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Oral corticosteroid (OCS) use in severe asthma remains all too common despite advances in asthma treatment. Use of OCS is associated with significant toxicity that can have a lasting adverse impact on a patient's overall health. Monoclonal antibodies have been developed that reduce both the rate of occurrence of OCS-treated exacerbations and the OCS requirements in patients with oral corticosteroid-dependent asthma. This article describes strategies to prevent and best manage endocrine complications associated with OCS use and provides guidance on OCS dose management after the introduction of steroid-sparing therapies. (1) We identify OCS-dependent patients and assess for comorbidities including bone health, glycemic control, and adrenal function; (2) we begin attempts at OCS dose optimization before or soon after introducing a steroid-sparing biologic therapy; (3) we taper OCS, using explicit criteria for asthma control; (4) we assess hypothalamic-pituitary-adrenal axis integrity once a physiologic dose of OCS is achieved to guide further the rate of OCS taper; and (5) we manage corticosteroid-related comorbidities as detailed in this article.

ObjectivesSteroid-induced osteoporosis (SIOP) is a secondary osteoporosis, which is a systemic bone disease characterized by low bone mass, bone microstructure damage, increased bone fragility, and easy fracture. However, the specific mechanism remains unclear. Glucocorticoid-induced death of osteoblasts and bone marrow mesenchymal stem cells (BMSCs) is an important factor in SIOP. Ferroptosis is an iron-dependent programmed cell death that differs from apoptosis, cell necrosis, and autophagy, which can be induced by many factors. Herein, we aimed to explore whether glucocorticoids (GCs) cause ferroptosis in BMSCs and determine possible treatment pathways and mechanisms of action. Melatonin (MT), a hormone secreted by the pineal gland, displays strong antioxidant abilities to scavenge free radicals and alleviates ferroptosis in many tissues and organs. MethodsIn this study, we used high-dose dexamethasone (DEX) to observe whether glucocorticoids induced ferroptosis in BMSCs. We then assessed whether MT can inhibit the ferroptotic pathway, thereby providing early protection against GC-induced SIOP, and investigated the signaling pathways involved.ResultsIn vitro experiments showed that MT intervention significantly improved GC-induced ferroptosis in BMSCs and significantly improved SIOP in vivo. Pathway analysis showed that MT improves ferroptosis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis. MT upregulates expression of PI3K, which is an important regulator of ferroptosis resistance. PI3K activators mimic the anti-ferroptosis effect of MT, but after blocking the PI3K pathway, the effect of MT is weakened. Obviously, MT can protect against SIOP induced by GC. Notably, even after GC-induced ferroptosis begins, MT can confer protection against SIOP. Conclusion Our research confirms that GC-induced ferroptosis is closely related to SIOP. Melatonin can inhibit ferroptosis by activating the PI3K-AKT-mTOR signaling pathway, thereby reducing the occurrence of steroid-induced osteoporosis. Therefore, MT may provide a novel strategy for preventing and treating SIOP.

Osteoporosis and fragility fractures are a major public health issue. Secondary osteoporosis is characterised by the presence of an underlying disease, deficiency, or use of a drug. Conditions that increase speculation for secondary osteoporosis include fragility fractures amongst the younger men or premenopausal women, markedly decreased Bone Mineral Density (BMD) values, and fractures despite conforming to anti-osteoporotic therapy. Since the emphasis is on the treatment of the primary disorder, a diagnosis of osteoporosis and thus the opportunity of preventive intervention can be missed. With this review, the authors objective is to emphasise the importance of secondary osteoporosis, discuss the causes and their mechanism and summarise treatment options.

Glucocorticoid (or steroid) induced osteoporosis (GIOP) is the leading form of secondary osteoporosis, affecting up to 50% of patients receiving chronic glucocorticoid therapy. Bone quantity (bone mass) changes in GIOP patients alone are inadequate to explain the increased fracture risk, and bone material changes (bone quality) at multiple levels have been implicated in the reduced mechanics. Quantitative analysis of specific material-level changes is limited. Here, we combined multiscale experimental techniques (scanning small/wide-angle X-ray scattering/diffraction, backscattered electron imaging, and X-ray radiography) to investigate these changes in a mouse model (Crh-120/+) with chronic endogenous steroid production. Nanoscale degree of orientation, the size distribution of mineral nanocrystals in the bone matrix, the spatial map of mineralization on the femoral cortex, and the microporosity showed significant changes between GIOP and the control, especially in the endosteal cortex. Our work can provide insight into the altered structure-property relationship leading to lowered mechanical properties in GIOP. SIGNIFICANCE STATEMENT: As a natural nanocomposite with a hierarchical structure, bone undergoes a staggered load transfer mechanism at the nanoscale. Disease and age-related deterioration of bone mechanics are caused by changes in bone structure at multiple length scales. Although clinical tools such as dual-energy X-ray absorptiometry (DXA) can be used to assess the reduction of bone quantity in these cases, little is known about how altered bone quality in diseased bone can increase fracture risk. It is clear that high-resolution diagnostic techniques need to be developed to narrow the gap between the onset and diagnosis of fracture-related changes. Here, by combining several scanning probe methods on a mouse model (Crh-120/+) of glucocorticoid-induced osteoporosis (GIOP), we developed quantitative and spatially resolved maps of ultrastructural changes in collagen fibrils and mineral nanocrystals, mineralization distribution (microscale), and morphology (macroscale) across femoral osteoporotic bone. Our results indicate that the altered bone remodelling in GIOP leads to 1) heterogeneous bone structure and mineralization, 2) reduced degree of orientation of collagen fibrils and mineral nanocrystals, and 3) reduced length and increased thickness of mineral nanocrystals, which contribute to mechanical abnormalities. The combined multiscale experimental approach presented here will be used to understand musculoskeletal degeneration in aging and osteoporosis.

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects multiple organs and requires long term treatment with GCs. GC-related end organ damage in SLE appears in the form of: osteoporosis, Avascular Necrosis (AVN), cataracts, diabetes (DM) and cardiovascular disease. Aim of the work: the present work was to assess the prevalence of the complications in SLE patients who were treated with GCs for long periods and with moderate to severe cumulative steroid doses. Patients and Methods: This study was done on 50 SLE patients who fulfilled the SLICC criteria for diagnosis of SLE. All patients subjected to full history taking, clinical examination, slit-lamp examination to assess cataract, laboratory investigations (ESR, CRP, FBS, 2-H PP, CBC, C3, C4 and anti-dsDNA), DEXA scan, MRI scan (when needed), SLEDAI score and SLICC score assessments. All data were collected, tabulated and statistically analyzed. Results: Regarding the frequency of steroid induced complications, 38% were osteopenic, while 18% were osteoporotic patients. 10% had AVN. 18% had cataract. 14% had DM. There was very strong relationship between steroid duration and the frequency of DM and cataract. But in osteopenia, osteoporosis and AVN, there were weak relationship regarding steroid duration. There was very strong relationship between cumulative steroid dose and the frequency of DM, cataract, osteoporosis and AVN. There was no relationship between age and osteoporosis and AVN but in cataract and DM, there was strong relationship. There was no relationship between sex and complications (DM, cataract, osteopenia, osteoporosis and AVN). There was no relationship between disease activity (measured by SLEDAI score) and frequency of steroid complications (DM, cataract, osteopenia, osteoporosis and AVN). There was strong relationship between end organ damage (measured by SLICC damage index) and frequency of steroid complications (DM, cataract, osteoporosis and AVN). Conclusion: Steroid intake (duration and dose) were major risk factors for developing end organ damage in SLE patients.

This study is an evaluation of the effect of gastrointestinal cancer chemotherapy with short‐term periodic steroid premedication on bone metabolism. Primary endpoints were changes in bone mineral densities and metabolic bone turnover 16 weeks after initiation of chemotherapy., Background. A multicenter prospective observational study evaluated the effect of gastrointestinal cancer chemotherapy with short‐term periodic steroid premedication on bone metabolism. Patients and Methods. Seventy‐four patients undergoing chemotherapy for gastrointestinal cancer were studied. The primary endpoints were changes in bone mineral densities (BMDs) and metabolic bone turnover 16 weeks after initiation of chemotherapy. BMDs, measured by dual‐energy x‐ray absorptiometry, and serum cross‐linked N‐telopeptides of type I collagen (sNTX), and bone alkaline phosphatase (sBAP) were assessed for evaluation of bone resorption and formation, respectively. Results. In 74.3% (55/74) of the patients, BMDs were significantly reduced at 16 weeks relative to baseline. The percent changes of BMD were −1.89% (95% confidence interval [CI], −2.67% to −1.11%: p

As bone is used in a dynamic mechanical environment, understanding the structural origins of its time-dependent mechanical behaviour – and the alterations in metabolic bone disease – is of interest. However, at the scale of the mineralized fibrillar matrix (nanometre-level), the nature of the strain-rate dependent mechanics is incompletely understood. Here, we investigate the fibrillar- and mineral-deformation behaviour in a murine model of Cushing’s syndrome, used to understand steroid induced osteoporosis, using synchrotron small- and wide-angle scattering/diffraction combined with in situ tensile testing at three strain rates ranging from 10-4 to 10-1 s-1. We find that the effective fibril- and mineral-modulus and fibrillar-reorientation show no significant increase with strain-rate in osteoporotic bone, but increase significantly in normal (wild-type) bone. By applying a fibril-lamellar two-level structural model of bone matrix deformation to fit the results, we obtain indications that altered collagen-mineral interactions at the nanoscale – along with altered fibrillar orientation distributions – may be the underlying reason for this altered strain-rate sensitivity. Our results suggest that an altered strain-rate sensitivity of the bone matrix in osteoporosis may be one of the contributing factors to reduced mechanical competence in such metabolic bone disorders, and that increasing this sensitivity may improve biomechanical performance.

Background Bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DEXA) is one of the most important markers for osteoporosis diagnosis. The serum creatinine-to-cystatin C ratio (Cr/CysC) is in focus as a sarcopenia marker because it represents total muscle volume. Recently, Cr/CysC was suggested to have correlation with bone fragility fracture risk [1]. Objectives This study aimed to assess whether Cr/CysC is correlated with BMD. Methods BMD at the lumbar spine (LS) and femoral neck (FN) were measured in women diagnosed with postmenopausal osteoporosis. Steroid induced osteoporosis patients were eliminated. Cr/CysC was assessed at the time. Clinical factors, such as age, concurrent rheumatoid arthritis treatment (RA), concomitant biological drug administration (BIO), body mass index (BMI), concurrent dementia treatment (dementia), number of comorbidities other than dementia (N.Com), frailty score (FS), bone fragility fracture (BFF), and drug intervention for osteoporosis (DI), were evaluated. Multivariate linear regression (MLR) was used to assess the correlation of these factors with BMD at each part. The relationships between Cr/CysC and other parameters were statistically evaluated using MLR. Additionally, the relationships between the BMD change at each part and parameters were evaluated in the same manner. Results The study enrolled 207 subjects. BMD at the LS was significantly correlated with BMI and N.Com (p After effect of age was corrected, BMD at the FN demonstrated significant positive correlation with Cr/CysC (p Conclusion Cr/CysC represents BMD at the FN and is a candidate for BMD substitution. References [1] Komorita Y, et al. Diabetes Res Clin Pract2018;146:202-10. Acknowledgement The author would like to thank Saori Tamura for the enthusiastic DXA and BMD measurements and Kaoru Kuwabara, Sayori Masuoka, and Mariko Osaki for their dedicated data collection Disclosure of Interests None declared

Nanocomposites like bone are used in vivo in a dynamic mechanical environment, and musculoskeletal fracture during traumatic events lead to pain and immobilisation, especially significant in elderly and patients with metabolic bone diseases. To mitigate against these occurrences, it is essential to understand the dynamic mechanical response of bone over short timescales, but the underlying matrix-level mechanisms are not well understood. Here, we studied the mechanical response of cortical bone at nano- and micro-scale in a mouse model with glucocorticoid induced osteoporosis and their wild type littermates using real-time synchrotron small-angle X-ray diffraction (SAXD) combined with in situ compression testing and micro-tensile testing under controlled strain rates. Under compression, the tissue modulus, yield stress, effective fibril modulus and fibrillar reorientation rate in osteoporotic bone is significantly lower than that in healthy bone. Under tension, when going from low to high strain rates, the effective fibril modulus of healthy bone increase by a factor of 4.8, but this tendency is suppressed in osteoporotic bone. Also, bone microstructure in osteoporotic showed large fraction of cavities with disrupted mineralization. Our results demonstrate how the nano- and microscale deformation mechanisms of bone ultrastructure change in osteoporotic bone under compression and tension. Our results suggest that material level changes of bone matrix contributed to the reduced mechanical competence of bone in metabolic bone diseases such as osteoporosis.

Background Glucocorticoid therapy is a major risk factor for osteoporosis related fractures. A previous meta-analysis conducted by Homik et al reported that bisphosphonates therapy increased BMD in glucocorticoid- induced osteoporosis (GIO) when compared to placebo, whereas results for incident vertebral fracture did not reach statistical significance Objectives To evaluate the efficacy of bisphosphonates in GIO based on randomized controlled trials (RCTs). Both placebo controlled and active comparator trials were analyzed. Methods Two authors screened citations from the following electronic databases: Medline (1998–2015), EMBASE (1998–2015), Cochrane Library (1998–2015). A manual search was completed for conference proceedings from the ACR (2010–2015), CRA (2009–2015), and ASBMR (2009–2014). We used the study by Homik et al to identify RCTs published prior to 1998. Only RCTs that had a minimum prednisone dosage of 5 mg/day or equivalent and treatment duration of at least 3 months were included. Primary outcomes were changes in BMD and incident fractures. Two authors abstracted data using a standardized data abstraction form. We used the Cochrane Risk of Bias Tool to evaluate the quality of the selected RCTs and devised a quality score ranging from 0 to 6, where 6 represents the highest quality. Results A total of 466 citations were identified (239 Medline, 217 EMBASE, and 10 Cochrane Library). Fourteen RCTs met the inclusion criteria. An additional two RCTs were identified from conference proceedings. Eleven RCTs compared bisphosphonates to a placebo, three RCTs compared bisphosphonates to a vitamin D derivative, one RCT compared alendronate to teriparatide, and one RCT compared zoledronic acid to risedronate. The RCTs were of reasonably good quality with a mean quality score of 4. Overall, of the 11 RCTs that compared bisphosphonates to a placebo, all found that the bisphosphonates were superior. Nine RCTs were pooled for mean percentage change in lumbar spine BMD (bisphosphonates n=667, placebo n=654). The pooled mean percentage change was in favor of bisphosphonates compared to placebo [weighted mean difference (WMD) of 4.03%, 95% CI (1.59–6.47), p=0.001]. Six RCTs were pooled for mean percentage change in femoral neck BMD (bisphosphonates n=486, placebo n=481) and the results favored bisphosphonates compared to placebo [WMD of 2.95%, 95% CI (0.09 -5.82), P=0.04]. Seven RCTs were pooled for outcome of incident fractures (bisphosphonates n=613, placebo n=469) and the results favored bisphosphonates compared to placebo [RR of 0.65, 95% CI (0.48–0.88), P=0.006] (Figure 1). Results were pooled using RevMan (version 5.3). Conclusions Bisphosphonates mitigate adverse changes in BMD and lower fracture risk in patients treated with glucocorticoids. References Homik JE, Cranney A, Shea B, et al. Bisphosphonates for steroid induced osteoporosis. Cochrane Database of Systematic Reviews 1999, Issue 1. Art. No.: CD001347. Disclosure of Interest None declared

Background Corticosteroids are widely used for various diseases, from chronic respiratory conditions to auto-immune disorders. However, there are few epidemiological data about long-term steroid therapy in southern Europe (1, 2, 3). Objectives To describe chronic glucocorticoid prescriptions in a large cohort. Methods Information was collected from a national public health-insurance database that covers 4.1 million individuals and 83% of the population, in our geographic area of Provence-Alpes-Cote-d9Azur and Corsica, from September 1, 2009 through August 31, 2011. We identified subjects aged of 15 years and over starting glucocorticoid therapy. Chronic glucocorticoid therapy was defined as ≥7.5mg of prednisone equivalent per day during at least 90 days consecutive. We identified the incident cases of long-term glucocorticoid therapy, defined as those prevalent cases who did not fill glucocorticoid prescriptions during the first 6 months of the 24-month study period. Results We identified 32,812 patients who were prescribed glucocorticoid therapy, yielding 0.97% prevalence. Of these 32,812 patients, 14,205 (43.3%) met our definition of incident cases, yielding an incidence of 0.42% for 18 months in the overall population aged at least 15 years, corresponding to an incidence of long-term glucocorticoid therapy of 2.8/1000 inhabitants/year. Among these incident cases, the most currently prescribed glucocorticoids were prednisolone (64%) and prednisone (32%). Sixty-three per cent of patients received only one type of glucocorticoid while 33% received two and 5% received 3 or more of them. The average treatment duration was 270.9 days (CI 95% 267.7 – 274). Most prescriptions (55,4%) were initiated by general practitioners. The median prednisone-equivalent dose was 11mg/day (IQR, 8.8–17.8) and varied very little with age and sex. Rheumatoid arthritis was the most common disease associated with chronic glucocorticoid prescriptions in this cohort (30%), followed by chronic respiratory failure (21%), internal medicine diseases such as connectivite tissue diseases, polymyalgia rheumatica or Giant-cell arteritis (21%), asthma (15%) and infammatory bowel diseases like ulcerative colitis or Crohn9s disease (13%). Conclusions Long-term corticosteroid therapy is frequent in France, its description is close to what is already known in Europe. References Overman RA, Heh JY, Deal CL. Prevalence of oral glucocorticoid usage in the United States: a general population perspective. Arthritis Care Res (Hoboken) 2013;65:294–8. Gudbjornsson B, Juliusson UI, Gudjonsson FV. Prevalence of long term steroid treatment and the frequency of decision making to prevent steroid induced osteoporosis in daily clinical practice. Ann Rheum Dis 2002;61:32–6. Fardet L, Petersen I, Nazareth I. Prevalence of long-term oral glucocorticoid prescriptions in the UK over the past 20 years. Rheumatology 2011;50:1982–90. Disclosure of Interest None declared

BACKGROUND: Systemic glucocorticoids are often used in the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), and osteoporosis is a well-known complication to steroid treatment, associated with significant morbidity. Nevertheless, the burden of steroid induced osteoporosis is unknown in patients with CRSwNP. We aimed to assess the risk of acquiring osteoporosis caused by oral steroids in patients with CRSwNP, and provide recommendations on future research and guidelines.METHODOLOGY: Cochrane Review Database, EMBASE, Ovid Medline, and PubMed were searched for studies including adult patients with CRSwNP treated with oral steroids. Outcomes were Bone Mineral Density (BMD) and prevalence of fractures in relation to dose and duration of oral steroids. In addition, we reviewed general guidelines for treatment with oral steroids.RESULTS: We identified two studies (n=243) that met the inclusion criteria. Doses and durations of oral steroids were over 5 mg/day for more than 3 months and 1 mg/kg body weight/day for 6 to 10 days for 4 or more courses/year. The prevalence of low bone mass was 39% and 61%, respectively. It was not possible to quantify the overall risk of osteoporosis induced by oral steroids from the studies. No studies evaluated prevalence of fracture.CONCLUSIONS: Registry studies and randomized controlled trials would be needed to assess the risk of osteoporosis in CRSwNP patients and future guidelines should include recommendations regarding preventive treatment and recommendations on doses and durations of oral steroids.

Previous reports demonstrated that bone density decreased rapidly during the initial few months of steroid therapy and continued decreasing at a rate of 2 to 4% annually. Our data indicates that denosumab can also play a role in the treatment of osteoporosis in the steroid-taking population. 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 60 mg every 6 months, 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 28 months. 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 28 months increased significantly from the 12-month follow-up (P = 0.0259), though the first 12 months 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.

Objective: To evaluate the anti-osteoporotic activity of ethanolic extract of Daucus carota (DC) roots on steroid induced Osteoporosis in rats. Material and Methods: Female wistar rats were divided into five groups of (n=6) each. Osteoporosis was induced by intramuscular administration of dexamethasone 7mg/kg once a week for four weeks to all groups of rats except normal control group. Group I served as normal control and received normal saline. Group II served as disease control injected with dexamethasone 7mg/kg (i.m). Group III served as standard control and treated with sodium alendronate 0.2mg/kg orally from 15th to 28th day. Group IV and V were treated with DC at doses of 200mg/kg and 400mg/kg (p.o) respectively from 15th to 28th day. Following treatment, antiosteoporotic effect of DC was evaluated by biochemical and biomechanical analysis and radiological observation along with histopathological examination among the experimental groups. Results: Rats treated with ethanolic extract of DC (200mg/kg and 400mg/kg) showed significant (P

Therapy with bisphosphonates (BP) is recognized to be "the golden standard" for the treatment of osteoporosis of different etiology. However, the data on the use of BP by the women during pregnancy and lactation are scarce. This paper reports a case of gestation, labour, and lactation in a patient treated with ibandronic acid (Bonviva) for severe steroid-induced osteoporosis attributable to Cushing's disease. To our knowledge, the application of ibandronic acid during pregnancy has never been described in the literature before. The present study has demonstrated that therapy with ibandronic acid does not necessarily require the interruption of pregnancy or cessation of birth feeding. Nevertheless, the treatment of the women of reproductive age with BP can be prescribed only upon strict indications.

Background This is an update of a Cochrane Review first published in 1999. Corticosteroids are widely used in inflammatory conditions as an immunosuppressive agent. Bone loss is a serious side effect of this therapy. Several studies have examined the use of bisphosphonates in the prevention and treatment of glucocorticosteroid-induced osteoporosis (GIOP) and have reported varying magnitudes of effect. Objectives To assess the benefits and harms of bisphosphonates for the prevention and treatment of GIOP in adults. Search methods We searched CENTRAL, MEDLINE and Embase up to April 2016 and International Pharmaceutical Abstracts (IPA) via OVID up to January 2012 for relevant articles and conference proceedings with no language restrictions. We searched two clinical trial registries for ongoing and recently completed studies (ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal). We also reviewed reference lists of relevant review articles. Selection criteria We included randomised controlled trials (RCTs) satisfying the following criteria: 1) prevention or treatment of GIOP; 2) adults taking a mean steroid dose of 5.0 mg/day or more; 3) active treatment including bisphosphonates of any type alone or in combination with calcium or vitamin D; 4) comparator treatment including a control of calcium or vitamin D, or both, alone or with placebo; and 4) reporting relevant outcomes. We excluded trials that included people with transplant-associated steroid use. Data collection and analysis At least two review authors independently selected trials for inclusion, extracted data, performed ‘risk of bias’ assessment and evaluated the certainty of evidence using the GRADE approach. Major outcomes of interest were the incidence of vertebral and nonvertebral fractures after 12 to 24 months; the change in bone mineral density (BMD) at the lumbar spine and femoral neck after 12 months; serious adverse events; withdrawals due to adverse events; and quality of life. We used standard Cochrane methodological procedures. Main results We included a total of 27 RCTs with 3075 participants in the review. Pooled analysis for incident vertebral fractures included 12 trials (1343 participants) with high-certainty evidence and low risk of bias. In this analysis 46/597 (or 77 per 1000) people experienced new vertebral fractures in the control group compared with 31/746 (or 44 per 1000; range 27 to 70) in the bisphosphonate group; relative improvement of 43% (9% to 65% better) with bisphosphonates; absolute increased benefit of 2% fewer people sustaining fractures with bisphosphonates (5% fewer to 1% more); number needed to treat for an additional beneficial outcome (NNTB) was 31 (20 to 145) meaning that approximately 31 people would need to be treated with bisphosphonates to prevent new vertebral fractures in one person. Pooled analysis for incident nonvertebral fractures included nine trials with 1245 participants with low-certainty evidence (downgraded for imprecision and serious risk of bias as a patient-reported outcome). In this analysis 30/546 (or 55 per 1000) people experienced new nonvertebral fracture in the control group compared with 29/699 (or 42 per 1000; range 25 to 69) in the bisphosphonate group; relative improvement of 21% with bisphosphonates (33% worse to 53% better); absolute increased benefit of 1% fewer people with fractures with bisphosphonates (4% fewer to 1% more). Pooled analysis on BMD change at the lumbar spine after 12 months included 23 trials with 2042 patients. Eighteen trials with 1665 participants were included in the pooled analysis on BMD at the femoral neck after 12 months. Evidence for both outcomes was moderate-certainty (downgraded for indirectness as a surrogate marker for osteoporosis) with low risk of bias. Overall, the bisphosphonate groups reported stabilisation or increase in BMD, while the control groups showed decreased BMD over the study period. At the lumbar spine, there was an absolute increase in BMD of 3.5% with bisphosphonates (2.90% to 4.10% higher) with a relative improvement of 1.10% with bisphosphonates (0.91% to 1.29%); NNTB 3 (2 to 3). At the femoral neck, the absolute difference in BMD was 2.06% higher in the bisphosphonate group compared to the control group (1.45% to 2.68% higher) with a relative improvement of 1.29% (0.91% to 1.69%); NNTB 5 (4 to 7). Pooled analysis on serious adverse events included 15 trials (1703 participants) with low-certainty evidence (downgraded for imprecision and risk of bias). In this analysis 131/811 (or 162 per 1000) people experienced serious adverse events in the control group compared to 136/892 (or 147 per 1000; range 120 to 181) in the bisphosphonate group; absolute increased harm of 0% more serious adverse events (2% fewer to 2% more); a relative per cent change with 9% improvement (12% worse to 26% better). Pooled analysis for withdrawals due to adverse events included 15 trials (1790 patients) with low-certainty evidence (downgraded for imprecision and risk of bias). In this analysis 63/866 (or 73 per 1000) people withdrew in the control group compared to 76/924 (or 77 per 1000; range 56 to 107) in the bisphosphonate group; an absolute increased harm of 1% more withdrawals with bisphosphonates (95% CI 1% fewer to 3% more); a relative per cent change 6% worse (95% CI 47% worse to 23% better). Quality of life was not assessed in any of the trials. Authors' conclusions There was high-certainty evidence that bisphosphonates are beneficial in reducing the risk of vertebral fractures with data extending to 24 months of use. There was low-certainty evidence that bisphosphonates may make little or no difference in preventing nonvertebral fractures. There was moderate-certainty evidence that bisphosphonates are beneficial in preventing and treating corticosteroid-induced bone loss at both the lumbar spine and femoral neck. Regarding harm, there was low-certainty evidence that bisphosphonates may make little or no difference in the occurrence of serious adverse events or withdrawals due to adverse events. We are cautious in interpreting these data as markers for harm and tolerability due to the potential for bias. Overall, our review supports the use of bisphosphonates to reduce the risk of vertebral fractures and the prevention and treatment of steroid-induced bone loss.

Studies of oral corticosteroid dose and loss of bone mineral density have reported inconsistent results. In this meta-analysis, we used information from 66 papers on bone density and 23 papers on fractures to examine the effects of oral corticosteroids on bone mineral density and risk of fracture. Strong correlations were found between cumulative dose and loss of bone mineral density and between daily dose and risk of fracture. The risk of fracture was found to increase rapidly after the start of oral corticosteroid therapy (within 3 to 6 months) and decrease after stopping therapy. The risk remained independent of underlying disease, age and gender. We conclude that oral corticosteroid treatment using more than 5 mg (of prednisolone or equivalent) daily leads to a reduction in bone mineral density and a rapid increase in the risk of fracture during the treatment period. Early use of preventive measures against corticosteroid-induced osteoporosis is recommended.

Objective: The study was conducted to develop the glucocorticoid-induced osteoporosis (GIO) model in Sprague-Dawley weanling rats using different doses of methylprednisolone (MP) and evaluate the antiosteoporotic effect of a classical ayurvedic formulation, Panchatikta Ghrita (PG), in this model. Materials and Methods: Institutional Animal Ethics Committee approval was obtained. Development of model was done by subcutaneous injection of 2 doses of MP (14 and 28 mg/kg/week) for 4 weeks in 21-day old weanlings. Following confirmation of the dose of MP that induced osteoporosis, the antiosteoporotic effect of PG was tested in this model in comparison to a known antiosteoporotic agent, alendronate. Both alendronate (2.9 mg/kg/day) and PG (1.35 g/kg/day) were administered orally 2 weeks after MP - 14 mg/kg/week injection and continued for 4 weeks. Serum and urine calcium and inorganic phosphate were analyzed at weekly intervals. Animals were sacrificed after 6 weeks, and femur bones were processed to measure bone hardness and elasticity and for histological studies. Results: Rats treated with MP - 14 mg/kg/week showed optimum osteoporotic effect with no mortality as compared to MP - 28 mg/kg/week; hence, this dose of MP was used further for the efficacy study. Osteoporotic rats treated with PG 1.35 g/kg showed increase in serum calcium and inorganic phosphate levels, whereas urine calcium and phosphate levels were significantly reduced. A significant decrease in a number of osteoclasts, whereas an increase in bone hardness and elasticity was observed as compared to diseased group demonstrating antiosteoporotic effect of PG. Conclusion: PG has an antiosteoporotic effect in GIO rat model.

Objectives Minodronic acid hydrate, an oral bisphosphonate, has a greater inhibitory effect on bone resorption than do other approved drugs; however, this has been studied only in patients with primary osteoporosis. Here, we administered minodronic acid hydrate to patients with steroid-induced osteoporosis who have been treated with steroids for rheumatoid arthritis or other collagen diseases, and the efficacy and safety of minodronic acid hydrate were prospectively investigated. Methods Twenty-five patients treated in our rheumatology clinic received minodronic acid hydrate 1 mg/day. The changes in bone mineral density (BMD) and bone turnover markers were investigated at 3 and 6 months, and adverse events, including the presence or absence of an incident osteoporotic fracture, were examined over a period of 6 months. Results Percent changes in BMD of the lumbar spine and femur significantly increased. The values of bone turnover markers significantly decreased. There were no patients with a radiographically apparent incident fracture. Adverse events included toothache for which the patient discontinued the treatment and three cases of gastrointestinal disorder that did not lead to discontinuation, and thus minodronic acid hydrate was well tolerated. Conclusions Here, we show that minodronic acid hydrate is effectively and safely used for treatment of steroid-induced osteoporosis.

Glucocorticoids are quite commonly used in the treatment of many diseases and are one of the most common causes of secondary osteoporosis. Osteoporosis associated with chronic steroid therapy, appears to be an important medical problem. In the USA, glucocorticoids are prescribed to 1 million patients a year. Data from the UK reveal as many as 1.6 million prescriptions for steroid agents within 10 years. Glucocorticoids are used by 0.9% of the total population and approximately 2.5% in the age group of 70–79 years. It is very important to develop the knowledge about osteoporosis, which accompanies chronic steroid therapy, especially with regard to effective counteraction and prevention rules, not only among primary care physicians, but also among patients.

Despite their deleterious effects, glucocorticoids (GCs) are commonly used in various disorders in the paediatric age group. Children on GC therapy need close monitoring for growth failure and other side effects. This article gives an overview about the problems associated with GC use and the present status on their solutions.

Bone-related steroid involvement is one of the most frequent complications of steroid treatment. Epidemiological data demonstrate that osteoporosis starts early during the treatment, predominantly involves trabecular bone and is correlated to dosage and treatment duration. Mechanisms and consequences of steroid bone involvement are related to osseous and extra-osseous mechanisms. In clinical practice, steroid-induced osteoporosis remains underdiagnosed and undertreated both in preventive and curative approaches. Recently, new molecules as teriparatide and zoledronic acid got indication for the treatment of steroid-induced osteoporosis. To guide treatment strategies, several recommendations are available: French, not updated recommendations since 2003 (Afssaps, 2003), European elaborated by the EULAR in 2007 and those of the ACR updated in 2010.

Objective To examine the adequacy of primary prophylaxis for glucocorticoid-induced osteoporosis (GIOP) in patients taking long-term steroids. Methods We conducted a retrospective audit in our hospital to determine physician's awareness and preventive measure during treatment against GIOP. Hospital records of patients receiving =7.5mg/day of oral steroids for = 3 months were studied and relevant data was collected. Primary preventive measures instituted against GIOP were noted and analysed. Results One hundred and fifty one patients, 87 females and 64 males, fulfilling the inclusion criteria were included in this study. Of the 151 patients, 44 did not receive any prophylaxis, 73 received inadequate prophylaxis and only 34 were given appropriate prophylaxis. Conclusions The practice of instituting primary preventive measures against GIOP is not satisfactory among prescribing doctors. There is an urgent need to increase awareness and knowledge of GIOP management.

Background Minimal-change nephrotic syndrome (MCNS) is treated by the administration of prednisolone (PSL) at high doses. Steroid-induced osteoporosis is a serious adverse effect of this drug. Methods Patients with MCNS were randomly assigned to two groups, the risedronate (2.5 mg/day) + alfacalcidol (0.25 μg/day) group (n=20) and the alfacalcidol (0.25 μg/day)-alone group (n=20). All the patients had received PSL and the clinical characteristics were compared between the two groups at baseline and at 12 months. Results A significant decrease of the mean bone mineral density (BMD) of the lumbar spine from 0.710±0.162 (g/cm2) to 0.588±0.125 was observed in the alfacalcidol-alone group (p=0.02), while no such decrease of the bone mineral density was found in the risedronate + alfacalcidol group (0.663±0.169 at baseline and 0.626±0.129 at 12 months). No significant differences in the results of other biochemical tests performed at the baseline and at 12 months were observed between the two groups. The likelihood of development of steroid-induced osteoporosis was influenced by the cumulative dose of PSL, the mean BMD at the baseline, occurrence of disease relapse, and risedronate therapy. Conclusion Risedronate appears to be effective in preventing steroid-induced osteoporosis. It is necessary to use bisphosphonates to maintain the BMD in patients with MCNS receiving prolonged steroid therapy.

Glucocorticoid-induced osteoporosis (GIOP) is a serious complication resulting from long-term steroid treatment. In addition to several nonpharmacologic therapies recommended by the American College of Rheumatology, various pharmacologic therapies, such as calcium, vitamin D, hormone-replacement therapy, calcitonin, and bisphosphonates, can be used to prevent and/or treat GIOP. Bisphosphonates, which are potent inhibitors of bone resorption, are considered the most effective and first-line agents for increasing bone mineral density and decreasing the risk of fracture. Human parathyroid hormone has emerged as a promising agent for the treatment of severe GIOP when used alone or in combination with a bisphosphonate.

Aim: The objective of this study was to investigate the effects of bisphosphonate on the mandible of rats in the growing phase with steroid-induced osteoporosis, and to estimate the biomechanical response in the mandibular bone. Materials and methods: Eight-week-old male Wistar rats (n = 50) were assigned to a 6-week control (Co-6) group, 6-week steroid (St) group, 9-week control (Co-9) group, 9-week steroid + standard diet (StSD) group, or 9-week steroid + standard diet + bisphosphonate (StSDBp) group. The mandibular bone was evaluated by two-dimensional bone density measurement (PDS-15), three-dimensional pQCT, and quantitative analysis of Ca, P, Mg, and Zn using a sequential high frequency plasma spectrometer (ICPS-8000). Results: In PDS-15 analysis, the bone density converted to aluminum equivalent was higher in StSDBp group when compared with the StSD group, and no significant difference was observed in bone density between St group and Co-6 group. In pQCT analysis, trabecular bone density and mineral content were significantly higher, while all other bone parameters were significantly lower in St group when compared with the Co-6 group. The densities of trabecular and cortical bones, mineral content and cross-sectional area of cortical bone, and non-invasive stress strain index with reference to x and yaxes were higher in StSDBp group than in StSD group. In quantitative analyses, Ca and P were markedly higher in StSDBp group than in StSD group, while there were no differences in Mg and Zn. Conclusion: Bisphosphonate treatment increases trabecular and cortical bone parameters in the mandible of growing rats with steroid-induced osteoporosis.

In order to escape from the threat of calcium Paradox, we should fight with a two-edged sword. One is re-mobilization of the excessively mobilized Ca back to the bone though exercise, and the other Ca supplementation by providing a new source to disrupt the vicious cycle. AAACa, active absorbable algal calcium, is the most effective supplement shown to increase bone mineral density reduce fracture and to meet this requirement [7,8]. Extremely low Ca intake in Japan and other East Asian countries, 600 mg/day or less, should be doubled by effective Ca supplementation. Addition of vitamin D derivatives also helps. We have then nothing to worry about our bone health to continue a healthy and constructive life.