Article

Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis: A randomized, controlled study

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Abstract

To determine the effects of a short course of a low dose of a glucocorticoid agent on bone mass. Double-blind, placebo-controlled, randomized study. Outpatient clinic of a university hospital. Forty patients with active rheumatoid arthritis. All patients started receiving intramuscular gold salts. In addition, they were randomly allocated to receive either prednisone or placebo. The initial dose was 10 mg/d, which was tapered between weeks 12 and 20. Thereafter, patients were followed for an additional 24 weeks. Lumbar bone mineral density was measured with dual-energy, quantitative computed tomography in a trabecular and a cortical region of interest. Despite favorable effects on disease activity and functional capacity, trabecular bone mineral density decreased in the prednisone-treated patients between baseline and week 20 (mean change, -8.2%; 95% CI, -12.7% to -3.7%; P = 0.001). Little change was found in the placebo-treated patients (P > 0.2), and the prednisone group had a greater mean bone loss than the placebo group (9.5%; CI, 3.4% to 15.6%; P = 0.003). After discontinuation of prednisone, an increase was found in trabecular bone mineral density between weeks 20 and 44 (mean change, 5.3%; CI, 0.7% to 9.9%; P = 0.03). Little change was found after withdrawal of placebo (P > 0.2). The mean improvement in the prednisone group was 6.8% (CI, 0.8% to 12.8%; P = 0.03) greater than for placebo. In both treatment groups, cortical bone mineral density did not change markedly in either period (P > or = 0.2). Low doses of glucocorticoid agents cause marked vertebral trabecular bone loss in the initial months of therapy in patients with active rheumatoid arthritis. After discontinuation of treatment, this bone loss seems to be (partially) reversible.

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... A terme, le risque d'une ostéoporose cortico-induite est important entraînant une perte de la densité osseuse pouvant conduire à l'augmentation de l'incidence des fractures à basse énergie. Evaluée par de nombreuses études [90,91,92], la perte osseuse corticoinduite est précoce avec un risque fracturaire apparaissant dès trois mois après l'introduction. Les fractures sont observées chez 30 à 50 % des patients recevant une corticothérapie au long cours et prédominent sur l'os trabéculaire (vertèbres et côtes) [90,91,92] [42,43,44]. ...
... Evaluée par de nombreuses études [90,91,92], la perte osseuse corticoinduite est précoce avec un risque fracturaire apparaissant dès trois mois après l'introduction. Les fractures sont observées chez 30 à 50 % des patients recevant une corticothérapie au long cours et prédominent sur l'os trabéculaire (vertèbres et côtes) [90,91,92] [42,43,44]. ...
Thesis
Introduction : Les évènements osseux sont fréquents chez les patients atteints d’un cancer bronchique métastatique au niveau osseux. Ces complications sont responsables d’une détérioration de la qualité de vie, d’une diminution de la survie et impactent fortement les dépenses de santé.Méthode : Nous avons mené une étude épidémiologique rétrospective sur 100 patients atteints de cancer bronchique avec métastases osseuses afin d’identifier les facteurs prédictifs de la survenue d’évènement osseux.Résultats : quatre vingt deux patients ont présenté au moins un évènement osseux dont 69,5 % à l’inclusion et 43 % expérimentaient des complications osseuses multiples. L’évènement osseux survenait en moyenne à 4,5 mois et le plus fréquent était les douleurs osseuses sévères (56 %). En analyse bivariée, l’administration d’une chimiothérapie ([RR] = 0,5, IC95% 0,3 à 0,9 ; p = 0,019) et la présence d’un évènement osseux initial ([RR] = 0,2, IC95% 0,1 à 0,4 ; p #lt# 0,0001) étaient des facteurs protecteurs. Une corticothérapie au long cours ([RR] = 2,2, IC95% 1,2 à 4 ; p = 0,0046), un taux de phosphatases alcalines #gt# 120 UI/l ([RR] = 1,9, IC95% 1,0 à 3,5 ; p = 0,02) et une calcémie #gt# 2,6 mmol/l ([RR] = 6,3, IC95% 2,6 à 15, p = 0,002) étaient des facteurs prédictifs de la survenue de complications osseuses. En analyse multivariée, l’absence d’évènement osseux initial et les taux de phosphatases alcalines et de calcium élevés étaient des facteurs prédictifs.Conclusion : Nos résultats ont vocation à sensibiliser les médecins pour améliorer le dépistage des métastases osseuses et instaurer un traitement préventif précoce afin de diminuer la survenue des évènements osseux
... Наибольшие потери костной массы наблюдаются в первые 3-6 мес лечения ГК, после чего ее снижение про- исходит более медленно, но оно продолжается в течение всего периода гормональной терапии [14]. У детей прием ГК приводит к нарушению процессов формирования, рос- та и прочности кости, что не дает возможности достичь пи- ка костной массы во взрослом возрасте. ...
... Лечение ГК -потенциально обратимый фактор рис- ка (ФР) остеопороза (ОП): при их отмене минеральная плотность кости (МПК) может спонтанно увеличиваться, а риск переломов -снижаться, однако даже после отмены он остается более высоким, чем в популяции [10,14,17]. ...
Article
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Glucocorticoids (GCs) play an important role in treating many inflammatory diseases due to their anti-inflammatory and immunomodulatory activities and are used in many fields of medicine. Despite their clinical benefits of GCs used to treat patients with chronic inflammatory diseases, prolonged administration of these medications, especially oral ones, frequently causes serious complications, such as bone loss and fractures. The present paper reviews the latest American College of Rheumatology clinical guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis, which were published in 2017. It provides comments, by taking into account the Russian guidelines on the diagnosis, prevention, and treatment of glucocorticoid-induced osteoporosis.
... A balance between bone formation and resorption is an important mechanism that maintains healthy bone structure and function. Osteoporosis, a reduction in BMD, is a crucial side effect of Dex, where the therapeutic and supratherapeutic doses of Dex reduce bone formation and resorption, respectively (Caniggia et al., 1981;Laan et al., 1993;Hansen et al., 1999;Suzuki, 2015). Physical reduction in bone weight and size due to Dex treatment are likely mediated via metabolic changes in bone tissues. ...
Article
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Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats. The Dex-treated rats suffered from a ∼20% reduction in weight gain, hyperglycemia (145 mg/dL), changes in serum lipids, and reduction in total serum alkaline phosphatase (ALP) (∼600 IU/L). Also, compared to controls, Dex-treated rats showed a distinctive metabolomics profile. In particular, serum amino acids metabolism showed six-fold reduction in phenylalanine, lysine, and arginine levels and upregulation of tyrosine and hydroxyproline reflecting perturbations in gluconeogenesis and protein catabolism which together lead to weight loss and abnormal bone metabolism. Sorbitol level was markedly elevated secondary to hyperglycemia and reflecting activation of the polyol metabolism pathway causing a decrease in the availability of reducing molecules (glutathione, NADPH, NAD⁺). Overexpression of succinylacetone (4,6-dioxoheptanoic acid) suggests a novel inhibitory effect of Dex on hepatic fumarylacetoacetate hydrolase. The acylcarnitines, mainly the very long chain species (C12, C14:1, C18:1) were significantly increased after Dex treatment which reflects degradation of the adipose tissue. In conclusion, long-term Dex therapy in rats is associated with a distinctive metabolic profile which correlates with its side effects. Therefore, metabolomics based profiling may predict Dex treatment-related side effects and may offer possible novel therapeutic interventions.
... In short, bone loss in chronic GC users is a well-known issue, but most studies and observations involved patients given long-term treatment with various doses of GCs [5,6,9], while little is known about the effects on bone of shortterm, high-dose GC therapies. In vitro studies show how GCs play a role in the differentiation process of a mesenchymal precursor toward osteoblast rather than adipocyte [10], with GCs having both catabolic and anabolic effects on bone [11]. ...
Article
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Purpose Chronic GC administration has numerous side effects, but little is known about the side effects of their short-term use (< 3 months)—particularly, when high doses are involved, as in the treatment of Graves’ orbitopathy (GO). We investigated the effects of short-term, high-dose GC on bone turnover markers, bone mineral density (BMD), and trabecular bone scores (TBS). Methods Eleven patients (10 females and 1 male; median age 56 years) with active GO who were candidates for treatment with intravenous (iv) methylprednisone were consecutively enrolled. All patients were pretreated with a loading dose of 300,000 units of cholecalciferol, then given a median cumulative dose of 4.5 g (range 1.5–5.25 g) iv methylprednisone. Biochemical parameters of bone metabolism (25OHD3, PTH, P1NP, CTX and bALP) were measured at the baseline, and then 1 week and 1, 3, 6 and 12 months. BMD and TBS were obtained by X-ray absorptiometry (DXA) at the baseline and at 6 and 12 months. On DXA image, morphometric vertebral fracture assessment (VFA) was done. Results There were no significant changes in PTH, bALP or P1NP. A significant drop in CTX was seen at 1 month (down Δ49.31% from the baseline, p = 0.02), with a return to the baseline at the 3-month measurement. There was a moderate (not significant), but persistent reduction in P1NP. No changes in BMD or TBS came to light. No vertebral fractures were documented. Conclusions Short-term, high-dose GC treatment caused a rapid, transient suppression of bone resorption, with no effects on BMD or bone micro-architecture (TBS).
... Fragility fractures may occur in approximately 20% of patients treated with steroids in the first year of treatment [10][11][12]. Due to the strong connections between inflammatory cells and bone cells, the inflammatory process requiring steroid use is itself a key factor in bone fragility and is one of the determinants of rapid bone loss at the onset of steroid use [13]. Risk factors for GC-induced fracture include low bone strength at the onset of GC treatment and bone mass reduction rate in treatment; this is largely determined by the dose and duration of GC use. ...
... En muchos estudios se va disminuyendo la dosis progresivamente hasta llegar a lo que se considera como mínima dosis efectiva (criterio generalmente no definido) 34,35,78 . La tabla 2 describe los principales esquemas encontrados en la RSL 23,25,30,31,36,38,48,51,53,55,[58][59][60]64,79 . ...
Article
Objectives (1) To systematically and critically review the evidence on the characteristics, efficacy and safety of glucocorticoids (CS) in rheumatoid arthritis (RA); (2) to generate practical recommendations. Methods A systematic literature review was performed through a sensitive bibliographic search strategy in Medline, Embase and the Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of CS in patients with RA. Two reviewers performed the first selection by title and abstract. Then 10 reviewers selected the studies after a detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. In a nominal group meeting, based on the results of the systematic literature review, related recommendations were reached by consensus. Results A total of 47 articles were finally included. CS in combination with disease-modifying antirheumatic drugs help control disease activity and inhibit radiographic progression, especially in the short-to-medium term and in early RA. CS can also improve function and relieve pain. Different types and routes of administration are effective, but there is no standardized scheme (initial dose, tapering and duration of treatment) that is superior to others. Adverse events when using CS are very frequent and are dose-dependent and variable severity, although most are mild. Seven recommendations were generated on the use and risk management of CS. Conclusions These recommendations aim to resolve some common clinical questions and aid in decision-making for CS use in RA.
... 28 The effect of steroids on bone health seems to be a least partially reversible on discontinuation of the drug, but this is not an option for all patients, necessitating adequate antiosteoporotic therapy. 29 Antiresorptive therapies in glucocorticoid-induced osteoporosis ...
Article
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Introduction: Glucocorticoid-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. Aims: This 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 review: In 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 therapy: Major 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.
... 5 Glucocorticoid therapy causes a rapid decline in areal bone mineral density (BMD). In one study, 6 rheumatoid arthritis patients who took prednisone 10 mg daily for 12 weeks and then tapered off by the 20th week experienced an 8% decline in spine BMD, with partial recovery of BMD by week 44. Not surprisingly, up to 25% of patients taking systemic glucocorticoid therapy will develop fractures. ...
Article
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Objective: Glucocorticoid-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. Methods: We 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. Results: Three 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. Conclusion: Results 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.
... Grade: Good, A, W Rationale: Data from multiple studies show that the best indicator of fracture risk in untreated patients is BMD prior to therapy (26À31), performing equally well in women and men (32). Substantial bone loss can take many years (33), but is accelerated in many circumstances, such as inflammatory arthritis (34,35), immobility (36), menopause (37), depression (38), glucocorticoid therapy (39,40), hormonal therapy for breast and prostate cancer (41), and HIV treatment (42). Even among the general population, the rate of bone loss varies substantially among individuals (27,29À31). ...
Article
Bone mineral density (BMD) can be measured at multiple skeletal sites using various technologies to aid clinical decision-making in bone and mineral disorders. BMD by dual-energy X-ray absorptiometry (DXA) has a critical role in predicting risk of fracture, diagnosis of osteoporosis, and monitoring patients. In clinical practice, DXA remains the most available and best validated tool for monitoring patients. A quality baseline DXA scan is essential for comparison with all subsequent scans. Monitoring patients with serial measurements requires technical expertise and knowledge of the least significant change in order to determine when follow-up scans should be repeated. Prior ISCD Official Positions have clarified how and when repeat DXA is useful as well as the interpretation of results. The 2019 ISCD Official Positions considered new evidence and clarifies if and when BMD should be repeated. There is good evidence showing that repeat BMD measurement can identify people who experience bone loss, which is an independent predictor of fracture risk. There is good evidence showing that the reduction in spine and hip fractures with osteoporosis medication is proportional to the change in BMD with treatment. There is evidence that measuring BMD is useful following discontinuation of osteoporosis treatment. There is less documentation addressing the effectiveness of monitoring BMD to improve medication adherence, whether monitoring of BMD reduces the risk of fracture, or effectively discriminates patients who should and should not recommence treatment following an interruption of medication. Further research is needed in all of these areas.
... In the long term, RA reduced function which leads to difficulties of doing daily living activities (ADL), and subsequently impact negatively on psychosocial aspect [2]. Furthermore, it relates to increased risk of osteoporosis [3] cardiovascular disease, and premature death. Mortality rates are more than twice as high in patients with RA as in the general population [4], and this gap appears to be widening [5]. ...
... Therefore, patients could benefit from continuous risk assessment with an emphasis on the appropriate duration of GC use. [9,18,19] As evidence of fracture risk in patients using GCs accumulates, drugs that effectively prevent fractures have been developed. However, many primary care physicians and specialists fail to recognize the severity of GIOP or deter-mine which patients are at greatest risk for GIOP. ...
... Because even low doses of GC can increase fracture risk, clinicians must aggressively taper the dose of GC when disease is under control. 74 Whether treating SLE disease activity to target would improve long-term outcomes in bone health needs to be addressed in future studies. ...
Article
Full-text available
Improvement in survival of systemic lupus erythematosus has been brought about with new advancement in treatment. However, glucocorticoids remain the sole cornerstone and as patients live longer, there is a need to address long-term complications brought by long-term glucocorticoid use such as osteoporosis. In this review, glucocorticoid-induced osteoporosis in systemic lupus erythematosus will be extensively discussed. This would include prevalence of osteoporosis in systemic lupus erythematosus patients, the difficulties in measuring fracture risk and pitfalls in using conventional methods such as bone mineral density. In addition, the mechanism of actions of glucocorticoids and evidence for glucocorticoids in the treatment of specific systemic lupus erythematosus manifestations would be explored and we also discussed specific pathophysiological mechanisms in the development of glucocorticoid-induced osteoporosis in systemic lupus erythematosus. We also reviewed the latest guidelines in the treatment of glucocorticoid-induced osteoporosis and the evidence for various osteoporosis medications. Finally, we recommend an approach in monitoring bone health and the treatment of osteoporosis specifically in systemic lupus erythematosus patients.
... The decline in bone mass is largely determined by GC therapy dose and duration with the rate of bone loss highest during the first 3 to 6 months of steroid initiation. However, the loss is reversible once GC are discontinued [2]. In Sudan, It is surprisingly common to see patients on maintenance treatment with oral GC for their rheumatic diseases because of relative affordability and availability compared to other immunosuppressant medications and biologics. ...
... Отмена ГКС может приводить к увеличению мине-ральной плотности костной ткани и снижению риска переломов [21,[39][40][41]. ...
Article
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Osteoporosis (OP) along with myocardial infarction, oncological diseases and expected death takes the lead in the general morbidity and mortality profile of population. The indicators of primary and general incidence of OP are markedly different in the regions of Russia according to the Healthcare Monitoring, Analysis and Strategic Development Department of the Central Research Institute of Organization and Informatization of Healthcare of the Ministry of Health of Russia and according to the data of epidemiological studies. Osteoporosis is classified as primary, if it develops in postmenopausal women or in older men in the absence of any underlying predisposing disease, and as secondary if there is a pathogenetic relationship with the disease or drug intake. The glucocorticoidinduced osteoporosis, which is distinguished in the International Classification System of Diseases and Death Causes (X revision) under code M 81.4 - drug-induced osteoporosis is the most common form of secondary osteoporosis. The topic of glucocorticoidinduced OP affects the professional fields of a significant number of medical specialties in connection with the common use of glucocorticosteroids in medicine. This article presents the issues of epidemiology, pathogenesis, complications of glucocorticoid-induced OP. Particular attention is paid to the prevention of this disease, including such non-pharmacological methods as a balanced diet, body weight gain to the recommended values, smoking cessation, regular exercise against weightlifting and resistance, protection against falls. Drug prophylaxis of glucocorticoid-induced OP is focused on the rational treatment to target of the underlying disease and the use of complex drugs containing vitamin D, calcium and synergistic osteotropic micronutrients.
... Appropriate preventive management can reduce the risk of osteoporotic fracture in patients receiving a steroid treatment (33,34). Moreover, cessation of oral corticosteroid treatment drove the risk of fracture towards the baseline levels regardless of the cumulative dose of steroids (35,36). In the present study, there was an increase in osteoporosis occurrence during the first year after ESI, but this trend reversed during the second year, with the prevalence of osteoporosis declining remarkably (Table 4). ...
Article
Background: Glucocorticoids adversely affect bone mineral density (BMD) and increase the risk of fracture. Yet, the cause-and-effect relationship between epidural steroid injection (ESI) and BMD has not been thoroughly investigated, and available results are inconsistent. This is probably a consequence of differences in the dose of steroids and follow-up duration. Objective: This study aimed to evaluate changes in BMD and the risk of fracture according to duration of the follow-up and amount of steroids used for ESI. Setting: Department of Orthopedic Surgery at Seoul Metropolitan Government Seoul National University (SMG-SNU) Boramae Medical Center, Korea. Methods: We retrospectively reviewed the medical records of postmenopausal patients who underwent dual-energy x-ray absorptiometry (DEXA) at least 3 times in 5 years. Patients were divided into 2 groups. Group 1 consisted of 73 patients who received ESI, whereas Group 2 consisted of 294 patients who did not receive ESI. All patients took anti-osteoporotic medications. BMD measurements were performed in 4 different regions, and levels of bone turnover markers (BTMs) were measured. In Group 1, BMD and BTMs levels were measured before the last ESI and 1 and 2 years after. A sub-analysis was conducted in Group 1 to compare BMD values in sub-groups with different doses of steroids. Results: In Group 1, the absolute values of BMD of the spine were decreased at the 1-year follow-up, but by the 2-year follow-up they recovered and approached the values in Group 2. In Group 2, BMD increased both at the 1- and 2-year follow-ups. There was an increase in occurrence of osteoporosis during the first year after ESI, but the prevalence of osteoporosis declined remarkably during the second year. The levels of BTMs increased at the 1-year follow-up and decreased at the 2-year follow-up in Group 1. Higher cumulative doses of steroids induced greater decreases in BMD. However, the changes in spine BMD in the sub-analysis were insignificant. Limitations: This was a retrospective study. Additionally, administration of anti-osteoporotic medication might have prevented accurate evaluation of the effects of ESI. Conclusions: ESI adversely affects BMD in postmenopausal women, especially that of the spine, and the adverse effects increase with the dose of steroids. Gradual reduction of the effect of steroids one year after the cessation of ESI resulted in recovery of BMD to a level similar to that in the control group. Key words: Epidural steroid injection, bone mineral density, osteoporosis, postmenopausal women, glucocorticoids, bone turnover markers, osteoporotic fracture.
... En muchos estudios se va disminuyendo la dosis progresivamente hasta llegar a lo que se considera como mínima dosis efectiva (criterio generalmente no definido) 34,35,78 . La tabla 2 describe los principales esquemas encontrados en la RSL 23,25,30,31,36,38,48,51,53,55,[58][59][60]64,79 . ...
Article
Objectives: 1) To systematically and critically review the evidence on the characteristics, efficacy and safety of glucocorticoids (CS) in rheumatoid arthritis (RA); 2) to generate practical recommendations. Methods: A systematic literature review was performed through a sensitive bibliographic search strategy in Medline, Embase and the Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of CS in patients with RA. Two reviewers performed the first selection by title and abstract. Then 10 reviewers selected the studies after a detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. In a nominal group meeting, based on the results of the systematic literature review, related recommendations were reached by consensus. Results: A total of 47 articles were finally included. CS in combination with disease-modifying antirheumatic drugs help control disease activity and inhibit radiographic progression, especially in the short-to-medium term and in early RA. CS can also improve function and relieve pain. Different types and routes of administration are effective, but there is no standardized scheme (initial dose, tapering and duration of treatment) that is superior to others. Adverse events when using CS are very frequent and are dose-dependent and variable severity, although most are mild. Seven recommendations were generated on the use and risk management of CS. Conclusions: These recommendations aim to resolve some common clinical questions and aid in decision-making for CS use in RA.
... The most common form of secondary osteoporosis arises from long-term use of glucocorticoids, which even at low dosages causes a significant decrease in BMD. 12 Other conditions associated with an increased fracture risk and osteoporosis in children include endocrine disturbances, inflammatory diseases, certain forms of cancer and associated treatments, immobilisation and haematological disorders ( Table 1). Additional risk factors, such as limited physical activity and nutrition (especially low intake of vitamin D, calcium and proteins) also affect bone mass accrual in both healthy and chronically ill children. ...
Article
Osteoporosis is traditionally regarded as a disease of elderly women. However, this bone disorder occurs in patients of both sexes and of all ages and is also increasingly recognised in the paediatric setting. In particular, patients, including young children, with other chronic diseases are at risk of developing bone fragility. There are also several forms of hereditary osteoporosis, which should be identified at an early stage to ensure adequate treatment. The diagnosis of osteoporosis in children is challenging, since their bone mineral density (BMD) is affected by growth and pubertal development. In addition to low BMD, a child must also exhibit a significant proneness to fractures before the osteoporosis diagnosis can be made. Through early diagnosis and treatment for paediatric bone fragility, we can also ameliorate bone health in adulthood. In this article we review the aetiology, known risk factors and the diagnostic criteria of osteoporosis in the young.
... It has been shown that bone loss and an increased fracture rate occur early after the initiation of glucocorticoid therapy [4], due to relatively higher bone resorption and suppressed bone formation, which occur due to glucocorticoid treatment. Thus, the guidelines for glucocorticoid-induced osteoporosis in adults recommend the prevention of osteoporosis, rather than treatment, recommended for all patients for whom long-term glucocorticoids is planned [5]. ...
Article
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Background: Bisphosphonates are recommended for use as first-line therapy for the prevention and treatment of glucocorticoid-induced osteoporosis in adults. However, the appropriate usage of bisphosphonates for the prevention or treatment of glucocorticoid-induced osteoporosis in children remains unclear. Methods: We performed a cross-sectional study to clarify the factors associated with the development of glucocorticoid-induced bone loss and osteoporosis in patients with childhood-onset rheumatic disease and to investigate the impact of the early use of alendronate. We recruited 39 patients with childhood-onset rheumatic disease who were evaluated to detect bone loss or osteoporosis at 3 months to 1.5 years after the initiation of treatment. The primary outcome of the study was the presence of bone loss or osteoporosis at the initial evaluation of the bone mineral density after at least 3 months of glucocorticoid therapy. Results: Bone loss and a history of fracture were found in 56 and 18% of the participants, respectively. Weekly oral alendronate therapy (median, 25.4 mg/m2) had been started by the time of the evaluation of osteoporosis in 46% of the participants and within 3 months after the start of glucocorticoid in 31% of the participants. There were no significant differences between the participants with bone loss (wBL group) and without bone loss (w/oBL group) in terms of gender, primary disease, or the age at the onset of primary disease. In terms of glucocorticoid use, there was no significant difference in the age at the start of glucocorticoid therapy, the length of glucocorticoid use, or the dose of glucocorticoids. The proportion of patients in the w/oBL group who received alendronate within 3 months after the start of glucocorticoid therapy was significantly greater than that in the wBL group. In the logistic regression analysis, only "alendronate therapy within 3 months after the start of glucocorticoid therapy" had a statistically significant effect on the development of bone loss (OR, 0.08; 95% CI, 0.02-0.43). The analysis did not reveal any factors associated with the development of osteoporosis. Conclusions: The early use of alendronate may have a preventive effect against the development of bone loss in glucocorticoid-treated patients with childhood-onset rheumatic disease.
... In the long term, RA reduced function which leads to difficulties of doing daily living activities (ADL), and subsequently impact negatively on psychosocial aspect [2]. Furthermore, it relates to increased risk of osteoporosis [3] cardiovascular disease, and premature death. Mortality rates are more than twice as high in patients with RA as in the general population [4], and this gap appears to be widening [5]. ...
Article
Full-text available
Background: There is a growing interest in treatments involving natural means and procedures, alternative to those of conventional medicine. Some special sands are being used worldwide in therapeutic applications, especially in musculoskeletal problems. Objectives: To compare the effect of Siwan traditional therapy versus conventional therapy for functional disability and pain in rheumatoid arthritis. Design: A prospective, randomized, single-blind, pre-post-test, controlled trial. Setting: Four physical therapy departments in four multidiscipline, outpatient medical centers, located in Marsa Matrouh. The study was conducted between June 2015 and August 2016. Participants: Thirty patient’s rheumatoid arthritis (aged between 20 and 50 y) according to the American Rheumatism Association criteria 2010, participated in the study. Interventions: The patients were randomly assigned into 2 equal groups. Group (A) received Siwan traditional therapy in the form of sand bathing, followed by massage with olive oil for 7 d and group (B) received conventional physical therapy for two months’ day after day in the form of heat application, electrical stimulation (TENS), and exercise. Main outcome measure: The primary outcome was pain severity measured by visual analogue scale while the secondary outcome was functional disability measured by Health Assessment Questionnaire (HAQ). Results: Thirty patient with rheumatoid arthritis (group (A) n=15; group (B) n=15) were randomized and analysed. Comparing both groups post-program revealed that there were significant differences (P<0.05) in pain level and HAQ between both groups with a significant reduction in favor of the group (A). Conclusion: The Siwan therapy program was more effective than traditional physical therapy program in the treatment of rheumatic patients.
... Systemische Glucokortikoide führen je nach Dosis und Therapiedauer zu einer Abnahme der Knochenmineral dichte. In einer Studie von Laan et al. aus dem Jahr 1993 wurden 40 Patienten mit einer aktiven rheumatoiden Arthritis, behandelt mit intramuskulärem Gold, für drei Monate entweder mit 10 mg Prednison pro Tag per os oder Plazebo therapiert [4]. Im Verlauf wurde die Dosis der Glucokortikoide um 2,5 mg pro Woche reduziert und nach Woche 18 resp. ...
... Les glucocorticoïdes systémiques entraînent, selon la dose et la durée du traitement, une perte de densité minérale osseuse. Dans une étude de Laan et al. datant de 1993, 40 patients présentant une polyarthrite rhumatoïde active, traités par sels d'or injectés en intramusculaire, ont été traités par soit 10 mg de prednisone par jour par voie orale, soit par placebo, et ce durant trois mois [4]. Au fur et à mesure, la dose de glucocorti-coïdes a été réduite de 2,5 mg par semaine et supprimée après la semaine 18, soit à la semaine 19. ...
... One year should be sufficient to appreciate changes in T-scores as glucocorticoids seem to cause marked vertebral bone loss in the initial months of therapy. 15 Consistently, Svendsen et al showed that the BMD loss primarily occurred in the first year following treatment. 10 One new fracture occurred during follow-up in the placebo group, therefore no firm conclusions can be made on whether the reduced BMD loss at lumbar spine level eventually translates into a clinically relevant reduction in fractures. ...
Article
Lymphoma patients often receive high glucocorticoid doses as part of standard therapy. Observational studies have shown substantial risk of glucocorticoid-induced osteoporosis (GIO) with associated fractures. The aim of the SIESTA trial was to determine if oral alendronate (ALN) is a safe and effective prophylaxis against GIO in lymphoma. SIESTA was a single-center, randomized, double-blinded, phase 2 study of lymphoma patients planned for glucocorticoid-containing chemotherapy. After randomization, patients received weekly ALN 70mg or placebo for a total of 52 weeks. Bone mineral density (BMD) was assessed at baseline, after completion of chemotherapy (EOT, 4-6 month), and at end of study (EOS, 12 month). Vertebral fracture and biomarkers were assessed at baseline and EOS. Patients with baseline BMD assessment and at least one follow-up BMD assessment were analyzed for efficacy. Primary endpoint was change in lumbar spine T-score from baseline to EOS. Of the 59 patients enrolled, 23/30 in the ALN arm and 24/29 in the placebo arm were analyzed for efficacy. Mean change in T-score from baseline to 12 month at lumbar spine was +0.15 for ALN and -0.12 for placebo (P=0.023). The difference in ∆T_EOS between the ALN and placebo groups was larger among females (ALN 0.28; placebo -0.28) (P=0,01). Biomarker analyses confirmed reduced bone resorption in ALN treated patients. In conclusion, ALN is a safe and effective primary prophylaxis against loss in BMD following glucocorticoid-containing chemotherapy. Despite reduced BMD loss in the ALN arm, the treatment did not influence fracture risk in this small cohort of patients. This trial is registered at www.clinicaltrials.gov as 2015-005688-18.
... [33] The highest rate of bone loss is observed within the first 3-6 months of GC treatment, although a slower decline continues with persistent use. [34] The maximum impact is seen on the metabolically active trabecular bone such that most of the fractures involve the vertebrae. This fracture risk is a function of both the daily dose and the cumulative dose of GCs. ...
Article
Drug-induced bone disorders are a group of disorders characterized by osteomalacia or osteoporosis, with the common denominator being the iatrogenic nature of the disease. Drug-induced bone disorders are either due to the drug directly effecting the bone microarchitecture (osteoblastic or osteoclastic activity) or indirectly by interfering with Vitamin D metabolism, Vitamin D/calcium absorption, and excess calcium loss or due to altered hormone states which promote bone loss (hypogonadism, hyperthyroidism, somatostatin excess states, insulin deficiency, increased systemic inflammation, and oxidative stress). References for this review were identified through searches of PubMed, Medline, and Embase for articles published until July 2019 using the terms “drug induced bone disorders” (MeSH Terms) AND “osteoporosis” (All Fields) OR “osteomalacia” (All Fields). Anti-epileptics, proton pump inhibitors, glucocorticoids, immunosuppressants (calcineurin inhibitors), anticoagulants, glitazones, SGLT2 inhibitors, somatostatin analogs, anticancer medications, and protein kinase inhibitors are some of the commonly used medications associated with bone mineral loss. An increased awareness, minimizing the use of these medications in patients at increased risk of fractures, keeping dosage and duration of therapy to the lowest, ensuring Vitamin D and calcium adequacy either through diet or supplements, and prophylactic use of bisphosphonates (where indicated) can play a major role in preventing morbidity associated with drug-induced bone disorders.
... 32,40,49,[87][88][89][90] This observation is supported by literature from corticosteroidtreated adult populations, which shows that after corticosteroid termination, bone mineral density increases and clinical fracture risk declines. 102,103 However, the age of corticosteroid administration might play a role in this respect, as corticosteroid exposure during puberty, an important period for bone mass acquisition, could affect bone mineral density more severely and permanently than during the prepubertal period. 104,105 In addition, the fracture risk associated with corticosteroids in other populations might be due to mechanisms not definitively assessed by bone mineral density measure ments, such as altered bone structure and increased risk of falls due to muscle weakness. ...
Article
Childhood, adolescent, and young adult cancer survivors are at increased risk of reduced bone mineral density. Clinical practice surveillance guidelines are important for timely diagnosis and treatment of these survivors, which could improve bone mineral density parameters and prevent fragility fractures. Discordances across current late effects guidelines necessitated international harmonisation of recommendations for bone mineral density surveillance. The International Late Effects of Childhood Cancer Guideline Harmonization Group therefore established a panel of 36 experts from ten countries, representing a range of relevant medical specialties. The evidence of risk factors for very low and low bone mineral density and fractures, surveillance modality, timing of bone mineral density surveillance, and treatment of very low and low bone mineral density were evaluated and critically appraised, and harmonised recommendations for childhood, adolescent, and young adult cancer survivors were formulated. We graded the recommendations based on the quality of evidence and balance between potential benefits and harms. Bone mineral density surveillance is recommended for survivors treated with cranial or craniospinal radiotherapy and is reasonable for survivors treated with total body irradiation. Due to insufficient evidence, no recommendation can be formulated for or against bone mineral density surveillance for survivors treated with corticosteroids. This surveillance decision should be made by the survivor and health-care provider together, after careful consideration of the potential harms and benefits and additional risk factors. We recommend to carry out bone mineral density surveillance using dual-energy x-ray absorptiometry at entry into long-term follow-up, and if normal (Z-score > −1), repeat when the survivor is aged 25 years. Between these measurements and thereafter, surveillance should be done as clinically indicated. These recommendations facilitate evidence-based care for childhood, adolescent, and young adult cancer survivors internationally.
... Use of GC is the most common cause of secondary osteoporosis [2,3], and 30-40% of all patients treated with GC have radiological evidence of vertebral fractures [4,5]. Risk of bone loss and fracture rises rapidly after GC treatment initiation [6][7][8]. In addition, for persons with similar bone mineral density (BMD), the risk of vertebral fractures is larger for GC users than for nonusers [9], indicating an additional effect on bone quality. ...
Article
Full-text available
Glucocorticoid use is a risk factor for osteoporosis and fractures. We studied whether women initiating glucocorticoid treatment also started anti-osteoporotic treatment, according to clinical guidelines. Women with versus without previous fracture were twice as likely to start anti-osteoporotic treatment within 1 year after initiating glucocorticoid treatment, but the cumulative incidences were low 9.1% vs. 4.6%, respectively.PurposeUse of glucocorticoids (GC) is a risk factor for osteoporosis and fractures, and clinical guidelines suggest that preventive treatment with anti-osteoporotic drugs (AOD) should be considered when starting GC. Women with high risk of osteoporosis comprise those with previous fractures or a known inflammatory rheumatic disease, for whom the indication of AOD is even stronger. The purpose of these analyses was to investigate whether women initiating GC treatment also started AOD, especially those with high risk of osteoporosis.Methods We used data from the Norwegian Prescription Database to identify all women 55 years and older initiating GC treatment in Norway during 2010–2016 and to obtain information on use of AOD. Data from the Norwegian Patient Registry were used to obtain information on previous fractures and diagnoses.ResultsAmong 105,477 women initiating GC treatment during 2010–2016, 3256 had started AOD and 79,638 had discontinued GC treatment after 1-year follow-up. Cumulative incidence of starting AOD after 1 year was 9.1% (95% CI: 7.9, 10.4) for women with vs. 4.6% (95% CI: 4.4%, 4.8%) for women without a previous fracture. Women with rheumatoid arthritis or another inflammatory rheumatic disease were more likely to start AOD than women with other indications. For the whole cohort, the probability of starting AOD treatment within 1 year after initiating GC increased on average 3% per year (HR = 1.03, CI: 1.01, 1.05) from 2010 to 2016.Conclusions Having had a previous fracture or an inflammatory rheumatic disease increased the probability of treatment with AOD. However, the proportions starting AOD were much lower than clinically indicated.
... Many studies have investigated loss of bone density in patients undergoing chronic treatment with systemic corticosteroids, but most of these studies involved patients who had long-term treatment with various doses of corticosteroids [12,13]. In contrast, little is known about the effects on bone metabolism of short-term therapy with high doses of corticosteroids, such as in the treatment of AECOPD [14]. ...
Article
Full-text available
Background: Long-term treatment with corticosteroids causes loss of bone density, but the effects of using short-term high-dose systemic-corticosteroid therapy to treat acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to determine whether high-dose corticosteroid therapy affected bone turnover markers (BTMs) to a greater extent compared to low-dose corticosteroid therapy. Methods: The CORTICO-COP trial (NCT02857842) showed that an eosinophil-guided corticosteroid intervention led to approximately 60% lower accumulated corticosteroid dose for hospitalized patients with AECOPD (low-dose group) compared with 5-day standard corticosteroid treatment (high-dose group). We compared the levels of BTMs C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) in 318 participants during AECOPD and at 1- and 3-month follow-up visits. Results: CTX decreased and P1NP increased significantly over time in both treatment groups. There were no significant differences between the groups at 1- or 3-months follow-up for P1NP. A significant drop in CTX was seen at 3 months (down Δ24% from the baseline, p = 0.017) for the high dose group. Conclusion: Short-term, high-dose systemic corticosteroid treatment caused a rapid suppression of biomarkers of bone resorption. Corticosteroids did not suppress biomarkers of bone formation, regardless of patients receiving low or high doses of corticosteroids. This therapy was, therefore, harmless in terms of bone safety, in our prospective series of COPD patients.
... 32 In steroid-treated patients with normal renal function, treatment withdrawal is associated with a rapid increase in bone mineral density and a decrease in the fracture risk. [33][34][35] One can reasonably expect the same to be true of kidney transplant patients but these changes would need to be confirmed -especially since the bone microarchitecture is impaired in this population (as described above). ...
Article
Full-text available
Background Long-term corticosteroid use after kidney transplantation is associated with a decrease in bone mineral density (BMD) and a high fracture risk. We hypothesized that patients with early steroid withdrawal (ESW) would display a gain in BMD in the year following kidney transplantation, when compared with patients on long-term corticosteroid therapy. Methods In a cohort of kidney transplant recipients, 356 patients were included between 2012 and 2019. Dual-energy X-ray absorptiometry was performed 1 and 12 months after transplantation. The data were analyzed using linear regression with inverse probability-of-treatment weighting (based on a propensity score). Results At 1 year after transplantation, the gain in BMD was significantly greater in recipients with ESW than in recipients on long-term corticosteroid therapy for the lumbar spine (+0.036 g/cm ² , p < 0.001) and the femoral neck (+0.020 g/cm ² , p = 0.035). Among patients with ESW, (i) none had osteoporosis, (ii) the percentage with normal BMD increased from 33.3% at month 1 to 54.4% at month 12, and (iii) the percentage with osteopenia fell from 56.2% to 45.6%. In patients undergoing long-term corticosteroid therapy, the fracture incidence was 13.5 per 1000 person-years. None of the patients in the ESW group experienced a fracture. Conclusion ESW has a positive effect on bone in kidney transplant recipients.
... Rheumatoid arthritis (RA) is a usual risk associated with osteoporosis its investigation benchmarks dual energy X-ray absorptiometry (DEXA) for calculating bone mineral density (BMD) in RA [1,2].Early phase of rheumatoid arthritis occurs with loss of periarticular bone [3,4]. As stated, RA leads to bone loss; however contribution of multiple factors speculates its generalized bone loss [5][6][7]. Multifactorial postulates like functional loss and long time span of illness imposes a negative effect on bone mineral density (BMD) in case of both axial and peripheral bones. In early stage of RA, the disease activity relates more with functional capacity; though joint damage becomes severely indisposed in later stages. ...
Article
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Background:Osteoporosis (OP) is being increasingly recognized in inflammatory rheumatic diseases like rheumatoid arthritis (RA), characterized mainly by low bone mass, reduced bone strength, and an increased risk of fractures affecting bone metabolism influencing bone mineral density (BMD) and fracture risk.Results :Women in the RA with PRED group did not show lower BMD values than those in the RA without PRED group at baseline, in both lumbar spine L1-L4 (P=0.691), in femoral neck (P=0.332), in radius total (P=0.564) and radius UD (P=0.941). Women in the RA without PRED group had lower T score (Radius UD) (P=0.015) value than those in the RA with PRED group. However, during 12 months follow ups there was no statistically significant difference between the two groups in the change in BMD or projection area in the lumbar spine, femoral neck and radius UD.Conclusion: Premenopausal RA women with or without prednisolone treatment lost their bone mass statistically similar. Study assumes role of RA on axial bone mass development will be less important with better treatment of RA than our patients received.
... Glucocorticoid-related bone loss has also been shown to be potentially reversible. Termination of therapy is associated with increased bone mineral density and decreased risk of subsequent fractures [15][16][17]. ...
Article
Full-text available
Purpose of Review We aim to critically review recent recommendations regarding preventative strategies for glucocorticoid-induced osteoporosis and provide a summary of key evidence regarding available interventions. Recent Findings Lifestyle optimization remains the hallmark of bone health preservation. Early initiation of anti-osteoporotic agents in the setting of glucocorticoid exposure is essential, guided by appropriate risk stratification. Recommendations for calcium and vitamin D intake optimization are well-supported across all risk strata. Bisphosphonates are the mainstay of pharmacological therapy. Newer agents such as denosumab and teriparatide have demonstrated comparative benefit in terms of incident fracture risk reduction and bone mineral density preservation, with comparable adverse events. With due consideration to cost, resource availability, and patient values and preferences, these agents may warrant use as the first-line agents in this setting. Summary Glucocorticoid-induced osteoporosis remains preventable and warrants early and targeted evidence-based therapy.
... This leads to an increase in bone fragility and susceptibility to fracture. Beyond those factors affecting osteoporosis patients in general, the risk of bone loss and fracture in patients with RA is increased due to other factors such as the use of glucocorticoids, chronic inflammation, and physical inactivity [1][2][3][4][5][6][7]. Fractures can cause substantial pain and severe disability, often leading to a reduced quality of life. ...
Article
Less is known about the risk of fracture in people with rheumatoid arthritis aged under 50 than those in older age groups. The study shows that the risk of fracture before age 50 remains significantly higher in those with rheumatoid arthritis than matched controls. This has implications for fracture risk management. Introduction: To determine the risk of first and subsequent fracture occurring before age 50 in people diagnosed with rheumatoid arthritis (RA) before age 50. Methods: A retrospective observational cohort study of RA cases with matched controls using data from Clinical Practice Research Datalink (CPRD) of adults ≥ 18 years with diagnosis of RA recorded from 1992 to 2016 in the UK. Patients were followed from index date to the first fracture and subsequent fracture. A total of 36,858 cases were each matched to 3 controls. Incidence rates (IR) and incidence rate ratios (IRR) of first and subsequent fractures were calculated. A multivariate Cox's proportional hazards model was used to calculate the risk of first fracture and of subsequent fracture in the presence of different risk factors. Results: The IR of first and subsequent fractures at any age is significantly higher in cases than controls for patients with onset of RA at any age. This includes first fractures occurring before age 50 for those diagnosed with RA before this age. In women, the rate of first fracture before age 50 are significantly higher than matched controls (IRR 1.29 CI 1.12-1.49), the IRR for subsequent fracture is higher but not significantly so. For men, the IRRs of first and subsequent fractures below age 50 are also higher but not significantly so. Gender, previous fracture, glucocorticoid prescription, osteoporosis diagnosis, alcohol, smoking, and bisphosphonate prescription have a significant effect on the risk of first fracture at any age for RA patients; all these variables except osteoporosis diagnosis and alcohol have a significant effect on the risk of subsequent fracture and first fractures before age 50. Conclusions: These results indicate an increased risk of first fracture before age 50 in people with RA diagnosed before this age. It is important that patients with RA of all ages are given timely support from the time of diagnosis to protect their bone health.
... Higher doses of glucocorticoids are associated with rapid bone loss, affecting mostly the axial and appendicular skeleton, but also at the spine [27]. A prospective study by Laan et al. has demonstrated that 20 weeks of glucocorticoid treatment with a mean dose of 7.5 mg/day resulted in an 8% trabecular bone loss in the lumbar spine [28]. In addition, histomorphometric studies have shown that glucocorticoid treatment results in a significant decrease in osteoid seams and mean wall thickness [29], with the overall bone loss demonstrated to be 30% [26]. ...
Article
Full-text available
Osteoporosis is one of the most common disorders around the world. Osteoporotic fracture especially hip fracture are associated with an increased mortality rate in elders. However, elders with osteoporosis or at high risk of fractures remain largely underdiagnosed and undertreated. The screening, diagnosis, and treatment of osteoporosis must be improved to maintain pace with its fast-growing prevalence. This review will cover risk factors of osteoporosis, screening and diagnosis tools, newfound advancements, current medical treatments including options for special populations of concern, and future research directions.
... Die negativen Effekte einer GC-Behandlung auf den Knochen sind jedoch ein potenziell reversibler Risikofaktor für die GIOP. Die Beendigung einer GC-Behandlung ist mit einem potenziellen Anstieg der BMD und einer Erniedrigung des Frakturrisikos verbunden [39,48,90]. Zudem ist eine kurzzeitige hoch dosierte GC-Therapie nur mit einem geringen Anstieg des Frakturrisikos assoziiert [29]. ...
Article
Background 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.Objective To develop recommendations for the management of glucocorticoid-induced osteoporosis (GIOP) in adult patients on long-term glucocorticoid (GC) treatment.MethodsA systematic 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 a structured group consensus process.ResultsRecommendations include supplementation with calcium and vitamin D 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, a switch to another class of specific osteologic drugs should be performed. We recommend re-evaluation after a treatment duration of 3–5 years or after termination of long-term GC treatment.Conclusion 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.
Article
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Introduction Osteoporosis is one of the serious adverse effects associated with glucocorticoid therapy. Although bisphosphonates have been used for glucocorticoid-induced osteoporosis (GIO), some patients have shown an inadequate response. In such cases, denosumab or teriparatide are used. However, there is no consensus on which of these two drugs is superior. We prospectively compared denosumab's and teriparatide's effects on the bone mineral density (BMD) in GIO patients with prior bisphosphonate treatment. Materials and methods After receiving oral bisphosphonates for ≥2 years, GIO patients with low T-score BMD (<−2.5) were switched from bisphosphonates to denosumab (n = 20) or daily teriparatide (n = 21). We measured the BMD (lumbar spine, femoral neck, and total hip) in both groups every 6 months for 24 months. Results At 24 months of treatment, the lumbar spine BMD increased significantly from baseline in both the denosumab and teriparatide groups (baseline vs. denosumab and teriparatide; 5.9 ± 5.6%, P < .001 and 7.9 ± 5.4%, P < .001). A significant increase in femoral neck BMD from baseline occurred only in the teriparatide group (6.6 ± 10.8%, P < .05); denosumab (1.5 ± 5.0%). No significant changes occurred in the total hip BMD from baseline in either group (−0.1 ± 5.6% and 3.3 ± 7.5%, respectively). There was no significant difference between the denosumab and teriparatide groups at 24 months in lumbar spine and femoral neck BMD, but was significantly higher in the teriparatide group at 12 months (P < .01 and P < .05 in the lumbar spine and femoral neck, respectively). Conclusion Teriparatide might have some advantages over denosumab and be a good alternative for treating GIO patients with prior bisphosphonate treatment.
Chapter
The goals of this chapter will be to give a brief overview of bone biology, describe the molecular mechanisms of bone remodeling and pathologic uncoupling, and provide a general survey of the multiple pathways leading to aging bone and osteoporosis.
Article
Risk of fracture due to glucocorticoid-induced osteoporosis (GIO) can be reduced by anti-osteoporosis (OP) medications. The proportion of patients on long-term glucocorticoid therapy who received anti-OP medications according to the GIO management guidelines has increased in recent years, but is still suboptimal.IntroductionAdherence of physicians to guidelines for glucocorticoid (GC)-induced osteoporosis (GIO) management is currently unclear. This study aimed to clarify the state of guideline adherence by physicians in Japan and identify factors associated with guideline adherence using a nationwide health insurance claims database (NDBJ).Methods Patients aged ≥ 50 years who were prescribed GC for ≥ 90 days after 180 days without a GC prescription and who were followed up for osteoporosis (OP) management for the subsequent 360 days during the period spanning 2012–2018 were selected from the NDBJ. Guideline adherence was evaluated with the proportion of patients who received OP management as recommended by the Japanese guidelines. Information on previous vertebral and hip fractures, dementia, and polypharmacy was obtained. Factors associated with OP management were evaluated by logistic regression analysis.ResultsA total of 512,296 patients were considered to be at high risk of fracture according to the guidelines. Proportions of patients receiving OP management (BMD testing or anti-OP medications) have increased in recent years. In 2017, 33.7% of men and 55.3% of women received OP management in the initial 90 days of GC therapy. Female sex, previous anti-OP medications, polypharmacy, and higher GC dose were significantly associated with receiving OP management, while dementia showed an inverse association. A prior history of hip fracture, a strong risk factor for future fracture, was not significantly associated with receiving OP management.Conclusions Although guideline adherence by physicians has increased in recent years, it remains suboptimal. Further efforts to improve guideline adherence are necessary.Trial registration numberThe present study is not registered.
Chapter
Over the past decades, glucocorticoids booked its place as one of the most commonly prescribed classes of drugs for several medical conditions. Although the adverse skeletal effects of glucocorticoids have been recognized for decades, attention to this side effect has gained increased attention because of the widespread long-term clinical use of glucocorticoids. Glucocorticoid-induced osteoporosis has been considered the most common cause of secondary osteoporosis. For its negative impact on the musculoskeletal health and its subsequent significantly elevated fracture risk, several international societies have published recommendations for the prevention and management of glucocorticoid-induced osteoporosis. Glucocorticoids effect on bone is both direct and indirect, including a receptor activator of nuclear factor-κB ligand (RANKL)–induced increase in osteoclasts, osteocyte apoptosis, and decreased recruitment and accelerated osteoblast apoptosis. In addition, glucocorticoids increase the risk for falls, which has been attributed to the reduction of muscle mass and a decrease in calcium resorption. On the other hand, the fracture risk rapidly decreases after glucocorticoid discontinuation. This chapter will review the epidemiology and pathophysiology of glucocorticoid-induced osteoporosis. This will be followed by discussing the effect of glucocorticoids on the musculoskeletal health, namely bones and muscles, clinical correlations of glucocorticoid-induced osteoporosis, risk stratification, screening and assessment, and glucocorticoid associated changes in bone mineral density and bone architecture. The chapter will then discuss the monitoring of BMD and fracture risk assessment as well as management of the glucocorticoid-induced osteoporosis. The chapter will conclude with an algorithm for assessment and management of glucocorticoid-induced osteoporosis.
Article
Background: 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. Objective: To develop recommendations for the management of glucocorticoid-induced osteoporosis (GIOP) in adult patients on long-term glucocorticoid (GC) treatment. Methods: A systematic 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 a structured group consensus process. Results: Recommendations include supplementation with calcium and vitamin D 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, a switch to another class of specific osteologic drugs should be performed. We recommend re-evaluation after a treatment duration of 3-5 years or after termination of long-term GC treatment. Conclusion: 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.
Article
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Rheumatoid arthritis (RA) is an autoimmune chronic connective tissue disease that produces persistent systemic inflammation, with joint inflammation leading to function loss and joint destruction. Low bone mass causes skeletal bone loss, commonly referred to as osteopenia or osteoporosis. We conducted this literature review to examine the relationship between RA and osteoporosis and the variables contributing to this connection. We used articles from the US National Library of Medicine (PubMed), Google Scholar, Science Direct to access the required information. Eventually, our results concluded that RA could result in local periarticular and generalized bone loss. Many risk factors contribute to this association, such as chronic joints inflammation, glucocorticoid use, genetics, and estrogen hormone effects. Still, it is not clear yet whether this is due to a consequence of treatment, immobility, or the activity of the disease. There are many recommendations by the American College of Rheumatology for RA patients during the disease course to reduce the risk of osteoporosis development, which include early starts of disease-modifying anti-inflammatory drugs (DMARDs), doing a dual-energy x-ray (DXA) or quantitative ultrasound (QUS) for identifying a patient at risk of osteoporosis, taking vitamin D, calcium, and bisphosphonates. Further prospective studies and clinical trials are essential to provide a solid evidence-based recommendation that will help to prevent bone loss in RA patients.
Article
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Glucocorticoid-induced osteoporosis is a frequent complication of systemic glucocorticoid (GC) therapy and mainly characterized by suppressed osteoblast activity. Wnt16 derived from osteogenic cells is a key determinant of bone mass. Here, we assessed whether GC suppress bone formation via inhibiting Wnt16 expression. GC treatment with dexamethasone (DEX) decreased Wnt16 mRNA levels in murine bone marrow stromal cells (mBMSCs) time- and dose-dependently. Similarly, Wnt16 expression was also suppressed after DEX treatment in calvarial organ cultures. Consistently, mice receiving GC-containing slow-release prednisolone pellets showed lower skeletal Wnt16 mRNA levels and bone mineral density than placebo-treated mice. The suppression of Wnt16 by GCs was GC-receptor-dependent as co-treatment of mBMSCs with DEX and the GR antagonist RU-486 abrogated the GC-mediated suppression of Wnt16. Likewise, DEX failed to suppress Wnt16 expression in GR knockout-mBMSCs. In addition, Wnt16 mRNA levels were unaltered in bone tissue of GC-treated GR dimerization-defective GR dim mice, suggesting that GCs suppress Wnt16 via direct DNA-binding mechanisms. Consistently, DEX treatment reduced Wnt16 promoter activity in MC3T3-E1 cells. Finally, recombinant Wnt16 restored DEX-induced suppression of bone formation in mouse calvaria. Thus, this study identifies Wnt16 as a novel target of GC action in GC-induced suppression of bone formation.
Article
Objectives. Glucocorticosteroids (GCs) are recommended to suppress inflammation in people with active RA. This systematic review and meta-analysis aimed to quantify the effects of systemic GCs on RA pain. Methods. A systematic literature review of randomized controlled trials (RCTs) in RA comparing systemic GCs to inactive treatment. Three databases were and spontaneous pain and evoked pain outcomes were extracted. Standardized mean differences (SMDs) and mean differences were metaanalysed. Heterogeneity (I2, tau statistics) and bias (funnel plot, Egger’s test) were assessed. Subgroup analyses investigated sources of variation. This study was pre-registered (PROSPERO CRD42019111562). Results. A total of 18 903 titles, 880 abstracts and 226 full texts were assessed. Thirty-three RCTs suitable for the meta-analysis included 3123 participants. Pain scores (spontaneous pain) decreased in participants treated with oral GCs; SMD -0.65 (15 studies, 95% CI -0.82, -0.49, P <0.001) with significant heterogeneity (I2=56%, P =0.0002). Efficacy displayed time-related decreases after GC initiation. Mean difference visual analogue scale pain was -15mm (95% CI -20, -9) greater improvement in GC than control at 3 months, -8mm (95% CI -12, -3) at >3–6 months and -7mm (95% CI -13, 0) at >6 months. Similar findings were obtained when evoked pain outcomes were examined. Data from five RCTs suggested improvement also in fatigue during GC treatment. Conclusion. Oral GCs are analgesic in RA. The benefit is greatest shortly after initiation and GCs might not achieve clinically important pain relief beyond 3 months. Treatments other
Article
Half of the patients with systemic lupus erythematosus (SLE) will have a reduced bone density and more than one in ten will develop osteoporosis (OP) prematurely. Multiple risk factors have been related to loss of bone mass, but just a few are modifiable, such as adequate vitamin D and calcium intakes, weight bearing exercise, controlling SLE activity and limiting the use of glucocorticoids (GC). GC have also been strongly associated to osteonecrosis or avascular necrosis (AVN). The main consequences of OP and AVN are fractures, which lead to significant functional limitation, loss of quality of life and increased morbidity. OP-related fractures can be reduced by performing appropriate screening with bone densitometries and providing prophylactic treatment when long-term or high dose GC are needed. No formal screening is available for AVN; but diagnosis is made by imaging (X-ray, bone scan or advanced imaging where appropriate). Aiming for the lowest dose possible of GC in combination with immunosuppression as well as an early recognition of the symptoms will prevent further complications. This manuscript is a practical review of the epidemiology, pathophysiology, and management of OP and AVN in patients with SLE, based on the available evidence and guidelines.
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Drugs may cause bone loss by lowering sex steroid levels (e.g., aromatase inhibitors in breast cancer, GnRH agonists in prostate cancer, or depot medroxyprogestone acetate – DMPA), interfere with vitamin D levels (liver inducing anti-epileptic drugs), or directly by toxic effects on bone cells (chemotherapy, phenytoin, or thiazolidinedions, which diverts mesenchymal stem cells from forming osteoblasts to forming adipocytes). However, besides effects on the mineralized matrix, interactions with collagen and other parts of the unmineralized matrix may decrease bone biomechanical competence in a manner that may not correlate with bone mineral density (BMD) measured by dual energy absorptiometry (DXA).
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