Systemic osteoarthritis: the difficulty of categorically naming a continuous condition.

Osteoarthritis (OA) is a disease with systemic implications that go beyond joint problems. Its pathogenic mechanisms involve a variety of systemic conditions that contribute to joint damage. These include metabolic dysfunction, chronic low-grade inflammation, neuroplastic pain, and the influence of the central nervous system in the development of neuropathic pain. Besides, OA can negatively affect other aspects of health, such as quality of life, reduced physical activity, social isolation, depression, and anxiety. OA can be considered a complex system in which pathological interactions involve not only obesity and metabolic dysfunction, but also fragility syndrome, sarcopenia, neurological complications, and systemic energy redistribution. Complex systems are composed of multiple interacting and dynamic parts and exhibit emergent properties that cannot be fully explained by examining their individual components. Chronic low-grade inflammation is characteristic of OA, occurring both in the affected joint, and systemically, mainly due to adipose tissue inflammation in obese patients. Obesity is a key factor in the progression of OA, so primary treatment should focus on its control, while maintaining muscle health. The chronic inflammation could lead to changes in energy distribution among the affected joint tissues. Therefore, OA should be approached as a systemic disease, considering individual patient factors, such as genetics, inflammatory response, and lifestyle. Medical care should be more holistic and personalized. Consideration of a name change, such as "systemic OA", could help to move away from the perception of a disease focused only on the joints.

Sarcopenia and health-related quality of life: A systematic review and meta-analysis.

The decrease of physical abilities and functional decline that can be caused by musculoskeletal conditions such as sarcopenia, can lead to higher levels of dependency and disability. Therefore, it may influence patient reported outcome measures (PROM), such as the health-related quality of life (HRQoL). The purpose of this systematic review and meta-analysis is to provide a comprehensive overview of the relationship between sarcopenia and HRQoL. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed throughout the whole process of this work. A protocol was previously published on PROSPERO. The electronic databases MEDLINE, Scopus, Allied and Complementary Medicine (AMED), EMB Review - ACP Journal Club, EBM Review - Cochrane Central of Register of Controlled Trials and APA PsychInfo were searched until October 2022 for observational studies reporting a HRQoL assessment in both sarcopenic and non-sarcopenic individuals. Study selection and data extraction were carried out by two independent researchers. Meta-analysis was performed using a random effect model, reporting an overall standardized mean difference (SMD) and its 95% confidence interval (CI) between sarcopenic and non-sarcopenic individuals. Study quality was measured using the Newcastle-Ottawa Scale and the strength of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. The search strategy identified 3725 references from which 43 observational studies were eligible and included in this meta-synthesis study. A significantly lower HRQoL was observed for sarcopenic individuals compared with non-sarcopenic ones (SMD -0.76; 95% CI -0.95; -0.57). Significant heterogeneity was associated with the model (I2  = 93%, Q test P-value <0.01). Subgroup analysis showed a higher effect size when using the specific questionnaire SarQoL compared with generic questionnaires (SMD -1.09; 95% CI -1.44; -0.74 with the SarQoL versus -0.49; 95% CI -0.63; -0.36 with generic tools; P-value for interaction <0.01). A greater difference of HRQoL between sarcopenic and non-sarcopenic was found for individuals residing in care homes compared with community-dwelling individuals (P-value for interaction <0.001). No differences were found between age groups, diagnostic techniques, and continents/regions. The level of evidence was rated as moderate using the GRADE assessment. This systematic review and meta-analysis combining 43 observational studies shows that HRQoL is significantly reduced in sarcopenic patients. The use of disease-specific HRQoL instruments may better discriminate sarcopenic patients with respect to their quality of life.

Role of vitamin D supplementation in the management of musculoskeletal diseases: update from an European Society of Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group.

Vitamin D is a key component for optimal growth and for calcium-phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration.

Lifestyle approaches to prevent and retard sarcopenia: A narrative review.

Sarcopenia, with its high prevalence and its adverse health outcomes, amongst older adults is considered a major public health problem. Its primary, secondary and tertiary preventions are therefore very important. Our objective was to review the effects of lifestyle factors, including not only dietary habits and exercise but also social use of substances such as alcohol and tobacco, on the incidence of sarcopenia and on its health outcomes. We found that the effect of lifestyle on muscle parameters or physical function has been investigated in many trials of heterogeneous design and quality. However, based on data from interventional studies, we can be confident that loss of physical function and its consequences can be counteracted by physical activity. There are some interesting data, mainly evident from observational studies, suggesting that healthier dietary patterns may improve muscle health. The combination of exercise with dietary supplement has more conflicting results and the effect of other lifestyle changes, such as cessation of alcohol or tobacco use, is difficult to establish clearly. Further high-quality trials are needed to substantiate the mechanism of action of each intervention as well as to determine the optimal modalities of these in older adults.

Orthogeriatrics: a vital requirement for improving fragility fracture patient care internationally with particular reference to Turkey.

PURPOSE: Orthogeriatrics is a team approach that aims to provide adequate and timely intervention for individuals suffering from fragility fractures, particularly hip fractures. These patients are mostly the frailest older adults. The aim of orthogeriatrics is to re-gain functionality as early as possible and to decrease disability and mortality. Some developed countries have established orthogeriatric services, while many others, including Turkey, have so far not. Here, to identify areas for improvement, we outline the status of the orthogeriatrics in older adults in Turkey. METHODS: We present clear calls for action, emphasizing possible and noteworthy areas for improvement. RESULTS: Our proposals include the need for an easily applied, short version of comprehensive geriatric assessment; appropriate laboratory testing on admission; paracetamol with a special emphasis in its dosings and clues for state-of-the-art analgesic management; the essential need to introduce oral nutritional supplementation, irrespective of nutritional status; the need for vitamin D commencement, in almost all patients; and starting osteoporosis treatment in fracture hospitalization, whenever appropriate. Last but not least, the ever-increasing prerequisite to establish "fracture liaison services" is stipulated. CONCLUSION: We suggest that our recommendations offer great potential in Turkey, for the improvement of frail fracture patients' care. We call the other countries that do not have established orthogeriatric lines to model our approach to improve the management of fracture patients globally.

Cost-Effectiveness Assessment of Different Glucosamines in Patients with Knee Osteoarthritis: A Simulation Model Adapted to Germany.

BACKGROUND: The use of symptomatic slow-acting drugs for osteoarthritis (OA) (e.g., glucosamine, chondroitin) is largely debated in the scientific literature. Indeed, multiple formulations of these agents are available, both as pharmaceutical-grade products and as nutritional supplements , but while all preparations may claim to deliver a therapeutic effect, not all are supported by clinical evidence. Moreover, few data are available regarding the cost-effectiveness of all these formulations. Usually, access to individual patient data is required to perform economic evaluations of treatments, but it can be challenging to obtain. We previously developed a model to simulate individual health utility scores from aggregated data obtained from published OA trials. OBJECTIVE: In the present study, using our new simulation model, we investigated the costeffectiveness of different glucosamines used in Germany. METHODS: We used our validated model to simulate the utility scores of 10 published trials that used different glucosamine preparations. Using the simulated utility scores, the quality-adjusted life years (QALYs) were calculated using the area-under-the-curve method. We used the 2018 public costs of glucosamine products available in Germany to calculate the Incremental Cost/Effectiveness Ratio (ICER). We performed analyses for pharmaceutical-grade Crystalline Glucosamine Sulfate (pCGS) and other formulations of glucosamine (OFG). A cost-effectiveness cut-off of 30,000 €/QALY was considered. RESULTS: Of 10 studies in which utility was simulated, four used pCGS, and six used OFG. The ICER analyses showed that pCGS was cost-effective compared to a placebo, with an ICER of 4489 €/QALY at month 3, 4112 €/QALY at month 6, and 9983 €/QALY at year 3. The use of OFG was not cost-effective at any of the time points considered. CONCLUSION: Using our previously published model to simulate the individual health utility scores of patients, we showed that, in the German context, the use of pCGS could be considered costeffective, while the use of OFG could not. These results highlight the importance of the formulation of glucosamine.

Highly purified chondroitin sulfate: a literature review on clinical efficacy and pharmacoeconomic aspects in osteoarthritis treatment.

Osteoarthritis (OA) is the most prevalent musculoskeletal disease and a major cause of negative relevant outcomes, associated with an ever-increasing societal burden. Pharmaceutical-grade chondroitin sulfate (CS) was repeatedly reported to reduce pain and improve function in patients with OA. This article aims to review the evidence for the role of highly purified (hp) CS (Condrosulf®, IBSA) in the treatment of OA. We collected and reported evidence concerning (1) efficacy of hpCS 800 mg/day in the treatment of OA affecting the knee, hand and hip; (2) efficacy and safety of hpCS 1200 mg/day also in the oral gel formulation; (3) the safety profile of hpCS; (4) the difference of hpCS and pharmaceutical-grade formulations versus food supplements; (5) pharmacoeconomic added value of hpCS. The data support that hpCS is an effective and safe treatment of OA, with its effect already evident at 30 days; in addition, its beneficial action is prolonged, being maintained for at least 3 months after the drug is discontinued. Full safety reports' analyses confirm that CS is safe to use and has almost no side effects, in particular, it showed better gastrointestinal tolerance if compared with non-steroidal anti-inflammatory drugs (NSAIDs). Moreover, the therapeutic strategy has proved to be cost-effective: treatment with CS reduced the use of NSAIDs and their side effects.

Redesigning care for older people to preserve physical and mental capacity: WHO guidelines on community-level interventions in integrated care.

Islene Araujo de Carvalho and coauthors discuss the WHO guidelines on integrated care for older people.

Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

BACKGROUND: Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA). OBJECTIVE: We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports. METHODS: We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system. RESULTS: Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of total AEs (odds ratio [OR] 2.22; 95% confidence interval [CI] 1.58-3.13; I2 = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02-4.04; I2 = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36-4.96; I2 = 17.0%) compared with placebo. In studies that allowed concomitant OA medications, diacerein was associated with significantly more dermatological disorders (OR 2.47; 95% CI 1.42-4.31; I2 = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85-5.47; I2 = 13.4%) than was placebo. No significant increase in serious or severe AEs was found with diacerein versus placebo. CONCLUSIONS: GS and CS can be considered safe treatments for patients with OA. All eligible studies on ASU included in our analysis used the proprietary product Piascledine® and allowed other anti-OA medications; thus, the safety of ASU must be confirmed in future studies without concomitant anti-OA medications. Given the safety concerns with diacerein, its usefulness in patients with OA should be assessed, taking into account individual patient characteristics.

Efficacy of Chondroitin Sulfate in Patients with Knee Osteoarthritis: A Comprehensive Meta-Analysis Exploring Inconsistencies in Randomized, Placebo-Controlled Trials.

INTRODUCTION: There are some controversies about treatment modalities in osteoarthritis (OA), including chondroitin sulfate (CS). The objective of this study was to determine whether CS is effective at alleviating pain and improving function in patients with knee OA and to identify the factors that explain inconsistencies in clinical trial results. METHODS: We conducted a systematic review of randomized, placebo-controlled trials, searching the databases Medline, Cochrane central register for controlled trials and Scopus. Random effects meta-analysis was then performed, using tau2 and I2 statistics to assess heterogeneity. The pain and Lequesne index (LI) scores were expressed as standardized mean differences (SMDs), with a 95% confidence interval (CI). Heterogeneity was explored by stratifying the analyses according to pre-specified study-level characteristics and assessing the sources of funnel plot asymmetry. RESULTS: The inclusion criteria yielded 18 trials. Overall, CS significantly but inconsistently reduced pain (SMD: - 0.63; 95% CI: - 0.91, - 0.35; I2 = 94%) and improved function (SMD: - 0.82; 95% CI: - 1.31, - 0.33; I2 = 95%). When limiting the analysis to studies with a low risk of bias, the pharmaceutical grade CS of IBSA origin showed a greater reduction in pain (SMD: - 0.25; 95% CI: - 0.34, - 0.16; I2 = 75%) and function (SMD: - 0.33; 95% CI: - 0.47, - 0.20; I2 = 53%, p = 0.07) compared with the other preparations (SMDPain: - 0.08; 95% CI: - 0.19, + 0.02; I2 = 20%; SMDFunction: - 0.18; 95% CI: - 0.36, +0.01; I2 = 0%). Assessing funnel plot asymmetry in the studies with a low risk of bias, we found strong correlations between the treatment effects and study size (pain: rS = 0.93; LI: rS = 0.86; p < 0.05). Ultimately, there was no residual heterogeneity in the CS effects when the smallest studies were removed from the analyses. CONCLUSION: This new meta-analysis suggests that CS provides a moderate benefit for pain and has a large effect on function in knee OA, however with large inconsistency. The risks of bias, brand and study size were the factors explaining heterogeneity among the clinical trial results.

The effects of calorie restriction, intermittent fasting and vegetarian diets on bone health.

Uncountable health care organizations, clinicians, and individuals are striving to prevent obesity and the many chronic medical conditions linked to it by advocating a healthy lifestyle that includes measures such as reducing dietary calorie intake (i.e., calorie restriction = CR and intermittent fasting = IF) or limiting/abolishing animal source foods (i.e., practices termed vegetarianism and veganism). Although these regimens are traditionally considered healthy, their real impact on bone health has yet to be established, and some studies have reported that they have negative effects on bone outcomes. The current work provides an overview of the studies carried out to examine the effect/s of CR, IF and vegetarian/vegan diets on bone health, and, in particular, on bone mineral density (BMD) and fracture risk. Although data on this subject are limited to small studies and there is no information specifically referring to fractures, CR, but not IF, seems to reduce BMD but does not seem to affect bone quality. Vegetarian diets (particularly vegan ones) are associated with significantly lower BMD values with respect to omnivorous ones and could, potentially, increase the risk of fractures. Given these considerations, individuals who decide to follow these diets should be aware of the risk of osteoporosis and of bone fractures and should introduce dietary sources of calcium and Vitamin D and/or supplementation. Future studies examining fracture/osteoporosis incidence in selected populations will be able expand our knowledge about the safety of these diets and the risks linked to them.

Nutritional Status and Nutritional Treatment Are Related to Outcomes and Mortality in Older Adults with Hip Fracture.

Malnutrition is very prevalent in geriatric patients with hip fracture. Nevertheless, its importance is not fully recognized. The objective of this paper is to review the impact of malnutrition and of nutritional treatment upon outcomes and mortality in older people with hip fracture. We searched the PubMed database for studies evaluating nutritional aspects in people aged 70 years and over with hip fracture. The total number of studies included in the review was 44, which analyzed 26,281 subjects (73.5% women, 83.6 ± 7.2 years old). Older people with hip fracture presented an inadequate nutrient intake for their requirements, which caused deterioration in their already compromised nutritional status. The prevalence of malnutrition was approximately 18.7% using the Mini-Nutritional Assessment (MNA) (large or short form) as a diagnostic tool, but the prevalence was greater (45.7%) if different criteria were used (such as Body Mass Index (BMI), weight loss, or albumin concentration). Low scores in anthropometric indices were associated with a higher prevalence of complications during hospitalization and with a worse functional recovery. Despite improvements in the treatment of geriatric patients with hip fracture, mortality was still unacceptably high (30% within 1 year and up to 40% within 3 years). Malnutrition was associated with an increase in mortality. Nutritional intervention was cost effective and was associated with an improvement in nutritional status and a greater functional recovery. To conclude, in older people, the prevention of malnutrition and an early nutritional intervention can improve recovery following a hip fracture.

Inappropriate claims from non-equivalent medications in osteoarthritis: a position paper endorsed by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Osteoarthritis (OA) is a progressive joint disease, that occurs frequently in the aging population and is a major cause of disability worldwide. Both glucosamine and chondroitin are biologically active molecules that are substrates for proteoglycan, an essential component of the cartilage matrix. Evidence supports the use of glucosamine and chondroitin as symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) with impact on OA symptoms and disease-modifying effects in the long term. Glucosamine and chondroitin are administered in exogenous form as a sulfate salt and multiple formulations of these agents are available, both as prescription-grade products and nutritional supplements. However, while all preparations may claim to deliver a therapeutic level of glucosamine or chondroitin not all are supported by clinical evidence. Only patented crystalline glucosamine sulfate (pCGS) is shown to deliver consistently high glucosamine bioavailability and plasma concentration in humans, which corresponds to demonstrated clinical efficacy. Similarly, clinical evidence supports only the pharmaceutical-grade chondroitin sulfate. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) advocates, through careful consideration of the evidence base, that judicious choice of glucosamine and chondroitin formulation is essential to maximize clinical benefit, patient adherence and satisfaction with treatment. In future, the ESCEO recommends that complex molecules with biological activity such as pCGS may be treated as "biosimilars" akin to the European Medicines Agency guidance on biological medicinal products. It seems likely that for all other complex molecules classed as SYSADOAs, the recommendation to use only formulations clearly supported by the evidence-base should apply.

The projected public health and economic impact of vitamin D fortified dairy products for fracture prevention in France.

BACKGROUND: There is a paucity of research that projects the public health and economic impact of healthcare interventions in the future. In this study, we aimed to estimate the public health and economic impact of vitamin D fortified dairy products for the years 2020, 2030, 2040, 2050 and 2060. METHODS: We used a previously validated Markov microsimulation model that was designed to assess the public health and economic impact of dairy products for fracture prevention in the French general population aged over 60 years in the year 2015. RESULTS: The expected benefit (in terms of fractures prevented) of the recommended intake of dairy products compared to the absence of appropriate intake is expected to increase by 63% in 2040 and by 85% in 2060. The cost per quality-adjusted life years gained of the appropriate intake of dairy products is expected to decrease from €58,244 in 2015 to €42,616 in 2060. CONCLUSION: The potential public health and economic benefits of vitamin D fortified dairy products is expected to substantially increase in the future, especially in the population aged over 80 years. Decision makers should be aware of the current and future potential benefits of dairy products to protect bone fractures.

The prevention of fragility fractures in patients with non-metastatic prostate cancer: a position statement by the international osteoporosis foundation.

Androgen deprivation therapy is commonly employed for the treatment of non-metastatic prostate cancer as primary or adjuvant treatment. The skeleton is greatly compromised in men with prostate cancer during androgen deprivation therapy because of the lack of androgens and estrogens, which are trophic factors for bone. Men receiving androgen deprivation therapy sustain variable degrees of bone loss with an increased risk of fragility fractures. Several bone antiresorptive agents have been tested in randomized controlled trials in these patients. Oral bisphosphonates, such as alendronate and risedronate, and intravenous bisphosphonates, such as pamidronate and zoledronic acid, have been shown to increase bone density and decrease the risk of fractures in men receiving androgen deprivation therapy. Denosumab, a fully monoclonal antibody that inhibits osteoclastic-mediated bone resorption, is also effective in increasing bone mineral density and reducing fracture rates in these patients. The assessment of fracture risk, T-score and/or the evaluation of prevalent fragility fractures are mandatory for the selection of patients who will benefit from antiresorptive therapy. In the future, new agents modulating bone turnover and skeletal muscle metabolism will be available for testing in these subjects.

Vitamin D and osteosarcopenia: an update from epidemiological studies.

PURPOSE OF REVIEW: The review summarizes recent epidemiological studies that examined the relationship between osteoporosis and sarcopenia to assess the impact of vitamin D status or supplementation on health outcomes related to these two medical conditions. RECENT FINDINGS: Osteoporosis and sarcopenia are major public health problems, but whether these two diseases should be considered alone or combined into a single condition is not clear. No consensual definition of osteosarcopenia is largely accepted. Most observational studies demonstrate some relationship between muscle and bone health. Vitamin D status is generally lower in study participants with bone or muscle wasting. Studies on the effects of vitamin D supplementation on muscle or bone health have provided conflicting results, likely because of the heterogeneity between studies. However, the most positive results were observed in study participants with low vitamin D status and in studies that avoided massive boluses of vitamin D. SUMMARY: More observational and interventional studies are needed to confirm the exact role of vitamin D in the pathophysiology and treatment of osteosarcopenia.

A scoping review of the public health impact of vitamin D-fortified dairy products for fracture prevention.

PURPOSE: Dairy products are rich in nutrients that positively influence bone health and hence fracture risk, and have therefore been recommended and used for fracture prevention. To help decision makers to efficiently allocate scare resources, it is further important to assess the public health and economic impact of any health intervention. In recent years, several studies have been conducted to estimate the public health and/or economic impact of dairy products but no overview is currently available. This article aims therefore to summarize evidence and review articles that estimated the public health and/or economic impact of vitamin D-fortified dairy products for fracture prevention. METHODS: A literature review was conducted using PubMed to identify original studies that assessed the public health and/or economic impact of dairy products (or of calcium/vitamin D supplementation) for fracture prevention up to January 15, 2017. RESULTS: Seven articles were identified. Different strategies were used by the authors to model the economic/public health impact of dairy products. The four studies assessing the public health impact of dairy products revealed a substantial benefit in terms of fracture prevented, life years, disability-adjusted life years and/or quality-adjusted life years gained. Studies assessing the cost-effectiveness revealed that the use of dairy products is generally cost-effective in the general population aged above 70 years, and from the age of 60 years in populations at high risk of fractures. CONCLUSION: This systematic review suggests that the use of dairy products could substantially reduce the burden of osteoporotic fractures and seem to be an economically beneficial strategy.

Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG.

BACKGROUND: Several guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL). PATIENTS AND METHODS: A systematic literature review identified recent advances in the management of AIBL. Results with individual agents were assessed based on trial design, size, follow-up, and safety. RESULTS: Several fracture related risk factors in patients with EBC were identified. Although, the FRAX algorithm includes fracture risk factors (RF) in addition to BMD, it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women with a 34% relative risk reduction in bone metastasis and 17% relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL. CONCLUSIONS: In all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<-2.0 or with a T-score of <-1.5 SD with one additional RF, or with ≥2 risk factors (without BMD) for the duration of AI treatment. Patients with T-score>-1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12 - 24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.

Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO).

INTRODUCTION: Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures. A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects. PURPOSE AND METHODS: Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have reviewed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases, providing recommendations and guidelines for future studies in this field. RESULTS AND CONCLUSIONS: Robust mechanistic evidence is available from in vitro studies and in vivo animal studies, usually employing cholecalciferol, calcidiol or calcitriol in pharmacologic rather than physiologic doses. Although many cross-sectional and prospective association studies in humans have shown that low 25-hydroxyvitamin D levels (i.e., <50 nmol/L) are consistently associated with chronic diseases, further strengthened by a dose-response relationship, several meta-analyses of clinical trials have shown contradictory results. Overall, large randomized controlled trials with sufficient doses of vitamin D are missing, and available small to moderate-size trials often included people with baseline levels of serum 25-hydroxyvitamin D levels >50 nmol/L, did not simultaneously assess multiple outcomes, and did not report overall safety (e.g., falls). Thus, no recommendations can be made to date for the use of vitamin D supplementation in general, parental compounds, or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases. Moreover, attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health cannot be recommended based on current evidence, since safety has yet to be confirmed. Finally, the promising findings from mechanistic studies, large cohort studies, and small clinical trials obtained for autoimmune diseases (including type 1 diabetes, multiple sclerosis, and systemic lupus erythematosus), cardiovascular disorders, and overall reduction in mortality require further confirmation.

Adverse Health Events Related to Self-Medication Practices Among Elderly: A Systematic Review.

BACKGROUND: Older adults often resort to self-medication to relieve symptoms of their current illnesses; however, the risks of this practice are multiplied in old age. In particular, this age group is more vulnerable to adverse drug events because of the physiological changes that occur due to senescence. OBJECTIVE: The aim of the study was to obtain an overview of the adverse health events related to self-medication among subjects aged 60 years and over through a systematic review of the literature. METHODS: A study of relevant articles was conducted among databases (MEDLINE, PsycINFO, and EBM Reviews-Cochrane Database of Systematic Reviews). Eligibility criteria were established and applied by two investigators to include suitable studies. The results and outcomes of interest were detailed in a descriptive report. RESULTS: The electronic search identified 4096 references, and the full texts of 74 were reviewed, of which four were retained in the analysis: three had a cross-sectional design and one prospectively followed elderly subjects. The first study showed a 26.7% prevalence of adverse drug reactions (ADRs) among elders, the second study found a 75% prevalence of side effects, and, finally, a prospective study showed an ADR incidence of 4.5% among self-medicated elders. These studies showed that adverse health events related to self-medication are relatively frequently reported. They also highlighted that analgesics and anti-inflammatory drugs are the most self-medicated products, while vitamins and dietary supplements also appear to be frequently self-administered, but by older individuals. CONCLUSIONS: Studies on self-medication in the elderly and its adverse health effects are clearly lacking. There is a need to perform prospective studies on this topic to gain a clear understanding of the extent of this problem and to enhance the awareness of health professionals to better inform seniors.