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Background Social relationships play a fundamental role in individuals’ lives and health, and social isolation is prevalent among older people. Chronic non-communicable diseases (NCDs) and frailty are also common in older adults. Aims To examine the association between number of NCDs and social isolation in a cohort of community-dwelling older adults in the UK, and to consider whether any potential association is mediated by frailty. Methods NCDs were self-reported by 176 older community-dwelling UK adults via questionnaire. Social isolation was assessed using the six-item Lubben Social Network Scale. Frailty was assessed by the Fried phenotype of physical frailty. Results The median (IQR) age of participants in this study was 83.1 (81.5–85.5) years for men and 83.8 (81.5–85.9) years for women. The proportion of socially isolated individuals was 19% in men and 20% in women. More women (18%) than men (13%) were identified as frail. The number of NCDs was associated with higher odds of being isolated in women (unadjusted odds ratio per additional NCD: 1.65, 95% CI 1.08, 2.52, p = 0.021), but not in men, and the association remained robust to adjustment, even when accounting for frailty (OR 1.85, 95% CI 1.06, 3.22, p = 0.031). Discussion Number of self-reported NCDs was associated with higher odds of social isolation in women but not in men, and the association remained after considering frailty status. Conclusions Our observations may be considered by healthcare professionals caring for community-dwelling older adults with multiple NCDs, where enquiring about social isolation as part of a comprehensive assessment may be important.

Osteoporosis, a common chronic metabolic bone disease is associated with considerable morbidity and mortality. As the prevalence of osteoporosis increases with age, a paralleled elevation in the rate of incident fragility fractures will be observed. This narrative review explores the origins of bone and considers physiological mechanisms involved in bone homeostasis relevant to management and treatment. Secondary causes of osteoporosis, as well as osteosarcopenia are discussed followed by an overview of the commonly used pharmacological treatments for osteoporosis in older people. Supplementary Information The online version contains supplementary material available at 10.1007/s40520-021-01817-y.

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital., SCOPUS: re.j, info:eu-repo/semantics/published

Background In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. Aims The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. Methods This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. Results The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. Conclusion The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

Background: we consider the relationships between a clinical and radiological diagnosis of knee or hip OA and activities of daily-living (ADL) in older adults. Methods: data were available for 222 men and 221 women from the Hertfordshire Cohort Study (HCS) who also participated in the UK component of the European Project on Osteoarthritis (EPOSA). Participants completed the EuroQoL survey where they reported if they had difficulties with mobility, self-care, usual activities and movement around their house. Hip and knee radiographs were graded for overall Kellgren and Lawrence score (positive definition defined as a 2 or above). Clinical OA was defined using American College of Rheumatology criteria. Results: in men, a clinical diagnosis of hip or knee OA were both associated with reported difficulties in mobility, ability to self-care and performing usual-activities (hip OA: OR 17.6, 95% CI 2.07, 149, p = 0.009; OR 12.5, 95% CI 2.51, 62.3, p = 0.002; OR 4.92, 95% CI 1.06, 22.8, p = 0.042 respectively. Knee OA: OR 8.18, 95% CI 3.32, 20.2, p

The introduction of anti-resorptive agents over recent decades has changed the perception of osteoporosis from an inevitable consequence of ageing to a treatable non-communicable disease. Anti-resorptive agents such as the bisphosphonates, denosumab, raloxifene and selective oestrogen receptor modulators modulate fracture risk by inhibiting bone resorption and predominantly act to prevent post-menopausal and age-related bone loss. The widespread adoption of anti-resoptive therapies in westernised countries has contributed to a significant reduction in the incidence of fragility fracture. This chapter discusses some of the most commonly used anti-resorptive agents, in addition to calcium and vitamin D supplementation which are often used as adjunctive therapy.

To date conventional osteoporosis therapy has been largely dominated by the use of anti-resorptive therapy but more recently anabolic agents have emerged as an important option for bone health management. Teriparatide is the most well-known anabolic agent. Its efficacy with regard to bone mineral density increase and fracture reduction have been demonstrated in numerous studies while abaloparatide has been licenced in the United States for osteoporosis management. In the last year, a new therapeutic target, romosozumab, an anti-sclerostin monoclonal antibody, achieved approval in both Europe and the United States, for management of osteoporosis. This provides an overview of current and emerging potential therapeutic targets.

Muscle-bone interactions have long been of interest for basic, clinical and translational scientists. Skeletal muscle and bone are recognised as interacting tissues, the so-called ‘muscle-bone unit,’ in which these two tissues communicate to coordinate their development and their response to loading or injury. A wealth of epidemiological data supports the concept of muscle-bone interactions. In this chapter, we will describe how commonly the clinical conditions of both sarcopenia and osteoporosis occur together in individuals, review shared risk factors for the two conditions and discuss possible management strategies.

Osteoporosis is a skeletal disorder characterised by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in the fragility of bone and consequent susceptibility to fracture. The fractures most commonly reported are those of the proximal femur, distal radius and vertebra, but fractures at other sites such as the pelvis, proximal humerus, and proximal tibia, also show similar patterns. These fractures are the serious and important outcomes of the condition and lead to severe mortality and morbidity, a significant burden on society in general and a huge impact economically. Fracture rates vary by age and geography; absolute numbers are expected to rise in subsequent generations despite stabilisation of fracture rates due to demographic population changes. Clustering of fractures is commonly described and may help in the identification of those individuals at highest risk who would benefit most from therapy. This chapter will review the epidemiology of fragility fractures, and highlight the importance of fracture at a personal and societal level.

The bone turnover cycle is responsible for the maintenance of skeletal health and bone repair throughout the lifecourse, and is defined by the work of osteoblasts, which are responsible for bone formation, and osteoclasts, which stimulate bone resorption. Disruptions to the bone turnover cycle in middle or later life can lead to bone diseases characterized by bone loss, such as osteoporosis. Disequilibrium in osteoclast proliferation can lead to osteoporosis, meaning many anti-osteoporosis medications target these cells, as slowing bone resorption has been shown to effectively preserve bone mineral density and protect against fractures. Bone turnover markers found in serum and urine allow for less invasive, repeated measurement of the bone turnover cycle. These repeated measurements within individuals can provide information about both bone health at baseline and response to treatment, making bone turnover markers key tools in monitoring osteoporosis.

Osteoporosis is a disease characterised by poor bone strength and microarchitecture, causing bone fragility, which leads to an increased risk of fractures. Although primarily seen as a disease of old age, evidence is accumulating that in utero and early life environment can set an individual on a trajectory for osteoporosis and fragility fracture in later life. The development of osteoporosis is dependent on peak bone mass, and the subsequent rate of loss. The peak bone mass achieved by the third decade of life has been shown to be a powerful predictor of osteoporosis; although peak bone mass is partly genetically determined, the remaining majority contribution is attributable to environmental exposures in early life and modifiable lifestyle factors through life. Current osteoporosis management focuses on bone loss later in life, but it is important to consider strategies earlier in the lifecourse. This review will focus on events operating in utero, or early in post-natal life that influence bone health of the individual.

Funding: This meeting was founded by the European Society for Clinical and Economics Aspect of Osteoporosis and Osteoarthritis, a not for profit organization from Belgium. Osteoarthritis (OA), a disease affecting different patient phenotypes, appears as an optimal candidate for personalized healthcare. The aim of the discussions of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group was to explore the value of markers of different sources in defining different phenotypes of patients with OA. The ESCEO organized a series of meetings to explore the possibility of identifying patients who would most benefit from treatment for OA, on the basis of recent data and expert opinion. In the first meeting, patient phenotypes were identified according to the number of affected joints, biomechanical factors, and the presence of lesions in the subchondral bone. In the second meeting, summarized in the present article, the working group explored other markers involved in OA. Profiles of patients may be defined according to their level of pain, functional limitation, and presence of coexistent chronic conditions including frailty status. A considerable amount of data suggests that magnetic resonance imaging may also assist in delineating different phenotypes of patients with OA. Among multiple biochemical biomarkers identified, none is sufficiently validated and recognized to identify patients who should be treated. Considerable efforts are also being made to identify genetic and epigenetic factors involved in OA, but results are still limited. The many potential biomarkers that could be used as potential stratifiers are promising, but more research is needed to characterize and qualify the existing biomarkers and to identify new candidates. publishersversion published

Osteoarthritis is a syndrome affecting a variety of patient profiles. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the European Union Geriatric Medicine Society working meeting explored the possibility of identifying different patient profiles in osteoarthritis. The risk factors for the development of osteoarthritis include systemic factors (e.g., age, sex, obesity, genetics, race, and bone density) and local biomechanical factors (e.g., obesity, sport, joint injury, and muscle weakness); most also predict disease progression, particularly joint injury, malalignment, and synovitis/effusion. The characterization of patient profiles should help to better orientate research, facilitate trial design, and define which patients are the most likely to benefit from treatment. There are a number of profile candidates. Generalized, polyarticular osteoarthritis and local, monoarticular osteoarthritis appear to be two different profiles; the former is a feature of osteoarthritis co-morbid with inflammation or the metabolic syndrome, while the latter is more typical of post-trauma osteoarthritis, especially in cases with severe malalignment. Other biomechanical factors may also define profiles, such as joint malalignment, loss of meniscal function, and ligament injury. Early- and late-stage osteoarthritis appear as separate profiles, notably in terms of treatment response. Finally, there is evidence that there are two separate profiles related to lesions in the subchondral bone, which may determine benefit from bone-active treatments. Decisions on appropriate therapy should be made considering clinical presentation, underlying pathophysiology, and stage of disease. Identification of patient profiles may lead to more personalized healthcare, with more targeted treatment for osteoarthritis.