Diabetes and bone. Focus on DPP-4 inhibitors

Pathology of bone homeostasis in diabetes mellitus (DM) is a significant problem that must be considered when selecting anti-diabetic therapy. Many anti-diabetic drugs have a specific effect on bone homeostasis which should be taken into account when selecting treatment for type 2 diabetes, especially in patients at high risk of osteoporosis. This review discusses mechanisms of impact on bone metabolism and fracture risks of DM and various groups of antidiabetic drugs, focusing on new groups of drugs included in the Russian algorithms over the past decade (GLP-1 receptor agonists, DPP-4 inhibitors, sodium-glucose cotransporter 2 inhibitors). It can be useful to both researchers and clinicians who are striving to offer the therapy of choice to their patients today.

сахарный диабет, остеопороз, костный метаболизм, противодиабетические препараты, метформин, препараты сульфонилмочевины, ингибиторы натрий-глюкозного котранспортера 2-го типа, тиазолидиндионы, ингибиторы дипепидил-пептидазы-4б, агонисты рецепторов глюкагоноподобного пептида-1, diabetic nephropathy, osteoporosis, bone metabolism, antidiabetic drugs, metformin, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter 2 inhibitors

1. Karim L, Bouxsein ML. Effect of type 2 diabetes-related non-enzymatic glycation on bone biomechanical properties. Bone. 2015, 07, 028. pII: S8756-3282.

2. Nicodemus KK, Folsom AR. Iowa Women's Health Study. Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care. 2001, 24: 1192-1197.

3. Inzerillo AM, Epstein S. Osteoporosis and diabetes mellitus. RevEndocr Metab Disord. 2004, 5: 261-268.

4. Leiding-Bruckner G., Ziegler R. Diabetes mellitus - a risk for osteoporosis? Exp Clin Endocrinol Diabetes. 2001, 109: S493-514.

5. Patsch JM, Burghardt AJ, Yap SP, Baum T, Schwartz AV, Joseph GB, Link TM. Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. Journal of Bone and Mineral Research. 2013, 28(2): 313-324.

6. Saito M, Fujii K, Mori Y, Marumo K. Role of collagen enzymatic and glycation induced crosslinks as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporosis International. 2006, 17(10): 1514-1523.

7. Vestergaard P, Rejnmark L & Mosekilde L. Diabetes and its complications and their relationship with risk of fractures in type 1 and 2 diabetes. Calcified Tissue International. 2009, 84(1): 45-55.

8. Hough S, Pierroz D, Cooper C, Ferrari S. Mechanisms in endocrinology: Mechanisms and Evaluation of Bone Fragility in Type 1 Diabetes Mellitus. Eur J Endocrinol. 2015, 4(2): EJE-15-0820.

9. Clemens TL, Karsenty G. The osteoblast: an insulin target cell controlling glucose homeo-stasis. Journal of Bone and Mineral Research. 2011, 26(4): 677-680.

10. Wei J, Ferron M, Clarke CJ, Hannun YA, Jiang H, Blaner WS, Karsenty G. Bone-specific insulin resistance disrupts whole-body glucose homeo-stasis via decreased osteocalcin activation. Journal of Clinical Investigation. 2014, 124(4): 1781-1793.

11. McNair P, Madsbad S, Christiansen C, Christensen MS, Faber OK, Binder C, Transbol I. Bone loss in diabetes: effects of metabolic state. Diabetologia. 1979, 17(5): 283-286.

12. Eknoyan G, Lewin A, Levin N. National Kidney Foundation. K/DOOI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. American Journal of Kidney Diseases. 2003, 42 S1-S202.

13. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type

14. and type 2 diabetes - a meta-analysis. Osteoporosis International. 2007, 18(4): 427-444.

15. Khazai NB., Beck GR, and Umpierrez GE Diabetes and Fractures - An overshadowed association. Curr Opin Endocrinol Diabetes Obes. 2009, 16(6): 435-445.

16. Lee RH, Pieper CF, Colon-Emeric C. Functional Impairments Mediate Association Between Clinical Fracture Risk and Type 2 Diabetes Mellitus in Older Women. J Am Geriatr Soc. 2015, 63(8): 1546-1551.

17. Лесняк О.М., Никитинская О.А., Торопцова Н.В., Белая Ж.Е., Каронова Т.Л. и соавт. Профилактика, диагностика и лечение дефицита витамина D и кальция у взрослого населения России и пациентов с остеопорозом (по материалам клинических рекомендаций). Научно-практическая ревматология. 2015, 53(4): 403-408.

18. Mathen PG, Thabah MM, Zachariah B, Das AK. Decreased Bone Mineral Density at the Femoral Neck and Lumbar Spine in South Indian Patients with Type

19. Diabetes. J Clin Diagn Res. 2015, 9(9): OC08-12.

20. Benvenuti S, Cellai I, Luciani P, Deledda C, Baglioni S, Giuliani C, et al. Rosiglitazone stimulates adipo-genesis and decreases osteoblastogenesis in human mesenchymal stem cells. Journal of Endocrinological Investigation. 2007, 30(9): 26-30.

21. Vestergaard P, Rejnmark L, Mosekilde L. Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia. 2005, 48(7): 1292-1299.

22. Hegazy SK, Evaluation of the anti-osteoporotic effects of metformin and sitagliptin in postmen-opausal diabetic women. J Bone Miner Metab. 2015, 33(2): 207-212.

23. Ma P, Gu B, Xiong W, Tan B, Geng W, Li J, Liu H, Glimepiride promotes osteogenic differentiation in rat osteoblasts via the PI3K/Akt/eNOS pathway in a high glucose microenvironment. PLoS One. 2014, 9(11): e112243.

24. Ma P, Tan B, Liu H, Ma J, Gu B, Effect of glime-piride on the glucose uptake of rat mandibular osteoblasts in hyperglycemia. Hua Xi Kou Qiang Yi Xue Za Zhi. 2014, 32(2): 125-129.

25. Rajpathak SN, Fu C, Brodovicz KG, Engel SS, Lapane K, Sulfonylurea use and risk of hip fractures among elderly men and women with type 2 diabetes. Drugs Aging. 2015, 32(4): 321-327.

26. Henriksen DB, Alexandersen P, Bjarnason NH, Vilsboll T, Hartmann B, Henriksen EE, Byrjalsen I, Krarup T, Holst JJ & Christiansen C. Role of gastrointestinal hormones in postprandial reduction of bone resorption. Journal of Bone and Mineral Research. 2003. 18(12): 2180-2189.

27. Бабенко А.Ю., Неймарк А.Е., Анисимова К.А., Гринева Е.Н. Эффекты бариатрических операций на уровень гормонов, регулирующих массу тела. В чем основа успеха? Ожирение и метаболизм, 2014. 4: 3-11.