These findings suggest that sclerostin is increased in DM2. Moreover, the transcriptional suppression of sclerostin production by PTH might be impaired in both DM1 and DM2.

Aromatase is a specific component of the cytochrome P450 enzyme system responsible for the transformation of androgen precursors into estrogens. This enzyme is encoded by the CYP19A1 gene located at chromosome 15q21.2, that is, expressed in ovary and testis, but also in many extraglandular sites such as the placenta, brain, adipose tissue, and bone. The activity of aromatase regulates the concentrations of estrogens with endocrine, paracrine, and autocrine effects on target issues including bone. Importantly, extraglandular aromatization of circulating androgen precursors is the major source of estrogen in men. Clinical and experimental evidences clearly indicate that aromatase activity and estrogen production are necessary for longitudinal bone growth, the attainment of peak bone mass, pubertal growth spurt, epiphyseal closure, and normal bone remodeling in young individuals. Moreover, with aging, individual differences in aromatase activity may significantly affect bone loss and fracture risk in men.

Geriatric Medicine (GM) holds a crucial role in promoting health and managing the complex medical, cognitive, social, and psychological issues of older people. However, basic principles of GM, essential for optimizing the care of older people, are commonly unknown or undermined, especially in countries where GM is still under development. This narrative review aims at providing insights into the role of GM to non-geriatrician readers and summarizing the main aspects of the added value of a geriatric approach across the spectrum of healthcare. Health practitioners of all specialties are frequently encountered with clinical conditions, common in older patients (such as cancer, hypertension, delirium, major neurocognitive and mental health disorders, malnutrition, and peri-operative complications), which could be more appropriately managed under the light of the approach of GM. The role of allied health professionals with specialized knowledge and skills in dealing with older people’s issues is essential, and a multidisciplinary team is required for the delivery of optimal care in response to the needs and aspirations of older people. Thus, countries should assure the educational background of all health care providers and the specialized health and social care services required to meet the demands of a rapidly aging society.

ADVANTAGE Joint Action is a project co-founded by the European Commission and the Member States, with the aim of building a common understanding of frailty on which to base an approach for older people who are frail or at risk. Based on a systematic review of the literature, including grey literature and good practice, where possible, this paper proposes some key interventions to tackle frailty. Prevention should be based on a multifaceted approach, addressing factors that have resonance across the individual's life course. All older people (over 70 years of age) should be offered a screening test and, if positive, referred for diagnosis. The management of frailty must be based on comprehensive geriatric assessment, to enable effective planning. Multicomponent exercise programmes, adequate protein and vitamin D intake, when insufficient, as well as reduction in poly pharmacy and inadequate prescription are the most effective strategies to manage frailty. Objectives: ADVANTAGE Joint Action is a large collaborative project co-founded by the European Commission and its Member States to build a common understanding of frailty for Member States on which to base a common management approach for older people who are frail or at risk of developing frailty. One of the key objectives of the project is presented in this paper; how to manage frailty at the individual level. Methods: A systematic review of the literature was conducted, including grey literature and good practices when possible. Results: The management of frailty should be directed towards comprehensive and holistic treatment in multiple and related fields. Prevention requires a multifaceted approach addressing factors that have resonance across the individual's life course. Comprehensive geriatric assessment to diagnose the condition and plan a personalized multidomain treat ment improves outcomes. Multicomponent exercise programmes, adequate protein and vitamin D intake, when insufficient, and reduction in polypharmacy and inadequate prescription, are the most effective strategies found in the literature to manage frailty effectively. Conclusion: Frailty can be effectively prevented and managed with a multidomain intervention strategy based on comprehensive geriatric assessment.

Toremifene can be administered orally with an excellent bioavailability. The overall pharmacokinetic profile is remarkably similar to tamoxifen. Toremifene is highly metabolized in the liver and is eliminated primarily in the feces following enterohepatic circulation. Some of its metabolites retain biological activity. This SERM was approved by the FDA for the treatment of estrogen receptor-positive metastatic breast cancer and is under investigation for its potential skeletal benefits in men on androgen deprivation therapy. Despite the positive preclinical and clinical evidences for the prevention of bone loss and fractures, the chemopreventive effect on prostate cancer remains to be confirmed and an increased risk of venous thromboembolism was evidenced in a large Phase III trial. Thus, additional data are required to establish the full clinical profile of this compound and its potential advantages over antiresorptive agents commonly in use for the treatment of osteoporosis.