Search

The aim of this study was developing and testing a new tool for measuring quality of life (QoL) in patients with osteoporosis who had experienced nonvertebral fractures (NVFXs). Two main phases were carried out. First, the tool was developed based on expert opinion through three focus groups. Second, the tool was tested with exploratory factor analysis and confirmatory factor analysis in a sample of 458 postmenopausal women. The reliability of the developed Quality of Life Osteoporosis Scale-Nonvertebral Fractures (QoLOS-NVFX) was measured using Cronbach's α, maximal reliability (MR), composite reliability (CR), and average variance extracted (AVE). The QoLOS-NVFX resulted in a unidimensional scale with 23 items and showed good reliability, with a Cronbach's α of 0.94, an MR of 0.96, a CR of 0.96, and an AVE of 0.70. The QoLOS-NVFX shows good psychometric properties and can be used to assess the impact of NVFX on QoL in osteoporotic women. Furthermore, it can be easily used in clinical practice and research.

In this study, we investigated the relationship between sarcopenia (evaluated in term of fibers atrophy), vitamin d receptor protein expression and TaqI/Cdx2/FokI VDR genotypes in an Italian cohort of osteoporosis(n=44) and osteoarthritis (n=55) patients. Muscle biopsies were fixed and investigated by both immunohistochemistry (vitamin d receptor expression) and transmission electron microscopy (satellite stem cells niches). Vitamin d receptor polymorphisms were studied on DNA extracted from muscle paraffin sections. For the first time, we reported that aging differently affects the VDR activation in OA and OP patients. In particular, while in OP patients we observed a significant reduction of VDR positive myonuclei with age, no "age effect" was observed in OA patients. The frequent activation of VDR could explain the lower number of atrophic fiber that we observed in OA patients respect to OP. From genetic point of view, we showed a putative association among polymorphisms FokI and Cdx2 of VDR gene, vitamin d receptor activation and the occurrence of sarcopenia. Altogether these data open new prospective for the prevention and cure of age-related muscle disorders.

The aim of this study was developing and testing a new tool for measuring quality of life (QoL) in patients with osteoporosis who had experienced nonvertebral fractures (NVFXs). Two main phases were carried out. First, the tool was developed based on expert opinion through three focus groups. Second, the tool was tested with exploratory factor analysis and confirmatory factor analysis in a sample of 458 postmenopausal women. The reliability of the developed Quality of Life Osteoporosis Scale-Nonvertebral Fractures (QoLOS-NVFX) was measured using Cronbach's α, maximal reliability (MR), composite reliability (CR), and average variance extracted (AVE). The QoLOS-NVFX resulted in a unidimensional scale with 23 items and showed good reliability, with a Cronbach's α of 0.94, an MR of 0.96, a CR of 0.96, and an AVE of 0.70. The QoLOS-NVFX shows good psychometric properties and can be used to assess the impact of NVFX on QoL in osteoporotic women. Furthermore, it can be easily used in clinical practice and research.

Osteoporosis (OP) is a multifactorial disease influenced by genetic, epigenetic, and environmental factors. One of the main causes of the bone homeostasis alteration is inflammation resulting in excessive bone resorption. Long non-coding RNAs (lncRNAs), have a crucial role in regulating many important biological processes in bone, including inflammation. We designed our study to identify lncRNAs misregulated in osteoblast primary cultures derived from OP patients (n = 4), and controls (CTRs, n = 4) with the aim of predicting possible RNA and/or protein targets implicated in this multifactorial disease. We focused on 84 lncRNAs regulating the expression of pro-inflammatory and anti-inflammatory genes and miRNAs. In silico analysis was utilized to predict the interaction of lncRNAs with miRNAs, mRNAs, and proteins targets. Six lncRNAs were significantly down-regulated in OP patients compared to controls: CEP83-AS1, RP11-84C13.1, CTC-487M23.5, GAS5, NCBP2-AS2, and SDCBP2-AS1. Bioinformatic analyses identified HDCA2, PTX3, and FGF2 proteins as downstream targets of CTC-487M23.5, GAS5, and RP11-84C13.1 lncRNAs mediated by the interaction with miRNAs implicated in OP pathogenesis, including miR-21-5p. Altogether, these data open a new regulatory mechanism of gene expression in bone homeostasis and could direct the development of future therapeutic approaches.

Background: Osteoarthritis and osteoporosis are strongly coupled with alterations of muscles quality and fats metabolism. However, there are no studies for investigating possible differences between osteoporotic and osteoarthritic muscles. Understanding muscle-bone and muscle-cartilage interactions would be of high clinical value. Aim: Investigate potential microstructural and physiological differences between osteoporotic and osteoarthritic muscles by diffusion Nuclear Magnetic Resonance (NMR) imaging (diffusion MRI) and histological findings. Methods: Vastus-lateralis muscles excised from osteoporotic (n = 26, T Score < - 2.5, Kellgren-Lawrence - 2.5, Kellgren--Lawrence 3 and 4) age-matched women were investigated by NMR relaxometry, diffusion-tensor imaging (DTI) at 9.4 T, and histological techniques. Intramyocellular (IMCL) and extramyocellular (EMCL) lipid were quantified. The percentage and mean diameters of fibers I and II were evaluated. Relationship between mean diffusivity (MD), fractional anisotropy (FA), the DTI eigenvalues (?1, ?2, ?3), histological findings in muscles and clinical data (Kellgren-Lawrence and T score, age, menopausal age, body mass index) were studied. Pairwise comparisons between groups were made using one-way analysis of variance and correlation between variables was assessed with linear correlation analysis (Pearson's r coefficient). Results: Osteoporotic muscles showed higher MD, ?1,?2, ?3 compared to osteoarthritis ones. This is explainable with a significant higher density of IMCL droplets found inside the osteoarthritic muscles and a large amount of fibrotic tissue and IMCL infiltration between fibers, i.e. in endomysium and perimysium that lead to a more hindered diffusion. Furthermore, histological analysis suggests mitochondrial degeneration as the origin of the greatest amount of IMCL droplets in osteoarthritic muscles. Conclusion: This work highlights differences between muscles of osteoporotic and osteoarthritic subjects that can be quantified by NMR DTI investigations.

With increasing longevity in males, osteoporosis will become of increasing importance in both males and females. Men undergo gradual bone loss with aging, resulting in fragile bones. It is estimated that one in five men will suffer an osteoporotic fracture during their lifetime. The prognosis for men after a hip fracture is very grim. Many other factors result in secondary osteoporosis, including treatment for other diseases such as cancer and diabetes. Hip fracture is a common fracture, particularly in older female patients. However, about one-third of hip fractures occur in men. The causes underlying osteoporosis and susceptibility to falling differ between women and men, as do mortality rates; male patients appear to have higher standardized mortality ratios compared to female patients. The surgical treatment of the fractures of the upper extremity of the femur in the elderly is a challenge. The main problem is to conciliate the huge advancement of the biometrial technology with the incomplete knowledge of bone properties. After an initial low-trauma fracture, the absolute risk of subsequent fracture was similar for men and women. This increased risk occurred for virtually all clinical fractures and persisted for up to 10 years.

Background Targeting new molecular pathways leading to Osteoporosis (OP) and Osteoarthritis (OA) is a hot topic for drug discovery. Clusterin (CLU) is a glycoprotein involved in inflammation, proliferation, cell death, neoplastic disease, Alzheimer disease and aging. The present study focuses on the expression and the role of CLU in influencing the decrease of muscle mass and fiber senescence in OP-OA condition. Methods Vastus lateralis muscle biopsies were collected from 20 women with OP undergoing surgery for fragility hip fracture and 20 women undergoing arthroplasty for hip osteoarthritis. Results We found an overexpression of CLU in degenerated fibers in OP closely correlated with interleukin 6 (IL6) and histone H4 acetylation level. Conversely, in OA muscle tissues we observed a weak expression of CLU but no nuclear histone H4 acetylation. Ex vivo studies on isolated human myoblasts confirmed CLU overexpression in OP as compared to OA (p

Teriparatide (TPTD), the amino-terminal parathyroid hormone recombinant peptide [PTH (1–34)], is a drug with a proven anabolic action on the bone, effective in preventing vertebral and non-vertebral fragility fractures. Recent publications have investigated in great detail the TPTD action on the cortical bone, highlighting the increased strength in the critical zone of the hip with high risk of fracture in osteoporotic patients Poole (PLoS ONE 6:e16190, 2011). In November 2002, TPTD was approved by the FDA for use in post-menopausal women and men with osteoporosis at high risk of fracture and in patients with glucocorticoid-induced osteoporosis and, since then, has been used to treat more than 1 million patients worldwide (J Bone Miner Res 27(12):2429-2437, 2012). The unchanged safety profile and the well-known mechanism of action of this drug have led doctors to explore the use of TPTD in other conditions such as delayed fracture healing, non-union, osteonecrosis of the jaw, etc. The positive reports that have resulted from these studies are helping to hypothesize a new perspective on the wider use of this drug, but warrant further clinical investigation to consolidate these results.

An imbalance of the remodeling process for bone resorption leads to a loss of tissue with consequent microarchitectural damage, evident in conditions such as osteoporosis and related fragility fractures. Currently, pharmacological therapies are able to prevent or slow down bone resorption by inhibiting osteoclast activity. An innovative and targeted anti-resorptive approach is represented by the inhibition of RANK ligand (RANK-L), essential for the proliferation and activity of osteoclastic cells. The human monoclonal antibody against RANK-L (denosumab) has been approved for the treatment of osteoporosis. In clinical trials of patients with osteoporosis, inhibition of RANK-L has reduced bone loss and damage to the microarchitecture and was associated with an increase in mass and resistance at different skeletal sites, with most significant effects than those demonstrated by any other antiresorptive drugs. In addition, after 3 years of treatment, it showed a reduction in vertebral and non-vertebral fracture risk. Denosumab treatment also has not revealed any alteration in the physiological processes of fracture repair, showing no increase in the onset of complications 3 years after the fracture. The data show that denosumab offers an effective alternative therapeutic approach for the treatment of severe osteoporosis, with positive effects on BMD and reduction of fragility fractures risk. So, promising results in terms of therapeutic efficacy and reliability make desirable the wide clinical use of denosumab for the treatment of osteoporotic fractures in the near future. © 2013 Springer International Publishing Switzerland. An imbalance of the remodeling process for bone resorption leads to a loss of tissue with consequent microarchitectural damage, evident in conditions such as osteoporosis and related fragility fractures. Currently, pharmacological therapies are able to prevent or slow down bone resorption by inhibiting osteoclast activity. An innovative and targeted anti-resorptive approach is represented by the inhibition of RANK ligand (RANK-L), essential for the proliferation and activity of osteoclastic cells. The human monoclonal antibody against RANK-L (denosumab) has been approved for the treatment of osteoporosis. In clinical trials of patients with osteoporosis, inhibition of RANK-L has reduced bone loss and damage to the microarchitecture and was associated with an increase in mass and resistance at different skeletal sites, with most significant effects than those demonstrated by any other antiresorptive drugs. In addition, after 3 years of treatment, it showed a reduction in vertebral and non-vertebral fracture risk. Denosumab treatment also has not revealed any alteration in the physiological processes of fracture repair, showing no increase in the onset of complications 3 years after the fracture. The data show that denosumab offers an effective alternative therapeutic approach for the treatment of severe osteoporosis, with positive effects on BMD and reduction of fragility fractures risk. So, promising results in terms of therapeutic efficacy and reliability make desirable the wide clinical use of denosumab for the treatment of osteoporotic fractures in the near future. © 2013 Springer International Publishing Switzerland.

Recently has been highlighted that topological properties of trabecular microstructure and microarchitectural deterioration of bone tissue are important factors in determining bone strength and its resistance to fracture. Magnetic resonance (MR) techniques allow investigation of both trabecular networks and bone marrow providing precious information on the physiological and functional changes associated with osteoporosis. The aim of the present work was to show the ability of MR micro-imaging investigation to describe cancellous bone status as related to its trabecular bone density and quality. For this purpose we measured in vitro, at high magnetic field (9.4T), the MR parameter $$ T_{2}^{\text{APP}} $$ of cancellous bone samples extracted from femoral head of osteoporotic and osteoarthritic women as classified by dual energy X ray absorptiometry bone mineral density. We assessed $$ T_{2}^{\text{APP}} $$ associations with T-scores, Harris Hip score and age. Results show that $$ T_{2}^{\text{APP}} $$ is able to discriminate between osteoarthritic and osteoporotic bone samples. Moreover, the micro-imaging $$ T_{2}^{\text{APP}} $$ investigation has highlighted a different trabecular bone density in cancellous bone specimens of osteoarthritic patients only, which is higher in subchondral compared to metaphysis section of each sample.

Fracture healing is a complex event that involves the coordination of different processes: initial inflammatory response, soft and hard callus formation, initial bony union and bone remodeling. This well-orchestrated series of biological events follows a specific temporal and spatial sequence that can be affected by biological factors, such as age and bone quality. There is some evidence that increased age is a considerable factor in the inhibition of fracture repair in human subjects. During aging there is an accumulation of damage that depends on the activation of inflammation processes and on changes in the circulating levels of inflammatory cytokines. In addition to the physiological slow down in the repair process, other conditions such as multiple comorbidities leading to polymedication are a frequent occurrence in elderly patients and can have an influence on this process. A further factor that affects bone metabolism is nutrition: bone quality, fragility fractures risk and fracture healing process are all influenced by the nutritional status. This review provides a summary of the immunological aspects of physiological fracture healing and of those nutritional factors which might play an important role in this process.

Aim: To evaluate the hospitalization rate of femoral neck fractures in the elderly Italian population over ten years. Methods: We analyzed national hospitalizations records collected at central level by the Ministry of Health from 2000 to 2009. Age- and sex-specific rates of fractures occurred at femoral neck in people ≥ 65 years old. We performed a sub-analysis over a three-year period (2007-2009), presenting data per five-year age groups, in order to evaluate the incidence of the hip fracture in the oldest population. Results: We estimated a total of 839008 hospitalizations due to femoral neck fractures between 2000 and 2009 in people ≥ 65, with an overall increase of 29.8% over 10 years. The incidence per 10000 inhabitants remarkably increased in people ≥ 75, passing from 158.5 to 166.8 (+5.2%) and from 72.6 to 77.5 (+6.8%) over the ten-year period in women and men, respectively. The oldest age group (people > 85 years old) accounted for more than 42% of total hospital admissions in 2009 (n = 39000), despite representing only 2.5% of the Italian population. Particularly, women aged > 85 accounted for 30.8% of total fractures, although they represented just 1.8% of the general population. The results of this analysis indicate that the incidence of hip fractures progressively increased from 2000 to 2009, but a reduction can be observed for the first time in women ≤ 75 (-7.9% between 2004 and 2009). Conclusion: Incidence of hip fractures in Italy are continuously increasing, although women aged 65-74 years old started showing a decreasing trend. © 2014 Baishideng Publishing Group Inc.

Osteoporosis is a diffuse skeletal disease in which a decrease in bone strength leads to an increased risk of fractures. A wide variety of types of bone densitometry measurements are available, including quantitative computed tomography measurements of the spine, quantitative ultrasound devices for measurements of the heel and other peripheral sites and dual-energy X-ray absorptiometry (DXA) for measurement of bone mineral density (BMD) at the lumbar spine, proximal femur, forearm and total body scans. Compared with alternative bone densitometry techniques, hip and spine DXA examinations have a number of advantages that include a consensus that BMD results can be interpreted using the World Health Organization T score definition of osteoporosis, a proven ability to predict fracture risk, proven effectiveness at targeting anti-fracture therapies, and the ability to monitor response to treatment. However, in recent years, the authors have raised some important questions about the objective limits of this method that have led to doubts about its effectiveness in terms of clinical outcome.

Osteoporosis and sarcopenia are the most frequent musculoskeletal disorders affecting older people. Osteoporosis is a widespread disorder affecting millions of individuals of all ethnic backgrounds worldwide, particularly among older women. It is characterized by reduced bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in the risk of fracture. Sarcopenia is considered to be one of the major factors responsible for functional limitations and motor dependency in elderly persons. In age-related muscle atrophy, a decrease in muscle fiber size and number, and a preferential loss of type II fibers have been reported. A decrease in the circulating levels of specific hormones (e.g., estrogen, testosterone, growth hormone, and insulin-like growth factor-1) has been shown to be associated with sarcopenia and this appears to play an important role in its pathogenesis.

Osteoporosis is a common skeletal disease in older populations, leading to more than a million fractures annually in the United States (Rockville, 2004) and Europe (O’Neil, 1996). Epidemiologic studies show that increased fracture risk in adults begins around the age of 45 years, particularly in women, progressing notably more with each decade of aging (Siris et al., 2010). About half of adult women and one third of adult men will sustain a fracture (Moayyeri,2008).

The progressive aging of the population inevitably leads to an increase in all age-related diseases, with osteoporosis arising as a health and social priority. Fragility fractures, resulting by Osteoporosis, may have important consequences such as hospitalizations with long periods of immobility, need of surgery, increased risk of disability and partial or complete loss of autonomy in the ordinary activities of daily life and related economical burden. It is therefore essential to implement immediately a tertiary prevention to reduce the risk of further fractures through a diagnostic-therapeutic evidence-based pathway. So, starting from the fracture, the orthopaedic surgeon is meant to play an essential role in the management of osteoporotic patients, both to reduce the risk of further fractures and improve long-term outcome in these people, thus lowering the health and life quality downward spiral that often results in fractures in the elderly.

A correct fracture healing depends on the synergy between biomechanical, molecular and cellular factors. Focusing on different stages, fracture hematoma represents the starting point of the inflammatory process, with a critical role in triggering the process of fracture healing. The essential factors for bone repair are the activation of mesenchymal stem cells and the release of growth and regulatory factors. Moreover, the efficacy of fracture healing is determined by three ideal conditions: adequate blood supply, good contact between bone fragments and good stability. It is remarkable how the implant choice influences fracture healing after surgical treatment. In osteoporosis, bone quality adversely affects the tissue structural competence, increasing the risk of a complicated fracture healing. The qualitative and quantitative alterations established at the cellular level during osteoporosis explain the progressive deterioration of bone tissue healing ability.

The knowledge of factors modulating the behaviour of bone mass is crucial for preventing and treating osteoporotic disease; among these factors, body weight (BW) has been shown to be of primary importance in postmenopausal women. Nevertheless, the relative effects of body composition indices are still being debated. Our aim was to analyze the relationship between body mass index (BMI), fat and lean mass and bone mineral density (BMD) in a large population of women. Moreover, this study represents a first important report on reference standard values for body composition in Italian women.Between 2005 and 2008, weight and height of 6,249 Italian women (aged 30-80 years) were measured and BMI was calculated; furthermore BMD, bone mineral content, fat and lean mass were measured by dual-energy X-ray absorptiometry. Individuals were divided into five groups by decades (group 1, 30.0-39.9; group 2, 40.0-49.9; group 3, 50.0-59.9; group 4, 60.0-69.9; group 5, 70.0-79.9). Differences among decades for all variables were calculated using a one-way analysis of variance (ANOVA) and Bonferroni test by the SPSS programme.Mean BW was 66.8±12.1 kg, mean height 159.1±6.3 cm and mean BMI 26.4±4.7 kg/m(2). According to BW and BMI, there was an increase of obesity with age, especially in women older than 50 years (p0.001). Lean mass increased until 50 years of age but significantly decreased after this age (p0.001). The percentage of osteopenia and osteoporosis in the examined population was 43.0% and 16.7%, respectively.Our data show that obesity significantly decreased the risk for osteoporosis but did not decrease the risk for osteopenia. It is strongly recommended that a strong policy regarding prevention of osteopenia and osteoporosis be commenced. An overall examination of our results suggests that both fat and lean body mass can influence bone mass and that their relative effect on bone could be modulated by their absolute amount and ratio to total BW.

Summary We demonstrated that osteoporosis is associated with a preferential type II muscle fiber atrophy, which correlates with bone mineral density and reduced levels of Akt, a major regulator of muscle mass. In osteoarthritis, muscle atrophy is of lower extent and related to disease duration and severity. Introduction Osteoarthritis (OA) and osteoporosis (OP) are associated with loss of muscle bulk and power. In these diseases, morphological studies on muscle tissue are lacking, and the underlying mechanisms of muscle atrophy are not known. The aim of our study was to evaluate the OP- or OA-related muscle atrophy and its correlation with severity of disease. Muscle levels of Akt protein, a component of IGF-1/PI3K/Akt pathway, the main regulator of muscle mass, have been determined. Methods We performed muscle biopsy in 15 women with OP and in 15 women with OA (age range, 60–85 years). Muscle fibers were counted, measured, and classified by ATPase reaction. By statistical analysis, fiber-type atrophy was correlated with bone mineral density (BMD) in the OP group and with Harris Hip Score (HHS) and disease duration in the OA group. Akt protein levels were evaluated by Western blot analysis. Results Our findings revealed in OP a preferential type II fiber atrophy that inversely correlated with patients’ BMD. In OA, muscle atrophy was of lower extent, homogeneous among fiber types and related to disease duration and HHS. Moreover, in OP muscle, the Akt level was significantly reduced as compared to OA muscles. Conclusions This study shows that in OP, there is a preferential and diffuse type II fiber atrophy, proportional to the degree of bone loss, whereas in OA, muscle atrophy is connected to the functional impairment caused by the disease. A reduction of Akt seems to be one of the mechanisms involved in OP-related muscle atrophy.

Introduction. Osteoporosis is a chronic condition leading to an increased risk of developing fractures, with high morbidity and mortality in aging population. Efficacy of anti-osteoporotic treatment is based on drug potency but also on compliance and persistence to treatment regimen, which is very low, as already described for other diseases. Teriparatide (TPTD) is the first anabolic agent developed for the treatment of osteoporosis. Since it appears that persistence to Teriparatide declines over time, aim of this pilot multicenter observational study was to evaluate persistence and adherence to TPTD (20 μg daily injection regimen for 18 months) treatment (PATT) in patients affected by severe osteoporosis in an every day clinical practice. Methods. Patients affected by severe osteoporosis were selected among those who referred to 5 different specialized centers for osteoporosis in North, Center and South of Italy. A sample of 475 women with severe postmenopausal osteoporosis treated with TPTD in accordance to the Italian osteoporosis guidelines was included. At the beginning of TPTD treatment patients were instructed on the use of the device by the referring specialist of the center, a resident fellow or a nurse. Bone biochemical markers were evaluated the same morning and after 1, 3, 6, 12 and 18 months. Patients were visited at time 0 and after 6, 12 and 18 months for clinical follow up. Results. The results included observations of 441/475 patients (98% women) who completed the 18 months treatment; mean age for women was 73±8 and for men 65±9. After 6 months of TPTD treatment persistence was of 89,79%, 87,75% after 12 months and 86,85% after 18 months. Adherence was of 100% at 6,12 and 18 months. Total dropouts were 13,15% (71/441), which was usually higher within the first 6 months of TPTD treatment. Most common adverse events (arthralgies 2,7%, dizziness 1,8%, migraine 1,8%, depression 1,6%, hypertension 1,1%) were reported in 62/441 patients (14%) of patients, but were not reason for stopping treatment. Conclusions. The persistence and adherence to TPTD treatment obtained in this multicenter observational real life study was very high as compared to studies performed by others. These encouraging results suggest that different key factors such quality of information, frequency of visits, motivations given to patients, opportunity to call the doctor might play a pivotal role in the high persistence and adherence to TPTD treatment obtained in our study and need to be carefully considered before prescribing chronic anti-osteoporotic therapy