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Muscle mass and bone mineral indices: does the normalized bone mineral content differ with age?
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European Journal of Clinical Nutrition advance online publication 23 January 2008; doi: 10.1038/sj.ejcn.1602977
Sanada K, Miyachi M, Tabata I, Miyatani M, Tanimoto M, Oh TW, Yamamoto K, Usui C, Takahashi E, Kawano H, Gando Y, Higuchi M.
[1] 1Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Tokyo, Japan [2] 2Health Promotion and Exercise Program, National Institute of Health and Nutrition, Tokyo, Japan.
Summary
We assessed the relationship between regional SM mass (skeletal muscle mass) and bone mineral indices, and whether BMC (bone mineral content) normalized to site-matched SM mass differed with age. This cross-sectional study concluded that whole-body and regional SM mass are associated with site-matched BMD and BMC in both young and postmenopausal women. Moreover, the age-related differences in BMC were found to be independent of the ageing of SM mass in the arm and trunk region. However, differences in BMC measures of the leg and whole body were found to correspond to age-related decline of SM mass in postmenopausal women. These results support that the preservation of ageing of SM mass is an important factor for maintenance of leg and whole-body BMC especially in older women.
ABSTRACT
Objective: To investigate the relationships between regional skeletal muscle mass (SM mass) and bone mineral indices and to examine whether bone mineral content (BMC) normalized to SM mass shows a similar decrease with age in young through old age.
Subjects/Methods: One hundred and thirty-eight young and postmenopausal women aged 20-76 years participated in this study and were divided into three groups: 61 young women, 49 middle-aged postmenopausal women and 28 older postmenopausal women. Muscle thickness (MTH) was determined by ultrasound, and regional SM mass (arm, trunk and leg) was estimated based on nine sites of MTH. Whole-body and regional lean soft tissue mass (LSTM), bone mineral density (BMD) and BMC (whole body, arms, legs and lumbar spine) were measured using dual-energy X-ray absorptiometry.
Results: Ultrasound spectroscopy indicated that SM mass is significantly correlated with site-matched regional bone mineral indices and these relationships correspond to LSTM. The BMC and BMD in older women were significantly lower than those in middle-aged women. When BMC was normalized to site-matched regional SM mass, BMC normalized to SM mass in arm and trunk region were significantly different with age; however, whole-body and leg BMC normalized to SM mass showed no significant difference between middle-aged and older postmenopausal women.
Conclusions: The age-related differences in BMC were found to be independent of the ageing of SM mass in the arm and trunk region. However, differences in BMC measures of the leg and whole body were found to correspond to age-related decline of SM mass in postmenopausal women.
Introduction
Fractures in the elderly are associated with the loss of bone mineral density (BMD) and an increased risk of falls (Pfeifer et al., 2004). Femoral neck and lumbar fractures are especially common problems in the elderly and can have a devastating impact on their ability to remain independent. Many investigators have shown that muscle strength (Gleeson et al., 1990; Peterson et al., 1991; Blain et al., 2001; Sinaki et al., 2002) and muscle mass (Pluijm et al., 2001; Szulc et al., 2005; Walsh et al., 2006) are associated with site-matched bone mineral indices, that is, BMD or bone mineral content (BMC). The greater rates of age-related loss of skeletal muscle mass (SM mass) occur in the legs and lower trunk regions, while only moderate losses occur in the upper trunk and arm regions (Reimers et al., 1998; Kanehisa et al., 2004). These regions correspond to the segments where fractures occur frequently. However, it is not sufficiently clear whether the age-related decrease of regional SM mass (for example, arm, leg and trunk region) affects the age-related decline of bone mineral indices in postmenopausal women.
According to Schiessl et al. (1998), more bone mass is accrued per lean body mass after puberty in girls than in boys. It has been speculated that this bone mass is not mechanically needed and serves as a surplus for reproduction. Schonau (2004) has repeated this finding in more depth in a series of papers based upon the forearm, but other authors (Ferretti et al., 2000; Rittweger et al., 2000) were unable to detect the surplus bone in the lower body. The accelerated bone loss observed around menopause is predominantly due to oestrogen deficiency (Kassem et al., 1996). The phase of rapid bone loss normally lasts 4-8 years, and after this period, age-related bone loss is considered to occur in women.
Although the dual-energy X-ray absorptiometry (DXA) method can be used to accurately estimate SM mass (appendicular muscle mass), it is not capable of accurate distinguish of SM mass from the trunk region. Ultrasound muscle thickness (MTH) has been widely employed for accurate measurement of SM size in vivo (Kawakami et al., 1993; Abe et al., 1997; Reimers et al., 1998), and previous studies have shown it to be highly reliable and valid in measuring MTH (Kawakami et al., 1993; Reimers et al., 1998). These characteristics make ultrasound a useful alternative to other more expensive imaging methods for assessing changes in SM mass. Moreover, ultrasound-derived prediction equations can accurately estimate the regional SM mass involving the measurement of arm, leg and trunk muscles (Sanada et al., 2006).
The present cross-sectional study investigates the relationships between regional SM mass and bone mineral indices, and examines whether regional BMC normalized to SM mass shows a similar decrease with age in young subjects through old age.
Discussion
This study investigated the relationships between regional SM mass and bone mineral indices, and sought to determine whether regional BMC normalized to SM mass showed a similar decrease with age in young subjects through old age. The major findings of this cross-sectional study were as follows: (1) SM mass were associated with the site-matched bone mineral indices, and these associations corresponded to the relationships between LSTM and the site-matched bone mineral indices; (2) BMC normalized to SM mass estimated by ultrasound in arm and trunk region were also significantly different with age, but not in leg and whole body in middle-aged and older postmenopausal women. These results suggest that the age-related decline of BMC normalized to SM mass was different in the body segments. Thus, the age-related differences in BMC were found to be independent of the ageing of SM mass in the arm and trunk region. However, differences in BMC measures of the leg and whole body were found to correspond to age-related decline of SM mass in postmenopausal women.
Age-related decline in SM mass and bone mineral indices
As both SM mass and bone mineral indices decrease with age, it is not yet clear how the age-related decrease in SM mass (for example, arm, leg and trunk region) affects the age-related decline of bone mineral indices in young and postmenopausal women. The age-related differences in BMC normalized to the site-matched SM mass in MW were significantly lower than those in YW (15-22%, Table 3), and serum estradiol in MW were also significantly lower than those in YW (87%, P<0.05, Table 1). In addition, serum estradiol in MW was significantly lower than that in YW. These results suggest that age-related decrease of BMC from youth through middle age was associated with age-related change of oestrogen deficiency (NIH Consensus Development Panel on Osteoporosis Prevention, 2001). However, when postmenopausal women were divided into MW and OW, age-related differences in whole-body and leg BMC normalized to SM mass were absent in older postmenopausal women (Table 3) with no changes in serum estradiol and osteocalcin. Furthermore, the interaction (age times BMI) of the age-related differences of BMD, BMC and normalized BMC was not significant. Therefore, the age-related differences in whole-body and leg BMC among middle-aged and older postmenopausal women were considered partly due to the age-related changes in SM mass independent of the differences of BMI. These results support that the preservation of ageing of muscles is an important factor for maintenance of leg and whole-body BMC, especially in older women.
Relationships between SM mass, muscle function and bone mineral indices
The SM mass were associated with the site-matched bone mineral indices, and these associations show equivalent to better correlations among LSTM determined by DXA and the site-matched bone mineral indices. The final outcome is so much stronger when adjusted data use independent measurements. Every DXA-derived component from BMC to FM to LSTM is likely to co-vary, since they are all derived from the same scan. These results can be applied to the future studies such as the development of prediction equation for bone mineral indices using ultrasound technique. A compact-type ultrasound machine weighs approximately 3 kg, making it easily portable. Ultrasound-derived prediction equations are capable of taking measurements in the field, and are safe and valid in predicting total and regional SM mass (Sanada et al., 2006).
Some investigators have shown that prolonged low-to-moderate intensity exercise is independently associated with higher BMD (Nguyen et al., 1998; Hagberg et al., 2001; Pongchaiyakul et al., 2004), while cardiorespiratory fitness (VO2peak) is only slightly correlated with bone mineral indices (Henderson et al., 1995; Ryan and Elahi, 1998; Ryan et al., 1998; Lynch et al., 2002). In this study, VO2peak (normalized to body mass) in young women was significantly correlated with BMD (P<0.05), while VO2peak (normalized to whole-body SM mass) was not significantly associated with BMD (Table 5). These results indicate that although the present and previous studies have shown aerobic fitness to be associated with BMD, this relationship may be due to the magnitude of SM mass. However, in older women, even absolute VO2peak (l min-1) was not significantly correlated with whole-body BMD. In the same way, low grip strength is associated with low BMD and an increased risk of incident vertebral fracture (Bevier et al., 1989; Osei-Hyiaman et al., 1999; Di Monaco et al., 2000; Dixon et al., 2005). The absolute handgrip strength in older women were significantly correlated with BMD, but not normalized to body mass and SM mass, in present study. These results suggest the relation of BMD and handgrip strength associated with body mass. However, the absolute leg extension power (W) and leg extension power normalized to body mass (W kg-1) were significantly correlated with leg BMD, but not normalized to leg SM mass (W kg-1). There is no difference in leg BMC (normalized to SM) between middle-aged and older women, there may be a difference but this study does not have the power to demonstrate a difference, particularly as the numbers are much less in the older groups.
Results
The physical characteristics of the subjects are presented in Table 1. The BMI and body fat percentage in MW and OW were significantly higher than those in YW (P<0.05). There were no significant differences in the NASA/JSC physical activity scale among the groups. Serum estradiol in MW and OW were significantly lower than those in YW (P<0.05). Serum osteocalcin in MW and OW were significantly higher than those in YW (P<0.05). Handgrip strength in OW was significantly lower than that in YW and MW (P<0.05). Leg extension power in MW and OW were significantly lower than those in YW (P<0.05). VO2peak (normalized to body mass) in MW and OW were significantly lower than those in YW (P<0.05).
Age-related decline of body composition and bone mineral indices
Leg SM mass and LSTM in MW and OW were significantly lower than those in YW (P<0.05, Table 2). Leg SM mass in OW was significantly lower than that in MW (P<0.05), but there was no such difference in leg LSTM. Table 3 shows the mean BMC, BMD and bone mineral indices normalized to SM mass. The BMC and BMD in MW and OW were significantly lower than those in YW (P<0.05), while BMC (whole body, arms, trunk and legs) and BMD (whole body, arms and legs) in OW were significantly lower than in those MW (P<0.05). The BMC normalized to SM mass in MW and OW was significantly lower than that in YW (P<0.05). The arm BMC normalized to arm SM mass and the trunk BMC normalized to trunk SM mass in OW were significantly lower than those in MW. However, whole-body and leg BMC normalized to leg SM mass were not significantly different between MW and OW. Furthermore, the interaction (age times BMI) of the age-related differences of BMD, BMC and normalized BMC was not significant.
There was significantly negative correlation between age and BMC normalized to SM mass in all women (P<0.001, Table 4). However, when the subjects were divided into three age groups, there was no significant correlation between age and BMC normalized to SM mass in middle-aged and older women.
Relationships between SM mass, muscle functions and bone mineral indices
Lean soft tissue mass was significantly correlated with site-matched BMC (arm, trunk, leg and whole body; r=0.57, 0.73, 0.53 and 0.47, respectively; P<0.05, Figure 1) and BMD (arm, L-spine, leg and whole body; r=0.38, 0.40, 0.60 and 0.42, respectively; P<0.05, Figure 2). These associations corresponded to the relationships between SM mass measured by ultrasound and the site-matched BMC (arm, trunk, leg and whole body; r=0.53, 0.49, 0.66 and 0.55, respectively; P<0.05, Figure 1) and BMD (arm, L-spine, leg and whole body; r=0.38, 0.44, 0.55 and 0.52, respectively; P<0.05, Figure 2) in all women. The BMD in YW, MW and OW is also significantly correlated with the site-matched SM mass; r=0.29-0.54, 0.36-0.44 and 0.46-0.60, respectively (P<0.05). The correlation coefficients in OW were comparatively higher than those in YW or MW. In older women, absolute VO2peak (l min-1) was not significantly correlated with whole-body BMD (Table 5). Moreover, the absolute leg extension power (W) and leg extension power normalized to body mass (W kg-1) were significantly correlated with leg BMD, but not leg extension power normalized to leg SM mass (W kg-1).
Methods
Subjects
One hundred and thirty-eight young and postmenopausal women aged 20-76 years participated in this study and were divided into three groups: 61 young women (YW: 23.7plusminus0.5, 20-39 years), 49 middle-aged postmenopausal women (MW: 58.3plusminus0.6, 40-64 years) and 28 older postmenopausal women (OW: 70.3plusminus0.7, 65-76 years). The NASA/JSC physical activity scale, a questionnaire method, was used to survey the subject's physical activity (Ross and Jacson, 1990). This scale was developed to provide an assessment score of 0-7 on a person's level of regular physical activity. There are a series of eight statements about routine physical activity.
None of the subjects smoked and they were not taking any medications, such as beta-blockers, steroids or hormone replacement therapy. The subjects involved in this study were both sedentary and active women. Active young women participated in continuous aerobic exercise for at least one session per week for 1 h per session. Active postmenopausal women participated in a swimming programme for at least two sessions per week for 1 h per session. However, they were not highly trained athletes.
The purpose, procedures and risks of the study were explained to each participant prior to inclusion, and all subjects gave their written informed consent before participating in the study approved by the Human Research Committee of the National Institute of Health and Nutrition. The study was performed in accordance with the guidelines of the Declaration of Helsinki.
Whole-body DXA
Lean soft tissue mass (LSTM), fat mass, BMC and BMD were determined for the whole body using DXA (Hologic QDR-4500A scanner; Hologic, Waltham, MA, USA). Subjects were positioned for whole-body scans according to the manufacturer's protocol. Participants lay in the supine position on the DXA table with the limbs close to their bodies. The bone densitometer delivers a very low dose of radiation (1.5 mR for the whole body) using quantitative digital radiography. Daily DXA calibration of phantoms showed a coefficient of variation of 0.35% for BMD over the past 156 measurement points. The whole-body BMC and LSTM were divided into several regions, that is, arms, legs, trunk and head. The body compositions were analysed using manual DXA analysis software (version 11.2:3). The arm region was defined as the region extending from the head of the humerus to the distal tip of the fingers. The reference point between the head of the humerus and the scapula was positioned at the glenoid fossa. The leg region was defined as the region extending from the inferior border of the ischial tuberosity to the distal tip of the toes. The whole body was defined as the region extending from the shoulders to the distal tip of the toes. To minimize inter-observer variation, all scans and analyses were carried out by the same investigator, and the day-to-day coefficient of variations of his observations were 0.72% for BMD, 2.95% for LSTM and 6.98% for fat mass in the whole body.
Blood samples
Before all measurements, fasting (>12 h) blood samples were collected by venipuncture in EDTA-containing tubes, refrigerated immediately and centrifuged at 1500 r.p.m. for 30 min at 4 C within 2 h. Serum samples from each participant were stored frozen at -20 C. Estradiol was assessed by radioimmunoassay (Amersham Biosciences, Piscataway, NJ, USA). In postmenopausal women, menopausal status was confirmed by concentrations of estradiol less than 20 pg ml-1. In this study, estradiol concentrations were 11.4plusminus0.3 pg ml-1 (range of 10.0-17.0 pg ml-1) in MW and 11.8plusminus0.4 pg ml-1 (range of 10.0-16.0 pg ml-1; Table 1) in OW. Serum intact osteocalcin was measured with a sandwich enzyme immunoassay that uses polyclonal antibodies against 20 N-terminal residues (amino acids 1-20) and against seven C-terminal residues (amino acids 43-49; MBC, Tokyo, Japan). The inter- and intra-assay coefficient of variations for the estradiol and osteocalcin were <10%.
Ultrasound MTH and measurements
Muscle thickness determined by B-mode ultrasound was assessed at nine sites on the anterior and posterior surfaces of the body as described previously by Abe et al. (1994). The sites were lateral forearm, anterior and posterior upper arm, abdomen, subscapula, anterior and posterior thigh, and anterior and posterior lower leg. Ultrasonographic evaluation of MTH was performed using a real-time linear electronic scanner with a 5 MHz scanning head (SSD-500; Aloka, Tokyo, Japan). The scanning head with water-soluble transmission gel was placed perpendicular to the tissue interface at the marked sites and provided acoustic contact without depression of the skin surface. MTHs were measured directly from the screen with electronic callipers, and determined as a distance from the adipose tissue-muscle interface to the muscle-bone interface. Whole-body and regional SM mass were estimated using the equations of Sanada et al. (2006). MTHs were converted to mass units in kilograms by ultrasound-derived prediction equations using site-matched MTH times height, which were then used to calculate arm, trunk, thigh and lower leg SM mass. The reliability of image reconstruction and distance measurements were confirmed by comparing the ultrasonic and manual measurements of tissue thickness in human cadavers, and the coefficient of variation for the MTH measurements was 1% (Kawakami et al., 1993).
Measurement of fitness values
The peak oxygen uptake (VO2peak) was measured by an incremental cycle exercise test using a cycle ergometer (Monark, Varberg, Sweden). The subjects were encouraged during the ergometer test to exercise at the level of maximum intensity. Subjects breathed through a low-resistance two-way valve, and the expired air was collected in Douglas bags. Expired O2 and CO2 gas concentrations were measured by mass spectrometry (WSMR-1400; Westron, Chiba, Japan), and gas volume was determined using a dry gas metre (NDS-2A-T; Shinagawa Dev., Tokyo, Japan). The system of mass spectrometer was calibrated during every measurement by the standard reference gas. The highest value of VO2 during the exercise test was designated as VO2peak.
Leg extension power was measured with an isokinetic leg power system (Anaero Press 3500; Combi wellness, Tokyo, Japan) in the sitting position. Handgrip strength of the right upper limb was measured with a hand-held dynamometer, with the subject standing and arms extended by their side.
Statistical analysis
All measurements and calculated values are expressed as the meanplusminuss.e.m. We compared the mean values of general criteria, bone mineral indices, body composition values and fitness values among the three age groups using one-way analysis of variance with body mass index (BMI) adjusted for the covariate. In cases with a significant F-value, a post-hoc test using the Newman-Keuls method was used to identify significant differences among the mean values. Pearson's product correlations were calculated between LSTM, SM mass or fitness values and bone mineral indices. The alpha level for testing significance was set at P<0.05. All statistical analyses were performed using Stat View v5.0 for Windows (SYS Institute).
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