Abstract

Purpose: Reduced bone mineral density (BMD) and an increased risk of fragility fractures are common complications in individuals with anorexia nervosa (AN). Traditional BMD assessments using Dual-energy X-ray Absorptiometry (DXA) present limitations in subjects with AN. This study explores the potential of Radiofrequency Echographic Multi-Spectrometry (REMS) as a non-invasive and reliable alternative to evaluate bone status in young women with AN.

Methods: A cohort of 50 subjects diagnosed with restrictive AN and 30 healthy controls were studied. BMD was measured at the lumbar spine, femoral neck, and total hip using both DXA and REMS.

Results: BMD measurements using both techniques were significantly lower in the AN group compared to controls (p < 0.01). A good correlation was found between DXA and REMS measurements at all skeletal sites (lumbar spine, femoral neck, and total hip) in subjects with AN. Bland–Altman analysis confirmed a strong agreement between the two methods. Women with previous vertebral fragility fractures showed lower BMD values, especially at the total hip site by REMS (p < 0.05).

Conclusions: REMS appears to be a precise and reproducible technique for assessing bone health in young women with AN, particularly during their reproductive years or in cases of pregnancy and breastfeeding, where non-ionizing radiation is preferred. Further studies are needed to explore REMS’s potential to identify bone quality alterations and predict fracture risk in this population.

Introduction

Anorexia nervosa (AN) is a severe psychiatric disorder characterized by extreme weight loss, self-induced starvation, and an intense fear of gaining weight. This disorder is particularly prevalent in adolescent and young adult women, with the lifetime prevalence of AN in the female population over 18 years estimated at 0.9%. Anorexia nervosa leads to numerous comorbidities, including endocrine and bone-related complications. One of the most concerning consequences of AN is the reduced bone mineral density (BMD), which increases the risk of bone fragility and fractures.

Bone Complications in AN: Bone loss is one of the most significant complications of anorexia nervosa. Both cortical and trabecular bones are affected, with rapid loss of trabecular bone linked to estrogen deficiency. In fact, adolescents with AN exhibit a decrease in cortical area, reduced cortical thickness, and increased cortical porosity. These abnormalities in bone structure often precede the changes in BMD, which contributes to a higher risk of fractures.

Traditional BMD Measurement Limitations: Traditionally, BMD is assessed using Dual-energy X-ray Absorptiometry (DXA), which measures bone density at specific skeletal sites, including the lumbar spine, femoral neck, and total hip. However, DXA uses ionizing radiation, which poses risks when frequent measurements are required, especially in young women who may need repeated evaluations over time.

Emergence of REMS: Radiofrequency Echographic Multi-Spectrometry (REMS) is an innovative, non-ionizing technique that uses ultrasound waves to assess bone status. REMS has the potential to overcome the limitations of DXA, providing a reliable, non-invasive, and radiation-free method for evaluating bone density. The aim of this study was to assess the effectiveness of REMS in evaluating BMD in young women with anorexia nervosa, compared to the standard DXA method.

Methods

Study Population: A total of 50 Caucasian young women diagnosed with restrictive anorexia nervosa and 30 age-matched healthy controls were enrolled. The inclusion criteria for the AN group included women aged 18 years and older, with a BMI less than 18 kg/m², and a diagnosis of restrictive anorexia nervosa as defined by the DSM-5. Control subjects were normal-weight women (BMI between 18 and 25 kg/m²) with no history of eating disorders or menstrual irregularities. The study was approved by the Institutional Review Board of Siena University Hospital, and informed consent was obtained from all participants.

BMD Measurements: BMD was measured at the lumbar spine (LS-BMD), femoral neck (FN-BMD), and total hip (TH-BMD) using both DXA and REMS techniques. DXA was performed using a Discovery W system (Hologic, Waltham, MA), and REMS scans were conducted using an EchoStation device (Echolight, Lecce, Italy), which operates with a convex transducer at 3.5 MHz.

Biochemical Parameters: Fasting blood samples were collected to assess serum levels of 25-hydroxyvitamin D, parathyroid hormone (PTH), calcium, and phosphate. These biochemical parameters were analyzed to ensure that no underlying metabolic disorders were affecting bone health.

Statistical Analysis: Descriptive statistics were used to compare demographic and clinical characteristics between the AN group and controls. Pearson’s correlation coefficient and Bland-Altman analysis were used to assess the agreement between DXA and REMS measurements. All tests were performed using SPSS statistical software.

Results

Demographic and Clinical Characteristics: There were no significant differences between the two groups regarding age, height, or biochemical parameters. As expected, the BMI was significantly lower in subjects with AN compared to controls (15.7 ± 2.5 vs. 23.4 ± 4.0 kg/m², p < 0.01). The mean duration of anorexia nervosa was 12.3 ± 11.3 years.

Bone Mineral Density Measurements: BMD measurements by both DXA and REMS were significantly lower in the AN group compared to the control group at all skeletal sites. The mean BMD values (g/cm²) for DXA and REMS at lumbar spine, femoral neck, and total hip were as follows:

• Lumbar Spine (LS-BMD): DXA: 0.854 ± 0.163, REMS: 0.854 ± 0.120
• Femoral Neck (FN-BMD): DXA: 0.687 ± 0.124, REMS: 0.592 ± 0.080
• Total Hip (TH-BMD): DXA: 0.785 ± 0.160, REMS: 0.701 ± 0.092

In both groups, a good correlation was found between the BMD values obtained by DXA and REMS. The correlation coefficients were as follows:

• Lumbar Spine (r = 0.64, p < 0.01)
• Femoral Neck (r = 0.86, p < 0.01)
• Total Hip (r = 0.84, p < 0.01)

Schematic Representation of REMS Acquisition on Femoral Neck

A diagram illustrating how the REMS device is used to acquire bone data at the femoral neck. This image highlights the placement of the probe and the detection of bone interfaces.

Bland-Altman Analysis: Bland-Altman analysis showed good agreement between DXA and REMS measurements. The average bias for lumbar spine BMD was 0.012 ± 0.350 g/cm² and for total hip BMD was -0.080 ± 0.288 g/cm².

Fracture History: Among the AN subjects, 16.3% had experienced at least one vertebral fragility fracture. Women with previous fractures showed lower BMD values at both lumbar spine and total hip sites, particularly with REMS (p < 0.05 for BMD at the total hip).

BMD Z-Scores for DXA and REMS

A bar graph comparing the BMD Z-scores obtained using DXA and REMS techniques at the lumbar spine (LS), femoral neck (FN), and total hip (TH). It demonstrates the significant reduction in BMD in AN subjects compared to controls.

Discussion

This study is the first to evaluate REMS for assessing bone status in young women with anorexia nervosa. The results suggest that REMS provides a reliable and non-ionizing alternative to DXA for evaluating BMD in this population. The correlation between DXA and REMS measurements was strong at all skeletal sites, and the Bland-Altman analysis confirmed good agreement between the two techniques.

One of the major advantages of REMS is its ability to assess BMD without using ionizing radiation, which is particularly important for young women who require repeated BMD assessments. Furthermore, REMS has the potential to provide additional information on bone quality and microarchitecture, which could improve the prediction of fracture risk in patients with AN.

Bland–Altman Plots Comparing DXA and REMS BMD Measurements

Two plots showing the differences between BMD values obtained from DXA and REMS at the lumbar spine (A) and total hip (B). These plots illustrate the agreement between the two techniques.

BMD at Lumbar Spine and Total Hip in AN Subjects with and without Vertebral Fractures

A comparison of BMD values by DXA and REMS in anorexic women with and without previous vertebral fractures. The chart highlights the significant differences in BMD values for those with fractures, particularly at the total hip site measured by REMS.

Conclusions

The findings from this study indicate that Radiofrequency Echographic Multi-Spectrometry (REMS) is a promising tool for assessing bone health in young women with anorexia nervosa. Its precision, reproducibility, and non-ionizing nature make it an excellent option for monitoring bone status, especially in women of reproductive age and during pregnancy and breastfeeding.

Further research is needed to confirm these preliminary results and explore the potential of REMS in identifying other aspects of bone quality, such as microarchitecture and structural defects, which are crucial in predicting fracture risk in this high-risk population.