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Background: Postmenopausal osteoporosis (PMOP) is a serious condition that affects elderly individuals. Our previous study revealed that Yigu decoction (YGD) effectively improved bone mineral density (BMD) in elderly individuals, but the mechanism underlying this effect remains unclear. In this study, we investigated the relationships among YGD, microRNAs (miRNAs), and bone metabolism by assessing the effects of YGD on the miRNA levels in patient plasma to provide a scientific basis for treating PMOP with YGD. Methods: In this clinical trial, 60 patients were randomly assigned to the YGD group or the control group (ratio of 1:1) and treated for 3 months. The primary outcome measure was BMD, and the secondary outcome measures included plasma miRNA levels, visual analogue scale (VAS) scores, alkaline phosphatase (ALP) levels, anti-tartrate acid phosphatase (TRACP-5b) levels and traditional Chinese medicine (TCM) syndrome scores. We assessed the regulatory roles of miRNAs in PMOP patients by analysing publicly available data from the Gene Expression Omnibus (GEO) database. Bioinformatics methods were also used to explore the mechanism by which YGD regulates miRNAs that are involved in bone metabolism. Results: Compared with those before treatment, the BMD, ALP levels, TRACP-5b levels, TCM syndrome scores and VAS scores improved in both groups after 3 months of treatment (P < 0.05). A total of 82 miRNAs differed between the groups. After analysing data from the GEO database, we confirmed that miR-133a-3p is the key molecule that mediates the effects of YGD intervention on PMOP. GO analysis of key genes suggested that gene enrichment was more pronounced in response to hormones, cellular response to growth factor stimulation, and positive regulation of physiological and metabolic processes. KEGG analysis revealed that these genes were enriched mainly in the PI3K-Akt, FOXO, and JAK-STAT pathways and other pathways. The results of the protein‒protein interaction (PPI) network analysis revealed that epidermal growth factor receptor (EGFR), Insulin-like growth factor 1 (IGF-1), Caveolin-1 (Cav-1) and others were core proteins. Conclusion: This study demonstrated that YGD is beneficial in the treatment of PMOP, ameliorating clinical symptoms and bone turnover indices. Moreover, the inhibition of miR-133a-3p expression may be the key mechanisms by which YGD regulates bone metabolism in the treatment of PMOP, although YGD regulates bone metabolism in a multitarget and multipathway manner. [ABSTRACT FROM AUTHOR]

Background: Evidence shows that the total flavonoids of Rhizoma Drynariae (TFRD) can improve bone mineral density (BMD). However, there is no evidence to summarize the improvement of biochemical indicators of bone metabolism (BIBM). Methods: The PubMed, Web of Science, Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP Information Database (VIP) and SinoMed were searched from inception to 6 May 2024. The final included studies performed meta-analyses using RevMan 5.3. Results: Nine randomized controlled trials (RCTs) were ultimately included. The TFRD group had higher bone gla protein (BGP) and type I procollagen-N-propeptide (PINP) compared to theOther therapies (WMD: 5.11; 95% CI: 3.37, 6.84; p < 0.00001; WMD: 13.89; 95% CI: 11.81, 15.97; p < 0.00001). The tartrate-resistant acid phosphatase (TRACP) decreased significantly (WMD: -1.34; 95% CI: -1.62, -1.06; p < 0.00001). The alkaline phosphatase (ALP) increased significantly (WMD: 7.47; 95% CI: 6.29, 8.66; p < 0.00001). There were no significant differences in serum calcium (SC) or serum phosphorus (SP) levels between the TFRD and control groups (WMD: 0.08; 95% CI: -0.04, 0.20; p = 0.17; WMD: 0.02; 95% CI: -0.02, 0.05; p = 0.36). Conclusion: TFRD can stimulate bone formation and prevent bone resorption in osteoporosis (OP) patients, but it has no effect on SC and SP. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/. [ABSTRACT FROM AUTHOR]

Background: Recent epidemiological studies and animal experiments have highlighted the significant role of oxidative stress in the development of osteoporosis (OP). The provision of antioxidants is widely considered a fundamental strategy to combat free radical-induced stress, inhibit oxidative damage, and potentially reverse the adverse effects of oxidative stress on bone health. However, there is no consensus in the scientific literature regarding the practical effectiveness of antioxidants in OP prevention and treatment. Some studies have not shown a clear connection between antioxidant supplementation and decreased OP risk. Therefore, it is essential to clarify the potential causal relationship between antioxidants and the development of OP. Methods: The study utilized the inverse variance weighted (IVW) approach as the primary analytical method in the Mendelian Randomization (MR) framework to investigate the causal effects of five exogenous and six endogenous antioxidants on the risk of OP. To thoroughly assess potential pleiotropic effects and heterogeneity among the data analyzed, the MR-Egger intercept test was employed, and Cochran's Q statistic was calculated. Results: In the evaluation of exogenous antioxidants, single-directional twosample MR analyses did not reveal any statistically significant relationship between these agents and the risk of OP. Regarding endogenous antioxidants, bidirectional two-sample MR analyses were conducted, which generally indicated that most genetically regulated endogenous antioxidants had no significant association with the onset risk of OP. A significant causal relationship was found between OP and serum albumin levels (β: 0.0552, 95%CI: 0.0879 to 0.0225, p <0.0011 after Bonferroni adjustment, power = 100%). Conclusion: The research uncovers OP as a possible determinant contributing to a decrement in serum albumin levels, and further suggests a potentially intimate relationship between the downward trajectory of serum albumin concentrations and the advancement of the OP disease process. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is the second most common neurodegenerative illness and has the highest increase rate in recent years. There is growing evidence to suggest that PD is linked to higher osteoporosis rates and risk of fractures. Objective: This study aims to estimate the prevalence and factors associated with osteoporosis as defined by the National Osteoporosis Foundation (NOF) and World Health Organization in patients with mild to moderate PD. Methods: We performed a cross-sectional study at a tertiary public hospital in Fortaleza, Brazil, dating from May 2021 until April 2022. The study sample was comprised of patients with mild to moderate PD who were at least 40 years old and who had the ability to walk and stand unassisted. Bone Mineral Density (BMD) of both the hip (neck of the femur) and the lumbar spine were obtained via properly calibrated Dual Energy X-ray Absorptiometry (DXA) scanning. The FRAX (Fracture Risk Assessment Tool) score was used to determine a person's 10-year risk of major osteoporotic fracture. The Revised European Working Group on Sarcopenia in Older People (EWGSOP 2) was used as a basis to confirm a sarcopenia diagnosis with the following parameters: low muscle strength gauged by handgrip strength and low muscle quantity by DXA. Physical performance was carefully evaluated by using the Short Physical Performance Battery test. Osteoporosis and osteopenia were diagnosed following the NOF guidelines and WHO recommendations. Results: We evaluated 107 patients in total, of whom 45 (42%) were women. The group's mean age was 68 ± 9 years, and the mean disease time span was 9.9 ± 6.0 years and mean motor UPDRS was 43 ± 15. We found that 42.1% and 34.6% of the sample had osteopenia and osteoporosis following NOF criteria, respectively, and 43% and 33.6% following the WHO recommendations. Lower lean appendicular mass was associated to osteopenia and osteoporosis in multinomial logistic regression analysis in both diagnostic criteria. Conclusion: Our findings provide additional evidence for the protective role of lean mass against osteoporosis in patients with PD. [ABSTRACT FROM AUTHOR]

It is generally accepted that radiolysis of water on the surface of PuO2 by alpha particles is the source of H2 which can cause pressurisation in sealed storage containers if the material is not adequately conditioned before packing. The mechanisms for this have not been discussed in detail previously. Radiolysis mechanisms of bulk water are summarised and then applied to water at the surface of PuO2. It is shown that the radiolysis processes occurring on timescales of less than 1 ps after energy deposition could have an impact on the storage behaviour of the PuO2 and the potential gas volume generated. Some of the radiolysis products are highly reactive and would be expected to react with plutonium at the surface, affecting the usual water radiolysis processes. A corollary of this observation is that the surface should not be considered a completely crystalline PuO2 solid. It is also highlighted that whilst there are significant uncertainties in the radiolysis process at the PuO2 surface there are also significant uncertainties in H2 formation mechanisms in bulk water. Finally, methods to model the radiolysis process at the surface and the prospects for predictive models are briefly discussed with suggestions for future areas of development. [ABSTRACT FROM AUTHOR]

Osteoporosis, arthritis, and fractures are examples of orthopedic illnesses that not only significantly impair patients' quality of life but also complicate and raise the expense of therapy. It has been discovered in recent years that the pathophysiology of orthopedic disorders is significantly influenced by the microbiota. By employing machine learning and deep learning techniques to conduct a thorough analysis of the disease-causingmicrobiome, we can enhance our comprehension of the pathophysiology of many illnesses and expedite the creation of novel treatment approaches. Today's science is undergoing a revolution because to the introduction of machine learning and deep learning technologies, and the field of biomedical research is no exception. The genesis, course, and management of orthopedic disorders are significantly influenced by pathogenic microbes. Orthopedic infection diagnosis and treatment are made more difficult by the lengthy and imprecise nature of traditional microbial detection and characterization techniques. These cutting-edge analytical techniques are offering previously unheard-of insights into the intricate relationships between orthopedic health and pathogenic microbes, opening up previously unimaginable possibilities for illness diagnosis, treatment, and prevention. The goal of biomedical research has always been to improve diagnostic and treatment methods while also gaining a deeper knowledge of the processes behind the onset and development of disease. Although traditional biomedical research methodologies have demonstrated certain limits throughout time, they nevertheless rely heavily on experimental data and expertise. This is the area in which deep learning and machine learning approaches excel. The advancements in machine learning (ML) and deep learning (DL) methodologies have enabled us to examine vast quantities of data and unveil intricate connections between microorganisms and orthopedic disorders. The importance of ML and DL in detecting, categorizing, and forecasting harmful microorganisms in orthopedic infectious illnesses is reviewed in this work. [ABSTRACT FROM AUTHOR]

Glucocorticoid-induced osteoporosis (GIO) is a significant side effect of prolonged glucocorticoid (GC) treatment. Chronic GC treatment also leads to trabecular bone loss and gut microbiota dysbiosis in mice. The gut dysbiosis is mechanistically linked to GIO, which indicates that the microbiota can be targeted to prevent GIO. Prunes, a dried fruit and prebiotic, have emerged in the literature as an effective treatment for sex-steroid deficiency induced osteoporosis (primary osteoporosis). Prunes also significantly alter the composition of the gut microbiota in both rodent models and human studies. Therefore, we tested if dietary prune (DP) supplementation could prevent GC-induced bone loss and affect microbiota composition in an established model of GIO. Sixteen-week-old, skeletally mature, female C57BL/6J mice were treated with a subcutaneous 5mg placebo or prednisolone pellet for 8 weeks and fed an AIN-93M control diet or a diet modified to include 5, 15, or 25% (w/w) dried California prune powder. As expected, GC treated mice developed significant trabecular bone loss in the distal femur. More importantly, as little as 5% DP supplementation effectively prevented trabecular bone loss. Further, dose dependent increases in trabecular bone volume fraction were observed in GC + 15% and GC + 25% DP mice. Amazingly, in the placebo (non-GC treated) groups, 25% DP supplementation caused a ~3-fold increase in distal femur trabecular bone volume fraction; this sizable bone response has not been previously observed in healthy mice with gut targeted natural treatments. Along with the striking effect on bone health, GC treatment and 25% DP supplementation led to drastic shifts in gut microbiota composition and several specific changes are strongly associated with bone health. Taken together, these results are the first to demonstrate that DP supplementation effectively prevents the negative effects of prolonged GC therapy on trabecular bone health and strongly associates with shifts in the composition of the gut microbiota. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP), characterized by continuous bone loss and increased fracture risk, has posed a challenge to patients and society. Long-term administration of current pharmacological agents may cause severe side effects. Traditional medicines, acting as alternative agents, show promise in treating OP. Osthole, a natural coumarin derivative separated from Cnidium monnieri (L.) Cusson and Angelica pubescens Maxim. f., exhibits protective effects against the pathological development of OP. Osthole increases osteoblast-related bone formation and decreases osteoclast-related bone resorption, suppressing OP-related fragility fracture. In addition, the metabolites of osthole may exhibit pharmacological effectiveness against OP development. Mechanically, osthole promotes osteogenic differentiation by activating the Wnt/β-catenin and BMP-2/Smad1/5/8 signaling pathways and suppresses RANKL-induced osteoclastogenesis and osteoclast activity. Thus, osthole may become a promising agent to protect against OP development. However, more studies should be performed due to, at least in part, the uncertainty of drug targets. Further pharmacological investigation of osthole in OP treatment might lead to the development of potential drug candidates. [ABSTRACT FROM AUTHOR]

We have recently published the notion of the “vitals” of Parkinson’s, a conglomeration of signs and symptoms, largely nonmotor, that must not be missed and yet often not considered in neurological consultations, with considerable societal and personal detrimental consequences. This “dashboard,” termed the Chaudhuri’s vitals of Parkinson’s, are summarized as 5 key vital symptoms or signs and comprise of (a) motor, (b) nonmotor, (c) visual, gut, and oral health, (d) bone health and falls, and finally (e) comorbidities, comedication, and dopamine agonist side effects, such as impulse control disorders. Additionally, not addressing the vitals also may reflect inadequate management strategies, leading to worsening quality of life and diminished wellness, a new concept for people with Parkinson’s. In this paper, we discuss possible, simple to use, and clinically relevant tests that can be used to monitor the status of these vitals, so that these can be incorporated into clinical practice. We also use the term Parkinson’s syndrome to describe Parkinson’s disease, as the term “disease” is now abandoned in many countries, such as the U.K., reflecting the heterogeneity of Parkinson’s, which is now considered by many as a syndrome. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the effects of different exercise dose on lumbar spine and femoral neck bone mineral density (BMD) in individuals with osteoporosis (OP). Design: A systematic search was conducted in four electronic databases, namely, PubMed, Embase, Web of Science, and Cochrane, with the topic of the impact of exercise on BMD in individuals with OP. Randomized controlled trials comparing exercise intervention with no intervention were identified, and changes in lumbar spine and femoral neck BMD were reported and evaluated using standardized mean difference (SMD) and 95% confidence interval (95% CI). The intervention measures in the studies were evaluated and categorized as high adherence with the exercise testing and prescription recommendations for individuals with OP developed by the American College of Sports Medicine (ACSM) or low/uncertainty adherence with ACSM recommendations. A random effects model was used to conduct meta-analyses and compare the results between subgroups. Results: A total of 32 studies involving 2005 participants were included in the analyses, with 14 studies categorized as high adherence with ACSM recommendations and 18 studies categorized as low or uncertain adherence. In the analyses of lumbar spine BMD, 27 studies with 1,539 participants were included. The combined SMD for the high adherence group was 0.31, while the combined SMD for the low or uncertain adherence group was 0.04. In the analyses of femoral neck BMD, 23 studies with 1,606 participants were included. The combined SMD for the high adherence group was 0.45, while the combined SMD for the low or uncertain adherence group was 0.28. Within resistance exercise, the subgroup with high ACSM adherence had a greater impact on lumbar spine BMD compared to the subgroup with low or uncertain ACSM adherence (SMD: 0.08 > -0.04). Similarly, for femoral neck BMD, resistance exercise with high ACSM adherence had a higher SMD compared to exercise with low or uncertain ACSM adherence (SMD: 0.49 > 0.13). Conclusion: The results suggest that exercise interventions with high adherence to ACSM recommendations are more effective in improving lumbar spine and femoral neck BMD in individuals with OP compared to interventions with low or uncertain adherence to ACSM recommendations. [ABSTRACT FROM AUTHOR]

Sarcopenia and osteoporosis, two degenerative diseases in older patients, have become severe health problems in aging societies. Muscles and bones, the most important components of the motor system, are derived from mesodermal and ectodermal mesenchymal stem cells. The adjacent anatomical relationship between them provides the basic conditions for mechanical and chemical signals, which may contribute to the co-occurrence of sarcopenia and osteoporosis. Identifying the potential common crosstalk genes between them may provide new insights for preventing and treating their development. In this study, DEG analysis, WGCNA, and machine learning algorithms were used to identify the key crosstalk genes of sarcopenia and osteoporosis; this was then validated using independent datasets and clinical samples. Finally, four crosstalk genes (ARHGEF10, PCDH7, CST6, and ROBO3) were identified, and mRNA expression and protein levels of PCDH7 in clinical samples from patients with sarcopenia, with osteoporosis, and with both sarcopenia and osteoporosis were found to be significantly higher than those from patients without sarcopenia or osteoporosis. PCDH7 seems to be a key gene related to the development of both sarcopenia and osteoporosis. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP) is a metabolic disease that affects bone, resulting in a progressive decrease in bone mass, quality, and micro-architectural degeneration. Natural products have become popular for managing OP in recent years due to their minimal adverse side effects and suitability for prolonged use compared to chemically synthesized products. These natural products are known to modulate multiple OP-related gene expressions, making epigenetics an important tool for optimal therapeutic development. In this study, we investigated the role of epigenetics in OP and reviewed existing research on using natural products for OP management. Our analysis identified around twenty natural products involved in epigenetics-based OP modulation, and we discussed potential mechanisms. These findings highlight the clinical significance of natural products and their potential as novel anti-OP therapeutics. [ABSTRACT FROM AUTHOR]

Oxytocin (OT) is a neuropeptide known to affect social behavior and cognition. The epigenetic modification of the oxytocin receptor (OTR) via DNA methylation stimulates parturition and breast milk secretion and inhibits craniopharyngioma, breast cancer, and ovarian cancer growth significantly as well as directly regulates bone metabolism in their peripheral form rather than the central form. OT and OTR can be expressed on bone marrow mesenchymal stem cells (BMSCs), osteoblasts (OB), osteoclasts (OC), osteocytes, chondrocytes, and adipocytes. OB can synthesize OT under the stimulation of estrogen as a paracrine-autocrine regulator for bone formation. OT/OTR, estrogen, and OB form a feed-forward loop through estrogen mediation. The osteoclastogenesis inhibitory factor (OPG)/receptor activator of the nuclear factor kappa-B ligand (RANKL) signaling pathway is crucially required for OT and OTR to exert anti-osteoporosis effect. Downregulating the expression of bone resorption markers and upregulating the expression of the bone morphogenetic protein, OT could increase BMSC activity and promote OB differentiation instead of adipocytes. It could also stimulate the mineralization of OB by motivating OTR translocation into the OB nucleus. Moreover, by inducing intracytoplasmic Ca2+ release and nitric oxide synthesis, OT could regulate the OPG/RANKL ratio in OB and exert a bidirectional regulatory effect on OC. Furthermore, OT could increase the activity of osteocytes and chondrocytes, which helps increase bone mass and improve bone microstructure. This paper reviews recent studies on the role of OT and OTR in regulating cells in bone metabolism as a reference for their clinical use and research based on their reliable anti-osteoporosis effects. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP) is a metabolic bone disorder characterized by low bone mass and deterioration of micro-architectural bone tissue. The most common type of OP is postmenopausal osteoporosis (PMOP), with fragility fractures becoming a global burden for women. Recently, the gut microbiota has been connected to bone metabolism. The aim of this study was to characterize the gut microbiota signatures in PMOP patients and controls. Fecal samples from 21 PMOP patients and 37 controls were collected and analyzed using amplicon sequencing of the V3-V4 regions of the 16S rRNA gene. The bone mineral density (BMD) measurement and laboratory biochemical test were performed on all participants. Two feature selection algorithms, maximal information coefficient (MIC) and XGBoost, were employed to identify the PMOP-related microbial features. Results showed that the composition of gut microbiota changed in PMOP patients, and microbial abundances were more correlated with total hip BMD/T-score than lumbar spine BMD/T-score. Using the MIC and XGBoost methods, we identified a set of PMOP-related microbes; a logistic regression model revealed that two microbial markers (Fusobacteria and Lactobacillaceae) had significant abilities in disease classification between the PMOP and control groups. Taken together, the findings of this study provide new insights into the etiology of OP/PMOP, as well as modulating gut microbiota as a therapeutic target in the diseases. We also highlight the application of feature selection approaches in biological data mining and data analysis, which may improve the research in medical and life sciences. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whole-body vibration (WBV) osteogenic potential in physically inactive postmenopausal women using high-frequency and combined amplitude stimuli. Methods: Two-hundred fifty-five physically inactive postmenopausal women (55–75 years) with 10-year major osteoporotic fracture risk (3%–35%) participated in this 18-month study. For the first 12 months, the vibration group experienced progressive 20-min WBV sessions (up to 3 sessions/ week) with rest periods (30–60 s) between exercises. Frequencies (30–50 Hz), with low (0.2–0.4 mm) and high (0.6–0.8 mm) amplitude stimuli were delivered via PowerPlate Pro5 platforms producing accelerations of (0.75–7.04 g). The last 6 months for the treatment group were a follow-up period similar to control. Serum bone remodelling markers [C-terminal crosslinked telopeptide of type-1 collagen (CTX), procollagen type-1 N-terminal propeptide (P1NP), bone alkaline phosphatase (BAP) and sclerostin] were measured at fasting. CTX and P1NP were determined by automated chemiluminescence immunoassay, bone alkaline phosphatase (BAP) by automated spectrophotometric immunoassay, and sclerostin by an enzyme-immunoassay. Bone mineral density (BMD) of the whole-body, proximal femur and lumbar vertebrae was measured by dual-energy X-ray absorptiometry (DXA). Bone microarchitecture of the distal non-dominant radius and tibia was measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results: Femoral neck (p = 0.520) and spine BMD (p = 0.444) failed to improve after 12 months of WBV. Bone macro and microstructural parameters were not impacted by WBV, as well as estimated failure load at the distal radius (p = 0.354) and tibia (p = 0.813). As expected, most DXA and HR-pQCT parameters displayed age-related degradation in this postmenopausal population. BAP and CTX increased over time in both groups, with CTX more marginally elevated in the vibration group when comparing baseline changes to month-12 (480.80 pmol/L; p = 0.039) and month-18 (492.78 pmol/L; p = 0.075). However, no differences were found when comparing group concentrations only at month-12 (506.35 pmol/L; p = 0.415) and month-18 (518.33 pmol/L; p = 0.480), indicating differences below the threshold of clinical significance. Overall, HR-pQCT, DXA bone parameters and bone turnover markers remained unaffected. Conclusion: Combined amplitude and high-frequency training for one year had no ameliorating effect on DXA and HR-pQCT bone parameters in physically inactive postmenopausal women. Serum analysis did not display any significant improvement in formation and resorption markers and also failed to alter sclerostin concentrations between groups. [ABSTRACT FROM AUTHOR]

Senile osteoporosis is a chronic skeletal disease, leading to increased bone brittleness and risk of fragile fractures. With the acceleration of population aging, osteoporosis has gradually become one of the most serious and prevalent problems worldwide. Bone formation is highly dependent on the proper osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in the bone marrow microenvironment, which is generated by the functional relationship among different cell types, including osteoblasts, adipogenic cells, and bone marrow stromal cells in the bone marrow. It is still not clear how osteoporosis is caused by its molecular mechanism. With aging, bone marrow is able to restrain osteogenesis. Discovering the underlying signals that oppose BMSC osteogenic differentiation from the bone marrow microenvironment and identifying the unusual changes in BMSCs with aging is important to elucidate possible mechanisms of senile osteoporosis. We used 3 gene expression profiles (GSE35956, GSE35957, and GSE35959) associated with osteoporosis. And a protein-protein interaction (PPI) network was also built to identify the promising gene CD137. After that, we performed in vivo experiments to verify its function and mechanism. In this experiment, we found that significant bone loss was observed in aged (18-month-old) mice compared with young (6-month-old) mice. The adipose tissue in bone marrow cavity from aged mice reached above 10 times more than young mice. Combining bioinformatics analysis and vivo experiments, we inferred that CD137 might be involved in the p53 and canonical Wnt/β-catenin signaling pathways and thereby influenced bone mass through regulation of marrow adipogenesis. Importantly, osteoporosis can be rescued by blocking CD137 signaling in vivo. Our research will contribute to our understanding not only of the pathogenesis of age-related bone loss but also to the identification of new targets for treating senile osteoporosis. [ABSTRACT FROM AUTHOR]

Parathyroid hormone (PTH) 1–34 is the first anabolic agent approved for the treatment of osteoporosis. Preclinical evidence shows a potential association between PTH and osteosarcoma. The mechanisms mediating the bone- and neoplasm-forming effects of PTH remain incompleted understood, few studies on the role of Insulin-like growth factor-binding protein 7 (IGFBP7) in mediating the anabolic effects of PTH has been reported. Intermittent PTH administration was found to increase the expression of IGFBP7 in mesenchymal stem cells (MSCs) and pre-osteoblasts. The results indicated that the anabolic effects of PTH were interrupted when knockdown of IGFBP7, while supplementation with IGFBP7 protein could enhance the bone-forming efficacy of PTH and regulate the signaling pathways. Moreover, bone healing was accelerated by the administration of IGFBP7 along with PTH in a mouse model of fracture. The obtained results proved that IGFBP7 was necessary for the anabolic effects of PTH, and combined administration of PTH and IGFBP7 showed stronger bone-forming effects relative to administration of PTH alone. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a multifactorial joint disease characterized by degeneration of articular cartilage, which leads to joints pain, disability and reduced quality of life in patients with OA. Interpreting the potential mechanisms underlying OA pathogenesis is crucial to the development of new disease modifying treatments. Although multiple factors contribute to the initiation and progression of OA, gut microbiota has gradually been regarded as an important pathogenic factor in the development of OA. Gut microbiota can be regarded as a multifunctional "organ", closely related to a series of immune, metabolic and neurological functions. This review summarized research evidences supporting the correlation between gut microbiota and OA, and interpreted the potential mechanisms underlying the correlation from four aspects: immune system, metabolism, gut-brain axis and gut microbiota modulation. Future research should focus on whether there are specific gut microbiota composition or even specific pathogens and the corresponding signaling pathways that contribute to the initiation and progression of OA, and validate the potential of targeting gut microbiota for the treatment of patients with OA. [ABSTRACT FROM AUTHOR]

Systemic vasculitides are a range of conditions characterized by inflammation of blood vessels which may manifest as single organ or life-threatening multisystem disease. The treatment of systemic vasculitis varies depending on the specific disease but historically has involved initial treatment with high dose glucocorticoids alone or in conjunction with other immunosuppressive agents. Prolonged glucocorticoid treatment is frequently required as maintenance treatment. Patients with small and large vessel vasculitis are at increased risk of fracture. Osteoporosis may occur due to intrinsic factors such as chronic inflammation, impaired renal function and to a large extent due to pharmacological therapy with high dose glucocorticoid or combination treatments. This review will outline the known mechanism of bone loss in vasculitis and will summarize factors attributing to fracture risk in different types of vasculitis. Osteoporosis treatment with specific consideration for patients with vasculitis will be discussed. The use of glucocorticoid sparing immunosuppressive agents in the treatment of systemic vasculitis is a significant area of ongoing research. Adjunctive treatments are used to reduce cumulative doses of glucocorticoids and therefore may significantly decrease the associated fracture risk in patients with vasculitis. Lastly, we will highlight the many unknowns in the relation between systemic vasculitis, its treatment and bone health and will outline key research priorities for this field. [ABSTRACT FROM AUTHOR]

Glucocorticoid-induced osteoporosis (GIOP) leads to fractures in up to 40% of patients with chronic glucocorticoid (GC) therapy when left untreated. GCs rapidly increase fracture risk, and thus many patients with anticipated chronic GC exposures should start anti-osteoporosis pharmacotherapy to prevent fractures. In addition to low awareness of the need for anti-osteoporosis therapy among clinicians treating patients with GCs, a major barrier to prevention of fractures from GIOP is a lack of clear guideline recommendations on when to start and stop anti-osteoporosis treatment in patients with GC use. The aim of this narrative review is to summarize current evidence and provide considerations for the duration of anti-osteoporosis treatment in patients taking GCs based on pre-clinical, clinical, epidemiologic, and pharmacologic evidence. We review the pathophysiology of GIOP, outline current guideline recommendations on initiating and stopping anti-osteoporosis therapy for GIOP, and present considerations for the duration of anti-osteoporosis treatment based on existing evidence. In each section, we illustrate major points through a patient case example. Finally, we conclude with proposed areas for future research and emerging areas of interest related to GIOP clinical management. [ABSTRACT FROM AUTHOR]

There is growing recognition of the role of diet and physical activity in modulating bone mineral density, bone mineral content, and remodeling, which in turn can impact bone health later in life. Adequate nutrient composition could influence bone health and help to maximize peak bone mass. Therefore, children's nutrition may have lifelong consequences. Also, physical activity, adequate in volume or intensity, may have positive consequences on bone mineral content and density and may preserve bone loss in adulthood. Most of the literature that exists for children, about diet and physical activity on bone health, has been translated from studies conducted in adults. Thus, there are still many unanswered questions about what type of diet and physical activity may positively influence skeletal development. This review focuses on bone requirements in terms of nutrients and physical activity in childhood and adolescence to promote bone health. It explores the contemporary scientific literature that analyzes the impact of diet together with the typology and timing of physical activity that could be more appropriate depending on whether they are children and adolescents to assure an optimal skeleton formation. A description of the role of parathyroid hormone (PTH) and gut hormones (gastric inhibitory peptide (GIP), glucagon-like peptide (GLP)-1, and GLP-2) as potential candidates in this interaction to promote bone health is also presented. [ABSTRACT FROM AUTHOR]

Neurological diseases, particularly in the context of aging, have serious impacts on quality of life and can negatively affect bone health. The brain-bone axis is critically important for skeletal metabolism, sensory innervation, and endocrine cross-talk between these organs. This review discusses current evidence for the cellular and molecular mechanisms by which various neurological disease categories, including autoimmune, developmental, dementia-related, movement, neuromuscular, stroke, trauma, and psychological, impart changes in bone homeostasis and mass, as well as fracture risk. Likewise, how bone may affect neurological function is discussed. Gaining a better understanding of brain-bone interactions, particularly in patients with underlying neurological disorders, may lead to development of novel therapies and discovery of shared risk factors, as well as highlight the need for broad, whole-health clinical approaches toward treatment. [ABSTRACT FROM AUTHOR]

Masters endurance runners can epitomize healthy aging; being reflective of the physiological processes of aging without the compounded effects of inactivity. The primary aim of the present study was to determine, using cross-sectional data, whether individuals taking up training after the age of 50 years can achieve the same level of athletic performance and musculoskeletal characteristics in their older age as those who trained all of their adult lives. A total of 150 master endurance runners [age 68 (5) years; 111 male, 39 female] were divided into early starters (training all of their adulthood) and late starters (started training after age 50 years). A comparative non-athletic group of 59 healthy older adults [age 73 (4) years; 30 female, 29 male] were additionally included for analysis. Training intensity, age-graded performance (AGP) and musculoskeletal assessments were performed. Results showed that there was no difference between athlete groups for training intensity or age-graded performance, despite the 30-year difference in training history. Body fat percentage and leg lean mass did not differ between athlete groups, but were 17% lower and 12% greater, respectively, in athlete groups compared with controls. Power normalized to body mass did not differ between any groups. Spine BMD was lower in late starters than controls, while early starters did not differ from late starters or controls. Hip BMD did not differ between any of the groups. These findings show that the Masters athletes we studied that started intense endurance running after the age of 50 years had lower body fat and higher leg lean mass compared to non-athletes. Body composition and athletic performance of the late starters was very similar to those who trained all of their adult lives. [ABSTRACT FROM AUTHOR]

Background: Recent studies in several countries show a significant decrease in the consumption of osteoporosis drugs from a peak around 2009, mainly attributed to bisphosphonate safety warnings issued by regulatory agencies on jaw osteonecrosis, atypical fractures, and esophageal cancer, but no studies have assessed the impact of these warnings by risk of fracture strata. Aim: The aim of this work is to assess changes in the utilization of osteoporosis drugs in the region of Valencia (Spain) after safety warnings from regulatory agencies and cost-sharing changes, according to patient socio-demographic and risk of fracture characteristics. Patients and Methods: We constructed a monthly series of osteoporosis drug consumption for 2009–2015 from the ESOSVAL cohort (n = 11,035; women: 48%; mean age: 65 years old) and used interrupted time series and segmented linear regression models to assess changes in osteoporosis drug utilization while controlling for previous levels and trends after three natural intervention dates: the issue of the Spanish Agency for Drugs and Medical Products (AEMPS) Osteonecrosis Jaw Warning (Sept 2009), the AEMPS Atypical femur Fracture Warning (Apr 2011), and the modification of the cost-sharing scheme (Jul 2012). Results: The AEMPS Osteonecrosis Jaw Warning was not associated with a decline in the consumption of osteoporosis drugs, while the warning on atypical fracture (a downward trend of 0.11% fewer people treated each month) and the increase in the cost-sharing scheme (immediate change level of -1.07% in the proportion of people treated) were associated with a strong decline in the proportion of patients treated, so that by the end of 2015 osteoporosis drug consumption was around half that of 2009. The relative decline was similar in people with both a high and low risk of fracture. Conclusion: The AEMPS Atypical femur Fracture Warning of Apr 2010 was associated with a significant decrease in the number of people treated, reinforced by the increase in the pharmaceutical cost-sharing in 2012. Decreases in treatment affected patients both at a low and higher risk of fracture. [ABSTRACT FROM AUTHOR]

Objective: In aging population, postmenopausal osteoporosis and decline of musculoskeletal function, referred to as "frailty syndrome" lead to loss of bone and muscle, causing falls, and fall-related injuries. To limit the impact of this portentous duo, simultaneous treatment of both is needed. Urocortin (UCN) has been reported to improve osteoporotic bone properties while its effect on muscle has not been addressed yet. Design and Methods: We aimed to investigate the effect of urocortin in vivo on skeletal muscle structure in osteopenic rats. Sixty Sprague-Dawley rats were divided into five groups: four were ovariectomized (OVX) and one underwent sham operation (SHAM). One ovariectomized group was left untreated (OVX), while one was treated with urocortin s.c. in 3 μg/kg body weight (bw) (OVX+UCN low), one with 30 μg/kg (OVX+UCN high), while one group was treated with estradiol orally (OVX+E: 0.2 mg/kg bw), each for 35 days. Mm. gastrocnemius, longissimus , and soleus were isolated and capillary density as well as diameters of type I and II fibers were measured. In addition, we examined the effect of UCN on tibia using biomechanical, micro-CT and ashing analysis and investigated the blood serum. Results: We demonstrated a positive effect of UCN on M. soleus , in which fiber diameter was positively influenced. The biomechanical and structural parameters of bone were not changed in UCN treated rats. The higher cholesterol, glucose and triglyceride levels in the "UCN high" group raise concern about this treatment. Conclusions: Our results portray urocortin as a substance that can be assessed for future therapeutic treatments of estrogen deficiency. New and Noteworthy: Urocortin has a positive effect on M. soleus (diameter). Urocortin raises serum cholesterol and triglyceride levels. Bone tissue was not affected by UCN. [ABSTRACT FROM AUTHOR]

Osteoporosis is the most common bone disease affecting millions of people worldwide, particularly in elderly or in post-menopausal women. The pathogenesis is useful to understand the possible mechanism of action of anti-osteoporotic drugs. Early diagnosis, possible with several laboratory and instrumental tests, allows a major accuracy in the choice of anti-osteoporosis drugs. Treatment of osteoporosis is strictly related to severity of pathology and consists on prevention of fragility fractures with a correct lifestyle and adequate nutritional supplements, and use of pharmacological therapy, started in patients with osteopenia and history of fragility fracture of the hip or spine. The purpose of this review is to focus on main current pharmacological products to treat osteoporotic patients. [ABSTRACT FROM AUTHOR]

Key points • Significantly lower BMD in PD compared to healthy subjects in both genders. • Less than 35 mg2/dl2 of Ca-P product in >80% of PD patients. • Significant correlations between BMD and severity of PD. • Lower BMD at H&Y stage III/IV than that at H&Y stage I/II. Objectives: Although several lines of evidence have suggested that patients with Parkinson's disease (PD) have a higher risk of osteoporosis and fracture, the association between bone mineral density (BMD) and severity of PD patients is unknown. Methods: We performed a cross-sectional study of 54 patients with PD and 59 healthy age-matched controls. Multiple clinical scales were used to evaluate the severity of PD, and serum levels of calcium, phosphorus, and homocysteine were measured to determine BMD's association with PD severity. results: BMD in PD patients was significantly lower than that in healthy controls. The BMD scores of the spine, femoral neck (FN), and hip were lower in females than in males in the healthy group. In the PD group, BMD in the hip was significantly lower in females compared to males. There was a negative correlation between daily l-DOPA dosage and BMD in the spine and hip in the PD group, while BMD in the spine, neck, and hip was significantly correlated with severity of PD. Besides, we found that among the lumbar spine (LS), FN, and hip, bone loss in the LS was the most severe in PD patients based on the T-scores. conclusion: Our findings support the hypothesis that patients with PD have a higher risk of osteoporosis, and that low BMD in the spine, FN, and hip may indirectly reflect the severity of PD. Our findings have prompted us to pay more attention to osteoporosis in the LS in Chinese PD patients. [ABSTRACT FROM AUTHOR]

Acetaminophen (APAP) is widely used as an over-the-counter fever reducer and pain reliever. However, the current therapeutic use of APAP is not optimal. The inter-patient variability in both efficacy and toxicity limits the use of this drug. This is particularly an issue in pediatric populations, where tools for predicting drug efficacy and developmental toxicity are not well established. Variability in toxicity between age groups may be accounted for by differences in metabolism, transport, and the genetics behind those differences. While pharmacogenomics has been revolutionizing the paradigm of pharmacotherapy for many drugs, its application in pediatric populations faces significant challenges given the dynamic ontogenic changes in cellular and systems physiology. In this review we focused on the ontogenesis of the regulatory pathways involved in the disposition of APAP and on the variability between pediatric, adolescent, and adult patients. We also summarize important polymorphisms of the pharmacogenes associated with APAP metabolism. Pharmacogenetic studies in pediatric APAP treatment are also reviewed.We conclude that while a consensus in pharmacogenetic management of APAP in pediatric populations has not been achieved, a systems biology based strategy for comprehensively understanding the ontogenic regulatory pathway as well as the interaction between age and genetic variations are particularly necessary in order to address this question. [ABSTRACT FROM AUTHOR]