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Published on: March 1, 2022
Effect of Low-Magnitude Mechanical Stimuli on Bone Density and Structure in Pediatric Crohn's Disease: A Randomized
Mary B Leonard1, Justine Shults2, Jin Long1
1Departments of Pediatrics and Medicine, Stanford University, Stanford, CA, USA.
Insights
Low-magnitude mechanical stimulation (LMMS) showed potential for improving bone density in pediatric Crohn's Disease (CD) patients. Daily LMMS increased vertebral bone mineral density (BMD) in a 12-month trial, particularly with higher adherence.
Area of Science:
- Pediatric Endocrinology
- Bone Metabolism
- Gastroenterology
Background:
- Pediatric Crohn's Disease (CD) is linked to reduced bone mineral density (BMD), cortical area, and muscle mass.
- Low-magnitude mechanical stimulation (LMMS) is a potential anabolic intervention for bone health.
- Understanding the impact of LMMS on bone and body composition in pediatric CD is crucial for management.
Purpose of the Study:
- To evaluate the efficacy of daily low-magnitude mechanical stimulation (LMMS) in improving bone mineral density (BMD) and lean mass in pediatric Crohn's Disease (CD) patients.
- To assess the impact of LMMS on tibia and vertebral bone parameters, as well as whole body, hip, and spine BMD via DXA and pQCT.
- To explore the relationship between treatment adherence and treatment outcomes in the context of LMMS intervention.
Main Methods:
- A 12-month, randomized, double-blind, placebo-controlled trial involving 121 pediatric CD patients (ages 8-21) with low tibia trabecular BMD.
- Participants received daily 10-minute LMMS (30 Hz, 0.3g acceleration) or placebo, alongside calcium and cholecalciferol supplementation.
- Primary outcomes included tibia trabecular BMD and cortical area (pQCT) and vertebral trabecular BMD (QCT); secondary outcomes included DXA measures and leg lean mass.
Main Results:
- LMMS demonstrated a significant increase in spine QCT trabecular BMD Z-score (+0.22 vs. -0.02, p=0.02) compared to placebo.
- Higher adherence (>50%) to LMMS was associated with a greater increase in spine QCT BMD Z-score (0.38, p<0.0005).
- No significant effects of LMMS were observed on pQCT or DXA outcomes; however, overall improvements in height and some bone parameters were noted across all participants.
Conclusions:
- Daily low-magnitude mechanical stimulation (LMMS) was associated with improved vertebral trabecular bone mineral density (BMD) in pediatric Crohn's Disease (CD) patients, particularly with high adherence.
- LMMS did not significantly impact peripheral bone measures (pQCT) or DXA-derived BMD in this cohort.
- Further research is warranted to optimize LMMS protocols and confirm its long-term benefits for bone health in pediatric CD.
Abstract:
Pediatric Crohn's Disease (CD) is associated with low trabecular bone mineral density (BMD), cortical area, and muscle mass. Low-magnitude mechanical stimulation (LMMS) may be anabolic. We conducted a 12-month randomized double-blind placebo-controlled trial of 10 minutes daily exposure to LMMS (30 Hz frequency, 0.3 g peak-to-peak acceleration). The primary outcomes were tibia trabecular BMD and cortical area by peripheral quantitative CT (pQCT) and vertebral trabecular BMD by QCT; additional outcomes included dual-energy X-ray absorptiometry (DXA) whole body, hip and spine BMD, and leg lean mass. Results were expressed as sex-specific Z-scores relative to age. CD participants, ages 8 to 21 years with tibia trabecular BMD <25th percentile for age, were eligible and received daily cholecalciferol (800 IU) and calcium (1000 mg). In total, 138 enrolled (48% male), and 121 (61 active, 60 placebo) completed the 12-month trial. Median adherence measured with an electronic monitor was 79% and did not differ between arms. By intention-to-treat analysis, LMMS had no significant effect on pQCT or DXA outcomes. The mean change in spine QCT trabecular BMD Z-score was +0.22 in the active arm and -0.02 in the placebo arm (difference in change 0.24 [95% CI 0.04, 0.44]; p = 0.02). Among those with >50% adherence, the effect was 0.38 (95% CI 0.17, 0.58, p < 0.0005). Within the active arm, each 10% greater adherence was associated with a 0.06 (95% CI 0.01, 1.17, p = 0.03) greater increase in spine QCT BMD Z-score. Treatment response did not vary according to baseline body mass index (BMI) Z-score, pubertal status, CD severity, or concurrent glucocorticoid or biologic medications. In all participants combined, height, pQCT trabecular BMD, and cortical area and DXA outcomes improved significantly. In conclusion, LMMS was associated with increases in vertebral trabecular BMD by QCT; however, no effects were observed at DXA or pQCT sites. © 2016 American Society for Bone and Mineral Research.
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