Management Of Glucocorticoid-induced Osteoporosis Research Articles

Extensive Expertise in Endocrinology: Advances in the Management of Glucocorticoid-Induced Osteoporosis.

Osteoporosis is a common consequence of long-term oral glucocorticoid therapy and the resulting fractures cause significant morbidity. Bone loss occurs rapidly after initiation of glucocorticoid therapy; the accompanying increase in risk of fracture is dose-dependent and occurs within a few months of starting therapy. The adverse effects of glucocorticoids on bone are mediated by inhibition of bone formation accompanied by an early but transient increase in bone resorption, due both to direct and indirect effects on bone remodelling. Fracture risk assessment should be performed as soon as possible after long-term glucocorticoid therapy (≥3 months) is initiated. FRAX can be adjusted for the dose of prednisolone but does not currently take fracture site, recency or number into account and therefore may underestimate fracture risk, particularly in individuals with morphometric vertebral fractures. Vertebral fracture assessment should therefore be regarded as a routine part of fracture risk estimation in individuals receiving long-term glucocorticoid therapy. Bone protective therapy should be started promptly in individuals at high-risk, together with calcium and vitamin D supplements. Bisphosphonates are generally regarded as first line options on the grounds of their low cost, but anabolic therapy should be considered as an alternative first line option in very high-risk individuals.

German Society of Rheumatology recommendations for management of glucocorticoid-induced osteoporosis.

Glucocorticoids are of substantial therapeutic importance in the treatment of inflammatory diseases, but are also associated with bone mineral density loss, osteoporosis, and fractures, especially with long-term use. To develop recommendations for the management of glucocorticoid-induced osteoporosis (GIOP) in adult patients on long-term glucocorticoid (GC) treatment. Asystematic literature search (SLR) was conducted to synthesize the evidence for GIOP prevention and treatment options. Recommendations were developed based on SLR/level of evidence and by previously defined questions and in astructured group consensus process. Recommendations include supplementation with calcium and vitaminD under long-term GC therapy in adults. If specific osteologic treatment is indicated, we recommend bisphosphonates or denosumab as first-line treatment. If fracture risk is high, we recommend teriparatide as primary specific osteologic treatment. Denosumab should be used in cases of severe renal insufficiency, and specific osteologic treatment should not be given in pregnancy. For patients who have not reached the treatment goal, aswitch to another class of specific osteologic drugs should be performed. We recommend re-evaluation after atreatment duration of 3-5years or after termination of long-term GC treatment. This work aims to provide evidence-based and consensus-based recommendations for the best possible management of GIOP in Germany and to support treatment decisions.

Дискусійні питання визначення порога втручання при глюкокортикоїдіндукованому остеопорозі: кого лікувати?

Глюкокортикоїдіндукований остеопороз є найпоширенішою причиною вторинного остеопорозу. Після початку перорального прийому глюкокортикоїдів протягом декількох місяців відзначається швидка втрата кісткової маси й зростання ризику переломів. Важливість глюкокортикоїдіндукованого остеопорозу як проблеми охорони здоров’я асоційована з частим застосуванням глюкокортикоїдів пацієнтами з різними хронічними захворюваннями та високим рівнем остеопорозу, виявленого в цих груп пацієнтів. Розвиток глюкокортикоїдіндукованого остеопорозу обумовлений пригніченням процесу утворення кістки, що супроводжується раннім, але короткочасним збільшенням резорбції кістки. Серед численних механізмів, що лежать в основі порушення кісткового метаболізму при тривалому прийомі глюкокортикоїдів, необхідно відзначити збільшення співвідношення RANKL/OPG, підвищення експресії склеростину, активацію PPARγR2, а також гіпогонадизм, порушення всмоктування кальцію в кишечнику й зниження вироблення інсуліноподібного фактора росту 1. Незважаючи на доступні й ефективні профілактичні заходи, багато пацієнтів, які починають або отримують глюкокортикоїдну терапію, недостатнім чином оцінені в плані стану кісткової тканини й ризику переломів. Установлено порогові значення добових доз глюкокортикоїдів (≥ 2,5 мг/добу) і тривалість їх прийому (≥ 3 місяців), при яких пацієнти повинні бути обов’язково піддані оцінці ризику переломів і необхідності проведення лікування антиостеопоротичними препаратами. Національні керівництва з менеджменту глюкокортикоїдіндукованого остеопорозу пропонують різні підходи до визначення порогу втручань, базуючись на використанні різних критеріїв. Алгоритм FRAX® розраховує 10-річну ймовірність переломів за клінічними факторами ризику з тестуванням мінеральної щільності кістки або без нього і калібрується для регіональної частоти переломів і смертності. Незважаючи на обмеження, цей інструмент є найдієвішим у визначенні порога втручань. У рекомендаціях ACR — 2017 вказується, що початковий абсолютний ризик переломів слід оцінювати з використанням алгоритму FRAX® з урахуванням доз глюкокортикоїдів і тестування мінеральної щільності кістки якомога швидше (до 6 місяців від початку прийому глюкокортикоїдів).

German Society of Rheumatology Recommendations for the management of glucocorticoid-induced Osteoporosis. German version

Glucocorticoids are of substantial therapeutic importance in the treatment of inflammatory diseases, but are also associated with bone mineral density loss, osteoporosis, and fractures, especially with long-term use. To develop recommendations for the management of glucocorticoid-induced osteoporosis (GIOP) in adult patients on long-term glucocorticoid (GC) treatment. Asystematic literature search (SLR) was conducted to synthesize the evidence for GIOP prevention and treatment options. Recommendations were developed based on SLR/level of evidence and by previously defined questions and in astructured group consensus process. Recommendations include supplementation with calcium and vitaminD under long-term GC therapy in adults. If specific osteologic treatment is indicated, we recommend bisphosphonates or denosumab as first-line treatment. If fracture risk is high, we recommend teriparatide as primary specific osteologic treatment. Denosumab should be used in cases of severe renal insufficiency, and specific osteologic treatment should not be given in pregnancy. For patients who have not reached the treatment goal, aswitch to another class of specific osteologic drugs should be performed. We recommend re-evaluation after atreatment duration of 3-5years or after termination of long-term GC treatment. This work aims to provide evidence-based and consensus-based recommendations for the best possible management of GIOP in Germany and to support treatment decisions.

Epidemiology of glucocorticoid-induced osteoporosis and management of associated fracture risk in Japan.

Glucocorticoid-induced osteoporosis (GIOP) is associated with a high fracture risk. Practice guidelines by the Japanese Society for Bone and Mineral Research in 2014 recommend bone densitometry and appropriate treatment to reduce this risk. The study objectives were to describe characteristics of GIOP patients in Japan and to evaluate their management in a subgroup of patients without comorbid cancer. This retrospective cohort study was performed using the Medical Data Vision (MDV) database from Japan. Adult patients initiating oral glucocorticoid treatment with a total GIOP risk score ≥ 3, based on the 2014 practice guideline, identified between 2009 and 2019 were eligible. A subgroup of patients without any cancer diagnosis was also identified. Data were extracted on demographics, concurrent medical conditions, use of bone densitometry, and osteoporosis treatment. 25,569 patients were eligible, of whom 12,227 had a confirmed cancer diagnosis. Mean age was 68.5 years and 12,356 patients (48.3%) were women. Concurrent medical conditions of interest were documented in 14,887 patients, most frequently rheumatoid arthritis (n = 4185) and asthma (n = 3085). Yearly bone densitometry was performed in 6.5% (n = 865) of the cancer-free subgroup; 51.8% (n = 6905) were prescribed an osteoporosis treatment, most frequently bisphosphonates (n = 5132; 74.3%). Between 2011 and 2018, rates of densitometry were stable, whereas prescription rates increased from 40.0 to 51.8%. In spite of publication of guidelines for GIOP management, there is an important treatment gap in their application in everyday practice. For this reason, public health measures to increase physician awareness of GIOP are needed.

Management of glucocorticoid-induced osteoporosis.

Long-term glucocorticoid (GC) therapy is frequently indicated to treat autoimmune and chronic inflammatory diseases in daily clinical practice. Two of the most devastating untoward effects are bone loss and fractures. Doses as low as 2.5mg of prednisone for more than 3months can impair bone integrity. Population at risk is defined based on the dose and duration of GC therapy and should be stratified according to FRAX (Fracture Risk Assessment Tool), major osteoporotic fracture, prior fractures, and bone mineral density values (BMD). General measures include to prescribe the lowest dose of GC to control the underlying disease for the shortest possible time, maintain adequate vitamin D levels and calcium intake, maintain mobility, and prescribe a bone acting agent in patients at high risk of fracture. These agents include oral and intravenous bisphosphonates, denosumab, and teriparatide.

High bisphosphonate treatment rates and the prevalence of atypical femoral fractures in patients with systematic lupus erythematosus: a single-center retrospective study performed in Japan

Treatment of systemic lupus erythematosus (SLE) often continues with moderate-to-low doses of glucocorticoids for the long term. Bisphosphonates aid in the prevention and management of glucocorticoid-induced osteoporosis (GIOP). However, long-term use of bisphosphonates increases the relative risk of atypical femoral fracture (AFF) and the incidence is typically 16 or 113 per 100,000 person-years in patients treated with bisphosphonates for 5 or 10years, respectively. Here, we explored bisphosphonate prescription rate and prevalence of AFF in patients with SLE. In total, 270 patients with SLE were enrolled. The Japanese Society for Bone and Mineral Research Guideline 2014 for GIOP management and treatment was used. We also explored AFF history through medical records. Most (n = 251) patients were recommended to treat by the GIOP guideline (scores ≥ 3); bisphosphonates, denosumab, teriparatide, or active vitamin D was prescribed for 85.7%. Bisphosphonates were currently used by 66.1% of the patients, and 65% had used them for ≥ 5years. Of all patients, 76.7% had a history of bisphosphonate use, 5 of 270 (1.9%) had histories of AFF. Four of five patients with AFF had taken bisphosphonates for ≥ 3.5years, in addition to moderate doses (≥ 10mg/day) of glucocorticoids. For the SLE patients with a history of bisphosphonate use, the incidence of AFF was calculated to be 278 per 100,000 person-years. Our single-center study found that bisphosphonates were commonly used long term by Japanese patients with SLE. As AFF is not rare, AFF should be cared in patients with SLE.

Anabolics in the management of glucocorticoid-induced osteoporosis: an evidence-based review of long-term safety, efficacy and place in therapy.

IntroductionGlucocorticoid-induced osteoporosis is an underrecognized complication of chronic glucocorticoid therapy characterized by a decrease in new bone formation. Anabolic therapies, such as teriparatide, a recombinant human parathyroid hormone, combat the disease by promoting new bone growth.AimsThis article outlines the pathophysiology of glucocorticoid-induced osteoporosis and details the evidence of efficacy, safety, and patterns of use of teriparatide and other future anabolic therapies.Evidence reviewIn multiple clinical trials, teriparatide has been shown to significantly increase lumbar spine bone mineral density (BMD) in patients with glucocorticoid-induced osteoporosis when compared with placebo, alendronate, and risedronate. When compared with alendronate, significantly fewer vertebral fractures were noted in the teriparatide group. Adverse effects noted in clinical trials include nausea, insomnia, flushing, myalgias, and mild hypercalcemia/hyperuricemia. Early studies in rats noted an increased incidence of osteosarcoma; however, an increased rate beyond levels seen in general populations has not been noted in human studies or with long-term pharmacovigilance. Abaloparatide and romosozumab are newer anabolic therapies that have shown some benefit in postmenopausal osteoporosis but have not yet been studied in the chronic glucocorticoid population.Place in therapyMajor specialty organizations continue to recommend bisphosphonates as first-line therapy in glucocorticoid-induced osteoporosis due to the proven benefit and relative affordability. However, the use of anabolics shows promise to improve outcomes by increasing BMD and reducing fracture-associated morbidity and mortality and has a role for selected populations at high fracture risk.

Denosumab in the treatment of glucocorticoid-induced osteoporosis: a systematic review and meta-analysis.

ObjectiveGlucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. In May 2018, denosumab was approved for the treatment of GIOP in men and women at high risk of fracture. We undertook a systematic review and meta-analysis to summarize the efficacy and safety of denosumab in the prevention and treatment of GIOP.MethodsWe searched PubMed, CINAHL, American College of Rheumatology and American Society for Bone and Mineral Research meeting abstracts for relevant studies. We included studies in which subjects were taking systemic glucocorticoid therapy and were assigned to take denosumab or control therapy, and assessed the effect of treatment on areal bone mineral density (BMD), fractures and/or safety.ResultsThree eligible studies were included in the primary meta-analysis. Denosumab significantly increased lumbar spine BMD (2.32%, 95% CI 1.73%, 2.91%, P<0.0001) and hip BMD (1.52%, 95% CI 1.1%,1.94%, P<0.0001) compared to bisphosphonates. Adverse events, serious adverse events and fractures were similar between denosumab and bisphosphonate arms.ConclusionResults suggest that denosumab is superior to bisphosphonates in its effects on lumbar spine and total hip BMD in patients with GIOP. There was no difference in the incidence of infections, adverse events or serious adverse events. Studies were underpowered to detect differences in the risk of fracture. Denosumab is a reasonable option for treatment of GIOP. However, further studies are needed to guide transitions off denosumab.

Current Treatments and New Developments in the Management of Glucocorticoid-induced Osteoporosis.

Glucocorticoids (GCs) are often used for improvement of quality of life, particularly in the elderly, but long-term GC use may cause harm; bone loss and fractures are among the most devastating side effects. Fracture risk is particularly high in patients with a severe underlying disease with an urgent need for treatment with high-dose GCs. Moreover, it is important to realize that these patients suffer from an augmented background fracture risk as these patients have a high presence of traditional risk factors for osteoporosis, such as high age, low body mass index (BMI), smoking and relatives with osteoporosis or hip fractures. It is thus crucial for prevention of osteoporotic fractures to use the lowest dose of GC for a short period of time to prevent fractures. Another important task is optimal treatment of the underlying disease; for instance, fracture risk is higher in patients with active rheumatoid arthritis than in patients in whom rheumatoid arthritis is in remission. Thus, fracture risk is generally highest in the early phase, when GC dosage and the disease activity of the underlying disease are high. Finally, some of the traditional risk factors can be modulated, e.g., smoking and low BMI. Life-style measures, such as adequate amounts of calcium and vitamin D and exercise therapy are also crucial. In some patients, anti-osteoporotic drugs are also indicated. In general, oral bisphosphonates (BPs) are the first choice, because of their efficacy and safety combined with the low cost of the drug. However, for those patients who do not tolerate oral BPs, alternatives ("second-line therapies") are available: BP intravenously (zoledronic acid), denosumab (Dmab), and teriparatide. Both zoledronic acid and Dmab have been proven to be superior to oral bisphosphonates like risedronate in improvement of bone mineral density. For teriparatide, vertebral fracture reduction has been shown in comparison with alendronate. Thus, to reduce the global burden of GC use and fracture risk, fracture risk management in GC users should involve at least involve life-style measures and the use of the lowest possible dose of GC. In high-risk patients, anti-osteoporotic drugs should be initiated. First choice drugs are oral BPs; however, in those with contraindications and those who do not tolerate oral BPs, second-line therapies should be started. Although this is a reasonable treatment algorithm, an unmet need is that the most pivotal (second-line) drugs are not used in daily clinical practice at the initial phase, usually characterized by high-dose GC and active underlying disease, when they are most needed. In some patients second-line drugs are started later in the disease course, with lower GC dosages and higher disease activity. As this is a paradox, we think it is a challenge for physicians and expert committees to develop an algorithm with clear indications in which specific patient groups second-line anti-osteoporotic drugs should or could be initiated as first-choice treatment.

Glucocorticoid-Induced Osteoporosis: Update on Management

Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressant drugs that are used to treat many inflammatory conditions across different fields of medicine. Glucocorticoid-induced osteoporosis (GIOP) is a significant comorbidity associated with long-term steroid use (> 3 months). The purpose of this review is to provide an update in the management of glucocorticoid-induced osteoporosis. New data for use of denosumab in GIOP includes a large clinical trial showing greater gains in bone density and no differences in adverse effects compared to risedronate. Another study suggests a reduction in hip fractures with alendronate. Meta-analyses and systematic reviews demonstrate an increase in bone mineral density as well as reduction in vertebral fractures with bisphosphonates in GIOP. Recent guidelines from the American college of Rheumatology provide concise suggestions for screening, prevention, and treatment of patients with GIOP. Adequate clinical fracture risk assessment should be obtained for each patient who is expected to receive glucocorticoids for long term. All patients should receive calcium, vitamin D supplementation, and lifestyle counselling. Pharmacologic treatment should be offered to patients who have a moderate to high risk of fractures. Oral followed by IV bisphosphonate remain the first line of treatment. The guidelines recommend other agents including teriparatide and denosumab to be considered as second- and third-line agents, respectively. Glucocorticoid-induced osteoporosis caused by long-term steroid use is associated with significant comorbidity and is often under-treated by clinicians. New clinical trials, meta-analyses, and guidelines offer new strategies for assessment and management.

Effects of quality indicator monitoring for glucocorticoid-induced osteoporosis and trends of drug treatment in a Japanese hospital.

Globally, the appropriate prescription rate for glucocorticoid-induced osteoporosis (GIOP) is low. Thus, we aimed to examine the improvement in real-world GIOP care using a hospital-wide systematic approach with quality indicator (QI) monitoring. We defined a novel QI for GIOP care for the prescription rate of anti-osteoporotic drugs according to 2010 American College of Rheumatology GIOP management recommendations, with the target being patients prescribed ≥7.5mg prednisolone daily or its equivalent for ≥3months. We monitored the glucocorticoid and osteoporotic medication dose for all patients who visited our hospital. From May 2011, we began interventions to improve QI: monthly QI monitoring providing QI-trend feedback to each department in a hospital-wide QI meeting every 3months and organizing lectures on GIOP. We retrospectively analyzed QI trends from 2010 to 2013. We categorized groups by sex and age for subanalyses: group A, men; group B, women, aged <50years; group C, women, aged ≥50years. The numbers of participants were 401, 420, 520 and 513 in 2010, 2011, 2012 and 2013, respectively, with pooled QI rates of 45.8%, 51.3%, 55.0% and 54.8%, respectively. Changes in QI between each consecutive 2years were statistically significant. Subanalyses showed statistically significant QI improvements in groups A and C. We observed a decreasing trend of daily bisphosphonate use throughout the study period, especially at the Immuno-Rheumatology Center. Quality indicator monitoring for GIOP significantly improved appropriate anti-osteoporotic drug prescriptions, especially in men and postmenopausal women.

Just the FRAX: Management of Glucocorticoid-Induced Osteoporosis

Just the FRAX: Management of Glucocorticoid-Induced Osteoporosis

A Nationwide Survey on the Management of Glucocorticoid-induced Osteoporosis at Kosei Hospitals

A Nationwide Survey on the Management of Glucocorticoid-induced Osteoporosis at Kosei Hospitals

Bone: Towards a better management of glucocorticoid-induced osteoporosis?

A new publication by the ACR provides clear recommendations for the prevention and treatment of osteoporosis in patients being treated with glucocorticoids, but will they improve the historically inadequate management of this patient population?

Glucocorticoid-Induced Osteoporosis and the New ACR Guideline

Glucocorticoid-induced osteoporosis (GIOP) continues to be the most common cause of secondary osteoporosis because at any time about 1% of the adult population has been prescribed oral glucocorticoids. Surprisingly, there are relatively few treatment studies of GIOP, particularly of younger individuals including women of child bearing potential and children. Thus, recommendations for management of patients at risk for fracture or who have already suffered an osteoporotic fracture are often based more on clinical experience than randomized controlled trials. Nonetheless, organizations such as the American College of Rheumatology have provided guidance on management of GIOP. In this review, the treatment of GIOP is discussed in light of the specific pathophysiology of this disorder. What separates GIOP from other types of osteoporosis is the profound decrease in osteoblastic function and fact that 3 months (or less) of glucocorticoid therapy leads to a demonstrable increase in fracture incidence. The new ACR Guideline uses FRAX and bone mineral density to categorize fracture risks in GIOP and advocates use of oral bisphosphonates for most patients. Other new findings and alternative management approaches are also discussed.

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.

Osteoporosis prevention among chronic glucocorticoid users: results from a public health insurance database

IntroductionLong-term glucocorticoid therapy is the leading cause of secondary osteoporosis. The management of glucocorticoid-induced osteoporosis (GIOP) seems to be inadequate in many European countries.ObjectiveTo evaluate the rate of screening and...

Assessment and management of glucocorticoid-induced osteoporosis

Glucocorticoid-induced osteoporosis (GIO) is the most prevalent form of secondary osteoporosis; however, many patients taking glucocorticoids are still missing out on fracture risk assessments and boneprotection therapy. This article describes the clinical features, assessment and recommended management of GIO.

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.