Bone Marrow Lipid Profiles from Peripheral Skeleton as Potential Biomarkers for Osteoporosis A1 H-MR Spectroscopy Study

Rationale and Objectives

To characterize the lipidic profile of bone marrow in the calcaneus and femoral neck of healthy, osteopenic, and osteoporotic women, by using magnetic resonance spectroscopy (MRS) at 3T. The final goal was to identify specific metabolites with the potential ability to discriminate between healthy, osteopenic, and osteoporotic subjects.

Materials and Methods

Sixty-two and thirty three postmenopausal women recruited to investigate calcaneus and femoral neck, respectively, underwent a bone mineral density (BMD) measurement to be classified as healthy subjects ( n = 22), osteopenic ( n = 45), or osteoporotic ( n = 28) patients.

MRS spectra were used to quantify and compare bone marrow fat resonances between the three BMD groups. Between-group differences were tested using a Welch analysis of variance. Multiple comparisons were made with the Games–Howell correction. Relationships between pairs of variables were assessed with linear correlation analysis. Reproducibility analysis was performed for all the lipid resonances in both sites.

Results

The reproducibility was satisfactory. In femoral neck, methylene (L13), glycerol (L41, L43), and total lipid resonances were significantly lower in healthy as compared to osteoporotic subjects. On the other hand, in calcaneus, L13/glycerol significantly discriminated between osteopenic and osteoporotic subjects whereas L13/(unsaturated lipid) discriminated between healthy and osteopenic group. However, the reproducibility of both unsaturated lipid and glycerol resonances were less optimal.

Conclusions

MRS of bone marrow lipid profiles from peripheral skeletal sites may be a promising tool for screening of large population to identify individuals with or at risk for developing osteoporosis. Moreover, it provides information about the metabolic changes occurring in bone marrow with the development of osteoporosis, which are skeletal site dependent.

Introduction

To date, several studies performed in different populations by using distinct measurement techniques have established that higher bone marrow fat is associated with lower bone mineral density (BMD) and prevalent vertebral fracture . This has led to a growing interest in the study of the interplay between marrow fat and bone mineral metabolism in connection to the development of osteoporosis.

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Materials and Methods

Subjects

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Table 1

Participant Characteristics \*

Group Group I: Calcaneus Group II: Femoral Neck_N_ Mean Age (years) BMI (Kg/m 2 ) T-score \\ N Mean Age (years) T-score \\\* BMI (kg/m 2 ) Healthy 11 60.0 ± 4.1 25.80 ± 3.20 −1.2 ± 0.5 11 67.2 ± 9.2 −0.5 ± 0.3 26.80 ± 2.90 Osteopenic 33 62.0 ± 6.4 26.90 ± 4.80 −2.6 ± 0.4 12 68.8 ± 7.1 −1.8 ± 0.3 25.95 ± 3.60 Osteoporosis 18 63.6 ± 4.7 24.70 ± 4.10 −3.8 ± 0.5 10 72.5 ± 6.7 −3.1 ± 0.4 25.80 ± 3.10

BMI, body mass index.

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MR Examination

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Calcaneus

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Femoral Neck

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Data Analysis

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FC%=(ILipidI∑iLipidi+IW)∗100 F

(

Lipid

∑

Lipi

)

∗

100

where I∑iLipidi I

∑

Lipi

i is the sum of the area amplitudes of the resonances: L09, L13, L16, L21, L23, L28, L43, L41, and L52+L53, and I W is the area amplitude of water resonance.

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UI=(IOlefinicIOlefinic+IMethylene+IMethyl) UI

(

Olefinic

Methylene

Methyl

)

where I Olefinic , I Methylene , I Methyl are the area amplitudes of the olefinic resonance (L53, L21, L28), methylene resonance (L13, L16, L21, L23, L43, and L41) and methyl resonance (L09), respectively .

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TL=(I∑iLipidiI∑iLipidi+IWater)∗100 T

(

∑

Lipi

∑

Lipi

Water

)

∗

100

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Statistical Analysis

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Reproducibility of Lipid Quantification

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Results

Subjects

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FC, Age, and T-Score

Calcaneus

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Table 2

The Short (CV s ) and Long-Time (CV l ) Reliability in Both Femoral and Calcaneus Site

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terms ranging from 0% to 5%.

terms ranging from 5% to 10%.

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Table 3

Person Correlation Coefficient between FC, L13/L41, L13/L43, L13/L51+L52, Age, T-Score in Femoral Neck and Calcaneus

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Significant correlation.

\\ P-value <0.01.

\* P-value <0.05.

FC, fat content.

Table 4

Bone Marrow FC in Calcaneus and Femoral Neck According to BMD Status to Show Differences between Groups (Healthy, Osteopenic, Osteoporotic)

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Statistically significant differences between FC of healthy and osteopenic subjects.

Statistically significant differences between FC of osteopenic and osteoporotic subjects.

Statistically significant differences between FC of healthy and osteoporotic subjects.

BMD, bone mineral content; FC, fat content; NS, No statistically significant differences.

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Femoral Neck

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Discussion

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Acknowledgments

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Bone Marrow Lipid Profiles from Peripheral Skeleton as Potential Biomarkers for Osteoporosis A1 H-MR Spectroscopy Study

Rationale and Objectives

Materials and Methods

Results

Conclusions

Introduction

Materials and Methods

Subjects

MR Examination

Calcaneus

Femoral Neck

Data Analysis

Statistical Analysis

Reproducibility of Lipid Quantification

Results

Subjects

FC, Age, and T-Score

Calcaneus

Femoral Neck

Discussion

Acknowledgments

References

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