title: Efficacy and harms of nasal calcitonin in improving bone density in young patients with inflammatory bowel disease: a randomized, placebo-controlled, double-blind trial.
abstract: OBJECTIVE
  There are very few published studies of agents having the potential to improve bone health in children with inflammatory bowel disease (IBD). The objective of this study was to establish the efficacy and safety of intranasal calcitonin in improving bone mineral density (BMD) in young patients with IBD and to define additional factors that impact bone mineral accrual.
  
  
  METHODS
  We conducted a randomized, placebo-controlled, double-blind clinical trial in 63 participants, ages 8-21 years, with a spinal BMD Z-score ≤ -1.0 s.d. measured by dual energy X-ray absorptiometry. Subjects were randomized to 200 IU intranasal calcitonin (n=31) or placebo (n=32) daily. All received age-appropriate calcium and vitamin D supplementation. Subsequent BMD measurements were obtained at 9 and 18 months.
  
  
  RESULTS
  Intranasal calcitonin was well tolerated. Adverse event frequency was similar in both treatment groups, and such events were primarily minor, reversible, and limited to the upper respiratory tract. The BMD Z-score change documented at screening and 9 months and screening and 18 months did not differ between the two therapeutic arms. In participants with Crohn's disease, the spinal BMD Z-score improved between screening and 9 months (change in spine BMD Z-score (ΔZSBMD)(9-0)) in the calcitonin group (ΔZSBMD(9-0)(calcitonin)=0.21 (0.37), ΔZSBMD(9-0)(placebo)=-0.15 (0.5), P=0.02); however, this was only a secondary subgroup analysis. Bone mineral accrual rate during the trial did not lead to normalization of BMD Z-score in this cohort. Factors favoring higher bone mineral accrual rate were lower baseline BMD and higher baseline body mass index Z-score, improvement in height Z-score, higher serum albumin, hematocrit and iron concentration, and more hours of weekly weight-bearing activity. Factors associated with lower bone mineral accrual rate were more severe disease-as indicated by elevated inflammatory markers, need for surgery, hospitalization, and the use of immunomodulators-and higher daily caffeine intake.
  
  
  CONCLUSIONS
  Intranasal calcitonin is well tolerated but does not offer a long-term advantage in youth with IBD and decreased BMD. Bone mineral accrual rate remains compromised in youth with IBD and low BMD raising concerns for long-term bone health outcomes. Improvement in nutritional status, catch-up linear growth, control of inflammation, increase in weight-bearing activity, and lower daily caffeine intake may be helpful in restoring bone density in children with IBD and low BMD.
authors.affiliation: Center for Inflammatory Bowel Disease, Children's Hospital Boston, Boston, Massachusetts 02115, USA. helen.pappa@childrens.harvard.edu
authors.forename: Helen M
authors.initials: HM
authors.lastname: Pappa
authors.forename: Tracee M
authors.initials: TM
authors.lastname: Saslowsky
authors.forename: Rajna
authors.initials: R
authors.lastname: Filip-Dhima
authors.forename: Diane
authors.initials: D
authors.lastname: DiFabio
authors.forename: Hajar
authors.initials: H
authors.lastname: Hassani Lahsinoui
authors.forename: Apurva
authors.initials: A
authors.lastname: Akkad
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Grand
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Gordon
mesh_terms: D015502:Absorptiometry, Photon; D000281:Administration, Intranasal; D000293:Adolescent; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002110:Caffeine / Q000008:administration & dosage / Q000009:adverse effects; D002116:Calcitonin / Q000008:administration & dosage* / Q000009:adverse effects*; D002118:Calcium / Q000008:administration & dosage; D002648:Child; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D018579:Patient Selection; D013997:Time Factors; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage; D016474:Weight-Bearing; D055815:Young Adult
chemical_list: D050071:Bone Density Conservation Agents; D014807:Vitamin D; D002110:Caffeine; C028815:salmon calcitonin; D002116:Calcitonin; D002118:Calcium