fluticasone and Osteoporosis

Inhaled administration of glucocorticoid doesn't mean lack of systemic effects of drug. Bioavailability of steroid depends on oral absorption and absorption from respiratory system. In case of fluticasone propionate (FP) swallowed dose can be neglected because almost total (>99%) inactivation in liver during first pass. In second part of paper the most important safety parameters of therapy with FP are discussed, it means; influence on hypothalamic-pituitary-adrenal axis, growth and bone metabolism. Interpretation of potential side effects should differentiate between abnormal value of laboratory test and clinically important symptoms. Adrenal suppression depends on dose of FP and was found even after low dose (about 200 microg per day), but clinical value of this findings is unknown. Prolonged administration of high doses can suppress hypothalamic-pituitary-adrenal axis; exceptionally, it can induce adrenal insufficiency. Recommended doses of FP given 1 to 2 years doesn't cause growth retardation. Long term studies on influence of drug on final height are needed. FP as other inhaled corticosteroids, may transiently alter bone metabolism. Till now there are no evidences that this drug, when prescribed appropriately in standard doses for asthma control, may decrease the bone mineral density or induce osteoporosis and may increase the risk of bone fractures in asthmatic children. Effective asthma control achieved with FP therapy permits normal activity and development of asthmatic children which prevails over exceptionally noticed side effects.

Topics: Administration, Inhalation; Adolescent; Age Factors; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bone Density; Child; Child, Preschool; Drug Administration Schedule; Female; Fluticasone; Humans; Hypothalamo-Hypophyseal System; Infant; Infant, Newborn; Male; Osteoporosis; Pituitary-Adrenal System; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome

Oral corticosteroids have adverse effects on bone density and metabolism. With the increased use of inhaled corticosteroids together with the use of higher doses for the treatment of asthma, the long-term effects of inhaled corticosteroids on bone metabolism and density must be evaluated. This article discusses the markers of bone resorption and formation together with techniques used to measure cortical and trabecular bone density. The effects of inhaled corticosteroids on bone density and metabolism as determined by these techniques are described in detail. Overall, inhaled corticosteroids are extremely safe, even at high doses, with the long-term risk of bone loss being extremely small compared with oral corticosteroids. In particular, fluticasone propionate at the recommended doses appears to be free of effects on bone density and metabolism. Finally, the use of inhaled corticosteroids results in the control of asthma, allowing patients to exercise, which itself improves bone density and protects against osteoporosis.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Biomarkers; Bone and Bones; Bone Density; Bone Resorption; Budesonide; Female; Fluticasone; Humans; Male; Osteoporosis

Topics: Administration, Inhalation; Administration, Topical; Adrenal Glands; Androstadienes; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Budesonide; Dose-Response Relationship, Drug; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Growth; Humans; Osteoporosis; Pregnenediones; Triamcinolone Acetonide

Osteoporosis is common in patients with COPD, but its prevalence and progression are not well characterized. Concerns have been raised over the possible deleterious effect of long-term therapy with inhaled corticosteroids (ICSs) on bone density in this population. Here, we investigated the long-term effects of therapy with fluticasone propionate (FP) alone, salmeterol (SAL) alone, and a SAL/FP combination (SFC) on bone mineral density (BMD) and bone fractures in patients with moderate-to-severe COPD in the TOwards a Revolution in COPD Health (TORCH) study.. A randomized, double-blind, parallel-group, placebo-controlled study conducted at 88 US centers involving 658 patients (a subset of 6,184 international subjects in TORCH). Therapy with placebo, SAL (50 microg), FP (500 microg), or SFC (SAL 50 microg/FP 500 microg) twice daily was administered for 3 years. Baseline and yearly measurements of BMD at the hip and lumbar spine were performed. The incidence of traumatic and nontraumatic bone fractures was recorded.. At baseline, 18% of men and 30% of women had osteoporosis, and 42% of men and 41% of women had osteopenia based on BMD assessments. Forty-three percent of subjects completed all testing. The changes in BMD at the hip and lumbar spine over 3 years were small. No significant differences were observed between treatment arms (adjusted mean percent change from baseline at hip was -3.1% for placebo, -1.7% for SAL, -2.9% for FP, and -3.2% for SFC therapy, respectively; while, the corresponding changes for the lumbar spine were 0, 1.5%, -0.3%, and -0.3% for placebo, respectively, SAL, FP, and SFC therapy). The incidence of fractures was low and was similar for all treatments (5.1% to 6.3%).. Osteoporosis is highly prevalent in patients with COPD, irrespective of gender. In the TORCH study, no significant effect on BMD was detected for ICS therapy compared with placebo.. ClinicalTrials.gov Identifier: NTC00268216.

Topics: Aged; Albuterol; Androstadienes; Bone Density; Bone Diseases, Metabolic; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Fractures, Bone; Humans; Male; Middle Aged; Osteoporosis; Prevalence; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Risk Factors; Salmeterol Xinafoate; Treatment Outcome; United States

Combination of inhaled corticosteroids (ICS) with long acting beta2 agonists has been used increasingly in the treatment of moderate-severe asthma, however there is indefinitive data about their effect on bone loss. The aim of this study was to compare the effects of treatment with single ICS and combination of ICS with long acting beta2 agonists (combination therapy) on BMD and biomarkers of bone metabolism in adult patients with asthma over 1 year period. Forty-three patients with asthma were enrolled. Patients were separated into two groups according to their use of asthma drugs: single ICS or combination therapy (ICS plus long-acting inhaled beta2-agonist). Change in bone mineral density (BMD) and biochemical markers of bone metabolism were measured at baseline and at the end of 1 year. Mean ages and basal BMD of patients did not differ between the two groups (P > 0.05). The decrease in BMD was higher in the single ICS group than the combination therapy group, however there was no significant difference between them (P > 0.05). One year change (%) in BMD and biochemical markers of bone metabolism were not different between two groups (P > 0.05). In conclusion, use of ICS-in the range of doses used- does not seem to have an effect on the change of BMD. However, our data indicate a nonsignificant trend towards reducing bone loss with the use of combination therapy. Future studies are needed to provide definitive evidence for this trend to allow us suggesting combination therapy for minimizing bone loss.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Asthma; Beclomethasone; Bone Density; Bone Resorption; Budesonide; Drug Therapy, Combination; Ethanolamines; Female; Fluticasone; Formoterol Fumarate; Humans; Male; Middle Aged; Osteoporosis; Salmeterol Xinafoate

Steroid therapy is the third most common cause of osteoporosis, after loss of gonad function and senescence. The aim of the present study was to evaluate the protective action of clodronate on bone mass loss induced by steroid therapy. Sixty patients with bronchial asthma receiving either fluticasone (250 mg x 4/day) or beclomethasone (250 mg x 4/day) inhaled corticosteroid treatment were enrolled. Half the patients received combination treatment with clodronate (100 mg i.m./14 days), for a total period of 12 months. All patients were evaluated at baseline and at the end of treatment for bone mineral density (BMD) and calcium/phosphor metabolism parameters (kalemia, kaluria, phosphoremia, phosphaturia, alkaline phosphatase and hydroxyprolinuria over a 24-h period). The results of this preliminary study confirm the protective influence of clodronate on bone mass loss, as documented by the increment in mean values in BMD reported at the end of treatment compared with baseline values.

Topics: Administration, Inhalation; Aged; Androstadienes; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bone Density; Chronic Disease; Clodronic Acid; Fluticasone; Humans; Infusion Pumps; Male; Middle Aged; Osteoporosis

Oral corticosteroids have adverse effects on bone density and metabolism. With the increased use of inhaled corticosteroids together with the use of higher doses for the treatment of asthma, the long-term effects of inhaled corticosteroids on bone metabolism and density must be evaluated. This article discusses the markers of bone resorption and formation together with techniques used to measure cortical and trabecular bone density. The effects of inhaled corticosteroids on bone density and metabolism as determined by these techniques are described in detail. Overall, inhaled corticosteroids are extremely safe, even at high doses, with the long-term risk of bone loss being extremely small compared with oral corticosteroids. In particular, fluticasone propionate at the recommended doses appears to be free of effects on bone density and metabolism. Finally, the use of inhaled corticosteroids results in the control of asthma, allowing patients to exercise, which itself improves bone density and protects against osteoporosis.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Androstadienes; Biomarkers; Bone and Bones; Bone Density; Bone Resorption; Budesonide; Female; Fluticasone; Humans; Male; Osteoporosis

The advent of highly active antiretroviral therapy for HIV infection dramatically changed the landscape of the disease. Ritonavir, a protease inhibitor (PI) frequently used in low doses to 'boost' the concentrations of other PIs, inhibits the cytochrome P450 3A4 isoenzyme, a common metabolic pathway to multiple drugs, so the potential for drug interactions is not negligible. A 39-year-old man with HIV-1 infection, treated with a ritonavir-boosted PI, was started on fluticasone/salmeterol inhaler and intranasal fluticasone, in 2009, in the setting of asthma and allergic rhinitis. In 2013, he presented with 1-year evolution of symptoms suggesting Cushing's syndrome, and was experiencing recurrent falls. A spine CT showed a vertical L3 fracture and thoracolumbar erosions; a bone density scan revealed severe osteoporosis. Hormonal assays were compatible with hypothalamic-pituitary-adrenal axis suppression, and iatrogenic Cushing's syndrome due to ritonavir-fluticasone interaction was considered. Fluticasone was suspended and oral corticosteroid replacement initiated, with a favourable outcome.

Topics: Accidental Falls; Adult; Anti-Allergic Agents; Asthma; Bronchodilator Agents; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Infections; HIV Protease Inhibitors; Humans; Iatrogenic Disease; Male; Osteoporosis; Rhinitis, Allergic; Ritonavir

Ritonavir, a protease inhibitor (PI), is a potent inhibitor of cytochrome P450 3A4. This pharmacological effect, even at low doses (

Topics: Administration, Inhalation; Adrenal Insufficiency; Adult; Androstadienes; Cushing Syndrome; Drug Interactions; Fluticasone; HIV Protease Inhibitors; Humans; Male; Middle Aged; Osteoporosis; Ritonavir

To evaluate osteoporosis in asthmatic patients.. Bone mineral density (BMD) was measured using three different methods, namely computed X-ray densitometry (CXD), digital image processing (DIP), and dual energy X-ray absorptiometry (DXA). The BMD data were standardized using the sex- and age-matched mean value of BMD.. One hundred and twenty-eight patients with persistent asthma.. The standardized BMD expressed as Z-score in asthmatic patients was significantly lower than the norm (Z-score -0.48 +/- 1.17, mean +/- SD). In patients who had been continuously treated with oral corticosteroids (OCS), the standardized BMD was significantly lower than that in patients treated without OCS. In addition, the standardized BMD in patients 60 years and over (Z-score -0.71 +/- 1.10, mean +/- SD, n = 58) had decreased to a greater extent than the decrease seen in patients under 60 years (Z-score -0.30 +/- 1.21, n=70). Moreover, BMD in these older patients decreased after a 6-month treatment protocol involving the use of an inhaled corticosteroid, fluticasone propionate (FP). During the 6 months, the treatment did not affect BMD in patients who were receiving FP for the first time. Although the BMD did not decrease in patients treated with FP without OCS, the BMD in patients treated with both FP and OCS decreased during the 6 months.. These results indicate that the continuous administration of OCS in patients with severe persistent asthma, particularly in older patients, may affect BMD in the short term even at a low OCS dose.

Topics: Absorptiometry, Photon; Administration, Inhalation; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Asthma; Bone Density; Female; Fluticasone; Humans; Male; Middle Aged; Osteoporosis; Radius

Allen & Hanburys recently launched Flixotide Nebules for prophylactic management of severe chronic asthma in patients requiring high-dose inhaled or oral corticosteroid therapy.

Topics: Androstadienes; Anti-Asthmatic Agents; Asthma; Fluticasone; Humans; Nebulizers and Vaporizers; Osteoporosis