Chronic Glucocorticoid Use Research Articles

Novel role for receptor dimerization in post-translational processing and turnover of the GR\u03b1

Glucocorticoids (GCs), acting via the glucocorticoid receptor (GRα), remain the mainstay therapeutic choice for the treatment of inflammation. However, chronic GC use, aside from generating undesirable side-effects, results in GRα down-regulation, often coupled to a decrease in GC-responsiveness, which may culminate in acquired GC resistance. The current study presents evidence for a novel role of the dimerization state of the GRα in mediating GC-mediated GRα turnover. Through comparing the effects of dimerization promoting GCs on down-regulation of a transfected human wild type GRα (hGRwt) or a dimerization deficient GRα mutant (hGRdim), we established that a loss of receptor dimerization restricts GRα turnover, which was supported by the use of the dimerization abrogating Compound A (CpdA), in cells containing endogenous GRα. Moreover, we showed that the dimerization state of the GRα influenced the post-translational processing of the receptor, specifically hyper-phosphorylation at Ser404, which influenced the interaction of GRα with the E3 ligase, FBXW7α, thus hampering receptor turnover via the proteasome. Lastly, the restorative effects of CpdA on the GRα pool, in the presence of Dex, were demonstrated in a combinatorial treatment protocol. These results expand our understanding of factors that contribute to GC-resistance and may be exploited clinically.

Increased risk of symptomatic progression of instability following decompression for lumbar canal stenosis in patients receiving chronic glucocorticoids therapy

BackgroundLumbar decompression surgery is a commonly used treatment for degenerative lumbar spinal stenosis; however, some patients develop symptomatic spinal instability following decompression surgery. The objective of this study was to reveal risk factors for delayed instability following decompression surgery for lumbar spinal stenosis. MethodsOne hundred ten patients who underwent single-level lumbar decompression between 2008 and 2014 were retrospectively reviewed. Surgical indication for decompression surgery was symptomatic lumbar canal stenosis without spondylolisthesis or with minimum spondylolisthesis (less than 4 mm translation). Patients with gross segmental motion (>10° in disc angle, >2 mm translation) on flexion-extension lumbar radiographs were excluded. Age, sex, body mass index, smoking history, diabetes mellitus, autoimmune connective tissue diseases including rheumatoid arthritis, and the use of glucocorticoids were investigated. Radiographic measurements included disc angle, disc height, slippage, facet angle, segmental motion (flexion-extension), lumbar alignment, facet effusion, and disc degeneration. Data were analyzed using multivariate forward selection stepwise logistic regression, chi-square tests, and Student t-test. ResultsSix of 110 patients (5.5%) developed symptomatic spinal instability at the operative level and underwent spinal fusion surgery at an average of 2.1 years postoperatively. Autoimmune connective tissue disorders and chronic use of glucocorticoids were associated with the occurrence of symptomatic spinal instability requiring spine fusion surgery, while there was no significant difference in radiographic parameters and demographic factors excluding autoimmune connective tissue diseases between reoperation and non-reoperation groups. ConclusionsPatients with autoimmune connective tissue disorders receiving chronic glucocorticoid therapy are more likely to develop symptomatic spinal instability following decompression surgery for lumbar canal stenosis without or with minimal spondylolisthesis.

Risk factors for early infection following hemiarthroplasty in elderly patients with a femoral neck fracture.

Periprosthetic joint infections (PJI) after hemiarthroplasty for geriatric femoral neck fractures are a devastating complication that results in serious morbidity and increased mortality. Identifying risk factors associated with early infection after HA for hip fractures may offer an opportunity to address and prevent this complication in many patients. The aim of this study was to evaluate preoperative risk factors for early PJI after HA in hip fracture patients. From January 2010 to December 2015, 312 femoral neck fractures (AO/OTA 31-B) in 305 patients were included in this single-center, retrospective study. PJI was defined according to the Centers for Disease Control (CDC) definition of deep incisional surgical site infection. Early infection referred to a postoperative period of 4 weeks. Binary univariable and multivariable regression analysis with backward elimination was applied to identify predictors of PJI. Median age of all patients was 83.0 (IQR 76-89)years. We identified 16 (5.1%) early PJI which all required surgical revision. Median length of in-hospital stay (LOS) was 20.0 (IQR 10-36)days after PJI compared to 10.0 (8-15)days without deep wound infection. In-hospital mortality was 30.8 vs. 6.6%, respectively. Preoperative CRP levels (OR 1.009; 95% CI 1.002-1.018; p = 0.044), higher BMI (OR 1.092; 95% CI 1.002-1.189; p = 0.044) and prolonged surgery time (OR 1.013; 95% CI 1.000-1.025; p = 0.041) were independent risk factors for PJI. Excluding infection following major revision due to mechanical complications identified preoperative CRP levels (OR 1.012; 95% CI 1.003-1.021; p = 0.007) and chronic glucocorticoid therapy (OR 6.314; 95% CI 1.223-32.587; p = 0.028) as risk factors, a clear trend was seen for higher BMI (OR 1.114; 95% CI 1.000-1.242; p = 0.051). A cut-off value at CRP levels ≥ 14mg/l demonstrated a sensitivity of 69% and a specificity of 70% with a fair accuracy (AUC 0.707). Preoperative serum CRP levels, higher BMI and prolonged surgery time are independent predictors of early PJI. Excluding PJI secondary to major revision surgery revealed chronic glucocorticoid use as a risk factor apart from preoperative CRP levels.

Can we manage lupus nephritis without chronic corticosteroids administration?

The outcome of lupus nephritis (LN) has changed since the introduction of glucocorticoids (GCs), which dramatically reduced the mortality related to one of the most severe complications of systemic lupus erythematosus (SLE). Since the 1950's, other immunosuppressants, including biologic drugs (i.e. rituximab) have aided in maintaining remission, preserving kidney function, but not preventing treatment-related toxicity. GCs still remain the cornerstone in the treatment of SLE, including LN, and they are widely used in clinical practice. However, GC administration represents a double-edged sword. Indeed, from one side they allow a fast and effective control of disease activity by dampening inflammation; from the other side, they have many and severe side effects leading to organ damage. In this paper, we will discuss pros and cons of the chronic use of GCs, especially focusing on LN.

Increased prevalence of fracture and hypoglycaemia in young adults with concomitant type 1 diabetes mellitus and coeliac disease.

Both Type 1 diabetes mellitus (T1DM) and coeliac disease (CD) are independently associated with reduced bone mineral density (BMD) and increased fracture risk. Whilst poorer glycaemic control and increased microvascular complications have been described, the literature examining bone health and fractures in adults with concomitant T1DM and CD (T1DM+CD) is limited. To evaluate fracture prevalence and explore associations with glycaemic control, hypoglycaemia and microvascular disease in T1DM+CD compared with T1DM alone. We conducted a retrospective cross-sectional study of young adults with T1DM, who attended diabetes clinics at a large tertiary referral centre between August 2016 and February 2017. Clinical information, radiological and biochemistry results were extracted from medical records. Patients with comorbid chronic kidney disease, glucocorticoid use, hypogonadism and untreated hyperthyroidism were excluded. A total of 346 patients with T1DM alone (median age 23years) and 49 patients with T1DM+CD (median age 24years) were included. Median age, gender distribution, BMI, haemoglobin A1c, daily insulin dose and serum 25-hydroxyvitamin D levels were similar between groups. Higher adjusted fracture risk was observed in T1DM+CD compared with T1DM (12.2% vs 3.5%; OR 3.50, 95% CI 1.01-12.12, P=.01), yet BMD was only measured in 6% of patients. The adjusted risk of hypoglycaemia ≥2/week was greater for T1DM+CD (55% vs 38%, OR 3.28, 95% CI 1.61-6.69, P=.001); however, this was not independently associated with fractures. Replete vitamin D (≥ 50nmol/L) was associated with less hypoglycaemia (OR 0.48, 95% CI 0.29-0.80; P=.005), but not with fractures. Coeliac disease status was independently associated with increased fracture prevalence in young adults with T1DM. Recurrent hypoglycaemia was also increased in T1DM+CD, although hypoglycaemia was not independently associated with fractures. Prospective studies are required to determine the long-term impacts of CD on bone health and glycaemic control in patients with T1DM.

Recovery of steroid induced adrenal insufficiency.

Secondary adrenal insufficiency can result from insufficient stimulation of the adrenal glands due to inadequate secretion or synthesis of adrenocorticotropic hormone (ACTH). This can be caused by hypopituitarism, central nervous system injury (tumors, radiation, and surgery) or long-term glucocorticoid therapy. Glucocorticoids were introduced in the 1950s, and have been used for their anti-inflammatory and other pharmacological effects, and also as replacement therapy for adrenal insufficiency. However, chronic glucocorticoid use may lead to suppression of the hypothalamic pituitary adrenal axis through negative feedback. This may lead to secondary adrenal insufficiency. Typically, the hypothalamic pituitary adrenal axis recovers after cessation of glucocorticoids, but the timing of recovery can be variable and can take anywhere from 6-12 months. Understanding the effect of exogenous glucocorticoids on the hypothalamic pituitary adrenal axis, recovery of the axis, and tests used to assess the recovery, are crucial to avoid prescribing unnecessary steroid replacement or missing a critical diagnosis with detrimental consequences.

To study the bone mineral density and vitamin D in patients suffering from rheumatoid arthritis irrespective of duration in comparison to age and sex-matched controls who were not having any musculoskeletal disorder

Background: Rheumatoid arthritis is a chronic inflammatory disease of synovial tissue of joints of unknown etiology marked by a symmetric, peripheral, polyarthritis. Osteoporosis is a progressive systemic skeletal disease characterised by reduced bone mass/density and micro-architectural deterioration of bone tissue. Osteoporosis is more common in patients with rheumatoid arthritis than an age and sex-matched population. Chronic use of glucocorticoids and disability-related immobility also contributes to osteoporosis.Methods: The present study was conducted at Department of Medicine, Dr. S. N. Medical College, Jodhpur, India. Case control study was conducted to determine bone mineral densities (BMD) and vitamin D levels among patients with rheumatoid arthritis attending the medicine OPD and IPD, Dr. S. N. Medical College, Jodhpur, Rajasthan, India. 25 patients with rheumatoid arthritis and 25 age and sex-matched controls were studied. All known cases of Rheumatoid Arthritis attending Medicine outdoor and patients who are admitted indoor. Patients with co-morbidities like diabetes mellitus, coronary artery disease, hypertension, chronic kidney disease and pre-existing osteoporosis.Results: Mean age of the study population was 49.68±8.4 yrs; most of the subjects were females. Vitamin D levels were found to be comparatively lower in females. Vitamin D deficiency was more prevalent of in urban population. As the age increased the levels of vitamin D and BMD decreased. Inadequacy in vitamin D levels was more prevalent in Rheumatoid arthritis patients, 74.99% females had low BMD values. Correlation of low BMD with RA was statistically significant. The duration of Rheumatoid arthritis was related to vitamin D levels significantly (p<0.013). The longer the duration of disease more number of RA patients had vitamin D deficiency. All patients with RA for more than 4 years had osteoporosis. The duration of Rheumatoid arthritis was related to low BMD significantly (p<0.025). The correlation of HAQ (health assessment questionnaire) with BMD is statistically significant; the correlation of DAS score with RA duration is statistically significant. The correlation of DAS score with BMD is statistically significant. The lesser the BMD more number of RA patients had moderate or severe scores.Conclusions: Vitamin D levels were found to be comparatively lower in females especially in urban areas. Vitamin D deficiency and low BMD is more prevalent in Patients of rheumatoid arthritis in comparison to controls. High index of suspicion is required during follow-up of rheumatoid arthritis patients.

Long-term prognosis of hematogenous vertebral osteomyelitis: Mortality, quality of life, and pain.

Hematogenous vertebral osteomyelitis (HVO) has a generally favorable prognosis if appropriate treatment is initiated in its early phase; however, some intractable cases with HVO can develop neurological impairment as well as spinal deformity during the course of treatment and these sequelae may lead to impaired quality of life (QOL). In this study, we aimed to evaluate the long-term relapse rate, mortality, and QOL of patients with HVO. In this retrospective case series study, medical records of 60 patients with HVO with a mean follow-up period of 8 years (5-23 years) were reviewed to assess demographic data, details of infection, and clinical course. Mortality rate was assessed using a Kaplan-Meier plot. QOL was measured using the EuroQol 5 Dimension (EQ-5D) questionnaire and residual pain using a numeric rating scale (NRS). HVO relapsed in 4 of 60 patients (7%). Overall 5-year survival rate in 60 patients with HVO was 85%. The factors associated with increased mortality were malignant tumor, diabetes mellitus, chronic use of glucocorticoids, and drug-resistant strains of staphylococcus. Female-to-male ratio, NRS, prevalence of neurological impairment were significantly higher in patients with low EQ-5D score (poor health) compared to those with high EQ-5D score (good health). Patients with HVO have shorter life expectancy if they have malignancy, diabetes mellitus, chronic use of glucocorticoids, and a history of drug-resistant strains of staphylococcus infection. Female gender, residual neurological defects and persistent back pain are associated with impaired QOL in patients with HVO.

Assessment of risk and use of prophylaxis for glucocorticoidinduced-osteoporosis among dermatologists in the Pacific Northwest: a survey study

Exposure to even physiologic doses of glucocorticoids can reduce one's bone mass and increase risk for osteoporotic fracture. There currently exists a wide variation in clinician approach to the assessment and management of glucocorticoid-induced osteoporosis (GIO). Our objectives were to characterize Pacific Northwest dermatology providers' general practices, assessment of risk for GIO, and preferred GIO prophylaxis measures by way of survey. To identify whether knowledge deficits exist with respect to preventing and managing GIO in dermatology patients. A self-administered, 22-question survey was sent electronically to respondent population. Surveyed population composed of 392 dermatology providers of the Washington State Dermatology Association and Oregon Dermatology Society registries. Survey responses were collected anonymously via Catalyst WebQ. Respondents over-estimated fracture risk and reported they would prescribe antiresorptive medications at a less-than-adequate rate. When given clinical scenarios and asked to assess risk of major osteoporotic fracture, respondents frequently overestimated risk compared to that estimated by the FRAX tool (67%-71%). When asked directly if one would prescribe bisphosphonates as GIO prophylaxis for a high-risk patient, only 49% responded always/almost always. This study suggests that a knowledge deficit exists within dermatology with respect to prevention and screening of GIO. The resultant practice gap is likely contributing to morbidity and mortality for dermatology patients requiring chronic glucocorticoid use for dermatologic disorders. Provider variability in practices suggests that dermatology could benefit from additional education in assessment and treatment of GIO, as well as a clear set of guidelines for GIO management.

Recovery of Adrenal Function in Patients with Glucocorticoids Induced Secondary Adrenal Insufficiency.

BackgroundThe chronic use of glucocorticoids (GC) suppresses function of the hypothalamic-pituitary-adrenal axis and often results in secondary adrenal insufficiency (AI). The present study aimed to determine the recovery rate of adrenal function in patients with secondary AI within 1 to 2 years and to assess the factors predictive of adrenal function recovery.MethodsThis was a retrospective observational study that enrolled patients diagnosed with GC-induced secondary AI between 2007 and 2013. AI was defined by peak serum cortisol levels <18 µg/dL during a standard-dose short synacthen test (SST). A follow-up SST was performed after 1 to 2 years, and responders were defined as those with adrenocorticotropic hormone (ACTH)-stimulated peak serum cortisol levels ≥18 µg/dL.ResultsOf the total 34 patients diagnosed with GC-induced secondary AI at first, 20 patients (58.8%) recovered normal adrenal function by the time of the follow-up SST (median follow-up period, 16.5 months). Although the baseline serum ACTH and cortisol levels at the first SST did not differ between responders and non-responders, the incremental cortisol response during the first SST was higher in responders than that of non-responders (7.88 vs. 3.56, P<0.01). Additionally, higher cortisol increments during the first SST were an independent predictive factor of the adrenal function recovery (odds ratio, 1.58; 95% confidence interval, 1.02 to 2.46; P<0.05).ConclusionIn the present study, adrenal function recovery was achieved frequently in patients with GC-induced secondary AI within 1 to 2 years. Additionally, an incremental cortisol response at the first SST may be an important predictive factor of adrenal function recovery.

Glucocorticoid-induced osteoporosis management among seniors, by year, sex, and indication, 1996-2012.

We identified that glucocorticoid-induced osteoporosis management (bone mineral density testing or osteoporosis treatment) among seniors improved among men (2 to 23 %) and women (10 to 48 %) between 1996 and 2007, and then remained relatively stable through to 2012. Differences were also noted by indication (from a low of 21 % for respiratory conditions to a high of 41 % for rheumatic conditions). The aim of our study was to describe the proportion of chronic oral glucocorticoid (GC) users that receive osteoporosis management (bone mineral density test or osteoporosis treatment) by sex and over time. We identified community-dwelling older adults initiating chronic oral GC therapy in Ontario using pharmacy data from 1996 to 2012. Chronic GC use was defined as greater than or equal to two oral GC prescriptions dispensed and ≥450 mg prednisone equivalent over a 6-month period. Osteoporosis management within 6 months of starting chronic GC therapy was examined by sex, year, indication for therapy, and osteoporosis management history. Results were summarized using descriptive statistics. We identified 72,099 men and 95,975 women starting chronic oral GC therapy (mean age = 74.9 years, SD = 6.5). Approximately two thirds of patients (65 %) received ≥900 mg within the 6-month chronic use window. GC-induced osteoporosis management increased from 2 to 23 % (men) and 10 to 48 % (women) between 1996 and 2007, and then remained relatively stable through to 2012. A higher proportion of patients with prior osteoporosis management were managed within 6 months (56 % men, 67 % women) of chronic GC use, compared to patients without prior management (12 % men, 23 % women). Patients with rheumatic disease were managed most commonly (41 %), and patients with respiratory conditions were managed least commonly (21 %). GC-induced osteoporosis management improved significantly over time for both sexes yet remains low. Significant care gaps by sex and between clinical areas represent a missed opportunity for fracture prevention among patients requiring chronic GC therapy.

Complementary effect of oral administration of Lactobacillus paracasei K71 on canine atopic dermatitis.

Atopic dermatitis is a common skin disease encountered in dogs. Glucocorticoids are commonly recommended for symptomatic therapy and well-tolerated adjunctive therapies may help to reduce the necessary dose and associated risks of chronic glucocorticoid use. The purpose of this study was to evaluate the complementary efficacy of oral administration of Lactobacillus paracasei K71 in canine atopic dermatitis (cAD). Forty one dogs with mild to moderate cAD were recruited by19 animal hospitals. Dogs were assigned to receive either the investigational agent (K71 group; n = 20) or cetirizine hydrochloride (control group; n = 21). Previously prescribed medications were allowed to be continued during the 12 week trial. Dogs were assessed by the investigators using the cAD Extent and Severity Index (CADESI) and a medication scoring system. Pet owners assessed their dogs using a visual analog scale (VAS) and pruritus scores. The CADESI scores, VAS and pruritus scores in both groups at 12 weeks were improved compared with their baselines. The CADESI and pruritus scores in the K71 group were slightly lower than those in the control group and the reduction of medication scores in the K71 group was significantly lower compared with the control group (P < 0.05; Student's t-test). Oral administration of K71 can be useful in dogs with cAD as a complementary therapy, by providing a steroid-sparing effect.

Prospective multicenter study evaluating adrenal suppression after dexamethasone therapy as an antiemetic in cancer patients: a KSWOG (Korean South West Oncology Group) study.

9605 Background: Dexamethasone has a high therapeutic index for the prevention of chemotherapy-induced nausea and vomiting; however, the chronic use of high-dose glucocorticoids is associated with ...

Fracture rate associated with quality metric-based anti-osteoporosis treatment in glucocorticoid-induced osteoporosis

Anti-osteoporosis medication (AOM) use in patients exposed to glucocorticoids is thought to reduce fractures. We found post-menopausal women using glucocorticoids for at least 90 days who also used an AOM within 90 days had 48 % fewer fractures by 1 year and 32 % fewer fractures by 3 years compared to non-AOM users. The purpose of this study is to explore the effectiveness of adherence to quality measures by estimating the effect of anti-osteoporosis medication (AOM) initiation within 90 days after chronic (≥90 days) glucocorticoid (GC) therapy on osteoporotic fracture. A new-user cohort was assembled using the MarketScan databases between 2000 and 2012. Included patients were female, age ≥50 at GC initiation, had a first GC fill daily dose ≥10 mg and persisted for at least 90 days. During a 365-day baseline period, patients were excluded for prior GC or AOM (bisphosphonate, denosumab, teriparatide) use, fracture, or cancer diagnosis. Initiators of an AOM in the 14 days pre- or 90 days post-GC fill were characterized as AOM users; those without, AOM non-users. Follow-up began 91 days after GC fill with patients followed until fracture, loss of continuous enrollment, initiation of AOM by AOM non-users, or end of study period. A propensity score was estimated for AOM receipt using all measured covariates and converted to a stabilized inverse probability of treatment weights (IPTW). Weighted hazard ratios (HR) and associated 95% confidence intervals (95% CI) were estimated using weighted Cox proportional hazard models. Of the 7885 women eligible for the study, 12.1% were AOM users. AOM use was associated with lower fracture incidence: weighted HR of 0.52 (95% CI 0.29, 0.94) at 1 year and weighted HR of 0.68 (95% CI 0.47, 0.99) at 3 years. AOM initiation within 90 days of chronic GC use was associated with a fracture reduction of 48% at 1 year and 32% at 3 years.

Glucocorticoids in systemic sclerosis: patients’ beliefs and treatment adherence

Objectives: To investigate how chronic intake of glucocorticoids (GCs) is perceived by patients with systemic sclerosis (SSc) in terms of necessity and concerns, and whether such beliefs influence treatment adherence.Method: Ninety-eight consecutive SSc patients who they had been taking oral GCs for > 3 months prior to the study were enrolled. All patients underwent a clinical evaluation and laboratory investigations, and were asked to complete four self-administered questionnaires: the Beliefs about Medicines Questionnaire (Specific-BMQ), the four-item Morisky Medication Adherence Scale (MMAS-4), the 36-item Short Form Health Survey (SF-36), and the Health Assessment Questionnaire Disability Index (HAQ-DI). Moreover, patients answered two additional questions investigating their knowledge about GC-related adverse events (AEs).Results: Seventy-seven patients (83.6%) believed in the necessity of GCs for maintaining health but 72.8% also reported concerns about potential AEs to GCs. A high adherence rate was recorded in 64.1% of patients. Only about 20% of patients reported knowing that a daily GC dose and treatment duration influence the burden of GC-related AEs. Patients who believed that GC-related AEs were influenced by the dose scored lower concerns (p = 0.043) and were more frequently labelled as accepting (perceiving high necessity and low concerns) (p = 0.009).Conclusions: The majority of patients taking GCs perceived them as necessary, but high concerns about chronic GC use exist. Patients with a poorer knowledge of the factors associated with GC-related AEs and those with a poorer quality of life were the most worried about these compounds. Experimental studies assessing the efficacy of educational programmes aiming to increase the adherence to GC therapy should be planned in these patients.

Chronic Glucocorticoid Use in Multi-Organ Donors May Be a Risk Factor for Primary Non-Function of Liver Allograft.

Chronic Glucocorticoid Use in Multi-Organ Donors May Be a Risk Factor for Primary Non-Function of Liver Allograft.

Review of New Guidelines for the Management of Glucocorticoid Induced Osteoporosis

The chronic use of glucocorticoids results in osteoporosis. Several sets of guidelines have been published on the management of glucocorticoid induced osteoporosis (GIO). These guidelines vary on their focus and highlight different aspects of the current concepts in the management of GIO. In this current article, we summarize recent guidelines for management of GIO and highlight similarities and differences as well as address some of the controversies generated by these guidelines.

Causes, mechanisms and management of paediatric osteoporosis

Osteoporosis, a skeletal disorder characterized by compromised bone strength and an increased risk of fractures, is an important paediatric disorder that involves almost all paediatric subspecialties. Osteogenesis imperfecta is the most common form of childhood-onset primary osteoporosis, but several other forms are also known. Secondary osteoporosis is caused by an underlying chronic illness or its treatment. The most common causes of secondary osteoporosis include chronic systemic inflammation, glucocorticoid use and neuromuscular disabilities. The skeletal sequelae can present in childhood as low-energy peripheral and vertebral fractures, or become evident in adulthood as low bone mass and an increased propensity to develop osteoporosis. Management should aim at prevention, as interventions to treat symptomatic osteoporosis in the paediatric age group are scarce. Bisphosphonates are the principal pharmacological agents that can be used in this setting, but data on their efficacy and safety in paediatric populations remain inadequate, especially in patients with secondary osteoporosis. Consequently, it is important to understand the potential skeletal effects of paediatric illnesses and their therapies in order to institute effective and timely prevention of skeletal complications.

Glicocorticoides e o desenvolvimento da osteoporose em pacientes com Síndrome de Cushing: uma revisão

A osteoporose é uma das complicações mais frequentes durante a utilização de glicocorticoides em pacientes portadores da Síndrome de Cushing e está associada a um alto índice de incapacitação devido a fraturas. Pode ocorrer em 30-50% dos pacientes em uso crônico de glicocorticoides principalmente em áreas ricas de osso trabecular. Na patogênese da osteoporose induzida por glicocorticoides estão envolvidos vários efeitos diretos e indiretos, sistêmicos e locais sobre o osso e sobre o metabolismo mineral de forma complexa, sendo que os mecanismos celulares da perda óssea não são claramente definidos. Sabe-se que o principal mecanismo é a ação nos osteoblastos, osteoclastos e osteócitos, unidade multicelular básica da estrutura óssea. O padrão para o tratamento farmacológico da osteoporose induzida por glicocorticoides envolve o uso de bisfosfonatos e reposição de cálcio, que deve ser iniciada logo após o início crônico da terapia glicocorticoide e o tratamento da Síndrome de Cushing envolve a suspensão gradual do uso do corticoide.

Significantly higher estimated 10-year probability of fracture in lupus patients with bone mineral density comparable to that of healthy individuals

This study aimed at comparing the FRAX 10-year fracture risk between SLE patients and demographically- and anthropometrically matched healthy individuals. Consecutive SLE patients aged ≥ 40 were analyzed for the FRAX 10-year probability of major osteoporotic and hip fractures and their risk was compared with healthy controls matched for age, gender and body mass index. Potential determinants associated with higher 10-year fracture probability in the SLE patients were studied by regression models. Ninety subjects (45 SLE patients and 45 healthy controls) were studied. While the bone mineral density (BMD) of the lumbar spine and dominant hip was comparable between the two groups, the FRAX 10-year probability of major and hip fractures was significantly higher in SLE patients. Significantly more SLE patients had high 10-year fracture risk as defined by the National Osteoporosis Foundation compared with healthy controls (16 vs. 2 %, p = 0.026). After controlling for glucocorticoid use and premature menopause which were significant univariate risk factors, the difference in the 10-year fracture risk became insignificant. Amongst SLE patients, increasing age, lower hip BMD and cumulative glucocorticoid dose independently predicted higher 10-year major fracture risk while higher anti-dsDNA level independently predicted higher hip fracture risk in addition to age and lower hip BMD. Chronic glucocorticoid use and premature menopause led to higher 10-year probability of major osteoporotic and hip fractures in SLE patients compared with their healthy counterparts although their BMD was comparable. Advanced age, lower hip BMD, cumulative glucocorticoid and higher anti-dsDNA level independently predicted higher 10-year fracture risk amongst SLE patients.