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.

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.

This study aimed to analyse the impact of sea buckthorn (SB) berry extract on the function of cultured rat primary osteoblasts, including the production of bone metabolism-related biomarkers and bone matrix formation. Primary osteoblasts best reflect in vivo conditions. Osteoblast apoptosis, viability, alkaline phosphatase (ALPL) activity, production of ALPL, osteocalcin (BGLAP), collagen type I alpha 1 (COL1A1), integrin-binding sialoprotein (IBSP), tumor necrosis factor ligand superfamily member 11 (TNFSF11), and calcium/collagen deposition were assessed. The composition of the extract showed that the main phenolic metabolites found were flavonol glycosides (67.1 %). SB berry extract significantly increased the levels of BGLAP (at 0.5 and 1 μg/mL), COL1A1 (at 1–100 μg/mL), IBSP (at 0.1–1 μg/mL), collagen deposition (at 1–10 μg/mL), and decreased TNFSF11 levels (at 0.1 and 0.5 μg/mL). Although higher doses of the extract (50 and 100 μg/mL) reduced osteoblast apoptosis, they also lowered cell viability, IBSP levels, and mineralization. It can be concluded that SB berry extract at concentrations up to 10 μg/mL favorably affected multiple bone metabolism-related biomarkers, indicating that it has encouraging potential for use as a nutraceutical to support bone health due to the unique composition of bioactive metabolites and the known synergistic interactions between them.

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.

Introduction: Type 2 diabetes is associated with compromised bone quality. Positive effects of sea buckthorn (SB, Elaeagnus rhamnoides (L.) A. Nelson) berry extract on bone biomarkers have been found in vitro , suggesting its therapeutic potential. This study provides the first evidence on the impact of dried SB berries versus metformin (MET) administration on the skeletal system of the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes. Material and Methods: A total of 30 male ZDF rats (n = 6 per group) were included in the study and randomly assigned to five experimental groups: L (untreated and lean), D (untreated and obese), DM (obese and treated with 150 mg/kg body weight (b.w.)/day of MET), DS1 (obese and treated with 250 mg/kg b.w./day of SB), and DS2 (obese and treated with 500 mg/kg b.w./day of SB). Treatment lasted four months. Biochemical and macroscopic analyses, micro-computed tomography and mechanical testing were performed. Results: The rats from group D had compromised femoral bone microstructure compared with group L (P-value < 0.05) as well as impaired glucose, lipid and liver profiles. Administration of MET (group DM) resulted not only in significant reductions in a bone resorption marker (C-terminal telopeptide of type I collagen) but also in significant increases in cortical and trabecular bone volume fraction and trabecular thickness versus group D (P-value < 0.05). The level of AST, a liver injury marker, was also lower. Supplementation with SB (group DS1) only lowered liver injury markers (AST and ALT) (P-value < 0.05). Conclusion: Administration of dried SB berries at the doses used in this study did not improve bone microstructure or bone turnover markers. Therefore, SB supplementation did not achieve the therapeutic effects of MET in the context of diabetic bone disease, likely because of its limited bioavailability, degradation of its bioactive metabolites during the hot-air drying process and/or insufficiency of dosage.