Prevention Of Glucocorticoid-induced Osteoporosis Research Articles

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.

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

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. To comprehensively analyze the role of miRNA regulation in GIOP based on human vertebrae and to explore the molecular mechanism, 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. 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, hsa-miR-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 5983 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 1939 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. 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.

Patient satisfaction and efficacy of switching from weekly bisphosphonates to monthly minodronate for treatment and prevention of glucocorticoid-induced osteoporosis in Japanese patients with systemic rheumatic diseases: a randomized, clinical trial.

Osteoporosis and associated fractures are major concerns for patients with systemic rheumatic diseases on long-term glucocorticoid therapy. Bisphosphonates increase bone mineral density (BMD) and reduce the frequency of vertebral fractures, but they are associated with poor adherence. The effects of monthly oral minodronate on patients' satisfaction, BMD, and bone turnover markers were investigated in patients with systemic rheumatic diseases on glucocorticoids and weekly oral alendronate or risedronate. Study patients with systemic rheumatic diseases on oral glucocorticoids and weekly alendronate 35mg or risedronate 17.5mg were randomly assigned either to switch to minodronate 50mg every 4weeks or to continue the currently taking weekly bisphosphonate for 52weeks after a 24-week run-in period.Patients were stratified by hospital site, sex, and menopausal status in women at enrollment. The primary endpoint was the difference between the proportions of patients who responded very satisfactory or satisfactory for the current bisphosphonate therapy at weeks 48 and 76 between the two groups. Secondary endpoints included percentage changes in lumbar spine BMD and bone turnover markers from the time of starting allocated treatment. Monthly minodronate was superior to weekly alendronate or risedronate for patients' satisfaction, the increase of lumbar spine BMD, and suppression of serum tartrate-resistant acid phosphatase 5b at week 76. Monthly minodronate is more acceptable and may be more effective than weekly alendronate or risedronate for prevention and treatment of bone loss in patients with systemic rheumatic diseases on glucocorticoid therapy.

Glucocorticoid-induced osteoporosis: presentation and comments on the new American College of Rheumatology guidelines

The article presents a review of the clinical guidelines of 2017 American College of Rheumatology for prevention and treatment of glucocorticoid-induced osteoporosis. The guidelines i contain fracture risk gradation not only for people over 40 years , based on the measurement of bone mineral density, 10-year probability of fractures by FRAX and prior osteoporotic fractures, but also for people under 40 years. The guidelines present , recommendations for initial and follow-up treatment for prevention of glucocorticoid-induced osteoporosis according the level of risk of fractures in different age groups of adults, and in children from 4 years of age, in patients with organ transplant and patients older than 30 years, receiving very high-dose of glucocorticoids . Oral bisphosphonates were recommended as first line treatment due to safety, cost, and because of lack of evidence for superior antifracture benefits from other OP medications. Oral bisohosphonates could be switched to another medication in case of intolerance. The issues of applicability of these recommendations in national clinical practice are being discussed.

Prevention of Glucocorticoid-Induced Osteoporosis: Clinical audit to evaluate the implementation of National Osteoporosis Guideline Group 2017 guidelines in a primary care setting

Treatment with glucocorticoids is the leading cause of drug-induced osteoporosis. National Osteoporosis Guideline Group (NOGG) 2017 guidelines advise a case-finding strategy for patients at risk. The aims of the audit were to evaluate the implementation of the NOGG 2017 guidelines for patients receiving long-term glucocorticoid therapy in a suburban general practice, to instigate changes to ensure 90% of patients are investigated and treated appropriately, and to evaluate impact at a 6-mo re-audit. Reporting Analysis and Intelligence Delivering Results (RAIDR) is a health-care intelligence tool accessing primary care clinical data. Using RAIDR, data on relevant osteoporotic risk factors were combined to produce FRAX scores for patients who had been prescribed glucocorticoids 3 or more times in the past 12 months. FRAX data were displayed in a NOGG guidance graph for major osteoporotic fracture probability. Patients were assessed as high, intermediate, or low risk. High- and intermediate-risk patients above the NOGG threshold were recommended to start bisphosphonates; these patients were sent a prescription for alendronate and a letter of explanation. There were no intermediate patients below the NOGG threshold. Low-risk patients were recommended to have lifestyle advice; a leaflet was produced and sent to these patients. Initial results showed that only 25% of patients recommended to be on bisphosphonates were taking them. Steps were taken to educate the general practitioners in the FRAX tool and NOGG guidelines; the chronic obstructive pulmonary disease annual template was amended to aid adherence by alerting the nurse to the number of glucocorticoid courses prescribed, with additional boxes for prescribing alendronate and printing the lifestyle leaflet; and 2-monthly RAIDR searches by the practice pharmacist were started. A re-audit 6 mo later showed improvement to 92%. This audit showed that education, reminders, and simple computer prompts can greatly improve the implementation of NOGG guidelines for glucocorticoid-induced osteoporosis.

Korean Guideline for the Prevention and Treatment of Glucocorticoid-induced Osteoporosis

Background To develop guidelines and recommendations to prevent and treat glucocorticoid (GC)-induced osteoporosis (GIOP) in Korea. Methods The Korean Society for Bone and Mineral Research and the Korean College of Rheumatology have developed this guideline based on Guidance for the Development of Clinical Practice Guidelines ver. 1.0 established by the National Evidence-Based Healthcare Collaborating Agency. This guideline was developed by adapting previously published guidelines, and a systematic review and quality assessment were performed. Results This guideline applies to adults aged ≥19 years who are using or plan to use GCs. It does not include children and adolescents. An initial assessment of fracture risk should be performed within 6 months of initial GC use. Fracture risk should be estimated using the fracture-risk assessment tool (FRAX) after adjustments for GC dose, history of osteoporotic fractures, and bone mineral density (BMD) results. All patients administered with prednisolone or an equivalent medication at a dose ≥2.5 mg/day for ≥3 months are recommended to use adequate calcium and vitamin D during treatment. Patients showing a moderate-to-high fracture risk should be treated with additional medication for osteoporosis. All patients continuing GC therapy should undergo annual BMD testing, vertebral X-ray, and fracture risk assessment using FRAX. When treatment failure is suspected, switching to another drug should be considered. Conclusions This guideline is intended to guide clinicians in the prevention and treatment of GIOP.

Korean Guideline for the Prevention and Treatment of Glucocorticoid-induced Osteoporosis.

BackgroundTo develop guidelines and recommendations to prevent and treat glucocorticoid (GC)-induced osteoporosis (GIOP) in Korea.MethodsThe Korean Society for Bone and Mineral Research and the Korean College of Rheumatology have developed this guideline based on Guidance for the Development of Clinical Practice Guidelines ver. 1.0 established by the National Evidence-Based Healthcare Collaborating Agency. This guideline was developed by adapting previously published guidelines, and a systematic review and quality assessment were performed.ResultsThis guideline applies to adults aged ≥19 years who are using or plan to use GCs. It does not include children and adolescents. An initial assessment of fracture risk should be performed within 6 months of initial GC use. Fracture risk should be estimated using the fracture-risk assessment tool (FRAX) after adjustments for GC dose, history of osteoporotic fractures, and bone mineral density (BMD) results. All patients administered with prednisolone or an equivalent medication at a dose ≥2.5 mg/day for ≥3 months are recommended to use adequate calcium and vitamin D during treatment. Patients showing a moderate-to-high fracture risk should be treated with additional medication for osteoporosis. All patients continuing GC therapy should undergo annual BMD testing, vertebral X-ray, and fracture risk assessment using FRAX. When treatment failure is suspected, switching to another drug should be considered.ConclusionsThis guideline is intended to guide clinicians in the prevention and treatment of GIOP.

2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP). We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence. We used a group consensus process to determine the final recommendations and grade their strength. The guideline addresses initial assessment and reassessment in patients beginning or continuing long-term (≥3 months) glucocorticoid (GC) treatment, as well as the relative benefits and harms of lifestyle modification and of calcium, vitamin D, bisphosphonate, raloxifene, teriparatide, and denosumab treatment in the general adult population receiving long-term GC treatment, as well as in special populations of long-term GC users. Because of limited evidence regarding the benefits and harms of interventions in GC users, most recommendations in this guideline are conditional (uncertain balance between benefits and harms). Recommendations include treating only with calcium and vitamin D in adults at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred) in adults at moderate-to-high fracture risk, continuing calcium plus vitamin D but switching from an oral bisphosphonate to another antifracture medication in adults in whom oral bisphosphonate treatment is not appropriate, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive GC treatment. Recommendations for special populations, including children, people with organ transplants, women of childbearing potential, and people receiving very high-dose GC treatment, are also made. This guideline provides direction for clinicians and patients making treatment decisions. Clinicians and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP). We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence. We used a group consensus process to determine the final recommendations and grade their strength. The guideline addresses initial assessment and reassessment in patients beginning or continuing long-term (≥3 months) glucocorticoid (GC) treatment, as well as the relative benefits and harms of lifestyle modification and of calcium, vitamin D, bisphosphonate, raloxifene, teriparatide, and denosumab treatment in the general adult population receiving long-term GC treatment, as well as in special populations of long-term GC users. Because of limited evidence regarding the benefits and harms of interventions in GC users, most recommendations in this guideline are conditional (uncertain balance between benefits and harms). Recommendations include treating only with calcium and vitamin D in adults at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred) in adults at moderate-to-high fracture risk, continuing calcium plus vitamin D but switching from an oral bisphosphonate to another antifracture medication in adults in whom oral bisphosphonate treatment is not appropriate, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive GC treatment. Recommendations for special populations, including children, people with organ transplants, women of childbearing potential, and people receiving very high-dose GC treatment, are also made. This guideline provides direction for clinicians and patients making treatment decisions. Clinicians and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

The clinical benefits of denosumab for prophylaxis of steroid-induced osteoporosis in patients with pulmonary disease.

Respiratory physicians are often faced with the dilemma that long-term steroid use will deteriorate bone mineral density and quality. Previous reports demonstrated that bone density decreased 8 to 12% during the initial few months of steroid therapy then continued decreasing at a rate of 2 to 4% annually. Several prospective trials revealed that denosumab increased bone density in patients with osteoporosis [2-4] and decreased the rate of occurrence of fractures. The long-term efficacy of denosumab for glucocorticoid-induced osteoporosis, however, has not yet been proven. This has been an ongoing prospective study since 2014. In our respiratory centre, the first preventative measure used to combat glucocorticoid-induced osteoporosis (GIO) is oral bisphosphonates. Thirty-six patients were enlisted, and their treatment courses were changed from oral bisphosphonate, if administered, to the subcutaneous injection of denosumab 60mg every 6months, combined with a daily oral intake of DENOTAS® chewable combination tablets. The primary efficacy measures were changes in lumbar spine (LS) bone mineral density (BMD) and femoral BMD from baseline at 4, 8, 12 and 28months. At the 12-month follow-up, bone mineral density in the lumbar spine area of these patients increased by 3.2%, while bone mineral density in the hip area showed no significant increase. At the 28-month follow-up, 25 patients were still included in this study. Femoral BMD at 28months increased significantly from the 12-month follow-up (P=0.0259), though the first 12months showed no significant increase. LS BMD continued to increase through the 28-month period. Very little is known regarding the active prevention of GIO. Our data indicates that denosumab can play a promising role in the treatment of GIO.

Tetramethylpyrazine Protects Against Glucocorticoid-Induced Apoptosis by Promoting Autophagy in Mesenchymal Stem Cells and Improves Bone Mass in Glucocorticoid-Induced Osteoporosis Rats.

Glucocorticoid-induced osteoporosis (GIOP) is a widespread clinical complication due to the common use of glucocorticoids. Excess glucocorticoids induce apoptosis of bone marrow-derived mesenchymal stem cells (BMSCs), which have been shown to play an increasingly important role in the pathogenesis and therapy of osteoporosis. Tetramethylpyrazine (TMP), an extract from one of the most recognized herbs in traditional Chinese medicine (Chuanxiong), has been reported to have antiapoptotic properties. In this study, we tested whether TMP protects rat BMSCs following exposure to glucocorticoids in vitro and in vivo. We treated BMSCs with different concentrations of TMP (50, 100, or 200 μM) and exposed them to 10-6 M dexamethasone (Dex) for 48 h in vitro. Our data showed that TMP inhibited Dex-induced cytotoxicity and protected BMSCs from apoptosis. Interestingly, further results demonstrated that TMP prevented apoptosis in BMSCs by promoting autophagy in an AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathway-dependent manner. In addition, calcein fluorescence double labeling and microcomputed tomography scanning indicated that 12 weeks of TMP administration augmented bone formation and protected trabecular bone mass in GIOP rats. We also discovered that first-passage BMSCs isolated from the TMP treatment group had a lower rate of apoptosis and a higher light chain 3 (LC3)-II/LC3-I ratio than the GIOP group. Our findings demonstrate for the first time that TMP can protect BMSCs from exposure to excess glucocorticoids by promoting autophagy through AMPK/mTOR pathway and might be an effective agent for the prevention and treatment of GIOP.

Comparison of acute side effect profile of zoledronic acid – Innovator versus generic preparation

BackgroundZoledronic acid is a bisphosphonate that has been approved for the treatment and prevention of glucocorticoid-induced osteoporosis, post-menopausal and male osteoporosis. The infusion is given intravenous annually. It is an antiresorptive agent with high affinity for mineralized bone and particularly for areas of high bone turnover. ObjectiveComparison of acute side effects of innovator and generic zoledronic acid infusion. MethodRetrospective data of 222 patients who were prescribed zoledronic acid (innovator or generic) over a 3-year period were recorded for any adverse effect. A total of 154 (69.37%) patients received zoledronic acid (innovator) infusion and the 68 patients received generic zoledronic acid infusion. ResultsThe indications of using the infusion were rheumatoid arthritis (58%), lupus (24%), systemic sclerosis (5.4%) and others (12.6%). The commonest adverse effect in both groups was musculoskeletal. The 30% of patients with rheumatoid arthritis experienced worsening of joint pains after the infusion which lasted maximally 48h. Transient low grade fever was seen in 21% in the innovator group versus 56% in generic group (p=0.0001). High grade fever (38°C or more) was less common and was seen in 6.5% in innovator group and 20.6% in generic group (p=0.002). Reinfusion was associated with 30% lesser side effects as compared to first infusion. ConclusionThe frequency of side effects was more common in generic (55.88%) than the innovator group (35.06%). Musculoskeletal and gastrointestinal symptoms were common after infusion; therefore, we would recommend paracetamol and anti-emetic agents to be added empirically for 48h of therapy.

Alendronate prevents glucocorticoid-induced osteoporosis in patients with rheumatic diseases: A meta-analysis.

Glucocorticoid-induced osteoporosis (GIOP) is a serious problem for patients with rheumatic diseases requiring long-term glucocorticoid treatment. Alendronate, a bisphosphonate, has been recommended in the prevention of GIOP. However, the efficacy and safety of alendronate in preventing GIOP remains controversial. We performed a meta-analysis to investigate the efficacy and safety of alendronate in preventing GIOP in patients with rheumatic diseases.We retrieved randomized controlled trials from PubMed, EMBASE, and the Cochrane Library. Two reviewers extracted the data and evaluated the risk of bias and quality of the evidence. We calculated the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes, and the mean difference (MD) with a 95% CI for continuous outcomes using Review Manager, version 5.3.A total of 339 studies were found, and 9 studies (1134 patients) were included. Alendronate was not able to reduce the incidence of vertebral fractures (RR = 0.63, 95% CI: 0.10-4.04, P = 0.62) and nonvertebral fractures (RR = 0.40, 95% CI: 0.15-1.12, P = 0.08). Alendronate significantly increased the percent change in bone mineral density (BMD) at the lumbar spine (MD = 3.66, 95% CI: 2.58-4.74, P < 0.05), total hip (MD = 2.08, 95% CI: 0.41-3.74, P < 0.05), and trochanter (MD = 1.68, 95% CI: 0.75-2.61, P < 0.05). Significant differences were not observed in the percent change in BMD at the femoral neck (MD = -0.33, 95% CI: -2.79 to 2.13, P = 0.79) and total body (MD = 0.64, 95% CI: -0.06 to 1.34, P = 0.07). No significant differences in the adverse events were observed in patients treated with alendronate versus the controls (RR = 1.00, 95% CI: 0.94-1.07, P = 0.89). The odds of gastrointestinal adverse events were significantly reduced (RR = 0.77, 95% CI: 0.62-0.97, P < 0.05).Our analysis suggests that alendronate can increase the percent change in BMD at the lumbar spine, total hip, and trochanter, and is not associated with an increased incidence of gastrointestinal adverse events; however, the vertebral and nonvertebral fractures cannot be reduced. However, the results should be interpreted with caution due to the poor statistical power.

Systemic glucocorticoids: important issues and practical guidelines for the dermatologist.

The potent anti-inflammatory and immunosuppressive effects of systemic glucocorticoids have led to their wide use in the treatment of dermatologic diseases. However, glucocorticoids have been designated the "archetypal double-edged sword of medicine" as a result of their various potential adverse side effects. Dermatologists face major challenges in their usage and require knowledge of both the risks related to their usage and strategies with which to manage them. This brief review includes an evidence-based, strategic approach to the general risk management of systemic glucocorticoids with a focus on preventing glucocorticoid-induced osteoporosis (GIOP). We assess which classes of corticosteroid are most likely to provoke allergic cross-reactions and outline the mechanism for glucocorticoid resistance. We examine how glucocorticoids both help and impair normal physiology. Five reactivity groups are defined, based on the structural and clinical characteristics of glucocorticoids. Tests for allergy reactions and mechanisms for glucocorticoid resistance are described. Guidelines for the prevention and treatment of GIOP are introduced. Glucocorticoids play an important teleologic role in maintaining blood glucose levels adequate for brain function by inducing a catabolic state through the production of carbohydrates at the expense of proteins and fat stores. It is hoped that the various recommendations for the protection of patients treated with systemic glucocorticoids will provide physicians with practical guidelines for prescribing.

GLUCOCORTICOID-INDUCED OSTEOPOROSIS: DIAGNOSIS, PREVENTION, AND TREATMENT

The lecture gives information on the epidemiology and pathogenesis of glucocorticoid-induced osteoporosis (GCOP). It presents the latest diagnostic criteria, a modified FRAX algorithm (assessment of 10-year osteoporotic fracture risk) in relation to the taken dose of glucocorticoids, the data of recent clinical guidelines for the treatment and prevention of GCOP, and the specific features in relation to patient age.

Glucocorticoid-induced osteoporosis: 2013 update.

Glucocorticoids are the most common cause of secondary osteoporosis leading to the so-called glucocorticoid-induced osteoporosis (GIO). A treatment with 10 mg/d of prednisone or equivalent for more than 3 months leads to a 7-fold increase in hip fractures and a 17-fold increase in vertebral fractures. The difference between bone quantity and quality in GIO makes bone mineral density measurements inadequate to detect patients at risk of fracture. The adverse effects of glucocorticoids on the skeleton derive from a direct impact on bone cells with a severe impairment of mechanical competence. Crucial to prevention of GIO is early timing of intervention. The World Health Organization has adopted a fracture prevention algorithm (FRAX) intended to estimate fracture risk in GIO. The American College of Rhematology modified its prevention and treatment guidelines taking into account the individual risk of fracture calculated in GIO on the basis of the FRAX algorithm. Recently, also a joint Guideline Working Group of the International Osteoporosis Foundation (IOF) and the European Calcified Tissue Society (ECTS) published a framework for the development of national guidelines for the management of GIO. Bisphosphonates are the first-line drugs to treat GIO; teriparatide counteracts several fundamental pathophysiologic aspects of GIO; denosumab is useful in patients with renal failure and in potentially pregnant young women. Vertebroplasty and kyphoplasty may be less beneficial in GIO than in primary involutional osteoporosis.

SAT0469 Ineffective Fracture Prevention by Bisphosphonate in Patients Undergoing High Dose Glucocorticoid Therapy with A Frax Ten Year Probability Greater than 5.8%

BackgroundHigh dose glucocorticoid (GC) therapy (PSL>0.8mg/kg/day) is often provided to patients with systemic rheumatic disease. GC induced osteoporosis (GIO) is a common complication of high dose GC therapy and bisphosphonate...

Bone safety of low-dose glucocorticoids in rheumatic diseases.

Glucocorticoids are widely used internationally for the treatment of inflammatory disease, such as rheumatoid arthritis (RA). Although the benefit of glucocorticoids in RA on both disease activity and severity are well known, there remain unanswered questions about the overall bone safety of chronic low-dose glucocorticoids in RA. Debate exists about the merits of glucocorticoids for bone health on the basis of their benefits in promoting activity and reducing proinflammatory cytokines. Overall current evidence supports the view that bone loss is a disease related both to RA and to glucocorticoid use independently. Calcium and vitamin D, along with prescription antiosteoporosis therapies, particularly bisphosphonates and teriparatide, play an important role in stabilizing bone mineral density and potentially lowering spinal fracture risk at the spine. International guidelines provide pathways for appropriate prevention of glucocorticoid-induced osteoporosis (GIOP). Despite the evidence and these guidelines, many patients do not receive adequate management to prevent GIOP.

Challenges in Defining Quality of Care for Glucocorticoid-induced Osteoporosis: Defending Good Against Perfect

In an era of increasing preventive care complexity coupled with progressively shorter doctor visits, asymptomatic conditions such as osteoporosis (OP) can easily be neglected. Despite a reported reduction in fracture burden in the United States and Canada1,2, OP continues to be a condition that is both underdiagnosed and undertreated. In the United States, the Healthcare Effectiveness Data and Information Set statistics from the National Committee on Quality Assurance estimates that less than 25% of persons who incur fracture receive a bone-specific medication; a proportion that has remained essentially stagnant over the past 10 years. These US findings are quite similar to the low rates of OP treatment in Canada, as highlighted in the paper in this issue of The Journal by Majumdar and colleagues3. Glucocorticoids constitute the most commonly administered drugs that are associated with bone loss and higher fracture risk. Despite a clear time- and dose-dependent association of glucocorticoids with fracture risk4,5 and international guidelines that support a variety of pharmacotherapies for both primary and secondary prevention6,7,8,9, the prevention and treatment statistics are also rather dismal for glucocorticoid-induced OP (GIOP). Curtis and colleagues observed temporal improvement in the rates of treatment with nonestrogen bone-acting agents among chronic glucocorticoid users of an Aetna managed-care plan over a 5- to 6-year period10. However, even among postmenopausal women, the group at highest fracture risk, less than two-thirds were being treated in the early 2000s. Majumdar and colleagues, using much newer data from Canada, reported that only 25% of over 15,000 older adults receiving supraphysiologic prednisone were managed in accord with the latest guidelines. Thus, an underuse gap persists for GIOP prevention and treatment. Underuse of many evidence-based therapeutics for chronic conditions such as … Address correspondence to Dr. Saag, 1720 2nd Avenue South, Birmingham, AL 35294, USA. E-mail: Ksaag{at}uab.edu

OP0252 Effect of Glucocorticoids and Bisphosphonates on PPAR-Gamma and Hedgehog Pathway in Glucocorticoid-Induced Osteoporosis

BackgroundPrevious studies have investigated the molecular mechanisms involved in Glucocorticoid-induced osteoporosis (GIOP), which found that glucocorticoids (GCs) treatment increased bone resorption by prolonging of the lifespan of osteoclasts [1] and...