It is widely accepted by the scientific community that T2DM impairs bone metabolism [8, 16], and the risk of fragility fractures is increased in these patients [9, 10]. The mechanisms by which the risk of fracture is increased, and this impairment occurs are not clear. In addition, BMD measurements or FRAX® tool cannot predict these risks. Therefore, there is a need to establish a relative risk assessment method in the clinical setting in patients with T2DM to predict possible impacts on bone fracture related to the disease. The purpose of our analysis was to study the impact in the microstructural and bone mechanics in T2DM patients with or without recent fragility fractures and the relationship of these fractures with type 2 diabetes mellitus.
To verify the influence of T2DM on quantity and quality of trabecular bone tissue from 28 patients, we have assessed BMD, microarchitecture and biomechanical properties of femoral heads from 4 patient groups: OA, OP, OA-T2DM and OP-T2DM. The control group is made up of patients with osteoarthritis, these patients tend to have a localized increase of bone density and/or sclerosis in subchondral bone of the femoral head, but minimal differences in bone density of the femoral neck , where we obtained the samples by micro-CT. Moreover, both our diabetic and non-diabetic subjects were undergoing total hip replacement, and therefore the groups should be comparable. Thus, we do not believe presence of osteoarthritis negatively affected our ability to draw conclusions about diabetes vs. non-diabetes. As expected, osteoporotic patients with hip fractures had lower BMD values than osteoarthritic patients, but no differences between osteoporotic patients with and without T2DM were found and neither between the OA group and OA-T2DM. Previous data demonstrated that T2DM patients have normal or increased BMD values [18–20], even when this variable was normalized by the BMI . Although it can be prevalent in juveniles, T2DM is very common in the elderly, and it frequently coexists with age-related bone loss . Therefore, the establishment of risk factors for fragility fractures during ageing should be identified since these factors can contribute to fracture risk in older diabetic patients. In our case, OP-T2DM and OP patients showed BMD values lower than − 2.5T (T-score score < -2.5) at all hip sites, which is consistent with the stablished World Health Organization Definitions. We found no differences in BMD between osteoarthritic groups with and without T2DM, and the values of BMD were considered normal or healthy by T-score in these groups. As our BMD values shown, clinical and epidemiological studies suggested an inverse relationship between many parameters studied in OP and OA patients [6, 22–25]. The increased BMD may minimize the expected negative effects on bone metabolism caused by diabetes.
The more relevant data obtained in the present study is based on decrease of the values observed of the bone microarchitecture and biomechanical properties that we tested in the trabecular hip bone of patients with both osteoarthritis and T2DM compared with non-diabetic osteoarthritic patients. Both groups of osteoarthritic patients were similar in terms of age, weight, lifestyle and evolutionary stage of degenerative disease. However, bone strength in the T2DM group was importantly damaged, and it was in a similar range in patients with osteoporotic hip fracture. These results show the negative effect of T2DM on trabecular bone structure and mechanical properties. Our findings are also broadly consistent with reports of lower bone material strength index in patients with T2D compared to non-diabetic controls [19, 26]. Conversely, improved properties of trabecular bone were noted in subjects with T2DM compared with controls; however, compromised cortical bone microarchitecture (e.g., increased cortical porosity) [26, 27] was observed. Cortical bone characteristics were not evaluated in this study, but we demonstrated damage in bone microstructure and the mechanics, which are important elements in trabecular bone quality in these subjects with T2DM [28, 29]. We also demonstrated a significant deterioration in these parameters in hip fracture patients. However, a lower quality of trabecular bone was not observed in OP-T2DM patients compared to non-diabetics. Patsch et al. showed similar results in younger people with diabetes using HR-pQCT of the ultradistal and distal radius and tibia . These data note that diabetic disease is a key factor that is directly involved in the deterioration of bone quality, which is likely responsible for the increased risk of fragility fractures.
We found no correlation between microstructure parameters and mechanical values with bone turnover markers. OP subjects exhibited more active bone remodeling, primarily because of bone resorption, as evidenced by the significantly higher levels of β-CrossLaps, which is consistent with a previous study . However, a trend of a reduced bone remodeling activity was observed in T2DM patients, which was demonstrated by the lower levels of formation and resorption markers than the respective controls [19, 20, 31, 32]. Some authors reported defects in bone formation that were produced by a decrease in osteoblast differentiation and an increase in apoptosis in these cells . These changes may lead to an imbalance between bone resorption and bone formation [32, 34].
Considerable evidence suggests that specific factors, such as poor glycemic control and T2DM duration (e.g., a glycated haemoglobin level ≥ 7.5%)  exacerbate risk factors in T2DM patients, although this relationship has not been established unequivocally . In the present study, both groups of diabetic patients were fairly well controlled. The average glycated haemoglobin level was lower than the previously mentioned average , and it was not associated with mechanical or microstructural parameters. We did not find a correlation among these values and the duration of diabetic disease, remaining very similar in OP-T2DM and OA-T2DM groups, which is consistent with a previous study .
The FRAX tool revealed that the OP and OP-T2DM subjects showed moderate to high risk. However, OA-T2DM patients of similar age showed low risk probability for both types of fracture, but mechanical and microstructure indicated the opposite risk. These results suggest that effective intervention thresholds for fracture prevention in patients with T2DM might be different than those that are effective for non-diabetic patients, as discussed recently [30, 37].
Despite the potential of the present entered data obtained from hip bone human samples, our study had several limitations. Our sample size was relatively small although with sufficient power to obtain significant differences between the differences found. Therefore, our results should be eventually confirmed. The lack of cortical bone microarchitecture and histomorphometry indices of the samples is an additional concern. Nevertheless, this study includes BMD, BTM, trabecular bone microarchitecture and mechanical strength measures in T2DM patients with and without recently suffered fragility hip fracture, thus allowing for establishment a relationship between osteoporotic fracture and diabetes.