**1. Introduction**

328 Biomaterials – Physics and Chemistry

Sinha, D.N. Johnston, R.G. Grace, W.K., Lemanski, C.L., (1992). Acoustic resonances in

Takabayashi, K., Raichel, D.R., (1998). Discernment of non-Newtonian behavior in liquids by

Yamamoto, H.M., Iwamoto, M., Haginuma, H., (1980). Acoustic Impulse Response Method

for Measuring Natural Frequency of Intact Fruits and Preliminary Applications to Internal Evaluation of Apples And Watermelons. Journal of Texture Studies, 11,

chicken eggs. Biotechnology Progress, 8, 240-243.

Temkin, S., (1981). Elements of Acoustics. John Wiley and Sons, New York.

acoustic means, Rheol. Acta, 37, 593–600.

117-136.

Densitometric measurement of bone mineral parameters has been developed in recent decades. Since bone strength is associated with bone mineral density (BMD) and/or bone mineral content (BMC), densitometric measurement is widely accepted and used as one golden standard in clinical settings to determine bone health. Based on this concept, some human studies have suggested that endurance training, such as long distance running, provides no benefit and may even be harmful to bone health or bone mineral accretion during development, since long distance runners often have low BMD and/or BMC and may even exhibit conditions associated with bone loss or osteopenia.1, 2 Conversely, serum bone marker assays in healthy distance runners show normal or positive bone metabolism status.3, 4 Therefore, the definite role of endurance running training (ERT) on bone health remains a controversial issue. It would be valuable to further clarify whether ERT benefits bone health through a pathway other than absolutely increasing BMD or BMC.

Clinical observations of human subjects require further basic studies to investigate possible mechanisms. Animal studies can provide unique ways not feasible in studies using human subjects of assessing the effects of endurance running on bone. Generally, previous animal studies further verified benefits of ERT to bone health. However, the limitations of animal studies must be clarified before applying their findings to human beings.

The present article reviews the phenomena shown in bone of adolescent or young adult distance runners. Moreover, previous animal studies which adopted growing and young adult rats as subjects are reviewed, and the applicability of the findings to humans is also discussed.

The Effects of Endurance Running Training on

Grimston et al.12

Robinson et al.13

> Taaffe et al.14

Mudd et al. (2007)9

Emslander et al.17

> Duncan et al.18

Moen et al.25

Greene et al.16

Jürimäe et al.11

MacDougall et al.15

Authors Subjects (gender, age, BMI,

training status)

♀, age (C:32.9, NR:32.2, LR:30.3), BMI (C: 20.6, NR:20.5, LR: 21.7), Training (NR:55.6km/wk for 7.7yr, LR: 53.0km/wk, 9.2yr)a

♀, collegiate gymnasts (n = 21, age 16.21.7 years) runners (n = 20, 14.41.7 years), and nonathletic college women (n = 19, 13.01.2 years), No BMI data.

♀, 19.71.2yr, 19.5, 4-5d/wk, college level runners

> ♀, 20.21.3yr, 21.01.6, college level athletes

♀, 20.30.6 yr, 21.9, 40mile/wk for 3yr

♀, 17.81.4 yr, 21.31.6, 8.41.2 h/wk for 6.21.7 yr, high school level athletes

♀, 15.1-18.8 yr, No BMI data, 58.1km/wk for >1.5yrs

♂, 16.80.6yr, 20.681.6, 6hr/wk for 2yr

♀, 22.64.3 yr, 20.61.6, 6h/wk for > 5yr

♂, 22-45yr, runners were divided into five groups per their training mile/wkb

Young Adult Bone: Densitometry vs. Biomaterial Properties 331

Results Vs.

Most subjects reveal normal menstrual cycle (11-13 cycle/yr), LR group showed lower BMD in L2-L4 , femoral neck, and tibia than C group

Lumbar spine BMD was lower in runners compared with both gymnasts and controls. Whole body BMD was lower in runners compared with gymnasts and controls.

Runners showed significantly lower BMD in femoral neck, lumbar spine but not in whole body BMD.

Runners had lowest lumbar spine and pelvis BMD when compared to other athletes

No significant difference was shown in total body, spine and proximal femoral BMD among runners, swimmers and control groups.

Areal BMD estimation was performed on mid-third femur. Runners had higher BMD only than cyclist. No difference was shown among groups of runners, swimmers, triathlete and controls.

There is no significant difference among amenorrheic runners, eumenorrheic runners, and controls in lumbar BMD.

After adjusting for lean tissue mass per kg of body weight, no difference in BMC was detected.

Endurance trained group showed no difference with normal-weight control group in BMD, but was lower than over-weight control group.

Runners with running mileage 15- 20mile/wk showed the highest BMD values in legs but not in total body and spine. Runners with higher

control group

↓

↓

↓

↓

=

=

=

=

=

SS↑

### **2. The effects of endurance training on human bone: results and limitations**

Conventionally, the extrinsic parameters of bone, such as BMD, BMC, and size-related measurements (*e.g.*, bone dimension, bone geometry), have been widely accepted as indicators of bone strength as well as predictors of fracture risk. Unfortunately, endurance running is usually considered an exercise mode that confers no benefit in terms of bone mineral accretion.1, 2 Moreover, distance runners reportedly have low BMD and are often candidates for osteoporosis or stress fracture.1, 2, 5-8 This section reviews studies on the effects of distance running training on both BMD and bone metabolism.

### **2.1 Results of human studies**

#### **2.1.1 BMD and BMC in distance runners**

For references to human studies, the NIH website (http://www.ncbi.nlm.nih.gov /sites/entrez/) was searched by subject (adolescent, young adult runners) and research type (cross-sectional studies). Additionally, the major purpose of this article is to describe the long-term effects of ERT on bone in runners without concomitant health problems. Hence, reports describing energy deficiencies and/or serious menstrual cycle disorders in runners were excluded. The summary of previous cross-sectional studies in Table 1 indicates that distance runners usually reveal lower BMD and BMC values than those who engage in higher impact sports.9 According to Frost's theory,10 the slenderer body dimensions (Body Mass Index = 20 ~ 22) of runners who have a relatively lower body weight (BW) might partially contribute to a lower BMD and BMC. However, when compared to body-size matched control groups or another non-weight bearing exercise group, runners still do not seem to have much advantage on whole body, lumbar spine or regional cortical bone BMD.11-18 Although oligomenorrhea or amenorrhea has been considered the cause of low BMD in female runners, even healthy female runners with normal menstrual cycles had lower BMD when compared to their size-matched control subjects.12-14 Thus, ERT is usually concluded to be profitless for bone mineral accretion and bone health as well. However, if the analysis is limited to weight-bearing sites, runners do reveal higher site-specific regional BMD and/or BMC (*e.g.*, femoral neck, distal tibia, calcaneus) than do controls.15, 19-21 Therefore, ERT is not entirely non-beneficial for bone mineral accretion when considering BMD and/or BMC as the major predictors of bone health.

Table 1 shows the findings of several studies indicating that distance runners have absolutely higher BMD values than do control groups.3, 22-24 In the research publicized by Brahm and associates,3 the runners showed only a slightly higher total-body BMD (3.6% higher, p=0.03), and no significant difference from the control group in total-body BMC was revealed. Interestingly, this study found that runners had distinctly higher BMD values in the legs and in the proximal femora. Regarding subject specificity, the training level of subjects or the normality of control subjects would be a major concern. Compared to elite distance runners, high school or club level runners may be trained at a more moderate intensity. Thus, these subjects did not really have typical body dimensions (e.g. slender body shape, low BMI) of elite distance runners.22, 24 On the other hand, the BMI of 20.7 in the control group recruited in Kemmler *et al.* may have been too low for a normal control group.23

**2. The effects of endurance training on human bone: results and limitations**  Conventionally, the extrinsic parameters of bone, such as BMD, BMC, and size-related measurements (*e.g.*, bone dimension, bone geometry), have been widely accepted as indicators of bone strength as well as predictors of fracture risk. Unfortunately, endurance running is usually considered an exercise mode that confers no benefit in terms of bone mineral accretion.1, 2 Moreover, distance runners reportedly have low BMD and are often candidates for osteoporosis or stress fracture.1, 2, 5-8 This section reviews studies on the effects

For references to human studies, the NIH website (http://www.ncbi.nlm.nih.gov /sites/entrez/) was searched by subject (adolescent, young adult runners) and research type (cross-sectional studies). Additionally, the major purpose of this article is to describe the long-term effects of ERT on bone in runners without concomitant health problems. Hence, reports describing energy deficiencies and/or serious menstrual cycle disorders in runners were excluded. The summary of previous cross-sectional studies in Table 1 indicates that distance runners usually reveal lower BMD and BMC values than those who engage in higher impact sports.9 According to Frost's theory,10 the slenderer body dimensions (Body Mass Index = 20 ~ 22) of runners who have a relatively lower body weight (BW) might partially contribute to a lower BMD and BMC. However, when compared to body-size matched control groups or another non-weight bearing exercise group, runners still do not seem to have much advantage on whole body, lumbar spine or regional cortical bone BMD.11-18 Although oligomenorrhea or amenorrhea has been considered the cause of low BMD in female runners, even healthy female runners with normal menstrual cycles had lower BMD when compared to their size-matched control subjects.12-14 Thus, ERT is usually concluded to be profitless for bone mineral accretion and bone health as well. However, if the analysis is limited to weight-bearing sites, runners do reveal higher site-specific regional BMD and/or BMC (*e.g.*, femoral neck, distal tibia, calcaneus) than do controls.15, 19-21 Therefore, ERT is not entirely non-beneficial for bone mineral accretion when considering BMD and/or BMC as the major predictors of bone

Table 1 shows the findings of several studies indicating that distance runners have absolutely higher BMD values than do control groups.3, 22-24 In the research publicized by Brahm and associates,3 the runners showed only a slightly higher total-body BMD (3.6% higher, p=0.03), and no significant difference from the control group in total-body BMC was revealed. Interestingly, this study found that runners had distinctly higher BMD values in the legs and in the proximal femora. Regarding subject specificity, the training level of subjects or the normality of control subjects would be a major concern. Compared to elite distance runners, high school or club level runners may be trained at a more moderate intensity. Thus, these subjects did not really have typical body dimensions (e.g. slender body shape, low BMI) of elite distance runners.22, 24 On the other hand, the BMI of 20.7 in the control group recruited in Kemmler *et al.* may have been too low for a normal control

of distance running training on both BMD and bone metabolism.

**2.1 Results of human studies** 

health.

group.23

**2.1.1 BMD and BMC in distance runners** 


The Effects of Endurance Running Training on

significantly differ in serum testosterone levels.15

**2.2 Limitation of human studies** 

buffered by HCO3

period.4

Young Adult Bone: Densitometry vs. Biomaterial Properties 333

It's well known that patients with pathological acidosis suffer negative bone turn-over, which causes a net bone mineral loss.26 Endurance exercise may induce acidosis, which negatively affects bone metabolism. However, transient acidosis caused by exercise is

suggested that acid buffer capacity is enhanced after a period of exercise training.28 At the cellular level, a single bout of intense exercise induces transient increases in serum and urine

With respect to the impact from abnormalities of hormone regulation, oligomenorrhea and amenorrhea related to bone loss are often reported in female runners undergoing intensive training. However, recent investigations suggest that endurance running does not directly cause menstrual disorders and the subsequent bone loss.31-33 Menstrual disorders in endurance runners are more likely due to either energy or nutrition deficiencies. Therefore, dietary adjustment is usually more effective than hormone replacement therapy for restoring menstrual cycles and bone metabolism.34 In males, ERT is known to lower testosterone, but lower testosterone does not necessarily correlate with lower BMD.35 In addition, runners with different training mileage (from 5 to 75 mile/week) do not

Regarding studies of bone metabolism status, healthy distance runners at rest usually exhibit normal bone metabolism, and some studies even show a positive bone metabolism status, as revealed by serum bone markers.3, 4 Brahm *et al.,* in a study of bone metabolism in runners using various serum markers, found that runners had lower bone formation as well as lower bone resorption activities.3 Moreover, triathletes reveal no difference in bone metabolism during the intense competitive season as compared to their non-training

To summarize the above, distance runners do not seem to acquire much benefit from their training when densitometric measurements are used to determine the bone health. However, as shown by serum bone marker assays, distance runners did not reveal an inadequate bone metabolism status. Actually, over the past decades, an increasing number of reports suggest that BMD does not accurately predict bone health or bone strength. Patients with fractures also show normal BMD values.36 The BMD and BMC measures

Today, "bone quality" is used as a new term to represent bone health, which is composed of various parameters, including tissue architecture, turnover, microfracture and mineralization, of a healthy bone.40 Further, the organization of the bone matrix may also play an important role in bone strength.41 Unfortunately, many of the bone quality measurements are too invasive to be feasible in human subjects. Thus, animal studies have

In biomedical science, animal experiments are performed to establish models that mimic human physiological phenomena. Either estimation methods or experimental designs, which may not be feasible in humans, can then be performed to further investigate possible mechanisms. Rodent models of treadmill activity are commonly used to investigate the effects and mechanisms of exercise on bone metabolism. This section reviews the findings of

calcium levels without showing cellular osteoclastical activities.29,30

apparently correlate strongly with body mass and body size.11, 37-39

**3. Comprehensive results of animal studies: BMD and BMC** 

been frequently used for further clarifying related issues.

and disappears within hours after exercise.27 In addition, it has been


Note: a, subjects were divided into three groups (NR, runners with normal BMD; LR, runners with low BMD, C, control group); b, runners were divided into five groups according to their training mileage per week, BMI value was not matched among groups that control group showed the highest value;↓, runners were comprehensively lower than control group in total body and local bone; =, no significant difference was shown between runners and control group; SS↑, runners showed site-specific increment in BMD;↑, runners showed higher BMD in total body as well as in local bone.

Table 1. Summary of cross-sectional studies of BMD in adolescent or young adult distance runners

#### **2.1.2 Results of human studies: Bone metabolism status in distance runners**

As mentioned above, ERT conferred no clear benefits to bone health. An important inquiry is whether endurance running influences the physiology (*e.g.* exercise-induced acidosis) or causes related abnormalities in hormonal homeostasis (*e.g.* menstrual disorders in females or lower testosterone in males) that negatively affect the bone.

♀, 161.7, 18.71.5, 6hr/wk for >2yr

8.43.4h/wk for 6.02.1yr

♂, 24.23.2 yr, 20.31.3, 70mile/wk for at least 1yr

12yr

♂, 27.66.1yr, 21.91.3, 8.72.7h/week, club level runners

♀, 17.61.4 yr, 21.31.6, 8.41.2 h/wk for 6.21.7 yr, high school level athlete

> ♂, 26.65.5yr, 20.9, 9.252h/wk for 8.9 yr

or lower testosterone in males) that negatively affect the bone.

Note: a, subjects were divided into three groups (NR, runners with normal BMD; LR, runners with low BMD, C, control group); b, runners were divided into five groups according to their training mileage per week, BMI value was not matched among groups that control group showed the highest value;↓, runners were comprehensively lower than control group in total body and local bone; =, no significant difference was shown between runners and control group; SS↑, runners showed site-specific increment in BMD;↑, runners showed higher BMD in total body as well as in

Table 1. Summary of cross-sectional studies of BMD in adolescent or young adult distance

As mentioned above, ERT conferred no clear benefits to bone health. An important inquiry is whether endurance running influences the physiology (*e.g.* exercise-induced acidosis) or causes related abnormalities in hormonal homeostasis (*e.g.* menstrual disorders in females

**2.1.2 Results of human studies: Bone metabolism status in distance runners** 

Egan et al.19 ♀, 21.52.6 yr, 20.23,

Brahm et al.3 ♀&♂, 32yr, 22, 7h/wk for

Greene et al.20

Fredericson et al.21

Stewart & Hannan24

Duncan et al.22

Kemmler et al.23

local bone.

runners

training mileage did not show difference in BMD as compared to control group.

Runner showed higher BMD and BMC in distal tibia, densitometric measurement performed only in distal tibia.

All sports groups had higher BMD values than did the controls. Runners showed a higher BMD only in legs and proximal femur, but lower than rugby athletes.

Soccer player was higher in BMD of the skeleton at all sites measured. Runners only showed higher BMD in calcaneus than control group.

Runners were significantly higher in total body, legs, femoral neck, trochanter wards triangle and calcaneus BMD than control group.

Runners showed higher total body and legs BMD.

Runner were significantly higher in total body, lumbar spine, femoral neck and leg BMD as compared to BMI-matched control group

Runners were higher in total body BMD, legs, pelvis, femoral neck, calcaneus BMD as compared to the BMI (20.7) matched control group

SS↑

SS↑

SS↑

↑

↑

↑

↑

It's well known that patients with pathological acidosis suffer negative bone turn-over, which causes a net bone mineral loss.26 Endurance exercise may induce acidosis, which negatively affects bone metabolism. However, transient acidosis caused by exercise is buffered by HCO3 and disappears within hours after exercise.27 In addition, it has been suggested that acid buffer capacity is enhanced after a period of exercise training.28 At the cellular level, a single bout of intense exercise induces transient increases in serum and urine calcium levels without showing cellular osteoclastical activities.29,30

With respect to the impact from abnormalities of hormone regulation, oligomenorrhea and amenorrhea related to bone loss are often reported in female runners undergoing intensive training. However, recent investigations suggest that endurance running does not directly cause menstrual disorders and the subsequent bone loss.31-33 Menstrual disorders in endurance runners are more likely due to either energy or nutrition deficiencies. Therefore, dietary adjustment is usually more effective than hormone replacement therapy for restoring menstrual cycles and bone metabolism.34 In males, ERT is known to lower testosterone, but lower testosterone does not necessarily correlate with lower BMD.35 In addition, runners with different training mileage (from 5 to 75 mile/week) do not significantly differ in serum testosterone levels.15

Regarding studies of bone metabolism status, healthy distance runners at rest usually exhibit normal bone metabolism, and some studies even show a positive bone metabolism status, as revealed by serum bone markers.3, 4 Brahm *et al.,* in a study of bone metabolism in runners using various serum markers, found that runners had lower bone formation as well as lower bone resorption activities.3 Moreover, triathletes reveal no difference in bone metabolism during the intense competitive season as compared to their non-training period.4
