BACKGROUND: It is well accepted that inhaled steroids help control childhood asthma. Questions remain, however, concerning long-term use of these medicines. This study evaluated the long-term outcomes of inhaled budesonide and nedocromil.

POPULATION STUDIED: A total of 1041 children were enrolled at 8 centers. The mean age was 8.9 years. Minorities represented 30% to 35% of the participants. The children had mild to moderate asthma defined as presence of symptoms, use of an inhaled bronchodilator twice or more times weekly, or daily medication for asthma. At baseline, the patients had been hospitalized 30 times per 100 person-years, averaged 10 episode-free days per month, and had pre-bronchodilator forced expiratory volume in 1 second (FEV1) values of 93% predicted. In general, this population seems similar to that of a typical family practice, although more information would be helpful about family income, education, tobacco exposure, and the type of clinical centers involved.

STUDY DESIGN AND VALIDITY: The participants were randomized to receive 200 mg of inhaled budesonide twice daily (n=311), 8 mg of inhaled nedocromil sodium twice daily (n=312), or placebo (n=418), in a single-blind fashion. Inhaled albuterol, oral prednisone, or inhaled beclomethasone was added as needed. Follow-up visits occurred 2 and 4 months after randomization and then at 4-month intervals.

OUTCOMES MEASURED: The primary outcome was the change in FEV1 after a bronchodilator. Secondary outcomes included health services utilization such as hospitalization, symptom severity, airway responsiveness, physical growth, incidence of cataracts, and psychological development. Cost of treatment, side effects, and patient/parent satisfaction were not directly assessed.

RESULTS: The groups were similar at baseline. Children were followed for a mean of 4.3 years. Neither budesonide nor nedocromil significantly improved lung function more than placebo. Hospitalization rates decreased in all groups, but compared with placebo, patients receiving budesonide had significantly fewer hospitalizations (2.5 vs 4.4/100 person-years, or 1.9 hospitalizations prevented for 20 children treated for 5 years; P=.004), visits for urgent care (12 vs 22/100 person-years, or 10 urgent visits prevented for 20 patients treated for 5 years; P <.001), and courses of prednisone (70 courses vs 122/100 person-years, 52 courses prevented for 20 patients treated over 5 years; P <.001). Compared with the placebo group the nedocromil group had no significant difference in hospitalization rates but did have fewer urgent care visits (16 vs 22/100 person-years, or 5 fewer visits prevented for 20 patients treated over 5years; P <.02) and fewer prednisone courses (102 vs 122/100 patient years, or 20 fewer courses for 20 children treated for 5 years; P <.01) versus placebo. Children taking budesonide but not nedocromil recorded significantly fewer symptoms, less frequent use of albuterol, and more episode-free days than those receiving just placebo. Increase in height was significantly less for the budesonide group (22.7 cm vs 23.8 cm, P=.005), although there was no significant difference in overall growth velocity, Tanner stage, or projected final height among the 3 groups at the end of the treatment period.

BACKGROUND: It is well accepted that inhaled steroids help control childhood asthma. Questions remain, however, concerning long-term use of these medicines. This study evaluated the long-term outcomes of inhaled budesonide and nedocromil.

POPULATION STUDIED: A total of 1041 children were enrolled at 8 centers. The mean age was 8.9 years. Minorities represented 30% to 35% of the participants. The children had mild to moderate asthma defined as presence of symptoms, use of an inhaled bronchodilator twice or more times weekly, or daily medication for asthma. At baseline, the patients had been hospitalized 30 times per 100 person-years, averaged 10 episode-free days per month, and had pre-bronchodilator forced expiratory volume in 1 second (FEV1) values of 93% predicted. In general, this population seems similar to that of a typical family practice, although more information would be helpful about family income, education, tobacco exposure, and the type of clinical centers involved.

STUDY DESIGN AND VALIDITY: The participants were randomized to receive 200 mg of inhaled budesonide twice daily (n=311), 8 mg of inhaled nedocromil sodium twice daily (n=312), or placebo (n=418), in a single-blind fashion. Inhaled albuterol, oral prednisone, or inhaled beclomethasone was added as needed. Follow-up visits occurred 2 and 4 months after randomization and then at 4-month intervals.

OUTCOMES MEASURED: The primary outcome was the change in FEV1 after a bronchodilator. Secondary outcomes included health services utilization such as hospitalization, symptom severity, airway responsiveness, physical growth, incidence of cataracts, and psychological development. Cost of treatment, side effects, and patient/parent satisfaction were not directly assessed.

RESULTS: The groups were similar at baseline. Children were followed for a mean of 4.3 years. Neither budesonide nor nedocromil significantly improved lung function more than placebo. Hospitalization rates decreased in all groups, but compared with placebo, patients receiving budesonide had significantly fewer hospitalizations (2.5 vs 4.4/100 person-years, or 1.9 hospitalizations prevented for 20 children treated for 5 years; P=.004), visits for urgent care (12 vs 22/100 person-years, or 10 urgent visits prevented for 20 patients treated for 5 years; P <.001), and courses of prednisone (70 courses vs 122/100 person-years, 52 courses prevented for 20 patients treated over 5 years; P <.001). Compared with the placebo group the nedocromil group had no significant difference in hospitalization rates but did have fewer urgent care visits (16 vs 22/100 person-years, or 5 fewer visits prevented for 20 patients treated over 5years; P <.02) and fewer prednisone courses (102 vs 122/100 patient years, or 20 fewer courses for 20 children treated for 5 years; P <.01) versus placebo. Children taking budesonide but not nedocromil recorded significantly fewer symptoms, less frequent use of albuterol, and more episode-free days than those receiving just placebo. Increase in height was significantly less for the budesonide group (22.7 cm vs 23.8 cm, P=.005), although there was no significant difference in overall growth velocity, Tanner stage, or projected final height among the 3 groups at the end of the treatment period.

BACKGROUND: It is well accepted that inhaled steroids help control childhood asthma. Questions remain, however, concerning long-term use of these medicines. This study evaluated the long-term outcomes of inhaled budesonide and nedocromil.

POPULATION STUDIED: A total of 1041 children were enrolled at 8 centers. The mean age was 8.9 years. Minorities represented 30% to 35% of the participants. The children had mild to moderate asthma defined as presence of symptoms, use of an inhaled bronchodilator twice or more times weekly, or daily medication for asthma. At baseline, the patients had been hospitalized 30 times per 100 person-years, averaged 10 episode-free days per month, and had pre-bronchodilator forced expiratory volume in 1 second (FEV1) values of 93% predicted. In general, this population seems similar to that of a typical family practice, although more information would be helpful about family income, education, tobacco exposure, and the type of clinical centers involved.

STUDY DESIGN AND VALIDITY: The participants were randomized to receive 200 mg of inhaled budesonide twice daily (n=311), 8 mg of inhaled nedocromil sodium twice daily (n=312), or placebo (n=418), in a single-blind fashion. Inhaled albuterol, oral prednisone, or inhaled beclomethasone was added as needed. Follow-up visits occurred 2 and 4 months after randomization and then at 4-month intervals.

OUTCOMES MEASURED: The primary outcome was the change in FEV1 after a bronchodilator. Secondary outcomes included health services utilization such as hospitalization, symptom severity, airway responsiveness, physical growth, incidence of cataracts, and psychological development. Cost of treatment, side effects, and patient/parent satisfaction were not directly assessed.

RESULTS: The groups were similar at baseline. Children were followed for a mean of 4.3 years. Neither budesonide nor nedocromil significantly improved lung function more than placebo. Hospitalization rates decreased in all groups, but compared with placebo, patients receiving budesonide had significantly fewer hospitalizations (2.5 vs 4.4/100 person-years, or 1.9 hospitalizations prevented for 20 children treated for 5 years; P=.004), visits for urgent care (12 vs 22/100 person-years, or 10 urgent visits prevented for 20 patients treated for 5 years; P <.001), and courses of prednisone (70 courses vs 122/100 person-years, 52 courses prevented for 20 patients treated over 5 years; P <.001). Compared with the placebo group the nedocromil group had no significant difference in hospitalization rates but did have fewer urgent care visits (16 vs 22/100 person-years, or 5 fewer visits prevented for 20 patients treated over 5years; P <.02) and fewer prednisone courses (102 vs 122/100 patient years, or 20 fewer courses for 20 children treated for 5 years; P <.01) versus placebo. Children taking budesonide but not nedocromil recorded significantly fewer symptoms, less frequent use of albuterol, and more episode-free days than those receiving just placebo. Increase in height was significantly less for the budesonide group (22.7 cm vs 23.8 cm, P=.005), although there was no significant difference in overall growth velocity, Tanner stage, or projected final height among the 3 groups at the end of the treatment period.

BACKGROUND: Although osteoporosis is more common in women, approximately one fourth of all hip fractures occur in men. There are no approved therapies in the United States for men with osteoporosis. The drug alendronate, a potent bisphosphonate, has been shown to increase bone mineral density and reduce the incidence of major osteoporotic fractures in women.

POPULATION STUDIED: The men were recruited at osteoporosis clinics and at community assessments of bone mineral density across 20 centers in the United States and 10 other countries. Men could qualify for the study in 2 ways: (1) bone mineral density (BMD) at the femoral neck that was 2 standard deviations (SDs) below the mean value of normal young men and BMD at the lumbar spine 1 SD below the mean in normal young men, or (2) BMD at the femoral neck 1 SD below the mean in normal young men and at least one vertebral deformity or a history of osteoporotic fracture. All men with secondary causes of osteoporosis other than low serum-free testosterone concentrations were excluded. A total of 241 men with a mean age of 63 years (range=31-87 years) were enrolled in the study.

STUDY DESIGN AND VALIDITY: In this 2-year double-blind trial the men were randomized to either alendronate 10 mg or matching placebo. Subjects who were androgen deficient or androgen replete were stratified to ensure equal distribution between the 2 treatment groups. Calcium and vitamin D supplements were provided to all of the men. BMD, height, and fractures were measured at the follow-up visits. The 2 groups were similar in age, race, testosterone levels, smoking history, consumption of alcohol, body mass index, baseline BMD scores, and vertebral fractures. Most of the men were white, which may limit generalization of these results to other racial groups. The authors did not report the method of randomization or how allocation to treatment or control groups was concealed from the patients and their physicians. Radiologists were blinded to the treatment assignment, and analysis was appropriately by intention to treat.

OUTCOMES MEASURED: The main patient-oriented outcome was the incidence of vertebral fractures between the placebo and the alendronate groups. Disease-oriented outcomes included changes in BMD (lumbar spine, femoral neck, and total body) and vertebral height.

RESULTS: The incidence of vertebral fractures was 7.1% in the placebo group and 0.8% in the alendronate group (P=.02). There were 4 painful vertebral fractures in the placebo group and 1 in the alendronate group (P=.3), but the study was too small and too short to prove this outcome. Men in the placebo group lost 2.4 mm in stature compared with a nonsignificant change of 0.6 mm in the alendronate group (P=.02). In the alendronate group, BMD increased by a mean of 7.1%±0.3% at the lumbar spine, 2.5%±0.4% at the femoral neck, and 2.0%± 0.2% for the total body (P <.001). For the placebo group, the BMD increased by a mean of 1.8%±0.5% at the lumbar spine (P <.001). No significant changes in BMD at the femoral neck or total body were found for the placebo group. At each site the alendronate group had a significantly greater increase in BMD than the placebo group. These effects were independent of baseline serum-free testosterone concentrations.

BACKGROUND: Although osteoporosis is more common in women, approximately one fourth of all hip fractures occur in men. There are no approved therapies in the United States for men with osteoporosis. The drug alendronate, a potent bisphosphonate, has been shown to increase bone mineral density and reduce the incidence of major osteoporotic fractures in women.

POPULATION STUDIED: The men were recruited at osteoporosis clinics and at community assessments of bone mineral density across 20 centers in the United States and 10 other countries. Men could qualify for the study in 2 ways: (1) bone mineral density (BMD) at the femoral neck that was 2 standard deviations (SDs) below the mean value of normal young men and BMD at the lumbar spine 1 SD below the mean in normal young men, or (2) BMD at the femoral neck 1 SD below the mean in normal young men and at least one vertebral deformity or a history of osteoporotic fracture. All men with secondary causes of osteoporosis other than low serum-free testosterone concentrations were excluded. A total of 241 men with a mean age of 63 years (range=31-87 years) were enrolled in the study.

STUDY DESIGN AND VALIDITY: In this 2-year double-blind trial the men were randomized to either alendronate 10 mg or matching placebo. Subjects who were androgen deficient or androgen replete were stratified to ensure equal distribution between the 2 treatment groups. Calcium and vitamin D supplements were provided to all of the men. BMD, height, and fractures were measured at the follow-up visits. The 2 groups were similar in age, race, testosterone levels, smoking history, consumption of alcohol, body mass index, baseline BMD scores, and vertebral fractures. Most of the men were white, which may limit generalization of these results to other racial groups. The authors did not report the method of randomization or how allocation to treatment or control groups was concealed from the patients and their physicians. Radiologists were blinded to the treatment assignment, and analysis was appropriately by intention to treat.

OUTCOMES MEASURED: The main patient-oriented outcome was the incidence of vertebral fractures between the placebo and the alendronate groups. Disease-oriented outcomes included changes in BMD (lumbar spine, femoral neck, and total body) and vertebral height.

RESULTS: The incidence of vertebral fractures was 7.1% in the placebo group and 0.8% in the alendronate group (P=.02). There were 4 painful vertebral fractures in the placebo group and 1 in the alendronate group (P=.3), but the study was too small and too short to prove this outcome. Men in the placebo group lost 2.4 mm in stature compared with a nonsignificant change of 0.6 mm in the alendronate group (P=.02). In the alendronate group, BMD increased by a mean of 7.1%±0.3% at the lumbar spine, 2.5%±0.4% at the femoral neck, and 2.0%± 0.2% for the total body (P <.001). For the placebo group, the BMD increased by a mean of 1.8%±0.5% at the lumbar spine (P <.001). No significant changes in BMD at the femoral neck or total body were found for the placebo group. At each site the alendronate group had a significantly greater increase in BMD than the placebo group. These effects were independent of baseline serum-free testosterone concentrations.

BACKGROUND: Although osteoporosis is more common in women, approximately one fourth of all hip fractures occur in men. There are no approved therapies in the United States for men with osteoporosis. The drug alendronate, a potent bisphosphonate, has been shown to increase bone mineral density and reduce the incidence of major osteoporotic fractures in women.

POPULATION STUDIED: The men were recruited at osteoporosis clinics and at community assessments of bone mineral density across 20 centers in the United States and 10 other countries. Men could qualify for the study in 2 ways: (1) bone mineral density (BMD) at the femoral neck that was 2 standard deviations (SDs) below the mean value of normal young men and BMD at the lumbar spine 1 SD below the mean in normal young men, or (2) BMD at the femoral neck 1 SD below the mean in normal young men and at least one vertebral deformity or a history of osteoporotic fracture. All men with secondary causes of osteoporosis other than low serum-free testosterone concentrations were excluded. A total of 241 men with a mean age of 63 years (range=31-87 years) were enrolled in the study.

STUDY DESIGN AND VALIDITY: In this 2-year double-blind trial the men were randomized to either alendronate 10 mg or matching placebo. Subjects who were androgen deficient or androgen replete were stratified to ensure equal distribution between the 2 treatment groups. Calcium and vitamin D supplements were provided to all of the men. BMD, height, and fractures were measured at the follow-up visits. The 2 groups were similar in age, race, testosterone levels, smoking history, consumption of alcohol, body mass index, baseline BMD scores, and vertebral fractures. Most of the men were white, which may limit generalization of these results to other racial groups. The authors did not report the method of randomization or how allocation to treatment or control groups was concealed from the patients and their physicians. Radiologists were blinded to the treatment assignment, and analysis was appropriately by intention to treat.

OUTCOMES MEASURED: The main patient-oriented outcome was the incidence of vertebral fractures between the placebo and the alendronate groups. Disease-oriented outcomes included changes in BMD (lumbar spine, femoral neck, and total body) and vertebral height.

RESULTS: The incidence of vertebral fractures was 7.1% in the placebo group and 0.8% in the alendronate group (P=.02). There were 4 painful vertebral fractures in the placebo group and 1 in the alendronate group (P=.3), but the study was too small and too short to prove this outcome. Men in the placebo group lost 2.4 mm in stature compared with a nonsignificant change of 0.6 mm in the alendronate group (P=.02). In the alendronate group, BMD increased by a mean of 7.1%±0.3% at the lumbar spine, 2.5%±0.4% at the femoral neck, and 2.0%± 0.2% for the total body (P <.001). For the placebo group, the BMD increased by a mean of 1.8%±0.5% at the lumbar spine (P <.001). No significant changes in BMD at the femoral neck or total body were found for the placebo group. At each site the alendronate group had a significantly greater increase in BMD than the placebo group. These effects were independent of baseline serum-free testosterone concentrations.