[Show abstract][Hide abstract] ABSTRACT: Sarcopenia, operationally defined as the loss of muscle mass and muscle function, is a major health condition associated with ageing, and contributes to many components of public health at both the patient and the societal levels. Currently, no consensual definition of sarcopenia exists and therefore it is still a challenge to establish the actual prevalence of sarcopenia or to establish the direct and indirect impacts of sarcopenia on public health. Anyway, this geriatric syndrome represents a huge potential public health issue because of its multiple clinical and societal consequences. Moreover, all these aspects have an impact on healthcare costs both for the patient and the society. Therefore, the implementation of effective and broadly applicable preventive and therapeutic interventions has become a medical and societal challenge for the growing number of older persons affected by sarcopenia and its disabling complications.
[Show abstract][Hide abstract] ABSTRACT: Objectives
Existing practice guidelines for osteoarthritis (OA) analyze the evidence behind each proposed treatment but do not prioritize the interventions in a given sequence. The objective was to develop a treatment algorithm recommendation that is easier to interpret for the prescribing physician, based on the available evidence and applicable in Europe and internationally. The knee was used as the model OA joint.
ESCEO assembled a task force of 13 international experts (rheumatologists, clinical epidemiologists, clinical scientists). Existing guidelines were reviewed, all interventions listed and recent evidence retrieved using established databases. A first schematic flow chart with treatment prioritization was discussed in a one-day meeting and shaped to the treatment algorithm. Fine tuning occurred by electronic communication and three consultation rounds until consensus.
Basic principles consist of the need of combined pharmacological and non-pharmacological treatment, with a core set of initial measures including information access/education, weight loss if overweight and an appropriate exercise program. Four multimodal steps are then established. Step 1 consists of background therapy, either non-pharmacological (referral to a physical therapist for re-alignment treatment if needed and sequential introduction of further physical interventions initially and at any time thereafter) and pharmacological. The latter consists of chronic Symptomatic Slow Acting Drugs for OA (e.g. prescription glucosamine sulfate and/or chondroitin sulfate) with paracetamol at-need; topical NSAIDs are added in the still symptomatic patient. Step 2 consists of the advanced pharmacological management in the persistent symptomatic patient and is centered on the use of oral COX-2 selective or non-selective NSAIDs, chosen based on concomitant risk factors, with intra-articular corticosteroids or hyaluronate for further symptom relief if insufficient. In Step 3, the last pharmacological attempts before surgery are represented by weak opioids and other central analgesics. Finally, Step 4 consists of end-stage disease management and surgery, with classical opioids as a difficult to manage alternative when surgery is contraindicated.
The proposed treatment algorithm may represent a new framework for the development of future guidelines for the management of OA, more easily accessible to physicians.
Seminars in Arthritis and Rheumatism 12/2014; · 3.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Among the adverse events of glucocorticoid treatment are bone loss and fractures. Despite available, effective preventive measures, many patients receiving or initiating glucocorticoid therapy are not appropriately evaluated and treated for bone health and fracture risk. Populations with, or at risk of, glucocorticoid-induced osteoporosis (GIOP) to target for these measures are defined on the basis of dose and duration of glucocorticoid therapy and bone mineral density. That patients with GIOP should be treated as early as possible is generally agreed upon; however, diversity remains in intervention thresholds and management guidelines. The FRAX(®) algorithm provides a 10-year probability of fracture that can be adjusted according to glucocorticoid dose. There is no evidence that GIOP and postmenopausal osteoporosis respond differently to treatments. Available anti-osteoporotic therapies such as anti-resorptives including bisphosphonates and the bone anabolic agent teriparatide are effective for the management of GIOP. Prevention with calcium and vitamin D supplementation is less effective than specific anti-osteoporotic treatment. Anti-osteoporotic treatment should be stopped at the time of glucocorticoid cessation, unless the patient remains at increased risk of fracture.
[Show abstract][Hide abstract] ABSTRACT: Gaucher disease is a relatively rare metabolic disease caused by the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Gaucher disease affects multiple organs, among which is the skeleton. Bone involvement occurs frequently in Gaucher disease, and is one of its most debilitating features, reducing the quality of life of patients. Bone status is an important consideration for treatment to ameliorate symptoms and reduce the risk of irreversible complications. We have conducted a systematic review of all the various aspects of Gaucher disease, focusing on different skeletal manifestations, pathophysiology of bone alterations, clinical symptoms, and current diagnostic and therapeutic approaches.
Calcified Tissue International 11/2014; · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis affects one out of three postmenopausal women. Their remaining lifetime risk of fragility fractures exceeds that of breast cancer. The risk of osteoporosis and/or fragility fractures can be reduced through healthy lifestyle changes. These include adequate dietary intakes of calcium, vitamin D and protein, regular weight-bearing exercise, reduction in alcohol intake and smoking cessation. European guidance for the diagnosis and management of osteoporosis in postmenopausal women recommends a daily intake of at least 1000 mg/day for calcium, 800 IU/day for vitamin D and 1 g/kg body weight of protein for all women aged over 50 years. The development of programs that encourage lifestyle changes (in particular balanced nutrient intakes) are therefore essential for the reduction of osteoporosis risk.
[Show abstract][Hide abstract] ABSTRACT: From 50 years of age, postmenopausal women are at an increased risk of developing sarcopenia and osteoporosis as a result of deterioration of musculoskeletal health. Both disorders increase the risk of falls and fractures. The risk of developing sarcopenia and osteoporosis may be attenuated through healthy lifestyle changes, which include adequate dietary protein, calcium and vitamin D intakes, and regular physical activity/exercise, besides hormone replacement therapy when appropriate. Protein intake and physical activity are the main anabolic stimuli for muscle protein synthesis. Exercise training leads to increased muscle mass and strength, and the combination of optimal protein intake and exercise produces a greater degree of muscle protein accretion than either intervention alone. Similarly, adequate dietary protein intake and resistance exercise are important contributors to the maintenance of bone strength. Vitamin D helps to maintain muscle mass and strength as well as bone health. These findings suggest that healthy lifestyle measures in women aged >50 years are essential to allow healthy aging. The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommends optimal dietary protein intake of 1.0–1.2 g/kg body weight/d with at least 20–25 g of high-quality protein at each main meal, with adequate vitamin D intake at 800 IU/d to maintain serum 25-hydroxyvitamin D levels >50 nmol/L as well as calcium intake of 1000 mg/d, alongside regular physical activity/exercise 3–5 times/week combined with protein intake in close proximity to exercise, in postmenopausal women for prevention of age-related deterioration of musculoskeletal health.
[Show abstract][Hide abstract] ABSTRACT: Progress in antiretroviral therapy (ART) has resulted in an almost normal life expectancy for HIV-infected individuals, but an increased risk of fragility fractures has been identified. We investigated the influence of long-term HIV infection on successful ART on bone microstructure in elderly men.
AIDS (London, England) 10/2014; 28(16):2417-27. · 6.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rapid bone defect with normal bone is a challenge in orthopaedics and dentistry. Strontium ranelate (SrRan) has been shown to in vitro decrease bone resorption and increase bone formation, and represents a potential agent with the capacity to accelerate bone defect In this study, bone tibial defects of mm in diameter were created in female rats orally fed SrRan (mg/kg/d; days) or vehicle for or weeks (rats per group per time point) from the time of surgery. Tibias were removed. Micro-architecture was determined by micro-computed tomography (CT) and material level properties by nanoindentation analysis. CT analysis showed that SrRan administration signi improved microarchitecture of trabecular bone growing into the defect a and weeks of treatment compared to vehicle. SrRan treatment also accelerated the growth of cortical bone over the defect, but with di kinetics compared to trabecular bone, as the e were already signi a weeks. Nanoindentation analysis demonstrated that SrRan treatment signi increased material level properties of both trabecular bone and cortical bone the defect compared to vehicle. SrRan accelerates the of bone defect by improving cortical and trabecular bone microarchitecture both quantitatively and qualitatively.
[Show abstract][Hide abstract] ABSTRACT: Prospective controlled evidence supporting the efficacy of long-term exercise to prevent physical decline and reduce falls in old age is lacking. The present study aimed to assess the effects of long-term music-based multitask exercise (i.e., Jaques-Dalcroze eurhythmics) on physical function and fall risk in older adults. A 3-year follow-up extension of a 1-year randomized controlled trial (NCT01107288) was conducted in Geneva (Switzerland), in which 134 community-dwellers aged ≥65 years at increased risk of falls received a 6-month music-based multitask exercise program. Four years following original trial enrolment, 52 subjects (baseline mean ± SD age, 75 ± 8 years) who (i) have maintained exercise program participation through the 4-year follow-up visit ("long-term intervention group", n = 23) or (ii) have discontinued participation following original trial completion ("control group", n = 29) were studied. They were reassessed in a blind fashion, using the same procedures as at baseline. At 4 years, linear mixed-effects models showed significant gait (gait speed, P = 0.006) and balance (one-legged stance time, P = 0.015) improvements in the long-term intervention group, compared with the control group. Also, long-term intervention subjects did better on Timed Up & Go, Five-Times-Sit-to-Stand and handgrip strength tests, than controls (P < 0.05, for all comparisons). Furthermore, the exercise program reduced the risk of falling (relative risk, 0.69; 95 % confidence interval, 0.5-0.9; P = 0.008). These findings suggest that long-term maintenance of a music-based multitask exercise program is a promising strategy to prevent age-related physical decline in older adults. They also highlight the efficacy of sustained long-term adherence to exercise for falls prevention.
Calcified Tissue International 08/2014; · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bone mass, geometry and microstructure, and bony tissue material level properties determine bone strength, hence the resistance to fracture. At a given age, all these variables are the consequence of the amount accumulated and of the structure developed during growth, up to the so-called peak bone mass, and of the bone loss and microstructure degradation occurring later in life. Genetic factors primarly contribute to the variance of the determinants of bone strength. Nutritional intakes are environmental factors that influence both processes, either directly by modifying modeling and remodeling, or indirectly through changes in calcitropic hormone secretion and action. Some effects of nutrition on the offspring bone could take place during fetal life. There are interplays between genetic factors, nutritional intakes and physical exercise. Among the nutrients, sufficient dietary intakes of calcium and protein are necessary for bone health in childhood and adolescence as well as later in life.
Best Practice & Research: Clinical Endocrinology & Metabolism 08/2014; · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: General recommendations for a reference case for economic studies in rheumatic diseases were published in 2002 in an initiative to improve the comparability of cost-effectiveness studies in the field. Since then, economic evaluations in osteoarthritis (OA) continue to show considerable heterogeneity in methodological approach.
Seminars in Arthritis and Rheumatism 06/2014; 44(3). · 3.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity has been associated with increased bone mass, but the mechanisms involved are still poorly understood. We aimed to explore the relationship between bone mineral density and factors known to influence bone formation, in obese and lean adolescents.
We recruited 24 obese and 25 lean adolescents in a case-control study. Total body bone mineral density (TB-BMD) z-scores and body composition were determined using DXA. We measured vitamin D (25-OH-D), glucose, insulin and leptin concentrations. Physical activity (PA) level was quantified using accelerometer.
TB-BMD z-score was higher, while 25-OH-D and PA levels were lower in obese compared to lean subjects (TB-BMD z-score: 1.06 ± 0.96 vs. 0.26 ± 0.91, p = .004; 25-OH-D: 9.9 ± 6.4 vs. 18.5 ± 7.4 ng.ml, p < 0.001; PA level: 308.3 ± 22.1 vs. 406.8 ± 29.2 count.min, p = .01). TB-BMD z-score was not related with 25-OH-D or PA levels, but positively with leptin concentration and fat mass (p < .05). Vitamin D concentration was negatively correlated with fat mass (p < .001).
Despite lower serum vitamin D and physical activity levels, BMD was higher in obese adolescents and associated with higher serum leptin concentrations. Furthermore, obese adolescents have lower vitamin D serum concentrations than lean controls, probably owing to its distribution in adipose tissue.
Journal of pediatric gastroenterology and nutrition 01/2014; · 2.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis is complicated by the occurrence of fragility fractures. Over past years, various treatment options have become available, mostly potent antiresorptive agents such as bisphosphonates and denosumab. However, antiresorptive therapy cannot fully and rapidly restore bone mass and structure that has been lost because of increased remodelling. Alternatively recombinant human parathyroid hormone (rhPTH) analogues do increase the formation of new bone material. The bone formation stimulated by intermittent PTH analogues not only increases bone mineral density (BMD) and bone mass but also improves the microarchitecture of the skeleton, thereby reducing incidence of vertebral and nonvertebral fractures. Teriparatide, a recombinant human PTH fragment available in Switzerland, is reimbursed as second-line treatment in postmenopausal women and men with increased fracture risk, specifically in patients with incident fractures under antiresorptive therapy or patients with glucocorticoid-induced osteoporosis and intolerance to antiresorptives. This position paper focuses on practical aspects in the management of patients on teriparatide treatment. Potential first-line indications for osteoanabolic treatment as well as the benefits and limitations of sequential and combination therapy with antiresorptive drugs are discussed.
Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology 01/2014; 144:w13952. · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Low protein intake is associated with an alteration of bone microstructure and material level properties. However, it remains unknown whether these alterations of bone tissue could influence the response to repeated mechanical loading. The authors investigated the in vitro effect of repeated loading on bone strength in humeri collected from 20 6-month-old female rats pair-fed with a control (15% casein) or an isocaloric low protein (2.5% casein) diet for 10 weeks. Bone specimens were cyclically loaded in three-point bending under load control for 2000 cycles. Humeri were then monotonically loaded to failure. The load-displacement curve of the in vitro cyclically loaded humerus was compared to the contralateral noncyclically loaded humerus and the influence of both protein diets. Material level properties were also evaluated through a nanoindentation test. Cyclic loading decreased postyield load and plastic deflection in rats fed a low protein diet, but not in those on a regular diet. Bone material level properties were altered in rats fed a low protein diet. This suggests that bone biomechanical alterations consequent to cyclic loading are more likely to occur in rats fed a low protein diet than in control animals subjected to the same in vitro cyclic loading regimen.
BioMed Research International 01/2014; 2014:185075. · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Besides its well-known effect on bone metabolism, recent researches suggest that vitamin D may also play a role in the muscular, immune, endocrine, and central nervous systems. Double-blind RCTs support vitamin D supplementation at a dose of 800 IU per day for the prevention of falls and fractures in the senior population. Ecological, case-control and cohort studies have suggested that high vitamin D levels were associated with a reduced risk of autoimmune diseases, type 2 diabetes, cardio-vascular diseases and cancer but large clinical trials are lacking today to provide solid evidence of a vitamin D benefit beyond bone health. At last, the optimal dose, route of administration, dosing interval and duration of vitamin D supplementation at a specific target dose beyond the prevention of vitamin D deficiency need to be further investigated.
[Show abstract][Hide abstract] ABSTRACT: To investigate the efficacy and safety of oral fixed-dose combination strontium ranelate 2 g/vitamin D3 1,000 IU daily vs. strontium ranelate 2 g daily for correction of vitamin D insufficiency in osteoporosis.
A 6-month international, randomized, double-blind, parallel-group, phase 3 study.
518 men and postmenopausal women aged ≥50 years with primary osteoporosis (T-score ≤-2.5 SD) and 25-hydroxyvitamin D [25(OH)D] >22.5 nmol/L were included. Patients were allocated to strontium ranelate 2 g/vitamin D3 1,000 IU daily (n=413) or strontium ranelate 2 g daily (n=105). Participants received calcium 1 g daily. The primary endpoint was serum 25(OH)D at last post-baseline evaluation during 3 months.
Both groups were comparable at baseline. Mean baseline 25(OH)D was 44.1±14.6 nmol/L. After 3 months, the percentage of patients with 25(OH)D ≥50 nmol/L was higher with strontium ranelate/vitamin D3 vs. strontium ranelate (84% vs. 44%, P<0.001) (adjusted between-group odds ratio=6.7; 95% CI, 4.2-10.9). The efficacy on 25(OH)D of the combination was maintained at 6 months (86% vs. 40%, P<0.001). Mean 25(OH)D was 65.1 and 49.5 nmol/L, respectively, after 3 months and 66.9 and 45.4 nmol/L after 6 months. Physical performance improved in both groups. Falls were 17% and 20% in the strontium ranelate/vitamin D3 and strontium ranelate groups, respectively. Parathyroid hormone levels were inversely correlated with 25(OH)D. No clinically relevant differences in safety were observed.
This study confirms the efficacy and safety of fixed-dose combination strontium ranelate 2 g/vitamin D3 1,000 IU for correction of vitamin D insufficiency in osteoporotic patients.
European Journal of Endocrinology 12/2013; · 3.69 Impact Factor