The purpose of this cross-sectional study was to examine the impact of long-term physical activity (PA) and calcium intake on non-weight-bearing radius and weight-bearing tibia. Altogether, 218 healthy, nonsmoking women, [92 premenopausal women, mean age, 32.6 years (SD, 2.2 years), and 126 postmenopausal women, mean age, 67.3 years (SD, 2.0 years)] participated. The subjects were divided according to their habitual levels of physical activity (PA+ or PA−) and calcium intake (Ca+ or Ca−). The distal end and shaft regions of the radius and tibia were evaluated with peripheral quantitative tomography (pQCT). For the shaft regions, bone mineral content (BMC), cortical cross-sectional area (CoA), cortical density (CoD), and bone strength index, that is, 1-11.9% of the density-weighted section modulus (BSI) were determined. For the distal ends, BMC, total cross-sectional area (ToA), trabecular density (TrD), and BSI were determined. The BMC at the distal radius in the young PA+ group was 6.6% (95% CI, 1-to 11.9%) lower than that of the PA− group. A similar nonsignificant trend was found for the radial shaft. The radial shaft showed a mechanically more competent structure among the older subjects with a BSI 8.5% (95% CI, 1.8-15.6%) higher in the older PA+ group than in the older PA− group. The associations between calcium intake and the radial bone characteristics were systematically positive in both age groups. PA seemed to benefit the distal tibia. In the younger age group the TrD was 6.9% (95% CI, 1.8-12.4%) higher in the PA+ group, and in the elderly the BMC was 5% (95% CI, 0.3-9.9%) higher in the PA+ group than in the PA− group. Note that in the younger age group the ToA was 5.1% (95% CI, 0-9.1%) smaller in the PA+ group than in the PA− group, and in the older age group the ToA was 4.2% (95% CI, −0.3-8.9%) greater in the PA+ group than in the PA− group. The association of PA and bone characteristics at the tibial shaft was positive in both age groups (statistically significant for the older subjects). The tibial shaft BSI of the older PA+ group was 8.6% (95% CI, 2.6-14.9%) better than that of the old PA− group. There was no association between calcium intake and the tibial bone characteristics in either age group. In conclusion, high calcium intake was positively associated with a mechanically competent structure in the radius among both younger and older women, whereas the influence of PA did not become apparent until older ages. PA seemed to benefit particularly the weight-bearing tibia, whereas calcium intake was not associated with the tibia.
INCREASING NUMBER of fractures caused by osteoporosis is a formidable health problem. Osteoporosis is characterized by increased bone fragility that is a more complex issue than simple low bone mass. Apart from falling, a major cause for osteoporotic fractures, high susceptibility to fracture is attributable to a decrease of tissue density in the cortical bone compartment (i.e., increased intracortical porosity, endosteal resorption, and thinning of the cortex) and the trabecular bone compartment (i.e., thinning and perforation of trabeculae) and, importantly, the subsequent mechanical deterioration of the whole bone structure and architecture. Although the importance of structure is well recognized,(1,2) the clinical diagnosis of osteoporosis is based on primarily assessment of areal bone mineral density (BMD, g/cm2) by dual-energy X-ray absorptiometry (DXA). However, BMD is not a volumetric bone density; instead it represents a lumped measure of bone size and volumetric density(3) and is subject to considerable patient-specific inaccuracies as well,(4) which may complicate and mislead interpretation of patient-specific bone fragility.(3,5) Planar DXA cannot depict the true cross-sectional bone mass distribution or separate trabecular bone from cortical bone, compartments that are known to respond differently, e.g., to aging and physical loading. In addition, there are some cross-sectional peripheral quantitative computed tomography (pQCT) data that indicate different associations of physical activity (PA) with trabecular and cortical bone.(6,7) Nevertheless, because BMD is the most readily available measurement that correlates strongly with bone fragility, although it is not itself a determinant of fragility, it has attained an overemphasized position in osteoporosis studies.(8,9)
It is important to recall that age-related bone loss may not result in a proportionate age-related decrease in bone strength because concurrent geometric adaptation may act as a compensatory mechanism; thus, the decrease in BMD with age does not go hand-in-hand with a loss of apparent bone strength.(2) In this respect, exercise studies that have reported only marginal, if any, increases in DXA-derived BMD even after substantial changes in exercise habits(10–13) may have omitted relevant endpoints regarding bone strength merely by ignoring the geometric properties of bone.(14) Indeed, in an exercise intervention trial, Adami et al.(15) recently showed that only a marginal change in bone mass was accompanied with a substantial improvement in the structure of the loaded forearm sites.
Osteoporosis generally is understood as a heterogeneous disorder, for which lifestyle factors are considered to play an influential role in the maintenance of bone mass and skeletal integrity. PA and calcium intake have been shown to be beneficial in terms of DXA-derived BMD,(12,13,16,17) but their role in modulating the compensatory adaptation that attempts to maintain the mechanical competence of bone structure is not known. Therefore, the purpose of this cross-sectional study was to examine associations of PA and calcium intake with the volumetric bone density and size of non-weight-bearing radius and weight-bearing tibia among healthy pre- and postmenopausal women.
MATERIALS AND METHODS
This study reports data from our prospective investigation of pre- and postmenopausal women.(18) However, the results are cross-sectional because pQCT was not at our disposal at the time of the baseline measurements.
Initially, we recruited 132 women in the age range of 25-30 years and 134 women with ages between 60 and 65 years from a total of 1017 women and divided them into four groups according to their concurrent levels of PA and calcium intake to obtain two physically active groups (PA+) with different calcium intakes [one with abundant calcium intake (Ca+) and the other with low-calcium intake (Ca−)] and two physically inactive groups (PA−) with the same contrast in calcium intake. Altogether 218 women participated in this study, 92 women (70% of the original cohort) were premenopausal [mean age, 32.6 years (SD, 2.2 years)], and 126 women (94% of the original cohort) were postmenopausal [mean age, 67.3 years (SD, 2.0 years)]. In the older age group, the forearm data of one woman was excluded because of fractured forearms. All the women were healthy, fully ambulatory, and nonsmoking, and the older women were not using estrogen-replacement therapy. All subjects gave their informed consent.
Data on the health status; history of PA as a child and as an adult; education; occupation and work history; workload; number of children; duration of breast-feeding; menstrual and menopausal status; and use of alcohol, medication, and estrogen therapy were collected from each participant in an interview.
Initially, PA was classified into the following four categories according to its type and frequency: (1) “high” for vigorous activity at least twice a week (at least 20 minutes per session causing enhanced breathing and clear elevation of heart rate), (2) “moderate” for vigorous PA no more than once a week or less-demanding activity a few times a week, (3) “low” for less-demanding activity once a week or very light activity several times a week (causing no enhanced breathing and only small elevation in heart rate), and (4) “no activity” for no mentionable daily PA. The women belonging to category 1 comprised the original PA+ groups, while the women belonging to categories 3 and 4 were combined to form the original PA− groups. The original groups were maintained in this study. In addition, current PA and possible changes from the baseline to the time of the current examination were inquired about separately. Each subject's daily walking distance was measured on 3 days (2 weekdays and a Sunday) with a pedometer (Fitty-3 Electronic, Uttenreucht, Germany).
Initially, daily calcium intake was estimated by a 3-day food record and a 7-day calcium intake diary.(19) The inclusion criteria were a daily dietary calcium intake of over 1200 mg (Ca+, higher intakes are not warranted as shown by supplement studies) or under 800 mg/day [Ca−, recommended daily allowance (RDA) for adult women]. Current daily calcium intake was assessed by a 7-day calcium intake diary and calculated by Micro-Nutrica software (Social Insurance Institution, Helsinki, Finland). Information on milk consumption at different ages and the use of calcium or other dietary supplements was obtained in an interview. If milk currently was not being used, the age at and reason for cessation were recorded.
The radius and tibia of the subjects were scanned with pQCT (Norland/Stratec XCT 3000; Norland/Stratec, Pforzheim, Germany) according to our standard procedures.(20) The tomographic slices were taken from the diaphyses and distal part of the dominant radius and the right tibia. For the radial and tibial shaft, the bone mineral content (BMC, g), cortical cross-sectional area (CoA, mm2), cortical density (CoD, mg/cm3), and bone strength index, that is, density-weighted section modulus (BSI, mm3) were determined. For the distal radius and distal tibia, the evaluated variables were BMC, total cross-sectional area (ToA, mm2), trabecular density (TrD, mg/cm3), and BSI. In the upper limbs, the forearm slices were taken at 4% and 30% of the approximated segment length (0.146 ∗ height) proximal to the distal endplate of the ulna. In the lower limbs, the shank slices were taken at 5% and 50% of the approximated segment length (0.246 ∗ height) proximated to the distal endplate of the tibia. The BSI denotes the bone mass distribution around the center of mass of the given bone section (the larger the outer dimensions of bone, the higher the BSI) and thus reflects the bone's ability to resist torsional loading. In our laboratory, the in vivo precision of these parameters varied between 1.5% (BMC) and 3.5% (BSI) for the tibial shaft and between 0.9% (TrD) and 4.2% (BSI) for the distal tibia.(20)
Muscle strength, body balance, and physical fitness
The maximal isometric strength of the leg extensors and forearm flexors was measured by dedicated strain gauge dynamometers.(21) The leg-extensor power was evaluated with a vertical counter-movement jumping test using a contact platform (Newtest, Oulu, Finland) and recording the flying time of the jump.(22) Dynamic balance was tested by a figure-8 running test, the test being performed by running around two poles placed 10 m apart.(23) Body balance was estimated with a postural sway platform (Biodex Stability System; Biodex Medical Systems, Shirley, NY, USA).(24) Body balance was expressed as a stability index, a unitless measure that reflect the variance of platform displacement from level. A high number indicates less motion control and poor postural stability. Cardiorespiratory fitness (estimated maximal oxygen uptake) was assessed by a standardized 2-km walk test.(25)
Means and SDs were used as descriptive statistics. As the primary analysis of this study, the associations of PA and calcium intake with pQCT-derived bone variables were analyzed by analysis of covariance models in which PA, calcium intake, and age were used as factor variables. Body weight was used as the covariate in the model for adjusting the effect of body size. All group differences were adjusted for body weight. The relative differences between the study groups were determined through log transformation of the variables. When the 95% CI did not include zero, the difference was regarded as statistically significant at α = 0.05.
The group characteristics are presented in Table 1. There were no significant intergroup differences in age or body height between the groups in either of the age groups. Because there was no interaction between PA and calcium intake for any bone variable, the results are described separately in terms of these two factors.
Table Table 1.. Characteristics of the Study Groups (Mean and SD)
The crude physical fitness characteristics are described in Table 2. In line with the original grouping of the subjects, both the muscle strength of the lower extremities and the cardiorespiratory performance were better in the PA+ groups than in the PA− groups in both age categories. For the younger subjects, body balance also was better in the PA+ group than in the PA− group, while among the older subjects there was no between-group difference. Both physical fitness and body balance of the younger group were better than those of the older group.
Table Table 2.. Crude Physical Fitness Characteristics of the Study Groups (Mean and SD)
The crude bone characteristics are described in Table 3. The mean volumetric (either cortical or trabecular) bone density of the older subjects was lower and the mean bone cross-sectional area was greater than those of the younger subjects.
Table Table 3.. Crude Bone Characteristics of the Study Groups and the p Values for Age-Adjusted Effects of PA, Ca Intake, and Age
PA was negatively associated with the radial bone variables of the younger subjects. However, the situation was the opposite for the older ones. In particular, the distal radius BMC of the younger PA+ subjects was statistically significantly (6.6%; 95% CI, 1.0-11.9%) lower than that of the PA− subjects. For the older subjects, the radial BMC was 5.5% (95% CI, −1.0-12.4%) greater in the PA+ group. Of note, the BMC difference between the age groups was statistically significant (p < 0.05; Fig. 1). The BSI of the younger subjects was 8.1% (95% CI, 3.9-18.7%) greater in the PA− group and among the older subjects was 13.4% (95% CI, 3.6-33.5%) greater in the PA+ group (Fig. 1), showing a tendency to age relation.
A similar trend was found for the radial shaft. PA was associated negatively with the bone variables among the younger subjects, whereas the association was positive for the older subjects (Fig. 2). Although the 4.4% (95% CI, −3.2-11.5%) lower BSI of the younger PA− group was not statistically significantly lower than that of the younger PA+ group, the difference between the age groups was statistically significant (p < 0.05). In fact, the radial shaft even showed a mechanically more competent structure among the older subjects; i.e., the BSI was 8.5% (95% CI, 1.8-15.6%) higher in the older PA+ group than in the older PA− group. Although the differences of some 3% in the BMC and CoA between the PA+ and PA− groups were not statistically significant within the age groups, there was a difference between the age groups (Fig. 2).
The associations of calcium intake with the radial bone characteristics were systematically positive among both the younger and older subjects (Figs. 1 and 2). In particular, the radial shaft seemed to benefit from high calcium intake showing, the BSI being 7.8% (95% CI, 0-16.3%) higher in the younger Ca+ group than in the younger Ca− group and the CoA being 5.2% (95% CI, 0-10.7%) greater in the older Ca+ group than in the older Ca− group (Fig. 2).
The CoD of the radial shaft was similar in all the groups within the age group, and there was no association with PA or calcium intake. However, the CoD of the younger age group was greater than that of the older age group (Table 3).
In contrast to the findings for the radius, PA was positively associated with the tibial bone characteristics of younger and older subjects, except that there was 5.1% (95% CI, −9.1-0%) less ToA at the distal tibia in the younger PA+ group than in the younger PA− group (Figs. 3 and 4). The ToA difference between the age groups was statistically significant (p < 0.05); among the older subjects the ToA of the PA+ group was 4.2% (95% CI, −0.3-8.9%) greater than in the PA− group. There was a significant difference in the TrD between the age groups, too. Among the younger PA+ subjects, the TrD was 6.9% (95% CI, 1.8-12.4%) higher at the distal tibia, whereas there was no difference among the older subjects (0.6%; 95% CI, −4.8-6.3%). However, the distal tibia BMC was 5.0% (95% CI, 0.3-9.9%) higher among the older PA+ subjects than among the older PA− subjects (Fig. 3).
The tibial shaft of the older PA+ subjects was mechanically more competent, these subjects had an 8.6% (95% CI, 2.6-14.9%) better BSI than in the older PA− subjects (Fig. 4). There was no difference between the age groups regarding the tibial shaft BMC and CoA. Among the younger subjects, the BMC of the PA+ group was 4.1% (95% CI, −0.8-9.4%) greater than in the PA− group and the CoA was 4.2% (95% CI, −0.8-9.4%) greater. The respective difference was 5.9% (95% CI, 0.6-11.6%) for the BMC and 6.3% (95% CI, 1.5-11.4%) for the CoA for the older subjects.
Again, the CoD of the tibial shaft was similar in all the groups, showing no association with PA or calcium intake, but showing lower volumetric cortical density in the older subjects compared with the younger subjects.
Our pQCT findings confirmed the associations that we had found some 4 years earlier for PA and calcium intake with bone characteristics when using DXA on virtually the same cohort.(26) In both studies, the non-weight-bearing radius seemed to benefit from high calcium intake, whereas the weight-bearing bones of the lower extremities benefited from PA. The impact of calcium intake, if evident, could be seen already among the younger subjects whereas the beneficial influence of PA on skeleton became apparent later, the mechanically relevant benefits (i.e., a large bone) not being present until old age. The enlargement of bone size and the decline in volumetric bone density with age are well-known phenomena.(27–31) The former change apparently represents a partial compensation against age-related bone loss and helps to maintain the mechanical competence of the skeleton. Beneficial, although relatively small, effects of exercise on load-bearing skeleton at different ages have been shown in many DXA studies,(10–13) but the specific effects of PA on bone volumetric (trabecular or cortical) density and size or bone structure are very scarce.(6,7,30,32,33)
In our study, PA was not associated with cortical density in any of the groups. This characteristic seems to be an inherent feature of cortical density as regards the influence of exercise.(7,32,33)
The modulation of the trabecular density by PA may not be so trivial. Site specificity was obvious, but the exact description was not straightforward. PA seemed to be associated negatively with radial bone mass. There are similar findings from our intervention studies both in premenopausal(34) and postmenopausal women.(35) PA seemed to increase bone loss in the nonloaded radius. Also, in the cross-sectional study of athletes, in which training did not intensively load the upper limbs, a lower radial bone density was evident than compared with sedentary referents.(36) These observations are suggestive of a “steal phenomenon” or redistribution of bone mineral from nonloaded sites to loaded sites. However, the possibility of an artifact due to size scaling may not be ruled out completely.
We found no association between PA and the trabecular density of the distal radius among either the younger or the older subjects, whereas the trabecular density of the distal tibia was associated with PA in the younger PA+ group but not in the older PA+ group. However, previously, we found that the trabecular density of the distal tibia was associated with PA among women of about the same age (mean age, 63 years), but the habitual activity regimen of these women had been somewhat different.(7) Perhaps the prevailing loading modality may play some role in this respect. As regards the trabecular density of the distal radius, our pQCT results are in line with those of Rico et al.,(6) who found no significant difference between the dominant and nondominant distal radii of young male and female subjects. Our results agree also with those of Haapasalo et al.(33) and Ashizawa et al.,(32) who observed no significant difference between the forearms of male tennis players and respective control data. However, it should be remembered that the detailed trabecular structure underlying the pQCT-derived trabecular density (i.e., trabecular thickness, trabecular number, connectivity, anisotropy, plate, or rod type of trabecular architecture) and its influence on the actual mechanical competence of the given bone remains unresolved because of the limited resolution of pQCT.
The differences in bone geometry caused by PA were site specific. Positive effects of PA on bone were largely associated with differences in bone size or gross structure rather than with volumetric bone density. This finding is perfectly in line with what has been observed earlier in pQCT or CT studies.(7,32,33,37) In our earlier study with DXA-estimated bone variables, PA was associated positively with bone width and estimated bone strength in the diaphyses of the radius in the older age group.(26) Also, in this study, using pQCT, PA was associated positively with radial bone size in the older age group only. For the load-bearing tibia, the positive association was found in both age groups. This finding also is in agreement with the results of that earlier DXA study(26) with the positive association between PA and femoral shaft variables.
Bigger bone size is a logical adaptation to enhance the mechanical competence of bone because a larger cross-sectional area can bear larger compressive loads and cope more efficiently with bending loading.(38) Because physical loading causes bending and torsion loading, the role of the cortex in resisting this type of loading is important in terms of bone fragility, and cortical properties have been shown to be associated closely with the failure load of femoral neck and radius.(39) Judged from the BSI data in our study, the cortex of both the radius and the tibia seemed to benefit clearly from PA, particularly with advancing age. This relatively good conservation of BSI with age maintains the mechanical competence of the given bone despite the concurrent bone loss and reduced cross-sectional area in long bone diaphyses.
The efficiency of calcium supplementation with respect to bone mass has been shown mainly in DXA-based BMD studies,(16,17) and there are only a few studies in which the effect of calcium intake on volumetric bone density and size has been assessed. Boonen et al.(40) found no significant association between calcium intake and volumetric bone density. In an intervention study by Rüegsegger et al.,(41) calcium compounds were able to slow down trabecular bone loss from both the distal radius and the distal tibia. In our study, too, high calcium intake was associated positively with bone variables, particularly those of the radius. In addition, a weak although nonsignificant positive association was observed for the tibia. As with PA, there was no association between calcium intake and cortical density in any of the groups.
Regarding the association between calcium intake and bone geometry, we are not aware of any previous pQCT studies. The two studies(29,40) already mentioned did not evaluate bone size. In our previous study with DXA-estimated bone variables, we found calcium intake to be associated positively with bone width and estimated bone strength in the diaphyses of the radius.(26) Also, in this study, using pQCT, calcium intake was positively associated with radial bone size in both age groups. For the load-bearing tibia, the only positive association was found in the younger age group. This finding also is in agreement with the results of an earlier DXA study,(26) in which the association of calcium intake with femoral shaft variables indicated a weak positive influence without apparent cumulation with age. When the associations of PA and calcium intake with bone size are compared, it seems that the effect of PA overrides the effect of calcium intake at the loaded skeleton in the long run. On the other hand, the observations support the importance of an adequate calcium supply for building mechanically competent bones in young adulthood, probably already determined during childhood and adolescence.
PA and calcium intake influenced site-specific bone characteristics in different ways. High calcium intake was associated with higher radial BMC, but it was not associated with tibial BMC. On the contrary, greater PA was associated with higher tibial shaft BMC but lower radial BMC. These contrasting associations of the two lifestyle factors may explain some earlier observations showing no effects of lifestyle factors on BMD.
In conclusion, high calcium intake was positively associated with a mechanically competent structure of the radius among both younger and older women, whereas the influence of PA did not become apparent until an older age. PA seemed to benefit particularly the weight-bearing tibia, whereas calcium intake was not associated with the mechanical competence of the tibia.
The authors thank the Juho Vainio Foundation for its financial support.