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ARTICLE |
a Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
b Johns Hopkins Center for Clinical Trials, Baltimore, Maryland
c National Jewish Medical and Research Center, Denver, Colorado
d Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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METHODS. This was a cohort follow-up study for a median of 7 years of children who had mild-to-moderate asthma and initially were randomly assigned into the Childhood Asthma Management Program trial. Serial dual-energy radiograph absorptiometry scans of the lumbar spine for bone mineral density were performed for all patients. Annual bone mineral accretion was calculated for 531 boys and 346 girls who had asthma and were aged 5 to 12 years at baseline (84% of the initial cohort).
RESULTS. Oral corticosteroid bursts produced a dosage-dependent reduction in bone mineral accretion (0.052, 0.049, and 0.046 g/cm2 per year) and an increase in risk for osteopenia (10%, 14%, and 21%) for 0, 1 to 4, and 
5 courses, respectively, in boys but not girls. Cumulative inhaled corticosteroid use was associated with a small decrease in bone mineral accretion in boys but not girls but no increased risk for osteopenia.
CONCLUSIONS. Multiple oral corticosteroid bursts over a period of years can produce a dosage-dependent reduction in bone mineral accretion and increased risk for osteopenia in children with asthma. Inhaled corticosteroid use has the potential for reducing bone mineral accretion in male children progressing through puberty, but this risk is likely to be outweighed by the ability to reduce the amount of oral corticosteroids used in these children.
Key Words: cohort study • bone mineral density • corticosteroids • asthma • children • osteopenia
Abbreviations: OCS—oral corticosteroid • BMD—bone mineral density • ICS—inhaled corticosteroid • CAMP—Childhood Asthma Management Program • DEXA—dual-energy radiograph absorptiometry
Oral corticosteroids (ocss) can reduce bone mineral density (BMD) and produce osteoporosis in adults.1 Both current daily dosage and cumulative dosage have been shown to correlate with bone loss and increased fracture risk.2,3 Frequent short courses (bursts) of OCSs (>2.5 courses per year) have been associated with decreased BMD in adults with asthma4; however, cross-sectional studies of children on the effect of OCSs on BMD or fracture risk have been inconsistent.5–8 No prospective studies of the effect of multiple bursts of OCSs on bone mineral accretion in children have been published.
Studies of adults and children on the effects of inhaled corticosteroids (ICSs) on BMD and fracture risk are also conflicting.6,9–20 The prospective trials that evaluated the effect of ICSs on BMD in children with asthma have been limited by small sample sizes and short durations.21–26
Childhood Asthma Management Program (CAMP) was a long-term, randomized, placebo-controlled, prospective clinical trial that compared budesonide 200 µg twice a day or nedocromil 4 mg twice a day with placebo in 1041 children with mild-to-moderate asthma for 4 to 6 years, followed by a 4-year posttrial follow-up study.27 Lumbar spine BMD was assessed serially by dual-energy radiograph absorptiometry (DEXA) scans to determine the safety of chronic corticosteroid use. Lumbar spine was selected because corticosteroids preferentially affect trabecular bone.1,2
We previously reported no effect of asthma severity or previous corticosteroid use on BMD in this cohort at the time of randomization into the CAMP trial.28 We also found no difference in final BMDs between treatments at the end of the CAMP treatment phase27; however, this was an intention-to-treat analysis that would not have identified outliers with low rates of bone accretion. In addition, the protocol allowed use of prednisone "bursts" for exacerbation, the introduction of open-label treatment with beclomethasone or other ICSs as indicated for worsening symptoms over time, and weaning of study medication for well-controlled status. Open-label ICS and prednisone use were seen disproportionately in the nonbudesonide groups. Last, most of the patients may not have been at an age of maturity that was sensitive to possible intervention effects on bone mineral accretion. After the CAMP trial, the study drugs were discontinued and treatment was directed by primary care physicians with advice from CAMP physicians. Participants were followed for an additional 4.5 years in a posttrial follow-up study. The purpose of this analysis was to assess further the potential effects of both bursts of OCSs and long-term use of ICSs on bone mineral accretion in the CAMP cohort followed prospectively.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Corticosteroid Dosages
During the CAMP trial phase, patients received prednisone bursts per protocol with a standard regimen of 2 mg/kg per day up to 60 mg of prednisone for 2 days followed by 1 mg/kg per day up to 30 mg for 2 days, with an option to continue dosing if there was insufficient improvement in peak flows. Duration and dosage during the trial phase were recorded on daily diaries as well as reports of bursts by interview (date started, duration, and daily dosage) at 3 per year of follow-up visits (in-person) and during interim telephone contacts. During the follow-up study, patients received OCS bursts of variable duration and dosage as determined by their asthma care providers, with the number of bursts since the last contact obtained by interview at semiannual follow-up visits and interim telephone contacts. Bursts during the follow-up study were assumed to conform to the CAMP trial regimen and were assumed to be equally spaced through the interval since the last contact. For analysis purposes, the total dosage (mg) received during the 2 phases was divided by 180 to reexpress the total dosage received by each patient as the number of equivalent 4-day bursts (60/60/30/30 mg/day over 4 days) for a patient who weighed at least 30 kg. Cumulative number of bursts was divided into 3 categories (0, 1–4, and 5). The 5 category represented a median of 8.9 (quartiles: 6.5, 12.3) bursts during the study period.
The ICSs included the blinded budesonide and unblinded ICSs during the CAMP treatment phase and then any ICS that the patients' primary care physicians prescribed during the follow-up study. Dosage form, dosage, and frequency were recorded at each visit, and total dosage for the duration was calculated. The ICS dosage was divided into 3 categories (0, 1–437, and 438 mg). The cut point of 438 mg was somewhat arbitrary and represents 3 years of full dosage (400 µg/day) of budesonide. The median cumulative dosage in the 1- to 437-mg category was 153 mg, whereas patients in the 438 category had a median dosage of 690 mg. Thus, the 438 category represents patients who received almost continuous ICSs through the trial and follow-up study phases, whereas the 1- to 437-mg category represents a periodic or intermittent use.
BMD and Fracture Measurements
The BMD measurements were made at baseline, yearly during the treatment phase, and then twice during the follow-up study, at 7 and 9 years after randomization. Lumbar spine (L1–L4) BMD was measured by DEXA using either the Hologic (Waltham, MA) QDR-1500 (6 centers) or the Lunar (Madison, WI) DPX at 2 centers initially; however, the DEXA machines were not purchased by the study, so upgrades and changes were made at a number of the clinical centers (ie, changing from Lunar to Hologic and vice versa, and changing within Hologic from pencil beam to fan beam). Density measures on an anthropomorphic spine Phantom (Hologic model DPA/QDR-1, S/N: 1550) were obtained annually at each clinical center; these density measures were used to derive equations for converting density measurements to a Hologic fan-beam equivalent. Lunar measures were converted to Hologic by the following: Hologic BMD = 0.885 x Lunar BMD.33 As patients became larger, the pencil-beam and fan-beam values deviate, requiring additional correction.33 This occurred at the height of 1.40 m in our patients (Fig 1), so all values were standardized to Hologic fan beam by the following: fan-beam BMD = pencil-beam BMD + 0.0549 if height 1.40 m. The final corrected BMD measures are reported as total BMD (g/cm2). The BMD z scores were calculated using CAMP internal references, mean, and SD of patients in the lowest to medium category for cumulative oral and inhaled corticosteroid dosages (n = 398 [45% of the population]). Because children with asthma might not be considered as references, we also analyzed our patients on the basis of references provided by both Boot et al34 and vanderSluis et al.35 Fractures were prospectively collected on the data history forms.
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2 analysis. Assessment of risk factors for causing fracture used the Cox model with time to first fracture as the outcome. P values are nominal and 2-sided. All analyses were performed by using SAS/STAT 8 software (SAS Institute, Inc, Cary, NC). |
RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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5 bursts resulted in a decreased bone mineral accretion in boys (P = .0009) but not in girls (P = .29; Table 2). Test for trend indicated that the effect in boys was dosage dependent (P = .0002). Boys who received ICSs had a significantly decreased bone mineral accretion that did not seem to be dosage dependent. There was no effect of ICSs on bone mineral accretion in girls. No significant interaction between OCS and ICS on bone mineral accretion was found (P = .97 for girls and P = .23 for boys).
Using the World Health Organization's definition of osteopenia (BMD between 1 and 2.5 SDs below age- and gender-adjusted means), 80 (15%) boys and 77 (22%) girls were classified as having osteopenia at their last BMD determination.37 Only 4 patients (2 boys and 2 girls) were classified as having osteoporosis (z score less than –2.5) and so were included with the children with osteopenia for analysis. Similar to the effects on bone mineral accretion, only cumulative dosage of OCSs in boys demonstrated a dosage-dependent risk for developing osteopenia (10.2%, 13.8%, and 20.6%) for 0, 1 to 4, and 5 courses, respectively (P = .02 for trend; Table 4). 2 analysis showed that a significantly greater proportion of children who were classified with osteopenia were in the lowest quartile of bone mineral accretion (72% for boys, P < .0001; 58% for girls, P < .0001). Using the other published reference values,34,35 the percentage of patients who were classified as having osteopenia varied at most by 4%, and the OCS dosage-dependent increase in percentage of male patients who were classified as having osteopenia was not significantly changed (Table 4).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Our findings are consistent with a recent 4-year longitudinal study of adults with asthma that reported a significantly greater BMD loss in patients who received >2.5 courses per year compared with 
2.5 courses per year.4 Our study suggests that a lower number of courses of OCSs (median: 8.9 over median of 7 years) can produce diminished bone mineralization in children. In contrast, Ducharme et al8 reported no difference in mean lumbar spine BMD z score for 48 children who had asthma and were exposed to a median of 4 OCS bursts (range: 3–11) in the preceding year versus 35 unexposed children with asthma; however, both groups had lower than normal mean z scores (–0.61 ± 1.0 [exposed] vs –0.67 ± 0.9 [unexposed]). Harris et al6 reported a significant reduction in lumbar spine BMD z score for patients who were 4 to 12 years of age and received both high-dosage ICSs and at least 1 OCS burst in the previous 6 months compared with patients who received medium-dosage ICSs. Patients who received only high-dosage ICSs did not have decreased z scores. We did not find an interaction between OCSs and ICSs on bone mineral accretion.
Most cross-sectional6–7,18–20 and even prospective longitudinal21,23,26,27 studies of children with asthma reported no negative effect of ICSs on BMD. Allen et al25 compared 48 prepubertal children who received budesonide dry-powder inhaler or beclomethasone dipropionate metered-dose inhaler (400–2000 µg/day) with 9 aged-matched control subjects who had asthma and did not receive ICSs over 9 to 20 months; however, patients were excluded only when the number of OCS bursts exceeded 3 during the study period. Roux et al26 assessed lumbar spine and femoral neck BMD in 174 children aged 6 to 14 years receiving fluticasone propionate 200 µg/day by dry-powder inhaler or nedocromil sodium by metered-dose inhaler. Their patients were also allowed OCSs for asthma exacerbations, and significantly more patients in the nedocromil group required OCSs (43% vs 26% [P < .001] and 16% vs 3% for 3 courses). Although they reported neither a difference in bone mineral accretion between treatments nor a significant effect of OCSs on treatment effect, they did report a slightly greater percentage increase (1.2%) in BMD in the fluticasone propionate group.
The relevant concern for inadequate bone mineral accretion relates to potential for fracture risk and suboptimal attainment of peak bone mass. We found no increase in risk for fracture from either OCSs or ICSs but likely had an insufficient number of fractures in our population to determine risk for this outcome. A large, nested, case-control study of 22 846 children who were 4 to 17 years of age and had fractures reported a significant increase in the risk for fractures in children who were taking 4 OCS bursts over a mean follow-up of 2.7 years (median: 2.3 years)5; however, they were unable to discern adequately whether the increased risk was attributable to the OCSs or severity of underlying disease. Our data demonstrating an increased risk for osteopenia in children who received 5 bursts over 7 years suggest a role for OCSs as a contributing cause. An epidemiologic study of 97 387 children who were 4 to 17 years of age and receiving ICSs reported an increased crude risk for fracture in those who were receiving >200 µg/day beclomethasone equivalent, but when adjusted for measures of asthma severity, the increased risk disappeared.16 A nested case-control analysis also failed to demonstrate a significant increase in fracture risk from current ICS use or long-term exposure (20 prescriptions).38 Thus, the literature concerning risks for potential adverse effects of ICS on bone mineralization is reassuringly negative.
Why we saw the decreased accretion in boys only is unclear. There were fewer girls than boys and a slightly higher percentage of girls who were above Tanner stage 2 on enrollment (Table 1). More girls may have reached the flat portion of their bone mineral accretion curves and therefore were less susceptible to an intervention.39–42 Estrogen surge during pubertal development in girls may overcome the small effect associated with the relatively low-dosage corticosteroids seen in the CAMP cohort because exogenous estrogen replacement therapy has been shown to be protective against corticosteroid-induced bone loss.43,44
A weakness of our study is that during the 4.5-year follow-up study, therapy was controlled by the primary care physician and data were gathered over 4 visits per year (2 in-clinic visits and 2 telephone visits). Conversely, this could be considered a strength of the study in that it is likely to reflect better the use of both OCSs and ICSs in the general population of children who have mild-to-moderate asthma and are cared for by community physicians. Although we did not control for asthma severity, this cohort had mild-to-moderate asthma on entry into the study and initial measures of asthma severity were not associated with baseline height or BMD.28 The lack of accepted normal values for BMD in children to establish z scores for defining osteopenia and osteoporosis is problematic, but that the number of patients whom we defined as having osteopenia was not significantly altered by using 2 published external populations validates our use of internal references.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Clinical Centers of the CAMP Research Group
ASTHMA, Inc, Seattle, WA: Gail G. Shapiro, MD (director); Thomas R. DuHamel, PhD (co-director); Mary V. Lasley, MD (co-director); Tamara Chinn, MSN, ARNP (coordinator); Michele Hinatsu, MSN, ARNP; Clifton T. Furukawa, MD; Leonard C. Altman, MD; Frank S. Virant, MD; Paul V. Williams, MD; Michael S. Kennedy, MD; Jonathan W. Becker, MD; Grace White; C. Warren Bierman, MD (1992–1997); Dan Crawford, RN (1996–2002); Heather Eliassen, BA (1996–1999); Babi Hammond (1996–1999); Dominick A. Minotti, MD (1992–2003); Chris Reagan (1992–2003); Marian Sharpe, RN (1992–1994); and Timothy G. Wighton, PhD (1994–1998).
Brigham & Women's Hospital, Boston, MA: Scott Weiss, MD, (director); Anne Fuhlbrigge, MD (principal investigator); Anne Plunkett, NP, MS (coordinator); Nancy Madden, RN, BSN; Peter Barrant, MD; Christine Darcy; Kelly Thompson, MD; Walter Torda, MD (co-investigator director, 1993–2003); Martha Tata, RN (1993–2002); Sally Babigian, RN (1997–1999); Linda Benson (1998–2004); Jose Caicedo (1998–1999); Tatum Calder (1998–2001); Anthony DeFilippo (1994–2000); Cindy Dorsainvil (1998–2001); Julie Erickson (1998–1999); Phoebe Fulton (1997); Mary Grace, RN (1994–1996); Jennifer Gilbert (1997–1998); Dirk Greineder, MD (1993–2000); Stephanie Haynes (1993–1998); Margaret Higham, MD (1996–1998); Deborah Jakubowski (1999); Susan Kelleher (1993–1997); Jay Koslof, PhD (1993–1995); Dana Mandel (1996–1998); Patricia Martin (2001–2003); Agnes Martinez (1994–1997); Jean McAuliffe (1994–1995); Erika Nakamoto (2002–2004); Paola Pacella (1993–1998); Paula Parks (1993–1995); Johanna Sagarin (1998–1999); Kay Seligsohn, PhD (1995–2004); Susan Swords (2003–2005); Meghan Syring (1998–2001); June Traylor, MSN, RN (1996–1998); Melissa VanHorn, PhD (1996–1999); Carolyn Wells, RN (1993–1995); and Ann Whitman, RN (1994–1996).
Hospital for Sick Children, Toronto, Ontario, Canada: Ian MacLusky, MD, (director); Joe Reisman, MD, MBA (director, 1996–1999); Henry Levison, MD, (director, 1992–1996); Anita Hall, RN (coordinator); Jennifer Chay; Melody Miki, RN, BScN; Renée Sananes, PhD; Yola Benedet (1994–1999); Susan Carpenter, RN (1998–2001); Michelle Collinson, RN (1994–1998); Jane Finlayson-Kulchin, RN (1994–1998); Kenneth Gore, MA (1993–1999); Noreen Holmes, RRT (1998–1999); Sharon Klassen, MA (1999–2000); Joseé Quenneville, MSc (1993–1995); and Christine Wasson, PhD (1999).
Johns Hopkins Asthma and Allergy Center, Baltimore, MD: N. Franklin Adkinson, Jr, MD (director); Peyton Eggleston, MD (co-director); Elizabeth H. Aylward, PhD; Karen Huss, DNSc (co-investigator); Leslie Plotnick, MD (co-investigator); Margaret Pulsifer, PhD (co-investigator); Cynthia Rand, PhD (co-investigator); Nancy Bollers, RN (coordinator); Deborah Bull, LPN; Robert Hamilton, PhD; Kimberly Hyatt; Susan Limb, MD; Mildred Pessaro; Stephanie Philips, RN; and Barbara Wheeler, RN, BSN.
National Jewish Medical and Research Center, Denver, CO: Stanley Szefler, MD (director); Harold S. Nelson, MD (co-director); Bruce Bender, PhD (co-investigator); Ronina Covar, MD (co-investigator); Andrew Liu, MD (co-investigator); Joseph Spahn, MD (co-investigator); D Sundström (coordinator); Melanie Phillips; Michael P. White; Kristin Brelsford (1997–1999); Jessyca Bridges (1995–1997); Jody Ciacco (1993–1996); Michael Eltz (1994–1995); Jeryl Feeley, MA (coordinator, 1992–1995); Michael Flynn (1995–1996); Melanie Gleason, PA-C (1992–1999); Tara Junk-Blanchard (1997–2000); Joseph Hassell (1992–1998); Marcia Hefner (1992–1994); Caroline Hendrickson, RN (1995–1998; coordinator, 1995–1997); Daniel Hettleman, MA (1995–1996); Charles G. Irvin, PhD (1992–1998); Jeffrey Jacobs, MD (1996–1997); Alan Kamada, PharmD (1994–1997); Sai Nimmagadda, MD (1993–1996); Kendra Sandoval (1995–1997); Jessica Sheridan (1994–1995); Trella Washington (1993–1997); and Eric Willcutt, MA (1996–1997). We also thank the pediatric allergy and immunology fellows for participation (Kirstin Carel, MD; Neal Jain, MD; Harvey Leo, MD; Beth Macomber, MD; Chris Mjaanes, MD; Lora Stewart, MD; and Ben Song, MD).
University of California, San Diego and Kaiser Permanente Southern California Region, San Diego, CA: Robert S. Zeiger, MD, PhD (director); Noah Friedman, MD (co-investigator); Michael H. Mellon, MD (co-investigator); Michael Schatz, MD (co-investigator); Kathleen Harden, RN (coordinator); Elaine M. Jenson; Serena Panzlau; Eva Rodriguez, RRT; James G. Easton, MD (co-director, 1993–1994); M. Feinberg (1997–1998); Linda L. Galbreath (1991–2002); Jennifer Gulczynski (1998–1999); Ellen Hansen (1995–1997); Al Jalowayski, PhD (co-investigator, 1991–2005); Alan Lincoln, PhD (co-investigator, 1991–2003); Jennie Kaufman (1994); Shirley King, MSW (1992–1999); Brian Lopez (1997–1998); Michaela Magiari-Ene, MA (1994–1998); Kathleen Mostafa, RN (1994–1995); Avraham Moscona (1994–1996); Catherine A. Nelle, RN (1991–2005); Jennifer Powers (2001–2003); Karen Sandoval (1995–1996); and Nevin W. Wilson, MD (co-director, 1991–1993).
University of New Mexico, Albuquerque, NM: H. William Kelly, PharmD (director); Aaron Jacobs (co-investigator); Mary Spicher, RN (coordinator); Hengameh H. Raissy; Robert Annett, PhD (co-investigator, 1993–2004); Teresa Archibeque (1994–1999); Naim Bashir, MD (co-investigator, 1998–2005); H. Selda Bereket (1995–1998); Marisa Braun (1996–1999); Shannon Bush (2002–2006); Michael Clayton, MD (co-investigator, 1999–2001); Angel Colon-Semidey, MD (co-investigator, 1997–2000); Sara Devault (1993–1997); Roni Grad, MD (co-investigator, 1993–1995); David Hunt, RRT (1995–2004); Jeanne Larsson, RN (1995–1996); Sandra McClelland, RN (coordinator, 1993–1995); Bennie McWilliams, MD (co-investigator, director, 1992–1998); Elisha Montoya (1997–2000); Margaret Moreshead (1996–1999); Shirley Murphy, MD (co-investigator, 1992–1994); Barbara Ortega, RRT (1993–1999); David Weers (1997–1998); and Jose Zayas (1995–1996).
Washington University, St Louis, MO: Robert C. Strunk, MD (director); Leonard Bacharier, MD (co-investigator); Gordon R. Bloomberg, MD (co-investigator); James M. Corry, MD (co-investigator); Denise Rodgers, RFPT (coordinator); Lila Kertz, MSN, RN, CPNP; Valerie Morgan, RRT; Tina Oliver-Welker, CRTT; and Deborah K. White, RPFT, RRT.
Resource Centers of the CAMP Research Group
Chair's Office, National Jewish Medical and Research Center, Denver, CO: Reuben Cherniack, MD (study chair).
Coordinating Center, Johns Hopkins University, Baltimore, MD: James Tonascia, PhD (director); Curtis Meinert, PhD (co-director); Patricia Belt; Karen Collins; Betty Collison; Ryan Colvin, MPH; John Dodge; Michele Donithan, MHS; Judith Harle; Rosetta Jackson; Hope Livingston; Jill Meinert; Kapreena Owens; Michael Smith; Alice Sternberg, ScM; Mark VanNatta, MHS; Margaret Wild; Laura Wilson, ScM; Robert Wise, MD; and Katherine Yates, ScM.
Project office, National Heart, Lung, and Blood Institute, Bethesda, MD: Virginia Taggart, MPH (project officer); Lois Eggers; James Kiley, PhD; Gang Zheng, PhDl Paul Albert, PhD (1991–1999); Suzanne Hurd, PhD (1991–1999); Sydney Parker, PhD (1991–1994); Pamela Randall (1992–2003); and Margaret Wu, PhD (1991–2001).
Committees of the CAMP Research Group
Data and Safety Monitoring Board: Howard Eigen, MD (chair); Michelle Cloutier, MD; John Connett, PhD; Leona Cuttler, MD; David Evans, PhD; Meyer Kattan, MD; Rogelio Menendez, MD; F. Estelle R. Simons, MD; Clarence E. Davis, PhD (1993–2003); and Sanford Leikin, MD (1993–1999).
Executive Committee: Reuben Cherniack, MD (chair);Robert Strunk, MD; Stanley Szefler, MD; Virginia Taggart, MPH; James Tonascia, PhD; and Curtis Meinert, PhD (1992–2003).
Steering Committee: Reuben Cherniack, MD (chair); Robert Strunk, MD (vice chair); N. Franklin Adkinson, MD; Robert Annett, PhD (1992–1995, 1997–1999); Bruce Bender, PhD (1992–1994, 1997–1999); Mary Caesar, MHS (1994–1996); Thomas R. DuHamel, PhD (1992–1994, 1996–1999); H. William Kelly, PharmD; Henry Levison, MD (1992–1996); Alan Lincoln, PhD (1994–1995); Ian MacLusky, MD; Bennie McWilliams, MD (1992–1998); Curtis L. Meinert, PhD; Sydney Parker, PhD (1991–1994); Joe Reisman, MD, MBA (1991–1999); Denise Rodgers (2003–2005); Kay Seligsohn, PhD (1996–1997); Gail G. Shapiro, MD; Marian Sharpe (1993–1994); D Sundström (1998–1999); Stanley Szefler, MD; Virginia Taggart, MPH; Martha Tata, RN (1996–1998); James Tonascia, PhD; Scott Weiss, MD; Barbara Wheeler, RN, BSN (1993–1994); Robert Wise, MD; and Robert Zeiger, MD, PhD.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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Address correspondence to H. William Kelly, PharmD, University of New Mexico, Department of Pediatrics: Pediatrics/Pulmonary, MSC10-5590, 1 University of New Mexico, Albuquerque, NM 87131-0001. E-mail: hwkelly{at}salud.unm.edu
Financial Disclosure: Dr Kelly has participated on ad hoc scientific advisory boards for AstraZeneca, GlaxoSmithKline, Merck, Novartis, Schering, Genentech, MAP Pharmaceuticals, and Sepracor, has received honoraria for speaking from GlaxoSmithKline and AstraZeneca, and has received research funding from AstraZeneca, GlaxoSmithKline, and Sepracor; Dr Covar has participated on an ad hoc scientific advisory board for Merck and received a research grant from AstraZeneca. Mr VanNatta and Drs Tonascia, Green, and Strunk have indicated they have no financial relationships relevant to this article to disclose.
All authors participated in discussion of initial data analysis. All data analysis was performed by Mr Van Natta. After initial data analysis and consensus of the writing group, Dr Kelly wrote the initial draft that was reviewed and edited by all authors. Dr Green, an endocrinologist, then identified the issue of standardization of DEXA measures and, with Mr Van Natta, developed the procedure for standardization of measures. Dr Tonascia, as director of the CAMP Coordinating Center, oversaw all data analysis and assisted in writing the data-analysis section of a number of the drafts of the manuscript. Drs Strunk and Covar participated in all writing committee conference calls and provided significant editing and preparations of drafts 1 through 4 of the manuscript. Drs Kelly and Tonascia prepared the final draft of the manuscript.
Some of these data were presented at the American Thoracic Society International Conference; May 23, 2007; San Francisco, CA.
| What's Known on This Subject
Systemic corticosteroids and high dosages of ICSs are known to reduce BMD in both adults and children. Frequent short bursts (
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| What This Study Adds Multiple bursts of OCSs for asthma exacerbations produce a dosage dependent risk for decreased bone mineral accretion and increased risk for osteopenia in boys. The use of ICSs over a median of 7 years reduces bone mineral accretion but does not increase the risk of osteopenia.
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