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

Background & Aims There are very few published studies of agents having the potential to improve bone health in children with inflammatory bowel disease (IBD). Our aim 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 sixty-three participants, ages 8 to 21 yrs, with a spinal BMD Z-score ≤ −1.0 SD measured by dual energy X-Ray absorptiometry (DXA). 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 (CD) the spinal BMD Z-score improved between screening and 9 months [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 rates during the trial did not lead to normalization of BMD Z-scores in this cohort. Factors favoring higher bone mineral accrual rate were: lower baseline BMD and higher baseline body mass index (BMI) 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 amount of 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 rates remain compromised in youth with IBD and low bone mineral density 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 caffeine intake may be helpful in restoring bone density, especially in children with IBD and low baseline BMD.

Impaired Bone Health in Inflammatory Bowel Disease: A Case–Control Study in 80 Pediatric Patients

“…Although most of the patients had inactive disease, their bone health was still impaired. The results on lower aBMD in pediatric IBD patients are in concordance with previous studies demonstrating persistently impaired BMD after diagnosis of the disease [6,14,31,32]. One-third of the patients had delayed BA, and BA-adjusted aBMD Z scores were significantly higher than CA-adjusted values, which emphasizes the importance of correcting the BMD values for delayed pubertal maturation when analyzing DXA results in both CD and UC patients.…”

“…One-third of the patients had delayed BA, and BA-adjusted aBMD Z scores were significantly higher than CA-adjusted values, which emphasizes the importance of correcting the BMD values for delayed pubertal maturation when analyzing DXA results in both CD and UC patients. Most previous studies that have evaluated BA of pediatric IBD patients have reported significant delay of BA, with a mean difference of 0.5-1.2 years to CA [6,16,17,[32][33][34]. Two studies on IBD patients found no difference between BA and CA [3,5].…”

“…This shows the deleterious effect of high GC dose on bone health. In previous studies on pediatric IBD patients, cumulative GC dose has been associated with reduced aBMD in one [16], while others have found no association between GC treatment and bone parameters or bone mineral accrual rate [3,6,14,31,32,34]. Longitudinal assessment of bone structure in CD patients with peripheral quantitative computed tomography has associated GCs with increases in cortical volumetric BMD [4].…”

Bone Loss Prevention of Bisphosphonates in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

“…The studies enrolled in this meta-analysis showed that bisphosphonates can also reduce the risk of fractures in IBD patients. Only one clinical trial thus far showed that intranasal calcitonin is not able to increase BMD in young IBD patients [ 34 ]. Two prospective studies revealed the beneficial effect of infliximab on bone metabolism both in CD and in UC patients [ 35 , 36 ].…”

Prevalence of Vertebral Compression Fractures and Associated Factors in Children and Adolescents with Severe Juvenile Idiopathic Arthritis

“…Three patients received calcitonin at the time of the study; the effect of calcitonin on BMD was also considered insignificant 28 and these patients' DEXA values were included in further analyses. Two patients had discontinued bisphosphonate therapy 7-10 months (mean 8.5 mo) before the study; 3 patients were still receiving intravenous pamidronate and 1 patient once-weekly alendronate.…”