Physical exercise and sarcopenia in older people: position paper of the Italian Society of Orthopaedics and Medicine (OrtoMed).

Sarcopenia is the age-associated loss of skeletal muscle mass and function. It is a major clinical problem for older people and research in understanding of pathogenesis, clinical consequences, management, and socioeconomic burden of this condition is growing exponentially. The causes of sarcopenia are multifactorial, including inflammation, insulin resistance, changing endocrine function, chronic diseases, nutritional deficiencies and low levels of physical activity. Operational definition of sarcopenia combines assessment of muscle mass, muscle strength and physical performance. The diagnosis of sarcopenia should be based on having a low appendicular fat free mass in combination with low handgrip strength or poor physical functioning. Imaging techniques used for estimating lean body mass are computed tomography, magnetic resonance imaging, bioelectrical impedance analysis and dual energy X-ray absorptiometry, the latter considered as the preferred method in research and clinical use. Pharmacological interventions have shown limited efficacy in counteracting the age-related skeletal muscle wasting. Recent evidence suggests physical activity and exercise, in particular resistance training, as effective intervention strategies to slow down sarcopenia. The Italian Society of Orthopaedics and Medicine (Or-toMed) provides this position paper to present the update on the role of exercise on sarcopenia in the elderly.

Spatial-Temporal resolution implementation of cloud-aerosols data through satellite cross-correlation.

The Moderate Resolution Imaging Spectroradiometer (MODIS) instrument aboard Terra and Aqua satellites provides measurements of several atmospheric parameters. This paper focuses on the cloud fraction data representing the number of cloudy pixels divided by the total number of pixels, and available through 1° x 1° grids spatial resolution with daily or monthly temporal resolution. The aim of the study is to propose a novel method called The Spatial-Temporal Implementation Algorithm (STIA) for analysing satellite daily 1° x 1°grid cloud fraction average values for•Comparing two datasets retrieved by MODIS aboard Aqua and Terra satellites to obtain information on the cloud formation in the afternoon and morning, respectively, thus enhancing the temporal resolution.•Comparing the actual parameter with others retrieved by instruments aboard of different satellites characterized by a better resolution. As an example of STIA application, this study uses the Aerosol Optical Depth (AOD) collected by the Ozone Monitoring Instrument (OMI) on board of Aura satellite for comparison with MODIS instrument to achieve and enhanced spatial resolution of the grid-cell.

Artificial neural network analysis of bone quality DXA parameters response to teriparatide in fractured osteoporotic patients.

Teriparatide is a bone-forming therapy for osteoporosis that increases bone quantity and texture, with uncertain action on bone geometry. No data are available regarding its influence on bone strain. To investigate teriparatide action on parameters of bone quantity and quality and on Bone Strain Index (BSI), also derived from DXA lumbar scan, based on the mathematical model finite element method. Forty osteoporotic patients with fractures were studied before and after two years of daily subcutaneous 20 mcg of teriparatide with dual X-ray photon absorptiometry to assess bone mineral density (BMD), hip structural analysis (HSA), trabecular bone score (TBS), BSI. Spine deformity index (SDI) was calculated from spine X-ray. Shapiro-Wilks, Wilcoxon and Student's t test were used for classical statistical analysis. Auto Contractive Map was used for Artificial Neural Network Analysis (ANNs). In the entire population, the ameliorations after therapy regarded BSI (-13.9%), TBS (5.08%), BMD (8.36%). HSA parameters of femoral shaft showed a worsening. Dividing patients into responders (BMD increase >10%) and non-responders, the first presented TBS and BSI ameliorations (11.87% and -25.46%, respectively). Non-responders presented an amelioration of BSI only, but less than in the other subgroup (-6.57%). ANNs maps reflect the mentioned bone quality improvements. Teriparatide appears to ameliorate not only BMD and TBS, but also BSI, suggesting an increase of bone strength that may explain the known reduction in fracture risk, not simply justified by BMD increase. BSI appears to be a sensitive index of TPD effect. ANNs appears to be a valid tool to investigate complex clinical systems.

Genetic epidemiology of Paget's disease of bone in italy: sequestosome1/p62 gene mutational test and haplotype analysis at 5q35 in a large representative series of sporadic and familial Italian cases of Paget's disease of bone.

Families affected by Paget's disease of bone frequently harbor mutations in the SQSTM1/p62 gene. In this multicentric study we collected 345 sporadic and 12 familial PDB cases throughout Italy, identifying 12 different mutations, 5 of which are newly reported and 3, D335E, A381V, and Y383X, external to the UBA domain. Subjects with truncating mutations, E396X, showed a significantly younger age at clinical diagnosis, while the Y383X subjects had a higher average number of affected skeletal sites. All the mutants exhibited the CGTG-H2 haplotype. In two pairs and one triad of unrelated Italian PDB families from different Italian regions, we detected a common SQSTM1/p62 mutation for each P392L, M404V, and G425R group. Since the CGTG-H2 haplotype frequency was also high in normal subjects, and genetic influence due to migratory fluxes of different ethnic groups exists in the Italian population, to refine the search for a more geographically specific founder effect, we extended the haplotype analysis in these families using polymorphic microsatellite repeat markers, within and flanking the SQSTM1/p62 locus, from chromosome 5q35, other than the exon 6 and 3'UTR polymorphisms. All mutant carriers from two of the three M404V families and from the G425R families exhibited common extended chromosome 5q35 haplotypes, IT01 and IT02, respectively, which may be reflecting influences of past migrations. This may be helpful in estimating the true rate of de novo mutations. We confirm the data on the existence of both a mutational hotspot at the UBA domain of SQSTM1/p62 and a founder effect in the PDB population.

Measurements of Night Sky Brightness in the Veneto Region of Italy: Sky Quality Meter Network Results and Differential Photometry by Digital Single Lens Reflex.

In this paper, we present the implementation of a monitoring network for artificial light at night (ALAN), based on Sky Quality Meter devices (SQM) installed in seven locations of the Veneto region. The system is coordinated by the Regional Environmental Protection Agency (ARPA-Veneto) and the Department of Physics and Astronomy of the University of Padova, in collaboration with a local dark-sky association, Venetostellato. A new centralized database containing zenith night sky brightness (NSB) data was implemented to collect data from all SQM stations of the regional territory, not only in real time (since 2017), but in some stations since 2011. We now have a dataset to determine how light pollution is affecting astronomical observatories. A WEB portal was created to offer different downloads from these NSB data. We present the results of some elaborations for the 2018 dataset (statistics, histograms, annual and cumulative plots) for seven monitoring sites. For Ekar and Pennar sites, we also present the NSB monthly trend from 2014 until the time of the study. We purchased a reflex camera with a fish eye lens, appropriately calibrated with the software (SW) Sky Quality Camera, which allowed us to study ALAN using differential photometry. Here, we present our first results obtained by studying the night evolution of light pollution in the urban location of Padova.

The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis.

BACKGROUND: Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. METHODS: To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months. RESULTS: New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P<0.001 for both comparisons). There were no significant differences between the groups in the incidence of serious adverse events. CONCLUSIONS: Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.

Intravenous zoledronic acid in postmenopausal women with low bone mineral density.

BACKGROUND: Bisphosphonates are effective agents for the management of osteoporosis. Their low bioavailability and low potency necessitate frequent administration on an empty stomach, which may reduce compliance. Gastrointestinal intolerance limits maximal dosing. Although intermittent intravenous treatments have been used, the optimal doses and dosing interval have not been systematically explored. METHODS: We studied the effects of five regimens of zoledronic acid, the most potent bisphosphonate, on bone turnover and density in 351 postmenopausal women with low bone mineral density in a one-year, randomized, double-blind, placebo-controlled trial. Women received placebo or intravenous zoledronic acid in doses of 0.25 mg, 0.5 mg, or 1 mg at three-month intervals. In addition, one group received a total annual dose of 4 mg as a single dose, and another received two doses of 2 mg each, six months apart. Lumbar-spine bone mineral density was the primary end point. RESULTS: There were similar increases in bone mineral density in all the zoledronic acid groups to values for the spine that were 4.3 to 5.1 percent higher than those in the placebo group (P<0.001) and values for the femoral neck that were 3.1 to 3.5 percent higher than those in the placebo group (P<0.001). Biochemical markers of bone resorption were significantly suppressed throughout the study in all zoledronic acid groups. Myalgia and pyrexia occurred more commonly in the zoledronic acid groups, but treatment-related dropout rates were similar to that in the placebo group. CONCLUSIONS: Zoledronic acid infusions given at intervals of up to one year produce effects on bone turnover and bone density as great as those achieved with daily oral dosing with bisphosphonates with proven efficacy against fractures, suggesting that an annual infusion of zoledronic acid might be an effective treatment for postmenopausal osteoporosis.

Strontium ranelate: an increased bone quality leading to vertebral antifracture efficacy at all stages.

Strontium ranelate is a new antiosteoporotic treatment with a dual mode of action, both increasing bone formation and decreasing bone resorption, which rebalances bone turnover in favor of bone formation and increases bone strength. The antifracture efficacy of strontium ranelate, 2 g per day orally, in the treatment of postmenopausal osteoporosis has been investigated in a large-scale, international, multicenter, phase 3 program in which more than 7000 patients were recruited. This article deals with the vertebral antifracture efficacy of strontium ranelate in postmenopausal women with osteoporosis. A significant early (after 1 year) and sustained (over 3 years) antifracture efficacy of strontium ranelate, compared with placebo, was demonstrated in patients with prevalent vertebral fracture with reductions in risk of new vertebral fracture of 49% after 1 year (P < 0.001) and 41% over 3 years (P < 0.001). In addition, the relative risk of clinical vertebral fracture was significantly reduced by 52% (P = 0.003) after 1 year and by 38% (P < 0.001) over 3 years in the strontium ranelate group compared with placebo. Strontium ranelate was also demonstrated to significantly decrease the relative risk of vertebral fractures by 45% (P < 0.001) in patients without prevalent vertebral fracture over 3 years, vs. placebo. Bone mineral density was linearly increased during 3 years of treatment with strontium ranelate in comparison with placebo. Strontium ranelate was well tolerated throughout the entire duration of the clinical trials. Thus, strontium ranelate, 2 g per day orally, is a new, effective, and safe treatment for postmenopausal patients with osteoporosis, to reduce the vertebral fracture risk in patients with or without a history of vertebral fracture.

Do strong opioids have a role in the early management of back pain? Recommendations from a European expert panel.

BACKGROUND: Since chronic low back pain (CLBP) is a complex biopsychosocial problem the ideal treatment is multimodal and multidisciplinary. However, in many countries, primary-care physicians care for many people with CLBP and have a pivotal role in selecting patients for more intensive treatments when these are available. Guidelines on the general use of strong opioids in chronic non-cancer pain have been published but, until now, no specific guidelines were available on their use in chronic low back pain. Given the prevalence of CLBP, and the complex nature of this multifactorial condition, it was felt that specific, evidence-based recommendations, with a focus on primary-care treatment, would be helpful. METHODS: An expert panel drawn from across Europe including pain specialists, anaesthetists, neurologists, rheumatologists, a general practitioner, an epidemiologist and the chairman of a pain charity was therefore convened. The aim of the group was to develop evidence-based recommendations that could be used as a framework for more specific guidelines to reflect local differences in the availability of specialist pain services and in the legal status and availability of strong opioids. Statements were based on published evidence (identified by a literature search) wherever possible, and supported by clinical experience when suitable evidence was lacking. RECOMMENDATIONS: Strong opioids have a role in the treatment of low back pain when other treatments have failed. They should be prescribed as part of a multimodal, and ideally interdisciplinary, treatment plan. The aim of treatment should be to relieve pain and facilitate rehabilitation.

Quality of life in post-menopausal osteoporosis.

BACKGROUND: To evaluate the impact of osteoporosis on the patients' quality of life, particularly in the absence of fractures. METHODS: 100 post-menopausal women (age 50-85)--62 with uncomplicated primary osteoporosis and 38 with primary osteoporosis complicated by vertebral fractures; all already treated--were studied using two validated questionnaires: Qualeffo-41 for quality of life in osteoporosis, and Zung for depression. Data were compared to those of 35 controls of comparable age, affected by a different chronic disease (hypothyroidism). RESULTS: Family history of osteoporosis and T-score of spine were similar in the two subgroups of osteoporotic women. Body mass index, age at menopause and education level were similar in the two subgroups of osteoporotic women and in the control group. The patients affected by osteoporosis perceived it as a disease affecting their personal life with undesirable consequences: chronic pain (66% of women with fractures and 40% of women without fractures), impaired physical ability, reduced social activity, poor well-being (21% of women without fractures) and depressed mood (42% of women irrespective of fractures). Overall, 41% of the women showed a reduced quality of life. On the contrary, in the control group only 11% reported a reduced quality of life. CONCLUSION: The quality of life of osteoporotic patients should be investigated even before fractures, in order to develop appropriate counselling, support and care interventions to help patients develop efficient strategies for accepting the disease and coping with it.

Effect of trabecular orientation on mechanical resistance and ultrasound propagation in specimens of equine vertebrae.

Osteoporosis involves alterations, not only in density, but also in the architectural organisation of the bone; in particular, trabecular orientation, following the skeletal load directions, lends a high degree of stiffness to the whole bone. We investigated the relationship between trabecular orientation, density, stiffness and ultrasound (US) propagation in two orthogonal directions (par. = parallel to, and ort. = orthogonal to the main orientation of the trabeculae) in cylindrical equine bone specimens (thoracic vertebrae) where a preferential orientation is present. A total of 15 cylinders were progressively decalcified with 0.2 mol/L ethylenediaminetetraacetic acid (EDTA). At different levels of decalcification, we measured the apparent density (g/cm(3)), bone mineral density or BMD (g/cm(2)), stiffness coefficient (MPa) and various US parameters. Before decalcification, stiffness values were the same in all directions. As the decalcification proceeded, the stiffness declined and, at low BMD values, it was significantly different in the two directions, being the highest in the par. one. Different behaviours of US parameters were observed in the two directions: SoS (speed of sound) was closely related to apparent density, BMD and stiffness in the par. direction (r = 0.88, 0.92 and 0.88, respectively, p < 0.0001). In the ort. direction, no significant association has been found between SoS and apparent density, BMD or stiffness. In the same experimental setup, US fast wave amplitude (FWA) was related to apparent density and BMD in the par. direction (r = 0.72 and 0.67, respectively, p < 0.0001) and in the ort. direction (r = 0.83 and r = 0.84 respectively, p < 0.0001). FWA was also correlated to stiffness in both directions (r = 0.61 par.; 0.81 ort., p < 0.0001). These results show that trabecular orientation strongly influences both mechanical properties of bone and US propagation. Furthermore, we found that US parameters can be predictors of mechanical properties of the bone independent of bone density.

When the government actively faces the burden of osteoporosis: the Italian experience.

EPIDEMIOLOGY AND COSTS OF FRAGILITY FRACTURES IN ITALY: The problem of osteoporosis is emerging as growing phenomenon, with an enormous impact on quality of life and on health expenses. As a consequence, a reduction in the social and health impact of bone fragility would be associated with an improved quality of life of all elderly citizens and with valuable cost savings at the health system level. OSTEOPOROSIS: EVOLUTION OF THE CONCEPT IN ITALY: In the last 20 years, there have been enormous advances in the knowledge of diagnostic and therapeutic options and thus we would be in the position of starting effective therapies in at risk populations. However, this not always happens. NEW APPROACHES TO THE FRAGILITY FRACTURES BY THE ITALIAN GOVERNMENT: In this paper we offer to the reader the possibility to know the history of osteoporosis, its diagnosis and its therapy in Italy, a country where life expectancy is one of the highest in the world. THE FUTURE OF OSTEOPOROSIS IN ITALY: We hope that the example of Italy would serve as an inspiration to those countries where the history of osteoporosis only recently began.

Analysis of the costs and consequences of adherence to therapy in hip fracture patients. Results of a longitudinal analysis of.

The aim of this study, a retrospective cohort analysis, was to calculate the costs and consequences of exposure to and compliance with drug treatments recommended for refracture prevention in post-menopausal women with hip fracture. All women aged ≥65 years and admitted to hospital with a main or secondary diagnosis of hip fracture in the period 1 January 2006 - 31 December 2008 were included. These patients were classified as exposed /not exposed to a drug treatment for fracture prevention. Adherence to treatment was calculated in the group of patients treated with bisphosphonates. The following items were considered in the cost analysis: drug treatments supplied, diagnostic tests administered and hospital admissions recorded during the observation period. In total, 5,167 patients were included in the analysis, of whom only 33.9% received drug therapy post hip fracture; of those treated with bisphosphonates, only 21.1% were found to have adhered to the treatment. Exposure to drug treatment reduced the risk of refracture by 39.5% and the risk of death by 55.1%. The mean cost increases observed in the patients who, according to indication, were exposed to drug treatment (+ € 256) or submitted to a diagnostic test (+ € 40) were offset by a sizeable reduction in costs of hospitalisation for refracture (- € 703).Drug treatment for the prevention of bone refractures in hip fracture patients was found to be effective in reducing the risk of refracture and death, and cost-effective, reducing overall patient management costs.

Baseline observations from the POSSIBLE EU® study: characteristics of postmenopausal women receiving bone loss medications.

SUMMARY: Prospective Observational Scientific Study Investigating Bone Loss Experience in Europe (POSSIBLE EU®) is an ongoing longitudinal cohort study that utilises physician- and patient-reported measures to describe the characteristics and management of postmenopausal women on bone loss therapies. We report the study design and baseline characteristics of 3,402 women recruited from general practice across five European countries. PURPOSE: The POSSIBLE EU® is a study describing the characteristics and management of postmenopausal women receiving bone loss medications. METHODS: Between 2005 and 2008, general practitioners enrolled postmenopausal women initiating, switching or continuing treatment with bone loss treatment in France, Germany, Italy, Spain and the UK. Patients and physicians completed questionnaires at study entry and at 3-month intervals, for 1 year. RESULTS: Of 3,402 women enrolled (mean age 68.2 years [SD] 9.83), 96% were diagnosed with low bone mass; 55% of these using dual energy X-ray absorptiometry. Most women (92%) had comorbidities. Mean minimum T score (hip or spine) at diagnosis was -2.7 (SD 0.89; median -2.7 [interquartile range, -3.2, -2.2]) indicating low bone mineral density. Almost 40% of the women had prior fractures in adulthood, mostly non-vertebral, non-hip in nature, 30% of whom had at least two fractures and more than half experienced moderate/severe pain or fatigue. Bisphosphonates were the most common type of bone loss treatment prescribed in the 12 months preceding the study. CONCLUSIONS: POSSIBLE EU® characterises postmenopausal women with low bone mass, exhibiting a high rate of prevalent fracture, substantial bone fragility and overall comorbidity burden. Clinical strategies for managing osteoporosis in this population varied across the five participating European countries, reflecting their different guidelines, regulations and standards of care.

Determinants of bone turnover markers in healthy premenopausal women.

Bone turnover markers (BTMs) are widely used for the management of osteoporosis, and the premenopausal reference range is the target value for the treatment of postmenopausal osteoporosis with antiresorbing agents. Three serum BTMs (serum C-telopeptide of type I collagen [CTX], osteocalcin [OC], and N-terminal propeptide of type I procollagen [P1NP]), serum calcium, creatinine, phosphate, magnesium, and follicle-stimulating hormone (FSH) were measured in 638 healthy premenopausal women aged 20-50 years. In 83 women on the contraceptive pill (CP), the levels of the three BTMs adjusted for all confounding factors were 14-26% lower (P < 0.005) than in non-CP users. In 18 women considered perimenopausal for serum FSH levels >30 IU/mL despite having regular menses, BTM levels were significantly higher than in age-matched women. This group of subjects and the women on the CP were excluded from further analysis. The three BTMs significantly decreased with advancing age and were negatively and independently correlated with body mass index (P < 0.001) and serum phosphate. In conclusion, we confirm that CP use is associated with significantly lower BTM values. An increase in BTM concentrations can be observed in perimenopausal women, i.e., women with normal menses but FSH levels >30 IU/mL. BTMs decrease substantially with advancing age, and this appears to be associated with changes in body weight and serum phosphate. New normative ranges for serum OC, CTX, and P1NP were identified; and our findings in general impose a redefinition of the criteria for establishing the normal ranges for BTMs.