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What are effective strategies for reducing the risk of steroid-induced osteoporosis?
Calcium, in combination with vitamin D, prevents bone loss and is recommended in all patients. (Grade of recommendation: A, based on systematic reviews of randomized controlled trials [RCTs]). Alendronate and risedronate prevent fractures and should be considered for all patients at increased risk of fracture (5 mg of prednisone or equivalent, daily for longer than 3 months). (Grade of recommendation: A, based on RCTs) Replacement of sex hormones in hypogonadal patients prevents bone loss and increases bone mineral density (BMD). (Grade of recommendation: A for women, based on RCTs; B for men, based on one randomized, crossover trial.) Calcitonin prevents bone loss for up to 1 year. (Grade of recommendation: A, based on systematic review.)
Evidence summary
A systematic review of 5 RCTs (N=274) confirmed clinically and statistically significant prevention of bone loss at the lumbar spine for patients receiving glucocorticoids who also received calcium (500–1000 mg daily) and vitamin D (400–800 IU) daily.1 A systematic review found that patients receiving steroids longer than 3 months gained bone mass when placed on a bisphosphonate.2 A two-year RCT of 208 patients receiving steroids who also received alendronate or placebo demonstrated an incidence of vertebral fracture of 0.7% and 6.8% (NNT=16; RRR=90%; ARR = 5.9%; P= .026), respectively.3 A 48-week RCT involving 477 patients receiving steroids who also received alendronate or placebo demonstrated a 2.3% and 3.7% in incidence of vertebral fracture, respectively (RRR = 38%; ARR = 1.4%; P= NS).4 A 1-year RCT of 184 men on or off steroids using risedronate found an 82.4% decreased incidence of vertebral fractures compared with those who received placebo (NNT = 5; P= .008).5
In hypogonadal patients, several small studies have shown that replacement of sex hormones (estrogen in women and testosterone in men) increases lumbar spine BMD (women 2% and 3–4%; men 5%; all P< .05). Fracture reduction and risk of long-term use were not studied.6-8 In a systematic review of 9 RCTs, including 441 patients, calcitonin preserved bone mass in the lumbar spine but not the femoral neck during the first year of steroid therapy. Lumbar spine BMD values with calcitonin were significantly higher than with placebo at 6 and 12 months, but were similar at 24 months.9
Recommendations from others
The American College of Rheumatology recommends calcium and vitamin D be offered to all patients initiating a regimen of prednisone 5 mg/d or its equivalent with expected duration of longer than 3 months. Bisphosphonates should be prescribed for all patients starting steroids and for patients receiving steroids with a T-score less than -1.0; however they should be used with caution in pre-menopausal women.8 A leading researcher states the rank order for prevention is a bisphosphonate followed by a vitamin D metabolite or hormone replacement.10
Clinical Commentary by Michael Fisher, MD, at http://www.fpin.org.
1. Homik J, Suarez-Almazor ME, Shea B, Cranny A, et al. Cochrane Database Syst Rev. Issue 2, 2002.
2. Blair MM, Carson DS, Barrington R. J Fam Pract 2000;49:839-48.
3. Adachi JD, Saag KG, Delmas PD, Liberman UA, et al. Arthritis Rheum 2001;44:202-11.
4. Saag KG, Emkey R, Schnitzer TJ, Brown JP, et al. N Engl J Med 1998;339:292-9.
5. Reid DM, Adami S, Devogelaer JP, Chines AA. Calcif Tissue Int 2001;69:242-7.
6. Kung AW, Chan TM, Lau CS, Wong RW, et al. Rheumatology 1999;38:1239-44.
7. Reid IR, Wattie DJ, Evans MC, Stapleton JP. Arch Intern Med 1996;156:1173-7.
8. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001;44:1496-503.
9. Cranney A, Welch V, Adachi JD, Homik J, et al. Cochrane Database Syst Rev. Issue 2, 2002.
10. Sambrook PN. Ann Acad Med Singapore 2002;31:48-53.
Calcium, in combination with vitamin D, prevents bone loss and is recommended in all patients. (Grade of recommendation: A, based on systematic reviews of randomized controlled trials [RCTs]). Alendronate and risedronate prevent fractures and should be considered for all patients at increased risk of fracture (5 mg of prednisone or equivalent, daily for longer than 3 months). (Grade of recommendation: A, based on RCTs) Replacement of sex hormones in hypogonadal patients prevents bone loss and increases bone mineral density (BMD). (Grade of recommendation: A for women, based on RCTs; B for men, based on one randomized, crossover trial.) Calcitonin prevents bone loss for up to 1 year. (Grade of recommendation: A, based on systematic review.)
Evidence summary
A systematic review of 5 RCTs (N=274) confirmed clinically and statistically significant prevention of bone loss at the lumbar spine for patients receiving glucocorticoids who also received calcium (500–1000 mg daily) and vitamin D (400–800 IU) daily.1 A systematic review found that patients receiving steroids longer than 3 months gained bone mass when placed on a bisphosphonate.2 A two-year RCT of 208 patients receiving steroids who also received alendronate or placebo demonstrated an incidence of vertebral fracture of 0.7% and 6.8% (NNT=16; RRR=90%; ARR = 5.9%; P= .026), respectively.3 A 48-week RCT involving 477 patients receiving steroids who also received alendronate or placebo demonstrated a 2.3% and 3.7% in incidence of vertebral fracture, respectively (RRR = 38%; ARR = 1.4%; P= NS).4 A 1-year RCT of 184 men on or off steroids using risedronate found an 82.4% decreased incidence of vertebral fractures compared with those who received placebo (NNT = 5; P= .008).5
In hypogonadal patients, several small studies have shown that replacement of sex hormones (estrogen in women and testosterone in men) increases lumbar spine BMD (women 2% and 3–4%; men 5%; all P< .05). Fracture reduction and risk of long-term use were not studied.6-8 In a systematic review of 9 RCTs, including 441 patients, calcitonin preserved bone mass in the lumbar spine but not the femoral neck during the first year of steroid therapy. Lumbar spine BMD values with calcitonin were significantly higher than with placebo at 6 and 12 months, but were similar at 24 months.9
Recommendations from others
The American College of Rheumatology recommends calcium and vitamin D be offered to all patients initiating a regimen of prednisone 5 mg/d or its equivalent with expected duration of longer than 3 months. Bisphosphonates should be prescribed for all patients starting steroids and for patients receiving steroids with a T-score less than -1.0; however they should be used with caution in pre-menopausal women.8 A leading researcher states the rank order for prevention is a bisphosphonate followed by a vitamin D metabolite or hormone replacement.10
Clinical Commentary by Michael Fisher, MD, at http://www.fpin.org.
Calcium, in combination with vitamin D, prevents bone loss and is recommended in all patients. (Grade of recommendation: A, based on systematic reviews of randomized controlled trials [RCTs]). Alendronate and risedronate prevent fractures and should be considered for all patients at increased risk of fracture (5 mg of prednisone or equivalent, daily for longer than 3 months). (Grade of recommendation: A, based on RCTs) Replacement of sex hormones in hypogonadal patients prevents bone loss and increases bone mineral density (BMD). (Grade of recommendation: A for women, based on RCTs; B for men, based on one randomized, crossover trial.) Calcitonin prevents bone loss for up to 1 year. (Grade of recommendation: A, based on systematic review.)
Evidence summary
A systematic review of 5 RCTs (N=274) confirmed clinically and statistically significant prevention of bone loss at the lumbar spine for patients receiving glucocorticoids who also received calcium (500–1000 mg daily) and vitamin D (400–800 IU) daily.1 A systematic review found that patients receiving steroids longer than 3 months gained bone mass when placed on a bisphosphonate.2 A two-year RCT of 208 patients receiving steroids who also received alendronate or placebo demonstrated an incidence of vertebral fracture of 0.7% and 6.8% (NNT=16; RRR=90%; ARR = 5.9%; P= .026), respectively.3 A 48-week RCT involving 477 patients receiving steroids who also received alendronate or placebo demonstrated a 2.3% and 3.7% in incidence of vertebral fracture, respectively (RRR = 38%; ARR = 1.4%; P= NS).4 A 1-year RCT of 184 men on or off steroids using risedronate found an 82.4% decreased incidence of vertebral fractures compared with those who received placebo (NNT = 5; P= .008).5
In hypogonadal patients, several small studies have shown that replacement of sex hormones (estrogen in women and testosterone in men) increases lumbar spine BMD (women 2% and 3–4%; men 5%; all P< .05). Fracture reduction and risk of long-term use were not studied.6-8 In a systematic review of 9 RCTs, including 441 patients, calcitonin preserved bone mass in the lumbar spine but not the femoral neck during the first year of steroid therapy. Lumbar spine BMD values with calcitonin were significantly higher than with placebo at 6 and 12 months, but were similar at 24 months.9
Recommendations from others
The American College of Rheumatology recommends calcium and vitamin D be offered to all patients initiating a regimen of prednisone 5 mg/d or its equivalent with expected duration of longer than 3 months. Bisphosphonates should be prescribed for all patients starting steroids and for patients receiving steroids with a T-score less than -1.0; however they should be used with caution in pre-menopausal women.8 A leading researcher states the rank order for prevention is a bisphosphonate followed by a vitamin D metabolite or hormone replacement.10
Clinical Commentary by Michael Fisher, MD, at http://www.fpin.org.
1. Homik J, Suarez-Almazor ME, Shea B, Cranny A, et al. Cochrane Database Syst Rev. Issue 2, 2002.
2. Blair MM, Carson DS, Barrington R. J Fam Pract 2000;49:839-48.
3. Adachi JD, Saag KG, Delmas PD, Liberman UA, et al. Arthritis Rheum 2001;44:202-11.
4. Saag KG, Emkey R, Schnitzer TJ, Brown JP, et al. N Engl J Med 1998;339:292-9.
5. Reid DM, Adami S, Devogelaer JP, Chines AA. Calcif Tissue Int 2001;69:242-7.
6. Kung AW, Chan TM, Lau CS, Wong RW, et al. Rheumatology 1999;38:1239-44.
7. Reid IR, Wattie DJ, Evans MC, Stapleton JP. Arch Intern Med 1996;156:1173-7.
8. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001;44:1496-503.
9. Cranney A, Welch V, Adachi JD, Homik J, et al. Cochrane Database Syst Rev. Issue 2, 2002.
10. Sambrook PN. Ann Acad Med Singapore 2002;31:48-53.
1. Homik J, Suarez-Almazor ME, Shea B, Cranny A, et al. Cochrane Database Syst Rev. Issue 2, 2002.
2. Blair MM, Carson DS, Barrington R. J Fam Pract 2000;49:839-48.
3. Adachi JD, Saag KG, Delmas PD, Liberman UA, et al. Arthritis Rheum 2001;44:202-11.
4. Saag KG, Emkey R, Schnitzer TJ, Brown JP, et al. N Engl J Med 1998;339:292-9.
5. Reid DM, Adami S, Devogelaer JP, Chines AA. Calcif Tissue Int 2001;69:242-7.
6. Kung AW, Chan TM, Lau CS, Wong RW, et al. Rheumatology 1999;38:1239-44.
7. Reid IR, Wattie DJ, Evans MC, Stapleton JP. Arch Intern Med 1996;156:1173-7.
8. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001;44:1496-503.
9. Cranney A, Welch V, Adachi JD, Homik J, et al. Cochrane Database Syst Rev. Issue 2, 2002.
10. Sambrook PN. Ann Acad Med Singapore 2002;31:48-53.
Evidence-based answers from the Family Physicians Inquiries Network
Intravenous albuterol effective for acute severe asthma
ABSTRACT
BACKGROUND: Bolus intravenous (IV) albuterol (salbutamol) improved outcomes in pediatric patients with severe asthma exacerbations in 1 earlier small study. Previous studies demonstrated that the addition of nebulized ipratropium bromide to initial emergency department therapy improves pulmonary function, but it is unclear whether combining the therapies results in earlier hospital discharge. This study compared these 2 approaches to determine their relative benefit in children with acute severe asthma.
POPULATION STUDIED: The researchers studied 55 children (aged 1–14 years) presenting with severe acute asthma to the emergency department of a ter-tiary children’s hospital in Sydney, Australia. Children were classified as having severe asthma if they had all 4 features of respiratory distress (wheezing, sternal retraction, accessory muscle use, and dyspnea) or had any of the absolute criteria (cyanosis, pulsus paradoxus, altered consciousness, or a silent chest auscultation). Baseline demographics and clinical characteristics were similar. Children who were excluded included those with life-threatening asthma, age younger than 12 months, presence of heart disease, family history of Wolff-Parkinson-White or past supraventricular tachycardia, other respiratory disease, or pneumonia, and those who had received inhaled ipratropium bromide that day.
STUDY DESIGN AND VALIDITY: This was a randomized, double-blind, double-dummy trial. The enrolling physician, treating physician, and assessor of outcome were all blinded. All children received 1 dose of nebulized albuterol 2.5 or 5 mg, then were assessed for asthma severity. Children meeting inclusion criteria received oxygen as needed, 1 mg/kg IV bolus methylprednisolone, and nebulized albuterol every 20 minutes for the first hour. The frequency of nebulized albuterol was then decreased based on clinical improvement. Patients were then randomized to receive IV albuterol (15 μg/kg); IV saline and inhaled ipratropium bromide (250 mg) every 20 minutes; or IV albuterol (15 μg/kg) and inhaled ipratropium bromide (250 μg) every 20 minutes. Asthma severity was assessed at 1 and 2 hours into the study using the clinical assessment scale and pulmonary index score. All 55 children completed the study.
OUTCOMES MEASURED: The primary outcomes for this study were mean recovery time (time from randomization to when patients no longer needed nebulized albuterol of a given frequency) and mean discharge time from the hospital. Secondary outcomes included clinical signs of moderate to severe asthma 2 hours after randomization and incidence of medication-related side effects.
RESULTS: Children treated with IV albuterol showed a significant benefit over those treated with inhaled ipratropium in recovery at 90, 120, and 180 minutes (P = .007, .01, and .004, respectively). Children in the IV albuterol group were ready for discharge 28.0 hours earlier than those in the ipratropium group (48.3 vs 76.3 hours; P = .005). The combination of IV albuterol and ipratropium showed a significant benefit over ipratropium alone in recovery time at 90 and 120 minutes (P = .02 and .008, respectively). However, no significant difference was evident between the combination and ipratropium alone in time to discharge (57.6 vs 76.3 hours, respectively; P = .2). The combination demonstrated no significant benefit over IV albuterol for any outcome. No significant adverse effects were documented in any of the patients, including tachycardia of more than 200 beats per minute for at least 5 minutes.
In children with severe acute asthma, IV albuterol (15 μg/kg) in addition to nebulized albuterol and IV methylprednisolone, resulted in more rapid improvement of symptoms and decreased length of stay as compared with the use of nebulized ipratropium. However, because IV albuterol is not available in the United States and a Cochrane Database Review1 concluded there is no evidence to support use of IV 2-agonists in patients with severe asthma, larger trials need to be conducted to determine the place in therapy for IV albuterol.
ABSTRACT
BACKGROUND: Bolus intravenous (IV) albuterol (salbutamol) improved outcomes in pediatric patients with severe asthma exacerbations in 1 earlier small study. Previous studies demonstrated that the addition of nebulized ipratropium bromide to initial emergency department therapy improves pulmonary function, but it is unclear whether combining the therapies results in earlier hospital discharge. This study compared these 2 approaches to determine their relative benefit in children with acute severe asthma.
POPULATION STUDIED: The researchers studied 55 children (aged 1–14 years) presenting with severe acute asthma to the emergency department of a ter-tiary children’s hospital in Sydney, Australia. Children were classified as having severe asthma if they had all 4 features of respiratory distress (wheezing, sternal retraction, accessory muscle use, and dyspnea) or had any of the absolute criteria (cyanosis, pulsus paradoxus, altered consciousness, or a silent chest auscultation). Baseline demographics and clinical characteristics were similar. Children who were excluded included those with life-threatening asthma, age younger than 12 months, presence of heart disease, family history of Wolff-Parkinson-White or past supraventricular tachycardia, other respiratory disease, or pneumonia, and those who had received inhaled ipratropium bromide that day.
STUDY DESIGN AND VALIDITY: This was a randomized, double-blind, double-dummy trial. The enrolling physician, treating physician, and assessor of outcome were all blinded. All children received 1 dose of nebulized albuterol 2.5 or 5 mg, then were assessed for asthma severity. Children meeting inclusion criteria received oxygen as needed, 1 mg/kg IV bolus methylprednisolone, and nebulized albuterol every 20 minutes for the first hour. The frequency of nebulized albuterol was then decreased based on clinical improvement. Patients were then randomized to receive IV albuterol (15 μg/kg); IV saline and inhaled ipratropium bromide (250 mg) every 20 minutes; or IV albuterol (15 μg/kg) and inhaled ipratropium bromide (250 μg) every 20 minutes. Asthma severity was assessed at 1 and 2 hours into the study using the clinical assessment scale and pulmonary index score. All 55 children completed the study.
OUTCOMES MEASURED: The primary outcomes for this study were mean recovery time (time from randomization to when patients no longer needed nebulized albuterol of a given frequency) and mean discharge time from the hospital. Secondary outcomes included clinical signs of moderate to severe asthma 2 hours after randomization and incidence of medication-related side effects.
RESULTS: Children treated with IV albuterol showed a significant benefit over those treated with inhaled ipratropium in recovery at 90, 120, and 180 minutes (P = .007, .01, and .004, respectively). Children in the IV albuterol group were ready for discharge 28.0 hours earlier than those in the ipratropium group (48.3 vs 76.3 hours; P = .005). The combination of IV albuterol and ipratropium showed a significant benefit over ipratropium alone in recovery time at 90 and 120 minutes (P = .02 and .008, respectively). However, no significant difference was evident between the combination and ipratropium alone in time to discharge (57.6 vs 76.3 hours, respectively; P = .2). The combination demonstrated no significant benefit over IV albuterol for any outcome. No significant adverse effects were documented in any of the patients, including tachycardia of more than 200 beats per minute for at least 5 minutes.
In children with severe acute asthma, IV albuterol (15 μg/kg) in addition to nebulized albuterol and IV methylprednisolone, resulted in more rapid improvement of symptoms and decreased length of stay as compared with the use of nebulized ipratropium. However, because IV albuterol is not available in the United States and a Cochrane Database Review1 concluded there is no evidence to support use of IV 2-agonists in patients with severe asthma, larger trials need to be conducted to determine the place in therapy for IV albuterol.
ABSTRACT
BACKGROUND: Bolus intravenous (IV) albuterol (salbutamol) improved outcomes in pediatric patients with severe asthma exacerbations in 1 earlier small study. Previous studies demonstrated that the addition of nebulized ipratropium bromide to initial emergency department therapy improves pulmonary function, but it is unclear whether combining the therapies results in earlier hospital discharge. This study compared these 2 approaches to determine their relative benefit in children with acute severe asthma.
POPULATION STUDIED: The researchers studied 55 children (aged 1–14 years) presenting with severe acute asthma to the emergency department of a ter-tiary children’s hospital in Sydney, Australia. Children were classified as having severe asthma if they had all 4 features of respiratory distress (wheezing, sternal retraction, accessory muscle use, and dyspnea) or had any of the absolute criteria (cyanosis, pulsus paradoxus, altered consciousness, or a silent chest auscultation). Baseline demographics and clinical characteristics were similar. Children who were excluded included those with life-threatening asthma, age younger than 12 months, presence of heart disease, family history of Wolff-Parkinson-White or past supraventricular tachycardia, other respiratory disease, or pneumonia, and those who had received inhaled ipratropium bromide that day.
STUDY DESIGN AND VALIDITY: This was a randomized, double-blind, double-dummy trial. The enrolling physician, treating physician, and assessor of outcome were all blinded. All children received 1 dose of nebulized albuterol 2.5 or 5 mg, then were assessed for asthma severity. Children meeting inclusion criteria received oxygen as needed, 1 mg/kg IV bolus methylprednisolone, and nebulized albuterol every 20 minutes for the first hour. The frequency of nebulized albuterol was then decreased based on clinical improvement. Patients were then randomized to receive IV albuterol (15 μg/kg); IV saline and inhaled ipratropium bromide (250 mg) every 20 minutes; or IV albuterol (15 μg/kg) and inhaled ipratropium bromide (250 μg) every 20 minutes. Asthma severity was assessed at 1 and 2 hours into the study using the clinical assessment scale and pulmonary index score. All 55 children completed the study.
OUTCOMES MEASURED: The primary outcomes for this study were mean recovery time (time from randomization to when patients no longer needed nebulized albuterol of a given frequency) and mean discharge time from the hospital. Secondary outcomes included clinical signs of moderate to severe asthma 2 hours after randomization and incidence of medication-related side effects.
RESULTS: Children treated with IV albuterol showed a significant benefit over those treated with inhaled ipratropium in recovery at 90, 120, and 180 minutes (P = .007, .01, and .004, respectively). Children in the IV albuterol group were ready for discharge 28.0 hours earlier than those in the ipratropium group (48.3 vs 76.3 hours; P = .005). The combination of IV albuterol and ipratropium showed a significant benefit over ipratropium alone in recovery time at 90 and 120 minutes (P = .02 and .008, respectively). However, no significant difference was evident between the combination and ipratropium alone in time to discharge (57.6 vs 76.3 hours, respectively; P = .2). The combination demonstrated no significant benefit over IV albuterol for any outcome. No significant adverse effects were documented in any of the patients, including tachycardia of more than 200 beats per minute for at least 5 minutes.
In children with severe acute asthma, IV albuterol (15 μg/kg) in addition to nebulized albuterol and IV methylprednisolone, resulted in more rapid improvement of symptoms and decreased length of stay as compared with the use of nebulized ipratropium. However, because IV albuterol is not available in the United States and a Cochrane Database Review1 concluded there is no evidence to support use of IV 2-agonists in patients with severe asthma, larger trials need to be conducted to determine the place in therapy for IV albuterol.