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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

The aim was to study the association between bone microarchitecture and muscle mass and strength in older men. Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed in 810 men aged ≥60 years at the distal radius by high-resolution peripheral computed tomography (HR-pQCT). Areal bone mineral density (aBMD) and appendicular muscle mass (ASM) were assessed by dual-energy X-ray absorptiometry (DXA). Relative ASM of the upper limbs (RASM-u.l.) was calculated as ASM of the upper limbs/(height)2. Grip strength was measured by dynanometry. In multivariable models, men in the lowest RASM-u.l. quartile had lower cross-sectional area (CSA), cortical area (Ct.Ar), cortical thickness (Ct.Th), and trabecular area (Tb.Ar) at distal radius compared with men in the highest quartile. The trends remained significant after adjustment for grip strength. Men in the lowest quartile of the normalized grip strength (grip strength/[height]2) had lower aBMD, total vBMD, Ct.Ar, Ct.Th, Tb.vBMD, and Tb.N, and higher Tb.Sp and Tb.Sp.SD. The associations for Ct.Ar, total vBMD, Ct.Th, Tb.vBMD, and Tb.Sp remained significant after adjustment for RASM-u.l. In the models including RASM-u.l. and normalized grip strength, CSA and Tb.Ar were associated with RASM-u.l. but not with the strength. Lower Ct.Th, Tb.vBMD, and Tb.N were associated with lower grip strength but not with RASM-u.l. Lower Ct.Ar was associated with lower grip strength and with lower RASM-u.l. In conclusion, in older men, low RASM-u.l. and low grip strength are associated with poor cortical and trabecular microarchitecture partly independently of each other, after adjustment for confounders. © 2013 American Society for Bone and Mineral Research


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

Osteoporosis is characterized by low bone mass and microarchitectural deterioration that result in increased bone fragility. Several studies have shown that muscle mass and strength are positively associated with bone mass and size.1, 2 This relationship between muscle mass and bone mass may be direct (local), with skeletal structure adapting to mechanical loads exerted on the skeleton through muscles. It may also be indirect and depend on genetic, hormonal, environmental, and lifestyle factors that act on both bone and muscle.3

Appendicular skeletal muscle mass (ASM) decreases with age.4, 5 Because muscle mass depends on height, relative appendicular skeletal muscle mass index (RASM), ie, ASM/(body height)2, is used to account for differences in height.6 Lean mass, ASM, and RASM correlate positively with areal bone mineral density (aBMD) as measured by dual-energy X-ray absorptiometry (DXA).7, 8 However, one of the limitations of DXA is that it provides a two-dimensional areal view of a three-dimensional structure. By contrast, quantitative computed tomography (QCT) and peripheral QCT (pQCT) permit one to distinguish between cortical and trabecular compartments. In 677 male siblings aged 25 to 45 years, whole-body lean mass correlated positively with cortical area and thickness, and negatively with cortical density (all measured by pQCT) at the radius and tibia.9 In 317 men aged 20 to 97 years, RASM was positively correlated with bone area and cortical thickness of the femoral neck, distal tibia, and distal radius after adjustment for age and physical activity.10 In similar models, RASM correlated positively with trabecular number but negatively with trabecular thickness.

Muscle strength decreases with age, even to a greater degree than muscle mass.11 Grip strength was positively associated with both aBMD12–16 and volumetric BMD17–19 at the distal forearm but less consistently at other sites of measurement. Because muscle mass and strength are closely related in young adult individuals, it is difficult in this group to apportion the relative associations of bone microarchitecture with muscle mass and muscle strength. By contrast, during aging, age-related changes in muscle mass and strength may contribute differently to the age-related decrease in aBMD and deterioration of bone microarchitecture.

In this context, the aim of the current study was to investigate cross-sectionally the association of muscle mass and grip strength with bone microarchitecture at the distal radius in a cohort of community-dwelling men aged 60 years and older.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

Subjects

The STRAMBO study is a single-center prospective cohort study of skeletal fragility and its determinants in men.20 It is carried out as collaboration between INSERM (National Institute of Health and Medical Research) and MTRL (Mutuelle des Travailleurs de la Région Lyonnaise), a private health insurance company. Participants were recruited between 2006 and 2008 from the MTRL lists in Lyon. Invitation letters were sent to a randomly selected sample of men. The study was authorized by the local ethics committee and performed in agreement with the Helsinki Declaration of 1975 and 1983. All men able to give informed consent, to complete the questionnaire, and to participate in the diagnostic exams were included. No specific exclusion criteria were used. The current analysis was performed in 810 men aged ≥60 years.

Dual-energy X-ray absorptiometry

Body composition and aBMD of the nondominant distal radius were estimated by DXA (Hologic Discovery A, Hologic Inc., Bedford, MA, USA). Its long-term stability was assessed by daily measurements of the Hologic lumbar spine phantom. The long-term coefficient of variation (CV) was 0.35%. The body composition software provides values for the masses of lean soft tissue and fat for the whole body and specific regions. The arms were isolated from the trunk using DXA regional computer-generated lines with manual adjustment. They were defined as the soft tissue extending from the center of the arm socket to the phalange tips. Relative appendicular skeletal muscle mass index of the upper limbs (RASM-u.l.) was calculated as the sum of arm skeletal muscle mass of both arms divided by (body height)2.

Grip strength

Grip strength was measured three times by a hand dynamometer (Martin Vigorimeter, Martin Gebrüder GmBH & Co, Tuttlingen, Germany) at the dominant hand. The grip strength normalized for body height was calculated as the mean of these three measures divided by (body height)2.

Bone mass measurement and estimates of structural geometry

Cross-sectional area (CSA), total volumetric BMD (Tt.vBMD), and bone microarchitecture were assessed by high-resolution peripheral computed tomography (HR-pQCT, XtremeCT; Scanco Medical AG, Brüttisellen, Switzerland) at the nondominant distal radius. A scout view was used to define the volume of interest (VOI).20, 21 A stack of 110 CT slices with a nominal voxel size of 82 µm was obtained with the most distal CT slice placed 9.5 mm proximal to the endplate of the radius. CV of a phantom containing HA rods embedded in resin (QRM, Moehrendorf, Germany) was 0.7% to 1.5%. VOI was automatically separated into a cortical area (Ct.Ar) and trabecular area (Tb.Ar). Cortical thickness (Ct.Th) was defined as the cortical volume divided by the outer bone surface. Trabecular (Tb.vBMD) and cortical vBMD (Ct.vBMD) corresponded to the average vBMD in the respective VOIs. Trabecular bone volume fraction (BV/TV, %) was derived from Tb.vBMD, assuming that fully mineralized bone has a density of 1.2 g HA/cm3. Trabecular elements were identified by the mid-axis transformation method. Trabecular number (Tb.N, mm−1) was defined as the inverse of the mean spacing of mid-axes. Trabecular thickness (Tb.Th, µm) and separation (Tb.Sp, µm) were derived from BV/TV and Tb.N. Intra-individual distribution of Tb.Sp (Tb.Sp.SD, µm) reflects heterogeneity of trabecular network and is quantified using the standard deviation of the distance between the mid-axes. Sixty-five scans of the distal radius (8%) were excluded because of poor quality (movement and/or nonuniform contour of the cortical bone).

Epidemiological questionnaire

Men replied to an interviewer-administered questionnaire covering self-reported lifestyle factors and health status. Smoking was assessed as current smoker versus nonsmoker. Alcohol intake was calculated as average amount of alcohol consumed weekly. Current and former leisure physical activity was calculated as the amount of time spent on walking, gardening, and participating in leisure sport activity including seasonal activities. The amount of time spent in current physical activity and the amount of time spent in former physical activity were added. Preliminary analyses provided evidence in support of separating physical activities according to the loaded bone (eg, radius in tennis) and the intensity (high or not). A “high” physical activity implies that the participant had practiced a sport for ≥1 year at a competition level. Occupational physical activity was self-reported and classified as weak, average, high, or very high. Comorbidities (diabetes, ischemic heart disease, history of stroke, Parkinson's disease) were self-reported, classified as present or absent and not further ascertained.

Biochemical measurements

Testosterone was measured by tritiated radioimmunologic assay (RIA) with diethylether extraction.22 Detection limit was 0.06 nmol/l.22 Interassay CV was 8% for 6 nmol/l. Serum 17β-estradiol (17β-E2) was measured using ultrasensitive RIA (Cis Bio International, Gif sur Yvette, France) with a detection limit of 5 pmol/l, intra-assay CV of 18%, and interassay CV of 5.7%.23 Sex hormone-binding globulin (SHBG) was measured by RIA with an intra- and interassay CV of 3.8% and 4.6% (Cis Bio International).22 Apparent free testosterone concentration (AFTC) and bioavailable 17β-E2 (bio-17β-E2) were calculated as previously described.24 Serum parathyroid hormone (PTH) was measured using a human specific two-site immunochimiluminescence assay (ELECSYS; Roche, Indianapolis, IN, USA).23 Detection limit was 3 pg/mL. Intra- and interassay CVs were <5%. Serum 25-hydroxycholecalciferol (25OHD) was measured by RIA (DiaSorin, Stillwater, MN, USA) after acetonitril extraction.25 Detection limit was 3 ng/mL. Intra-assay CV was 5% to 7% for 10 to 50 ng/mL. Interassay CVs were 9% to 11%.

Statistical methods

All calculations were performed using SAS 9.1 software (SAS Institute Inc., Cary, NC, USA). Tb.Sp and Tb.Sp.SD had skewed distribution and were log-transformed. Simple correlations were calculated using the Pearson's correlation coefficient. Comparisons between quartiles of RASM-u.l. or normalized grip strength were performed by ANOVA followed by post hoc analyses for continuous variables, and chi-square test or Fisher's exact test was used for class variables. Association of groups of RASM-u.l. and/or grip strength with bone parameters was assessed using ANCOVA followed by post hoc analyses. The initial variables in models were age, body mass index (BMI), height, smoking, alcohol intake, calcium intake, AFTC, bio-17β-E2, PTH, and 25OHD (continuous), leisure and occupational physical activity, and comorbidities (categorical) and interactions between these variables. Covariables were selected by stepwise backward analyses. Variables with p < 0.15 in multivariable analyses and interactions significant for at least one bone parameter were retained in the final model: age, BMI, height, smoking, occupational and leisure physical activity, diabetes mellitus, Parkinson's disease, bio-17β-E2, AFTC, PTH, calcium intake, and PTH and calcium intake interaction. The same variables were retained by the backward selection for the analyses according to the quartiles of grip strength and according to the groups defined using the medians of RASM-u.l. and of the grip strength. The same variables were used to adjust partial correlation coefficients and multiple linear regression relating RASM-u.l. and bone parameters.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

RASM of the upper limbs

Lean mass of the upper limbs was correlated with height (r = 0.55, p < 0.001), whereas RASM-u.l. was not (r = 0.03, p = 0.36). Men in the lowest quartile of RASM-u.l. (<2.33 kg/m2) were older; had lower fat body mass, grip strength, and bio-17β-E2 levels; and reported less leisure physical activity than men in the highest quartile (≥2.73 kg/m2) (Table 1).

Table 1. Unadjusted Clinical Characteristics According to the Quartiles of Relative Appendicular Skeletal Muscle Mass of the Upper Limbs (RASM-u.l.)
 QIQIIQIIIQIVp Value
<2.33 kg/m2 (n = 198)2.33–2.52 kg/m2 (n = 200)2.52–2.73 kg/m2 (n = 206)≥2.73 kg/m2 (n = 206)
  • Norm. = normalized; PA = physical activity; AFTC = apparent free testosterone concentration; Bio-17β-E2 = bioavailable 17β − estradiol, 25OHD = 25-hydroxyvitamin D; PTH = parathyroid hormone.

  • a

    p < 0.001 versus the fourth (highest) quartile assessed by post hoc analysis after ANOVA.

  • b

    p < 0.005 versus the fourth (highest) quartile assessed by post hoc analysis after ANOVA.

  • c

    p < 0.05 versus the fourth (highest) quartile assessed by post hoc analysis after ANOVA.

    dMedian [QI; QIII], Kruskall-Wallis test.

Age (years)74.7 ± 7.3a72.9 ± 7.0b70.9 ± 7.370.4 ± 6.6<0.001
Body mass index (kg/m2)25.2 ± 3.0a26.9 ± 2.7a28.0 ± 2.8a30.4 ± 3.6<0.001
Body height (cm)168 ± 6168 ± 6169 ± 6168 ± 60.25
Body weight (kg)71 ± 10a76 ± 9a80 ± 9a86 ± 11<0.001
Fat body mass (kg)17.9 ± 5.7a19.7 ± 5.8b19.9 ± 5.8b21.8 ± 6.7<0.001
Grip strength (kPa)62.8 ± 15.7a69.7 ± 16.9c71.1 ± 15.373.7 ± 17.3<0.001
Norm. grip strength (kPa/m2)22.3 ± 5.1a24.5 ± 5.4c24.8 ± 5.026.0 ± 5.8<0.001
Current smokers (n, %)11 (6%)10 (5%)21 (10%)5 (3%)<0.01
Alcohol intake (g/week)7 [1; 15]7 [2; 15]8 [1; 15]8 [1; 15]0.30
Calcium intake (mg/d)756 ± 239734 ± 231788 ± 252778 ± 2460.12
Leisure PA: radius (high)16 (8%)27 (14%)42 (20%)43 (21%)<0.001
Occupational PA
 Weak46 (23%)49 (24%)46 (22%)32 (15%)0.08
 Average53 (27%)63 (32%)69 (33%)53 (26%) 
 High62 (31%)47 (23%)51 (25%)68 (33%) 
 Very high37 (19%)41 (21%)40 (20%)53 (26%) 
Diabetes mellitus (n, %)17 (9%)29 (15%)26 (13%)33 (16%)0.14
Ischemic heart disease (n, %)35 (18%)32 (16%)34 (16%)28 (14%)0.72
History of stroke (n, %)10 (5%)10 (5%)5 (2%)7 (3%)0.43
Parkinson's disease (n, %)4 (2%)4 (2%)2 (1%)5 (2%)0.72
AFTC (pmol/L)237 ± 97239 ± 86247 ± 91245 ± 940.66
Bio-17β-E2 (pmol/L)34.1 ± 14.3a37.5 ± 15.238.8 ± 16.040.3 ± 14.6<0.001
25OHD (ng/mL)20.6 ± 10.321.8 ± 9.523.0 ± 10.822.7 ± 9.10.07
PTH (pg/mL)51.1 ± 29.9c50.5 ± 22.0c49.6 ± 26.044.1 ± 21.1<0.05

After adjustment for confounders, men in the lowest RASM-u.l. quartile had lower aBMD at the distal forearm compared with the highest quartile (Table 2). Areal BMD increased across the quartiles (p < 0.001 for trend).

Table 2. Analysis of Covariance Between Bone Microarchitecture Parameters and Quartiles of RASM-u.l.
 QI (<2.33 kg/m2)QII (2.33–2.52 kg/m2)QIII (2.52–2.73 kg/m2)QIV (≥2.73 kg/m2)p Value
  • Total CSA = total cross-sectional area; total vBMD = total volumetric bone mineral density (vBMD); Ct.Ar = cortical area; Ct.vBMD = cortical vBMD; Ct.Th = cortical thickness; Tb.Ar = trabecular area; Tb.vBMD = trabecular vBMD; Tb.N = trabecular number; Tb.Th = trabecular thickness; Tb.Sp = trabecular spacing; Tb.Sp.SD = trabecular distribution.

  • Results are presented as adjusted means ± SD. Models were adjusted for age, body mass index, height, smoking, leisure and occupational physical activity, diabetes mellitus, Parkinson's disease, bioavailable 17β-estradiol, apparent free testosterone concentration, parathyroid hormone (PTH), calcium intake, and PTH and calcium intake interaction.

  • a

    p < 0.001 versus the fourth (highest) quartile assessed by post hoc analysis after ANCOVA.

  • b

    p < 0.01 versus the fourth (highest) quartile assessed by post hoc analysis after ANCOVA.

  • c

    p < 0.005 versus the fourth (highest) quartile assessed by post hoc analysis after ANCOVA.

  • d

    p < 0.05 versus the fourth (highest) quartile assessed by post hoc analysis after ANCOVA.

  • e

    Comparisons were obtained on log-transformed variable; nonadjusted medians [1st quartile; 3rd quartile] are given.

Areal BMD (g/cm2)(n = 196)(n = 200)(n = 199)(n = 199) 
 One-third distal radius0.747 ± 0.078a0.755 ± 0.070a0.759 ± 0.076a0.786 ± 0.074<0.001
 Middle distal radius0.620 ± 0.079a0.628 ± 0.075a0.636 ± 0.074b0.658 ± 0.070<0.001
 Ultradistal radius0.442 ± 0.073a0.451 ± 0.073c0.458 ± 0.072d0.475 ± 0.067<0.001
 Total distal radius0.597 ± 0.074a0.605 ± 0.069a0.612 ± 0.070b0.634 ± 0.066<0.001
Distal radius(n = 185)(n = 191)(n = 188)(n = 181) 
 CSA (cm2)3.63 ± 0.57a3.88 ± 0.60c4.03 ± 0.664.10 ± 0.65<0.001
 Total vBMD (mg/cm3)290 ± 63286 ± 66288 ± 65299 ± 600.26
 Ct.Ar (mm2)56.6 ± 16.4a56.4 ± 17.1a59.8 ± 17.2d64.3 ± 17.4<0.001
 Ct.vBMD (mg/cm3)805 ± 77791 ± 74797 ± 71803 ± 640.14
 Ct.Th (µm)665 ± 205d684 ± 234690 ± 228730 ± 219<0.05
 Tb.Ar (cm2)2.96 ± 0.58a3.19 ± 0.643.31 ± 0.703.34 ± 0.67<0.001
 Tb.vBMD (mg/cm3)168 ± 42171 ± 41171 ± 37178 ± 370.23
 Tb.N (mm−1)1.80 ± 0.281.84 ± 0.261.83 ± 0.241.89 ± 0.240.09
 Tb.Th (µm)77 ± 1376 ± 1278 ± 1278 ± 110.62
 Tb.Spe (µm)489 [436; 553]474 [420; 522]464 [418; 512]443 [395; 488]0.10
 Tb.Sp.SDe (µm)211 [183; 249]202 [172; 235]200 [172; 232]186 [162; 217]0.26

In the adjusted models, men in the lowest RASM-u.l. quartile had lower CSA, Ct.Ar, Ct.Th, and Tb.Ar of the distal radius compared with the highest quartile. Men in the second RASM-u.l. quartile had lower CSA and Ct.Ar too. CSA, Ct.Ar, and Tb.Ar increased across the RASM-u.l. quartiles (p < 0.001 for trend). After adjustment for the normalized grip strength, the differences and trends across the RASM-u.l. quartiles remained significant (p < 0.001) for CSA, Ct.Ar, and Tb.Ar.

Grip strength

Grip strength was strongly correlated with height (r = 0.38, p < 0.001), whereas grip strength normalized by (height)2 was correlated with height only weakly (r = 0.08, p = 0.05). Men in the lowest quartile of normalized grip strength (<20.5 kPa/m2) were older and slightly shorter than men in the highest one (>28.3 kPa/m2). They also had higher fat mass and PTH level but lower RASM-u.l. and lower serum levels of AFTC, bio-17β-E2, and 25OHD (Table 3). They reported lower leisure and occupational physical activity and more comorbidities.

Table 3. Unadjusted Comparisons of Clinical Characteristics for Quartiles of Grip Strength Normalized by (Height)2
 QIQIIQIIIQIVp Value
<20.5 kPa/m2 (n = 202)20.5–24.0 kPa/m2 (n = 204)24.0–28.3 kPa/m2 (n = 203)≥28.3 kPa/m2 (n = 201)
  • PA = physical activity; AFTC = apparent free testosterone concentration; Bio-17β-E2 = bioavailable 17β − estradiol; 25OHD = 25-hydroxyvitamin D; PTH = parathyroid hormone.

  • a

    p < 0.001 versus the fourth (highest) quartile assessed by post hoc analysis after ANOVA.

  • b

    p < 0.05 versus the fourth (highest) quartile assessed by post hoc analysis after ANOVA.

  • c

    p < 0.01 versus the fourth (highest) quartile assessed by post hoc analysis after ANOVA.

  • d

    p < 0.005 versus the fourth (highest) quartile assessed by post hoc analysis after ANOVA.

  • e

    Median [QI; QIII], Kruskall-Wallis test.

Age (years)77.0 ± 6.6a73.4 ± 7.0a70.7 ± 6.3a67.8 ± 5.7<0.001
Body mass index (kg/m2)27.6 ± 3.728.0 ± 3.927.6 ± 3.427.5 ± 3.40.58
Body height (cm)167 ± 7b168 ± 6169 ± 6169 ± 6<0.05
Body weight (kg)78 ± 1278 ± 1279 ± 1179 ± 100.10
Fat body mass (kg)20.4 ± 6.4b20.4 ± 6.2b19.6 ± 6.218.9 ± 5.8<0.05
RASM-u.l. (kg/m2)2.43 ± 0.30a2.54 ± 0.32a2.56 ± 0.26c2.65 ± 0.31<0.001
Current smokers (n, %)6 (3%)18 (9%)10 (5%)13 (6%)0.09
Alcohol intake (g/week)e7 [0; 15]7 [1; 15]7 [2; 15]7 [2; 15]0.15
Calcium intake (mg/d)775 ± 244743 ± 232756 ± 250790 ± 2470.23
Leisure PA: radius (high)15 (8%)36 (18%)35 (17%)42 (21%)<0.01
Occupational PA
 Weak32 (16%)33 (16%)56 (28%)52 (26%)<0.001
 Average46 (22%)61 (30%)70 (34%)62 (31%) 
 High69 (35%)63 (31%)40 (20%)55 (27%) 
 Very high55 (27%)47 (23%)37 (18%)32 (16%) 
Diabetes mellitus (n, %)39 (19%)32 (16%)22 (11%)13 (6%)<0.001
Ischemic heart disease (n, %)45 (22%)39 (19%)30 (15%)15 (7%)<0.001
History of stroke (n, %)9 (4%)12 (6%)7 (3%)4 (2%)0.22
Parkinson's disease (n, %)10 (5%)3 (2%)2 (1%)0 (0%)<0.005
AFTC (pmol/L)221 ± 92a238 ± 104d243 ± 79b266 ± 89<0.001
Bio-17β-E2 (pmol/L)36.1 ± 16.0b36.6 ± 14.9d37.0 ± 14.9c41.7 ± 14.9<0.001
25OHD (ng/mL)20.4 ± 9.2a21.9 ± 10.6b21.8 ± 9.3b24.3 ± 9.8<0.001
PTH (pg/mL)54.6 ± 32.7a49.8 ± 26.646.6 ± 18.444.1 ± 18.3<0.001

After adjustement for confounders, men in the lowest normalized grip strength quartile had lower aBMD at the distal radius versus men in the highest quartile (Table 4). In the adjusted models, men in the lowest grip strength quartile had lower total vBMD at the distal radius versus the highest quartile. They also had lower Ct.Ar, Ct.Th, Tb.vBMD, and Tb.N, and higher Tb.Sp and Tb.Sp.SD. Moreover, total vBMD, Ct.Ar, Ct.Th, Tb.vBMD, and Tb.N increased, whereas Tb.Sp and Tb.Sp.SD decreased across the increasing quartiles of the normalized grip strength (p < 0.005 to p < 0.001 for trend). After adjustment for RASM-u.l., the associations with the normalized grip strength remained significant for Ct.Ar (p < 0.01) and, more weakly (p < 0.05), for total vBMD, Ct.Th, Tb.vBMD, and Tb.Sp.

Table 4. Analysis of Covariance Between Bone Microarchitecture Parameters and Quartiles of Grip Strength Normalized by (Height)2
 QIQIIQIIIQIVp Value
<20.5 kPa/m220.5–24.0 kPa/m224.0–28.3 kPa/m2≥28.3 kPa/m2
  • Total CSA = total cross-sectional area; total vBMD = total volumetric bone mineral density (vBMD); Ct.Ar = cortical area; Ct.vBMD = cortical vBMD; Ct.Th = cortical thickness; Tb.Ar = trabecular area; Tb.vBMD = trabecular vBMD; Tb.N = trabecular number; Tb.Th = trabecular thickness; Tb.Sp = trabecular spacing; Tb.Sp.SD = trabecular distribution.

  • Results are presented as adjusted means ± SD. Models were adjusted for age, body mass index, height, smoking, leisure and occupational physical activity, diabetes mellitus, Parkinson's disease, bioavailable 17β-estradiol, apparent free testosterone concentration, parathyroid hormone (PTH), calcium intake, and PTH and calcium intake interaction.

  • a

    p < 0.001 versus the fourth (highest) quartile assessed by post hoc analysis after ANCOVA.

  • b

    p < 0.05 versus the fourth (highest) quartile assessed by post hoc analysis after ANCOVA.

  • c

    p < 0.005 versus the fourth (highest) quartile assessed by post hoc analysis after ANCOVA.

  • d

    p < 0.01 versus the fourth (highest) quartile assessed by post hoc analysis after ANCOVA.

  • e

    Comparisons were obtained on log-transformed variable; nonadjusted median [1st quartile; 3rd quartile] are given.

Areal BMD (g/cm2)(n =192)(n = 200)(n = 203)(n = 201) 
 One-third distal radius0.747 ± 0.078a0.752 ± 0.079a0.770 ± 0.0720.779 ± 0.066<0.001
 Middle distal radius0.623 ± 0.073a0.625 ± 0.079a0.644 ± 0.0710.652 ± 0.068<0.001
 Ultradistal radius0.445 ± 0.069a0.446 ± 0.075a0.459 ± 0.069b0.476 ± 0.073<0.001
 Total distal radius0.599 ± 0.069a0.602 ± 0.075a0.619 ± 0.0670.629 ± 0.065<0.001
Distal radius(n = 184)(n = 192)(n = 187)(n = 182) 
 Total CSA (cm2)3.87 ± 0.713.91 ± 0.603.91 ± 0.653.97 ± 0.580.51
 Total vBMD (mg/cm3)282 ± 57c283 ± 65b295 ± 64303 ± 62<0.01
 Ct.Ar (mm2)56.3 ± 15.7a56.9 ± 17.0a60.4 ± 17.463.3 ± 17.4<0.001
 Ct.vBMD (mg/cm3)792 ± 71792 ± 74803 ± 70807 ± 610.08
 Ct.Th (µm)661 ± 192d666 ± 219d705 ± 221734 ± 221<0.01
 Tb.Ar (cm2)3.18 ± 0.713.22 ± 0.633.19 ± 0.673.22 ± 0.580.89
 Tb.vBMD (mg/cm3)167 ± 40d168 ± 40b174 ± 38179 ± 39<0.05
 Tb.N (mm−1)1.81 ± 0.28b1.81 ± 0.27b1.86 ± 0.251.89 ± 0.24<0.05
 Tb.Th (µm)77 ± 1276 ± 1278 ± 1279 ± 120.27
 Tb.Spe (µm)485 [424; 542]d475 [427; 532]b460 [415; 506]446 [402; 490]<0.05
 Tb.Sp.SDe (µm)212 [180; 255]b204 [177; 245]199 [172; 226]188 [163; 215]<0.05

RASM of the upper limbs (RASM-u.l.), grip strength, and radial microarchitecture

RASM-u.l. and normalized grip strength were correlated positively (r = 0.25, p < 0.001) (Fig. 1). In partial correlations including grip strength or RASM-u.l., CSA and Tb.Ar of the radius correlated with RASM-u.l. (partial r2 = 4% to 7%) but not with normalized grip strength. Ct.Ar correlated with RASM-u.l. (partial r = 0.14, p < 0.001 adjusted for normalized grip strength) and with normalized grip strength (partial r = 0.13, p < 0.001 adjusted for RASM-u.l.). Ct.Th and Ct.vBMD correlated with normalized grip strength (partial r2 = 1%) but not with RASM-u.l. Tb.vBMD, Tb.N, and Tb.Sp correlated weakly with RASM-u.l. (partial r2 = 1% to 2%). These variables and Tb.Sp.SD also correlated weakly with normalized grip strength (partial r2 ≤ 1%).

thumbnail image

Figure 1. Correlation between relative appendicular skeletal muscle mass of the upper limbs (RASM-u.l.) and normalized grip strength in 810 men aged ≥60 years from the STRAMBO cohort.

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Age, BMI, height, smoking, leisure and occupational physical activity, Parkinson's disease, diabetes, AFTC, bio-17β-E2, as well as PTH, calcium intake, and their interaction explained jointly 11% to 28% of variability of aBMD and bone microarchitecture of distal radius (p < 0.001). Addition of RASM-u.l. increased total determination coefficient by 2% to 6% for aBMD, CSA, Tb.Ar, and Ct.Ar (all p < 0.001) and by 1% for Ct.Th, Tb.vBMD, Tb.N, and Tb.Sp (p < 0.005 to 0.001). Addition of the normalized grip strength (instead of RASM-u.l.) increased total determination coefficient by 2% for aBMD and Ct.Ar and by 1% for total vBMD, Ct.vBMD, Ct.Th, Tb.vBMD, Tb.N, Tb.Sp, and Tb.Sp.SD (p < 0.005 to 0.001). Then, RASM-u.l. and grip strength were assessed in one model with other confounders. Jointly, they increased total determination coefficient (versus the model including only the confounders) by 4% for aBMD and Ct.Ar (p < 0.001) and by 2% for Tb.vBMD, Tb.N, and Tb.Sp (p < 0.05). RASM-u.l. (but not normalized grip strength) increased total determination coefficients for CSA by 6% and for Tb.Ar by 4% (p < 0.001). Normalized grip strength (but not RASM-u.l.) increased total determination coefficients for total vBMD, Ct.vBMD, Ct.Th, and Tb.Sp.SD by 1% to 2% (p < 0.05 to 0.005).

Men who had both RASM-u.l. and normalized grip strength below the respective medians had 5% to 7% lower aBMD of distal radius and 14% lower Ct.Ar compared with the reference group (RASM-u.l. and normalized grip strength above the medians) (Table 5). Men who had either RASM-u.l. or normalized grip strength below the median had 3% lower aBMD and 8% lower Ct.Ar versus the reference group. Lower CSA and Tb.Ar were found in men with lower RASM-u.l. regardless of grip strength. Lower total vBMD, Ct.Th, and Tb.vBMD were found in men with lower normalized grip strength regardless of RASM-u.l. Men who had both RASM-u.l. and normalized grip strength below the medians had 4% lower Tb.N and higher Tb.Sp and Tb.Sp.SD versus the reference group. In all the above analyses, interaction between the normalized grip strength and RASM-u.l. was not significant for all the microarchitectural parameters.

Table 5. Analysis of Covariance of Bone Microarchitecture of the Distal Radius in Four Groups of Men Classified According to the Medians of the Normalized Relative Appendicular Muscle Mass of the Upper Limbs (2.52 kg/m2) and of the Normalized Grip Strength (24.0 kPa/m2)
 <2.52 kg/m2≥2.52 kg/m2<2.52 kg/m2≥2.52 kg/m2p Value
<24.0 kPa/m2<24.0 kPa/m2≥24.0 kPa/m2≥24.0 kPa/m2
  • Total CSA = total cross-sectional area; total vBMD = total volumetric bone mineral density (vBMD); Ct.Ar = cortical area; Ct.vBMD = cortical vBMD; Ct.Th = cortical thickness; Tb.Ar = trabecular area; Tb.vBMD = trabecular vBMD; Tb.N = trabecular number; Tb.Th = trabecular thickness; Tb.Sp = trabecular spacing; Tb.Sp.SD = trabecular distribution.

  • Results are presented as adjusted means ± SD. Models were adjusted for age, body mass index, height, smoking, leisure and occupational physical activity, diabetes mellitus, Parkinson's disease, bioavailable 17β-estradiol, apparent free testosterone concentration, parathyroid hormone (PTH), calcium intake, and PTH and calcium intake interaction.

  • a

    p < 0.001 versus the reference group (≥2.52 kg/m2 and ≥24.0 kPa/m2) assessed by post hoc analysis after ANCOVA.

  • b

    p < 0.01 versus the reference group (≥2.52 kg/m2 and ≥24.0 kPa/m2) assessed by post hoc analysis after ANCOVA.

  • c

    p < 0.05 versus the reference group (≥2.52 kg/m2 and ≥24.0 kPa/m2) assessed by post hoc analysis after ANCOVA.

  • d

    p < 0.005 versus the reference group (≥2.52 kg/m2 and ≥24.0 kPa/m2) assessed by post hoc analysis after ANCOVA.

  • e

    Comparisons were obtained on log-transformed variable; nonadjusted median [1st quartile; 3rd quartile] are given.

Areal BMD (g/cm2)(n = 234)(n = 166)(n = 172)(n = 222) 
 One-third distal radius0.745 ± 0.076a0.755 ± 0.081a0.763 ± 0.068b0.783 ± 0.069<0.001
 Middle distal radius0.617 ± 0.078a0.632 ± 0.072a0.638 ± 0.069c0.656 ± 0.069<0.001
 Ultradistal radius0.440 ± 0.070a0.452 ± 0.069d0.458 ± 0.074c0.474 ± 0.068<0.001
 Total distal radius0.594 ± 0.072a0.608 ± 0.069a0.613 ± 0.065c0.631 ± 0.065<0.001
Distal radius(n = 216)(n = 165)(n = 159)(n = 205) 
 Total CSA (cm2)3.78 ± 0.61a4.03 ± 0.693.79 ± 0.56a4.06 ± 0.62<0.001
 Total vBMD (mg/cm3)282 ± 62c283 ± 60c295 ± 64301 ± 62<0.01
 Ct.Ar (mm2)55.1 ± 15.9a58.7 ± 16.3b58.7 ± 16.9b64.1 ± 17.2<0.001
 Ct.vBMD (mg/cm3)791 ± 75794 ± 70805 ± 72804 ± 620.14
 Ct.Th (µm)656 ± 199d676 ± 214c698 ± 221736 ± 220<0.005
 Tb.Ar (cm2)3.10 ± 0.62b3.32 ± 0.723.09 ± 0.60d3.30 ± 0.65<0.001
 Tb.vBMD (mg/cm3)167 ± 42b167 ± 37c173 ± 40179 ± 37<0.05
 Tb.N (mm−1)1.81 ± 0.28c1.82 ± 0.271.86 ± 0.261.88 ± 0.22<0.05
 Tb.Th (µm)76 ± 1376 ± 1177 ± 1279 ± 120.14
 Tb.Spe (µm)492 [433; 548]c461 [419; 522]c466 [420; 523]449 [400; 488]<0.05
 Tb.Sp.SDe (µm)213 [183; 252]202 [171; 252]199 [170; 232]188 [165; 216]0.12

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

In this study, older men with low RASM-u.l. had lower aBMD, CSA, Ct.Ar, Ct.Th, and Tb.Ar at the distal radius. Lower normalized grip strength was associated with lower aBMD and poor microarchitecture at the distal radius. Bone size seems to correlate mainly with muscle mass, whereas bone microarchitecture correlates mainly with muscle strength.

RASM-u.l. and normalized grip strength correlated positively with aBMD of distal radius. In previous studies, higher muscle mass and strength correlated with higher aBMD regardless of age and sex.1, 2, 7, 8, 12–14, 18, 19 These associations were stronger for anatomically related sites of measurement (grip strength and distal radius, hip aBMD, and knee extension) and remained significant after adjustment for age, height, physical activity, and hormones.

Our results confirm previous data1, 9 showing a positive relation between RASM and bone size. CSA was 0.72 SD lower in the lowest RASM quartile compared with the highest quartile, whereas the difference in total vBMD between the extreme quartiles was nonsignificant. These findings suggest that the association between aBMD and muscle mass is determined mainly by the association of muscle mass with bone size, not density.

Muscle mass and strength are intercorrelated, but most studies do not apportion their relative contributions to investigated associations. In our models including muscle mass and strength, distal radius CSA and Tb.Ar correlated positively with RASM-u.l. but not grip strength. Our cross-sectional data do not permit us to infer mechanisms of this relation; however, we can speculate. Bone size, muscle mass, and strength increase in parallel during growth.26, 27 During aging, periosteal expansion continues, whereas muscle mass and strength decrease3, 4, 6, 28 Thus, the relation of RASM-u.l. with CSA and Tb.Ar may depend on growth-related and lifelong factors (genetics, hormones, nutrition, lifestyle). For instance, in teenaged boys, distal radius width correlated positively with protein intake and mother's distal radius width.29 In young men, physical activity correlated positively with CSA of distal radius and tibia.30 In older men, lean mass correlated positively with duration of former physical activity, whereas distal femur CSA correlated positively with an index combining duration and intensity of physical activity.31 These data strengthen mainly the role of long-term physical activity as the common determinant of muscle mass and bone size.

Data on hormones are not consistent. In older men, low testosterone levels correlated with RASM positively but negatively with CSA of bones.4, 32 Also in older men, serum insulin-like growth factor I level correlated positively with fat-free mass but not with bone width.33, 34 The major limitation in the interpretation of these data is that serum hormonal levels in older men may not reflect the hormonal secretion during growth. Thus, more direct studies of the determinants of the link between muscle mass and bone size are needed.

We found that low RASM-u.l. and low normalized grip strength were associated with low Ct.Th and Ct.Ar but not with Ct.vBMD. Previous data are inconsistent. In young men, lean body mass correlated positively with Ct.Ar and negatively with Ct.vBMD at the distal radius and tibia (both measured by pQCT).9 By contrast, in older men, grip strength correlated positively with Ct.vBMD at the distal radius and tibia measured by pQCT.19 Trabecular parameters did not differ across the quartiles of RASM-u.l. By contrast, lower grip strength correlated with lower Tb.vBMD and Tb.N but higher Tb.Sp.SD at the distal radius.

Our models including RASM-u.l. and normalized grip strength showed that CSA and Tb.Ar correlated mainly with RASM-u.l. By contrast, Ct.Th, Tb.vBMD, and Tb.N correlated mainly with normalized grip strength. Ct.Ar correlated positively with the normalized grip strength (what was explained by higher Ct.Th) and with RASM-u.l. (what was explained by greater CSA). The correlations of Tb.Th and Ct.vBMD with RASM-u.l. and grip strength were nonsignificant.

Our data show, in line with previous studies, that the independent contribution of RASM-u.l. and of the grip strength to the variability of bone microarchitecture is limited.9, 10 However, the multivariate models permit us to remove the effect of several confounders that can be common determinants of, on one hand, muscle mass and strength and, on the other hand, of bone size and microarchitecture. In addition, the correlation between these parameters may be artifactually weakened by the intrinsic errors in their measurement.

Interpretation of our data is limited by the cross-sectional design of the study. The associations may depend on genetic factors and factors acting during growth or young adulthood. Several studies support this possibility. Male mice with inactivated 5a-reductase type 1 had lower muscle strength, Tb.vBMD, and Ct.Th (not Ct.vBMD).35 In young men, higher physical activity correlated with higher Tb.vBMD and Ct.Th but not Ct.vBMD.30 Young athletes had higher Tb.N (not Tb.Th) at the distal femur and in bones adjacent to the knee joint than age- and body size-matched controls.36 In rat models of unloading, stimulated resistance training increased trabecular bone formation and Tb.Th.37 In this model, dynamic muscle stimulation increased Tb.N and trabecular connectivity at the femur.

Lifelong acting and aging-related factors may also contribute to these associations. Tobacco smoking was associated with lower muscle strength and poor trabecular microarchitecture.38, 39 In men, low testosterone levels are associated with lower RASM and strength and poor trabecular microarchitecture.4, 40, 41 Lower grip strength and lower Tb.vBMD were found in secondary hyperparathyroidism.42, 43 However, the trends we observed were significant after adjustment for physical activity, smoking, and hormonal levels. Overall, the available data do not allow us to establish whether any of the potential determinants of the associations between muscle parameters and bone microarchitecture act on bone through an effect on muscle or by independent effects on muscle and bone tissue.

We also recognize the following limitations. Because the men are clients of an insurance company, social groups with lower incomes may be underrepresented. Volunteers participating in a research study may be a healthier subset of the population. The cross-sectional design does not allow inferences on the cause and effect. Tb.Th, Tb.Sp, and Ct.Th are calculated by the software. Despite its high resolution, partial volume effects exist with HR-pQCT and may contribute to an erroneous estimation of Ct.Th and Ct.vBMD in men with low Ct.Th. In men with very thin trabeculae, Tb.N may be underestimated. HR-pQCT was performed at the nondominant arm, whereas grip strength was measured at the dominant arm. However, grip strength on both arms is strongly correlated.44 DXA-assessed RASM may be overestimated, mainly in the oldest men. Connective tissues and water increase with age and are included in the measures of lean mass. Comorbidities were self-reported.

In summary, in older men, low RASM-u.l. and low normalized grip strength are associated with impaired bone microarchitecture independently of each other. The associations were significant after adjustment for confounders including body size. These findings suggest different underlying mechanisms; however, we need prospective studies to clarify these relationships. In addition, low muscle mass and strength are risk factors for fall and fracture,45–47 whereas impaired bone microarchitecture was associated with fragility fractures.18, 19, 48–50 Thus, our data suggest that low muscle mass and strength contribute to the risk of fracture not only through the increased risk of falling but also through the impairment of bone microarchitecture and the consequent deterioration of bone strength. However, this speculation inferred from the cross-sectional analysis needs to be confirmed in a prospective study.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References

S Boonen is senior clinical investigator of the Fund for Scientific Research-Flanders, Belgium (FWO-Vlaanderen) and holder of the Leuven University Chair in Gerontology and Geriatrics.

This study is supported by grants from the Roche Pharmaceutical Company, Baselle, Switzerland, from Agence Nationale de la Recherche and from Hospices Civils de Lyon.

Authors' roles: PS designed and conducted the study, wrote the manuscript, and has primary responsibility for the final version of the manuscript. S Blaizot made the statistical analyses. S Boutroy and NV were responsible for the acquisition and quality control of the HR-pQCT data. PS and RC obtained funding for the study. PS, S Boonen, RC, and S Boutroy interpreted the results. All authors read and approved the manuscript.

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  6. Discussion
  7. Disclosures
  8. Acknowledgements
  9. References
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