Bone mineral density predictors in long-standing type 1 and type 2 diabetes mellitus

Abstract

Background Despite the increased fracture risk, bone mineral density (BMD) is variable in type 1 (T1D) and type 2 (T2D) diabetes mellitus. We aimed at comparing independent BMD predictors in T1D, T2D and control subjects, respectively. Methods Cross-sectional case-control study enrolling 30 T1D, 39 T2D and 69 age, sex and body mass index (BMI) – matched controls that underwent clinical examination, dual-energy X-ray absorptiometry (BMD at the lumbar spine and femoral neck) and serum determination of HbA1c and parameters of calcium and phosphate metabolism. Results T2D patients had similar BMD compared to T1D individuals (after adjusting for age, BMI and disease duration) and to matched controls, respectively. In multiple regression analysis, diabetes duration – but not HbA1c- negatively predicted femoral neck BMD in T1D (β= -0.39, p = 0.014), while BMI was a positive predictor for lumbar spine (β = 0.46, p = 0.006) and femoral neck BMD (β = 0.44, p = 0.007) in T2D, besides gender influence. Age negatively predicted BMD in controls, but not in patients with diabetes. Conclusions Long-standing diabetes and female gender particularly increase the risk for low bone mass in T1D. An increased body weight partially hinders BMD loss in T2D. The impact of age appears to be surpassed by that of other bone regulating factors in both T1D and T2D patients.

The Potential Therapeutic Role of Metformin in Diabetic and Non-Diabetic Bone Impairment

“…The accumulation of AGEs and upregulation of the expression of RAGEs are common in diabetic patients because the cells regulate their own stress state in response to the changes in the environment under hyperglycemia [ 107 , 108 , 109 , 110 ]. The binding of insulin and its receptors on the surface of osteoblasts stimulated the secretion of OCN, which in turn promoted the proliferation of β-cells in the pancreas and insulin sensitivity, however, hyperglycemia and high levels of ROS regulated the production of OCN negatively [ 111 ]. Moreover, the activation of AMPKa by metformin inhibited intracellular levels of nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), and the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase in the mevalonate pathway, which exerted a positive influence on bone tissue [ 112 , 113 , 114 ].…”

The pathophysiology of osteoporosis in obesity and type 2 diabetes in aging women and men: The mechanisms and roles of increased bone marrow adiposity

“…Osteoporosis and aging are characterized with decreased BMD, along with increased BMAT and accompanied by increased resorption activity in the BM in mice and humans ( 90 , 91 ). Metabolic complications associated with impairment of glucose homeostasis have been shown to contribute to higher risk of bone fractures and accelerate the manifestation of bone fragility and osteoporosis.…”

Crosstalk Between Senescent Bone Cells and the Bone Tissue Microenvironment Influences Bone Fragility During Chronological Age and in Diabetes

“…Bone mass, as evaluated by bone mineral density (BMD), is only modestly reduced in adult T1D patients compared to age- and sex- matched controls ( Napoli et al, 2017 ), and does not fully explain the high fracture risk. Moreover, BMD in T2D is higher or normal compared to age- and sex-matched controls potentially because higher body mass imposes greater mechanical loading ( Bilha et al, 2021 ), however, fracture risk is significantly higher. Alterations in bone architecture and reduced bone quality that are not captured by BMD have been implicated in the pathogenesis of reduced bone mechanical strength in T1D and T2D.…”