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.

Current knowledge of bone-derived factor osteocalcin: its role in the management and treatment of diabetes mellitus, osteoporosis, osteopetrosis and inflammatory joint diseases.

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.

Honey: A Promising Therapeutic Supplement for the Prevention and Management of Osteoporosis and Breast Cancer.

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.

The link between bone-derived factors osteocalcin, fibroblast growth factor 23, sclerostin, lipocalin 2 and tumor bone metastasis.

The skeleton is the third most common site of metastatic disease, which causes serious bone complications and short-term prognosis in cancer patients. Prostate and breast cancers are responsible for the majority of bone metastasis, resulting in osteolytic or osteoblastic lesions. The crosstalk between bone cells and their interactions with tumor cells are important in the development of lesions. Recently, both preclinical and clinical studies documented the clinical relevance of bone-derived factors, including osteocalcin (OC) and its undercarboxylated form (ucOC), fibroblast growth factor 23 (FGF23), sclerostin (SCL), and lipocalin 2 (LCN2) as prognostic tumor biomarkers and potential therapeutic targets in bone metastasis. Both OC and ucOC could be useful targets for the prevention of bone metastasis in breast cancer. Moreover, elevated OC level may be a metastatic marker of prostate cancer. FGF23 is particularly important for those forms of cancer that primarily affect bone and/or are characterized by bone metastasis. In other tumor entities, increased FGF23 level is enigmatic. SCL plays a significant role in the pathogenesis of both osteolytic and osteoblastic lesions, as its levels are high in metastatic breast and prostate cancers. Elevated expression levels of LCN2 have been found in aggressive subtypes of cancer. However, its role in anti-metastasis varies significantly between different cancer types. Anyway, all aforementioned bone-derived factors can be used as promising tumor biomarkers. As metastatic bone disease is generally not curable, targeting bone factors represents a new trend in the prevention of bone metastasis and patient care.