Studying the Effects of Cold Plasma Phosphorus Using Physiological and Digital Image Processing Techniques.

The goal of this study is to see how cold plasma affects rabbit bone tissue infected with osteoporosis. The search is divided into three categories: control, infected, and treated. The rabbits were subjected to cold plasma for five minutes in a room with a microwave plasma voltage of "175 V" and a gas flow of "2." A histopathological photograph of infected bone cells is obtained to demonstrate the influence of plasma on infected bone cells, as well as the extent of destruction and effect of plasma therapy before and after exposure. The findings of the search show that plasma has a clear impact on Ca and vitamin D levels. In the cold plasma, the levels of osteocalcin and alkali phosphates (ALP) respond as well. Image processing techniques (second-order gray level matrix) with textural elements are employed as an extra proof. The outcome gives good treatment indicators, and the image processing result corresponds to the biological result.

Marine n-3 Polyunsaturated Fatty Acids and Bone Mineral Density in Kidney Transplant Recipients: A Randomized, Placebo-Controlled Trial.

Kidney transplant recipients are at high risk of progressive bone loss and low-energy fractures in the years following transplantation. Marine n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation may have beneficial effects on bone strength. The Omega-3 fatty acids in Renal Transplantation (ORENTRA) trial was an investigator initiated, randomized, placebo-controlled trial investigating the effects of marine n-3 PUFA supplementation after kidney transplantation. Effects of supplementation on bone mineral density (BMD) and calcium metabolism were pre-defined secondary endpoints. Adult kidney transplant recipients (n = 132) were randomized to 2.6 g marine n-3 PUFA supplement or olive oil (control) from 8 to 52 weeks post-transplant. Dual energy X-ray absorptiometry was performed to assess changes in bone mineral density of hip, spine, and forearm, as well as trabecular bone score (TBS) of the lumbar spine. Student's t test was used to assess between-group differences. There were no differences in ΔBMD between the two groups (intervention vs. control) at lumbar spine (-0.020 ± 0.08 vs. -0.007 ± 0.07 g/cm², p = 0.34), total hip (0.001 ± 0.03 vs. -0.005 ± 0.04, p = 0.38), or other skeletal sites in the intention-to-treat analyses. There was no difference in the change in TBS score (0.001 ± 0.096 vs. 0.009 ± 0.102, p = 0.62). Finally, no effect on biochemical parameters of mineral metabolism was seen. Results were similar when analyzed per protocol. In conclusion, we found no significant effect of 44 weeks of supplementation with 2.6 g of marine n-3 PUFA on BMD in kidney transplant recipients.

Assessment of the Methods Used to Develop Vitamin D and Calcium Recommendations-A Systematic Review of Bone Health Guidelines.

BACKGROUND: There are numerous guidelines developed for bone health. Yet, it is unclear whether the differences in guideline development methods explain the variability in the recommendations for vitamin D and calcium intake. The objective of this systematic review was to collate and compare recommendations for vitamin D and calcium across bone health guidelines, assess the methods used to form the recommendations, and explore which methodological factors were associated with these guideline recommendations. METHODS: We searched MEDLINE, EMBASE, CINAHL, and other databases indexing guidelines to identify records in English between 2009 and 2019. Guidelines or policy statements on bone health or osteoporosis prevention for generally healthy adults aged ≥40 years were eligible for inclusion. Two reviewers independently extracted recommendations on daily vitamin D and calcium intake, supplement use, serum 25 hydroxyvitamin D [25(OH)D] level, and sunlight exposure; assessed guideline development methods against 25 recommended criteria in the World Health Organization (WHO) handbook for guideline development; and, identified types identified types of evidence underpinning the recommendations. RESULTS: we included 47 eligible guidelines from 733 records: 74% of the guidelines provided vitamin D (200~600-4000 IU/day) and 70% provided calcium (600-1200 mg/day) recommendations, 96% and 88% recommended vitamin D and calcium supplements, respectively, and 70% recommended a specific 25(OH)D concentration. On average, each guideline met 10 (95% CI: 9-12) of the total of 25 methodological criteria for guideline development recommended by the WHO Handbook. There was uncertainty in the association between the methodological criteria and the proportion of guidelines that provided recommendations on daily vitamin D or calcium. Various types of evidence, including previous bone guidelines, nutrient reference reports, systematic reviews, observational studies, and perspectives/editorials were used to underpin the recommendations. CONCLUSIONS: There is considerable variability in vitamin D and calcium recommendations and in guideline development methods in bone health guidelines. Effort is required to strengthen the methodological rigor of guideline development and utilize the best available evidence to underpin nutrition recommendations in evidence-based guidelines on bone health.

Oxidative Stress and Osteoporosis.

➤: Oxidative stress has been implicated as a causative factor in many disease states, possibly including the diminished bone mineral density in osteoporosis. ➤: Understanding the effects of oxidative stress on the development of osteoporosis may lead to further research improving preventative and therapeutic measures that can combat this important contributor to morbidity and mortality worldwide. ➤: A diet rich in whole plant foods with high antioxidant content along with antioxidant-preserving lifestyle changes may improve bone mineral density and reduce the risk of fragility-related fractures. While it is not explicitly clear if antioxidant activity is the effector of this change, the current evidence supports this possibility. ➤: Supplementation with isolated antioxidants may also provide some osteoprotective benefits, but whole plant food-derived antioxidants potentially have more overall benefits. Larger-scale clinical trials are needed to give credence to definitive clinical recommendations.

Electroacupuncture stimulation at BL20, BL23 and SP6 prevents hind limb unloading-induced osteoporosis in rats.

BACKGROUND: Bone loss induced by microgravity is a serious problem in space flight. However, the effects of acupuncture stimulation on osteoporosis induced by microgravity have not been studied. With the goal of developing an effective countermeasure, our aim was to evaluate the effects of electroacupuncture (EA) stimulation at BL20, BL23, and SP6 on osteoporosis induced by simulated microgravity in rats. METHODS: Thirty male Wistar rats (aged 10 weeks) were randomly divided into three groups: healthy control group (CON, n = 10), hind limb unloading by tail-suspension group (T-S, n = 10), and EA treatment group (TRE, n = 10). Rats in the T-S and TRE groups were subjected to tail-suspension at -30° for 30 days, while the CON group experienced freedom of activity. In this period, the TRE group received EA treatment at BL20, BL23, and SP6 for 30 min every other day, which continued for 30 days. The microarchitecture of the proximal tibia and the biomechanical features of the femur in the rats were analyzed. In addition, the levels of serum biomarkers bone alkaline phosphatase (BALP) and osteocalcin (BGP) were measured. RESULTS: Compared with the CON group, the value of bone volume/total volume (BV/TV) and trabecular number (Tb.N) of the tibias in the TRE group remarkably decreased (p < 0.01). However, these changes were markedly less than those of the T-S group after 4 weeks of EA treatment (p < 0.05). Moreover, the serum concentration of BGP in the TRE group was also significantly higher than that of the T-S group (p < 0.05). CONCLUSIONS: These findings indicate that EA stimulation at BL20, BL23, and SP6 retards osteoporosis induced by hind limb unloading in rats.

Impairment of type H vessels by NOX2-mediated endothelial oxidative stress: critical mechanisms and therapeutic targets for bone fragility in streptozotocin-induced type 1 diabetic mice.

Rationale: Mechanisms underlying the compromised bone formation in type 1 diabetes mellitus (T1DM), which causes bone fragility and frequent fractures, remain poorly understood. Recent advances in organ-specific vascular endothelial cells (ECs) identify type H blood vessel injury in the bone, which actively direct osteogenesis, as a possible player. Methods: T1DM was induced in mice by streptozotocin (STZ) injection in two severity degrees. Bony endothelium, the coupling of angiogenesis and osteogenesis, and bone mass quality were evaluated. Insulin, antioxidants, and NADPH oxidase (NOX) inhibitors were administered to diabetic animals to investigate possible mechanisms and design therapeutic strategies. Results: T1DM in mice led to the holistic abnormality of the vascular system in the bone, especially type H vessels, resulting in the uncoupling of angiogenesis and osteogenesis and inhibition of bone formation. The severity of osteopathy was positively related to glycemic levels. These pathological changes were attenuated by early-started, but not late-started, insulin therapy. ECs in diabetic bones showed significantly higher levels of reactive oxygen species (ROS) and NOX 1 and 2. Impairments of bone vessels and bone mass were effectively ameliorated by treatment with anti-oxidants or NOX2 inhibitors, but not by a NOX1/4 inhibitor. GSK2795039 (GSK), a NOX2 inhibitor, significantly supplemented the insulin effect on the diabetic bone. Conclusions: Diabetic osteopathy could be a chronic microvascular complication of T1DM. The impairment of type H vessels by NOX2-mediated endothelial oxidative stress might be an important contributor that can serve as a therapeutic target for T1DM-induced osteopathy.

Current Evidence and Possible Future Applications of Creatine Supplementation for Older Adults.

Sarcopenia, defined as age-related reduction in muscle mass, strength, and physical performance, is associated with other age-related health conditions such as osteoporosis, osteosarcopenia, sarcopenic obesity, physical frailty, and cachexia. From a healthy aging perspective, lifestyle interventions that may help overcome characteristics and associated comorbidities of sarcopenia are clinically important. One possible intervention is creatine supplementation (CR). Accumulating research over the past few decades shows that CR, primarily when combined with resistance training (RT), has favourable effects on aging muscle, bone and fat mass, muscle and bone strength, and tasks of physical performance in healthy older adults. However, research is very limited regarding the efficacy of CR in older adults with sarcopenia or osteoporosis and no research exists in older adults with osteosarcopenia, sarcopenic obesity, physical frailty, or cachexia. Therefore, the purpose of this narrative review is (1) to evaluate and summarize current research involving CR, with and without RT, on properties of muscle and bone in older adults and (2) to provide a rationale and justification for future research involving CR in older adults with osteosarcopenia, sarcopenic obesity, physical frailty, or cachexia.

Arecanut (Areca catechu L.) Seed Polyphenol-Ameliorated Osteoporosis by Altering Gut Microbiome via LYZ and the Immune System in Estrogen-Deficient Rats.

Polyphenol can improve osteoporosis and is closely associated with gut microbiota, while the mechanism and the relationship among polyphenol, osteoporosis, and gut microbiota colonization remain unclear. Here, an osteoporosis rat model established by ovariectomy was employed to investigate the improving mechanism of arecanut (Areca catechu L.) seed polyphenol (ACP) on osteoporosis by regulating gut microbiota. We analyzed the bone microstructure, Paneth cells, regulating microbial protein (lysozyme (LYZ)), proinflammatory cytokines, macrophage infiltration levels, and gut microbial communities in a rat. ACP improved the trabecular microstructure compared to OVX, including the increased trabecular number (Tb.N) (P < 0.01) and trabecular thickness (Tb.Th) (P < 0.001) and decreased trabecular separation (Tb.Sp) (P < 0.01). At the phylum level, Bacteroidetes was increased after ovariectomy (P < 0.001) and Firmicutes and Proteobacteria were increased in ACP (P < 0.001). Antiosteoporosis groups with lower LYZ and Paneth cells (P < 0.001) showed that the microbiota Alistipes, which have a negative effect on bone metabolism were decreased in ACP (P < 0.001). Altogether, these studies showed that the estrogen deficiency could induce the shedding of Paneth cells, which leads to the decrease of LYZ, while ACP could increase the LYZ expression by maintaining the population of Paneth cells in an estrogen-deficient host, which were implicated in gut microbiota regulation and improved osteoporosis by controlling the inflammatory reaction.

A promising biomarker of elevated galanin level in hypothalamus for osteoporosis risk in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) and osteoporosis are two major healthcare problems worldwide. T2DM is considered to be a risk factor for osteoporosis. Interestingly, several epidemiological studies suggest that bone abnormalities associated with diabetes may differ, at least in part, from those associated with senile or post-menopausal osteoporosis. The growing prevalence that patients with T2DM simultaneously suffer from osteoporosis, puts forward the importance to discuss the relationship between both diseases, as well as to investigate correlative agents to treat them. Emerging evidences demonstrate that neuropeptide galanin is involved in the pathogenesis of T2DM and osteoporosis. Galanin via activation of central GALR2 increases insulin sensitivity as well as bone density and mass in animal models. The disorder of galanin function plays major role in development of both diseases. Importantly, galanin signaling is indispensable for ΔFosB, an AP1 antagonist, to play the bone mass-accruing effects in the ventral hypothalamic neurons of diabetic models. This review summarizes our and other recent studies to provide a new insight into the multivariate relationship among galanin, T2DM and osteoporosis, highlighting the beneficial effect of galanin on the comorbid state of both diseases. These may help us better understanding the pathogenesis of osteoporosis and T2DM and provide useful clues for further inquiry if elevated galanin level may be taken as a biomarker for both conjoint diseases, and GALR2 agonist may be taken as a novel therapeutic strategy to treat both diseases concurrently.

The emerging role of miR-128 in musculoskeletal diseases.

MicroRNA-128 (miR-128) is associated with cell proliferation, differentiation, migration, apoptosis, and survival. Genetic analysis studies have demonstrated that miR-128 participates in bone metabolism, which involves bone marrow-derived mesenchymal stem cells, osteoblasts, osteoclasts, and adipocytes. miR-128 also participates in regeneration of skeletal muscles by targeting myoblast-associated proteins. The deregulation of miR-128 could lead to a series of musculoskeletal diseases. In this review, we discuss recent findings of miR-128 in relation to bone metabolism and muscle regeneration to determine its potential therapeutic effects in musculoskeletal diseases, and to propose directions for future research in this significant field.

Treatment of osteoporosis with a modified zeolite shows beneficial effects in an osteoporotic rat model and a human clinical trial.

The severity of osteoporosis in humans manifests in its high incidence and by its complications that diminish quality of life. A societal consequence of osteoporosis is the substantial burden that it inflicts upon patients and their families. Several bone-modifying drugs have been prescribed to patients with osteoporosis. However, evidence for their anti-fracture efficacy remains inconclusive. To the contrary, long-term use of anti-osteoporotic drugs such as bisphosphonates and Denosumab, an RANKL inhibitor, have resulted in adverse events. We now present an alternative and adjuvant approach for treatment of osteoporosis. The data derive from in vivo studies in an ovariectomized rat model and from a randomized double blind, placebo-controlled human clinical study. Both studies involved treatment with Panaceo Micro Activation (PMA)-zeolite-clinoptilolite, a defined cation exchange clinoptilolite, which clearly improved all bone histomorphometric parameters examined from ovariectomized animals, indicative for increased bone formation. Moreover, intervention with PMA-zeolite-clinoptilolite for one year proved safe in humans. Furthermore, patients treated with PMA-zeolite-clinoptilolite showed an increase in bone mineral density, an elevated level of markers indicative of bone formation, a significant reduction in pain, and significantly improved quality of life compared with patients in the control (placebo) group. These encouraging positive effects of PMA-zeolite-clinoptilolite on bone integrity and on osteoporosis warrant further evaluation of treatment with PMA-zeolite-clinoptilolite as a new alternative adjuvant therapy for osteoporosis.

Denosumab-associated hypocalcemia: Does gender play a role?

OBJECTIVE: It is well recognized that the presentation, treatment, and outcomes of various diseases may differ between men and women. We recently reported a 7.4% rate of denosumab-associated hypocalcemia in community-dwelling osteoporotic patients. This study sought to investigate the role of gender in this complication. STUDY DESIGN: Retrospective community-dwelling cohort. METHOD: The databases of a large health maintenance organization were searched for adult patients treated with denosumab for osteoporosis in 2010-2018. Rates and predictors of denosumab-associated hypocalcemia (serum calcium ≤8.5 mg/mL) were analyzed by gender. RESULTS: The cohort included 1871 women and 134 men. Compared with the women, the men were characterized by older median age (81 vs. 77 years, p = 0.005), higher likelihood to receive denosumab as a first-line treatment (22% vs. 6%, p < 0.001), less treatment with calcium supplements (42% vs. 53%, p = 0.012), and lower median eGFR level (66.1 vs. 79.8 mL/min/1.73m2, p < 0.001). Denosumab-associated hypocalcemia developed in 133 women (7.1%) and 16 men (11.9%) (p = 0.04); the drug was discontinued in 75% and 61%, respectively. The strongest predictors of hypocalcemia in women were levels of pretreatment albumin-adjusted serum calcium (OR 0.08, 95% CI (0.04, 0.14)) and creatinine (OR 2.43, 95% CI (1.45, 4.05)). There were no predictors in men. On propensity matching of 126 men and 126 women, gender was not a predictor of hypocalcemia. CONCLUSION: Denosumab-treated men were significantly older than treated women and had a lower eGFR and more advanced osteoporosis. These findings suggest that selection bias rather than male genderper se underlies the higher rate of denosumab-associated hypocalcemia in men.

Genistein Improves Bone Healing via Triggering Estrogen Receptor Alpha-Mediated Expressions of Osteogenesis-Associated Genes and Consequent Maturation of Osteoblasts.

Osteoporosis-associated fractures may cause higher morbidity and mortality. Our previous study showed the effects of genistein, a phytoestrogen, on the induction of estrogen receptor alpha (ERα) gene expression and stimulation of osteoblast mineralization. In this study, rat calvarial osteoblasts and an animal bone defect model were used to investigate the effects of genistein on bone healing. Treatment with genistein caused a time-dependent increase in alkaline phosphatase (ALP) activity in rat osteoblasts. Levels of cytosolic and nuclear ERα significantly augmented following exposure to genistein. Subsequently, genistein elevated levels of ALP mRNA and protein in rat osteoblasts. Moreover, genistein induced other osteogenesis-associated osteocalcin and Runx2 mRNA and protein expressions. Knocking-down ERα using RNA interference concurrently inhibited genistein-induced Runx2, osteocalcin, and ALP mRNA expression. Attractively, administration of ICR mice suffering bone defects with genistein caused significant increases in the callus width, chondrocyte proliferation, and ALP synthesis. Results of microcomputed tomography revealed that administration of genistein increased trabecular bone numbers and improved the bone thickness and volume. This study showed that genistein can improve bone healing via triggering ERα-mediated osteogenesis-associated gene expressions and subsequent osteoblast maturation.

Pharmacological agents and natural compounds: available treatments for osteoporosis.

Osteoporosis, a systemic skeletal disease characterized by a decrease in bone mass and deterioration of bone structure leading to an increased risk of fragility fractures, represents one of the major health problems worldwide. Currently, there are numerous pharmacological products used for the treatment of osteoporosis. Anti-resorptive drugs include bisphosphonates, hormone therapy, selective estrogen-receptor modulators, calcitonin, denosumab, calcium and vitamin D supplementation. Anabolic drugs such as teriparatide, strontium ranelate, romosozumab have recently become available based on advanced clinical trials. In recent years, combination therapy of anabolic and anti-resorptive agents is expected to be ideal anti-osteoporosis option. The adverse side effects caused by the long-term administration of pharmacological drugs have prompted researchers to study natural therapeutic compounds to find an alternative and effective way for osteoporosis treatment. Natural compounds including phytoestrogens with estrogenic effects (e.g. genistein, daidzein, icariin, dioscin, Ginkgo biloba), antioxidant and anti-inflammatory agents (e.g. acteoside, curcumin, resveratrol, Camellia sinensis), treatments that exert their effects by multiple actions (e.g. kinsenoside, berberine, Olea europaea, Prunus domestica, Allium cepa) could provide a safer alternative to primary pharmacological strategies. In this review, both pharmacological agents and natural compounds as available treatments for osteoporosis are characterized. In addition, possible mechanisms of action of all aforementioned treatments associated with bone remodelling, osteoclastogenesis, osteoblastogenesis, bone cell activity, death, and oxidative stress are presented. Nevertheless, more high-quality clinical studies with natural compounds are needed to provide greater evidence of the beneficial and safer antiosteoporotic application for the candidate.

Osteoporosis in Patients with Chronic Kidney Diseases: A Systemic Review.

Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. Among CKD patients, adynamic bone disease or low bone turnover is the most common type of renal osteodystrophy. The consequences of CKD-MBD include increased fracture risk, greater morbidity, and mortality. Thus, the goal is to prevent the occurrences of fractures by means of alleviating CKD-induced MBD and treating subsequent osteoporosis. Changes in mineral and humoral metabolism as well as bone structure develop early in the course of CKD. CKD-MBD includes abnormalities of calcium, phosphorus, PTH, and/or vitamin D; abnormalities in bone turnover, mineralization, volume, linear growth, or strength; and/or vascular or other soft tissue calcification. In patients with CKD-MBD, using either DXA or FRAX to screen fracture risk should be considered. Biomarkers such as bALP and iPTH may assist to assess bone turnover. Before initiating an antiresorptive or anabolic agent to treat osteoporosis in CKD patients, lifestyle modifications, such as exercise, calcium, and vitamin D supplementation, smoking cessation, and avoidance of excessive alcohol intake are important. Managing hyperphosphatemia and SHPT are also crucial. Understanding the complex pathogenesis of CKD-MBD is crucial in improving one's short- and long-term outcomes. Treatment strategies for CKD-associated osteoporosis should be patient-centered to determine the type of renal osteodystrophy. This review focuses on the mechanism, evaluation and management of patients with CKD-MBD. However, further studies are needed to explore more details regarding the underlying pathophysiology and to assess the safety and efficacy of agents for treating CKD-MBD.

Nutrients and Dietary Patterns Related to Osteoporosis.

Osteoporosis is a common chronic disease characterized by a decrease in bone mineral density, impaired bone strength, and an increased risk of fragility fractures. Fragility fractures are associated with significant morbidity, mortality and disability and are a major public health problem worldwide. The influence of nutritional factors on the development and progression of this disease can be significant and is not yet well established. Calcium intake and vitamin D status are considered to be essential for bone metabolism homeostasis. However, some recent studies have questioned the usefulness of calcium and vitamin D supplements in decreasing the risk of fractures. The adequate intake of protein, vegetables and other nutrients is also of interest, and recommendations have been established by expert consensus and clinical practice guidelines. It is important to understand the influence of nutrients not only in isolation but also in the context of a dietary pattern, which is a complex mixture of nutrients. In this review, we evaluate the available scientific evidence for the effects of the main dietary patterns on bone health. Although some dietary patterns seem to have beneficial effects, more studies are needed to fully elucidate the true influence of diet on bone fragility.

Bajitianwan attenuates D-galactose-induced memory impairment and bone loss through suppression of oxidative stress in aging rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoporosis and Alzheimer's disease (AD) are both senile diseases, which are closely related to oxidative stress. Bajitianwan (BJTW) is a classic Chinese formulation consisting of seven herbal drugs: the root of Morinda officinalis F.C.How., root and rhizome of Acorus tatarinowii Schott, the root bark of Lycium chinense Mill., the sclerotium of Poria cocos (Schw.) Wolf, the root of Polygala tenuifolia Willd., sclerotium with host wood of Poria cocos (Schw.) Wolf and root and rhizome of Panax ginseng C. A. Mey. BJTW has been used for the treatment of osteoporosis and AD for hundreds of years. AIM OF THE STUDY: This study aimed to investigate the protective effects of BJTW in the amelioration of memory impairment and bone loss induced by D-galactose and to explore the underlying mechanism. MATERIALS AND METHODS: The aging model was established in male Wistar rats by subcutaneous injection of D-galactose (100 mg/kg), and the rats were treated with huperzine-A, alendronate sodium, or the aqueous extract of BJTW for 4 months. Cognitive performance was evaluated with the Morris water maze. Rat femurs were scanned using microcomputed tomography to obtain three-dimensional imagery of bone microstructure. The impact of D-galactose on the expression of Forkhead box O1 and superoxide dismutase 2 in femur tissue was also evaluated. RESULTS: For the model group, BJTW treatment significantly reduced the latency time for finding the target platform in the directional swimming test and increased time spent swimming in the target quadrant with the probe test. Additionally, BJTW treatment alleviated D-galactose-induced bone loss through regulation of levels of alkaline phosphatase, osteocalcin, osteoprotegerin, and receptor activator of nuclear factor kappa B ligand. Furthermore, BJTW treatment increased catalase and glutathione peroxidase levels in serum, reduced malondialdehyde content in hippocampus, and upregulated expression of Forkhead O1, which upregulated superoxide dismutase 2 in the femur. CONCLUSIONS: BJTW had positive effects on age-related memory impairments and bone loss. It may be a promising antioxidant candidate for treatment of Alzheimer's disease and osteoporosis.

Updates in epidemiology, pathophysiology and management strategies of glucocorticoid-induced osteoporosis.

INTRODUCTION: Endogenous or exogenous (corticosteroid-induced) glucocorticoids (GCs) excess represents, together with diabetes, the most common cause of secondary osteoporosis. AREAS COVERED: We present a comprehensive overview about the pathophysiology, clinical management and treatment of GCs induced osteoporosis (GIOP). According to PRISMA guidelines, a literature search identifying articles about bone and GCs was done. EXPERT OPINION: Despite the progress over the years and the increase in therapeutic options, there still are controversial issues about the management of GIOP. These mainly include the failure of BMD or FRAX to completely account for the rapid increase in fracture risk of most GC-treated patients, the understanding about the independent contribution on bone fragility of the underlying disease requiring GCs therapy, and the necessity of clearer information about the anti-fracture efficacy and long term-safety of most therapeutic options. Moreover, there are no specific indications for the management of bone fragility in endogenous hypercortisolism. Notwithstanding the above limitations there is a general consensus to recommend an assessment of fracture risk in all individuals >40 years committed to receive (or continuing) high dose (>7.5 mg of prednisone equivalent) GCs for ≥3 months and in all patients with fragility fracture history.

Effects of mild hyperbaric oxygen on osteoporosis induced by hindlimb unloading in rats.

INTRODUCTION: Disuse-induced bone loss is caused by a suppression of osteoblastic bone formation and an increase in osteoclastic bone resorption. There are few data available for the effects of environmental conditions, i.e., atmospheric pressure and/or oxygen concentration, on osteoporosis. This study examined the effects of mild hyperbaric oxygen at 1317 hPa with 40% oxygen on unloading-induced osteoporosis. MATERIALS AND METHODS: Eighteen 8-week old male Wistar rats were randomly divided into three groups: the control for 21 days without unloading and mild hyperbaric oxygen (NOR, n = 6), the unloading for 21 days and recovery for 10 days without mild hyperbaric oxygen (HU + NOR, n = 6), and the unloading for 21 days and recovery for 10 days with mild hyperbaric oxygen (HU + MHO, n = 6). RESULTS: The cortical thickness and trabecular bone surface area were decreased in the HU + NOR group compared to the NOR group. There were no differences between the NOR and HU + MHO groups. Osteoclast surface area and Sclerostin (Sost) mRNA expression levels were decreased in the HU + MHO group compared to the HU + NOR group. These results suggested that the loss of the cortical and trabecular bone is inhibited by mild hyperbaric oxygen, because of an inhibition of osteoclasts and enhancement of bone formation with decreased Sost expression. CONCLUSIONS: We conclude that exposure to mild hyperbaric oxygen partially protects from the osteoporosis induced by hindlimb unloading.

Decreased bone mineral density and reproductive axis dysfunction: more than oestrogen.

Decreased bone mineral density (BMD) in oestrogendeficient states has long been thought to be a direct outcome of the reduction in oestrogen. In physiologic and many pathologic hypo-oestrogenic states, oestrogen supplementation improves BMD. However, the relationship between oestrogen replacement and BMD is less clear in the case of reproductive axis dysfunction secondary to decreased caloric intake or increased energy expenditure, such as in female athletes or anorexia nervosa. This decrease in oestrogen is associated with decreased BMD, but oestrogen replacement in these states fails to conclusively improve BMD. This suggests that the decrease in BMD in these states is not driven solely by low oestrogen. Cortisol and other markers of inflammation may play a role in BMD reduction but further research is needed. What is clear is that increased caloric consumption and restoration of menses and the reproductive axis are essential to improving BMD, while pharmacologic therapy, including oestrogen replacement through hormone therapy or contraceptives, does not provide conclusive benefit.