Cumulative Oral Corticosteroid Research Articles

Association of Different Prescribing Patterns for Oral Corticosteroids With Fracture Preventive Care Among Older Adults in the UK and Ontario

Identifying and mitigating modifiable gaps in fracture preventive care for people with relapsing-remitting conditions such as eczema, asthma, and chronic obstructive pulmonary disease who are prescribed high cumulative oral corticosteroid doses may decrease fracture-associated morbidity and mortality. To estimate the association between different oral corticosteroid prescribing patterns and appropriate fracture preventive care, including treatment with fracture preventive care medications, among older adults with high cumulative oral corticosteroid exposure. This cohort study included 65 195 participants with UK electronic medical record data from the Clinical Practice Research Datalink (January 2, 1998, to January 31, 2020) and 28 674 participants with Ontario, Canada, health administrative data from ICES (April 1, 2002, to September 30, 2020). Participants were adults 66 years or older with eczema, asthma, or chronic obstructive pulmonary disease receiving prescriptions for oral corticosteroids with cumulative prednisolone equivalent doses of 450 mg or higher within 6 months. Data were analyzed October 22, 2020, to September 6, 2022. Participants with prescriptions crossing the 450-mg cumulative oral corticosteroid threshold in less than 90 days were classified as having high-intensity prescriptions, and participants crossing the threshold in 90 days or more as having low-intensity prescriptions. Multiple alternative exposure definitions were used in sensitivity analyses. The primary outcome was prescribed fracture preventive care. A secondary outcome was major osteoporotic fracture. Individuals were followed up from the date they crossed the cumulative oral corticosteroid threshold until their outcome or the end of follow-up (up to 1 year after index date). Rates were calculated for fracture preventive care and fractures, and hazard ratios (HRs) were estimated from Cox proportional hazards regression models comparing high- vs low-intensity oral corticosteroid prescriptions. In both the UK cohort of 65 195 participants (mean [IQR] age, 75 [71-81] years; 32 981 [50.6%] male) and the Ontario cohort of 28 674 participants (mean [IQR] age, 73 [69-79] years; 17 071 [59.5%] male), individuals with high-intensity oral corticosteroid prescriptions had substantially higher rates of fracture preventive care than individuals with low-intensity prescriptions (UK: 134 vs 57 per 1000 person-years; crude HR, 2.34; 95% CI, 2.19-2.51, and Ontario: 73 vs 48 per 1000 person-years; crude HR, 1.49; 95% CI, 1.29-1.72). People with high- and low-intensity oral corticosteroid prescriptions had similar rates of major osteoporotic fractures (UK: crude rates, 14 vs 13 per 1000 person-years; crude HR, 1.07; 95% CI, 0.98-1.15 and Ontario: crude rates, 20 vs 23 per 1000 person-years; crude HR, 0.87; 95% CI, 0.79-0.96). Results from sensitivity analyses suggested that reaching a high cumulative oral corticosteroid dose within a shorter time, with fewer prescriptions, or with fewer or shorter gaps between prescriptions, increased fracture preventive care prescribing. The results of this cohort study suggest that older adults prescribed high cumulative oral corticosteroids across multiple prescriptions, or with many or long gaps between prescriptions, may be missing opportunities for fracture preventive care.

REAL-WORLD EFFECTIVENESS OF DUPILUMAB ON ORAL CORTICOSTEROID USE IN PATIENTS WITH MODERATE-TO-SEVERE ASTHMA

<h3>Introduction</h3> Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/-13, key and central drivers of type 2 inflammation in asthma. Patients with oral-corticosteroid (OCS)-dependent severe asthma are at increased risk of OCS-related adverse events. In phase 3 VENTURE (NCT02528214), add-on dupilumab 300 mg every 2 weeks vs placebo reduced OCS maintenance dose in patients with OCS-dependent severe asthma. Dupilumab demonstrated an acceptable safety profile. We investigated the real-world effectiveness of dupilumab in reducing OCS use in patients with OCS-dependent severe asthma. <h3>Methods</h3> This retrospective, single-arm study analyzed data from the Avalere Claims database, a large US insurance claims database. Patients diagnosed with moderate-to-severe asthma (GINA 4/5) initiating dupilumab between November 1, 2018, and July 31, 2019, were included. Exclusion criteria were chronic obstructive pulmonary disease (COPD) diagnosis or treatment with another biologic for asthma in the previous year. There were 141 OCS-dependent patients included in this analysis (<b>Table</b>). The proportions of patients with any OCS use, mean annualized cumulative OCS dose, and percentage of patients with ≥90 days of OCS use were assessed pre and post 12 months of dupilumab initiation. <h3>Results</h3> Dupilumab significantly reduced the proportion of patients with any OCS use by 20.6% [<i>P</i>=<0.0001], the mean annualized cumulative OCS dose by 33.4% [<i>P</i>=<0.01], and patients with ≥90 days of OCS-use by 42% [<i>P</i>=<0.0001] in OCS-dependent patients from the 12-month pre baseline to the 12-month follow-up period. <h3>Conclusion</h3> Dupilumab is effective in reducing OCS use in patients with moderate-to-severe OCS-dependent asthma in real-world settings.

Primary antibody deficiencies represent an underestimated comorbidity in asthma patients: efficacy of immunoglobulin replacement therapy in asthma control

Objective Primary antibody deficiencies (PAD) are an underestimated comorbidity in asthma and its treatment could improve disease control. Methods a retrospective cohort of asthmatics, affected by IgG subclass deficiency or unclassified antibody deficiency and treated with low-dose intravenous immunoglobulin replacement therapy (IRT) was recruited. Demographic and clinical data, chest CT scan, blood eosinophils, atopy, chronic oral corticosteroid (OCS) therapy were evaluated at baseline. Asthma exacerbations, lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI) and asthma-related hospitalizations were assessed after one and two years of IRT. Results 57 moderate-to-severe asthmatics were enrolled, mostly affected by T2 low asthma (39/57, 68.4%). After one year, IRT was effective in improving, irrespective of bronchiectasis, atopy, eosinophils and PAD type: 1) trough IgG (826.9 ± 221.3 vs 942.2 ± 195.1 mg/dl; p < 0.0001) and IgG subclasses (IgG1 355.4 ± 88.4 vs 466.7 ± 122.3, p < 0.0001; IgG2 300.1 ± 130.1 vs 347.6 ± 117.3, p < 0.0005) serum levels. 2) asthma exacerbations (6.4 ± 4.1 vs 2.4 ± 1.9, p < 0.0001), LRTI (4.3 ± 3.9 vs 1.3 ± 1.5, p < 0.0001) and hospitalization rate (0.26 ± 0.7 vs 0.05 ± 0.2, p < 0.01). These results persisted after 2 years of therapy. Estimated mean cumulative OCS exposure was reduced by 4500 mg over the 2-year period. Conclusions low-dose IRT is effective in improving asthma control and lessening OCS burden in asthmatics affected by PAD.

A 4-Year Retrospective Claims Analysis of Oral Corticosteroid Use and Health Conditions in Newly Diagnosed Medicare FFS Patients with COPD.

PurposeWe analyzed population-level administrative claims data for Medicare fee-for-service (FFS) beneficiaries to provide insights on systemic oral corticosteroid (OCS) use patterns and associated health conditions and acute events among patients newly diagnosed with chronic obstructive pulmonary disease (COPD).BackgroundCOPD is a progressive inflammatory disease of the lungs, characterized by acute exacerbations that may lead to increased mortality. Short courses of systemic corticosteroids (SCS) are recommended to reduce recovery time from exacerbations, although SCS use has been associated with increased risk of adverse events.MethodsThis study used 2013–2019 Medicare 100% FFS research identifiable files, which contain all Medicare Parts A, B, and D paid claims incurred by 100% of Medicare FFS beneficiaries. Descriptive statistics for patients newly diagnosed with COPD were analyzed, including OCS use, select health conditions and acute events, and COPD exacerbations. Statistical models were used to analyze the relationship between the incidence of select health conditions and events and cumulative OCS dosage.ResultsOf Medicare FFS patients newly diagnosed with COPD, 36% received OCS in the 48 months following diagnosis, and 38% of OCS episodes lasted longer than the recommended 5–7 days. Patients had a variety of health conditions or acute events in the 24-month period prior to new COPD diagnosis, such as hypertension, depression/anxiety, type 2 diabetes, or osteoporosis, that could heighten the risks of OCS use. Patients treated with >1000 mg of prednisolone equivalent OCS in the 48 months following COPD diagnosis had a higher incidence of new conditions or events, including cardiovascular disease, heart failure, hypertension, obesity, dyspepsia, infections, and depression/anxiety, than patients with no OCS use.ConclusionThese results highlight the potential risks of OCS in COPD treatment, including prolonged use among complex Medicare patients, and reinforce the importance of preventive treatment strategies and therapy optimization early in the disease course.

The Contribution of Oral and Inhaled Glucocorticoids to Adrenal Insufficiency in Asthma

Exposure to any form of glucocorticoid preparation is associated with a risk of adrenal insufficiency (AI). To establish the contribution of oral corticosteroid (OCS) and inhaled corticosteroid (ICS) exposure to the risk of AI in a cohort of patients (n= 80) with severe, uncontrolled asthma. We compiled individualized cumulative OCS and ICS exposure data using a combination of health care records and electronic inhaler monitoring using an Inhaler Compliance Assessment device and estimated the risk of AI for each participant using a morning serum cortisol concentration. The predicted prevalence of AI based on morning cortisol concentrations was 25% (20 of 80). Participants on maintenance OCS therapy had the highest risk of AI at 60% (6 of 10) compared with 17% (11 of 65) in those with no recent OCS exposure. Morning serum cortisol correlated negatively with both OCS exposure (mg/kg prednisolone) (r=-0.4; P<.0002) and ICS exposure (mg/kg fluticasone propionate) (r=-0.26; P= .019). Logistic regression of risk of AI against the number of standard treatment courses of OCS demonstrated a positive relationship although this did not reach statistical significance (odds ratio, 1.41; 95% CI, 0.97-2.05; P= .073). Logistic regression analysis, categorizing patients as high-risk AI (cortisol <130 nmol/L) or not (cortisol >130 nmol/L), showed that cumulative ICS exposure remained a significant predictor of AI, even when exposure to OCS was controlled for (odds ratio, 2.17 per 1 mg/kg increase in cumulative fluticasone propionate exposure; 95% CI, 1.06-4.42; P= .033). Our data suggest that AI is common among patients with asthma and highlights that the risk of AI is associated with both high-dose ICS therapy and intermittent treatment courses of OCS.

Long-term retention rate of mepolizumab treatment in severe asthma: a 36-months real-life experience

Objective: Mepolizumab is an anti-IL-5 monoclonal antibody that has shown, in different trials, the capacity to induce a reduction of exacerbations, an improvement of asthma control and a significant oral corticosteroid (OCS)-sparing effect. At present, there is limited real-life data about its long-term effects. The aim of the study was to evaluate the long-term effects of mepolizumab in real-life.Methods: We conducted a 36-months single-center retrospective study in 51 patients suffering from severe eosinophilic asthma treated with mepolizumab 100 mg/4 weeks. Clinical outcomes (symptoms, annual asthma exacerbation rates) were monitored. Additionally, we estimated annualized OCS dosage before and after mepolizumab treatment. Mepolizumab retention rate in the follow-up period was also evaluated.Results: A significant decrease of the annual rate of asthma exacerbations in association with significant changes in asthma control was observed. Specifically, the exacerbation rate significantly fell from 5.1 ± 4 per person/year in the pre-mepolizumab treatment period to 0.8 ± 1.2 per person/year in the 12-follow-up. The clinical benefit was maintained throughout the study follow up period of 36 months. Mepolizumab treatment induced significant changes in both ACT and ACQ5 scores. The majority of patients (65.2%) experienced a more pronounced improvement of 50% or more in SNOT-22. A mean cumulative OCS exposure reduction of 5365.5 mg over a 3-year period for patients receiving mepolizumab was estimated. The drug retention rate was: 96% at 12 months; 93.7% at 18 months, 88.9% at 24 months and 82.3% at 36 months.Conclusions: Our real-life results confirm that mepolizumab treatment allows to control asthma symptoms, reduce exacerbations and OCS exposure in a significant and sustained manner.

Effectiveness of mepolizumab in patients with severe eosinophilic asthma: results from real-world clinical practice in Finland

Objectives Mepolizumab treatment provides clinical benefits for patients with severe eosinophilic asthma in randomized controlled trials. However, real-world data for patients in Finland are lacking. Methods This retrospective, non-interventional, chart review study included patients with severe eosinophilic asthma ≥18 years of age initiating mepolizumab between January 1, 2016 and January 31, 2019 at three investigational sites in Finland. Patient characteristics during the 12 months prior to mepolizumab initiation (baseline) were recorded and primary and secondary endpoints included changes from baseline in disease outcomes during follow-up (up to 24 months following mepolizumab initiation). Exploratory endpoints included association between patient characteristics and exacerbation frequency/annual cumulative oral corticosteroid (OCS) dose. Results Overall, 51 patients were included (mean 17.8 months follow-up). At baseline, patients had a mean (standard deviation) blood eosinophil count of 550 (410) cells/µL; impaired lung function and health-related quality of life; poor symptom control; frequent exacerbations (2.78/year); and 90% were using OCS (mean: 9.80 mg/day). At the last follow-up visit, reductions from baseline in blood eosinophil count (84%) and fractional exhaled nitric oxide (26%) were observed, as were improvements in Asthma Quality of Life Questionnaire score (36%) and Asthma Control Test score (34%). Reductions in the mean number of annual exacerbations (82%) and mean daily OCS dose (39%) were also seen; reductions were observed even after adjustment for several patient baseline characteristics. Conclusions Results are consistent with previous randomized clinical trials, indicating that Finnish patients experience clinically relevant improvements when treated with mepolizumab in real-world clinical practice.

German regional variation of acute and high oral corticosteroid use for asthma

Objective: To improve understanding of real-world asthma treatment and inform physician education, we evaluated regional variation in asthma prevalence and oral corticosteroid (OCS) use across Germany. Methods: We developed a machine learning gradient-boosted tree model with IMS® Disease Analyzer electronic medical records, which cover 3% of German patients. This model had a 91% accuracy in predicting the presence of asthma and chronic obstructive pulmonary disease. We applied the model to the IMS® Longitudinal Prescription database, with 82% national coverage, to classify patients receiving treatment for airflow obstruction from October 2017–September 2018 in 63 regions in Germany. Results: Of 2.4 million individuals under statutory health insurance predicted to have asthma, 13.7%, 18.7%, 36.5%, 29.4%, and 1.7% received treatment classified as Global Initiative for Asthma (GINA) Steps 1, 2, 3, 4, and 5, respectively. Approximately 7–15% of those at GINA Steps 1–4 and 35% at Step 5 treatment received ≥1 acute OCS prescription (duration <10 days). Of patients receiving GINA Steps 1–4 and Step 5 treatments, 1–3% and 86%, respectively, received ≥1 high-dosage OCS prescription. Cumulative OCS dosage and percentages of patients receiving OCS differed substantially across regions, and regions with lower OCS use had greater use of biologic therapies. Conclusions: Both acute and high OCS use varied regionally across Germany, with overall use suggesting patients are considerable risk of adverse effects and long-term health consequences. Supplemental data for this article can be accessed at publisher’s website.

Burden of Asthma in Elderly Japanese Patients: Using Hospital-Based Administrative Claims Data.

IntroductionData are lacking on severe asthma burden in elderly people in Japan. We assessed the prevalence and clinical/economic burden of severe asthma and asthma-related hospitalizations in elderly and younger Japanese patients.MethodsThis retrospective study analyzed outpatient claims data and inpatient hospital discharge records among patients aged ≥ 15 years with asthma (defined as ≥ 2 prescriptions of inhaled corticosteroids [ICS] or ICS/long-acting beta-agonists [LABA]) between 1 July 2014 and 30 June 2017. We analyzed the outpatient visit assessment population with severe asthma (≥ 240-day prescription of high-dose ICS and ≥ 90-day prescription of ≥ 1 additional controllers) and the asthma-related hospitalization population (≥ 1 hospital admission[S] with a primary diagnosis of asthma/status asthmaticus and use of systemic corticosteroids) over a 1-year observation period before the date of each patient’s latest asthma prescription or asthma-related hospitalization within the study period. The primary outcome was the proportion of elderly (≥ 65 years) and younger (15–39 and 40–64 years) patients among the outpatient visit assessment population. Secondary outcomes included outpatient and inpatient characteristics, asthma-related healthcare resource utilization, and asthma-associated costs, by age group.ResultsOf the outpatient visit assessment population (n = 35,742), 4211 had severe asthma, with the prevalence of 8.2%, 12.8%, and 12.4% for the 15–39, 40–64, and ≥ 65 years age groups, respectively. Elderly versus younger outpatients with severe asthma had higher cumulative oral corticosteroid doses. Among both outpatient visit assessment population and hospitalization assessment population, elderly versus younger outpatients with severe asthma or asthma-related hospitalizations had more comorbidities, required more biological, hematological, immunological, and microbiological tests, and incurred higher asthma-associated costs.ConclusionsIn addition to reaffirming the higher prevalence of severe asthma in Japanese patients ≥ 40 years versus those < 40 years of age, our results demonstrated higher clinical and economic burden in elderly versus younger patients.Electronic supplementary materialThe online version of this article (10.1007/s41030-020-00121-w) contains supplementary material, which is available to authorized users.

Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management

Systemic corticosteroid use to manage uncontrolled asthma and its associated healthcare burden may account for important health-related adverse effects. We conducted a systematic literature review to investigate the real-world extent and burden of systemic corticosteroid use in asthma. We searched MEDLINE and Embase databases to identify English-language articles published in 2010–2017, using search terms for asthma with keywords for oral corticosteroids and systemic corticosteroids. Observational studies, prescription database analyses, economic analyses, and surveys on oral/systemic corticosteroid use in children (>5 yr old), adolescents (12–17 yr old), and adults with asthma were included. We identified and reviewed 387 full-text articles, and our review included data from 139 studies. The included studies were conducted in Europe, North America, and Asia. Overall, oral/systemic corticosteroids were commonly used for asthma management and were more frequently used in patients with severe asthma than in those with milder disease. Long-term oral/systemic corticosteroid use was, in general, less frequent than short-term use. Compared with no use, long-term and repeated short-term oral/systemic corticosteroid use were associated with an increased risk of acute and chronic adverse events, even when doses were comparatively low. Greater oral/systemic corticosteroid exposure was also associated with increased costs and healthcare resource use. This review provides a comprehensive overview of oral/systemic corticosteroid use and associated adverse events for patients with all degrees of asthma severity and exposure duration. We report that oral/systemic corticosteroid use is prevalent in asthma management, and the risks of acute and chronic complications increase with the cumulative oral corticosteroid dosage.

Two-year integrated steroid-sparing analysis and safety of benralizumab for severe asthma

Objective Treatment with benralizumab significantly reduces exacerbations and improves lung function after 1 year and decreases oral corticosteroid (OCS) use after 28 weeks for patients with severe, uncontrolled eosinophilic asthma. We assessed whether these effects on OCS reduction are sustained for up to an additional year of treatment while maintaining an acceptable safety profile. Methods Data on OCS maintenance dosage were collected for adult patients with baseline blood eosinophil counts ≥150 cells/μL treated with add-on benralizumab 30 mg (every 4 [Q4W] or 8 weeks [Q8W; first three doses Q4W]) from the 28-week ZONDA study and were integrated with results from the predefined 56-week adult completion phase of the BORA extension study. Efficacy and safety were summarized descriptively. Results For patients receiving benralizumab Q8W, the median daily OCS dosage reduction of 75% from baseline to end of treatment achieved in ZONDA was sustained at the end of the BORA extension period (median 67% reduction from baseline). This was estimated to result in a median cumulative OCS dosage of 2.98 g over the 1.5-year period for patients receiving benralizumab Q8W compared with 5.74 g if these patients had remained on their baseline OCS dosages prior to benralizumab initiation. All adverse event rates were similar between the BORA extension and ZONDA periods, with no new or unexpected safety findings. Conclusion This benralizumab 1.5-year integrated analysis demonstrates that OCS reductions and safety were maintained with further follow up and supports long-term use of benralizumab for patients with severe, uncontrolled eosinophilic asthma.

Oral corticosteroid use during pregnancy and risk of preterm birth.

To evaluate the associations between oral corticosteroid (OCS) dose early and late in pregnancy and preterm birth (PTB) among women with RA. Pregnant women in the MotherToBaby Pregnancy Studies (2003-2014) with RA (n = 528) were included in the primary analysis. Information was collected by phone interview and from medical records. We estimated risk ratios (RR) for OCS dose trajectories and other disease-related medications before gestational day 140 and hazard ratios (HR) for time-varying exposures after gestational day 139. PTB risk was 15.5% overall. Compared with no OCS, PTB risk was increased in high (adjusted (a)RR: 4.77 (95% CI: 2.76, 8.26)) and medium (aRR: 1.81 (95% CI: 1.10, 2.97)) cumulative OCS dose trajectories during the first 139 gestational days. The low cumulative trajectory group was associated with an increased risk of PTB that was not statistically significant (aRR: 1.38 (95% CI: 0.79, 2.38)), and DMARDs were not associated with PTB (biologic DMARDs aHR: 1.08 (95% CI: 0.70, 1.66); non-biologic DMARDs aHR: 0.87 (95% CI: 0.55, 1.38)). OCS exposure to ⩾10 mg of prednisone equivalent daily dose after gestational day 139 vs none was associated with increased PTB rate (aHR: 2.45 (95% CI: 1.32, 4.56)), whereas <10 mg was associated with a modestly increased rate of PTB that was not statistically significant (aHR: 1.18 (95% CI: 0.60, 2.30)). Higher OCS doses vs no OCS use, both earlier and later in pregnancy, were associated with an increase in PTB among women with RA.

Cumulative oral corticosteroid use increases risk of glucocorticoid-related adverse events in patients with newly diagnosed pemphigus

Cumulative oral corticosteroid use increases risk of glucocorticoid-related adverse events in patients with newly diagnosed pemphigus

128 Cumulative oral corticosteroid use increases risk of glucocorticoid-related adverse events in patients with pemphigus

128 Cumulative oral corticosteroid use increases risk of glucocorticoid-related adverse events in patients with pemphigus

Cumulative oral corticosteroid (OCS) exposure is associated with dose-proportionate increases in the risks of osteoporosis, fracture and cataracts

Cumulative oral corticosteroid (OCS) exposure is associated with dose-proportionate increases in the risks of osteoporosis, fracture and cataracts

The role of non-corticosteroid related factors in osteonecrosis (ON) in systemic lupus erythematosus: a nested case-control study of inception patients

Several factors have been associated with the development of osteonecrosis (ON) in SLE but corticosteroid (CS) therapy has been the most consistent association. We sought to determine factors that predisposed to, or protected from, the development of ON in lupus patients when cumulative oral corticosteroid doses were matched between cases and controls, thereby removing presence of corticosteroid therapy and cumulative dose as risk factors. A nested case-control study of an inception cohort of SLE patients was used to determine the clinical, laboratory and therapeutic differences between patients who developed their first ON event and patients who did not develop ON, having matched these groups for their cumulative oral corticosteroid doses. Of the 570 patients seen within the first year after diagnosis 65 (11.4%) developed ON. None of the variables examined were found to confer additional ON risk in multivariate analysis. It appears that the major factor associated with the development of ON is corticosteroid therapy. Factors which may protect a majority of patients on corticosteroids from developing ON remain to be elucidated.

Oral corticosteroids and fracture risk: relationship to daily and cumulative doses.

This study examined the effects of daily and cumulative oral corticosteroid doses on the risk of fractures. Information was obtained from the General Practice Research Database, which contains medical records of general practitioners in England and Wales. The study included 244 235 oral corticosteroid users and 244 235 controls. Patients taking higher doses (at least 7. 5 mg daily of prednisolone or equivalent) had significantly increased risks of non-vertebral fracture [relative rate (RR)=1.44, 95% confidence interval (CI) 1.34-1.54], hip fracture (RR=2.21, 95% CI 1.85-2.64) and vertebral fracture (RR=2.83, 95% CI 2.35-2.40) relative to patients using oral corticosteroids at lower doses (less than 2.5 mg per day). Fracture risk was also elevated among people with higher cumulative exposure to oral corticosteroids over the study period, but this effect was almost wholly removed by adjustment for daily dose, age, gender and other confounding variables. These findings suggest that the adverse skeletal effects of oral corticosteroids manifest rapidly and are related to daily dose. The level of previous exposure to oral corticosteroids was not a strong determinant of the risk of fracture. Preventive measures against corticosteroid-induced osteoporosis should therefore be instituted as soon after the commencement of glucocorticoid therapy as possible.

Aseptic Necrosis of Bone Following Renal Transplantation: Relation with Hyperparathyroidism

Bone status, calcium and phosphate metabolism were prospectively evaluated in 98 renal transplant recipients with stable renal function. Aseptic necrosis of bone was found in 30 patients, leading to arthroplasty in 12 patients. Plasma parathyroid hormone and nephrogenic cyclic adenosine monophosphate (cAMP) values were greater and the duration of pre-transplant chronic renal failure longer in patients with aseptic necrosis of bone than in those who were not affected. Cumulative oral corticosteroid doses and the number of acute rejection episodes treated by intravenous methylprednisolone pulses were similar in patients with or without aseptic necrosis of bone. Hyperparathyroidism was confirmed histologically in 14 patients, comprising 4 cases of adenoma and 10 of diffuse hyperplasia. Serum parathyroid hormone correlated positively with serum creatinine (r = 0.47; P less than 0.001) and with cumulative corticosteroid dose (r = 0.30; P less than 0.003). This study suggests that hyperparathyroidism is a factor in the pathogenesis of aseptic bone necrosis. The frequency and severity of bone necrosis may be decreased by early detection and treatment of post-transplant hyperparathyroidism.