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Deutsche Medizinische Wochenschrift... Mar 2016Glucocorticoid-induced osteoporosis is the most common cause of secondary osteoporosis. Moreover, it is the most common reason for an osteoporosis among young adults.... (Review)
Review
Glucocorticoid-induced osteoporosis is the most common cause of secondary osteoporosis. Moreover, it is the most common reason for an osteoporosis among young adults. The clinical use of oral glucocorticoids increases the fracture incidence already within three months after starting the therapy. There does not seem to be a lower threshold: even doses as low as 2,5 mg of prednisone equivalent increase the risk of fractures. Adequate diagnostic and therapy are able to significantly reduce the resulting fracture risk. This article will discuss the pathophysiology of glucocorticoid-induced osteoporosis and give a summary of the current recommendations including the recently updated German guidelines.
Topics: Administration, Oral; Bone Density; Calcium, Dietary; Cholecalciferol; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Long-Term Care; Osteoporosis; Osteoporotic Fractures; Prednisolone; Risk; Young Adult
PubMed: 26939107
DOI: 10.1055/s-0042-101896 -
BMC Veterinary Research Aug 2017In Europe, synthetic corticosteroids are not allowed in animal breeding for growth-promoting purposes. Nevertheless, a high prevalence of non-compliant urine samples was...
BACKGROUND
In Europe, synthetic corticosteroids are not allowed in animal breeding for growth-promoting purposes. Nevertheless, a high prevalence of non-compliant urine samples was recently reported for prednisolone, however, without any indication of unauthorized use. Within this context, 20β-dihydroprednisolone and the prednisolone/cortisol ratio have been suggested as potential tools to discriminate between exogenous and endogenous urinary prednisolone. In this study, the validity of these strategies was verified by investigating the plasma pharmacokinetic and urinary excretion profiles of relevant glucocorticoids in bovines, subjected to exogenous prednisolone treatment or tetracosactide hexaacetate administration to induce endogenous prednisolone formation. Bovine urine and plasma samples were analysed by liquid chromatography and mass spectrometry.
RESULTS
Based on the plasma pharmacokinetics and urinary profiles, 20β-dihydroprednisolone was confirmed as the main prednisolone-derived metabolite, being detected in the biological fluids of all 12 bovines (plasma AUC of 121 h μg L and urinary concentration > 0.695 μg L). However, this metabolite enclosed no potential as discriminative marker as no significant concentration differences were observed upon exogenous prednisolone treatment or tetracosactide hexaacetate administration under all experimental conditions. As a second marker tool, the prednisolone/cortisol ratios were assessed along the various treatments, taking into account that endogenous prednisolone formation involves the hypothalamic-pituitary-adrenal axis and is associated with an increased cortisol secretion. Significantly lower ratios were observed in case of endogenous prednisolone formation (i.e. ratios ranging from 0.00379 to 0.129) compared to the exogenous prednisolone treatment (i.e. ratios ranging from 0.0603 to 36.9). On the basis of these findings, a discriminative threshold of 0.260 was proposed, which allowed classification of urine samples according to prednisolone origin with a sensitivity of 94.2% and specificity of 99.0%.
CONCLUSION
The prednisolone/cortisol ratio was affirmed as an expedient strategy to discriminate between endogenous and exogenous prednisolone in urine. Although the suggested threshold value was associated with high specificity and sensitivity, a large-scale study with varying experimental conditions is designated to optimize this value.
Topics: Animals; Biomarkers; Cattle; Cosyntropin; Drug Monitoring; Female; Hormones; Hydrocortisone; Prednisolone
PubMed: 28806969
DOI: 10.1186/s12917-017-1158-5 -
Drug Testing and Analysis Mar 2021Prednisolone (PRED) and prednisone (PSONE) are prohibited in sports competitions when administered by systemic routes, and they are allowed by other routes for... (Clinical Trial)
Clinical Trial Comparative Study
Elimination profiles of prednisone and prednisolone after different administration routes: Evaluation of the reporting level and washout periods to ensure safe therapeutic administrations.
Prednisolone (PRED) and prednisone (PSONE) are prohibited in sports competitions when administered by systemic routes, and they are allowed by other routes for therapeutic purposes. There is no restriction of use in out-of-competition periods. The present study aimed to evaluate the urinary excretion of PRED, PSONE, and their most important metabolites after systemic and nonsystemic treatments in order to verify the suitability of the current reporting level of 30 ng/ml used to distinguish allowed and prohibited administrations and to establish washout periods for oral treatments performed in out-of-competition periods. PRED was studied after dermatological administration (5 mg/day for 5 days, n = 6 males) and oral administration (5 mg, n = 6 males; 10 mg, n = 2 males). PSONE was studied after oral administration (10 mg, n = 2 males; 30 mg, n = 1 male and 1 female). Concentrations in urine were measured using an LC-MS/MS method. Concentrations after dermatological treatment were low for all metabolites. After oral administration, concentrations were very high during the first 24 h after administration ranging from 1.6 to 2261 ng/ml and from 4.6 to 908 ng/ml for PRED and PSONE, respectively. Concentrations of most of the metabolites measured were lower than 30 ng/ml from 24 h after all oral administrations. New reporting levels are proposed for PRED and PSONE considering data of our study and other information published after nonsystemic administrations of the compounds. Washout periods of at least 24 h are recommended to ensure no false positives when oral treatments need to be performed in out-of-competition periods.
Topics: Administration, Cutaneous; Administration, Oral; Chromatography, Liquid; Cross-Over Studies; Doping in Sports; Female; Humans; Male; Prednisolone; Prednisone; Substance Abuse Detection; Tandem Mass Spectrometry; Time Factors
PubMed: 33161623
DOI: 10.1002/dta.2966 -
Drug Testing and Analysis Nov 2019The urinary excretion profile of prednisolone and prednisone after both systemic (i.e., oral) and topical (i.e., ocular and intranasal) administration was studied by...
The urinary excretion profile of prednisolone and prednisone after both systemic (i.e., oral) and topical (i.e., ocular and intranasal) administration was studied by liquid chromatography coupled to mass spectrometry, also to select the most appropriate marker(s) of intake for doping control purposes. Urines were collected from ten subjects every 3 h before and after the administration of therapeutic doses of pharmaceutical formulations containing either prednisone or prednisolone. Samples were subjected to enzymatic hydrolysis (performed for the investigation on the glucuronide profile) followed by liquid/liquid extraction with tert-butylmethylether in alkaline conditions. The chromatographic separation was carried out on C18 column, employing as mobile phases ultrapurified water and acetonitrile, both containing 0.1% of formic acid. Detection was achieved using as mass spectrometric analyzer a triple quadrupole, with positive ion electrospray ionization and multiple reaction monitoring as acquisition mode. After both systemic and topical use, the compounds excreted in urine in higher concentration were prednisone, prednisolone and 20β-dihydro-prednisolone followed by 20α-dihydro-prednisolone and 20α/β-dihydro-prednisone. All were excreted mainly as unconjugated compounds, with a maximum of excretion in the first 3-9 h after the administration. After systemic use, prednisone and prednisolone were both detectable for at least 24 h in concentrations ranging from 5 to 500 ng/mL and from 5 to 900 ng/mL respectively. Whereas, after topical administration, prednisone and prednisolone were detectable for at least 18 h in concentrations ranging from 5 to 140 ng/mL and from 5 to 50 ng/mL respectively.
Topics: Administration, Oral; Administration, Topical; Adult; Chromatography, Liquid; Glucocorticoids; Humans; Male; Prednisolone; Prednisone; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 31701669
DOI: 10.1002/dta.2733 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2022The aim: To establish the clinical and pathogenetic role of glucocorticoid imbalance as an important link of impairment of the adaptive system homeostasis and to...
OBJECTIVE
The aim: To establish the clinical and pathogenetic role of glucocorticoid imbalance as an important link of impairment of the adaptive system homeostasis and to determine ways of its correction as a way to increase the effectiveness of the pulmonary tuberculosis treatment.
PATIENTS AND METHODS
Materials and methods: The effectiveness of glucocorticoids in the pulmonary tuberculosis treatment was studied in 304 patients, of which 134 patients (group 1) received only antibacterial therapy, 67 patients (group 2) were supplemented with glucocorticoids (20-30 mg of prednisolone, daily, in 3 doses, with their cessation by gradual reduction of dose). 103 patients (group 3) also received antibacterial therapy in combination with glucocorticoids (20-30 mg of prednisolone, in the morning, in a daily dose every other day, cessation was carried out simultaneously without reducing the dose).
RESULTS
Results: The study found that the level of cortisol in patients with pulmonary tuberculosis was significantly higher than normal, did not have age and gender dependence, but showed a connection with the severity of clinical forms of tuberculosis, the duration of disease development and the presence of intoxication. It was established that the daily fluctuations of cortisol persist in tuberculosis patients, but its level significantly exceeds the norm, which indicates the functional stressing of the adaptive system.
CONCLUSION
Conclusions: The article substantiates the homeostatic role of glucocorticoids in the complex treatment of tuberculosis patients when administered in a double physiological dose every other day, taking into account the daily biorhythm of the hypothalamic-pituitary-adrenal axis function.
Topics: Humans; Glucocorticoids; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Hydrocortisone; Prednisolone; Homeostasis; Tuberculosis, Pulmonary; Anti-Bacterial Agents
PubMed: 36256937
DOI: 10.36740/WLek202209111 -
Journal For Immunotherapy of Cancer Jul 2023There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs).
BACKGROUND
There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs).
METHODS
In this single-arm phase II study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The primary endpoint was a pneumonitis control rate at 6 weeks from the start of the study treatment, defined as complete disappearance or partial improvement of irP in high-resolution CT of the chest.
RESULTS
Among 57 patients enrolled, 56 were included in the final analysis. The most frequent cause of irP was single ICI therapy (51.8%), followed by combination with chemotherapy plus ICI (39.3%). Thirty-five (62.5%) patients had grade 2 irP and 21 (37.5%) had grade ≥3. Fifty-one (91.1%) patients completed the study treatment while 5 discontinued the study treatment because of relapse of irP (n=1), death from cancer (n=1), occurrence of immune-related hepatitis (n=1), extension of the treatment duration more than 6 weeks (n=1), and attending physician's decision (n=1). Six weeks after the start of the study treatment, 16 (28.5%) patients demonstrated complete recovery from irP, 35 (62.5%) had a partial improvement in irP, 1 (1.8%) had a relapse of irP, and 4 (7.1%) were not evaluable. The pneumonitis control rate at 6 weeks was 91.1% (95% CI, 80.7% to 96.1%). Twelve weeks after the start of the study treatment, 5 (8.9%), 27 (48.2%), and 15 (26.8%) patients demonstrated complete recovery, partial improvement, and relapse, respectively, and 9 (16.1%) were not evaluable. The pneumonitis control rate at 12 weeks was 57.1% (95% CI, 44.1% to 69.2%). During the observation period, 18 (32.1%) patients experienced a relapse of irP, and of those, 17 received re-treatment with corticosteroids. Grade ≥3 adverse events occurred in 10 (17.9%) patients, in which hyperglycemia was most frequent (n=6). There was no treatment-related death.
CONCLUSIONS
In this first prospective study for irP, prednisolone at 1 mg/kg/day, tapered over 6 weeks, demonstrated a promising clinical benefit and manageable toxicity, suggesting a potential treatment option for irP.
TRIAL REGISTRATION NUMBER
jRCT: 1041190029.
Topics: Humans; Prospective Studies; Pneumonia; Prednisolone; Neoplasms; Recurrence
PubMed: 37500182
DOI: 10.1136/jitc-2023-007056 -
Journal of Equine Veterinary Science Sep 2023This research was performed to compare the effects of prednisolone and fluorometholone on intraocular pressure (IOP) and Schirmer tear test (STT) in the normal equine...
This research was performed to compare the effects of prednisolone and fluorometholone on intraocular pressure (IOP) and Schirmer tear test (STT) in the normal equine eye. Sixteen normal mares aged between 6 and 10 years were used for this study. Horses were randomly assigned to two groups. Eight horses in the first group received 0.2 mL of topical 1% prednisolone in one eye and the contralateral eye was used as control (0.2 mL of saline was instilled). The second group received 0.2 mL of 0.1% fluorometholone in a randomly selected eye and the contralateral eye served as control and received 0.2 mL of saline. STT values and IOP were determined using STT strips and rebound, respectively, at the baseline, and 30-, 60-, 90-, and 180-minutes post eyedrop instillation. Mean (SD) IOPs at the baseline in the treated eyes of the first and second groups were 28.5 (5.4) and 27.5 (4.9) mm Hg, respectively. STT values at the baseline in the treated eyes of the first and second groups were 26.0 (1.8) mm/min and 24.0 (4.0) mm/min, respectively. Neither prednisolone nor fluorometholone caused significant changes in the IOP during 3 hours of monitoring (P > .05). There were no significant differences in the mean levels of STT in the control and treatment eyes, either between groups or within each group (P > .05). In conclusion, one dose (0.2 mL) of 1% prednisolone or 0.1% fluorometholone after 3 hours did not alter the IOP and STT in healthy horses. Further research for a longer period on normal horses and horses with uveitis is warranted.
Topics: Horses; Animals; Female; Intraocular Pressure; Fluorometholone; Prednisolone; Tears; Ophthalmic Solutions
PubMed: 37348824
DOI: 10.1016/j.jevs.2023.104840 -
The Journal of Craniofacial Surgery Oct 2023The authors show a case with immunoglobulin G4 (IgG4)-related bilateral palpebral conjunctival mass and reviewed 7 similar previously reported cases. Our case was a...
The authors show a case with immunoglobulin G4 (IgG4)-related bilateral palpebral conjunctival mass and reviewed 7 similar previously reported cases. Our case was a 42-year-old woman who presented with a 2-year history of a left palpebral conjunctival mass. Pathologic examination of the specimens harvested from the mass revealed marked IgG4-positive plasma cell infiltration. The serum IgG4 level was within the normal limit. Although the mass was completely excised, the lesion recurred 1 month after the surgery, and another new lesion developed in the right upper palpebral conjunctiva. The patient was given 30 mg of oral prednisolone daily, which was tapered gradually. At a 10-month follow-up, the patient continued to take 15 mg of oral prednisolone. The lesions subsided on both sides. On the basis of the literature review, normal serum IgG4 level and upper eyelid lesions may be features of IgG4-related bilateral palpebral conjunctival lesions, and systemic steroids may be effective for this entity.
Topics: Female; Humans; Adult; Prednisolone; Conjunctiva; Eyelids; Glucocorticoids; Immunoglobulin G
PubMed: 37246303
DOI: 10.1097/SCS.0000000000009426 -
Medical Science Monitor : International... Jan 2019BACKGROUND Osteoporosis is a common disorder leading to bone loss. At present, the treatment options available for the management of osteoporosis are limited. The...
BACKGROUND Osteoporosis is a common disorder leading to bone loss. At present, the treatment options available for the management of osteoporosis are limited. The present investigation evaluated the protective effect of fangchinoline against osteoporosis and also postulates the possible mechanism of action. MATERIAL AND METHODS Osteoporosis was induced by subcutaneously injecting prednisolone (2.5 mg/pellet) for 4 weeks. Fangchinoline 1, 3 and 10 mg/kg was given intraperitoneally for the period. Protective effects of fangchinoline were assessed by estimating microarchitectural parameters and bone mineral density (BMD) in the vertebrae tissues, and biochemical parameters were also determined in the serum of rats with prednisolone-induced osteoporosis. Moreover, gene expression of microtubule-associated protein 1A/1B-light chain 3 (LC3), B cell lymphoma 2 (Bcl-2), caspase-3, bone morphogenetic protein 2 (BMP2), Beclin-1, autophagy-related 5 (ATG-5), Runt-related transcription factor 2 (RUNX-2), and receptor activator of nuclear factor kappa-b ligand (RANKL) protein in the vertebrae tissue were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay. RESULTS There was a significant (p<0.01) decrease in the BMD and microarchitectural parameters in the vertebrae tissue of the fangchinoline-treated group compared to the prednisolone group. We also found that treatment with fangchinoline attenuated the altered expressions of LC3, Bcl-2, caspase-3, BMP2, Beclin-1, ATG-5, RUNX-2, and RANKL protein in the prednisolone-induced osteoporosis rats. Moreover, levels of biochemical parameters were attenuated in the serum of fangchinoline-treated and prednisolone-induced osteoporosis rat. Histopathology revealed that the apoptosis of osteoblasts was decreased in the fangchinoline-treated group compared to the prednisolone group of rats. CONCLUSIONS Fangchinoline inhibits apoptosis of osteoblasts and protects against bone loss in prednisolone-induced osteoporosis rats by inducing autophagy.
Topics: Animals; Apoptosis; Autophagy; Benzylisoquinolines; Bone Density; Bone Resorption; China; Disease Models, Animal; Male; Osteoblasts; Osteoporosis; Prednisolone; Rats; Rats, Wistar
PubMed: 30632520
DOI: 10.12659/MSM.912624 -
Human Gene Therapy Jul 2022Intravenous onasemnogene abeparvovec is approved for the treatment of spinal muscular atrophy in children < 2 years. For later-onset patients, intrathecal onasemnogene...
Intravenous onasemnogene abeparvovec is approved for the treatment of spinal muscular atrophy in children < 2 years. For later-onset patients, intrathecal onasemnogene abeparvovec may be advantageous over intravenous administration. Recently, microscopic dorsal root ganglion (DRG) changes were observed in nonhuman primates (NHPs) following intrathecal onasemnogene abeparvovec administration. To characterize these DRG findings, two NHP studies evaluating intrathecal onasemnogene abeparvovec administration were conducted: a 12-month study with a 6-week interim cohort and a 13-week study with a 2-week interim cohort. The latter investigated the potential impact of prednisolone or rituximab plus everolimus on DRG toxicity. An additional 6-month, single-dose, intravenous NHP study conducted in parallel evaluated onasemnogene abeparvovec safety (including DRG toxicity) with or without prednisolone coadministration. Intrathecal onasemnogene abeparvovec administration was well tolerated and not associated with clinical observations. Microscopic onasemnogene abeparvovec-related changes were observed in the DRG and trigeminal ganglion (TG) and included mononuclear cell inflammation and/or neuronal degeneration, which was colocalized with high vector transcript expression at 6 weeks postdose. Incidence and severity of DRG changes were generally decreased after 52 weeks compared with 6 weeks postdose. Other onasemnogene abeparvovec-related microscopic findings of axonal degeneration, mononuclear cell infiltrates and/or gliosis in the spinal cord, dorsal spinal nerve root/spinal nerves, and/or peripheral nerves were absent or found at decreased incidences and/or severities after 52 weeks. DRG and/or TG microscopic findings following intravenous onasemnogene abeparvovec dosing included minimal to slight neuronal degeneration and mononuclear cell inflammation at 6 weeks and 6 months postdose. Nervous system microscopic findings following intrathecal onasemnogene abeparvovec (≥1.2 × 10 vg/animal) trended toward resolution after 52 weeks, supporting nonprogression of changes, including in the DRG. Onasemnogene abeparvovec-related DRG findings were not associated with electrophysiology changes and were not ameliorated by prednisolone or rituximab plus everolimus coadministration. The pathogenesis is possibly a consequence of increased vector genome transduction and/or transgene expression.
Topics: Animals; Everolimus; Ganglia, Spinal; Humans; Inflammation; Macaca fascicularis; Prednisolone; Rituximab
PubMed: 35331006
DOI: 10.1089/hum.2021.255