T2DM is linked to an increase in the fracture rate as compared to the nondiabetic population even with normal or raised bone mineral density (BMD). Hence, bone quality plays an important role in the pathogenesis of skeletal fragility due to T2DM. This study analyzed the changes in the trabecular bone microstructure due to T2DM at various time points in ovariectomized and nonovariectomized rats. Animals were divided into four groups: (I) control (sham), (II) diabetic (sham), (III) ovariectomized, and (IV) ovariectomized with diabetes. The trabecular microarchitecture of the femoral head was characterized using a micro-CT. The differences between the groups were analyzed at 8, 10, and 14 weeks of the onset of T2DM using a two-way analysis of variance and by post hoc multiple comparisons. The diabetic group with and without ovariectomies demonstrated a significant increase in trabecular separation and a decrease in bone volume fraction, trabecular number, and thickness. BMD decreased in ovariectomized diabetic animals at 14 weeks of the onset of T2DM. No significant change was found in connectivity density and degree of anisotropy among groups. The structural model index suggested a change towards a weaker rod-like microstructure in diabetic animals. The data obtained suggested that T2DM affects the trabecular structure within a rat's femoral heads negatively and changes are most significant at a longer duration of T2DM, increasing the risk to hip fractures.

BackgroundDiabetes mellitus (DM) is associated with osteoporosis and increase fracture risk1. Increase fractures in type 1 DM are linked to decrease bone mineral density (BMD) but BMD alone does not explain the increase fracture rate seen in diabetics. Alterations in bone quality which entails bone microarchitecture, material and composition of bone tissue also contributes to diabetic osteopathy2. Chronic state of hyperglycaemia, hypoinsulinemia, inflammation, low levels of insulin growth factor-1 (IGF-1), increased marrow adiposity, altered adipokine and endocrine factors, increased cell death and accumulation of advanced glycation products that compromise matrix properties impairs normal bone metabolism in type 1 DM1. While BMD is detected clinically using a dual-energy X-ray absorptiometry (DEXA) scan, methods to detect changes in bone quality are limited. Estimating bone markers in serum and urine are used in assessing bone quality. An imbalance in bone remodelling as measured by various bone markers is observed in type I DM. But due to discrepancy in results of various studies the exact mechanisms is still elusive.ObjectivesTo investigate the underlying mechanism of altered bone quality in type 1diabetes:1. By measuring the bone formations and resorption markers.2. By measuring the advanced glycation end products.3. By analysing the changes at cellular level in type I diabetesMethodsExperimental diabetes mellitus was induced in 24 Wistar rats by injecting streptozotocin 60 mg/kg body weight intraperitoneally. Rats were sacrificed at 6th, 8th and 12th week of developing diabetes. Blood and bone specimens were collected. Serum levels of osteocalcin, bone alkaline phosphatase, C-terminal cross-linked telopeptide of type-I collagen (CTX) and pentosidine were measured using ELISA to investigate bone turnover in type I DM. The bone specimens were fixed, processed, sectioned and stained for bone histomorphometry3. Histological analysis was carried out using an ‘Olympus Research Inverted Microscope Model IX53’ complete with fluorescent attachment equipped with a DP73 camera (Olympus). Statistical analysis was carried out using sigmastat 4.0.ResultsLow levels of osteocalcin and bone alkaline phosphatase and increased levels of pentosidine and CTx levels in serum were found in 6th and 12th week duration of diabetes. Additionally increase number of mast cells p<0.05 were observed in diabetic bones as compared to control specimensConclusionsChronic hyperglycaemic state in type I DM impairs bone remodelling by decreasing bone formation and increasing bone resorption. Increase in advanced glycation end products and mast cells also contribute to diabetic osteopathy.References[1] Napoli N, Chandran M, Pierroz DD, Abrahamsen B, Schwartz AV, Ferrari SL & On behalf of the IOF Bone and Diabetes Working Group. Mechanisms of diabetes mellitus-induced bone fragility. Nature Reviews Endocrinology2017;13:208–219.[2] Motyl K, McCabe LR. Streptozotocin, type I diabetes severity and bone. Biol Proced Online2009;11:296–315.[3] Mohsin S, ...