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.

Type 2 diabetes mellitus (T2DM), a serious metabolic disorder, is a worldwide health problem due to the alarming rise in prevalence and elevated morbidity and mortality. Chronic hyperglycemia, insulin resistance, and ineffective insulin effect and secretion are hallmarks of T2DM, leading to many serious secondary complications. These include, in particular, cardiovascular disorders, diabetic neuropathy, nephropathy and retinopathy, diabetic foot, osteoporosis, liver damage, susceptibility to infections and some cancers. Polyphenols such as flavonoids, phenolic acids, stilbenes, tannins, and lignans constitute an extensive and heterogeneous group of phytochemicals in fresh fruits, vegetables and their products. Various in vitro studies, animal model studies and available clinical trials revealed that flavonoids (e.g., quercetin, kaempferol, rutin, epicatechin, genistein, daidzein, anthocyanins), phenolic acids (e.g., chlorogenic, caffeic, ellagic, gallic acids, curcumin), stilbenes (e.g., resveratrol), tannins (e.g., procyanidin B2, seaweed phlorotannins), lignans (e.g., pinoresinol) have the ability to lower hyperglycemia, enhance insulin sensitivity and improve insulin secretion, scavenge reactive oxygen species, reduce chronic inflammation, modulate gut microbiota, and alleviate secondary complications of T2DM. The interaction between polyphenols and conventional antidiabetic drugs offers a promising strategy in the management and treatment of T2DM, especially in advanced disease stages. Synergistic effects of polyphenols with antidiabetic drugs have been documented, but also antagonistic interactions that may impair drug efficacy. Therefore, additional research is required to clarify mutual interactions in order to use the knowledge in clinical applications. Nevertheless, dietary polyphenols can be successfully applied as part of supportive treatment for T2DM, as they reduce both obvious clinical symptoms and secondary complications.

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.

Acrylamide (AA) is one of the most common toxins in foods. Its effect on bone microstructure has not been investigated. The aim of our study was to analyze the impact of acute exposure to AA on femoral bone microstructure in mice. Adult animals were treated perorally with 2 doses of AA (E1 group, 1 mg/kg b.w.) in a 24-h period and with 3 doses of AA (E2 group, 1 mg/kg b.w.) in a 48-h period. Mice exposed to AA had smaller sizes of primary osteon's vascular canals. Secondary osteons were significantly smaller in mice from E2 group; however their increased number (from 38 % to 77 %) was identified in both E1 and E2 groups. In these groups, a higher number of resorption lacunae (from 100 % to 122 %) was also found. The values for bone volume, trabecular number were increased and that for trabecular separation was decreased in mice administered AA. Significantly higher value of bone surface was observed in mice from E1 group whereas trabecular thickness was increased in E2 group. The effect of AA on microstructure of compact and trabecular bone tissues is different. In our study, one dose of AA was used and acute effects of AA were investigated. Therefore, further studies are needed to study mechanisms by which AA acts on bone.

Diabetes mellitus represents a group of metabolic disorders that can adversely affect numerous organ systems, including the skeletal system. It elevates bone fragility and causes secondary osteoporosis, known as diabetic bone disease (DBD). The treatment of DBD depends on the control of hyperglycemia supplemented with anti-osteoporotic agents, but this has unsatisfactory efficiency. This article provides a comprehensive review on the effects of Elaeagnus rhamnoides (L.) A. Nelson (sea buckthorn; family Elaeagnaceae), a prospective anti-diabetic and osteoprotective supplement, and its most abundant flavonoids (quercetin, isorhamnetin, kaempferol) on major mechanisms related to DBD. 'Sea buckthorn' (SB), 'quercetin', 'isorhamnetin', 'kaempferol', 'DBD', 'hyperglycemia', 'inflammatory state', 'insulin resistance' (IR), 'advanced glycation end products' (AGEs) were used as keywords, and relevant literature was obtained from online databases (PubMed, Web of Science, Scopus). SB and flavonoids mentioned above exert hypoglycemic and anti-inflammatory properties, attenuate IR, inhibit AGEs formation, thereby positively affecting the main DBD-related mechanisms. The direct effect of SB on DBD has not been investigated yet, but the beneficial impact of quercetin on DBD has been revealed. Therefore, it can be assumed that SB could favorably influence DBD, as its great potential to treat other bone-related diseases (osteoporosis, rheumatoid arthritis) has been reported. Further research, including high-quality in vitro and animal model studies, as well as large-scale clinical trials, is needed to confirm such a putative positive effect and to identify more efficient therapies against various diabetic complications, including DBD.

The service tree (Sorbus domestica L.) fruits are rich in polyphenols, which exhibit promising therapeutic effects on bone health. This review summarizes the potential benefits of polyphenols identified in Sorbus domestica L. fruits, such as chlorogenic acid (CGA), protocatechuic acid (PCA), rutin, epicatechin, and naringin on bone biology and on bone-related diseases, including osteoporosis and diabetes mellitus. Current evidence suggests that the aforementioned polyphenols may modulate osteoblast and osteoclast activity, enhance mineralization, mitigate oxidative stress and inflammation, thereby supporting overall bone health. Specific studies highlight the anabolic and anti-resorptive effects of CGA, the osteoprotective potential of PCA, and the ability of rutin, epicatechin, and naringin to promote osteogenic differentiation and inhibit osteoclastogenesis. Although the exact mechanisms are still unclear, it is believed that these bioactive metabolites can act through a variety of signalling pathways and epigenetic mechanisms. Despite existing preclinical evidence, there is a significant gap in clinical trials evaluating the direct impact of polyphenols mentioned above on bone health in humans. Therefore, further research is needed to confirm their effectiveness in clinical settings. The therapeutic potential of the most common polyphenols from Sorbus domestica L. fruits has been evaluated by available in vitro and in vivo studies, which highlight their promising potential as dietary interventions to prevent bone loss and improve skeletal integrity in metabolic bone diseases. Based on available information, maximum health benefits may be achieved if mature Sorbus domestica L. fruits are consumed approximately two weeks after harvest or as unripe fruit-based fermented products.