Links among Obesity, Type 2 Diabetes Mellitus, and Osteoporosis: Bone as a Target.

Obesity, type 2 diabetes mellitus (T2DM) and osteoporosis are serious diseases with an ever-increasing incidence that quite often coexist, especially in the elderly. Individuals with obesity and T2DM have impaired bone quality and an elevated risk of fragility fractures, despite higher and/or unchanged bone mineral density (BMD). The effect of obesity on fracture risk is site-specific, with reduced risk for several fractures (e.g., hip, pelvis, and wrist) and increased risk for others (e.g., humerus, ankle, upper leg, elbow, vertebrae, and rib). Patients with T2DM have a greater risk of hip, upper leg, foot, humerus, and total fractures. A chronic pro-inflammatory state, increased risk of falls, secondary complications, and pharmacotherapy can contribute to the pathophysiology of aforementioned fractures. Bisphosphonates and denosumab significantly reduced the risk of vertebral fractures in patients with both obesity and T2DM. Teriparatide significantly lowered non-vertebral fracture risk in T2DM subjects. It is important to recognize elevated fracture risk and osteoporosis in obese and T2DM patients, as they are currently considered low risk and tend to be underdiagnosed and undertreated. The implementation of better diagnostic tools, including trabecular bone score, lumbar spine BMD/body mass index (BMI) ratio, and microRNAs to predict bone fragility, could improve fracture prevention in this patient group.

Antagonistic Impact of Acrylamide and Ethanol on Biochemical and Morphological Parameters Consistent with Bone Health in Mice.

The aim of present study was to verify antagonistic effect of acrylamide (AA) and ethanol (Et) on bone quality parameters. Adult mice (n = 20) were segregated into four groups following 2 weeks administration of toxins: group E1, which received AA (20 mg/kg body weight daily); group E2, which received 15% Et (1.7 g 100% Et/kg body weight daily); group E12, which received simultaneously both toxins; and a control group. An insignificant impact of individual applications of AA, Et or their simultaneous supplementation on the total body weight of mice and the length and weight of their femoral bones was identified. In group E1, higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), a decreased level of glutathione (GSH) and elevated endocortical bone remodelling were determined. A significantly lower relative volume of cortical bone, bone mineral density (BMD), elevated endocortical bone remodelling and cortical porosity, higher levels of ALT, AST, lower values for total proteins (TP), GSH, alkaline phosphatase (ALP), calcium, and phosphorus were recorded in group E2. In the mice from group E12, the highest endocortical bone remodelling, decreased values for BMD, TP, GSH and ALP and increased levels of ALT and AST were found. Our findings confirmed the antagonistic impact of AA and Et at doses used in this study on biochemical and morphological parameters consistent with bone health in an animal model.

Long-term peroral administration of bitter apricot seeds influences cortical bone microstructure of rabbits.

Apricot seeds due to the presence of cyanogenic glycoside amygdalin belong to the popular "alternative cancer cures", although anticancer effect of amygdalin remains controversial. This in vivo study points to the effect of long-term peroral administration of bitter apricot seeds on bone microstructure of rabbits since chronic amygdalin toxicity in relation to bone parameters has not been investigated yet. Rabbits (n = 16) were randomly divided into four experimental groups of 4 animals each. Three experimental groups S1, S2 and S3 received commercial feed for rabbits mixed with crushed bitter apricot seeds at doses 60, 300 and 420 mg/kg bw during five months, respectively. The control (C) group received no apricot seeds. The long-term consumption of apricot seeds had no impact on total body weight, femoral weight and femoral length of rabbits. Also, microcomputed tomography (3D analysis) of cortical and trabecular bone tissues did not reveal any significant impact of amygdalin toxicity on relative bone volume, BMD, cortical bone thickness, bone surface, trabecular number, thickness, and their separation. On the other hand, histological (2D) analysis demonstrated evident changes in cortical bone microstructure consistent with a decreased density of secondary osteons in the middle part of substantia compacta due to a replacement of Haversian bone tissue by plexiform bone tissue, vasoconstriction in the primary osteons' vascular canals, Haversian canals, and decreased sizes of secondary osteons in rabbits from S1, S2 and S3 groups. These negative changes are associated with different vascularization and biomechanical properties of cortical bones.

Single and simultaneous effects of acrylamide and ethanol on bone microstructure of mice after one remodeling cycle.

BACKGROUND: This study aimed to examine femoral bone microstructure of mice after single and simultaneous administration to acrylamide and ethanol since both substances are often consumed separately and/or together by humans. Interactive effects of these toxins were analysed after one remodeling cycle. METHODS: Twenty clinically healthy adult mice were randomly divided into four groups following 2 weeks administration of toxins: A group - mice were fed with acrylamide (40 mg/kg bw); E group - mice were ethanol-fed (15% ethanol); AE group - mice were simultaneously fed with both toxins, and a C group - control (without acrylamide and/or ethanol supplementation). Generally, 2D and 3D imaging methods were used to determine cortical and trabecular bone tissues microstructure. Biochemical analyses of plasma parameters were also realized using commercially available ELISA tests and spectrophotometrically. RESULTS: Single and simultaneous exposure to acrylamide and ethanol affected only cortical bone microstructure. No significant changes in trabecular bone morphometry were detected among all groups. In mice from the A group, increased endocortical remodeling associated with a higher level of serum calcium and vasoconstriction of primary osteon's vascular canals (POVC) were identified. On the contrary, increased cortical porosity consistent with a decreased relative bone volume, bone mineral density (BMD) and lower levels of alkaline phosphatase (ALP), glutathione (GSH), calcium in plasma and also with vasodilation of POVC were observed in the E group. In the AE group, the highest density of secondary osteons associated with a lower BMD and decreased levels of ALP, GSH were documented. The parameters of POVC and Haversian canals approximated to the C group. In addition, single and simultaneous exposure to both toxins caused liver disease consistent with a higher values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in plasma of all experimental groups. CONCLUSIONS: Single administration to acrylamide and ethanol had negative effects on cortical bone structure of mice after one remodeling cycle. However, we identified possible antagonistic impact of these toxins on the structure of the cortical bone.

Changes in the microstructure of compact and trabecular bone tissues of mice subchronically exposed to alcohol.

BACKGROUND: Alcohol is one of the most commonly consumed neurotoxins by humans. Its negative effect on bone health is known for a long time. However, its impact on qualitative and quantitative 2D characteristics of the compact bone is still unclear. Therefore, the aim of this study was to investigate in detail the effects of subchronic alcohol exposure on compact and trabecular bone tissues microstructure of laboratory mice using 2D and 3D imaging methods. Ten clinically healthy 12 weeks-old mice (males) were randomly divided into two groups. Animals from experimental group (group E; n = 5) drank a solution composed of 15% ethanol and water (1.7 g 100% ethanol kg-1 b.w. per day) for 8 weeks, while those from control group (group C; n = 5) drank only water. RESULTS: Subchronic exposure to alcohol leads to several changes in qualitative 2D characteristics of the compact bone such as the presence of primary vascular radial bone tissue in pars anterior of endosteal border and a higher number of resorption lacunae (five times more) in the middle part of substantia compacta. Morphometrical 2D evaluations of the compact bone showed significantly increased sizes of primary osteons' vascular canals (p < 0.05) in mice from the experimental group (E group). Sizes of Haversian canals and secondary osteons were not affected by alcohol consumption. In mice from the E group, significantly lower values for relative bone volume and bone mineral density of the compact bone were observed. In the trabecular bone, decreased values for bone volume, trabecular number, trabecular thickness and bone surface (p < 0.05) were documented. CONCLUSIONS: Alcohol decreased not only bone volume and density of the compact bone, but it also reduced trabecular bone volume and leads to trabecular thinning. It caused vasodilation of primary osteons' vascular canals and increased porosity in the compact bone.