pulmicort and Osteoporosis

Ulcerative colitis is a chronic inflammatory bowel disease. The disease is diagnosed on the basis of clinical parameters and endoscopic-histologic evaluation. 5-aminosalicylic acid (5-ASA, mesalamine) represents the first-line treatment of choice. For patients with distal and left-sided disease the use of rectal preparations is effective. Most patients respond to 5-ASA suppositories or to topic steroids such as budesonide suppositories or hydrocortisone foam. For patients with extended disease, oral medications are mandatory. In case of low- to moderate-grade inflammation, 5-ASA preparations should be implemented. In the case of severe disease treatment with steroids is required. Following induction of remission, prophylactic treatment with 5-ASA (1.5 g/d) should be maintained. For patients with frequent or severe relapses, immunosuppressive therapy with azathioprine or 6-mercaptopurine is indicated. In case of a fulminant course of disease, treatment with intravenous cyclosporine is required in patients who have not responded to high-dose intravenous steroids. When all conservative treatment options fail, proctocolectomy with construction of an ileoanal pouch should be performed. New therapeutic strategies such as infliximab and interferons are being evaluated in clinical trials. The long-term complications of ulcerative colitis include steroid-induced osteoporosis and anemia and should be treated adequately. Finally, the risk for development of colorectal cancer increases steadily with disease duration and dysplasia should be screened for by endoscopic surveillance programs.

Topics: Administration, Oral; Adrenal Cortex Hormones; Aminosalicylic Acids; Anemia; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antiviral Agents; Azathioprine; Budesonide; Clinical Trials as Topic; Colectomy; Colitis, Ulcerative; Colonic Pouches; Colonoscopy; Colorectal Neoplasms; Cyclosporins; Gastrointestinal Agents; Humans; Hydrocortisone; Immunosuppressive Agents; Infliximab; Injections, Intravenous; Interferons; Mercaptopurine; Mesalamine; Osteoporosis; Placebos; Practice Guidelines as Topic; Recurrence; Remission Induction; Risk Factors; Suppositories; Time Factors

In this chapter, the state-of-the-art treatment of Crohn's disease is summarized; the chapter intends to provide an uptodate knowledge of current treatment strategies of Crohn's disease. The indications for steroids and for immunomodulators are described and compared to newer approaches based on neutralizing tumor necrosis factor by specific antibodies (Infliximab). An attempt was made to clearly differentiate between evidence-based treatment schemes and those which are not supported by good evidence. The chapter was written for daily practice; the proposed treatment algorithms should support the physician in his daily work.

Topics: Acute Disease; Adjuvants, Immunologic; Adrenal Cortex Hormones; Algorithms; Aminosalicylic Acids; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Azathioprine; Budesonide; Case-Control Studies; Clinical Trials as Topic; Crohn Disease; Drug Therapy, Combination; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Infliximab; Mesalamine; Methotrexate; Metronidazole; Osteoporosis; Prednisolone; Prednisone; Randomized Controlled Trials as Topic; Time Factors

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

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Glucocorticoids; Growth; Humans; Longitudinal Studies; Osteoporosis; Pregnenediones

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

To evaluate the safety of budesonide in primary biliary cirrhosis.. 77 primary biliary cirrhosis patients, with stages I-III at entry, were randomized to use either budesonide 6 mg and ursodeoxycholic acid 15 mg/kg (group A), or ursodeoxycholic acid alone (group B) daily for 3 years. In 22 patients, budesonide pharmacokinetics was determined after 3 years. Bone mass density was measured in 62 patients at baseline and 3 years; in 57 patients also liver biopsies were performed.. At 3 years, no significant differences in the pharmacokinetics of budesonide were found between the patients with stages 0-I, II and III primary biliary cirrhosis. In group A, bone mass density in femoral neck and lumbar spine were decreased by 3.6% (P = 0.0002) and 2.8% (P = 0.003) from the baseline. In group B, the corresponding decreases were 1.9% (P = 0.029) and 0.7% (P = 0.25), but the differences between the groups were not statistically significant (P = 0.16 for femoral neck and P = 0.08 for lumbar spine).. The plasma concentrations of budesonide do not significantly differ within stages I-III primary biliary cirrhosis patients. The combination of budesonide and ursodeoxycholic acid may decrease bone mass density in the femoral neck and lumbar spine in some primary biliary cirrhosis patients, and bone mass density is recommended to be monitored during budesonide therapy.

Topics: Anti-Inflammatory Agents; Bone Density; Budesonide; Female; Humans; Liver Cirrhosis, Biliary; Male; Osteoporosis; Treatment Outcome

Topics: Asthma; Bone Density; Budesonide; Drug Therapy, Combination; Etidronic Acid; Glucocorticoids; Humans; Osteoporosis; Prednisone

Osteoporosis frequently occurs in Crohn's disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone.. In 34 international centers, 272 patients with Crohn's disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored.. Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, -1.04% vs -3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups.. Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn's disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.

Topics: Administration, Oral; Adult; Aged; Analysis of Variance; Bone Density; Budesonide; Crohn Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Osteoporosis; Prednisolone; Probability; Reference Values; Risk Assessment; Severity of Illness Index; Single-Blind Method

Topics: Anti-Inflammatory Agents; Bone Density; Budesonide; Crohn Disease; Delayed-Action Preparations; Double-Blind Method; Follow-Up Studies; Glucocorticoids; Humans; Osteoporosis; Prednisolone; Treatment Outcome

There is a need for studying the effects of long-term inhaled corticosteroid therapy on bone mineral density (BMD) and vertebral fracture rates in patients with mild chronic obstructive pulmonary disease (COPD). Patients (n=912, mean age 52 yrs) with mild COPD (mean forced expiratory volume in one second (FEV1) 77% of predicted; mean FEV1/slow vital capacity ratio 62%) were randomized to receive budesonide 400 microg, or placebo twice daily via Turbuhaler. BMD was measured at the L2-L4 vertebrae and the femoral neck, trochanter and Ward's triangle by dual-energy X-ray absorptiometry at baseline and after 6, 12, 24 and 36 months (n=161). Radiographs of the thoracic and lumbar spine were obtained at the beginning and end of treatment (n=653). Previous fractures were present at baseline in 43 budesonide-treated patients (13.4%) and 38 placebo-treated patients (11.5%). New fractures occurred in five budesonide-treated patients, compared with three in the placebo group (p=0.50). There were no significant changes in BMD at any site in budesonide-treated patients, compared with the placebo group, during the course of the study. Budesonide treatment was associated with a slight but statistically significant decrease in the area under the concentration-time curve for serum osteocalcin. In the present study, involving a large group of patients with chronic obstructive pulmonary disease, long-term treatment with budesonide 800 microg x day(-1) via Turbuhaler had no clinically significant effects on bone mineral density or fracture rates.

Topics: Administration, Inhalation; Adult; Aged; Anti-Inflammatory Agents; Bone Density; Budesonide; Female; Humans; Male; Middle Aged; Osteocalcin; Osteoporosis; Pulmonary Disease, Chronic Obstructive; Radiography; Risk Factors; Spinal Fractures

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

Inhaled glucocorticoids are pivotal in maintenance therapy of chronic bronchial asthma; however, conflict exists over their effects on bone and mineral metabolism. We measured bone mineral density (BMD), bone turnover markers, and adrenal steroid hormones in 53 patients (34 female, 19 male) with chronic bronchial asthma who had taken either inhaled beclomethasone or budesonide in doses of > or = 1500 microg/day for at least 12 months to determine pathogenetic mechanisms of bone loss. To account for the effect of prior oral glucocorticoid exposure we divided patients into two groups: one with (OG) and the other without (IG) a past history of maintenance (> 1 month) oral glucocorticoid therapy. Lumbar spine (LS) and proximal femur BMDs were approximately 1 SD lower in men and women taking OG or high-dose IG for chronic bronchial asthma, potentially equivalent to a doubling of the risk of fracture at these sites. Prior exposure to OG in women was also associated with lower LS and proximal femur BMDs, while men were more sensitive to the adverse effects of IG on LS and Ward's triangle BMDs. Bone formation markers were decreased; however, bone resorption marker concentrations were normal. All patients had evidence of suppression of both endogenous glucocorticoid and adrenal androgen production. Both total duration of OG and biochemical bone turnover marker concentrations were negatively related to proximal femur and rib BMDs and total body bone mineral content, but not to LS BMD. These were stronger for bone resorption markers. Uncoupling of ongoing normal bone resorption from suppressed bone formation may therefore contribute to glucocorticoid-associated bone loss in asthma. Adrenal androgen suppression may also increase the susceptibility of postmenopausal women in particular to bone loss with OG. Although the effects of high-dose IG on BMD are associated with lower LS BMD in men, this observation should now be investigated further in prospective studies.

Topics: Absorptiometry, Photon; Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Beclomethasone; Biomarkers; Bone Density; Budesonide; Dehydroepiandrosterone Sulfate; Female; Femur; Glucocorticoids; Humans; Hydrocortisone; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Ribs

Bone mass and biochemical bone markers were prospectively studied in 33 patients with chronic obstructive pulmonary disease treated for 1 year with inhaled beclomethasone 200 micrograms/q.i.d. (group A, 8 men and 4 women), inhaled budesonide 200 micrograms/q.i.d. (group B, 6 men and 5 women), or not requiring steroids (group C, 6 men and 4 women). Both inhaled corticosteroids decreased serum concentrations of the osteoblastic markers, osteocalcin and carboxy-terminal propeptide of type I collagen (PICP). The osteoclastic marker cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) increased significantly more in patients on beclomethasone than in those on budesonide. The decrease in bone mineral density was more pronounced in patients treated with beclomethasone (1.1% in the spine 1.7% in the hip P < 0.05) compared to those treated with budesonide (0.6% in both spine and hip) or in the control group. Inhaled corticosteroids affect biochemical bone markers and bone mineral density, but there is a different effect for the two corticosteroids evaluated in the present study.

Topics: Administration, Inhalation; Adult; Aged; Alkaline Phosphatase; Beclomethasone; Biomarkers; Bone Density; Budesonide; Calcium; Collagen; Collagen Type I; Female; Glucocorticoids; Homeostasis; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Osteocalcin; Osteoporosis; Peptide Fragments; Peptides; Pregnenediones; Procollagen; Prospective Studies

In a randomized, double-blind crossover study, the effects of 0.8, 1.6 and 3.2 mg/day inhaled budesonide and 5, 10 and 20 mg/day oral prednisolone on mineral metabolism were compared. Twelve healthy subjects (4 m, 8 f) were treated for 1 week at each dosage level, the graduated dosages being given in ascending order. Budesonide and prednisolone were given twice daily and once daily, respectively, which reflects the schedules common in clinical practice. Serum calcium and the regulatory hormones of calcium metabolism (parathyroid hormone, vitamin D metabolites and calcitonin) were not changed either by prednisolone or budesonide. Prednisolone significantly increased 24 h and 08.00 h fasting urinary calcium excretion and decreased renal calcium reabsorption, while budesonide had little or no effect on urinary calcium loss and increased renal reabsorption at the highest dose level. Both drugs significantly increased renal phosphate reabsorption and serum phosphate levels, but prednisolone caused greater increases than budesonide. In conclusion, during short-term treatment with the dosages used, inhaled budesonide had less effect on calcium and phosphate metabolism than oral prednisolone, and so it may have a lesser action on the skeleton of the type contributing to osteoporosis during long-term treatment.

Topics: Administration, Inhalation; Adult; Aerosols; Budesonide; Calcium; Double-Blind Method; Glucocorticoids; Humans; Middle Aged; Osteoporosis; Phosphates; Prednisolone; Pregnenediones; Tablets

Outcomes and safety of budesonide maintenance therapy in microscopic colitis (MC) are not well known.. Adult residents of Olmsted County, Minnesota, diagnosed with MC (2002-2019) and treated with budesonide were identified using the Rochester Epidemiology Project. Response was assessed at 12 ± 4 weeks after initiation of therapy and defined as complete (resolution of diarrhea), partial (≥50% improvement in the number of bowel movements), nonresponse (<50% improvement), and intolerance (discontinued because of side effects). For safety outcomes, cases (budesonide maintenance) and MC controls (no budesonide therapy) were matched by sex and age at diagnosis (±2 years).. A total of 450 patients were identified, of whom 162 (36.0%) were treated with budesonide for induction of clinical remission (median age 67 [23-91] years and 126 women [77.8%] ). Clinical outcomes for induction were as follows: 130 (80.2%) complete response, 22 (13.6%) partial response, 8 (4.9%) no response, and 2 (1.2%) intolerance. After induction, 96 (63.2%) had recurrence after discontinuation, of whom 27 (28.1%) required further budesonide induction treatment without maintenance, 56 (58.3%) required long-term budesonide maintenance, and 13 (13.5%) were treated with other therapies. Of those receiving budesonide maintenance, all responded (55 [98.2%] complete and 1 [1.8%] partial). No patient stopped maintenance from adverse events. The median duration of follow-up was 5.6 years (0.3-18.9). There was no significant difference between cases and controls in the incidence of osteopenia/osteoporosis, diabetes mellitus, hypertension, glaucoma, or cataracts.. The long-term use of budesonide in MC seems to be effective and generally well tolerated with limited adverse effects.

Topics: Adult; Aged; Bone Diseases, Metabolic; Budesonide; Colitis, Microscopic; Female; Humans; Osteoporosis; Remission Induction

Patients with microscopic colitis (MC) have several risk factors for osteoporosis. The prevalence of osteopenia and osteoporosis in MC is unknown. The primary purpose of this study was to evaluate bone mineral status in MC.. Patients with MC and disease activity within the last 2 years were included. Bone turnover markers were analyzed and bone mineral density (BMD) was measured with Dual Energy X-ray Absorptiometry (DXA) at inclusion and after one year. Medical history, demographics, risk factors for osteoporosis, disease activity and treatment with cumulative budesonide dosage at least 3 years before inclusion was registered. Adrenal function was tested by adrenocortico-tropic hormone (ACTH) and an ACTH stimulation test at inclusion. Results were compared with age and sex-matched controls.. Fifty MC patients (44 women) were included. Median age 67 (range 45-93); median disease duration 28 month (range 2-163); median cumulative budesonide dosage 702 mg (range 0-5400). No difference in number of patients with osteoporosis or osteopenia and BMD was detected between groups. The bone mineral formation marker specific alkaline phosphatase was lower in MC than controls 12 (5-69) µg/l versus 16 (10-35) µg/l (p <. The risk of osteoporosis in patients with MC is not increased. However, DXA scan is recommended in MC patients with known risk factors or active disease requiring longstanding budesonide treatment. Supplementation of calcium and vitamin-D in patients treated with budesonide is recommended.

Topics: Absorptiometry, Photon; Adrenal Glands; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Biomarkers; Bone Density; Bone Diseases, Metabolic; Budesonide; Colitis, Microscopic; Female; Humans; Male; Middle Aged; Osteoporosis; Prospective Studies; Risk Factors; Severity of Illness Index; Smoking; Socioeconomic Factors; Time Factors

Bilateral proximal femoral fractures without trauma are very rare conditions. They have been reported in connection with osteoporosis, renal osteodystrophy, parathyroid disease, tumors, epileptic seizures, electroconvulsive therapy, and postirradiation.. We present a case of a 75-year-old man with bilateral hip fractures. No trauma, neurological, endocrinological disorder, or malignancy was reported in his history. He had a background of chronic obstructive pulmonary disease (COPD) and had been taking inhaled steroids (budesonide) 800 µg per day for 10 years. He was a heavy smoker with a smoking history of 120 packs/year. His complaints had initially started as pain on the left hip and groin and then had progressed to the right in 10 days. Plain x-rays of the pelvis showed left femoral neck and right subtrochanteric femoral fractures. Fixation with proximal femoral nail of the right hip and partial arthroplasty of the left hip was performed on the following day after his admission. Pathological examination revealed osteoporosis in bone samples from both hips.. COPD and osteoporosis have some common risk factors. Smoking, decreased exercise capacity, inhaled, or oral steroid therapy may increase osteoporosis and risk of bone fractures by decreasing bone mineral density. Non-traumatic femoral fractures may occur in patients on long-term inhaled steroid treatment for chronic airway diseases such as asthma and COPD.. History of COPD with corticosteroid use may be used as a diagnostic tool to identify patients having osteoporosis. Preventive measures can be performed by monitoring high-risk patients with bone mineral densitometry, WHO fracture risk assessment tool (FRAX tool), serum calcium, and vitamin D levels to prevent bone fractures. Treating those patients with the lowest effective dose of corticosteroids should be targeted.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Bone Density; Budesonide; Femoral Neck Fractures; Hip Fractures; Humans; Male; Osteoporosis; Pulmonary Disease, Chronic Obstructive; Risk Factors; Smoking

To investigate the extent of inhaled glucocorticoid (IGC) treatment in general and to what extent general practitioners (GPs) manage the risk of glucocorticoid-induced osteoporosis.. A questionnaire was sent to all 3,617 GPs in Denmark.. The results are divided into criteria for recommending prophylaxis with calcium and vitamin D for patients in actual IGC treatment, routine examinations for osteoporosis before starting asthma or chronic obstructive pulmonary disease (COPD) treatment with IGC, and criteria for starting anti-osteoporotic treatment (bisphosphonates + calcium + vitamin D) for patients in IGC treatment. A total of 535 questionnaires were eligible for evaluation and covered almost 25% of the Danish population. In general, the questionnaires documented that physicians do not use primary nor secondary prophylaxis in their patients treated with IGC with or without risk factors of osteoporosis.. More studies are warranted to verify the effects of IGC treatment on bone health and the importance of prophylaxis to prevent osteoporosis in IGC-treated patients before outlining specific recommendations for the management of the disease.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Asthma; Bone Density Conservation Agents; Bronchodilator Agents; Budesonide; Calcium; Diphosphonates; Family Practice; Glucocorticoids; Humans; Osteoporosis; Practice Patterns, Physicians'; Surveys and Questionnaires; Vitamin D

Ursodeoxycholic acid (UDCA) is a safe and effective medical therapy for most patients with primary biliary cirrhosis (PBC). However, some patients show an incomplete response to UDCA therapy. Treatment with corticosteroids may be of benefit although at the expense of systemic side effects. Budesonide, a corticosteroid with an extensive first-pass hepatic metabolism appeared promising for the treatment of PBC. The aim of this study was to evaluate the safety and estimate the efficacy of budesonide in patients with PBC, who have shown a suboptimal response to UDCA. Twenty-two patients with PBC, 16 women, median age of 50 who had been on UDCA (13-15 mg/kg/d) for a mean of 46 months (range 6-108 months) and had shown a persistent elevation of alkaline phosphatase activity at least 2 times the upper limit of normal were enrolled. Oral budesonide, 9 mg daily was administered for 1 year and patients continued on the same dosage of UDCA. There was a significant, but transitory improvement in serum levels of total bilirubin (P =.001) and a significant, but marginal improvement in serum alkaline phsophatase (P =.001) with combination therapy. The Mayo risk score increased significantly (P =.02) and there was a significant loss of bone mass (P <.001) of the lumbar spine. Budesonide-induced hyperglycemia and cosmetic adverse effects were noted in 2 patients. In conclusion, oral budesonide appears to add minimal, if any, additional benefit to UDCA, and it is associated with a significant worsening of osteoporosis in patients with PBC.

Topics: Administration, Oral; Administration, Topical; Adult; Aged; Alkaline Phosphatase; Anti-Inflammatory Agents; Bilirubin; Bone Density; Budesonide; Cholagogues and Choleretics; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Liver Cirrhosis, Biliary; Male; Middle Aged; Osteoporosis; Pilot Projects; Retreatment; Treatment Failure; Ursodeoxycholic Acid

Inhaled corticosteroids have become a key element in the maintenance treatment of bronchial asthma. It is well-known that long-term systemic steroid use causes osteoporosis, whereas its inhaled counterpart has been believed to be devoid of such a side-effect. However, recent studies showed that administration of inhaled corticosteroids was associated with biochemical evidence of derangement in bone turnover. We therefore studied bone mineral density (BMD) by dual energy x-ray absorptiometry in 30 patients (18 females, 12 males) with bronchial asthma treated with steroids, essentially by the inhaled route only (both nasal and tracheobronchial), and compared them with healthy subjects individually matched for age, sex, menopausal status, and body mass index (BMI). There was a significant decrease in BMD in the patient group at the hip (neck of femur, p = 0.007; trochanter of femur, p = 0.034; Ward's triangle, p = 0.016) and the lumbar area of the spine (L2-4, p = 0.041). Further analysis showed that this difference from control subjects was mainly seen in the female patients and not in the male patients (neck of femur, p = 0.049; Ward's triangle, p = 0.025; lumbar spine, p = 0.039). In the female patients, there was significant negative correlation of BMD of the lumbar area of the spine and the trochanter of femur with daily inhaled steroid dose and positive correlation of BMD of the trochanter with BMI.

Topics: Absorptiometry, Photon; Administration, Inhalation; Adult; Aerosols; Asthma; Beclomethasone; Bone Density; Bronchodilator Agents; Budesonide; Female; Humans; Male; Osteoporosis; Pregnenediones; Premenopause; Risk Factors; Time Factors

We investigated the effects of the antiasthmatic inhaled steroid budesonide at low and high dosage (0.6 and 2.4 mg/day) on calcium and phosphate metabolism (Ca, P) in 10 normal adults. Their endogenous production of cortisol dropped with budesonide treatment (p less than or equal to 0.0005), as did androgen production (p less than or equal to 0.003). This was associated with an increase in the renal tubular maximal reabsorption of Ca (p = 0.003) and P (p = 0.03), a decrease in the urinary output of Ca in the fasting morning state (p = 0.03), and an increase in serum P (p = 0.02). However, there was no change in the 24-h urinary excretion of Ca (p = 0.76) or P (p = 0.08) or the serum Ca level (p = 0.19). Similarly, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, parathyroid hormone, and urinary cAMP levels were not affected, indicating that absorption of Ca from the gut was not compromised. Thus, in contrast to the expected effects of oral steroid treatment, inhaled budesonide had no discernible short-term adverse effect on Ca or P metabolism under the conditions of this study, despite purposely using a dosage high enough to partially inhibit adrenocortical function. These data tend to support a broadening of the therapeutic role of budesonide, and possibly other inhaled steroid drugs, to include higher doses and more severe asthmatics. However, additional clinical and metabolic studies are needed to fully clarify the effects of high-dose inhaled steroid therapy on bone.

Topics: Absorption; Administration, Inhalation; Budesonide; Calcium; Dose-Response Relationship, Drug; Female; Glucocorticoids; Humans; Male; Middle Aged; Osteoporosis; Phosphates; Pregnenediones; Risk Factors

Topics: Adrenergic beta-Agonists; Aerosols; Airway Obstruction; Aspirin; Asthma; Bronchi; Bronchodilator Agents; Budesonide; Calcium Channel Blockers; Cromolyn Sodium; Drug Administration Schedule; Epinephrine; Glucocorticoids; Gold; Humans; Inflammation; Mucous Membrane; Osteoporosis; Parasympatholytics; Patient Education as Topic; Prednisone; Pregnenediones; Theophylline