçimoğlu

https://doi.org/10.28982/josam.617669

Öz

Amaç: Birçok çalışma, farklı kalsitropik hormonların kırık iyileşmesi üzerindeki etkilerini incelemiş, az sayıda çalışma ise büyüme faktörlerine odaklanmıştır. Kırık kallusunda lokal somatomedin C (IGF-1) tespiti, büyüme hormonu (GH) ve IGF-1'in kaynamama tedavisi olarak uygulanması ve osteoporotik kırıklarda saptanan düşük GH ve IGF-1 seviyeleri, bu hormonların kırık iyileşmesinde etkili olduğunu göstermektedir. Bununla birlikte, bu çalışmaların tümü kırık sonrası GH ve IGF-1 seviyelerine dayanır, ancak GH ve IGF-1 akut faz yanıtında rol oynar ve travma nedeniyle seviyeleri değişebilir. Bu çalışmanın amacı osteotomi ile tedavi edilen böylece bir iatrojenik kırık oluşturulan hastalarda GH ve IGF-1 seviyelerindeki değişimi araştırmak ve bu hormonların kırık iyileşmesi üzerindeki etkisini kırık öncesi ve sonrası sonuçları karşılaştırarak değerlendirmektir.

Yöntemler: Bu prospektif kohort çalışma için, 2014-2015 yılları arasında gelişimsel kalça çıkığı nedeniyle cerrahi olarak tedavi edilen hastalar tarandı. 41 hasta çalışmaya dahil edildi ve iki grup oluşturuldu. Sadece açık redüksiyon ve yumuşak doku gevşetmesi yapılan hastalar ilk grup olarak belirlendi. Pelvik osteotomi yapılan ve böylece bir iatrojenik kırık oluşturulan hastalar ikinci grup olarak belirlendi. Birinci gruba 20 hasta, ikinci gruba 21 hasta dahil edildi. Operasyon öncesi, postoperatif 1. gün ve 28. günde tüm hastalardan kan örneği alındı. İstatistiksel analizler için Friedman ve Mann-Whitney U testleri kullanıldı.

Bulgular: İlk grupta ortalama yaş 11,25 aydı (6-25 ay). Hastaların 19’u (95%) kadın, biri (5%) erkekti. İkinci grupta ortalama yaş 74,4 aydı (24-120 ay) ve 17 (85,7%) hasta kadın, dört (14,3%) hasta erkekti. İlk grupta pre-operatif ve postoperatif GH değerleri arasında anlamlı fark bulunmazken (P=0,05); ikinci grupta postoperatif GH değerleri daha yüksekti (P<0,001). Postoperatif IGF-1 düzeyleri her iki grupta anlamlı düşüş göstermekteydi (P<0,001). Pre-operatif ve postoperatif GH ve IGF-1 değerleri iki grup arasında karşılaştırıldığında, ikinci grupta postoperatif 1. günde GH değerleri anlamlı olarak daha yüksek seyrederken (P<0,001) aynı ölçümlerde serum IGF-1 düzeylerinde anlamlı düşüş saptandı (P=0,043).

Sonuç: IGF-1, kısa yarı ömrü ve yerel üretimi nedeniyle kırık iyileşmesinin araştırılmasında yetersizdir. Öte yandan, GH kırık iyileşmesinde aktif bir rol oynar ve kırık öncesi değerlere kıyasla önemli ölçüde artar. GH seviyesinin kırık iyileşmesi sırasında vücutta arttığı göz önüne alındığında, kırık iyileşmesinin patolojik olduğu düşünülen hastalarda GH desteği verilmesi yararlı olabilir.

Anahtar Kelimeler

Kırık iyileşmesi, İatrojenik kırık, Büyüme hormonu, Somatomedin C

Effect of growth hormone and somatomedin-C axis on fracture healing

Öz

Aim: Many studies have examined the effects of different calciotropic hormones on fracture healing, whereas few studies focus on growth factors. Local detection of somatomedin C (IGF-1) in fracture callus, application of growth hormone (GH) and IGF-1 as non-union treatment, and low GH and IGF-1 levels in osteoporotic fractures indicate that these hormones are effective in fracture healing. However, most of these studies are based on post fracture GH and IGF-1 levels. GH and IGF-1 are also involved in acute phase response and can change due to trauma. The aim of this study is to investigate the change in GH and IGF-1 levels in patients treated with osteotomy, in which an iatrogenic fracture is created, and to evaluate the effect of these hormones on fracture healing by comparing the results before and after the fractures. 

Methods: Patients who were diagnosed with developmental dysplasia of the hip and underwent surgery between 2014-2015 were prospectively followed for this cohort study. Forty-one patients were included, and two groups were formed. Patients who underwent open reduction and soft tissue release without osteotomy (n=20) were included in the first group. Patients who underwent pelvic osteotomy (n=21), in which iatrogenic fractures were created, were included in the second group. Blood samples were obtained from all patients pre-operatively and on the 1st and 28th postoperative days. Friedman and Mann-Whitney U tests were used for statistical analysis. 

Results: Mean age of the first group, comprising 19 females (95%) and 1 male (5%), was 11.25 months (Range: 6-25 months). Mean age of the second group, including 17 females (85.7%) and 4 males (14.3%), was 74.4 months (Range: 24-120 months). While there was no significant difference between pre- and postoperative GH values in the first group (P=0.05), postoperative GH levels were significantly higher than preoperative GH levels in the second group (P<0.001). Postoperative IGF-1 levels were significantly lower than preoperative IGF-1 levels in both groups (P<0.001). When the difference of preoperative and postoperative 1st day GH and IGF-1 values were compared between two groups, GH changes were found significantly higher in the second group (P<0.001) whereas serum IGF-1 changes were significantly lower in the second group (P=0.043). 

Conclusion: IGF-1 is inadequate in the investigation of fracture healing due to its short half-life and local production. On the other hand, GH plays an active role in fracture healing and increases significantly in comparison to pre-fracture values. Considering the GH increase during fracture healing, it may be beneficial to support patients with pathological fracture healing with growth hormone.

Anahtar Kelimeler

Fracture healing, Iatrogenic fracture, Growth hormone, Somatomedin C

Kaynakça

• 1. Canalis E. Insulin like growth factors and the local regulation of bone formation. Bone. 1993;14:273-6.
• 2. Mohan S, Baylink DJ. Bone growth factors. Clin Orthop. 1991;263:30-48.
• 3. Einhorn TA, Dimon G, Devlin VJ, Warman J, Sidhu SPS, Vigorita VJ. The osteogenic response to distant skeletal injury. J Bone Joint Surg. 1990;72-A:1374-8.
• 4. Gazit D, Karmish M, Holzman L, Bab I. Regenerating marrow induces systemic increase in osteo- and chondrogenesis. Endocrinology. 1990;126(5):2607-13.
• 5. Weiss S, Zimmermann G, Baumgart R, Kasten P, Bidlingmaier M, Henle P. Systemic regulation of angiogenesis and matrix-degradation in bone regeneration- distraction osteogenesis compared to rigid fracture healing. Bone. 2005;37:781-90.
• 6. Colon G, Saccon T, Schneider A, Cavalcante MB, Hufmann DM, Berryman D, et al. The enigmatic role of growth hormone in age-related diseases, cognition and longevity. Geroscience. 2019 Sep 4. doi: 10.1007/s11357-019-00096-w.
• 7. Strobl JS, Thomas MJ. Human growth hormone. Pharmacol Rev. 1994 Mar;46(1):1-34
• 8. Bourque WT, Gross M, Hall BK. Expression of four growth factors during fracture repair. Int J Dev Biol. 1993;37:573-9.
• 9. Andrew JG, Hoyland J, Freemont AJ, Marsh D. Insulin-like growth factor gene expression in human fracture callus. Calcif Tissue Int. 1993;53:97-102.
• 10. Edwall D, Prisell PT, Levinovitz A, Jeniische E, Norstedt G. Expression of insulin-like growth factor I messenger ribonucleic acid in regenerating bone after fracture: influence of indomethacin. J Bone Miner Res. 1992;7:207-13.
• 11. Koskinen EV, Lindholm RV, Nieminen RA, Puranen J, Atila U. Human growth hormone in delayed union and non-union of fractures. Int Orthop. 1978;1:317-22.
• 12. Bak B, Jorgensen PH, Andreassen TT. Increased mechanical strength of healing rat tibial fractures treated with biosynthetic human growth hormone. Bone. 1990;11:233-9.
• 13. Kutlu O, Üzüm İ, Durmuşcan M, Kekilli E, Parlakpınar H, Kutlu NO. Anti-osteoporotic effects of melatonin and misoprostol in glucocorticoid-induced osteoporosis: An experimental study. J Surg Med. 2019;3(8):568-73. doi: 10.28982/josam.595295.
• 14. Aron DC, Findling JW, Tyrell JB. Hypothalamus and pituitary. In: Greenspan SF, Gardner DG, eds. Basic and Clinical Endocrinology. McGraw Hill Medical Books; 2001. pp. 100-158.
• 15. Locatelli V, Bianchi VE. Effect of GH/IGF-1 on Bone Metabolism and Osteoporosis. Int J Endocrinol. 2014;2014:235060. doi: 10.1155/2014/235060.
• 16. Dogan O, Caliskan E, Gencer B, Bicimoglu A. Is male gender a prognostic factor for developmental dysplasia of the hip? Mid-long-term results of posteromedial limited surgery. Acta Orthop Traumatol Turc. 2019 Jul 4. doi: 10.1016/j.aott.2019.05.001.
• 17. Bicimoglu A, Caliskan E. The long-term outcomes of posteromedial limited surgery for developmental dysplasia of the hip: a mean 17.3-year follow-up. J Pediatr Orthop B. 2019 Mar;28(2):115-21. doi: 10.1097/BPB. 0000000000000555.
• 18. Solheim E. Current concepts review: Growth factors in bone. Int Orthop. 1998;22:410-6.
• 19. Toogood AA, Nass RM, Pezzol SS, O’neil PA, Thorner MO, Shalet SM. Preservation of growth hormone pulsatility despite pituitary pathology, surgery and irradiation. J Clin Endocrinol Metab. 1997 Jul;82(7):2215-21.
• 20. Chapman IM, Hartman ML, Straume ML, Johnson ML, Veldhuis JD, Thorner MO. Enhanced sensitivity growth hormone (GH) chemiluminescence assay reveals lower post glucose nadir GH concentrations in men than women. J Clin Endocrinol Metab. 1994;78:1312-9.
• 21. Weiss S, Henle P, Bidlingmaier M, Moghaddam A, Kasten P, Zimmermann G. Systemic response of the GH/IGF-1 axis in timely versus delayed fracture healing. Growth Horm IGF Res. 2008;18:205-12.
• 22. Raschke M, Rasmussen MH, Govender S, Segal D, Suntum M, Christiansen JS. Effects of growth hormone in patients with tibial fracture: a randomized, double-blind, placebo-controlled clinical trial. Eur J Endocrinol. 2007 Mar;156(3):341-51.
• 23. Tran GT, Pagkalos J, Tsiridis E, Narvani AA, Heliotis M, Mantalaris A, et al. Growth hormone: does it have a therapeutic role in fracture healing? Expert Opin Investig Drugs. 2009 Jul;18(7):887-911. doi: 10.1517/13543780902893069.
• 24. Jeevanandam M, Holaday NJ, Petersen SR. Posttraumatic hormonal environment during total parenteral nutrition. Nutrition. 1993;9:333-8.
• 25. Di Monaco M, Vallero F, Di Monaco R, Tappero R, Cavanna A. Serum levels of insulin-like growth factor-I are positively associated with functional outcome after hip fracture in elderly woman. Am J Phys Med Rehabil. 2009 Feb;88(2):119-25. doi: 10.1097/PHM.0b013e31818e002d.
• 26. Myers TJ, Yan Y, Granero-Molto F, Weis JA, Longobardı L, Li T, et al. Systemically delivered insulin-like growth factor-I enhances mesenchymal stem cell-dependent fracture healing. Growth Factors. 2012 August;30(4):230-41.