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Bone loss induced by ovariectomy is due to the direct activity on bone cells and mesenchymal cells and to the dysregulated activity of bone marrow cells, including immune cells and stromal cells, but the underlying mechanisms are not completely known. Here, we demonstrate that ovariectomy induces the T-cell co-stimulatory cytokine LIGHT, which stimulates both osteoblastogenesis and osteoclastogenesis by modulating osteoclastogenic cytokine expression, including TNF, osteoprotegerin, and the receptor activator of nuclear factor-κB ligand (RANKL). Predictably, LIGHT-deficient (Tnfsf14-/- ) mice are protected from ovariectomy-dependent bone loss, whereas trabecular bone mass increases in mice deficient in both LIGHT and T and B lymphocytes (Rag -/- Tnfsf14 -/- ) and is associated with an inversion of the TNF and RANKL/OPG ratio. Furthermore, women with postmenopausal osteoporosis display high levels of LIGHT in circulating T cells and monocytes. Taken together, these results indicate that LIGHT mediates bone loss induced by ovariectomy, suggesting that patients with postmenopausal osteoporosis may benefit from LIGHT antagonism. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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.

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.

Background The incidence of post-surgical chronic pain ranges between 20% and 40% in Europe. Osteoarthritis pain after prosthesis implantation is one of the most severe secondary syndromes, depending not only on surgery but also on organic changes before and after joints replacement. No data are available about risk factors. An excessive inflammatory response plays a central role but a best therapy is not defined yet. It is not clear whether opioid administration could influence post-surgical pain and lead to tolerance or addiction. Interestingly, the immune system, together with the nervous and peptidergic ones, is involved in hypersensibility. The connection across the three biological systems lies in the presence of opioid receptors on immune cells surface. Here, we show a method to analyze whether opioids could modulate lymphocytes, by proposing opioid receptors as biological markers to prevent chronic pain and opioid tolerance or addiction after hip surgery. Methods/design After institutional independent ethics committee approval, 60 patients, in pain and undergoing hip surgery, will be enrolled in a single-blind, randomized, phase IV, pilot study. Pain treatment will be selected inside a class of non-steroidal anti-inflammatory drugs (NAISDs) or paracetamol or a class of opioids, into three medication arms: 25 mg tapentadol twice daily; 75 mg tapentadol twice daily; NSAIDs or paracetamol in accordance with surgeon’s custom. For each group, we will collect blood samples before, during and after surgery, to apply molecular analysis. We will perform lymphocyte opioid receptors genes and proteins expression and functional analysis. Data will be statistically analyzed. Discussion This project has the potential to obtain a personalized diagnostic kit, by considering lymphocyte opioid receptors as biological markers. Starting from a simple blood sample, it will be possible to decide the best therapy for a single patient. Using a noninvasive approach, we expect to fix a daily standard dose and timing, before and after surgery, to bypass hip chronic pain and the insurgence of tolerance or addiction. The analysis of opioid receptors sensitivity will help to identify the best drug administration in each specific case (tailored therapy). Trial registration ISRCTN, ISRCTN12559751. Retrospectively registered on 23 May 2017. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2363-z) contains supplementary material, which is available to authorized users.

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

Irisin is a new peptide produced mainly by the skeletal muscle playing an important role both in glucose/energy homeostasis and bone metabolism. Childhood type 1 diabetes mellitus (T1DM) is associated with decreased bone mass. We aimed to evaluate irisin levels in TD1M children and their correlation with bone metabolism and glycaemic control.Ninety-six T1DM subjects (12.2 ± 4 years), 56 on multiple daily injections (MDI), 40 on continuous subcutaneous insulin infusion (CSII), and 34 controls were included in the study. Irisin and bone remodeling markers were quantified in sera from patients and controls. Bone mineral density (BMD) was evaluated by QUS.Increased irisin levels were found in T1DM patients respect to controls (p 0.001). With adjustment for age, irisin levels significantly correlated negatively with HbA1c% (r = -0.105, p 0.001), years of diabetes (r = -0.07, p 0.04), 25(OH)-Vitamin D (r = -0.175, p 0.0001), and positively with BTT-Z-score (r = 0.088, p = 0.016), and osteocalcin (r = 0.059, p 0.04). We detected the highest levels of irisin in CSII patients compared to MDI and controls (p 0.001 and p 0.007 respectively).We demonstrated high irisin levels in T1DM children and the association of highest irisin amounts to a better glycaemic control and bone health in TDM1 subjects on CSII.

Currently, an increasing number of younger patients undergo total hip arthroplasty surgery. This has led to a minimal invasive approach and the use of short, bone preserving, femoral stems. In this study, we sought to evaluate osseointegration of the Fitmore stem (Zimmer, Inc; Warsaw, IN) during the first 12 mo after surgery, which reflects the biological phenomenon of osseointegration with radiographic evaluation and bone densitometry (dual-energy X-ray absorptiometry). We evaluated 33 patients (mean age 62.3) using dual-energy X-ray absorptiometry scan around the stem and X-ray. Moreover, we studied functional recovery using the Harris Hip Score, timed up and go test, and a quality of life form (SF-36), during the follow-up period. At 12 mo, we observed an increased periprosthetic bone mineral density in region of interest 1 (1.7%) and region of interest 7 (8.3%), where there is usually a greater amount of bone resorption. Also Harris Hip Score, timed up and go test, and SF-36 showed an improvement of clinical conditions of all patients. We also used a control group with a standard stem implanted. Because this is the first study correlating osseointegration and clinical outcome of the Fitmore stem, further clinical studies will be necessary to confirm good/positive results and a long stable fixation.

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.

Apoptosis can occur throughout the life span of osteoblasts (OBs), beginning from the early stages of differentiation and continuing throughout all stages of their working life. Here, we investigated the effects of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on normal human OBs showing for the first time that the expression of TRAIL receptors is modulated during OB differentiation. In particular, the TRAIL receptor ratio was in favor of the deaths because of the low expression of DcR2 in undifferentiated OBs, differently it was shifted toward the decoys in differentiated ones. Undifferentiated OBs treated with TRAIL showed reduced cell viability, whereas differentiated OBs displayed TRAIL resistance. The OB sensitiveness to TRAIL was due to the up-regulation of DR5 and the down-regulation of DcR2. The main death receptor involved in TRAIL-reduced OB viability was DR5 as demonstrated by the rescue of cell viability observed in the presence of anti-DR5 neutralizing antibody. Besides the ratio of TRAIL receptors, the sensitivity of undifferentiated OBs to TRAIL-cytotoxic effect was also associated with low mRNA levels of intracellular anti-apoptotic proteins, such as cFLIP, the activation of caspase-8 and -3, as well as the DNA fragmentation. This study suggests that apoptotic effect exerted by TRAIL/TRAIL-receptor system on normal human OB is strictly dependent upon cell differentiation status.

Major depressive disorder (MDD) and osteoporosis are two common disorders with high morbidity and mortality rates. Conflicting data have found associations between MDD and low bone mineral density (BMD) or osteoporosis, although causative factors are still unclear. A pilot study was designed with the aim to assess the relationship between MDD and BMD in postmenopausal women with MDD compared to healthy volunteers. We hypothesized that attachment style (AS) mediated this relationship.The sample was made of 101 postmenopausal women, 49 with MDD and 52 age-matched healthy volunteers. Structured clinical interview and Beck Depression Inventory (BDI) were performed to assesse MDD. AS was evaluated using the Relationship Questionnaire (RQ). BMD was measured by dual energy X-ray absorptiometry.The univariate analysis showed that women with MDD had lower BMD values as compared to healthy volunteers. In the regression models MDD diagnosis and BDI score were not significant predictors of low BMD. The “preoccupied” pattern of insecure AS was a significant, independent predictor of decreased BMD in all skeletal sites: lumbar spine (p=0.008), femoral neck (p=0.011), total hip (p=0.002).This is the first study exploring the relationship between AS, MDD and BMD. Our results support the link between MDD and low BMD. We found that insecure AS was a risk factor for decreased BMD, regardless of depression. Insecure AS may play a role in the relationship between MDD and BMD or may constitute a risk factor itself. Therapeutic interventions focused on AS could improve psychiatric disorders and physical diseases related to low BMD.

To assess the effects of a moderately hypoenergetic Mediterranean diet (MHMD) and exercise program on body cell mass (BCM) and cardiovascular disease risk factors in obese women.Forty-seven obese women, 39.7+/-13.2 years of age, with a body mass index (BMI)=30.7+/-6.0 kg/m(2), completed the study. The following were measured at baseline, 2 and 4 months: BCM, BCM index (BCMI), body weight, BMI, fat-free mass (FFM), fat mass (FM), total body water (TBW), extracellular water (ECW) and intracellular water (ICW) using bioelectrical impedance analysis; fasting blood glucose (FBG), serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations; systolic (SBP) and diastolic (DBP) blood pressure.Body weight, BMI, FM, TC and TG significantly decreased (P0.001; P0.002 (TG)) at 2 and 4 months. FFM, TBW, ECW, FBG and DBP significantly decreased at 2 months (P0.05 (FFM); P0.001). LDL-C significantly decreased (P0.001), while HDL-C significantly increased (P0.002) at 4 months. BCM, BCMI, ICW and SBP remained stable over time.BCM was preserved and cardiovascular disease risk factors improved in obese women placed on a MHMD and exercise program for 4 months.

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.

A 20-year-old man sustained an open medial dislocation of the ankle without an associated fracture after a low-energy inversion injury. Prompt debridement and reduction with primary wound closure of the skin were performed without suture of the capsule. Immobilisation in a non-weight-bearing cast for 30 days followed by ankle bracing for two weeks and subsequent physiotherapy, produced full functional recovery by three months. At follow-up at one year there was a full range of pain-free movement, although the radiographs and MR scan showed early post-traumatic degenerative change at the medial aspect of the tibiotalar and the calcaneocuboid joints.

In the last years, the number of total hip arthroplasty is increased both in young patients and elderly with a poor bone quality due to extension of surgical indications. According to this trend, also revision surgery showed a growth of its number, especially in elderly patients, because of implant loosening, failed osseointegration of prosthetic components, errors in biomechanical restoration and infections. The aim of this study is to analyze life quality improvement through evaluation of articular functionality and postoperative pain, and to examine osseointegration of implant components with periprosthetic bone. During total hip arthroplasty revision, the orthopedic surgeon often has to face complex cases, especially in elderly patients with a preexisting status of poor bone quality and sarcopenia. In these cases, a correct planning and a surgical procedure well-executed are able to ensure a good outcome that led to pain relief and functional recovery. Furthermore anti-osteoporotic therapy surely represents a useful resource both in primary total hip arthroplasty and in revisions, mainly for elderly patients with a poor bone quality.

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.

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder affecting, among others, the endocrine system, with derangement of steroid hormones functions. Vitamin D is a steroid recognized for its role in calcium homeostasis. In addition, vitamin D influences muscle metabolism by genomic and non-genomic actions, including stimulation of the insulin-like-growth-factor 1 (IGF1), a major regulator of muscle trophism. To verify the presence of vitamin D deficit in DM1 and its possible consequences, serum 25-hydroxyvitamin D (25(OH)D), calcium, parathormone (PTH), and IGF1 levels were measured in 32 DM1 patients and in 32 age-matched controls. Bone mineral density (BMD) and proximal muscle strength were also measured by DXA and a handheld dynamometer, respectively. In DM1 patients, 25(OH)D levels were reduced compared to controls, and a significant decrease of IGF1 was also found. 25(OH)D levels inversely correlated with CTG expansion size, while IGF1 levels and muscle strength directly correlated with levels of 25(OH)D lower than 20 and 10 ng/ml, respectively. A significantly higher percentage of DM1 patients presented hyperparathyroidism as compared to controls. Calcium levels and BMD were comparable between the two groups. Oral administration of cholecalciferol in 11 DM1 patients with severe vitamin D deficiency induced a normal increase of circulating 25(OH)D, ruling out defects in intestinal absorption or hepatic hydroxylation. DM1 patients show a reduction of circulating 25(OH)D, which correlates with genotype and may influence IGF1 levels and proximal muscle strength. Oral supplementation with vitamin D should be considered in DM1 and might mitigate muscle weakness.

Background Patients with low back pain frequently demonstrate recumbent magnetic resonance imaging (MRI) alterations not always related to homogeneous clinical symptoms. The purpose of this study was to evaluate and quantify the statistical significance of variations of some anatomical parameters of the lumbosacral spine and reveal occult disc pathologies from recumbent to upright position in patients with acute and chronic low back pain. Materials and methods Fifty-seven patients complaining of low back pain (27 women, 30 men) underwent dynamic lumbosacral MRI with a 0.25-T tilting system (G-scan Esaote). We settled five parameters for which variations have been evaluated: lumbosacral angle, lordosis angle, L3–L4 intersomatic disc height, L3–L4 interspinous processes distance, and widest anteroposterior dural sac diameter. Images were obtained in both recumbent and upright positions. Results Statistically significant differences [one-way analysis of variance (ANOVA), p = 0.0043] were found between each pair of values of parameters sampled in recumbent and upright positions. In 70 % of patients, on visual qualitative analysis only, an increment of disc protrusions and/or spondylolisthesis was found in the upright position; in three cases, in the upright position only, an interarticular pseudocyst was found. Conclusions Dynamic MRI with an open-configuration, low-field tilting MRI system is a feasible and promising tool to study degenerative pathology of the spine. Moreover, in cases of low back pain with negative MRI in the recumbent position or in patients with pain in the upright position only, tilting MRI permits visualization of occult spine and disc pathologies in patients with acute or chronic low back pain.

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.

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.