Treatment Of Glucocorticoid-induced Osteoporosis Research Articles

Effects of Denosumab and Bisphosphonates on Glucocorticoid-induced Osteoporosis in Patients with Neuroimmunological Disorders.

Objective Although patients with neuroimmunological disorders often need to be treated with glucocorticoids and are at risk of developing glucocorticoid-induced osteoporosis, no research has focused on the treatment of glucocorticoid-induced osteoporosis in such patients. Methods We compared the efficacy of denosumab and bisphosphonates in glucocorticoid-induced osteoporosis in neuroimmunological diseases. In 57 patients with neuroimmunological disorders treated with corticosteroids (34 with neuromyelitis optica spectrum disorders, 16 with myasthenia gravis, and 7 with others), we retrospectively studied the long-term effects of denosumab (n=23) and bisphosphonates (n=34) on spine and total hip bone mineral density (BMD) measured by dual energy X-ray absorptiometry. Results There were no significant differences in the age, lumbar spine BMD, or mean dose or duration of prednisolone administration at baseline between the denosumab and bisphosphonate groups. During the follow-up period of up to 6 years, the increase in the lumbar spine and total hip BMD was greater in the denosumab group than in the bisphosphonate group (p<0.01). Insufficient bone fractures were observed in 2 (9%) of the 23 patients in the denosumab group and in 2 (6%) of the 34 patients in the bisphosphonate group (not significant). Conclusion Denosumab is more effective than bisphosphonates in increasing the BMD of patients with neuroimmunological disorders receiving glucocorticoids.

Combined application of mesenchymal stem cells and different glucocorticoid dosing alleviates osteoporosis in SLE murine models.

Bone mesenchymal stem cells (BMSCs) have been tentatively applied in the treatment of glucocorticoid-induced osteoporosis (GIOP) and systemic lupus erythematosus (SLE). However, the effects of BMSCs on osteoporosis within the context of glucocorticoid (GC) application in SLE remain unclear. Our aim was to explore the roles of BMSCs and different doses of GC interventions on osteoporosis in SLE murine models. MRL/MpJ-Faslpr mice were divided into eight groups with BMSC treatment and different dose of GC intervention. Three-dimensional imaging analysis and hematoxylin and eosin (H&E) staining were performed to observe morphological changes. The concentrations of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in serum were measured by enzyme-linked immunosorbent assay (ELISA). The subpopulation of B cells and T cells in bone marrows and spleens were analyzed by flow cytometry. Serum cytokines and chemokines were assessed using Luminex magnetic bead technology. BMSCs ameliorated osteoporosis in murine SLE models by enhancing bone mass, improving bone structure, and promoting bone formation through increased bone mineral content and optimization of trabecular morphology. BMSC and GC treatments reduced the number of B cells in bone marrows, but the effect was not significant in spleens. BMSCs significantly promoted the expression of IL-10 while reducing IL-18. Moreover, BMSCs exert immunomodulatory effects by reducing Th17 expression and rectifying the Th17/Treg imbalance. BMSCs effectively alleviate osteoporosis induced by SLE itself, as well as osteoporosis resulting from SLE combined with various doses of GC therapy. The therapeutic effects of BMSCs appear to be mediated by their influence on bone marrow B cells, T cell subsets, and associated cytokines. High-dose GC treatment exerts a potent anti-inflammatory effect but may hinder the immunotherapeutic potential of BMSCs. Our research may offer valuable guidance to clinicians regarding the use of BMSC treatment in SLE and provide insights into the judicious use of GCs in clinical practice.

Review of 2022 American College of Rheumatology (ACR) guideline for the prevention and treatment of glucocorticoid-induced osteoporosis: what’s new?

Glucocorticoids (GC) have been used in medicine since the middle of the twentieth century, including for the treatment of various systemic rheumatic diseases. However, long-term use of GC may be accompanied by the development of serious complications, one of which is secondary osteoporosis, leading to low-energy fractures, which affects the quality of life of patients and may lead to an increased risk of death. This article presents an overview with a discussion of the new edition of the guideline of the American College of Rheumatology (ACR) 2022 for the prevention and treatment of glucocorticoid-induced osteoporosis in adult patients.

Guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis in pediatrics.

Objective. To provide a framework for healthcare professionals managing pediatric patients who are on active glucocorticoid (GC) therapy and to develop recommendations for the prevention and treatment of GC-induced osteoporosis in the pediatric population. Methods. A panel of experts on bone and pediatric diseases developed a series of PICO questions that address issues related to the prevention and treatment of osteoporosis in patients on GC therapy. In accordance with the GRADE approach, we conducted a systematic review of the literature, summarized effect estimations, and classified the quality of the evidence. Then, voting and the formulation of recommendations followed. Results. Seven recommendations and six general principles were developed for GC-induced osteoporosis in the pediatric population. Conclusion. These recommendations provide guidance for clinicians who must make decisions concerning pediatric patients undergoing treatment with GC.

The 2023 Guidelines for the management and treatment of glucocorticoid-induced osteoporosis

IntroductionAlthough synthetic glucocorticoids (GCs) are commonly used to treat autoimmune and other diseases, GC induced osteoporosis (GIOP) which accounts for 25% of the adverse reactions, causes fractures in 30–50% of patients, and markedly decreases their quality of life. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) published the revised guidelines for the management and treatment of steroid-induced osteoporosis, providing the treatment criteria based on scores of risk factors, including previous fractures, age, GC doses, and bone mineral density, for patients aged ≥18 years who are receiving GC therapy or scheduled to receive GC therapy for ≥3 months.Materials and methodsThe Committee on the revision of the guidelines for the management and treatment of GIOP of the JSBMR prepared 17 clinical questions (CQs) according to the GRADE approach and revised the guidelines for the management and treatment of GIOP through systematic reviews and consensus conferences using the Delphi method.ResultsBisphosphonates (oral and injectable formulations), anti-RANKL antibody teriparatide, eldecalcitol, or selective estrogen receptor modulators are recommended for patients who has received or scheduled for GC therapy with risk factor scores of ≥3. It is recommended that osteoporosis medication is started concomitantly with the GC therapy for the prevention of fragility fractures in elderly patients.ConclusionThe 2023 guidelines for the management and treatment of GIOP was developed through systematic reviews and consensus conferences using the Delphi method.

Effects of Denosumab and Bisphosphonates on Glucocorticoid-induced Osteoporosis in Patients with Neuroimmunological Disorders.

Objective Although patients with neuroimmunological disorders often need to be treated with glucocorticoids and are at risk of developing glucocorticoid-induced osteoporosis, no research has focused on the treatment of glucocorticoid-induced osteoporosis in such patients. Methods We compared the efficacy of denosumab and bisphosphonates in glucocorticoid-induced osteoporosis in neuroimmunological diseases. In 57 patients with neuroimmunological disorders treated with corticosteroids (34 with neuromyelitis optica spectrum disorders, 16 with myasthenia gravis, and 7 with others), we retrospectively studied the long-term effects of denosumab (n=23) and bisphosphonates (n=34) on spine and total hip bone mineral density (BMD) measured by dual energy X-ray absorptiometry. Results There were no significant differences in the age, lumbar spine BMD, or mean dose or duration of prednisolone administration at baseline between the denosumab and bisphosphonate groups. During the follow-up period of up to 6 years, the increase in the lumbar spine and total hip BMD was greater in the denosumab group than in the bisphosphonate group (p<0.01). Insufficient bone fractures were observed in 2 (9%) of the 23 patients in the denosumab group and in 2 (6%) of the 34 patients in the bisphosphonate group (not significant). Conclusion Denosumab is more effective than bisphosphonates in increasing the BMD of patients with neuroimmunological disorders receiving glucocorticoids.

Association between dietary selenium intake and the prevalence of osteoporosis and its role in the treatment of glucocorticoid-induced osteoporosis

BackgroundLong-term glucocorticoid therapy may lead to osteoporosis (OP). Selenium (Se) is an essential microelement for human health and bone health. This study evaluated the association between dietary Se intake and the prevalence of OP and further explored the potential therapeutic effect of Se on glucocorticoid-induced OP (GIOP) in vivo and in vitro.MethodsData were collected from a population-based cross-sectional study conducted in our hospital. OP is diagnosed based on bone mineral density (BMD) measurements using compact radiographic absorptiometry. Dietary Se intake was assessed using a semi-quantitative food frequency questionnaire. The association between dietary Se intake and OP prevalence was analyzed by multivariable logistic regression. In animal experiments, male Sprague–Dawley rats were intramuscularly injected with dexamethasone (1 mg/kg) daily to induce GIOP, while different doses of Se were supplemented in rat drinking water for 60 d. BMD and biomechanical parameters of rat femur were measured. The histopathological changes of the femur were observed by HE staining, the number of osteoclasts was observed by TRAP staining, and OCN positive expression was detected by immunohistochemical staining. OPG, RANKL, Runx2, and BMP2 in rat femur were detected by Western blot. Bone turnover markers and oxidative stress markers were measured using commercial kits. MC3T3-E1 cells were induced to osteogenic differentiation, stimulated with DXM (100 μM), and/or treated with Se at different doses. Cell proliferation and apoptosis were assessed by CCK-8 and flow cytometry. ALP activity was detected by ALP staining and cell mineralization was observed by alizarin red staining.ResultsParticipants with lower dietary Se intake had higher OP prevalence. Se supplementation improved BMD, biomechanical parameters, and histopathological changes of the femur in GIOP rats. Se supplementation also suppressed DXM-induced changes in bone turnover- and oxidative stress-related markers. Under DXM conditions, Se treatment induced MC3T3-E1 cell proliferation, ALP activity, and mineralization.ConclusionLower Dietary Se intake is associated with OP prevalence. Moreover, Se takes a position in bone protection and anti-oxidative stress in GIOP models. Therefore, Se may be a complementary potential treatment for GIOP.

Argentine Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Postmenopausal Women and Men Aged 50 Years and Older.

Argentine Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Postmenopausal Women and Men Aged 50 Years and Older.

Part II: Interactive case: Drug‐induced endocrine disorders

Part <scp>II</scp>: Interactive case: <scp>Drug‐induced</scp> endocrine disorders

Guidelines for diagnosis and treatment of glucocorticoid-induced osteoporosis

Glucocorticoid-induced osteoporosis (GIOP) is a skeletal disease characterized by decreased bone strength and increased fracture risk associated with long-term glucocorticoid use. GIOP is the most common secondary osteoporosis that critically affects the quality of life of patients. Currently, the incidence of GIOP in China remains high, with insufficient awareness and lack of prevention and treatment norms. Therefore, the Chinese Rheumatology Association has established this standard based on domestic and international experience, with the aim of raising awareness of prevention and treatment among clinicians, guiding the standardized diagnosis and treatment of this disease, and improving the overall prognosis of patients with GIOP.

Cmpk2 regulates mitochondrial function in glucocorticoid-induced osteoblast senescence and affects glucocorticoid-inhibited osteoblast differentiation

Mitochondrial dysfunction plays a crucial role in the development of glucocorticoid-induced osteoporosis (GIO). Cytidine monophosphate kinase 2 (Cmpk2), an essential mitochondria-associated gene, promotes the production of free mitochondrial DNA, which leads to the formation of inflammasome-mediated inflammatory factors. However, the specific role of Cmpk2 in GIO remains unclear. In this study, we report that glucocorticoids induce cellular senescence within the bone, particularly in bone marrow mesenchymal stem cells and preosteoblasts. We discovered that glucocorticoids cause mitochondrial dysfunction in preosteoblasts, increasing cellular senescence. Moreover, we observed elevated expression of Cmpk2 in preosteoblasts following glucocorticoid exposure. Inhibiting Cmpk2 expression alleviates glucocorticoid-induced cellular senescence and promotes osteogenic differentiation by improving mitochondrial function. Our study uncovers new mechanisms underlying glucocorticoid-induced senescence in stem cells and preosteoblasts, highlighting the potential of inhibiting the mitochondrial gene Cmpk2 to reduce senescence and enhance osteogenic differentiation. This finding offers a potential therapeutic approach for the treatment of GIO.

Efficacy of Bushen Jiangu therapy in the treatment of glucocorticoid-induced osteoporosis: A systematic review and meta-analysis of randomized controlled trials.

Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis. Bushen Jiangu (BSJG), a classic traditional Chinese medicine (TCM) therapy, is widely used for treatment of GIOP. We conducted a meta-analysis to evaluate the effectiveness and safety of BSJG therapy on the treatment of GIOP. We searched randomized controlled trials (RCTs) of BSJG therapy for GIOP in 10 databases. Methodological quality assessment was performed by using the Cochrane collaboration tool. RevMan v5.3 and Stata v14.0 software were used for performing data analysis. This study was conducted and reported following the PRISMA checklist. Overall, 14 RCTs with 988 participants met the inclusion criteria. Pooled results indicated that BSJG therapy contributed to a betterment in improving the clinical efficacy rate of GIOP (risk ratio [RR] = 1.22, 95% confidence interval [CI]: 1.14, 1.30, P < .00001). The pooled results also indicated that BSJG therapy increased lumbar spine bone mineral density (LS-BMD) (weighted mean difference [WMD] = 0.21, 95% CI: 0.08, 0.33, P = .001), total hip bone mineral density (TH-BMD) (WMD = 0.16, 95% CI: 0.09, 0.24, P < .0001), and femoral neck bone mineral density (FN-BMD) (WMD = 0.07, 95% CI: 0.03, 0.10, P = .0001). Furthermore, our results indicated that BSJG therapy improved visual analogue scale (VAS) score (WMD = -0.60, 95% CI: -0.97, -0.23, P = .002), parathyroid hormone (PTH) (standardized mean difference [SMD] = -0.93, 95% CI: -1.58, -0.27, P = .006), and N-terminal propeptide of type I precollagen (PINP) (SMD = 0.69, 95% CI: 0.44, 0.95, P < .00001). In terms of safety, there was no significant difference in the adverse events (AEs) between the 2 groups (RR = 1.45, 95% CI: 0.63, 3.31, P = .38). Our analysis indicates that BSJG therapy has a valid and safe effect on the treatment of GIOP in the clinic. However, the results need to be confirmed in more well-designed and large-scale RCTs.

Linking the relation between gut microbiota and glucocorticoid-induced osteoporosis.

Osteoporosis (OP) is the most prevalent metabolic bone disease, characterized by the low bone mass and microarchitectural deterioration of bone tissue. Glucocorticoid (GC) clinically acts as one of the anti-inflammatory, immune-modulating, and therapeutic drugs, whereas the long-term use of GC may cause rapid bone resorption, followed by prolonged and profound suppression of bone formation, resulting in the GC-induced OP (GIOP). GIOP ranks the first among secondary OP and is a pivotal risk for fracture, as well as high disability rate and mortality, at both societal and personal levels, vital costs. Gut microbiota (GM), known as the "second gene pool" of human body, is highly correlated with maintaining the bone mass and bone quality, and the relation between GM and bone metabolism has gradually become a research hotspot. Herein, combined with recent studies and based on the cross-linking relationship between GM and OP, this review is aimed to discuss the potential mechanisms of GM and its metabolites on the OP, as well as the moderating effects of GC on GM, thereby providing an emerging thought for prevention and treatment of GIOP.

Chiral Selenium Nanotherapeutics Regulates Selenoproteins to Attenuate Glucocorticoid‐Induced Osteoporosis

AbstractGlucocorticoid (GC)‐induced osteoporosis (GIO) is a concurrent disease commonly appeared in chronic inflammatory and autoimmune disease patients. Stereoselective recognition between chiral drugs and homochiral biological molecules could directly affect their distribution, adhesion and transport. Herein, trace element selenium (Se) with bone formation‐regulating activity, is employed to construct cysteine‐decorated chiral nanoparticles (Cys@SeNPs) to attenuate GIO. Interestingly, comparing with the racemic (DL‐Cys@SeNPs) and D‐Cys@SeNPs, the L‐Cys@SeNPs displays higher uptake in osteoblast cells and could lessen reactive oxygen species overproduction to block dexamethasone (Dex)‐induced osteoblasts cells apoptosis. Intracellular L‐Cys@SeNPs could be predominantly transformed to selenocystine to upregulate the expression levels of antioxidative selenoproteins to effectively scavenge Dex‐induced excessive ROS accumulation in osteoblasts, and thus reduce the undesirable apoptosis through activating Wnt/β‐catenin pathway. Consistently, L‐Cys@SeNPs significantly alleviates the main osteoporosis symptoms of bone trabeculae destruction and decreased bone density in vivo, and also reduces the weight gain and fatty liver formation in Dex‐exposed mice, thus suppressing the overall side effects of Dex. This study not only demonstrates an effective strategy for treatment of GIO by using chiral Se nanomedicine, but also elucidates the important roles of selenoproteins in alleviating osteoporosis, which could help for future Se‐based drug design through chirality control engineering.

A novel BMP2 secretagogue ameliorates glucocorticoid induced oxidative stress in osteoblasts by activating NRF2 dependent survival while promoting Wnt/β-catenin mediated osteogenesis.

In our previous study, a novel BMP2 secretagogue was synthesized belonging to a class of galloyl conjugates of flavanones, with remarkable osteogenic potential that promoted bone regeneration. We aimed to establish the protective effect of our compound against bone loss that co-exists with excess Glucocorticoid (GC) therapy. GC therapy induces osteoblast damage leading to apoptosis by increasing reactive oxygen species (ROS). Our results delineate that compound 5e (a BMP2 secretagogue) activates NRF2 signalling to counter the disturbed cellular redox homeostasis and escalate osteoblast survival as assessed by Western blot and immunocytochemistry. Depletion of NRF2 by siRNA blocked activation of the NRF2/HO-1 pathway, magnified oxidative stress, increased apoptosis and abrogated the protective effects of compound 5e. 5e, on the other hand, increased ALP, mineralization activity, and promoted osteoblast differentiation by activating WNT/β-catenin signalling in BMP2 dependent manner, validated by Western blot of WNT3A, SOST, GSK3-β and β-catenin nuclear translocation. Treatment of 5e in presence of BMP inhibitor noggin attenuated the osteogenic efficacy and minimized Wnt//β-catenin signalling in presence of dexamethasone. Our compound prevents GC challenged trabecular and cortical bone loss assessed by micro-CT and promotes bone formation and osteocyte survival determined by calcein labelling and TUNEL assay in GC treated animals. The osteogenic potential of the compound was authenticated by bone turnover markers. On a concluding note, compounds with BMP upregulation can be potential therapeutics for the prevention and treatment of glucocorticoid-induced osteoporosis.

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club.

Glucocorticoids are effective immunomodulatory drugs used for many inflammatory disorders as well as in transplant recipients. However, both iatrogenic and endogenous glucocorticoid excess are also associated with several side effects including an increased risk of osteoporosis and fractures. Glucocorticoid-induced osteoporosis (GIOP) is a common secondary cause of osteoporosis in adults. Despite availability of clear evidence and international guidelines for the prevention of GIOP, a large treatment gap remains. In this narrative review, the Belgian Bone Club (BBC) updates its 2006 consensus recommendations for the prevention and treatment of GIOP in adults. The pathophysiology of GIOP is multifactorial. The BBC strongly advises non-pharmacological measures including physical exercise, smoking cessation and avoidance of alcohol abuse in all adults at risk for osteoporosis. Glucocorticoids are associated with impaired intestinal calcium absorption; the BBC therefore strongly recommend sufficient calcium intake and avoidance of vitamin D deficiency. We recommend assessment of fracture risk, taking age, sex, menopausal status, prior fractures, glucocorticoid dose, other clinical risk factors and bone mineral density into account. Placebo-controlled randomized controlled trials have demonstrated the efficacy of alendronate, risedronate, zoledronate, denosumab and teriparatide in GIOP. We suggest monitoring by dual-energy X-ray absorptiometry (DXA) and vertebral fracture identification one year after glucocorticoid initiation. The trabecular bone score might be considered during DXA monitoring. Extended femur scans might be considered at the time of DXA imaging in glucocorticoid users on long-term (≥ 3 years) antiresorptive therapy. Bone turnover markers may be considered for monitoring treatment with anti-resorptive or osteoanabolic drugs in GIOP. Although the pathophysiology of solid organ and hematopoietic stem cell transplantation-induced osteoporosis extends beyond GIOP alone, the BBC recommends similar evaluation, prevention, treatment and follow-up principles in these patients. Efforts to close the treatment gap in GIOP and implement available effective fracture prevention strategies into clinical practice in primary, secondary and tertiary care are urgently needed.

Update on the Treatment of Glucocorticoid-Induced Osteoporosis

Osteoporosis and osteoporotic fracture are one of the most common side effects of glucocorticoid therapy. All patients who are taking any dose of glucocorticoids for over 3 months should have a bone health assessment. After consideration of their clinical risk factors, glucocorticoid dose, bone mineral density measurement, and the Fracture Risk Assessment Tool score, patients can be stratified into low-, moderate-, and high-risk groups. General measures include optimization of calcium and vitamin D intake, reducing glucocorticoid dosage and lifestyle modifications. In patients with moderate to high risk of fracture, pharmacological agents should be prescribed, of which bisphosphonates, denosumab, and teriparatide are the most widely used.

The efficiency and safety of alendronate versus teriparatide for treatment glucocorticoid-induced osteoporosis: A meta-analysis and systematic review of randomized controlled trials.

Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis, alendronate (ALE) and teriparatide (TPTD) are widely used in the treatment of GIOP. However, which of these two drugs has a better curative effect needs the support of evidence-based medicine. We searched PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar for randomized controlled trials of ALE and TPTD in the treatment of glucocorticoid-induced osteoporosis until February 2022. These patients included in the study took glucocorticoid doses greater than 7.5 mg/d for more than 3 months before treatment with ALE and TPTD. The risk ratio (RR) and its 95% confidence interval (CI) are used as the influence index of discontinuous data, and the standardized mean difference (SMD) and its 95% CI are used as the influence index of continuous data. A total of 4102 patients were enrolled in all 5 studies that met the admission criteria. We found that compared with ALE, TPTD could reduce the rate of new vertebral fracture (RR = 0.13, 95% CI: 0.05-0.34, P<0.00001). TPTD increased LS bone mineral density (BMD) (0.53, 95% CI 0.42-0.64, P<0.00001), TH BMD (0.17, 95% CI 0.05-0.28, P = 0.004) and FN BMD (0.17, 95% CI 0.05-0.29, P = 0.006) compared to ALE. However, there was no significant difference in the incidence of non-vertebral fracture and adverse events between the two groups. Compared with ALE, TPTD is an effective drug to reduce vertebral fracture risk in patients with GIOP. Furthermore, long-term use of TPTD can increase the bone mineral density of LS, FN, and TH.

Metformin alleviates dexamethasone-induced apoptosis by regulating autophagy via AMPK/mTOR/p70S6K in osteoblasts

Glucocorticoid (GC)-induced osteoporosis (GIOP) is the most common type of secondary osteoporosis. Osteoblast apoptosis induced by GCs is now considered as a crucial factor for GIOP. Many clinical, in vivo, and in vitro studies have shown that metformin has a beneficial effect on bone metabolism and bone formation. To investigate whether metformin could be used to treat GIOP, we explored the influence of metformin on dexamethasone (Dex)-induced apoptosis of osteoblasts and its underlying mechanisms. In this study, the CCK8 assay was used to determine the optimal metformin concentration and processing time. The expression levels of target proteins were examined by Western blot and immunofluorescence; the expression levels of target genes were tested by quantitative PCR. Apoptotic cells were detected using flow cytometry. Characteristics of autophagy were observed by transmission electron microscopy. An autophagy inhibitor was administered to investigate whether autophagy decreases apoptosis. Sh-AMPK transfection and an mTOR activator were used to investigate the role of AMPK/mTOR signaling in metformin-induced autophagy. The results showed that metformin alleviated Dex-induced apoptosis of osteoblasts accompanied by increased autophagy. Treatment with the autophagy inhibitor 3-methyladenine (3-MA) attenuated the effect of metformin on apoptosis, autophagy, and the AMPK/mTOR/p70S6K signaling pathway. The anti-apoptotic effect of metformin on osteoblasts is associated with the promotion of autophagy. Furthermore, sh-AMPK transfection and the mTOR activator MHY1485 impaired metformin-mediated inhibition of osteoblast apoptosis and promotion of autophagy. The AMPK/mTOR/p70S6K signaling pathway plays a role in metformin-mediated apoptosis suppression and autophagy promotion. In conclusion, metformin can alleviate Dex-induced osteoblast apoptosis by inducing autophagy via the AMPK/mTOR/p70S6K pathway. This study highlights the potential value of metformin in the treatment of GIOP.

Glucocorticoid-induced osteoporosis-Focus treatment (part2)

The following substances are approved for the treatment of glucocorticoid-induced osteoporosis: the oral bisphosphonates alendronate and risedronate, the intravenous bisphosphonate zoledronate, the RANKL antibody denosumab as antiresorptive substances and teriparatide as osteoanabolic substance. In comparison to placebo areduction of vertebral fractures is proven for all mentioned substances. Thereby, teriparatide is more effective than alendronate and risedronate with respect to the reduction of vertebral fractures. The severity of osteoporosis, especially the presence of osteoporotic fractures, the approach of treatment (preventive or curative) and contraindications are factors that are important for the differentiated application of the mentioned substances. Furthermore, it must be noted that the effect of osteoanabolic treatment must be stabilized by asubsequent antiresorptive treatment and that after termination of antiresorptive treatment with denosumab atemporary bisphosphonate treatment is required to prevent arebound phenomenon.