Prevention Of Glucocorticoid-induced Osteoporosis Research Articles

Evaluation of Steroid-Induced Osteoporosis Prevention Using Tracing Reports in Collaboration between Hospitals and Community Pharmacists.

Glucocorticoid-induced osteoporosis (GIOP) is a side effect of glucocorticoid (GC) treatment; however, despite established prevention guidelines in various countries, a gap persists between these guidelines and clinical practice. To address this gap, we implemented a collaborative intervention between hospitals and community pharmacists, aiming to assess its effectiveness. Pharmacists recommended to the prescribing doctor osteoporosis treatment for patients who did not undergo osteoporosis treatment with a fracture risk score of ≥3 via tracing reports (TRs), between 15 December 2021, and 21 January 2022. Data were extracted from electronic medical records, including prescriptions, concomitant medications, reasons for not pursuing osteoporosis treatment, and TR contents. Of 391 evaluated patients, 45 were eligible for TRs, with 34 (75.6%) being males. Prednisolone was the most common GCs administered, and urology was the predominant treatment department. Among the 45 patients who received TRs, prescription suggestions were accepted for 19 (42.2%). After undertaking the intervention, guideline adherence significantly increased from 87% to 92.5%. This improvement indicates that TRs effectively bridged the evidence-practice gap in GIOP prevention among GC patients, suggesting their potential utility. Expansion of this initiative is warranted to further prevent GIOP.

Clinical efficacy of denosumab, teriparatide, and oral bisphosphonates in the prevention of glucocorticoid-induced osteoporosis: a systematic review and meta-analysis

BackgroundContinuous use of glucocorticoids (GCs) has become the primary cause of secondary osteoporosis. Bisphosphonate drugs were given priority over denosumab and teriparatide in the 2017 American College of Rheumatology (ACR) guidelines but have a series of shortcomings. This study aims to explore the efficacy and safety of teriparatide and denosumab compared with those of oral bisphosphonate drugs.MethodsWe systematically searched studies included in the PubMed, Web of Science, Embase, and Cochrane library databases and included randomized controlled trials that compared denosumab or teriparatide with oral bisphosphonates. Risk estimates were pooled using both fixed and random effects models.ResultsWe included 10 studies involving 2923 patients who received GCs for meta-analysis, including two drug base analyses and four sensitivity analyses. Teriparatide and denosumab were superior to bisphosphonates in increasing the bone mineral density (BMD) of the lumbar vertebrae [teriparatide: mean difference [MD] 3.98%, 95% confidence interval [CI] 3.61–4.175%, P = 0.00001; denosumab: MD 2.07%, 95% CI 0.97–3.17%, P = 0.0002]. Teriparatide was superior to bisphosphonates in preventing vertebral fractures and increasing hip BMD [MD 2.39%, 95% CI 1.47–3.32, P < 0.00001]. There was no statistically significant difference between serious adverse events, adverse events, and nonvertebral fracture prevention drugs.ConclusionsTeriparatide and denosumab exhibited similar or even superior characteristics to bisphosphonates in our study, and we believe that they have the potential to become first-line GC-induced osteoporosis treatments, especially for patients who have previously received other anti-osteoporotic drugs with poor efficacy.

Bisphosphonate use for glucocorticoid-induced osteoporosis in older patients with immune thrombocytopenia: a clinical perspective.

Prednisolone, used as a standard initial treatment for immune thrombocytopenia (ITP), is an important risk factor for osteoporosis. Recently, we found that prescription of bisphosphonate during initial loading of prednisolone may prevent reduction in bone mineral density and development of glucocorticoid-induced osteoporosis (GIO) in older patients with ITP receiving prolonged steroid therapy. In this review, I describe the treatment options for older patients with ITP, and present the best practices for screening, evaluating, and diagnosing ITP. I also summarize the literature from 2017 to 2022 on the treatment options for ITP, including discussions on the contraindications and side effects, with an emphasis on GIO, and the relative merits of bisphosphonates as a co-treatment for prevention of GIO. Finally, I present a perspective and an expert recommendation on how older patients with ITP would best be served in the future.

Linking the relation between gut microbiota and glucocorticoid-induced osteoporosis.

Osteoporosis (OP) is the most prevalent metabolic bone disease, characterized by the low bone mass and microarchitectural deterioration of bone tissue. Glucocorticoid (GC) clinically acts as one of the anti-inflammatory, immune-modulating, and therapeutic drugs, whereas the long-term use of GC may cause rapid bone resorption, followed by prolonged and profound suppression of bone formation, resulting in the GC-induced OP (GIOP). GIOP ranks the first among secondary OP and is a pivotal risk for fracture, as well as high disability rate and mortality, at both societal and personal levels, vital costs. Gut microbiota (GM), known as the "second gene pool" of human body, is highly correlated with maintaining the bone mass and bone quality, and the relation between GM and bone metabolism has gradually become a research hotspot. Herein, combined with recent studies and based on the cross-linking relationship between GM and OP, this review is aimed to discuss the potential mechanisms of GM and its metabolites on the OP, as well as the moderating effects of GC on GM, thereby providing an emerging thought for prevention and treatment of GIOP.

Actual Situation and Characteristics of Pharmacotherapy for Glucocorticoid-induced Osteoporosis Prevention

Actual Situation and Characteristics of Pharmacotherapy for Glucocorticoid-induced Osteoporosis Prevention

Bisphosphonate Use for Glucocorticoid-Induced Osteoporosis in Elderly Patients with Immune Thrombocytopenia Receiving Prolonged Steroid Therapy: A Single Institute Retrospective Study.

Prednisolone, used as a standard initial treatment for immune thrombocytopenia (ITP), is an important risk factor for osteoporosis. To investigate the prevention of glucocorticoid-induced osteoporosis (GIO) in elderly ITP patients receiving prolonged steroid therapy, associations between GIO prevention and the real-world data of score changes of a dual-energy X-ray absorptiometry (DXA) scan, FRAX® and the Garvan tool during the initial loading of prednisolone were examined. In our institute, 22 ITP patients aged ≥ 70 years received 0.5–1.0 mg/kg prednisolone for 2–3 weeks as the initial ITP treatment between 2014 and 2021. The femoral neck bone mineral density (BMD) measured by DXA scan was entered into FRAX® to define the risk-adapted approach to bisphosphonate during the initial loading of prednisolone. Bisphosphonate was administered according to <−1.0 femoral neck BMD T-score measured by DXA scan. Worse scores of FRAX® and the Garvan tool were associated with bisphosphonate use for short-term fracture prevention in primary GIO; however, there were no incidents of fracture or significant differences in probabilities determined by FRAX® and the Garvan tool. During the initial loading of prednisolone, prescribing bisphosphonate might prevent the reduction in BMD in elderly patients with ITP receiving prolonged steroid therapy.

Effectiveness of a computerized clinical decision support system for prevention of glucocorticoid-induced osteoporosis

Glucocorticoids are widely used for a variety of diseases, but the prevention of glucocorticoid-induced osteoporosis is sometimes neglected. Therefore, the effectiveness of a computerized clinical decision support system (CDSS) to improve the performance rate of preventive care for glucocorticoid-induced osteoporosis was evaluated. We conducted a prospective cohort study of outpatients who used glucocorticoids for three months or longer and who met the indication for preventive care based on a guideline. The CDSS recommended bisphosphonate (BP) prescription and bone mineral density (BMD) testing based on the risk of osteoporosis. The observation period was one year (phase 1: October 2017–September 2018) before implementation and the following one year (phase 2: October 2018–September 2019) after implementation of the CDSS. Potential alerts were collected without displaying them during phase 1, and the alerts were displayed during phase 2. We measured BP prescriptions and BMD testing for long-term prescription of glucocorticoids. A total of 938 patients (phase 1, 457 patients; phase 2, 481 patients) were included, and the baseline characteristics were similar between the phases. The median age was 71 years, and men accounted for 51%. The primary disease for prescription of glucocorticoids was rheumatic disease (28%), followed by hematologic diseases (18%). The prevalence of patients who needed an alert for BP prescription (67% vs. 63%, P = 0.24) and the acceptance rate of BP prescription (16% vs. 19%, P = 0.33) were similar between the phases. The number of patients who had orders for BMD testing was significantly increased (4% vs. 24%, P < 0.001) after CDSS implementation. The number of patients who needed an alert for BMD testing was significantly decreased from 93% in phase 1 to 87% in phase 2 (P = 0.004). In conclusion, the CDSS significantly increased BMD testing in patients with a higher risk of glucocorticoid-induced osteoporosis, but did not increase BP prescription.

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club.

Glucocorticoids are effective immunomodulatory drugs used for many inflammatory disorders as well as in transplant recipients. However, both iatrogenic and endogenous glucocorticoid excess are also associated with several side effects including an increased risk of osteoporosis and fractures. Glucocorticoid-induced osteoporosis (GIOP) is a common secondary cause of osteoporosis in adults. Despite availability of clear evidence and international guidelines for the prevention of GIOP, a large treatment gap remains. In this narrative review, the Belgian Bone Club (BBC) updates its 2006 consensus recommendations for the prevention and treatment of GIOP in adults. The pathophysiology of GIOP is multifactorial. The BBC strongly advises non-pharmacological measures including physical exercise, smoking cessation and avoidance of alcohol abuse in all adults at risk for osteoporosis. Glucocorticoids are associated with impaired intestinal calcium absorption; the BBC therefore strongly recommend sufficient calcium intake and avoidance of vitamin D deficiency. We recommend assessment of fracture risk, taking age, sex, menopausal status, prior fractures, glucocorticoid dose, other clinical risk factors and bone mineral density into account. Placebo-controlled randomized controlled trials have demonstrated the efficacy of alendronate, risedronate, zoledronate, denosumab and teriparatide in GIOP. We suggest monitoring by dual-energy X-ray absorptiometry (DXA) and vertebral fracture identification one year after glucocorticoid initiation. The trabecular bone score might be considered during DXA monitoring. Extended femur scans might be considered at the time of DXA imaging in glucocorticoid users on long-term (≥ 3 years) antiresorptive therapy. Bone turnover markers may be considered for monitoring treatment with anti-resorptive or osteoanabolic drugs in GIOP. Although the pathophysiology of solid organ and hematopoietic stem cell transplantation-induced osteoporosis extends beyond GIOP alone, the BBC recommends similar evaluation, prevention, treatment and follow-up principles in these patients. Efforts to close the treatment gap in GIOP and implement available effective fracture prevention strategies into clinical practice in primary, secondary and tertiary care are urgently needed.

The Use of Herbal Medicines for the Prevention of Glucocorticoid-Induced Osteoporosis.

Glucocorticoids are drugs that are widely used to suppress inflammation and the activation of the immune system. However, the prolonged use or at high doses of glucocorticoid can result in adverse side effects including osteoporosis, bone loss, and an increased risk of fracture. A number of compounds derived from natural plant sources have been reported to exert anti-inflammatory activity by interacting with the glucocorticoid receptor (GR), likely owing to their chemical similarity to glucocorticoids, or by regulating GR, without a concomitant risk of treatment-related side effects such as osteoporosis. Other herbal compounds can counteract the pathogenic processes underlying glucocorticoid-induced osteoporosis (GIOP) by regulating homeostatic bone metabolic processes. Herein, we systematically searched the PubMed, Embase, and Cochrane library databases to identify articles discussing such compounds published as of May 01, 2021. Compounds reported to exert anti-inflammatory glucocorticoid-like activity without inducing GIOP include escin, ginsenosides, and glycyrrhizic acid, while compounds reported to alleviate GIOP by improving osteoblast function or modulating steroid hormone synthesis include tanshinol and icariin.

German Society of Rheumatology recommendations for management of glucocorticoid-induced osteoporosis.

Glucocorticoids are of substantial therapeutic importance in the treatment of inflammatory diseases, but are also associated with bone mineral density loss, osteoporosis, and fractures, especially with long-term use. To develop recommendations for the management of glucocorticoid-induced osteoporosis (GIOP) in adult patients on long-term glucocorticoid (GC) treatment. Asystematic literature search (SLR) was conducted to synthesize the evidence for GIOP prevention and treatment options. Recommendations were developed based on SLR/level of evidence and by previously defined questions and in astructured group consensus process. Recommendations include supplementation with calcium and vitaminD under long-term GC therapy in adults. If specific osteologic treatment is indicated, we recommend bisphosphonates or denosumab as first-line treatment. If fracture risk is high, we recommend teriparatide as primary specific osteologic treatment. Denosumab should be used in cases of severe renal insufficiency, and specific osteologic treatment should not be given in pregnancy. For patients who have not reached the treatment goal, aswitch to another class of specific osteologic drugs should be performed. We recommend re-evaluation after atreatment duration of 3-5years or after termination of long-term GC treatment. This work aims to provide evidence-based and consensus-based recommendations for the best possible management of GIOP in Germany and to support treatment decisions.

The effect of oral bisphosphonate therapy on vertebral morphometry and fractures in patients with Duchenne muscular dystrophy and glucocorticoid-induced osteoporosis.

Glucocorticoid-induced osteoporosis with vertebral fractures is frequent in patients with Duchenne muscular dystrophy (DMD). In this study, we evaluated the effects of oral bisphosphonate (BP) therapy on the prevalence and severity of vertebral fractures by vertebral morphometry assessment. We reviewed the records and radiographs of patients with DMD who had been treated with oral BP (weekly alendronate) and had undergone routine spine radiographic monitoring for glucocorticoid-induced osteoporosis at Cincinnati Children's Hospital Medical Center between 2010 and 2017. Study outcomes were thoracic and lumbar vertebral fracture prevalence and severity, assessed by Genant semiquantitative grading of vertebral morphometry, for up to 5 years of treatment. Fifty-two patients (median age, 11.8 years; 88% prepubertal; 31% nonambulatory) had been treated with long-term glucocorticoids (median duration, 4.7 years at BP start). Most patients (75%) had mild vertebral height loss or fractures (Genant grade=0 or 1) at baseline. The prevalence of vertebral fractures at each year of treatment was not statistically different from that at baseline (P= .08-1.00). Serial radiographs showed no longitudinal change in severity by Genant grade in most vertebrae (64%-80%). Improvement in vertebral fracture grade was observed in some patients. We observed stable prevalence of vertebral fractures and no change in severity by Genant grade in most vertebrae for up to 5 years of treatment. Oral BP may mitigate development or progression of vertebral fractures and be beneficial for secondary prevention of glucocorticoid-induced osteoporosis in this population.

Efficacy of once-weekly teriparatide for primary prevention of glucocorticoid-induced osteoporosis: A post hoc analysis of the TOWER-GO study.

A post hoc analysis of the Teriparatide Once-Weekly Efficacy Research for Glucocorticoid-induced Osteoporosis (TOWER-GO) study was performed to examine the effect of once-weekly administration of 56.5 μg teriparatide on primary prevention of glucocorticoid-induced osteoporosis (GIOP). Of the subjects of the TOWER-GO study, 73 were included. The percentage changes from baseline in lumbar spine bone mineral density (BMD) and bone turnover markers were evaluated over 72 weeks with once-weekly teriparatide and once-weekly alendronate. The percentage change of lumbar spine BMD from baseline at 72 weeks was significantly increased in both groups. Bone formation markers were significantly increased by teriparatide administration, although they were slightly decreased by alendronate administration. Bone resorption markers were gradually decreased by teriparatide, whereas alendronate markedly decreased them within 4 weeks. No major safety concerns arose. In this primary prevention study of GIOP, comparable increases in BMD were observed between alendronate and once-weekly teriparatide. More desirable changes in bone markers were observed with teriparatide administration. These data suggest that once-weekly teriparatide is effective in primary prevention of GIOP.

German Society of Rheumatology Recommendations for the management of glucocorticoid-induced Osteoporosis. German version

Glucocorticoids are of substantial therapeutic importance in the treatment of inflammatory diseases, but are also associated with bone mineral density loss, osteoporosis, and fractures, especially with long-term use. To develop recommendations for the management of glucocorticoid-induced osteoporosis (GIOP) in adult patients on long-term glucocorticoid (GC) treatment. Asystematic literature search (SLR) was conducted to synthesize the evidence for GIOP prevention and treatment options. Recommendations were developed based on SLR/level of evidence and by previously defined questions and in astructured group consensus process. Recommendations include supplementation with calcium and vitaminD under long-term GC therapy in adults. If specific osteologic treatment is indicated, we recommend bisphosphonates or denosumab as first-line treatment. If fracture risk is high, we recommend teriparatide as primary specific osteologic treatment. Denosumab should be used in cases of severe renal insufficiency, and specific osteologic treatment should not be given in pregnancy. For patients who have not reached the treatment goal, aswitch to another class of specific osteologic drugs should be performed. We recommend re-evaluation after atreatment duration of 3-5years or after termination of long-term GC treatment. This work aims to provide evidence-based and consensus-based recommendations for the best possible management of GIOP in Germany and to support treatment decisions.

Strontium gluconate potently promotes osteoblast development and restores bone formation in glucocorticoid-induced osteoporosis rats

Glucocorticoid-induced osteoporosis (GIOP) has emerged as a challenge after long-term glucocorticoid administration during the clinical therapy of diverse diseases. Although some candidates for GIOP treatment have been explored, there is still a lack of reliable drugs for GIOP prevention. In this study, rat bone marrow stem cells (rBMSCs) were utilized to investigate the feasibility of applying strontium gluconate (GluSr), which displays mild activity, easy absorption and good biocompatibility, for GIOP prevention. Thirty-two SD rats were divided into 4 groups to explore the effects of GluSr on osteoporosis rescue in vivo. Our results suggested that GluSr markedly alleviated dexamethasone (DEX)-induced apoptosis of osteoblast precursor cells and rBMSCs and enhanced rBMSC osteogenesis differentiation in vitro. GluSr also effectively promoted osteoblast survival, inhibited osteoclast differentiation and restored bone formation in GIOP rat models. Microarray analysis of the femora from GIOP rats treated with GluSr revealed that the signalling pathways of the glucocorticoid receptor (GR), oestrogen receptor gene (ESR) and vitamin D receptor (VDR) were involved in bone restoration by GluSr. In summary, our study proved that GluSr enhanced osteoblast differentiation and suppressed osteoclast activity both in vitro and in vivo. GluSr might function as a novel strontium reagent for GIOP prevention.

Eldecalcitol is superior to alfacalcidol in maintaining bone mineral density in glucocorticoid-induced osteoporosis patients (e-GLORIA).

Eldecalcitol increases bone mineral density (BMD) and reduces vertebral fracture in patients with primary osteoporosis. However, the effect of eldecalcitol on BMD and fracture in glucocorticoid-induced osteoporosis (GIO) patients is unknown. This study was undertaken to compare the effect of eldecalcitol on BMD and fracture with that of alfacalcidol in GIO patients. A randomized, open-label, parallel group study was conducted to identify the effectiveness and safety of monotherapy with 0.75μg eldecalcitol compared with 1.0μg alfacalcidol in GIO patients. Lumbar spine BMD increased with eldecalcitol, but decreased with alfacalcidol at 12 and 24months (between group difference 1.29%, p < 0.01, and 1.10%, p < 0.05, respectively). Total hip and femoral neck BMD were maintained until 24months by eldecalcitol, but decreased by alfacalcidol (between group difference 0.97%, p < 0.05 and 1.22%, p < 0.05, respectively). Both bone formation and resorption markers were more strongly suppressed by eldecalcitol than by alfacalcidol. Eldecalcitol showed better effect on BMD than alfacalcidol in patients with no prevalent fracture and BMD > 70% of the young adult mean, and with ≤ 3months of previous glucocorticoid treatment. No significant difference in the incidence of vertebral fracture was found, and the incidence of adverse events was similar between the two groups. Eldecalcitol was more effective than alfacalcidol in maintaining BMD in GIO patients. Because eldecalcitol was effective in patients with no or short-term previous glucocorticoid treatment, as well as those without prevalent fracture or low BMD, eldecalcitol can be a good candidate for primary prevention of GIO. UMIN000011700.

A retrospective database study of oral corticosteroid and bisphosphonate prescribing patterns in England

Exposure to oral corticosteroids (OCS) is associated with an increased risk of osteoporosis and fragility fractures. Guidelines suggest bisphosphonate (BP) therapy as the first-line treatment of glucocorticoid-induced osteoporosis (GIOP). This population study used publicly available data, including prescription annual cost analysis and monthly practice-level data. Our aim was to examine the prescribing of OCS and BP at practice level and investigate reasons for variation using a mixed-effect negative binomial regression analysis. There was a rise in OCS and BP prescriptions of 55% and 1200% from 1998 to 2018, respectively. Of the 6586 included practices, the median (IQR) of OCS and BP prescriptions were 120.8 (84.8–160.4) and 107.7 (73.8–147.4) per 1000 patients, respectively. Asthma and chronic obstructive pulmonary disease (COPD) were significantly associated with OCS use (p < 0.0001), but only COPD was associated with BP use (p < 0.0001). Higher OCS prescribing rates were associated with higher BP prescribing rates (5th to 1st quintile—IRR = 1.99; 95% CI: 1.88–2.10). Practice list size, deprivation and advanced age were all associated with both drugs (p < 0.0001). In conclusion, although OCS use is positively associated with BP prescription, variation among practices and CCGs exists. The variation in prescribing suggests there is still a need to improve GIOP prevention.

Efficacy and Safety of First- and Second-Line Drugs to Prevent Glucocorticoid-Induced Fractures.

The evidence about benefits and harms of drugs for glucocorticoid (GC)-induced osteoporosis (GIOP) is limited, and the comparative efficacy and safety of first-line and second-line agents to prevent GC-induced (GI) fractures remains unclear. To assess the comparative clinical efficacy, safety, and tolerability of first-line and second-line agents in preventing GI fractures. We searched 3 different databases through March 5, 2019. We included randomized controlled trials enrolling patients receiving long-term GCs and compared a first-line and second-line agent with one another and with placebo. Two reviewers independently extracted study and participant characteristics and outcome data. We performed multivariate random-effects network meta-analyses including base, 3 subgroups, and 12 sensitivity analyses. We included 22 papers from 19 unique trials involving 4328 patients receiving GCs. Teriparatide (risk ratio [RR] 0.11, 95% confidence interval [CI] 0.03-0.47), denosumab (RR 0.21, 95% CI 0.09-0.49), and risedronate (RR 0.33, 95% CI 0.19-0.58) reduced the risk of GI vertebral fractures, and the former 2 were the most efficacious according to violin plots including the surface under the cumulative ranking curve values calculated by base and sensitivity analyses. Oral alendronate (RR 0.33, 95% CI 0.12-0.93) reduced this risk in patients receiving GCs with at least 7.5 mg/day, while intravenous ibandronate (RR 0.25, 95% CI 0.06-0.99) was efficacious for the primary prevention of GIOP. Six drugs were similar in terms of the 5 other outcomes. In terms of clinical efficacy and safety, second-line teriparatide and denosumab pose a challenge to first-line oral bisphosphonates for prevention of GI fractures.

P2. MiRNA-seq analysis of human vertebrae provides insight into the mechanism underlying GIOP

BACKGROUND CONTEXT High-throughput sequencing (HTS) was recently applied to detect microRNA (miRNA) regulation in age-related osteoporosis. However, miRNA regulation has not been reported in glucocorticoid-induced osteoporosis (GIOP) patients and the mechanism of GIOP remains elusive. PURPOSE To comprehensively analyze the role of miRNA regulation in GIOP based on human vertebrae and to explore the molecular mechanism. STUDY DESIGN/SETTING A high-throughput sequencing strategy was employed to identify miRNAs involved in GIOP. Twenty-six patients undergoing spinal surgery were included in this study. Six vertebral samples were selected for miRNA sequencing (miRNA-seq) analysis and 26 vertebral samples were verified by qRT-PCR. Bioinformatics was utilized for target prediction, to investigate the regulation of miRNA-mRNA networks, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. PATIENT SAMPLE Twenty-six patients undergoing spinal surgery were included in this study. Six vertebral samples were selected for miRNA sequencing (miRNA-seq) analysis and 26 vertebral samples were verified by qRT-PCR. OUTCOME MEASURES A high-throughput sequencing strategy was employed to identify miRNAs involved in GIOP. Twenty-six patients undergoing spinal surgery were included in this study. Six vertebral samples were selected for miRNA sequencing (miRNA-seq) analysis and 26 vertebral samples were verified by qRT-PCR. Bioinformatics was utilized for target prediction, to investigate the regulation of miRNA-mRNA networks, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. METHODS A high-throughput sequencing strategy was employed to identify miRNAs involved in GIOP. Twenty-six patients undergoing spinal surgery were included in this study. Six vertebral samples were selected for miRNA sequencing (miRNA-seq) analysis and 6 vertebral samples were verified by qRT-PCR. Bioinformatics was utilized for target prediction, to investigate the regulation of miRNA-mRNA networks, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. RESULTS Six significantly up-regulated miRNAs (including one novel miRNA) and three significantly down-regulated miRNAs were verified via miRNA-seq and verified in the vertebrae of GIOP patients. Up-regulated miRNAs included hsa-miR-214-5p, hsa-miR-10b-5p, hsa-miR-21-5p, hsa-miR-451a, hsamiR-186-5p, and hsa-miR-novel-chr3_49,413 while down-regulated miRNAs included hsa-let-7f-5p, hsa-let-7a-5p, and hsa-miR-27a-3p. Bioinformatics analysis revealed 5,983 and 23,463 predicted targets in the up-regulated and down-regulated miRNAs respectively, using the miRanda, miRBase and TargetScan databases. The target genes of these significantly altered miRNAs were enriched to 1,939 GO terms and 84 KEGG pathways. GO terms revealed that up-regulated targets were most enriched in actin filament-based processes (BP), anchoring junction (CC), and cytoskeletal protein binding (MF). Conversely, the down-regulated targets were mostly enriched in multicellular organismal development (BP), intracellular membrane-bounded organelles (CC), and protein binding (MF). Top-10 pathway analysis revealed that the differentially expressed miRNAs in GIOP were closely related to bone metabolism-related pathways such as FoxO, PI3K-Akt, MAPK and Notch signaling pathway. CONCLUSIONS These results suggest that significantly altered miRNAs may play an important role in GIOP by targeting mRNA and regulating biological processes and bone metabolism-related pathways such as MAPK, FoxO, PI3K-Akt and Notch signaling, which provides novel insight into the mechanism of GIOP and lays a good foundation for the prevention and treatment of GIOP. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Glucocorticoid-induced osteoporosis update.

Steroid-induced osteoporosis or glucocorticoid-induced osteoporosis (GIOP) is a common form of secondary osteoporosis and is a cause of increased morbidity and mortality. The pathogenesis of GIOP includes decreased bone formation and increased bone resorption. Clinicians can rely on several effective medications for the treatment and prevention of GIOP, including antiresorptive drugs (i.e. bisphosphonates) and bone anabolic drugs (i.e. teriparatide). Recent studies have further highlighted that GIOP is a major public health concern and have provided new insights on the pathogenesis of GIOP, in particular, the dose-dependent effects of glucocorticoids on bone. New evidence on the real-world effectiveness of established GIOP therapies have been recently published as well as the results of the 24-months denosumab randomized controlled trial in GIOP. GIOP and fragility fractures are important adverse events related to the long-term use of glucocorticoids. Recent studies have provided additional data on the epidemiology and pathogenesis of GIOP and on the efficacy and effectiveness of GIOP therapies.

The prevention of glucocorticoid-induced osteoporosis in patients with immune thrombocytopenia receiving steroids: aBritish Society for Haematology Good Practice Paper.

Methodology This Good Practice Paper was compiled according to the British Society for Haematology (BSH) process at http://www.b-s-h.org.uk/guidelines/proposing-and-writing-a-new-bsh-guideline/. The BSH produces Good Practice Papers to recommend good practice in areas where there is a limited evidence base but for which a degree of consensus or uniformity is likely to be beneficial to patient care. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org.