Glucocorticoid-Induced Osteoporosis: A Review

Glucocorticoid (GC)-induced osteoporosis is the main cause of secondary osteoporosis. Fractures, which are often asymptomatic, can occur in as many as 50% of patients receiving chronic GC therapy. GCs have direct and indirect effects on bone cells (osteoblasts, osteocytes, and osteoclasts) with a suppression of bone formation and an increased bone resorption. The management of patients exposed to GCs should include the use of the minimal effective dose of GC, general health measures, and adequate intakes of calcium and vitamin D. Bisphosphonates are nowadays largely used in GC-induced osteoporosis and teriparatide has proved its efficiency as well.     

Recognizing and treating glucocorticoid-induced osteoporosis in patients with pulmonary diseases

Glucocorticoids are frequently used to treat patients with pulmonary diseases, but continuous long-term use of glucocorticoids may lead to significant bone loss and an increased risk of fragility fractures. Patients with certain lung diseases, regardless of pharmacotherapy-particularly COPD and cystic fibrosis-and patients waiting for lung transplantation are also at increased risk of osteoporosis. Fragility fractures, especially of the hip, will have substantial effects on the health and well-being of older patients. Vertebral collapse and kyphosis secondary to glucocorticoid-induced osteoporosis (GIO) may affect lung function. Identification of patients with osteopenia, osteoporosis, or fragility fractures related to osteoporosis is strongly recommended and should lead to appropriate treatment. Prevention of GIO in patients receiving continuous oral glucocorticoids is also recommended. In patients receiving either high-dose inhaled glucocorticoids or low- to medium-dose inhaled glucocorticoids with frequent courses of oral glucocorticoids, bone mineral density measurements should be performed to screen for osteopenia and osteoporosis. A bisphosphonate (risedronate or alendronate), calcium and vitamin D supplementation, and lifestyle modifications are recommended for the prevention and treatment of GIO.     

Glucocorticoid-induced osteoporosis.

Endogenous cortisol excess and glucocorticoid (GC) treatment have a profound effect on bone metabolism, acting at many sites. The mechanism of GC action on bone turnover is complex and has not been elucidated completely. GCs increase bone resorption, inhibit bone formation and have an indirect action on bone by decreasing intestinal Ca2+ absorption, modifying vitamin D metabolism, and sustaining a marked hypercalciuria, with variable changes in plasma PTH levels; finally, GCs inhibit the gonadotropic and somatotropic axis. GC-induced osteoporosis is preventable, treatable and potentially reversible. The prevention and treatment of GC-induced osteoporosis include some general measures (as well as the use of the minimal effective dose of GC), Ca2+ and vitamin D supplementation and treatment with bone anabolic and antiresorptive agents. Recent trials suggest that bisphosphonates are an effective therapeutic tool in the treatment of GC-induced bone damage. Recent data on GC receptor-selective modulators indicate that these new molecules might induce only minimal bone loss while maintaining the typical anti-inflammatory properties of GC. Another new line of study for the prevention of GC-induced osteoporosis is the characterization of the individual's susceptibility to GC-induced bone damage.     

Oral pamidronate prevents high-dose glucocorticoid-induced lumbar spine bone loss in premenopausal connective tissue disease (mainly lupus) patients

Glucocorticoid (GC)-induced osteoporosis contributes to chronic damage in patients suffering from connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE). In this study, performed in an highly selected cohort of premenopausal female CTD (mostly lupus) patients, given high-dose GC therapy for severe disease, we show that lumbar spine bone loss can be averted by treatment with oral disodium pamidronate combined with calcium salts and vitamin D3 supplements and not by calcium salts and vitamin D3 supplements alone. We stress the need for optimal GC-induced bone loss prevention therapy in premenopausal patients, a too often neglected issue in patients whose survival has dramatically improved over the last decades.     

Glucocorticoid-induced osteoporosis: skeletal manifestations of glucocorticoid use and 2004 Japanese Society for Bone and Mineral Research-proposed guidelines for its management

Abstract

Glucocorticoid (GC) is widely used to treat a variety of inflammatory and allergic diseases, and about 0.9% of the adult population in Japan (approximately one million people) are known to take oral GC at any given time. GC causes a number of significant side effects, among which are skeletal manifestations such as osteoporosis and degenerative bone fracture, maor complications of GC therapy. Although the population of GC-induced osteoporosis patients is estimated to be approximately one-fifth of patients with primary osteoporosis, few physicians are aware of the increased risk of fracture caused of GC, and there is inadequate information concerning the effetiveness of prevention and treatment of GC-induced osteoporosis. Recently, mechanisms of GC-induced osteoporosis have been clarified, and treatment strategies have been developed. Accordingly, the 2004 Japanese Society for Bone and Mineral Research (JSBMR)-proposed guidelines for the management and treatment of GC-induced osteoporosis have been developed based on the results of a longitudinal study by subcommittee members and the results of an analysis of patients collected by the Subcommittee to Study Diagnostic Criteria for Corticosteroid-induced Osteoporosis, together with evidence obtained overseas and in Japan. The present guideline is prepared for clinical practice.     

Glucocorticoid-induced osteoporosis: skeletal manifestations of glucocorticoid use and 2004 Japanese Society for Bone and Mineral Research-proposed guidelines for its management

Glucocorticoid (GC) is widely used to treat a variety of inflammatory and allergic diseases, and about 0.9% of the adult population in Japan (approximately one million people) are known to take oral GC at any given time. GC causes a number of significant side effects, among which are skeletal manifestations such as osteoporosis and degenerative bone fracture, maor complications of GC therapy. Although the population of GC-induced osteoporosis patients is estimated to be approximately one-fifth of patients with primary osteoporosis, few physicians are aware of the increased risk of fracture caused of GC, and there is inadequate information concerning the effetiveness of prevention and treatment of GC-induced osteoporosis. Recently, mechanisms of GC-induced osteoporosis have been clarified, and treatment strategies have been developed. Accordingly, the 2004 Japanese Society for Bone and Mineral Research (JSBMR)-proposed guidelines for the management and treatment of GC-induced osteoporosis have been developed based on the results of a longitudinal study by subcommittee members and the results of an analysis of patients collected by the Subcommittee to Study Diagnostic Criteria for Corticosteroid-induced Osteoporosis, together with evidence obtained overseas and in Japan. The present guideline is prepared for clinical practice.     

Declining bone mass in men with chronic pulmonary disease: contribution of glucocorticoid treatment, body mass index, and gonadal function

BACKGROUND: Men with chronic lung disease (CLD) are at risk for osteoporosis, but the relative contributions of their chronic pulmonary disease, glucocorticoid therapy, and other factors toward loss of bone has not been established. Understanding the relative importance of these factors would assist in selecting patients for bone densitometry screening and in policy decisions regarding Medicare reimbursement. OBJECTIVE: To identify patients with CLD who are most likely to benefit from bone densitometry screening based on clinical and biochemical measures. DESIGN: Cross-sectional medical survey. PATIENTS: Patients with CLD who were treated with either oral, inhaled, or no glucocorticoid therapy. A control group without lung disease was recruited from the same clinic population. MEASUREMENTS: Dual-energy X-ray absorptiometry was obtained for each group, and the association between bone mass and clinical variables, glucocorticoid use, gonadal hormones, and biochemical markers of bone metabolism was determined. RESULTS: Osteoporosis (a T score < -2.5 at the hip or spine) was five times as likely in patients with CLD as in control subjects. Although the prevalence of osteoporosis was higher (ninefold) after chronic glucocorticoid therapy, patients with CLD who had never been treated with glucocorticoids had a substantial (fourfold) risk of osteoporosis. Chronic inhaled glucocorticoid therapy offered no protection from bone loss compared to treatment with oral glucocorticoids. Of the clinical and biochemical measures that were obtained, bone mass was weakly correlated with body mass index (BMI), serum estradiol-17beta, and N-telopeptide, but not with testosterone, alkaline phosphatase, bone-specific alkaline phosphatase, or osteocalcin. CONCLUSION: Patients with CLD should be considered for bone densitometry screening regardless of glucocorticoid use. Those patients with a low BMI and/or decreased serum estradiol-17beta comprise a subgroup with increased risk for osteoporosis.     

Advances in the management of corticosteroid-induced osteoporosis with bisphosphonates

Corticosteroids are widely used as anti-inflammatory and immunosuppressive agents to treat a variety of chronic conditions. Long-term (>1 year) corticosteroid use can lead to bone loss, and therefore, osteopenia or osteoporosis. Corticosteroid-induced osteoporosis (CIO) leads to increased bone fragility and subsequently fractures, which, in turn, lead to a loss of physical, emotional and social health for the patient and increased costs for healthcare providers. A wealth of data exists demonstrating the efficacy of the oral bisphosphonates, etidronate, alendronate and risedronate in increasing bone mineral density in patients with CIO or preventing bone loss in patients commencing corticosteroid therapy. Data regarding fracture prevention are less clear, as statistically significant reductions in the incidence of fractures have only been reported for patient subgroups or meta-analyses. However, many treatment guidelines recommend the use of oral bisphosphonates for the prevention and treatment of CIO. These guidelines are, however, not reflected in prescribing practice, and the majority of patients do not receive adequate concomitant therapy. This review summarizes the available data for bisphosphonates in CIO. Therapeutic adherence with oral bisphosphonates is an issue, with approximately 50% of patients discontinuing therapy within the first year. The primary reasons for this are poor gastrointestinal tolerability and the frequency with which complex dosing requirements must be followed. The inconvenience of taking daily or weekly bisphosphonate therapy is of particular importance in patients with CIO who may be regularly taking several other medications. Data obtained in studies with ibandronate indicate that bisphosphonate administration by rapid intravenous injection provides an effective, well-tolerated and practical alternative to current oral regimens in the management of patients with CIO.     

Correlation of different bone markers with bone density in patients with rheumatic diseases on glucocorticoid therapy

Osteoporosis is a common concomitant disease in patients with rheumatic diseases on glucocorticoid (GC) therapy. Bone status is usually evaluated by determination of bone density in combination with clinical examinations and laboratory tests. However, the strength of individual biochemical bone makers in GC-induced osteoporosis has yet to be fully clarified. For this reason, different bone markers were investigated in correlation with bone density in patients with rheumatic diseases. Approximately 238 patients (212 women, 26 men) with a rheumatic disease and under GC therapy were examined consecutively for the first time with regard to bone density (BMD) and bone markers {osteocalcin, bone-specific alkaline phosphatase (precipitation method/tandem-MP ostase), crosslinks [pyridinoline (PYD), deoxypyridinoline (DPX), N-terminal telopeptide (NTX)]}. The daily glucocorticoid dose was 10 mg prednisone equivalent (median), and the cumulative dose was 12 g prednisone equivalent (median). None of the patients had previously taken medication for osteoporosis. Osteoporosis was demonstrated in 35.3% of the patients, osteopenia in 47.5%, and a normal BMD in 17.2%. The results of tandem-MP ostase correlated with the BMD of the lumbar spine and of the femoral neck. The values for N-terminal telopeptide and pyridinoline correlated only with the bone density of the femoral neck. All results were statistically significant, although the correlation coefficients were low. After classification of the patients according to their BMD values (osteoporosis, osteopenia and normal BMD), there were significantly more patients with bone markers above the norm in the osteoporosis group and in the osteopenia group than in the group with normal bone density. All bone markers recorded behaved similarly in relation to the bone density values. The same analysis was also undertaken for the different disease groups. In these subgroups there was also a correlation between ostase/crosslinks with BMD, but the correlation coefficients were low. A general recommendation for the routine use of a specific bone marker in patients with rheumatic diseases on glucocorticoid therapy cannot be made from a cost-benefit point of view mainly because of limited predictive power (low correlation coefficients, incomplete correlation with different sites of BMD measurement).     

Should dehydroepiandrosterone replacement therapy be provided with glucocorticoids?

Adrenocorticotrophic hormone (ACTH) induces the concomitant secretion of glucocorticoids (GC) and dehydroepiandrosterone (DHEA) from the adrenal cortex. Whereas GC are catabolic, DHEA is anabolic. Long-term GC administration may result in some deleterious side-effects, such as muscular weakness, atrophy and necrosis, diabetes, fattiness, osteopenia, osteoporosis and avascular necrosis and susceptibility to infections. DHEA ameliorates some deleterious effects of GC, such as diabetes, amino acid deamination, fattiness, hypertension and susceptibility to viraemia. By its anabolic effects in muscles, bones and endothelium, DHEA may diminish the severity of GC-induced myopathy, osteopenia, osteoporosis and avascular necrosis. The natural concomitant secretion of DHEA with GC probably enables the latter to protect the body from ill-effects of stress without exerting their deleterious potency. DHEA secretion diminishes during aging and severe or chronic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Anti-inflammatory and immunosuppressive effects of GC and androgens, including DHEA, are now well established. On the other hand, administration of GC inhibits ACTH secretion, involutes the adrenal cortex and results in further DHEA deficiency, particularly harmful in chronic autoimmune diseases (i.e. RA, SLE). Therefore, the deleterious side-effects of chronic administration of GC emerges from both their direct catabolic activity and the suppression of DHEA production. Whereas, in males, most androgens come from the testes, in females, under GC supplementation, DHEA deficiency leads to nullification of the androgen-dependent anabolism, leaving them exposed to the GC-catabolic effects to a larger extent. The viewpoint presented here claims that under chronic GC supplementation, DHEA replacement therapy may reduce damage caused by GC administration.     

Glucocorticoid-induced osteoporosis and rheumatic diseases. Pathogenesis, prevention and treatment

Glucocorticoids (GC) are diffusely used to treat a wide variety of inflammatory and autoimmune disorders, including rheumatic diseases. GC-induced osteoporosis (GIO) is the most common and serious side-effect for patients receiving GC. Loss of bone mineral density (BMD) is greatest in the first few months of GC use; fracture (Fx) risk is significantly increased at the spine and hip on doses even as low as 2.5 mg of prednisolone daily; Fx risk increases rapidly from the onset of therapy and, for a given BMD, is higher in GIO than in postmenopausal OP. General measures to reduce bone loss include use of the lowest effective dose; consideration of alternative routes of administration; adequate calcium and vitamin D supplementation. Today, results from large randomised controlled clinical trials provide evidence that bone loss and Fx may be prevented through the use of bone sparing agents (hormone therapy, bisphosphonates, PTH 1-34). Bisphosphonates (alendronate, risedronate) are first-choice therapy for the prevention and treatment of GIO; patients at high risk for Fx, for example those in post-menopausal status or aged > or =65 years and those with a prior fragility Fx, should be advised to start bone-protective therapy at the time of starting GC. Due to the prevalence of GC use, it is imperative that there be a greater awareness of GIO and of therapies that may be offered to patients both for prevention and treatment.     

Asthma and chronic obstructive airway diseases are associated with osteoporosis and fractures: A literature review

The objective was to assess the association between asthma and/or chronic obstructive airway diseases (COAD), and osteoporosis, and appraise treatments of osteoporosis in these patients. MEDLINE and Excerpta Medica were searched for original research with control groups which tested the above association. One cohort and nine cross-section studies of bone density in patients with asthma and/or COAD were retrieved. These demonstrated clinically important bone density reductions of up to 29% in subjects, dependent upon daily oral corticosteroids, by a variety of measurement techniques, at various bone sites. Bone density reduction has also been less consistently reported in the absence of oral corticosteroids, suggesting that other factors including high-dose inhaled corticosteroids may have a role. Fracture studies. Three studies in oral corticosteroid-dependent asthmatics demonstrated a vertebral fracture prevalence up to 56%, and annual vertebral fracture incidence of up to 42%. The strength of the available evidence is limited, but suggests that patients with asthma and/or COAD are at increased risk of osteoporosis. The evidence of the association between osteoporosis and inhaled corticosteroids is much more limited than for oral corticosteroids. Bisphosphonates are promising agents to maintain and/or promote bone mass in this patient group.     

Inhaled insulin in patients with asthma and chronic obstructive pulmonary disease

The effect of inhaled insulin in subjects with diabetes and chronic lung disease, such as asthma or chronic obstructive pulmonary disease (COPD), is of particular interest because these diseases are quite common, and it is likely that patients with asthma or COPD who are poorly controlled on oral agents and are reluctant to start subcutaneous insulin would benefit from inhaled insulin to improve their glucose control. Since patients with asthma or COPD have varied pulmonary symptoms and abnormal pulmonary function, it is important to establish the pulmonary safety and efficacy of inhaled insulin in subjects with diabetes and asthma or COPD. Pharmacokinetic and pharmacodynamic studies in non-diabetic subjects with asthma consistently show lower absorption of inhaled insulin and lesser glucose lowering effects by approximately 30-40%, as compared to subjects without asthma. Thus, it would be expected that the dose of insulin required to obtain equivalent glycemic control would be higher by approximately 30-40% in subjects with asthma and diabetes (as compared to subjects without asthma but with diabetes). However, prior administration of a bronchodilator inhaler in individuals with asthma and diabetes reverses airway obstruction and thus may obviate the need for increased insulin requirements. In contrast to patients with asthma, in patients with COPD and diabetes, the absorption of inhaled insulin appears to be variable (higher or lower than in non-COPD subjects). Whether this variability is secondary to differences in inhalation devices or different study populations is not clear at present. Overall, data from the clinical studies indicate that inhaled insulin is effective and well tolerated in subjects with diabetes and chronic lung disease. However, preliminary, limited data from the longer-term clinical studies suggest that there is a marginally greater decline in pulmonary function tests in subjects with asthma/COPD and diabetes compared to subjects with diabetes and no chronic lung disease. Thus, there is a clear need for longer-term studies in subjects with diabetes and chronic lung disease in order to further clarify the safety and efficacy of inhaled insulin in this population.     

Osteoporosis in chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of osteoporosis because of their age, limited physical activity, low body mass index, smoking, hypogonadism, malnutrition, and use of corticosteroids. Systemic inflammation represents an additional pathomechanism contributing to the development of osteoporosis in COPD patients. Males in their mid to late 60s with a smoking history of greater than 60 pack-years have a prevalence rate of vertebral fractures similar to, and possibly greater than, postmenopausal women greater than or equal to 65 years old: in patients with severe COPD, up to 50-70% have osteoporosis or osteopenia, and up to 24-30% have compression vertebral fractures. Correlates of osteoporosis in COPD are mainly measures of body composition, disease severity and the use of corticosteroids, although causality has not been proven. Systemic corticosteroids remain the most common cause of drug-related osteoporosis, and a meta-analysis concluded that the use of more than 6.25 mg prednisone daily led to decreased bone mineral density (BMD) and increased fracture risk. In contrast, the effects of the long-term use of inhaled corticosteroids on BMD remain debatable. Effects of treatment of osteoporosis have not been investigated in samples consisting of COPD patients only but the recommendations follow the general recommendations for the diagnosis and treatment of osteoporosis. Early recognition of BMD loss is essential, and assumes close interdisciplinary cooperation between respirologists and reumatologists. Longitudinal follow-up to assess determinants of osteoporosis in COPD and randomised placebo-controlled trials on the effects of treatment of osteoporosis in patients with COPD only are warranted. In the future, novel therapeutical strategies such as monoclonal antibodies against osteoclasts activators may prove their beneficial effects in the treatment of COPD-related osteoporosis.     

Use of inhaled and oral glucocorticoids, severity of inflammatory disease and risk of hip/femur fracture: a population-based case-control study

BACKGROUND: Patients using higher dosages of inhaled or oral glucocorticoids (GCs) have an increased risk of hip/femur fractures. The role of the underlying disease in the aetiology of this increased risk has not been widely studied. OBJECTIVE: To evaluate the contribution of the underlying disease to the risk of hip/femur fracture in patients using inhaled or oral GCs. DESIGN AND SUBJECTS: A case-control study within the Dutch PHARMO-RLS database was conducted. Cases (n = 6763) were adult patients with a first hip/femur fracture during enrolment. Each case was matched to four controls by age, gender and region. RESULTS: The risk of hip/femur fracture increased with current use of inhaled GCs (crude OR 1.30, 95% CI:1.16-1.47) and with current use of oral GCs (crude OR 1.66, 95% CI: 1.46-1.90). After adjustment for disease severity, the risk of hip/femur fracture was no longer statistically significantly increased in inhaled GC users (adjusted OR 1.08, 95% CI: 0.91-1.27), whilst it remained elevated in oral GC users (adjusted OR 1.43, 95% CI: 1.22-1.67). Patients using inhaled GCs without any exposure to oral GCs had no increased risk of fracture (adjusted OR 0.98, 95% CI: 0.79-1.22). CONCLUSION: Inhaled GC users had no increased risk of femur/hip fracture after adjustment for underlying disease severity. Our data suggest that, even at higher dosages, inhaled GC use is not an independent risk factor for fracture. In contrast, oral GC use was associated with an increased risk of fracture, which was not fully explained by the underlying disease severity.     

Factors influencing the responsiveness to inhaled glucocorticoids of patients with moderate-to-severe asthma

STUDY OBJECTIVES: Inhaled glucocorticoids (GCs) are the most effective control therapy for asthma. Although the clinical effects of inhaled GCs vary, there are few data on the differences in the responsiveness of individuals to inhaled GCs. The purpose of this study was to identify those factors that are associated with responsiveness to high-dose inhaled GCs in patients with moderate-to-severe asthma. DESIGN: This study was a prospective analysis. SETTING: Outpatient clinics of tertiary hospitals. PATIENTS: Eighty-six adult outpatients with moderate-to-severe asthma. METHODS: Eighty-six patients with asthma who had initial FEV1 values of < 80% predicted after they had received inhaled GCs (fluticasone propionate, 1,000 microg/d) for 4 weeks. The primary end points were FEV1, FEV1/FVC ratio, forced expiratory flow (midexpiratory phase), and the score at presentation in the asthma-related quality-of-life questionnaire (AQLQ). RESULTS: The inhalation of GCs for 4 weeks had significant improvements in the FEV1% predicted and in the AQLQ score compared with the baseline values. Asthmatic patients with responses of > 12% (n = 46, 53.4%) in the change in FEV1 (deltaFEV1 = [FEV1 at 4 weeks--baseline FEV1]/baseline FEV1 x 100) also had significantly higher proportions of blood eosinophils and lower FEV1 values (in liters) prior to treatment. The change in FEV1 values correlated with the number of sputum eosinophils prior to GC inhalation (r = 0.242; p < 0.05) and correlated inversely with the FEV1 percent predicted values prior to GC inhalation (r = -0.462; p < 0.001). CONCLUSION: The FEV1 percent predicted and the blood and sputum eosinophil levels prior to GC inhalation are associated with the responsiveness to inhaled GCs in patients with moderate-to-severe asthma.     

Glucocorticoid treatment and osteoporosis in children

Glucocorticoid (GC) -induced osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone, leading to increased fragility and susceptibility to fracture due to GC excess. The main mechanisms of GC-induced osteoporosis are a decreased bone formation and increased bone absorption. Although diagnosis criteria and recommendations for the prevention and treatment of GC-induced osteoporosis are established in adults, there are no criteria and recommendation for children. Bisphosphonate, the most effective drug for the treatment of GC-induced osteoporosis in adults, is not approved for the treatment of GC-induced osteoporosis in children. And there in no available data that GC-induced osteoporosis would affect the peak bone mass and senile osteoporosis or not. Diagnosis criteria and recommendations for the prevention and treatment of GC-induced osteoporosis should be established in children.     

Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy

OBJECTIVE: To evaluate predictors of vertebral fractures, including a threshold for bone mineral density (BMD), in patients receiving oral glucocorticoids (GCs). METHODS: Data were obtained from 2 randomized clinical trials (prevention and treatment trials of risedronate) using similar methods, but different inclusion criteria were applied with regard to prior exposure to GCs. Predictors of vertebral fracture in the placebo group were identified using Cox regression with forward selection. The BMD threshold analysis involved a comparison of the 1-year fracture risk in postmenopausal women receiving placebo in the GC trials with that in postmenopausal women not taking GCs in 3 other trials. RESULTS: The study population comprised 306 patients with baseline and 1-year followup data on vertebral fractures (111 receiving placebo and 195 receiving risedronate). In the placebo group, the statistically significant predictors of incident fracture were the baseline lumbar spine BMD (for each 1-point decrease in T score, relative risk [RR] 1.85, 95% confidence interval [95% CI] 1.06-3.21) and the daily GC dose (for each 10-mg dose increase, RR 1.62, 95% CI 1.11-2.36). In the BMD threshold analysis, compared with nonusers of GCs, patients receiving GCs were younger, had a higher BMD at baseline, and had fewer prevalent fractures; nevertheless, the risk of fracture was higher in the GC users compared with nonusers (adjusted RR 5.67, 95% CI 2.57-12.54). The increased risk of fracture was observed in GC users regardless of whether osteoporosis was present. CONCLUSION: The daily, but not cumulative, GC dose was found to be a strong predictor of vertebral fracture in patients receiving GCs. At similar levels of BMD, postmenopausal women taking GCs, as compared with nonusers of GCs, had considerably higher risks of fracture.     

Glucocorticoid-induced osteoporosis

Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Glucocorticoids cause a rapid bone loss in the first few months of use, but the most important effect of the drug is suppression of bone formation. The administration of oral glucocorticoid is associated with an increased risk of fractures at the spine and hip. The risk is related to the dose, but even small doses can increase the risk. Patients on glucocorticoid therapy lose more trabecular than cortical bone and the fractures are more frequent at the spine than at the hip. Calcium, vitamin D and activated forms of vitamin D can prevent bone loss and antiresorptive agents are effective for prevention and treatment of bone loss and to decrease fracture risk. Despite the known effects of glucocorticoids on bone, only a few patients are advised to take preventive measures and treat glucocorticoid-induced osteoporosis.     

Risk factors for osteoporosis in inflammatory bowel disease patients

Inflammatory bowel disease (IBD) patients exhibit higher risk for bone loss than the general population. The chronic inflammation causes a reduction in bone mineral density (BMD), which leads to osteopenia and osteoporosis. This article reviewed each risk factor for osteoporosis in IBD patients. Inflammation is one of the factors that contribute to osteoporosis in IBD patients, and the main system that is involved in bone loss is likely RANK/RANKL/osteoprotegerin. Smoking is a risk factor for bone loss and fractures, and many mechanisms have been proposed to explain this loss. Body composition also interferes in bone metabolism and increasing muscle mass may positively affect BMD. IBD patients frequently use corticosteroids, which stimulates osteoclastogenesis. IBD patients are also associated with vitamin D deficiency, which contributes to bone loss. However, infliximab therapy is associated with improvements in bone metabolism, but it is not clear whether the effects are because of inflammation improvement or infliximab use. Ulcerative colitis patients with proctocolectomy and ileal pouches and Crohn’s disease patients with ostomy are also at risk for bone loss, and these patients should be closely monitored.