The ability of low-magnitude mechanical signals to normalize bone turnover in adolescents hospitalized for anorexia nervosa

Abstract

We sought to determine whether low-magnitude mechanical stimulation (LMMS) normalizes bone turnover among adolescents hospitalized for anorexia nervosa (AN). Brief, daily LMMS prevents the decline in bone turnover typically seen during bed rest in AN. LMMS may have application for patients with AN in the inpatient setting to protect bone health.

Introduction: Malnourished adolescents with AN requiring medical hospitalization are at high risk for rapid reduction in skeletal quality. Even short-term bed rest can suppress normal patterns of bone turnover. We sought to determine whether LMMS normalizes bone turnover among adolescents hospitalized for complications of AN.

Methods: In this randomized, double-blind trial, we prospectively enrolled adolescent females (n = 41) with AN, age 16.3 ± 1.9 years (mean ± SD) and BMI 15.6 ± 1.7 kg/m². Participants were randomized to stand on a platform delivering LMMS (0.3 g at 32-37 Hz) or placebo platform for 10 min/day for 5 days. Serum markers of bone formation [bone-specific alkaline phosphatase (BSAP)], turnover [osteocalcin (OC)], and bone resorption [serum C-telopeptides (CTx)] were measured. From a random coefficients model, we constructed estimates and confidence intervals for all outcomes.

Results: BSAP decreased by 2.8% per day in the placebo arm (p = 0.03) but remained stable in the LMMS group (p = 0.51, p_diff = 0.04). CTx did not change with placebo (p = 0.56) but increased in the LMMS arm (+6.2% per day, p = 0.04; p_diff = 0.01). Serum OC did not change in either group (p > 0.70).

Conclusions: Bed rest during hospitalization for patients with AN is associated with a suppression of bone turnover, which may contribute to diminished bone quality. Brief, daily LMMS prevents a decline in bone turnover during bed rest in AN. Protocols prescribing strict bed rest may not be appropriate for protecting bone health for these patients. LMMS may have application for these patients in the inpatient setting.

Keywords: Anorexia nervosa; Bed rest; Bone formation; Bone resorption; Bone turnover; Mechanical stimulation; Metabolic disorders; Osteoporosis.

Figure 1:

Patient recruitment, enrollment, and disposition.

Figure 2:

Raw data and trends in bone-specific alkaline phosphatase (BSAP), a marker of bone formation, in 41 adolescent females with anorexia nervosa randomized to 5 days of intervention with low-magnitude mechanical stimulation (LMMS, left graph) or placebo (right graph). The “x’s” represent the raw data for each subject. The solid black line represents the mean trend over time from a fitted random-coefficients model, adjusted for time-varying weight, age, percentage of median body weight for age, duration of anorexia nervosa, duration of amenorrhea, and history of fracture. The shaded gray areas represent the 95% confidence band for the mean trend.

Figure 3:

Raw data and trends in C-telopeptides (CTx), a marker of bone resorption, in 41 adolescent females with anorexia nervosa randomized to 5 days of intervention with low-magnitude mechanical stimulation (LMMS) or placebo. The “x’s” represent the raw data for each subject. The solid black line represents the mean trend over time from a fitted random-coefficients model, adjusted for time-varying weight, age, percentage of median body weight for age, duration of anorexia nervosa, duration of amenorrhea, and history of fracture. The shaded gray areas represent the 95% confidence band for the mean trend.