1Department of Internal Medicine and Medical Disciplines, University of Rome “Sapienza”, Rome, 2Unit of Internal Medicine, Istituto di Ricovero e Cura a Carattere Scientifico “Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo, 3Department of Methods and Models for Economics, Territory and Finance, University of Rome “Sapienza”, Rome, Italy
OBJECTIVE: The aim of this work was to examine the effects of age and menopause on muscle strength and on the muscle-bone interaction. DESIGN: One hundred ninety-four healthy women (mean age 49.8 ± 12.6 SD years) were assessed. Maximal Voluntary Contraction (MVC, Newton, N) by Hand Grip Dynamometer, bone mineral density at one third of the radius (R-BMD) by dual-energy X-ray absorptiometry (DXA) and phalangeal ultrasound by the DBM Sonic 1200 device were evaluated at the upper dominant limb. Ultrasonometric parameters considered were Amplitude-Dependent Speed of Sound (ADSoS) and Ultrasound Bone Profile Index (UBPI). RESULTS: MVC significantly decreased with age (r2=-0.12, p<0.005). For each level of age, fertile women had a greater MVC compared to postmenopausal women (r2=0.015, p<0.005).In the whole sample, a statistically significant correlation between MVC and R-BMD (r=0.354, p<0.001) and between MVC and ADSoS (r=0.294) and UBPI (r=0.311)(p<0.001 for both) were observed. CONCLUSIONS: We conclude that age and menopausal status significantly contributed to the reduction of muscle strength. The decline of muscular strength significantly correlated with quantitative and qualitative bone features.
Age, Bone, Menopause, Muscle, Strength
INTRODUCTION
Muscle strength plays a widely recognized key role in overall functional status, particularly in the elderly.1,2 Skeletal muscle impairment is closely associated with a decline of daily activities, increased risk of institutionalization, cognitive decline and accelerated mortality.1-3 Several important factors may affect muscle strength, including age, BMI, gonadal status, level of physical activity and nutritional factors.4-6 Age-related muscle loss occurs at an earlier time in women compared to men because of ensuing changes in hormonal status in menopause.7,8 In fact, however, though the age-related decline of muscle strength has been partly associated with the decreased estrogen levels of postmenopausal women,8 the effect of menopause and aging have not been clearly described in previous studies.8,9
To simply and accurately measure muscle strength, isometric strength has frequently been assessed, since it correlates with the force-producing capabilities of muscles.10 In particular, it has been demonstrated that handgrip strength is positively related to lower and upper muscular strength so that it is considered a surrogate measure of overall muscular strength.1,11,12 Accordingly, an increase in handgrip strength has been linked to an increased lean body mass; moreover, handgrip strength is considered a predictor of all-cause mortality among elderly people.1
Muscle mass and strength also exert an important impact on bone strength.13 The relationship between bone mineral density (BMD), lean mass and muscle strength has been widely described, and age-related bone loss has been associated with a decrease in muscle mass and function.14,15 Furthermore, several studies showed that muscle load exerts a positive influence on bone independent of body weight, which accounts for the well-known beneficial effect of physical activity on skeletal tissue.13-16 Some authors also suggested a regional effect of muscular strength on BMD. Blain et al. reported a site-specific effect of muscular strength of quadriceps on bone remodeling at the femoral neck in a group of healthy postmenopausal women,17 and Di Monaco et al. found a positive correlation between distal radius BMD and handgrip strength among postmenopausal women.18 Moreover, a correlation between handgrip strength, BMD and fractures has frequently been reported.14,15,19 However, to our knowledge, there are no data focusing on the relationship between muscle strength and skeletal tissue, both evaluated at specific sites in pre- and postmenopausal women.
The aim of this study was to evaluate changes of muscle strength of the upper dominant limb with respect to age and gonadal status in a large sample of healthy women. Muscle strength assessed via BMD at forearm and by phalangeal quantitative ultrasound, was also studied in order to assess the possible influence of muscle function on quantitative and qualitative parameters of skeletal tissue.
SUBJECTS AND METHODOLOGY
One hundred ninety-four healthy volunteers from the female personnel of our Hospital were studied. None of the women took drugs which interfere with bone metabolism, or was on hormone replacement therapy, or was engaged in resistance training activities, or was a current smoker. Postmenopausal status was defined as the absence of menses for more than 12 months.
We evaluated isometric grip strength of the upper dominant limb using a hand held dynamometer in all subjects (Hand Grip Dynamometer). This instrument is part of the experimental Facility “Hand Posture Analyzer”, a payload composed by a set of instruments designed and developed by Kayser Italia s.r.l. under ASI (Italian Space Agency) contract. The fact that the test is easy to perform and is completed in about five minutes allows us to routinely use the instrument in clinical practice in every age group. The “Hand Posture Analyzer” Facility consists of Hand Grip Dynamometer and Pinch Force Dynamometer tools, which are isometric dynamometers designed and manufactured respectively for best handgrip and pinch force application. Hand Grip Dynamometer and Pinch Force Dynamometer force ranges are respectively 40 – 1000 Newton and 0 – 270 Newton with a measurement accuracy of 0.75% of the full scale. Maximal voluntary contraction (MVC, Newton, N) force was measured in the sitting position in each subject. The short-term imprecision for MVC was calculated on 14 normal subjects measured 5 times each and was <5%.
BMD was measured by dual-energy X-ray absorptiometry (Hologic QDR 4500A, Hologic Inc., USA) at one third of the radius of the upper dominant limb (R). Quantitative ultrasound of the proximal phalanges was assessed using the DBM Sonic 1200 device (IGEA, Carpi, Italy) at the distal metaphysis of the last four fingers of the dominant hand. Ultrasonometric parameters considered were speed of propagation of ultrasound dependent on the amplitude of the ultrasound wave crossing bone tissue (Amplitude-Dependent Speed of Sound, ADSoS) and a parameter calculated by computer analysis of dynamic parameters of ultrasound signal (Ultrasound Bone Profile Index, UBPI). The short-term precision of ultrasonometric parameters was calculated on ten normal subjects measured five times each. The CVs for the single parameters were 0.63% for ADSoS and 2.1% for UBPI.20
Statistical analysis
Results are presented as mean values ± SD. The sample was subdivided according to gonadal status and, after normality testing, comparison between MVC in premenopausal and in postmenopausal women was performed by unpaired t-test. We used a linear and quadratic regression models and broken-line regression models to determinate the relative effect of age and menopause on muscle strength. In particular, the broken-line regression models may explain different linear relationships between the response variables and the covariates before and after unknown change points. All statistical analyses were performed in statistical software R (www.r-project.org). To investigate correlations between MVC, densitometric and ultrasonometric parameters we used the Spearman correlation coefficient. Significance was set at p value <0.05.
RESULTS
Table 1 depicts the mean values±SD of demographic characteristics and of the parameters studied. Out of 194 women, 92 were pre- and 102 postmenopausal; mean age±SD, 49.8 ± 12.6 years, range 21-82 yrs; BMI 24.1 ± 3.8 kg/m2. As shown, mean values of R-BMD, ADSoS, UBPI and MVC were significantly higher in premenopausal than in postmenopausal women (p<0.001 for all).
Figure 1A, depicts the relationship obtained by fitting a quadratic regression model between MVC and age and adjusting for the menopause variable. The estimated equation is: MVC = 116.69 + 4.89 × age – 0.05 × age2 – 26.64 × menopause. This model indicates that, for each level of age, fertile women had a greater MVC value than postmenopausal women. The r2 index was 0.015 and all the terms are significant (p<0.005 for linear term; p<0.005 for quadratic term; p<0.05 for menopause). This model fitted the data significantly better than the previous one (p<0.05).
Figure 1. A: Relationship between MVC and age in the whole sample (n=194) by adding the menopause variable. The estimated equation is MVC = 116.69 + 4.89 x age – 0.05 x age2 – 26.64 x menopause. B: Estimated split point in the correlation between MVC and age in the whole sample (n=194). MVC values significantly increases up to the age of 40.08 (s.e. 3.9 yrs), which represents the estimated split point.
Figure 1B depicts the relationship obtained by fitting a broken-line regression model between MVC and age. The model shows a statistically significant increase in MVC values up to the age of 40.08 (s.e. 3.9 yrs), which represents the estimated split point. With this model MVC increased at the rate of 2.388 N for years before the split point (p=0.1) and it decreased at the faster rate of 4.72 N for year after the split point (p<0.01). The r2 value was 0.14.
Table 2 depicts the statistically significant correlations between MVC and R-BMD (r=0.354, p<0.001) and MVC and ultrasonometric parameters (ADSoS r = 0.294; UBPI r = 0.311, p<0.001 for both) in the whole sample. These correlations were significant only in postmenopausal women group (MVC vs R-BMD r = 0.354 p<0.001; vs ADSoS r = 0.307; vs UBPI r = 0.319, p<0.01 for all). By contrast, handgrip strength values did not correlate with both densitometric and ultrasonometric parameters in the premenopausal group. As far as BMI is concerned, we found no significant correlation with MVC values, both in the whole sample and in the groups of pre- and postmenopausal women, separately considered (data not shown).
DISCUSSION
In this work we have investigated the relative influence of age and hormonal status on muscle strength of the upper dominant limb in a large sample of healthy women, as well as the correlation between muscle strength and quantitative and qualitative features of skeletal tissue. We have found that handgrip strength was strongly associated with age, with a trend that showed a significant increase of muscle strength up to the age of 40 years. Subsequently, muscle strength progressively and significantly decreased (Figures 1). Our results are in line with those of Lauretani et al who found a significant relationship between age and handgrip strength and suggested that isometric muscle strength and muscle power considerably decline with age.21 Previous studies reported a peak of muscle mass between the second and the fourth decade of life, with a subsequent steady decrease with aging of approximately 1% per year.9,21,22 Indeed, we observed a rapid decline of muscle strength after the age of 40 at the rate of 4.72 N per year (Figure 2).
The decline of muscle strength with age can be ascribed to the well-known decrease in muscle mass and quality, commonly defined as age-related sarcopenia.12 Sarcopenia is a common feature among elderly people, the prevalence of which ranges from 13% to 24% in persons aged over 60 years to more than 50% in those 80 yrs and older.24 Sarcopenia is also associated with several adverse outcomes, such as many chronic disorders, physical disability, poor quality of life and increased mortality.12,25 Several mechanisms contribute to age-related sarcopenia, such as decreased physical activity and nutritional intake, oxidative stress, inflammatory insults and hormonal changes.26 Among other factors, sex steroids are of huge importance for skeletal muscle health. Several studies reported a fast rate of loss in muscle mass and strength during perimenopausal years,23 the age-related changes in gonadal status significantly influencing the development and progression of sarcopenia and functional decline in the elderly.12 In this context, our data demonstrate that the mean level of MVC in premenopausal women was significantly higher than in postmenopausal women and that, at every age, postmenopausal women had a MVC value lower than the fertile ones (Figure 2). However, data on this matter are still conflicting and the effect of menopause on muscle strength has not been well established.8 Some authors reported that the relative contribution of menopause as compared to that of age on muscle loss remains
We have found that muscle strength was strongly associated with several quantitative and qualitative parameters of bone condition. As shown in Table 2, radial BMD and all ultrasonometric indices were significantly associated with MVC in all subjects (p<0.001) and also in postmenopausal women (p<0.001 and p<0.01, respectively). These findings are in line with previous studies reporting a positive correlation between BMD and muscle strength at both upper and lower limbs. A significant positive correlation between distal radius BMD and handgrip strength, the latter being the strongest independent predictor of radial BMD, was shown by Di Monaco et al. in postmenopausal women.18 Frank et al. reported that isometric, concentric and eccentric handgrip torques significantly contribute to the prediction of bone strength, evaluated by radial peripheral quantitative computed tomography, in postmenopausal women with forearm BMD T-score above the osteoporotic threshold.28 Blain et al. reported a significant influence of quadriceps strength on femoral neck BMD, but not on lumbar spine BMD variance, in a group of healthy women aged more than 60 years, suggesting the hypothesis of a regional effect of muscle forces on BMD.17 Our results further support the hypothesis of a site-specific effect of muscle strength: forces arising from muscular loading and contraction not only influenced BMD but also bone quality and microarchitecture, at least in postmenopausal women.14,17,29-32 Quantitative ultrasound is a validated technique in acquiring information about qualitative and structural features of bone and in identifying individuals at risk for fractures.20 To our knowledge, this is the first study evaluating the relationship between handgrip strength and qualitative features of bone, both assessed at the upper dominant limb. In adjunct, whilst previous studies chiefly focused on postmenopausal women, we investigated a large sample of both pre- and postmenopausal women. This is a major strength of our research, since it allowed us to effectively compare the effects of both age and menopausal status on muscle strength and the relationship between muscle strength and bone in women.
Hence, the influence of muscle strength on skeletal health seems to depend on gonadal status, since handgrip strength was significantly associated with BMD and ultrasonometric parameters in the whole sample, but not in premenopausal women. Our findings did not show any significant correlations between bone mass and quality on the one hand and muscle strength on the other in hormonally replete adults; on the contrary, the effect of muscle force on bone turned out to be significant only when the anabolic effects of estrogens on the skeleton was missing.
Our observation could partly be explained in the light of the previously reported low correlation between muscle strength and BMD in young and active individuals.33 Even in athletes, once the peak bone mass is reached, the further increase in muscle strength does not result in a further rise in bone mass.33 A possible influence of other factors, such as vitamin D status, can also be hypothesized. In this regard, the absence of data about estrogen and vitamin D serum levels also represents a limitation of our study.
The results we obtained have relevant clinical implications, since the loss of muscle strength with aging is associated with an increase in body sway, a greater risk of falls and fractures, increased disability and decreased survival rates following critical illness.24 Moreover, isometric handgrip strength has been correlated with bone mass and the risk of fracture, as well as with the functional decline, grade of disability and mortality risk in the elderly.1,12,14,15,19,21 We would therefore suggest that a clinical evaluation of muscle strength could be a useful additional tool in the overall evaluation of functional status and could valuably integrate any algorithm aimed to evaluate fracture risk in postmenopausal women. An important limitation is the fact that the cross-sectional design of our study does not allow us to draw firm conclusions on long-term change in muscle strength and its correlation with changes of bone mineral density and quality. Nevertheless, our results also suggest that physical training should be strongly recommended to ameliorate muscle strength and balance, to reduce fracture risk and to improve the overall functional status in postmenopausal women.15,18,34,35 Though the optimal type and regimen of physical exercise is still debated, a recent meta-analysis reported that in postmenopausal women non weight-bearing progressive resistance strength exercises for lower limbs and a combination of exercise programmes are the most effective physical interventions on BMD of femoral neck and lumbar spine, respectively.36 A significant decrease in bone loss and improvement in postural control was also reported in postmenopausal osteopenic women participating in Tai Chi training.37,38 Moreover, gender differences in the muscle-bone unit and in the age-related bone loss suggest that different training strategies may be needed in women and in men.39 For instance, in men aged 50-79 years lumbar spine and femoral neck BMD and strength improved after 18 months of progressive resistance training exercises with alternate days of weight-bearing activities.40 Despite these results, there is as yet no definition as to which are the most efficient types of exercise specifically improving bone mass and strength in subjects of different age and sex.41
In conclusion, our results show that age and menopause significantly contribute to the reduction of isometric contraction of skeletal muscles. The degree of muscle strength of the dominant arm significantly correlates with some quantitative and qualitative features of skeletal tissue at this level. This finding underlines the relevance of extra-skeletal factors in influencing bone health.
REFERENCES
1.Ling CH, Taekema D, de Craen AJ, Gussekloo J, Westendorp RG, Maier AB, 2010 Handgrip strength and mortality in the oldest old population: the Leiden 85-plus study. CMAJ 182: 429-435.
2.Samuel D, Rowe PJ, 2009 Effect of ageing on isometric strength through joint range at knee and hip joints in three age groups of older adults. Gerontology 55: 621-629.
3.Di Monaco M, Vallero F, Di Monaco R, Tappero R, 2011 Prevalence of sarcopenia and its association with osteoporosis in 313 older women following a hip fracture. Arch Gerontol. Geriatr 52: 71-74.
4.Janssen I, Heymsfield SB, Ross R, 2002 Low relative skeletal muscle mass (Sarcopenia) in older persons is associated with functional impairment and physical disability. J Am Geriatr Soc 50: 889-896.
5.Janssen HC, Samson MM, Verhaar HJ, 2002 Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nut 75: 611-615.
6.Iannuzzi-Sucich M, Prestwood KM, Kenny AM, 2002 Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol A Biol Sci Med Sci 57: 772-777.
7.Visvanathan R, Chapman I, 2010 Preventing sarcopaenia in older people. Maturitas 66: 383-388.
8.Maltais ML, Desroches J, Dionne IJ, 2009 Changes in muscle mass and strength after menopause. J Musculoskelet Neuronal Interact. 9: 186-197.
9.Walsh MC, Hunter GR, Livingstone MBM, 2006 Sarcopenia in premenopausal and postmenopausal women with osteopenia, osteoporosis and normal bone mineral density. Osteoporos Int 17: 61-67.
10.Samuel D, Rowe PJ, 2009 Effect of ageing on isometric strength trough joint range at knee and hip joints in three age groups of older adults. Gerontology 55: 621-629.
11.Daly RM, Ahlborg HG, Ringsberg K, Gardsell P, Sernbo I, Karlsson MK, 2008 Association between changes in habitual physical activity and changes in bone density, muscle strength, and functional performance in elderly men and women. J Am Geriatr Soc 56: 2252-2260.
12.Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al, 2010European Working Group on Sarcopenia in Older People Sarcopenia: European consensus on definition and diagnosis. Age Ageing 39: 412-423.
13.Hamrick MW, Samaddar T, Pennington C, McCormick J, 2006 Increased muscle mass with myostatin deficiency improves gains in bone strength with exercise. J Bone Miner Res 21: 477-483.
14.Dixon WG, Lunt M, Pye SR, et al, 2005 European Prospective Osteoporosis Study Group Low grip strength is associated with bone mineral density and vertebral fracture in women. Rheumatology (Oxford) 44: 642-646.
15.Marin RV, Pedrosa MA, Moreira-Pfrimer LD, Matsudo SM, Lazaretti-Castro M, 2010 Association between lean mass and handgrip strength with bone mineral density in physically active postmenopausal women. J Clin Densitom 13: 96-101.
16.Frost HM, 1997 Perspective: On our age-related bone loss: Insights from a new paradigm. J Bone Miner Res 12: 1539-1546.
17.Blain H, Vuillemin A, Teissier A, Hanesse B, Guillemin F, Jeandel C, 2001 Influence of muscle strength and body weight and composition on regional bone mineral density in healthy women aged 60 years and over. Gerontology 47: 207-212.
18.Di Monaco M, Di Monaco R, Manca M, Cavanna A, 2000 Handgrip strength is an independent predictor of distal radius bone mineral density in postmenopausal women. Clin Rheumatol 19: 473-476.
19.Albrand G, Munoz F, Sornay-Rendu E, DuBoeuf F, Delmas PD, 2003 Independent predictors of all osteoporosis-related fractures in healthy postmenopausal women: The OFELY Study. Bone 32: 78-85.
20.Cipriani C, Romagnoli E, Scarpiello A, Angelozzi M, Montesano T, Minisola S, 2009 Phalangeal quantitative ultrasound and bone mineral density in evaluating cortical bone loss: a study in postmenopausal women with primary hyperparathyroidism and subclinical iatrogenic hyperthyroidism. J Clin Densitom 12: 456-460.
21.Lauretani F, Russo CR, Bandinelli S, et al, 2003 Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol 95: 1851-1860.
22.Frontera WR, Hughes VA, Lutz KJ, Evans WJ, 1991 A cross-sectional study of muscle strength and mass in 45- to 78-yr-old men and women. J Appl Physiol 71: 644-650.
23.Brown M, 2008 Skeletal muscle and bone: effect of sex steroids and aging. Adv Physiol Educ 32: 120-126.
24.Lee CE, McArdle A, Griffiths RD, 2007 The role of hormones, cytokines and heat shock proteins during age-related muscle loss. Clin Nutr 26: 524-534.
25.Evans WJ, Campbell WW, 1993 Sarcopenia and Age-related changes in body composition and functional capacity. J Nutr 123: Suppl 2: 465-468.
26.Rolland YM, Perry HM 3rd, Patrick P, Banks WA, Morley JE, 2007 Loss of appendicular muscle mass and loss of muscle strength in young postmenopausal women. J Gerontol A Biol Sci Med Sci 62: 330-335.
27.Wiik A, Ekman M, Johansson O, Jansson E, Esbjörnsson M, 2009 Expression of both oestrogen receptor alpha and beta in human skeletal muscle tissue. Cell Biol Histochem 131: 181-189.
28.Frank AW, Lorbergs AL, Chilibeck PD, Farthing JP, Kontulainen SA, 2010 Muscle cross sectional area and grip torque contraction types are similarly related to pQCT derived bone strength indices in the radii of older healthy adults. J Musculoskelet Neuronal Interact 10: 136-141.
29.Sherk VD, Palmer IJ, Bemben MG, Bemben DA, 2009 Relationships between body composition, muscular strength, and bone mineral density in estrogen-deficient postmenopausal women. J Clin Densitom 12: 292-298.
30.Frost HM, 2001 From Wolff’s Law to the Utah paradigm: insights about bone physiology and its clinical applications. Anat Rec. 262: 398-419.
31.Kaji H, Kosaka R, 2005 Effects of age, grip strength and smoking on forearm volumetric bone mineral density and bone geometry by peripheral quantitative computed tomography: Comparisons between female and male. Endocr J 52: 659-666.
32.Snow-Harter C, Bouxsein M, Lewis B, Charette S, Weinstein P, Marcus R, 1990 Muscle strength as a predictor of bone mineral density in young women. J Bone Miner Res 5: 589-595.
33.Burr DB, 1997 Muscle strength, bone mass, and age-related bone loss. J Bone Miner Res 12: 1547-1551.
34.Taaffe DR, Cauley JA, Danielson M, et al, 2001 Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: the Health, Aging, and Body Composition Study. J Bone Miner Res 16: 1343-1352.
35.Marques EA, Mota J, Machado L, et al, 2010 Multicomponent training program with weight-bearing exercises elicits favorable bone density, muscle strength, and balance adaptations in older women. Calcif Tissue Int 88: 117-129.
36.Howe TE, Shea B, Dawson LJ, et al, 2011 Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev 6: CD000333.
37.Chan K, Qin L, Lau M, et al 2004 A randomised prospective study of the effects of Tai ChiChun exercise on bone mineral density in postmenopausal women. Arch Phys Med Rehabil 85: 717-722.
38.Wayne PM, Kiel DP, Buring JE, et al, 2012 Impact of Tai Chi exercise on multiple fracture-related risk factors in post-menopausal osteopenic women: a pilot pragmatic, randomized trial. BMC Complement Altern Med 12: 7.
39.Lang TF, 2011 The bone-muscle relationship in men and women. J Osteoporos 2011: 702735.
40.Kukuljan S, Nowson CA, Sanders KM, et al, 2011 Independent and combined effects of calcium-vitamin D3 and exercise on bone structure and strength in older men: an 18-month factorial design randomized controlled trial. J Clin Endocrinol Metab 96: 955-963.
41.Guadalupe-Grau A, Fuentes T, Guerra B, Calbet JA, 2009 Exercise and bone mass in adults. Sports Med 39: 439-468.
Address for correspondence:
Cristiana Cipriani, Department of Internal Medicine and Medical Disciplines, University of Rome “Sapienza”, Viale del Policlinico 155, 00161, Rome, Italy;
Tel.: +39-0649972379; Fax: +39-0644704916; e-mail: cristianac@alice.it
Received 12-01-12, Revised 17-02-12, Accepted 10-03-12