Skeletal Fragility in Type 2 Diabetes Mellitus

Abstract

Type 2 diabetes (T2D) is associated with an increased risk of fracture, which has been reported in several epidemiological studies. However, bone mineral density in T2D is increased and underestimates the fracture risk. Common risk factors for fracture do not fully explain the increased fracture risk observed in patients with T2D. We propose that the pathogenesis of increased fracture risk in T2D is due to low bone turnover caused by osteocyte dysfunction resulting in bone microcracks and fractures. Increased levels of sclerostin may mediate the low bone turnover and may be a novel marker of increased fracture risk, although further research is needed. An impaired incretin response in T2D may also affect bone turnover. Accumulation of advanced glycosylation endproducts may also impair bone strength. Concerning antidiabetic medication, the glitazones are detrimental to bone health and associated with increased fracture risk, and the sulphonylureas may increase fracture risk by causing hypoglycemia. So far, the results on the effect of other antidiabetics are ambiguous. No specific guideline for the management of bone disease in T2D is available and current evidence on the effects of antiosteoporotic medication in T2D is sparse. The aim of this review is to collate current evidence of the pathogenesis, detection and treatment of diabetic bone disease.

Role of Metformin on Osteoblast Differentiation in Type 2 Diabetes

“…Diabetes mellitus is manifested with abnormal bone mineral density (BMD), hyperglycemia, secondary calcium imbalance, disturbances in vitamin D [26], microvascular disease [27], and an increased risk of fall [28, 29]. With a high morbidity and mortality, it also adversely affects bone metabolism and increases the fracture risk [30–32].…”

Perbedaan petanda osteoporosis dan inflamasi pada pasien diabetes melitus tipe 2 terkontrol dan tidak terkontrol

“…10,19 Starup et al tahun 2014 mengungkapkan bahwa Oc signifikan lebih rendah pada pasien DM, hal ini dikarenakan perubahan pada bone turnover. 20 Pasien DMT2 dengan bone turnover berkurang sering dihubungkan dengan risiko komplikasi fraktur dikarenakan keadaan resistensi insulin dan aktivitas fisik rendah, semuanya dapat berperan dalam perkembangan penyakit tulang pada diabetes. Hiperglikemia dapat secara langsung mempengaruhi osteoklas dan osteoblas selain mempengaruhi osteosit.…”

“…Hiperglikemia memicu hipermineralisasi pada tulang yang menyebabkan kepadatan mineral tulang (BMD) tinggi dan berkurangnya bone turnover menyebabkan microcracks dan fraktur. 20,21 Beberapa penelitian tentang Oc berhubungan negatif dengan glukosa darah puasa, insulin puasa, HbA1c dan HOMA-IR. 22,[23][24][25][26] Penelitian ini menunjukkan bahwa pada DMT2 yang tidak terkontrol, kadar Oc serum menurun dapat disebabkan oleh peningkatan resistensi insulin dan peningkatan aktivitas enzim lisosom.…”

Association of glycaemic variables with trabecular bone score in post‐menopausal women with type 2 diabetes mellitus

“…There are multiple putative pathways via which type 2 diabetes may result in an increased fracture risk. Glucose has a direct inhibitory effect on osteoblasts [1], with osteocyte dysfunction leading to a low bone turnover state [2]. Obesity with concurrent altered adipokine release or altered marrow adiposity may also have detrimental effects on bone [1].…”

“…In contrast, non‐enzymatic glycation of collagen, via a change in its molecular conformation, may alter stiffness. Additionally, it has been proposed that non‐enzymatic glycation may also alter how that extracellular matrix interacts with the cellular elements of bone, particularly osteoblasts, or alter cell‐to‐cell interactions which are important for normal bone turnover [1,2]. AGEs have also been shown to have a direct toxic effect on osteoblasts [1].…”