The relationship between regional body composition and quantitative strength in facioscapulohumeral muscular dystrophy (FSHD)

Neuromuscular Disorders 18 (2008) 873–880 www.elsevier.com/locate/nmd

The relationship between regional body composition and quantitative strength in facioscapulohumeral muscular dystrophy (FSHD) Andrew J. Skalsky a,b,*, Richard T. Abresch a,b, Jay J. Han a,b, Chris S. Shin a, Craig M. McDonald a,b a

Department of Physical Medicine and Rehabilitation, University of California, Davis, 4860 Y Street, Suite 3850, Sacramento, CA 95817, USA b NIDRR Rehabilitation Research and Training Center in Neuromuscular Diseases, USA Received 20 February 2008; received in revised form 10 July 2008; accepted 17 July 2008

Abstract This study determines in facioscapulohumeral muscular dystrophy (FSHD) and able-bodied controls (1) the regional body composition and (2) the correlation between regional lean tissue mass and the corresponding regional strength. This is a cross-sectional, criterion standard, case-control study at a university based neuromuscular disease clinic. A dual-energy X-ray absorptiometry (DEXA) scanner was used to obtain regional body composition measurements in 14 FSHD and anthropometrically matched control pairs. A dynamometer determined peak isometric strength for the elbow and knee. Compared to controls, FSHD subjects showed increased regional fat tissue mass (p < 0.001–0.017), decreased regional lean tissue mass (p < 0.001–0.010), and decreased strength (p < 0.001–0.020). There was a correlation between quantitative strength and lean tissue mass for both FSHD and controls (r = 0.791–0.906; p < 0.001). FSHD subjects have higher regional fat tissue mass and lower regional lean tissue mass despite similar BMI and anthropometrics. Regional lean tissue mass correlates with strength. Ó 2008 Elsevier B.V. All rights reserved. Keywords: Facioscapulohumeral muscular dystrophy; Body composition; DEXA; Dual-energy X-ray absorptiometry; Muscle strength; BMI; Lean tissue mass; Fat tissue mass

1. Introduction There is evidence that patients affected with FSHD may have perturbed body composition different from the ablebodied population [1,2]. The clinical syndrome of FSHD is characterized by slowly progressive, stereotyped, regional weakness, and muscular wasting typically involving the lower face, scapular stabilizers, proximal arms, and anterior leg compartments [2–4]. FSHD is the third most common muscular dystrophy with an estimated prevalence * Corresponding author. Address: Department of Physical Medicine and Rehabilitation, University of California, Davis, 4860 Y Street, Suite 3850, Sacramento, CA 95817, USA. Tel.: +1 916/734 5291; fax: +1 916/734 7838. E-mail addresses: [email protected] (A.J. Skalsky), [email protected] (C.M. McDonald).

0960-8966/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.nmd.2008.07.005

of 1:20,000 [3]. The clinical spectrum ranges from asymptomatic individuals with minimal clinical weakness to individuals with wheelchair dependence [3]. Despite the stereotypical clinical pattern of weakness, no studies have evaluated the regional body composition including lean tissue mass (LTM), fat tissue mass (FTM), and bone mineral content (BMC) of individuals with FSHD and how they correlate with the clinically observed pattern of weakness. In most neuromuscular diseases (NMD), muscle wasting (or sarcopenia) is worse with disease progression [1,4,6–10]. Muscle wasting contributes to strength impairment, fatigue, diminished mobility, respiratory insufficiency, and decreased quality of life. Although there is no known cure for FSHD, one therapeutic strategy to ameliorate the disease and improve or maintain function involves the use of agents to improve muscle composition and

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function or increase muscle mass. Thus, a quantitative assessment of focal and generalized muscle wasting would be a useful monitor of the efficacy of therapeutic interventions as well as the natural history of disease progression in patients with FSHD. Studies evaluating the regional lean body composition in slowly progressive neuromuscular disorders are limited. Previous studies have evaluated whole-body composition by 24-h urine creatinine excretion, stereologic CT, and total body potassium using a scintillation counter [11–20]. These methods can be labor intensive and only give whole-body estimates of lean muscle mass or lean body mass. Dual-energy X-ray absorptiometry (DEXA) has been used successfully in the assessment of wholebody composition in subjects with neuromuscular diseases with both myogenic and neurogenic etiologies [1,5,21,22]. Regional assessment of body composition would provide essential information for the design and implementation of clinical trials involving progressive, distinctively and focally distributed muscle diseases such as FSHD [23]. DEXA is a well-validated instrument for measuring segmental body composition of the upper extremities, lower extremities, trunk, and pelvis in both adults and children [4–10,21,22,24–30]. DEXA is one of the only noninvasive body composition techniques that provides regional estimations of lean mass, fat mass, and bone mineral content. Quantitative strength measures are more sensitive measures of impaired strength than traditional manual muscle testing but cannot easily be used for muscles with less than grade 3 (antigravity) strength [8,31]. In persons with severe NMD and less than antigravity strength, lean tissue content by DEXA could be a useful surrogate of strength and an objective monitor of disease progression. Three studies have demonstrated significantly elevated fat/muscle ratio in subjects with myogenic atrophy. Both functional activity scales and strength correlated closely with the percentage of lean body mass measured by DEXA [1,5–10]. Despite the stereotypical clinical pattern of weakness in FSHD, no studies have evaluated regional lean tissue mass and how it correlates with the clinically observed pattern of weakness. This type of data will help distinguish whether the clinical weakness is simply due to muscle atrophy, a decrease in the muscles contractile function, dystrophic changes with associated atrophy, or most likely a combination of factors. Specifically, this study aims to (1) determine the regional as well as a whole-body composition using a three-compartment model of lean tissue mass (LTM), fat tissue mass (FTM), and bone mineral content (BMC) in FSHD as it compares to able-bodied controls and to (2) determine the correlation of regional LTM and the corresponding regional quantitative peak isometric strength in FSHD and controls. One of the main deficits appreciated in FSHD is the slowly progressive stereotyped regional weakness. To better understand and objectify the weakness experience in FSHD, we evaluated quantitative strength

in FSHD as compared to anthropometrically matched able-bodied controls. 2. Methods 2.1. Subjects Fourteen independent community ambulators with FSHD ages 10–64 years were recruited from a university based neuromuscular disease clinic. Fourteen gender, height, and weight matched able-bodied controls ages 13–52 years were selected from a larger pool of volunteers recruited from the community. The diagnosis of FSHD was confirmed by molecular genetic testing either in the subject or a first degree relative. There were seven male and seven female pairs. The subjects were matched using the following criteria: height within 3 cm and weight within 5 kg. All subjects reported to the laboratory in a 12-h postprandial and normally hydrated state. Approval for the study was obtained from the university Institutional Review Board and informed consent was obtained from all subjects. 2.2. Anthropometric measurements Standard linear anthropometric measurements of standing height were carried out in all subjects by a vertical stadiometer using a standard tape measure attached to a sliding L-bracket brought to rest on the head while parallel to the floor. Height was measured to the nearest 0.1 cm in all the subjects. Weight was determined on a digital scale to the nearest 0.1 kg. Body mass index (BMI) was calculated by the formula body weight (kg) divided by height squared (m2). 2.3. Body composition analysis A Hologic QDR-4500A dual-energy X-ray absorptiometry (DEXA) total body scanner (Hologic, Bedford, MA) was used to obtain regional body composition measurements using a three-compartment model of body composition: lean tissue mass (LTM), fat tissue mass (FTM), and bone mineral content (BMC). The entire body of each subject was scanned beginning at the top of the head and moved in a rectilinear pattern down the body to the feet. Scan speed was 0.6 cm/s, and the source collimation was 10 cm  0.2 cm. Total scan time was approximately 2 min 45 s and the radiation dose was 2.6 lSV, which is approximately 1/20th of the exposure from a standard chest X-ray (product information from Hologic). No shielding was necessary for the subject, operator, or room. To ensure quality control, the DEXA unit was calibrated daily using a standard calibration block of thermoplastic acrylic resin, which contained three bone equivalent chambers filled with hydroxyapatite. The measured bone mineral density and content were required to be within 2% of the known

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standard values before data collection. All scans were performed and analyzed by a certified technician. For regional body composition measures, Hologic software readings divided the body into trunk, entire arm, upper arm, entire leg, thigh, and lower leg. The forearm regions were calculated by subtracting the upper arm values from the whole arm values (entire arm–upper arm). The Hologic post-processing software (Whole-Body, version 8.26a:3a) was used to define body segments and measure body composition of each segment using standard regional settings previously described by Ley et al. and Ogle et al. [32,33]. The upper arm region was delineated by a vertical line passing through the shoulder joint and a horizontal line passing through the elbow. The thigh region was delineated by an upper border formed by an oblique line passing through the femoral neck to horizontal lines passing through the knee. The lower leg was delineated by horizontal lines passing through the knee to the foot (Fig. 1).

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2.4. Quantitative strength testing Peak isometric strength values in Newtons were obtained with a Lido Active Multi-Joint Dynamometer with LIDOAct software (Loredan Biomedical, Davis, CA, USA). For elbow flexion and extension, subjects were supine with the upper arm in approximately 45° of abduction and the elbow in 45° of flexion. For knee flexion and extension, subjects were seated with the hips flexed to 90° and positioned with their knees flexed to 45° as recommended by the manufacturer. Subjects performed three maximum extensions and three maximum flexions for each joint. The value used for analysis was the maximum of the three trials for each joint. 2.5. Statistical analysis Utilizing the pairing of a FSHD subject with an anthropometrically matched control, Student’s paired t-test for means was calculated to determine if a difference existed for the different parameters. In addition, we calculated percentile values for FSHD as compared to the anthropometrically matched controls’ values. The relationships between the different measures were explored using Pearson’s correlation statistical method. Significance was accepted at p-value < 0.05. 3. Results 3.1. Demographics and anthropometrics To ensure that there was no significant demographic or anthropometric selection bias, the FSHD and control pair’s age, height, weight, and BMI were evaluated. There was no significant difference between the FSHD and control subjects for age, height, weight, or BMI (Table 1). 3.2. Body composition analysis Since the two groups displayed nearly identical anthropometric measures, we assessed for any disparities in body composition in regard to LTM, FTM, and BMC. The right and left sides for all subjects were evaluated. There was no significant right/left difference for both the FSHD and control subjects for all limb body composition components including LTM, FTM, and BMC. Therefore, only the right limb data were utilized for statistical analysis. FSHD Table 1 Demographics and anthropometrics Mean (±SD)

Fig. 1. DEXA regional body segments used for measurement of regional LTM, FTM, and BMC.

Age (years) Height (cm) Weight (kg) BMI

p-Value

FSHD (n = 14)

Control (n = 14)

31.4 (±15.3) 170.2 (±7.8) 70.3 (±17.8) 24.0 (±4.7)

31.3 (±13.7) 170.5 (±7.6) 71.1 (±16.6) 24.2 (±4.3)

0.971 0.543 0.331 0.402

A.J. Skalsky et al. / Neuromuscular Disorders 18 (2008) 873–880

Table 2 Lean tissue mass by regional DEXA (kg) p-Value

FSHD (n = 14)

Control (n = 14)

40.44 (±11.07) 20.30 (±4.73) 1.25 (±0.50) 0.94 (±0.31) 4.01 (±1.96) 1.64 (±0.60)

48.76 (±12.33) 23.68 (±5.69) 1.72 (±0.75) 1.09 (±0.33) 5.36 (±1.52) 2.12 (±0.52)

Mean (±SD)

0.001 <0.001 0.015 0.061 0.009 0.005

p-Value

FSHD (n = 14)

Control (n = 14)

25.41 (±8.33) 11.45 (±4.59) 1.03 (±0.38) 0.41 (±0.24) 3.49 (±1.19) 1.25 (±0.43)

17.98 (±6.65) 7.65 (±3.64) 0.68 (±0.32) 0.36 (±0.16) 2.61 (±1.07) 0.91(±0.32)

Mean (±SD)

p-Value

FSHD (n = 14)

Control (n = 14)

2.24 6.29 0.71 0.89 1.86 1.69

2.35 6.30 0.74 0.94 2.05 1.88

(±4.52) (±1.36) (±0.16) (±0.23) (±0.46) (±0.47)

70 60 50 40 30 20 10 0 0

10

20

30

40

50

60

70

80

Age (yrs)

Fig. 2. Correlation of age and total body mass percentage of fat and lean tissue in FSHD. With increasing age, %fat also increases (r = 0.612, p = 0.020) while %lean decreases (r = 0.588, p = 0.027).

100

Fat Lean

90 80 70 60 50 40 30

(±4.36) (±1.23) (±0.18) (±0.24) (±0.38) (±0.40)

10

0

10

20

30

40 50 Age (yrs)

60

70

80

Fig. 3. Correlation of age and total body mass percentage of fat and lean tissue in controls. With increasing age, %fat and %lean vary little (r = 0.001, p = 0.998; r = 0.024, p = 0.934).

ciation for either percent LTM (r = 0.024, p = 0.934) or percent FTM (r = 0.001, p = 0.998) (Fig. 3). 3.3. Quantitative strength testing

0.001 0.004 0.001 0.466 <0.001 0.014

Table 4 Bone mineral content by regional DEXA (kg)

Whole-body Trunk Arm Forearm Thigh Leg

Lean

80

0

Table 3 Body fat mass by regional DEXA (kg)

Whole-body Trunk Arm Forearm Thigh Leg

Fat

90

20

Mean (±SD)

Whole-body Trunk Arm Forearm Thigh Leg

100 Total Body Mass (%)

subjects had significantly lower LTM for whole-body, upper arm, thigh, lower leg, and trunk but not for the forearm (Table 2). The FSHD subjects demonstrated a statistically higher FTM for the whole-body as well as all individual regions (Table 3) with exception of the forearm region. Only the lower leg BMC was significantly lower for the FSHD subjects and there was little difference for wholebody, trunk, upper arm, and forearm BMC between the groups (Table 4). In the regions with significantly different LTM and FTM, the FSHD values were calculated as a percentile value of control. The FSHD subjects demonstrated LTM ranging from 75% in the thigh to 86% in trunk and FTM ranging from 142% in the thigh to 176% in the trunk region as compared to the matched controls. The relationship between age and whole-body percent lean and fat tissue mass was examined. The FSHD subjects demonstrated decreased percent LTM with increased age as well as increased percent FTM with increased age (Fig. 2). In contrast, there was little change in the control subjectpercent LTM or FTM with age, and so there was no asso-

Total Mass (%)

876

0.290 0.965 0.476 0.356 0.053 0.040

One of the main deficits appreciated in FSHD is the slowly progressive stereotyped regional weakness. To better understand and objectify the weakness experience in FSHD, we evaluated quantitative strength in FSHD as compared to anthropometrically matched able-bodied controls. All subjects possessed sufficient strength to allow quantitative strength testing using the protocol described previously. The right and left sides for all subjects were evaluated. There was no significant right/left difference for both the FSHD and control subjects for all strength measures, so only the right limbs were utilized for statistical analysis. The FSHD subjects demonstrated significantly weaker peak isometric strength for all areas tested as compared to the matched controls. The arm strength for FSHD was 56% of control and the thigh strength was 45% of control. The limb strength was estimated by adding the flexion

A.J. Skalsky et al. / Neuromuscular Disorders 18 (2008) 873–880 Table 5 Peak isometric strength (Nm)

400

Mean (±SD)

19.1 (±15.3) 12.1 (±10.5) 36.1 (±33.0) 73.8 (±58.3) 31.2 (±24.4) 109.9 (±84.1)

FSHD

350

p-Value

Control

Control (n = 14) 40.2 (±16.6) 31.4 (±13.3) 81.4 (±30.3) 126.4 (±54.1) 71.6 (±28.8) 207.8 (±80.3)

0.001 <0.001 <0.001 0.013 <0.001 0.001

a

The arm strength was estimated by adding the flexion and extension values (i.e. arm strength = elbow flexion + elbow extension). b The thigh strength was estimated by adding the flexion and extension values (i.e. thigh strength = knee flexion + knee extension.

300 Thigh Strength (N)

FSHD (n = 14) Elbow flexion Elbow extension Knee flexion Knee extension Arm strengtha Thigh strengthb

877

250 200 150 100 50 0 0

2000

4000 6000 Thigh Lean (gm)

8000

Fig. 5. The correlation between thigh strength and thigh lean tissue mass in FSHD and controls. Both groups showed strong correlations between the thigh lean tissue mass and the thigh strength, FSHD (r = 0.876, p < 0.001) and control (r = 0.906, p < 0.001).

100% 90% 80% 70% % of Control

and extension values (i.e. thigh strength = knee flexion + knee extension) as shown in Table 5. For both FSHD and control subjects, there was a strong correlation for arm strength and arm LTM (Fig. 4) as well as thigh strength and thigh LTM (Fig. 5). The FSHD subjects had significantly lower absolute strength per LTM (N/ kg) for the arm (24.4 ± 12.6; 42.9 ± 8.4; p = 0.001) and thigh (24.7 ± 14.8; 38.3 ± 6.2; p = 0.007). Arm and thigh strength per respective regional LTM and per total body mass for FSHD subjects expressed as a percent of control is shown in Fig. 6. Changes in thigh strength per thigh LTM with age were evaluated for both FSHD subjects and control subjects. In FSHD, the thigh strength per thigh LTM decreased with age while it remained stable in controls (Fig. 7). When corrected for total body mass, a similar relationship was observed. The thigh strength per total body mass decreased with age while it remained unchanged in controls (Fig. 8).

60% 50% 40% 30% 20% 10% 0%

Arm Strength per Arm Lean

Thigh Strength Arm Strength per Thigh Lean per Body Mass

Thigh Strength per Body Mass

Fig. 6. FSHD values expressed as percent of control. Limb strength per limb lean tissue mass and limb strength per total body mass.

140 FSHD

120

Control

4. Discussion

Arm Strength (N)

100

80

60

40

20

0 0

1000

2000 Arm Lean (gm)

3000

4000

Fig. 4. The correlation between arm strength and arm lean tissue mass in FSHD and controls. Both groups showed strong correlations between the upper arm lean tissue mass and the upper arm strength, FSHD (r = 0.791, p = 0.001) and control (r = 0.862, p < 0.001).

Patients with facioscapulohumeral muscular dystrophy (FSHD) present with stereotyped regional weakness and muscle atrophy mainly affecting the shoulder girdle and facial musculature with relative sparing of the other regions of the body. Regional body composition evaluating LTM, FTM, and BMC in addition to quantitative regional strength had not been previously examined. Our study demonstrates the significant differences in regional and whole-body composition in FSHD as compared to anthropometrically matched controls. The difference is especially striking in regard to decreased LTM and increased FTM in FSHD. The decrease in regional and whole-body LTM was matched by an increase in regional and whole-body FTM. This study also demonstrates a

A.J. Skalsky et al. / Neuromuscular Disorders 18 (2008) 873–880 Thigh Strength per Lean Tissue Mass (N/kg)

878 60

FSHD 50

Control

40 30 20 10 0 0

20

40 Age (yrs)

60

80

Thigh Strength per Total Body Mass (N/kg)

Fig. 7. The correlation of thigh strength per lean tissue mass and age in FSHD and controls. There is a negative correlation in FSHD with strength per lean tissue decreasing with advancing age (r = 0.549, p = 0.042). In contrast, there is no correlation in the control group (r = 0.080, p = 0.785).

5 FSHD Control 4

3

2

1

0 0

10

20

30

40

50

60

70

Age (yrs)

Fig. 8. The correlation of thigh strength per total body mass and age in FSHD and controls. There is a negative correlation in FSHD with strength per kg body mass decreasing with advancing age (r = 0.580, p = 0.030). In contrast, there is no correlation in the control group (r = 0.037, p = 0.900).

correlation between age and increasing FTM and decreasing LTM in the FSHD population that is not observed in controls. Despite nearly identical BMI between FSHD and control subjects, there is a significant disparity in the body composition. The increased fat tissue in FSHD is not accurately reflected in the BMI. Although BMI has historically been used as a rough indicator of body fat percentage, it was developed for the able-bodied population and may not be an appropriate index for populations with NMD such as FSHD. Currently weight and BMI are two methods commonly used to guide clinical dosing regimens as estimations of lean body mass. However, the perturbed body composition in FSHD may impact dosing of pharmacotherapies that may be more optimally based on lean body mass.

In addition to a marked decrease in LTM in FSHD, this study quantifies the marked decrease in strength. Furthermore, the previous work in this area by Palmieri et al. demonstrated a significant correlation between whole-body lean mass and a composite of upper and lower body functional activity scores as well as manual muscle testing in Duchenne muscular dystrophy [5]. In this study, the regional lean tissue mass correlates very well with the corresponding regional peak isometric strength for both FSHD and controls, but there is a stronger correlation for control subjects. Since regional DEXA is not able to differentiate between anterior and posterior compartments of the thigh or arm, the flexion and extension values had to be taken into consideration together. This was done by adding the flexion and extension values. In order to get a more accurate representation of true strength per regional lean tissue mass, the elbow flexion strength per the anterior arm compartment lean tissue mass or the elbow extension strength per the posterior arm compartment lean tissue mass would be more precise. Unfortunately, these data are not able to be produced with a traditional two-dimensional DEXA scan despite the regional compartmentalization. By combining body composition measures with more traditional performance measures, this study was able to demonstrate a decrease in strength per lean tissue mass in FSHD. This study suggests that the weakness observed clinically in FSHD cannot be entirely attributed to the muscle atrophy or the decrease in lean tissue mass. This likely reflects the dystrophic changes observed histologically within the muscle tissue in FSHD. There may be abnormalities in muscle fiber contractility in FSHD due to muscle cell membrane abnormalities, intracellular or extracellular abnormalities of muscle cells, or progressive fibrosis. This also helps explain why the correlation between strength and lean tissue mass was stronger in controls than FSHD subjects. Furthermore, there is an association between increasing age and decreasing strength and lean tissue in FSHD. There is no significant change in strength per lean tissue mass for control subjects as compared to their age; however, the FSHD population demonstrates a significant decrease in strength per lean tissue mass as the subject age increases. This supports the premise that the dystrophic changes and muscle fiber contractility abnormalities are progressive over time and the degree of weakness is not just due to atrophy of muscle tissue. It should be noted that the lean tissue mass as measured by DEXA is an overestimation of muscle mass. The main reason for the overestimation of muscle mass is the use of simplifying assumptions that do not consider the magnitude of non-muscle compartments (i.e. skin, connective tissue, and fat-free portion of adipose tissue) included within DEXA lean tissue mass estimates. When skin, connective tissue, and the fat-free portion of adipose tissue are ignored for simplification purposes, the three compartments that are not muscle are incorporated into the lean tissue mass

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compartment. This assumption causes an overestimation of muscle mass [34]. Skin accounts for approximately 10% of lean tissue mass [35]. Neglecting the skin mass causes a corresponding overestimation of regional muscle mass. This overestimation is magnified in dystrophic muscle conditions like FSHD. As the muscle tissue gets replaced by fibrosis and fat, the fibrotic tissue is still represented as lean tissue. This overestimation of muscle tissue as lean tissue may explain the marked decrease in strength per lean tissue observed in FSHD as well as the decrease in strength per lean tissue with advancing age as more muscle is replaced by fibrotic tissue. There are several different ways to attempt to account for varied strength measures and anthropometric variations in the population. Some of these include the techniques employed in this study by factoring in regional lean tissue mass or total body mass. Additional techniques could include strength per total regional limb mass as well as strength per total body lean tissue mass. An argument can be made that the most informative technique is to utilize regional strength per regional lean tissue mass. This allows the combination of quantitative strength and regional DEXA to be utilized as both a clinical tool for observing the natural history of a progressive paretic condition such as NMD or examine the morphological changes due to potential therapeutic interventions such as anabolic agents like oxandrolone, myostatin inhibitors, and IGF-1. Utilizing the regional strength per regional lean tissue mass may yield the best estimation about whether the strength changes are simply due to muscle atrophy versus decreased contractile properties of the lean tissue mass secondary to pathologic changes such as fibrosis. This allows an investigator to determine some of the factors at play when witnessing strength changes in different populations or strength changes over time in the same population. An additional advantage to DEXA measures of body composition for clinical trials of more severely affected individuals is that lean tissue mass measured by DEXA may potentially serve as quantitative surrogate measure for quantitative isometric or isokinetic strength measurements. This may be particularly useful when muscle groups are less than antigravity strength and too weak to obtain quantitative strength measurements. Finally, regional DEXA is a cost-effective and time efficient imaging modality that can be utilized as a measurement of disease severity and disease progression for clinical trials. In comparison, regional and whole-body MRI provides the additional benefits of distinguishing between intra-muscular and extra-muscular lipid content using 1H MRS (magnetic resonance spectroscopy) [36] as well as information regarding the quality of muscle tissues in vivo utilizing (23Na) MRI [37]; however, a regional and whole-body DEXA scan can be performed in less than 10 min while it takes at least 30 min to acquire whole-body MRI data [38]. The utilization of regional DEXA in clinical trials in neuromuscular disorders will decrease study costs and time commitment on behalf of the investigators

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and subjects while still providing reliable and objective body composition data. Additional prospective, longitudinal studies in the context of both natural history investigations and clinical trials evaluating the sensitivity of regional body composition and lean tissue mass to change over time are needed to make regional DEXA a more precise therapeutic monitor. Acknowledgements A special thanks to Lana Widman for data acquisition. This study was funded by the National Institute of Disability and Rehabilitation Research Grant H133B03111805. References [1] Kanda F, Fujii Y, Takahashi K, Fujita T. Dual-energy X-ray absorptiometry in neuromuscular diseases. Muscle Nerve 1994;17(4):431–5. [2] Tyler FH, Stephens FE. Studies in disorders of muscle. II. Clinical manifestations and inheritance of facioscapulohumeral muscular dystrophy in a large family. Ann Intern Med 1950;32:640–60. [3] Padberg GW. Facioscapulohumeral disease. Thesis. Leiden, The Netherlands: University of Leiden; 1982. [4] Kilmer DD, Abresh RT, McCrory MA, Carter GT, Fowler Jr WM, Johnson ER, et al. Profiles of neuromuscular diseases: facioscapulohumeral muscular dystrophy. Am J Phys Med Rehabil 1995; 74(Suppl.):S131–9. [5] Palmieri MD, Bertorini MD, Griffin JW, Igarashi M, Karas JG. Assessment of whole body composition with dual energy X-ray absorptiometry in Duchenne muscular dystrophy: correlation of lean body mass with muscle function. Muscle Nerve 1996;19:777–9. [6] Carter GT, Abresh RT, Fowler Jr WM, Johnson ER, Kilmer DD, McDonald CM. Profiles of neuromuscular diseases: hereditary motor and sensory neuropathy, types I and II. Am J Phys Med Rehabil 1995;74(Suppl. 5):S140–9. [7] Carter GT, Abresh RT, Fowler Jr WM, Johnson ER, Kilmer DD, McDonald CM. Profiles of neuromuscular diseases: spinal muscular atrophy. Am J Phys Med Rehabil 1995;74(Suppl.):S150–9. [8] McDonald CM, Abresch RT, Carter GT, Fowler Jr WM, Johnson ER, Kilmer DD, et al. Profiles of neuromuscular diseases: Duchenne muscular dystrophy. Am J Phys Med Rehabil 1995;74(Suppl.): S70–92. [9] McDonald CM, Abresch RT, Carter GT, Fowler Jr WM, Johnson ER, Kilmer DD. Profiles of neuromuscular diseases: Becker’s muscular dystrophy. Am J Phys Med Rehabil 1995;74(Suppl.): S93–103. [10] McDonald CM, Johnson ER, Abresch RT, Carter GT, Fowler Jr WM, Kilmer DD. Profiles of neuromuscular diseases: limb-girdle syndrome. Am J Phys Med Rehabil 1995(Suppl.):S117–30. [11] Forbes GB, Gallup J, Hursh JB. Estimation of total body fat from potassium-40 content. Science 1961;133:101. [12] Blahd WH, Cassen B, Lederer M. Body potassium content in patients with muscular dystrophy. Ann NY Acad Sci 1963;110:2132–90. [13] Fitch CD, Sinton DW. A study of creatinine metabolism in diseases causing muscle wasting. J Clin Invest 1964;43:444–52. [14] Kossman M, Peterson DC, Andrews HL. Studies in neuromuscular disease: I. Total body potassium in muscular dystrophy and related diseases. Neurology (Minneap) 1965;15(85):1–65. [15] Blahd WH, Lederer M, Cassen B. The significance of decreased body potassium concentrations in patients with muscular dystrophy and nondystrophic relatives. N Engl J Med 1967;276:1349–52. [16] Forbes GB, Shultz F, Cafarelli C, Amirhakimi GH. Effects of body size on potassium-40 measurement in the whole body counter (tiltchair technique). Health Phys 1968;15:435–42.

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