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ORIGINAL ARTICLE

Exercise During Growth and Young Adulthood Is Independently Associated With Cortical Bone Size and Strength in Old Swedish Men Martin Nilsson,1,2 Daniel Sundh,1,2 Claes Ohlsson,2 Magnus Karlsson,3 Dan Mellström,1,2 and Mattias Lorentzon1,2 1

Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden Center for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden 3 Clinical and Molecular Osteoporosis Research Unit, Department of Orthopaedics and Clinical Sciences, Lund University, Malmo, Sweden 2

ABSTRACT Previous studies have reported an association between exercise during youth and increased areal bone mineral density at old age. The primary aim of this study was to investigate if exercise during growth was independently associated with greater cortical bone size and whole bone strength in weight‐bearing bone in old men. The tibia and radius were measured using both peripheral quantitative computed tomography (pQCT) (XCT‐2000; Stratec) at the diaphysis and high‐resolution pQCT (HR‐pQCT) (XtremeCT; Scanco) at the metaphysis to obtain cortical bone geometry and finite element–derived bone strength in distal tibia and radius, in 597 men, 79.9  3.4 (mean  SD) years old. A self‐administered questionnaire was used to collect information about previous and current physical activity. In order to determine whether level of exercise during growth and young adulthood or level of current physical activity were independently associated with bone parameters in both tibia and radius, analysis of covariance (ANCOVA) analyses were used. Adjusting for covariates and current physical activity, we found that men in the group with the highest level of exercise early in life (regular exercise at a competitive level) had higher tibial cortical cross‐sectional area (CSA; 6.3%, p < 0.001) and periosteal circumference (PC; 1.6%, p ¼ 0.011) at the diaphysis, and higher estimated bone strength (failure load: 7.5%, p < 0.001; and stiffness: 7.8%, p < 0.001) at the metaphysis than men in the subgroup with the lowest level of exercise during growth and young adulthood. Subjects in the group with the highest level of current physical activity had smaller tibial endosteal circumference (EC; 3.6%, p ¼ 0.012) at the diaphysis than subjects with a lower current physical activity, when adjusting for covariates and level of exercise during growth and young adulthood. These findings indicate that exercise during growth can increase the cortical bone size via periosteal expansion, whereas exercise at old age may decrease endosteal bone loss in weight‐bearing bone in old men. © 2014 American Society for Bone and Mineral Research. KEY WORDS: PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY; FINITE ELEMENT ANALYSIS; CORTICAL BONE; EXERCISE; OLD MEN

Introduction

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steoporosis is a disease characterized by reduced bone mass and microarchitectural deterioration of bone tissue leading to an increased risk of fracture.(1) The variance in bone mass is mostly genetically determined,(2–4) but exercise with loading of the bone also has a major impact on bone mass(5–7) as well as on bone strength.(5,8,9) The adaptive response to mechanical loading is highly site‐specific; only those bones that are actually loaded will adapt. This has been shown in several studies in racquet‐sport players, where the arm holding the racquet had significantly greater bone mass and size than the contralateral nonplaying arm.(5,8–10) Dynamic load in excess of loads encountered in daily life has the most favorable effect on the skeleton.(11,12) A study on older twin pairs suggested that the relative importance of physical activity compared to genetic

factors for structural bone strength was greater for the weight‐ bearing tibia than for the non–weight‐bearing radius.(13) In comparison to the mature skeleton, the young and growing skeleton seems to be more adaptive and has a higher responsiveness to loading stimuli by exercise.(5,9,14) Physical activity has been suggested as an intervention strategy to promote an optimal peak bone mass during growth and to reduce the rate of bone loss during adulthood.(15,16) In addition, high peak bone mass is associated with reduced risk of osteoporotic fractures later in life.(15) Physical exercise during skeletal growth may cause beneficial adaptations to bone size and structure, but it is still debated whether these benefits will be maintained with reduction in activity level.(14) Some studies demonstrate that the benefits of physical activity are lost after its cessation.(17,18) In contrast, several other studies have shown that the benefits of previous training will remain when the level of

Received in original form September 23, 2013; revised form February 18, 2014; accepted February 24, 2014. Accepted manuscript online March 2, 2014. Address correspondence to: Martin Nilsson, PhD, RPT, Geriatric Medicine, Dept. of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, K‐huset, Plan 6, Sahlgrenska University Hospital, Mölndal, S‐431 80 Mölndal, Sweden. E‐mail: [email protected] Journal of Bone and Mineral Research, Vol. 29, No. 8, August 2014, pp 1795–1804 DOI: 10.1002/jbmr.2212 © 2014 American Society for Bone and Mineral Research

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activity is decreased, even after complete cessation of training.(19–28) In the large majority of studies, bone properties have been measured using dual‐energy X‐ray absorptiometry (DXA).(20,24–28) Bone density measured by DXA is areal, can be confounded by differences in bone size, and cannot determine whether changes in areal bone mineral density (aBMD) are due to volumetric BMD (vBMD) or bone geometrical parameters.(29) Therefore, it is possible that studies which have observed bone mass by DXA reflect changes in bone size rather than changes in trabecular or cortical vBMD. The clinical importance of exercise‐ induced skeletal benefits could also be questioned if the benefits are not maintained into late adulthood, when fragility fractures occur. The mechanical strength of the bone and resistance against fracture have been reported to be dependent on bone size, volumetric density,(30,31) and trabecular bone architecture.(32) We have reported an association between exercises during youth and increased aBMD in old men.(20) However, using the DXA technique to measure aBMD, we could not determine whether the changes found in aBMD were caused by preserved BMD or bone geometrical parameters. The primary objective of this study was to investigate if exercise during growth and young adulthood was associated with cortical bone geometry, bone microstructure, and whole‐bone strength in weight‐bearing and non–weight‐bearing bone in old men. The secondary objective was to assess if current physical activity was associated with these bone traits. We hypothesized that men who exercised at a high level during growth and young adulthood would have greater cortical bone size and whole‐bone strength at old age in weight‐bearing bone than men who were less physically active, and that this association would be independent of current physical activity.

Subjects and Methods Subjects The study subjects were initially enrolled in the population‐ based Osteoporotic Fractures in Men (MrOS) study from Gothenburg, Sweden.(33) All study subjects in the original study were contacted and invited to participate in this 5‐year follow‐up study. Out of the original 1010 subjects, 597 men (79.9  3.4 years of age) were included in the present study (Table 1). To be included in the original MrOS study, subjects had to be men between 69 to 81 years of age. All subjects were randomly sampled from the Swedish national population register for Gothenburg and invited to participate on a voluntary basis. To be eligible for the study, the subjects had to be able to walk indoors unaided and to understand questions and instructions in Swedish. To determine whether the cohort of the present study was representative of the initial population, we compared the age, height, and weight (all variables measured at the time of inclusion in the original MrOS study) of the included subjects (n ¼ 597) with the subjects that did not participate (n ¼ 413) in the present study. The included subjects were younger than the excluded subjects at the first MrOs examination (74.4  2.9 versus 76.6  3.2 years; p < 0.001), but at that occasion there were no significant differences between the included and excluded subjects in, height (175.9  6.4 versus 175.5  6.4 cm; p ¼ 0.378), or weight (81.3  11.7 versus 80.5  13.0 kg; p ¼ 0.317) (using an independent‐samples t test (mean  SD). The regional ethical review board at the University of Gothenburg approved the

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Table 1. Characteristics and Bone Macrostructure and Microstructure of the Total Cohort Number of subjects

597

Age (years) Height (cm) Weight (kg) Calcium intake (mg/d) Smoking (%) Tibia pQCT at the diaphysis (n ¼ 575) Ct.CSA (mm2) Ct.Th (mm) PC (mm) EC (mm) Tibia HR‐pQCT at the metaphysis (n ¼ 457) Failure load (kN) Stiffness (kN/mm) Percent load trabecular distal (%) Percent load trabecular proximal (%) Ct.CSA (mm2) Ct.Th (mm) Ct.Pm (mm) D.Ct (mg/cm3) BV/TV (%) Tb.N (mm1) Tb.Th (mm) Tb.Sp (mm) Radius pQCT at the diaphysis (n ¼ 590) Ct.CSA (mm2) Ct.Th (mm) PC (mm) EC (mm) Radius HR‐pQCT at the metaphysis (n ¼ 372) Failure load (kN) Stiffness (kN/mm) Percent load trabecular distal (%) Percent load trabecular proximal (%) Ct.CSA (mm2) Ct.Th (mm) Ct.Pm (mm) D.Ct (mg/cm3) BV/TV (%) Tb.N (mm1) Tb.Th (mm) Tb.Sp (mm)

79.9  3.4 175.0  6.5 79.6  11.7 958  448 5.0 267.7  33.6 4.23  0.58 76.9  4.4 50.3  6.1 12.2  2.2 240  46 64.0  7.4 41.5  8.0 120  35 0.99  0.31 122  9 779  75 14.9  2.8 1.97  0.30 76.0  11.6 444  83 93.0  14.5 2.36  0.39 47.0  3.6 32.2  4.6 4.7  1.1 91  22 64.0  6.8 27.1  7.7 54  18 0.61  0.21 90  8 768  77 13.8  3.2 2.06  0.29 66.6  10.6 430  92

Values are given as mean  SD. Ct.CSA ¼ cortical cross‐sectional area; Ct.Th ¼ cortical thickness; PC ¼ periosteal circumference; EC ¼ endosteal circumference; D.Ct ¼ volumetric cortical bone density; BV/TV ¼ bone volume/total volume; Tb. N ¼ trabecular number; Tb.Th ¼ trabecular thickness; Tb.Sp ¼ trabecular separation; Ct.Pm ¼ cortical perimeter.

study. Written and oral informed consent was obtained from all study participants.

Assessment of physical activity A self‐administered questionnaire, based on a validated physical activity questionnaire,(34) was used to collect information about patterns of physical exercise from the perspective of a lifetime. The original questionnaire designed for interview was adapted to

Journal of Bone and Mineral Research

suit the self‐administered form. Briefly, this questionnaire divided the lifespan into five prior age periods: 10 to 20, 21 to 30, 31 to 50, 51 to 70, and 71 years of age. For each age period the participants were asked to identify the types of exercise and on what level they performed this exercise during each period. Bivariate correlations between the levels of exercise among the participants during the different age periods were tested using Pearson’s coefficient of correlation (r). Correlations ranged from r ¼ 0.15 to 0.71 (p < 0.001, respectively) with the highest correlation between the first to periods (10 to 20 years and 20 to 30 years of age) and the lowest correlation between the first and last period (10 to 20 years and 71 years of age). The identified levels of exercise during the first two periods (10 to 30 years of age) divided the subjects into four groups: level 1 ¼ low level (hardly any exercise or exercise sporadically a couple of times per month); level 2 ¼ moderate level (regular exercise but only part of the year); level 3 ¼ high level (regular exercise on a fixed time every week); and level 4 ¼ very high level (regular exercise on competitive level). A detailed description of the most common types of physical exercise and number of subjects participating in each type of activity is shown in Table 2. Current physical activity was assessed using the Physical Activity Scale for the Elderly (PASE), a validated self‐reporting questionnaire designed to measure physical activity in individuals aged 65 years or older.(35) This scale comprises 12 items regarding physical activity during a 7‐day time frame prior to the assessment, including walking outside; light, moderate, and strenuous sport and recreational activities; muscle strengthening; light and heavy housework, home repairs, lawn work, or yard care; caring for another person; and work for pay or as a volunteer. The PASE is a valid and reliable instrument that reflects the types of activities in which that older adults commonly participate.(35) The total PASE score was computed by multiplying the amount of time spent in each activity (hours per week) or participation in an activity (yes/no) by empirically derived weights and then summing the product for all 12 items. The obtained total PASE score was stratified in quartiles that divided the subjects into four groups for statistical analyses according to the levels of current physical activity.

Table 2. Number of Participants for Each Type of Physical Exercise During Growth and Young Adulthood Type of exercise Badminton Bandy Bicycling Cross‐country skiing Gardening Gymnastics Handball Middle and long distance running Orienteering Soccer Swimming Table tennis Tennis Track and field Walking

Subjects (n) 18 20 79 89 55 66 74 72 24 149 47 12 22 34 86

All activity with 10 participating subjects is shown. Subjects may have participated in several types of exercise.

Journal of Bone and Mineral Research

Assessment of cortical bone geometry A peripheral quantitative computed tomography (pQCT) device (XCT‐2000; Stratec Medizintechnik, Pforzheim, Germany) was used to scan the distal leg (tibia) and the distal arm (radius) of the nondominant leg and arm in 575 and 590 subjects, respectively. A 2‐mm‐thick single tomographic slice was scanned with a pixel size of 0.50 mm. The cortical cross‐sectional area (CSA, mm2), endosteal and periosteal circumference (EC and PC, mm), and cortical thickness (mm) were measured using a scan through the diaphysis (at 25% of the bone length in the proximal direction of the distal end of the bone) of the radius and tibia. Tibia length was measured from the medial malleolus to the medial condyle of the tibia, and length of the forearm was defined as the distance from the olecranon to the ulna styloid process. The coefficients of variation (CVs) for the bone measurements used were obtained by three repeated measurements according to the standardized protocol, including repositioning between the scans, on one subject (male 79 years of age). The CVs ranged from 0.1% to 1.1% of the tibia (cortical CSA, 0.8%; EC, 0.8%; PC,

Exercise during growth and young adulthood is independently associated with cortical bone size and strength in old Swedish men.

Previous studies have reported an association between exercise during youth and increased areal bone mineral density at old age. The primary aim of th...
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