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.

Osteocalcin (OC) is the most abundant non-collagenous and osteoblast-secreted protein in bone. It consists of two forms such as carboxylated OC (cOC) and undercarboxylated OC (ucOC). While cOC promotes bone mineralization and increases bone strength, ucOC is regarded an endocrinologically active form that may have several functions in multiple end organs and tissues. Total OC (tOC) includes both of these forms (cOC and ucOC) and is considered a marker of bone turnover in clinical settings. Most of the data on OC is limited to preclinical studies and therefore may not accurately reflect the situation in clinical conditions. For the stated reason, the aim of this review was not only to summarize current knowledge of all forms of OC and characterize its role in diabetes mellitus, osteoporosis, osteopetrosis, inflammatory joint diseases, but also to provide new interpretations of its involvement in the management and treatment of aforementioned diseases. In this context, special emphasis was placed on available clinical trials. Significantly lower levels of tOC and ucOC could be associated with the risk of type 2 diabetes mellitus. On the contrary, tOC level does not seem to be a good indicator of high bone turnover status in postmenopausal osteoporosis, osteoarthritis and rheumatoid arthritis. The associations between several pharmacological drugs used to treat all disorders mentioned above and OC levels have also been provided. From this perspective, OC may serve as a medium through which certain medications can influence glucose metabolism, body weight, adiponectin secretion, and synovial inflammation.

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.

Osteoporosis and breast cancer are serious diseases that have become a significant socioeconomic burden. There are biochemical associations between the two disorders in terms of the amended function of estrogen, receptor activator of nuclear factor kappa beta ligand, oxidative stress, inflammation, and lipid accumulation. Honey as a functional food with high antioxidant and anti-inflammatory properties can contribute to the prevention of various diseases. Its health benefits are mainly related to the content of polyphenols. This review aims to summarize the current knowledge from in vitro, animal, and human studies on the use of honey as a potential therapeutic agent for osteoporosis and breast cancer. Preclinical studies have revealed a beneficial impact of honey on both bone health (microstructure, strength, oxidative stress) and breast tissue health (breast cancer cell proliferation and apoptosis, tumor growth rate, and volume). The limited number of clinical trials, especially in osteoporosis, indicates the need for further research to evaluate the potential benefits of honey in the treatment. Clinical studies related to breast cancer have revealed that honey is effective in increasing blood cell counts, interleukin-3 levels, and quality of life. In summary, honey may serve as a prospective therapeutic supplement for bone and breast tissue health.

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.