Sage Journals: Discover world-class research

Abstract

The importance of optimal bone growth in childhood and adolescence has been recognized as one of the key strategies in osteoporotic fracture prevention. Low birth size, poor childhood growth, and low peak bone mass at the cessation of growth have been linked to the later risk of osteoporosis and hip fracture. Formerly, the focus was merely on maximizing bone mineral accrual because a high peak bone mineral mass may prevent attainment of a critical “fracture threshold” associated with age-related bone loss and osteoporosis. More recently, the focus has shifted away from bone mineral accrual—as measured by dual-energy X-ray absorptiometry (DXA)—toward the optimization of bone strength. This is partly because of the advances in bone imaging that have enabled estimation of bone strength beyond bone mass. In this review, we briefly describe long-bone growth and structural development and our abilities to assess bone properties by medical imaging tools. In addition, we summarize the evidence of factors contributing to skeletal growth, bone fragility, and the development of strong, healthy bones.

Keywords

bone structure bone strength pQCT DXA physical activity muscle nutrition

‘Encouraging optimal bone growth in childhood and adolescence has been recognized as one of the key strategies in osteoporotic fracture prevention.’

Introduction

Osteoporosis, through its association with age-related fractures, is one of the most common causes of long-standing pain, functional impairment, disability, and death in elderly populations.¹ Encouraging optimal bone growth in childhood and adolescence has been recognized as one of the key strategies in osteoporotic fracture prevention.² Low birth size, poor childhood growth and low peak bone mass at the cessation of growth have been linked to the later risk of osteoporosis and hip fracture.^2,3 Formerly, the focus was merely on maximizing bone mineral accrual because a high peak bone mineral mass may prevent attainment of a critical “fracture threshold” associated with age-related bone loss and osteoporosis.⁴ More recently, the focus has shifted away from bone mineral accrual—as measured by dual-energy X-ray absorptiometry (DXA)—toward the optimization of bone strength. This is partly a result of the advances in bone imaging that have enabled estimation of bone strength beyond bone mass.^5,6 New imaging techniques, such as peripheral quantitative computed tomography (pQCT) and high-resolution pQCT (HR-pQCT), can provide information on bone size, geometry, architecture, and tissue densities within the imaged portion of the long bone, and these parameters can be used to estimate bone strength. Moreover, both pQCT and HR-pQCT can distinguish trabecular (spongy bone) and cortical (compact bone) bone properties.⁷ It should be noted that peripheral imaging techniques can measure long bones in the upper and lower extremity only, and thus, the obtained information is limited to the assessment of long-bone growth and development. However, this information is important because long-bone ends are susceptible to fractures during growth and later in life.^8,9

In this review, we will first briefly describe long-bone growth and structural development in terms of alterations in length and size in addition to mineral mass and density. This is followed by a description of our abilities to assess bone properties by medical imaging tools. These considerations are important for our understanding of factors that contribute to skeletal growth, bone fragility, and the development of strong, healthy bones. Evidence of these factors will be summarized in the following sections.

Bone Growth Processes

There are 2 distinct skeletal growth processes in humans. Flat bones, such as the scapulae, are formed by a process called (intra)membranous ossification. Long bones, such as the femur, develop by a combination of membranous and endochondral bone formation.¹⁰ Because it is the long bones that are most susceptible to fragility fractures, a brief discussion of long-bone growth is warranted. During childhood and adolescence, bone structure is altered by growth in length and size (eg, width or area).¹¹ Bone growth in length occurs at the growth plate (also called the epiphyseal plate), located just before the long-bone end (epiphysis). At the growth plate, cartilage is replaced by bone, and this process is known as endochondral ossification. A child’s bone lengthens when bone formation proceeds outward from these growth plates. To maintain the structural stability of growing long bone, the bone diameter needs to enlarge along the long-bone shaft.^11,12 Growth in diameter occurs by apposition of new bone on the outer (periosteal) bone surface of the cortex. Concurrently, resorption in the inner (endosteal) bone surface excavates the marrow cavity in the tubular long-bone shaft. When periosteal apposition is greater than endosteal resorption, the cortical wall thickens or drifts farther away from the bone center in bone shafts.¹³ To preserve long-bone shape (wider ends and narrower shafts), the long bone undergoes metaphyseal inwaisting in the region between bone end and shaft (metaphysis).¹³ Metaphyseal inwaisting is achieved by periosteal resorption and endocortical apposition of bone.¹¹ Overall, growth in length and size are associated with increases in bone mass and density and constant alterations in bone structure.

Changes in skeletal length and size are closely tied to changes in bone mass, with approximately one-quarter of adult total-body bone mineral accrued during the 2 years around the adolescent growth spurt.¹⁴ These structural and material changes are under mechanical regulation and influenced by the hormonal environment.^6,10,15 During growth, bones must continually adapt their structure and mass to withstand loads from increases in bone length (ie, stature), muscle mass, and external forces.¹¹ However, the tempo, timing, and extent of such adaptations are also closely regulated by systemic hormones.^16,17 Changes in the bone mass, size, and structure are modified by 3 distinct processes: growth, modeling, and remodeling.¹⁸ During the life span, a single process may dominate at certain times, or the 3 processes may function concurrently at other times. In the immature skeleton, all 3 processes may be active simultaneously, with each having a different function.

Growth is the expression of the genetically programmed, hormone-mediated process of enlargement for the entire skeleton without regard to concurrent changes in shape that may be occurring regionally in response to local loading factors. In humans, skeletal growth is largely completed before the third decade of life.

Modeling is the main process altering the shape and mass of the skeleton.¹⁰ Modeling represents a regional response to specific loading conditions, whereby new bone is formed without prior resorption, resulting in a change in shape and size of bone. Because young bone has a greater potential for adaptation to loading than aging bone,¹⁹ the modeling process occurs primarily during growth and results in a net gain in bone over time.²⁰

Remodeling, although present in young individuals, is the predominant process modifying bone shape and mass in adults. It allows for the replacement of fatigue-damaged bone with new bone.²¹ In addition to serving a preservation function, it provides a mechanism for the maintenance of calcium homeostasis. The remodeling cycle begins with an activation phase, followed in sequence by a resorption phase and a formation phase, which are coupled.¹⁰ In mature bone, bone remodeling results in a net loss of bone over time because newly formed bone never completely replaces the bone that has been resorbed, resulting in a decrease in bone mineral mass (ie, bone mineral content, BMC) and alteration in bone structure.²² In contrast, growing skeleton is able to gain bone mineral from modeling or remodeling.¹⁸ Finally, bone remodeling is an integral part of fracture healing in both the growing and mature skeleton.²³

Measuring Bone Mass and Strength in Growing Skeleton

Medical imaging tools enable noninvasive assessment of bone properties, which can be used to estimate bone strength development during growth. Bone strength can be defined as the bone’s ability to resist fracture at a given loading condition. The strength of a long bone depends on the amount of bone mass, the spatial distribution of the bone mass (eg, bone size, geometry, and architecture), and the bone’s material properties.^6,24

The clinical assessment of bone strength in pediatric studies previously relied on DXA-derived BMC (g) or areal bone mineral density (aBMD, g/cm²).⁷ Because of a high correlation between actual skeletal mass and total-body BMC, the term bone mass is often used synonymously with BMC.²⁵ Although DXA-derived bone mass and aBMD predicts experimentally derived bone strength (eg, failure load),^7,26,27 aBMD is a poor indicator of fracture risk.^28,29 Fractures unrelated to aBMD could be a result of deterioration in bone size, structure, and strength, which 2-dimensional (2D) DXA measures cannot detect. Because of this 2D limitation, DXA-derived aBMD is influenced by bone size, and individuals with larger bones have (artificially) higher aBMD. Therefore, bone mass (BMC) rather than aBMD should be reported in pediatric DXA studies.³⁰ Limitations aside, a low effective radiation dose (eg, about 10 µSV for a whole-body scan³¹) from DXA scanning makes DXA suitable for monitoring bone mass changes in growing skeleton, especially during the pubertal growth spurt when bone mineral is accrued rapidly.^14,32 Figure 1 illustrates a total-body BMC change from 8 to 14 years of age in a healthy girl. During 6 years of growth, her total body BMC more than doubled, from 937 to 2098 g.

Figure 1.

Whole-Body DXA Scans From a Female PBMAS Participant Illustrates 6 Years of Skeletal Growth From (A) 8 Years to (B) 14 Years of Age.

3D Imaging techniques, such as pQCT and HR-pQCT, are common research tools. Peripheral QCTs provide (volumetric) information of bone structural and densitometric properties from total, trabecular, and cortical compartments^7,33 (Figure 2). Effective radiation doses are low for pQCT (about 0.3 µSV per scan) and HR-pQCT (about 3 µSV per scan), making these techniques suitable for pediatric studies.^34,35 Volumetric density is independent of bone size and thus can be assessed in pediatric studies.³⁶ However, the reliability of cortical density assessment depends on the cortical thickness and resolution of the obtained images.^37,38 Cortical density can be measured at long-bone-shaft sites using pQCT (resolution commonly 400-600 µm), whereas HR-pQCT (resolution 82 µm) is needed to assess cortical bone properties from thin cortex at the wrist (distal radius) and ankle (distal tibia).^35-37 High-resolution imaging also enables assessment of other microarchitectural characteristics of bone, such as cortical porosity, trabecular number, and trabecular thickness at the distal radius and tibia.^39,40 HR-pQCT can also be used in conjunction with engineering-based computer simulation, known as finite-element (FE) modeling, to estimate bone strength. This method evaluates how a structure with a complex shape and varying tissue properties behaves when subjected to loading. Its basic premise is to divide a complicated object into a finite number of small manageable pieces (elements), whereby the behavior of each element can be described mathematically and evaluated computationally.⁴¹ FE modeling of imaged bone provides estimates of bone failure load and whole bone stiffness (flexibility of bone),²⁷ which previously were only attainable via destructive mechanical testing of cadaveric bone samples. The FE method also provides unique information impossible to measure experimentally, such as stresses and strains inside whole bones. A specific advantage of FE modeling is that bones can be analyzed multiple times with different loading directions and bone properties to simulate how whole bone will behave under different conditions and disease states.

Figure 2.

A. High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Image Illustrating Trabecular Microarchitecture and Thin Cortical Shell at the Distal Radius (Metaphysis) From a 9-Year-Old Girl. B. Cross-sectional pQCT Image of the Wrist Demonstrating Ulna (Left) and Radius Metaphyses and Surrounding Soft Tissue. C. pQCT Image of the Forearm Illustrating Cortices of Ulna (Left) and Radius Shafts (Diaphyses) and Surrounding Muscle (Light Gray) and Subcutaneous Fat (Darker Gray) Tissues From the Same Girl Measured 10 Months Prior to HR-pQCT Scanning. Red Streaks in the Forearm Image Are Minor Movement Artifacts That Can Be Excluded From the Image During the Scan Analysis Process.

Skeletal Growth and Bone Fragility

Prospective follow-ups show that bone mineral mass more than doubles between 8 and 15 years at total-body and different skeletal sites.^14,42 The peak gains in BMC at the lumbar spine, femoral neck, and total body occur at about age 13.0 for girls and 14.4 years for boys, which is explained by the earlier onset of sexual maturation in girls.¹⁴ Longitudinal DXA data from the Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS) indicated that in the 3 years around peak height velocity (ie, growth spurt), about 30% of BMC in the total body and lumbar spine was laid down and about 20% of femoral neck BMC was accumulated.^14,43 These data are consistent with other studies showing that bone mineral accrual increases progressively in early childhood^44,45 and then accelerates during adolescence.^42,45 In a PBMAS cohort, both girls and boys achieved about 90% of their final adult height at the time of the peak height velocity but had only achieved about 57% of their estimated adult total-body and lumbar spine BMC and about 70% of the estimated femoral neck BMC values.⁴⁶ For all sites, peak velocity in BMC occurred over a year later than the growth spurt in both girls and boys.⁴⁶ This lag time between mineralization and rapid growth in bone length and size has important clinical implications because this dissociation may partly explain increased fracture incidence during adolescence.^38,47-49

During the adolescent growth spurt, the most common fracture site is the distal forearm.^47,50,51 It is poorly understood why fractures are common during the adolescent growth spurt.⁵² DXA-derived whole-body BMC continues to increase during puberty and thus cannot explain this temporary increase in bone fragility.⁴² Cross-sectional pQCT evidence indicates that total bone area at the distal radius increases across puberty but not always enough to offset the external load from a fall.^38,53 It is assumed that the rapid metaphyseal inwaisting results in a thin, weak cortex predisposing to fracture if a child falls.^11,38 To support this assumption, evidence from HR-pQCT comparison indicated lower cortical thickness and bone volume fraction and higher cortical porosity in boys and girls around the peak incidence of forearm fractures.^53,54

Growth during infancy, childhood, and adolescence is important for bone health later in life. Infant and early childhood growth predicts adult bone mass independently of adult lifestyle.² Both low birth size and poor childhood growth are directly linked to the later risk of hip fracture.⁵⁵ The evidence of mineral accrual during adolescence indicates that the population variance in bone mass and in structural traits is probably largely established by the end of the second decade.^56-58 Pubertal timing seems to determine some variance in bone development.

Earlier maturation may be beneficial for bone development and protective for fracture risk in adolescence and young adulthood. Evidence from the PBMAS cohort, followed for 15 years from adolescence to young adulthood, showed that late-maturing girls gained less mineral in their total body than their early or average maturing peers.⁵⁹ However, maturation timing was not associated with bone mass accrual in boys or development in the estimated structure and strength at the hip (proximal femur) in either sex in the PBMAS cohort.^56,59 In contrast, maturational timing predicted bone mass negatively at the age of 16 in both boys and girls in a shorter prospective follow-up.⁶⁰ Cross-sectional evidence from a large cohort of young adult men also suggested that maturational age is a negative predictor of both cortical and trabecular bone size and volumetric BMD.⁶¹ It is important to note that later maturational age was linked to fractures in this cohort.⁶¹ Recent evidence from studies of young women lends credence to this finding, showing later pubertal timing in women who had suffered one or more fractures during childhood and adolescence when compared with their fracture-free peers.⁶² Association between fractures and later maturity might be related to the observed deficits in trabecular density, thickness, and estimated strength (stiffness, failure load, and apparent modulus) in the distal radius or tibia in the women experiencing fractures when compared with their peers who did not.^62,63 Based on this evidence, the earlier maturing girl may have an advantage in her bone mass and strength development over the late-maturing girl, and this advantage may be protective against fractures. However, site- and sex-specificity in the role maturational timing plays in adult bone structure and strength needs to be addressed in future follow-ups.

Optimizing Bone Mass and Strength Development During Growth

To optimize bone strength development, we need to identify those modifiable factors that can enhance or retard the attainment of bone mass, structure, and strength during growth. Bones adapt their strength according to the mechanical forces they experience. Studies with healthy children and adolescents highlight the potential of modifiable factors such as physical activity, lean mass, or muscle cross-sectional area in determining bone mass accrual, bone size, tissue density, and estimated strength. Key factors that determine and influence the development of bone mass, structure, and strength are listed below.

Nonmodifiable Factors

Genetics and Sex

Evidence from familial resemblance and twin studies indicates that genes control about 50% to 85% of the variance in bone mass or aBMD⁶⁴ but a much smaller (<20%) proportion of the variance in rate of bone loss⁶⁵ or fractures.^66-69 Genetic influences on the skeleton are thought to contribute mainly to the acquisition of bone mass during childhood and adolescence,^70,71 possibly by interacting with environmental factors such as physical activity and nutrition. The trait variance in the population is largely the result of diversity in genetic makeup rather than lifestyle.^64,72 However, at the individual level, environmental effects such as muscle paralysis⁷³ or exercise¹⁹ have profound effects on bone structure and estimated strength.

As the heritability of bone mass is stronger than aBMD, some of the familial resemblance in aBMD may simply reflect the heritability of body size.⁷⁴ Only 1 study has reported the genetic influences on bone size, showing a heritability estimate of 27% for the cross-sectional area at the distal radius in young adults.⁷⁴ Heritability estimates for trabecular and cortical bone density has been shown to be higher: 40% to 60% depending on the bone site.⁷⁵ These results are in accordance with a meta-analysis of genome-wide scans, which concluded that genetic regulation of bone mass is sex and site specific.⁷⁶ Part of the collinearity between heritability of body and bone size (or mass) may also be related to lean mass and muscle size and their development.^77-80 The important aspect regarding bone fragility prevention is that these traits can be enhanced by a physically active lifestyle and healthy diet.

Fractures of the wrist and hip have strikingly different age- and sex-specific incidence patterns.⁹ To optimize preventive efforts, we need to understand how bone strength develops and declines for both sexes. Small or nonexistent sex differences in BMC, density, and structure at axial or appendicular skeletal sites have been reported in childhood and adolescence.^12,46,81-89 Observations appear to be specific to the measured site and technology used and how body size and composition—especially lean mass or muscle size—were controlled for in the analysis. The most comprehensive evidence of sex differences in bone development during pubertal growth comes from longitudinal PBMAS data. After adjusting for differences in maturation, height, and body composition, BMC development in the total body and femoral neck were noted to be slightly greater in boys than girls across puberty.⁴⁶ Structural analysis of hip bone scans from the same cohort indicated a greater estimated strength (section modulus) in femoral neck across the pubertal growth in boys when compared with girls but a smaller increase in the femoral neck area after the growth spurt.⁸⁵ This evidence of a greater bone mineral gain (relative to muscle) in the female skeleton occurring later in the pubertal growth period is supported by cross-sectional comparisons between male and female participants in studies.^77,84,90-92 It has been suggested that this “extra” bone mineral provides a calcium reservoir for reproductive purposes.^22,91-94 Observations of similar cortical thickness between sexes have indicated that girls have either endosteal apposition⁹⁵ or diminished resorption at the endosteal (inner) bone surface in puberty.¹² Because women may gain more endosteal than periosteal bone, their bones strengthen less than in men, who tend to have more periosteal bone formation and thus greater increase in overall bone size during the growth. Absolute sex differences in adult BMC and bone size may also reflect greater overall body growth because of the longer pubertal growth period in boys than girls. In women, earlier completion of longitudinal growth with epiphyseal fusion and earlier inhibition of periosteal apposition likely results in smaller bone size and generally weaker bone when compared with men.^12,95

Modifiable Factors

Physical Activity

It is important to note that modeling and remodeling described earlier in the article are essentially under the control of the mechanical strain environment (such as strain magnitude, rate, and frequency). This functional model of bone development is based on the mechanostat model.^22,96,97 In this model, bone cell action is coordinated by the mechanical requirements of the bone.^96,97 If bone is not exposed to mechanical loading, the lack of stimulus (strain) results in increased remodeling, with subsequent loss of bone mineral and likely alterations in bone structure. Mechanical loading that is familiar to bone will be sufficient to maintain bone mass and structure, thereby maintaining remodeling and modeling in a steady state. Loading that produces an unusual strain environment to bone tissue can initiate a remodeling and/or modeling response. In the mechanostat model, the bone response to an altered strain environment is based on physiological set points, which act as thresholds for the initiation or inhibition of bone modeling and remodeling. Increases in stature, body, and muscle mass during growth will, in part, increase the forces placed on bone, leading to greater bone strain and adaptation.⁹⁶ We have illustrated this concept of functional bone adaptation in Figure 3.⁹⁸ Similarly, the mechanostat model could be used to explain bone adaptation to increased bone loading and related increase in bone strain (tissue deflection) resulting from physical activity. For example, if a girl unaccustomed to gymnastics practices handsprings, her bones at the wrist are exposed to a new loading environment with increased strains. In response, these bones will model and adapt to the new loading environment by increasing bone mass, bone size, and modeling bone structure. After adapting bone structure and mass, the bone will be better able to resist applied loads, and strains will return to a steady state (Figure 3). Progressively increased training stimulus is needed for continuous bone adaptation, thereby avoiding acute and chronic injuries related to intensive training.⁹⁹ Bone adaptation can be measured noninvasively by assessing changes in bone properties using earlier described imaging techniques (Figure 3). Bone strain characteristics cannot be measured noninvasively or with these imaging techniques. However, there are some promising biomechanical modeling techniques that will likely enhance our ability to use noninvasive imaged data in modeling simulations to estimate bone strain in vivo.¹⁰⁰

Figure 3.

A Functional Model Illustrating the Regulation of Bone Strength Development During Growth. The Model Is Based on the Mechanostat Theory (Modified From References 6 and 98).

Observational studies have provided evidence of greater bone mineral mass, not only in child and adolescent athletes involved in gymnastics or other high-impact activities but also in children and adolescents who simply had a more physically active lifestyle.^14,101-103 Exercise trials have supported this evidence by showing a 3% to 6% greater bone mass accrual in children randomized to exercise intervention when compared with the bone accrual in the control group.^104-109 Weight bearing and high-impact activities such as jumping exercises and step aerobics have shown bone mass benefits at the loaded bone sites of the lower extremities and lumbar spine.¹¹⁰ However, what constitutes the optimal exercise program for bone adaptation remains unclear.¹¹⁰

Evidence remains inconclusive if the bone mass benefit acquired during the growing years persists into adulthood. To date, studies examining the effects of physical activity during childhood and adolescence on adult bone mass have been limited to retrospective assessments of physical activity^111-113 or earlier measured youth physical activity^114-117 to adult bone mineral status. Follow-up data of retired athletes have provided evidence of both sustained^116-119 and partially lost¹²⁰ bone benefit after reduced or ceased activity, whereas exercise-induced bone gain has been reported to persist 1 to 8 years after exercise intervention in prepubertal or early pubertal children.^121-123

Prospective observations from the Saskatchewan PBMAS cohort showed a 9% to 17% greater bone mineral accrual in physically active children when compared with their less-active peers.¹⁴ These studies have lent credence to the concept that physical activity in prepuberty and early puberty provides a unique opportunity to enhance bone accrual and peak bone mass. However, even if exercise during the growing years affects bone accrual, the importance of these effects from a clinical perspective depends on their permanence. The long-term implications of these benefits on adult bone mass can only be established with prospective longitudinal studies that follow individuals from childhood to adulthood. The follow-up data of these same individuals in young adulthood suggest that these benefits in bone mass persist into early adult life.¹²⁴

The effect of physical activities and loading on growing bone structure and strength relies mainly on observational evidence.¹²⁵ Unilateral tennis studies that compared side-to-side differences between players who begin their career prior to or after the growth spurt have provided the strongest observational evidence that increased BMC is a result of enlarged bone size, which leads to greater estimated strength in the long bone.¹⁹ Cross-sectional comparisons in young and retired gymnasts supported these findings.^126-132 Comparisons of the side-to-side differences in bone mass, structure, and strength between unilaterally loaded tennis players and their controls also pinpointed that the bone benefit is greater if physical activity was initiated prior to skeletal maturation.^19,133 Specifically, the benefit in estimated bone strength was more than twice as much (ie, 26%) in women who had begun playing prior to menarche when compared with the 11% strength benefit in the loaded site of the women who started the unilateral activity at a later age.¹⁹ There are no randomized controlled trials that have assessed the effect of exercise on bone structure and strength in the upper extremities.¹²⁵ To date, evidence from randomized controlled trials assessing bone structural and strength changes is limited to investigating bone adaptation in the lower limb.¹³⁴ In this 16-month trial, an additional 15-minute physical activity resulted in an increase in bone strength at the distal tibia (measured by pQCT) in prepubertal boys.¹³⁴ This intervention included a novel bone loading component of 3 short (3-minute) jumping sessions during the school day.¹³⁴ When bone strength adaptation was estimated in the proximal femur from DXA images, intervention benefit was noted in prepubertal and early pubertal girls only.¹³⁵ Further experimental evidence is needed to clarify site, maturity, and sex specificity in bone structural and strength adaptation to exercise during growth.

Muscle and Fat Tissue

Pediatric bone studies have been in the forefront to provide evidence of the importance of lean mass^136-139 and muscle cross-sectional area^140-142 on bone mass accrual and strength development. Lean mass and muscle size are commonly used as surrogate measures for forces from mechanical loading, and these traits have been associated with enlarged bone mass, size, and strength.^143,144 In contrast, higher fat mass has been associated with smaller and less-dense cortical and trabecular bone and lower bone strength in young girls.^145,146 In terms of absolute bone strength, overweight children seem to be at an advantage, but this is because of adaptation to their larger muscle size, not excess body fat.¹⁴⁷ These findings are in accordance with the mechanostat model, which postulates that the growing skeleton adapts its mass, structure, and strength to keep loading-induced strains within an acceptable range^{79,141,148,149} (Figure 3). The age of peak lean tissue velocity precedes the peaks in the estimated bone size and strength at the proximal femur.¹⁵⁰ These observations were derived from DXA images, using hip structure analysis,¹⁵⁰ and they support the theory that muscle development is an important factor in bone strength development. However, there is a lack of comprehensive longitudinal data from both sexes linking bone structural and strength development in growing years to bone strength in adulthood.

Nutrition

In addition to physical activity, diet during the growing years has been associated with bone mineral accrual in childhood and adolescence.^{42,114,151-153} Two important nutritional aspects related to bone mineral have been noted in the past years: (1) a shift in emphasis from calcium to vitamin D (especially D₃ form) influences on bone^154,155 and (2) an interest in dietary patterns, in particular the importance of fruit and vegetable consumption on bone health.^156,157 The average calcium accretion is 92 to 210 mg/d in 9- to 18-year-old boys and girls,¹⁵⁸ and bone calcium accretion can peak at 300 to 400 mg/d.⁴² The current recommendation of 1300 mg calcium per day for 9- to 18-year-olds meets the needs for skeletal growth in practically all adolescents.¹⁵⁹ Calcium supplementations produce a small (1% to 2%) effect in the upper-limb aBMD.¹⁶⁰ This small increase is probably not likely to result in a clinically significant decrease in fracture risk in the growing skeleton; thus, current evidence does not support the use of calcium supplementation in healthy children as a public health intervention.¹⁶⁰ However, according to the Institute of Medicine 2011 guidelines, adolescent girls continue to be a group at risk for low calcium intakes from food sources.¹⁵⁹

The recommended intake of vitamin D is 600 International Units (IU) per day for children and adolescents in North America.¹⁵⁹ Recommendations for vitamin D intakes from dietary sources are complicated because vitamin D is also synthesized in the skin through sunlight exposure, which varies from person to person. Minimal sun exposure was assumed when the current vitamin D recommendations were established.¹⁵⁹ Inconsistent vitamin D tests used in studies and variance in the description of normal and abnormal ranges for vitamin D (25OHD) levels in children further challenges vitamin D recommendations.¹⁶¹ In northern latitudes without assurance of adequate sun exposure, requirements and recommendations for vitamin D should probably be higher than those currently in place.^154,162 Estimated mean daily vitamin D intakes in PBMAS participants have been relatively constant: 200 to 240 IU for girls and 280 to 320 IU for boys. These are comparable to Canadian youth intakes¹⁵⁸ and lower than the recommended dietary allowance for vitamin D (600 IU/d).¹⁵⁹ The evidence of dose, time, and form of vitamin D for bone strength development and maintenance requires further evidence, especially from children and adolescents with limited exposure to sunlight (eg, northern latitude) and poor nutrition as a result of socioeconomic factors.

Some investigations have indicated a positive relationship between fruit and vegetable consumption and bone mineral accrual.^156,157 This evidence has provided some support to the theory that a low-fruit and low-vegetable diet may lead to chronic, low-grade metabolic acidosis, which may have detrimental effects on long-term bone health.^163-165 On the other hand, high fruit and vegetable consumption may reflect overall healthy dietary patterns. In addition, protein represents another key nutrient for bone health. Prospective studies have suggested that high protein consumption is associated with greater bone mass and lower incidence of osteoporotic fracture.¹⁶³ Furthermore, dietary protein intake of ~2 g protein/kg bodyweight was positively associated with cortical bone size and estimated strength in the radial shaft of healthy children aged 6 to 18 years.¹⁶⁶ Milk and milk products provide not only protein but also calcium and vitamin D, all of which are important for the developing skeleton.¹⁶³ However, North American adolescents have shifted their beverage intake away from milk to sugary, carbonated beverages.¹⁶⁷ High intakes of these beverages may reduce bone mass accrual in adolescents.¹⁶⁷

Smoking

A few studies have shown a negative association between bone mineral and smoking during growth and adulthood in young men^114,168 and women,¹⁶⁹ whereas others have not demonstrated such a relationship.⁷⁹ Smoking during adolescence was negatively associated with aBMD only in men but not in women¹¹⁴; therefore, this relationship may be gender dependent or related to the amount of cigarette consumption.¹⁶⁸ In elderly smokers (both men and women) in whom the effect of smoking has accumulated over several years, aBMD is reduced, bone resorption markers are increased, and fracture risk is elevated. There is limited evidence of an association between smoking and bone size, structure, and volumetric density. In a cohort of young Swedish men, daily smoking was associated with lower cortical thickness,¹⁷⁰ whereas no association was reported in older Spanish women.¹⁷¹

Recommendations

There are still many questions remaining about the complicated mechanisms controlling bone mineral accretion and structural development during the growing years. Prospective studies and well-designed trials are needed to assess adaptation in bone structure and strength, the role of nutrition in this process, and whether bone adaptation related to physical activity during growth is maintained into later years irrespective of adult activity levels.

From a public health perspective, perhaps the greatest questions have to do with the development of strategies directed at relating a condition that appears in elderly people to a largely disinterested teenage population that will not be at risk for 40 or 50 years. The ultimate target population for the prevention of osteoporosis may be the young and not the elderly population.¹⁷² Taking into account the fact that our knowledge of the complicated mechanisms controlling bone mass and structure is still incomplete, on the basis of what we do know, it is possible to offer some sound and prudent lifestyle advice to young people regarding how to optimize bone strength development in order to reduce the risk of bone fragility and fractures later in life.

For overall health benefits, WHO and several national guidelines recommend at least 60 minutes of moderate- to vigorous-intensity physical activity daily for children and adolescents.^173-176 In the US and Canada, this recommendation includes activities that strengthen muscle and bone at least 3 days per week. Examples of bone-strengthening activities include the following: running, jumping rope, basketball, tennis, soccer, playing tag, hiking, and hopscotch.¹⁷⁶ It has to be noted, however, that this recommendation relies on evidence from interventions limited to bone mass (or areal density) assessment and are supported by observational data linking greater bone mass with activities that generate relatively high ground-reaction forces on the lower extremities.^177,178 With further evidence from exercise trials assessing bone structural and strength adaptations in both sexes during skeletal growth, we anticipate that future recommendations will be based on observed dose relationships and include site-specific exercises to optimize bone strength development at fracture-prone sites, including the wrist and forearm. Finally, the accumulating evidence on the negative consequences of sedentary lifestyles on health will likely provide sufficient knowledge to formulate a basis of recommendations on physical inactivity in the near future.¹⁷³

In regard to the current knowledge of physical activities beneficial for bone development in the young, the following fundamentals should be kept in mind: (1) the skeletal response to exercise is greatest at the loaded site and (2) to cause an adaptive response, the training stimulus must be greater than that habitually encountered. On the basis of these fundamentals and the review of the pertinent literature, the following recommendations can safely be offered to the public at large.

An individual should make a lifelong commitment to physical activity at an early age. Growing bones respond to mechanical loading by the addition of new bone and/or a strengthened bone structure. The growing skeleton has better ability to adapt to mechanical loading than the mature skeleton.

Weight-bearing activities that provide impact loading like skipping, aerobics, squash, and basketball are beneficial to bone mass and strength development—especially at the lower extremity bones—than weight-supporting activities such as swimming or cycling.

A variety of physical activities (such as gymnastics) that can be short in duration and include diverse, impact-type loading stimuli to several skeletal sites, including non-weight-bearing upper extremities are recommended.

Progressive increased training allows musculoskeletal adaptation and prevents overloading and related injuries.

Activities that increase muscle size and strength should be encouraged because these can be osteogenic.

Inactivity and immobility should be avoided. When this is not possible because of sickness or injury, even brief periods of physical activity will likely help conserve bone mineral.

The responsiveness of the growing skeleton to physical activity is dependent on the sensitivity of bone to circulating hormone levels and nutritional adequacy. This has important implications for exercise prescription in adolescents, which leads to the following important recommendations.

Children should have a diet of nutritious foods that will meet the recommended dietary intake for calcium and vitamin D, provide adequate but not excessive protein, and limit the intake of sodium and caffeinated beverages (soft drinks and coffee).

A well-balanced diet that is sufficient to meet the energy demands of growth and physical activity should be encouraged.

Cigarettes should be avoided: they may interfere with the attainment of an optimum level of bone mineral and structure following skeletal maturation.

Footnotes

Acknowledgements

Dr Kontulainen acknowledges financial support from the Canadian Institute of Health Research and Saskatchewan Health Research Foundation New Investigator award.

References

US Dept. of Health and Human Services PHS. Bone health and osteoporosis: a report of the Surgeon General: 2003. http://www.surgeongeneral.gov/library/reports/bonehealth/full_report.pdf. Accessed April 16, 2013.

Cooper

Westlake

Harvey

. Review: developmental origins of osteoporotic fracture. Osteoporos Int. 2006;17:337-347.

Seeman

. Pathogenesis of bone fragility in women and men. Lancet. 2002;359:1841-1850.

Schonau

. The peak bone mass concept: is it still relevant? Pediatr Nephrol. 2004;19:825-831.

Genant

Engelke

Prevrhal

. Advanced CT bone imaging in osteoporosis. Rheumatology (Oxford). 2008;47(suppl 4):9-16.

Kontulainen

Hughes

Macdonald

. The biomechanical basis of bone strength development during growth. Med Sport Sci. 2007;51:13-32.

Petit

Beck

Kontulainen

. Examining the developing bone: what do we measure and how do we do it? J Musculoskelet Neuronal Interact. 2005;5:213-224.

Parfitt

. The two faces of growth: benefits and risks to bone integrity. Osteoporos Int. 1994;4:382-398.

Riggs

Melton

III Robb

. Population-based analysis of the relationship of whole bone strength indices and fall-related loads to age- and sex-specific patterns of hip and wrist fractures. J Bone Miner Res. 2006;21:315-323.

10.

Parfitt

. Skeletal heterogeneity and the purposes of bone remodeling: implications for the understanding of osteoporosis. In: Marcus

Feldman

Nelson

, eds. Osteoporosis. Burlington, MA: Elsevier; 2008:71-89.

11.

Rauch

. Bone growth in length and width: the yin and yang of bone stability. J Musculoskelet Neuronal Interact. 2005;5:194-201.

12.

Kontulainen

Macdonald

Khan

. Examining bone surfaces across puberty: a 20-month pQCT trial. J Bone Miner Res. 2005;20:1202-1207.

13.

Enlow

. A study of the post-natal growth and remodeling of bone. Am J Anat. 1962;110:79-101.

14.

Bailey

McKay

Mirwald

. A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the university of Saskatchewan bone mineral accrual study. J Bone Miner Res. 1999;14:1672-1679.

15.

Sievanen

. Hormonal influences on the muscle-bone feedback system: a perspective. J Musculoskelet Neuronal Interact. 2005;5:255-261.

16.

Nilsson

Marino

De Luca

. Endocrine regulation of the growth plate. Horm Res. 2005;64:157-165.

17.

Delemarre-van

Waal

van Coeverden

Rotteveel

. Hormonal determinants of pubertal growth. J Pediatr Endocrinol Metab. 2001;14(suppl 6):1521-1526.

18.

Parfitt

Travers

Rauch

. Structural and cellular changes during bone growth in healthy children. Bone. 2000;27:487-494.

19.

Kontulainen

Sievanen

Kannus

. Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: a peripheral quantitative computed tomography study between young and old starters and controls. J Bone Miner Res. 2003;18:352-359.

20.

Forwood

Burr

. Physical activity and bone mass: exercises in futility? Bone Miner. 1993;21:89-112.

21.

Burr

Forwood

Fyhrie

. Bone microdamage and skeletal fragility in osteoporotic and stress fractures. J Bone Miner Res. 1997;12:6-15.

22.

Frost

. On our age-related bone loss: insights from a new paradigm. J Bone Miner Res. 1997;12:1539-1546.

23.

Wilkins

. Principles of fracture remodeling in children. Injury. 2005;36(suppl 1):A3-A11.

24.

Bouxsein

Seeman

. Quantifying the material and structural determinants of bone strength. Best Pract Res Clin Rheumatol. 2009;23:741-753.

25.

Mazess

Barden

Bisek

. Dual-energy x-ray absorptiometry for total-body and regional bone-mineral and soft-tissue composition. Am J Clin Nutr. 1990;51:1106-1112.

26.

Liu

Manske

Kontulainen

. Tibial geometry is associated with failure load ex vivo: a MRI, pQCT and DXA study. Osteoporos Int. 2007;18:991-997.

27.

Pistoia

van Rietbergen

Lochmuller

. Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images. Bone. 2002;30:842-848.

28.

Marshall

Johnell

Wedel

. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. 1996;312:1254-1259.

29.

Baim

Leslie

. Assessment of fracture risk. Curr Osteoporos Rep. 2012;10:28-41.

30.

Heaney

. How should we evaluate bone mass in children? J Bone Miner Res. 2007;22:1313; author reply 1314.

31.

Blake

Naeem

Boutros

. Comparison of effective dose to children and adults from dual X-ray absorptiometry examinations. Bone. 2006;38:935-942.

32.

Shepherd

Wang

Fan

. Optimal monitoring time interval between DXA measures in children. J Bone Miner Res. 2011;26:2745-2752.

33.

Zemel

Bass

Binkley

. Peripheral quantitative computed tomography in children and adolescents: the 2007 ISCD Pediatric Official Positions. J Clin Densitom. 2008;11:59-74.

34.

Stratec. XCT 2000 Manual Software Version 5.50. Birkenfeld, Germany: Stratec; 2004.

35.

Burrows

Liu

Perdios

. Assessing bone microstructure at the distal radius in children and adolescents using HR-pQCT: a methodological pilot study. J Clin Densitom. 2010;13:451-455.

36.

Burrows

Liu

McKay

. High-resolution peripheral QCT imaging of bone micro-structure in adolescents. Osteoporos Int. 2010;21:515-520.

37.

Binkley

Specker

. pQCT measurement of bone parameters in young children: validation of technique. J Clin Densitom. 2000;3:9-14.

38.

Rauch

Neu

Manz

. The development of metaphyseal cortex: implications for distal radius fractures during growth. J Bone Miner Res. 2001;16:1547-1555.

39.

Nishiyama

Macdonald

Moore

. Cortical porosity is higher in boys compared with girls at the distal radius and distal tibia during pubertal growth: an HR-pQCT study. J Bone Miner Res. 2012;27:273-282.

40.

MacNeil

Boyd

. Accuracy of high-resolution peripheral quantitative computed tomography for measurement of bone quality. Med Eng Phys. 2007;29:1096-1105.

41.

van Lenthe

Mueller

Wirth

. Quantification of bone structural parameters and mechanical competence at the distal radius. J Orthop Trauma. 2008;22:S66-S72.

42.

Bailey

Martin

McKay

. Calcium accretion in girls and boys during puberty: a longitudinal analysis. J Bone Miner Res. 2000;15:2245-2250.

43.

Bailey

. The Saskatchewan Pediatric Bone Mineral Accrual Study: bone mineral acquisition during the growing years. Int J Sports Med. 1997;18(suppl 3):S191-S194.

44.

Slemenda

Reister

Hui

.Influences on skeletal mineralization in children and adolescents: evidence for varying effects of sexual maturation and physical activity. J Pediatr. 1994;125:201-207.

45.

Kroger

Kotaniemi

Kroger

. Development of bone mass and bone density of the spine and femoral neck: a prospective study of 65 children and adolescents. Bone Miner. 1993;23:171-182.

46.

Baxter-Jones

Mirwald

McKay

. A longitudinal analysis of sex differences in bone mineral accrual in healthy 8-19-year-old boys and girls. Ann Hum Biol. 2003;30:160-175.

47.

Bailey

Wedge

McCulloch

. Epidemiology of fractures of the distal end of the radius in children as associated with growth. J Bone Joint Surg Am. 1989;71:1225-1231.

48.

Wang

Alen

Nicholson

. Growth patterns at distal radius and tibial shaft in pubertal girls: a 2-year longitudinal study. J Bone Miner Res. 2005;20:954-961.

49.

Blimkie

Lefevre

Beunen

. Fractures, physical activity, and growth velocity in adolescent Belgian boys. Med Sci Sports Exerc. 1993;25:801-808.

50.

Landin

. Epidemiology of children’s fractures. J Pediatr Orthop B. 1997;6:79-83.

51.

Kawalilak

Baxter-Jones

Faulkner

. Does childhood and adolescence fracture influence bone mineral content in young adulthood? Appl Physiol Nutr Metab. 2011;35:235-243.

52.

Khosla

Melton

III Dekutoski

. Incidence of childhood distal forearm fractures over 30 years: a population-based study. JAMA. 2003;290:1479-1485.

53.

Kirmani

Christen

van Lenthe

. Bone structure at the distal radius during adolescent growth. J Bone Miner Res. 2009;24:1033-1042.

54.

Nishiyama

Macdonald

Moore

. Cortical porosity is higher in boys compared with girls at the distal radius and distal tibia during pubertal growth: an HR-pQCT study. J Bone Miner Res. 2012;27:273-282.

55.

Cooper

Eriksson

Forsen

. Maternal height, childhood growth and risk of hip fracture in later life: a longitudinal study. Osteoporos Int. 2001;12:623-629.

56.

Jackowski

Kontulainen

Cooper

. Maturational timing does not predict HSA estimated adult bone geometry at the proximal femur. Bone. 2011;49:1270-1278.

57.

Baxter-Jones

Faulkner

Forwood

. Bone mineral accrual from 8 to 30 years of age: an estimation of peak bone mass. J Bone Miner Res. 2011;26:1729-1739.

58.

Berger

Goltzman

Langsetmo

. Peak bone mass from longitudinal data: implications for the prevalence, pathophysiology, and diagnosis of osteoporosis. J Bone Miner Res. 2010;25:1948-1957.

59.

Jackowski

Erlandson

Mirwald

. Effect of maturational timing on bone mineral content accrual from childhood to adulthood: evidence from 15 years of longitudinal data. Bone. 2011;48:1178-1185.

60.

Gilsanz

Chalfant

Kalkwarf

. Age at onset of puberty predicts bone mass in young adulthood. J Pediatr. 2010;158:100-105, 105.e1-105.e2.

61.

Kindblom

Lorentzon

Norjavaara

. Pubertal timing predicts previous fractures and BMD in young adult men: the GOOD study. J Bone Miner Res. 2006;21:790-795.

62.

Chevalley

Bonjour

van Rietbergen

. Fractures in healthy females followed from childhood to early adulthood are associated with later menarcheal age and with impaired bone microstructure at peak bone mass. J Clin Endocrinol Metab. 2012;97:4174-4181.

63.

Chevalley

Bonjour

Ferrari

. Deleterious effect of late menarche on distal tibia microstructure in healthy 20-year-old and premenopausal middle-aged women. J Bone Miner Res. 2009;24:144-152.

64.

Parfitt

. Genetic effects on bone mass and turnover-relevance to black/white differences. J Am Coll Nutr. 1997;16:325-333.

65.

Pollitzer

Anderson

. Ethnic and genetic differences in bone mass: a review with a hereditary vs environmental perspective. Am J Clin Nutr. 1989;50:1244-1259.

66.

Andrew

Antioniades

Scurrah

. Risk of wrist fracture in women is heritable and is influenced by genes that are largely independent of those influencing BMD. J Bone Miner Res. 2005;20:67-74.

67.

Nguyen

Eisman

. Genetics of fracture: challenges and opportunities. J Bone Miner Res. 2000;15:1253-1256.

68.

Kannus

Palvanen

Kaprio

. Genetic factors and osteoporotic fractures in elderly people: prospective 25 year follow up of a nationwide cohort of elderly Finnish twins. BMJ. 1999;319:1334-1337.

69.

Michaelsson

Melhus

Ferm

. Genetic liability to fractures in the elderly. Arch Intern Med. 2005;165:1825-1830.

70.

Hirschhorn

. Genetic approaches to studying common diseases and complex traits. Pediatr Res. 2005;57:74R-77R.

71.

Peacock

Turner

Econs

. Genetics of osteoporosis. Endocr Rev. 2002;23:303-326.

72.

Seeman

Hopper

Bach

. Reduced bone mass in daughters of women with osteoporosis. N Engl J Med. 1989;320:554-558.

73.

Ralis

Randall

. Changes in shape, ossification and quality of bones in children with spina bifida. Dev Med Child Neurol Suppl. 1976;(37):29-41.

74.

Havill

Mahaney

Binkley

Specker

. Effects of genes, sex, age, and activity on BMC, bone size, and areal and volumetric BMD. J Bone Miner Res. 2007;22:737-746.

75.

Lenchik

Hsu

. Heritability of spinal trabecular volumetric bone mineral density measured by QCT in the Diabetes Heart Study. Calcif Tissue Int. 2004;75:305-312.

76.

Ioannidis

Sham

. Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass. J Bone Miner Res. 2007;22:173-183.

77.

Schoenau

Neu

Beck

. Bone mineral content per muscle cross-sectional area as an index of the functional muscle-bone unit. J Bone Miner Res. 2002;17:1095-1101.

78.

Macdonald

Kontulainen

Mackelvie-O’Brien

. Maturity- and sex-related changes in tibial bone geometry, strength and bone-muscle strength indices during growth: a 20-month pQCT study. Bone. 2005;36:1003-1011.

79.

Young

Hopper

Nowson

. Determinants of bone mass in 10- to 26-year-old females: a twin study. J Bone Miner Res. 1995;10:558-567.

80.

Macdonald

Kontulainen

Petit

. Bone strength and its determinants in pre- and early pubertal boys and girls. Bone. 2006;39:598-608.

81.

Schoenau

Neu

Rauch

. The development of bone strength at the proximal radius during childhood and adolescence. J Clin Endocrinol Metab. 2001;86:613-618.

82.

Burrows

Liu

Moore

McKay

. Bone microstructure at the distal tibia provides a strength advantage to males in late puberty: a HR-pQCT study. J Bone Miner Res. 2010;25:1423-1432.

83.

Clark

Ness

Tobias

. Gender differences in the ratio between humerus width and length are established prior to puberty. Osteoporos Int. 2007;18:463-470.

84.

Ferretti

Capozza

Cointry

. Gender-related differences in the relationship between densitometric values of whole-body bone mineral content and lean body mass in humans between 2 and 87 years of age. Bone. 1998;22:683-690.

85.

Forwood

Bailey

Beck

. Sexual dimorphism of the femoral neck during the adolescent growth spurt: a structural analysis. Bone. 2004;35:973-981.

86.

Garn

Poznanski

. Early attainment of sex and race differences in skeletal mass. Am J Dis Child. 1987;141:1251-1252.

87.

Gilsanz

Boechat

Roe

. Gender differences in vertebral body sizes in children and adolescents. Radiology. 1994;190:673-677.

88.

Kontulainen

Macdonald

McKay

. Change in cortical bone density and its distribution differs between boys and girls during puberty. J Clin Endocrinol Metab. 2006;91:2555-2561.

89.

Seeman

. Clinical review 137: sexual dimorphism in skeletal size, density, and strength. J Clin Endocrinol Metab. 2001;86:4576-4584.

90.

Hogler

Blimkie

Cowell

. A comparison of bone geometry and cortical density at the mid-femur between prepuberty and young adulthood using magnetic resonance imaging. Bone. 2003;33:771-778.

91.

Schoenau

Neu

Mokov

. Influence of puberty on muscle area and cortical bone area of the forearm in boys and girls. J Clin Endocrinol Metab. 2000;85:1095-1098.

92.

Schoenau

Neu

Rauch

. Gender-specific pubertal changes in volumetric cortical bone mineral density at the proximal radius. Bone. 2002;31:110-113.

93.

Jarvinen

Kannus

Sievanen

. Estrogen and bone: a reproductive and locomotive perspective. J Bone Miner Res. 2003;18:1921-1931.

94.

Schiessl

Frost

Jee

. Estrogen and bone-muscle strength and mass relationships. Bone. 1998;22:1-6.

95.

Garn

. The Earlier Gain and Later Loss of Cortical Bone, in Nutritional Perspective. Springfield, IL: Thomas; 1970.

96.

Schoenau

Fricke

Rauch

. The regulation of bone development as a biological system. Homo. 2003;54:113-118.

97.

Frost

. Bone “mass” and the “mechanostat”: a proposal. Anat Rec. 1987;219:1-9.

98.

Rauch

Schoenau

. The developing bone: slave or master of its cells and molecules? Pediatr Res. 2001;50:309-314.

99.

Caine

DiFiori

Maffulli

. Physeal injuries in children’s and youth sports: reasons for concern? Br J Sports Med. 2006;40:749-760.

100.

Al Nazer

Lanovaz

Kawalilak

. Direct in vivo strain measurements in human bone-a systematic literature review. J Biomech. 2012;45:27-40.

101.

Ginty

Rennie

Mills

. Positive, site-specific associations between bone mineral status, fitness, and time spent at high-impact activities in 16- to 18-year-old boys. Bone. 2005;36:101-110.

102.

Tobias

Steer

Mattocks

. Habitual levels of physical activity influence bone mass in 11-year-old children from the United Kingdom: findings from a large population-based cohort. J Bone Miner Res. 2007;22:101-109.

103.

Janz

Gilmore

Burns

. Physical activity augments bone mineral accrual in young children: The Iowa Bone Development study. J Pediatr. 2006;148:793-799.

104.

Bradney

Pearce

Naughton

. Moderate exercise during growth in prepubertal boys: changes in bone mass, size, volumetric density, and bone strength: a controlled prospective study. J Bone Miner Res. 1998;13:1814-1821.

105.

MacKelvie

Petit

Khan

. Bone mass and structure are enhanced following a 2-year randomized controlled trial of exercise in prepubertal boys. Bone. 2004;34:755-764.

106.

Mackelvie

McKay

Khan

. A school-based exercise intervention augments bone mineral accrual in early pubertal girls. J Pediatr. 2001;139:501-508.

107.

Heinonen

Sievanen

Kannus

. High-impact exercise and bones of growing girls: a 9-month controlled trial. Osteoporos Int. 2000;11:1010-1017.

108.

MacKelvie

Khan

Petit

. A school-based exercise intervention elicits substantial bone health benefits: a 2-year randomized controlled trial in girls. Pediatrics. 2003;112:e447.

109.

Fuchs

Bauer

Snow

. Jumping improves hip and lumbar spine bone mass in prepubescent children: a randomized controlled trial. J Bone Miner Res. 2001;16:148-156.

110.

Hind

Burrows

. Weight-bearing exercise and bone mineral accrual in children and adolescents: a review of controlled trials. Bone. 2007;40:14-27.

111.

Hara

Yanagi

Amagai

. Effect of physical activity during teenage years, based on type of sport and duration of exercise, on bone mineral density of young, premenopausal Japanese women. Calcif Tissue Int. 2001;68:23-30.

112.

Micklesfield

Rosenberg

Cooper

. Bone mineral density and lifetime physical activity in South African women. Calcif Tissue Int. 2003;73:463-469.

113.

Cooper

Cawley

Bhalla

. Childhood growth, physical activity, and peak bone mass in women. J Bone Miner Res. 1995;10:940-947.

114.

Valimaki

Karkkainen

Lamberg-Allardt

. Exercise, smoking, and calcium intake during adolescence and early adulthood as determinants of peak bone mass. Cardiovascular Risk in Young Finns Study Group. BMJ. 1994;309:230-235.

115.

Kemper

Twisk

van Mechelen

. A fifteen-year longitudinal study in young adults on the relation of physical activity and fitness with the development of the bone mass: The Amsterdam Growth And Health Longitudinal Study. Bone. 2000;27:847-853.

116.

Erlandson

Kontulainen

Chilibeck

Arnold

Faulkner

Baxter-Jones

. Higher premenarcheal bone mass in elite gymnasts is maintained into young adulthood after long-term retirement from sport: a 14-year follow-up. J Bone Miner Res. 2012;27:104-110.

117.

Erlandson

Kontulainen

Chilibeck

. Former premenarcheal gymnasts exhibit site-specific skeletal benefits in adulthood after long-term retirement. J Bone Miner Res. 2012;27:2298-2305.

118.

Kontulainen

Kannus

Haapasalo

. Good maintenance of exercise-induced bone gain with decreased training of female tennis and squash players: a prospective 5-year follow-up study of young and old starters and controls. J Bone Miner Res. 2001;16:195-201.

119.

Nordstrom

Olsson

Nordstrom

. Sustained benefits from previous physical activity on bone mineral density in males. J Clin Endocrinol Metab. 2006;91:2600-2604.

120.

Valdimarsson

Alborg

Duppe

. Reduced training is associated with increased loss of BMD. J Bone Miner Res. 2005;20:906-912.

121.

Kontulainen

Kannus

Pasanen

. Does previous participation in high-impact training result in residual bone gain in growing girls? One year follow-up of a 9-month jumping intervention. Int J Sports Med. 2002;23:575-581.

122.

Gunter

Baxter-Jones

Mirwald

. Impact exercise increases BMC during growth: an 8-year longitudinal study. J Bone Miner Res. 2008;23:986-993.

123.

Gunter

Baxter-Jones

Mirwald

. Jump starting skeletal health: a 4-year longitudinal study assessing the effects of jumping on skeletal development in pre and circum pubertal children. Bone. 2008;42:710-718.

124.

Baxter-Jones

Eisenmann

Mirwald

. The influence of physical activity on lean mass accrual during adolescence: a longitudinal analysis. J Appl Physiol. 2008;105:734-741.

125.

Nikander

Sievanen

Heinonen

.Targeted exercise against osteoporosis: a systematic review and meta-analysis for optimising bone strength throughout life. BMC Med. 2010;8:47.

126.

Dowthwaite

Kanaley

Spadaro

. Muscle indices do not fully account for enhanced upper extremity bone mass and strength in gymnasts. J Musculoskelet Neuronal Interact. 2009;9:2-14.

127.

Dowthwaite

Rosenbaum

Scerpella

. Mechanical loading during growth is associated with plane-specific differences in vertebral geometry: a cross-sectional analysis comparing artistic gymnasts vs. non-gymnasts. Bone. 2011;49:1046-1054.

128.

Dowthwaite

Rosenbaum

Scerpella

.Site-specific advantages in skeletal geometry and strength at the proximal femur and forearm in young female gymnasts. Bone. 2012;50:1173-1183.

129.

Dowthwaite

Scerpella

. Distal radius geometry and skeletal strength indices after peripubertal artistic gymnastics. Osteoporos Int. 2011;22:207-216.

130.

Erlandson

Kontulainen

Baxter-Jones

. Precompetitive and recreational gymnasts have greater bone density, mass, and estimated strength at the distal radius in young childhood. Osteoporos Int. 2011;22:75-84.

131.

Tournis

Michopoulou

Fatouros

. Effect of rhythmic gymnastics on volumetric bone mineral density and bone geometry in premenarcheal female athletes and controls. J Clin Endocrinol Metab. 2010;95:2755-2762.

132.

Ward

Roberts

Adams

. Bone geometry and density in the skeleton of pre-pubertal gymnasts and school children. Bone. 2005;36:1012-1018.

133.

Kannus

Haapasalo

Sankelo

. Effect of starting age of physical activity on bone mass in the dominant arm of tennis and squash players. Ann Intern Med. 1995;123:27-31.

134.

Macdonald

Kontulainen

Khan

. Is a school-based physical activity intervention effective for increasing tibial bone strength in boys and girls? J Bone Miner Res. 2007;22:434-446.

135.

Macdonald

Kontulainen

Petit

. Does a novel school-based physical activity model benefit femoral neck bone strength in pre- and early pubertal children? Osteoporos Int. 2008;19:1445-1456.

136.

Janz

. Physical activity and bone development during childhood and adolescence. Implications for the prevention of osteoporosis. Minerva Pediatr. 2002;54:93-104.

137.

Khan

McKay

Haapasalo

. Does childhood and adolescence provide a unique opportunity for exercise to strengthen the skeleton? J Sci Med Sport. 2000;3:150-164.

138.

Vatanparast

Whiting

. Calcium supplementation trials and bone mass development in children, adolescents, and young adults. Nutr Rev. 2006;64:204-209.

139.

Whiting

Vatanparast

Baxter-Jones

. Factors that affect bone mineral accrual in the adolescent growth spurt. J Nutr. 2004;134:696S-700S.

140.

Hsu

Venners

Terwedow

. Relation of body composition, fat mass, and serum lipids to osteoporotic fractures and bone mineral density in Chinese men and women. Am J Clin Nutr. 2006;83:146-154.

141.

Afghani

Goran

. Racial differences in the association of subcutaneous and visceral fat on bone mineral content in prepubertal children. Calcif Tissue Int. 2006;79:383-388.

142.

Adami

Braga

Zamboni

. Relationship between lipids and bone mass in 2 cohorts of healthy women and men. Calcif Tissue Int. 2004;74:136-142.

143.

Leonard

Shults

Wilson

. Obesity during childhood and adolescence augments bone mass and bone dimensions. Am J Clin Nutr. 2004;80:514-523.

144.

Clark

Ness

Tobias

. Adipose tissue stimulates bone growth in prepubertal children. J Clin Endocrinol Metab. 2006;91:2534-2541.

145.

Farr

Chen

Lisse

. Relationship of total body fat mass to weight-bearing bone volumetric density, geometry, and strength in young girls. Bone. 2010;46:977-984.

146.

Farr

Funk

Chen

. Skeletal muscle fat content is inversely associated with bone strength in young girls. J Bone Miner Res. 2011;26:2217-2225.

147.

Wetzsteon

Petit

Macdonald

. Bone structure and volumetric BMD in overweight children: a longitudinal study. J Bone Miner Res. 2008;23:1946-1953.

148.

Goulding

Grant

Williams

. Bone and body composition of children and adolescents with repeated forearm fractures. J Bone Miner Res. 2005;20:2090-2096.

149.

Weiler

Janzen

Green

. Percent body fat and bone mass in healthy Canadian females 10 to 19 years of age. Bone. 2000;27:203-207.

150.

Jackowski

Faulkner

Farthing

. Peak lean tissue mass accrual precedes changes in bone strength indices at the proximal femur during the pubertal growth spurt. Bone. 2009;44:1186-1190.

151.

Matkovic

Goel

Badenhop-Stevens

. Calcium supplementation and bone mineral density in females from childhood to young adulthood: a randomized controlled trial. Am J Clin Nutr. 2005;81:175-188.

152.

Cheng

Lyytikainen

Kroger

. Effects of calcium, dairy product, and vitamin D supplementation on bone mass accrual and body composition in 10-12-y-old girls: a 2-y randomized trial. Am J Clin Nutr. 2005;82:1115-1126.

153.

Macdonald

Kontulainen

Petit

Janssen

McKay

. Bone strength and its determinants in pre- and early pubertal boys and girls. Bone. 2006;39:598-608.

154.

Whiting

Calvo

. Dietary recommendations for vitamin D: a critical need for functional end points to establish an estimated average requirement. J Nutr. 2005;135:304-309.

155.

Sayers

Fraser

Lawlor

. 25-Hydroxyvitamin-D(3) levels are positively related to subsequent cortical bone development in childhood: findings from a large prospective cohort study. Osteoporos Int. 2012;23:2117-2128.

156.

Tylavsky

Holliday

Danish

Womack

Norwood

Carbone

. Fruit and vegetable intakes are an independent predictor of bone size in early pubertal children. Am J Clin Nutr. 2004;79:311-317.

157.

Vatanparast

Baxter-Jones

Faulkner

. Positive effects of vegetable and fruit consumption and calcium intake on bone mineral accrual in boys during growth from childhood to adolescence: the University of Saskatchewan Pediatric Bone Mineral Accrual Study. Am J Clin Nutr. 2005;82:700-706.

158.

Vatanparast

Calvo

Green

. Despite mandatory fortification of staple foods, vitamin D intakes of Canadian children and adults are inadequate. J Steroid Biochem Mol Biol. 2010;121:301-303.

159.

Ross

Manson

Abrams

. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53-58.

160.

Winzenberg

Shaw

Fryer

. Effects of calcium supplementation on bone density in healthy children: meta-analysis of randomised controlled trials. BMJ. 2006;333:775.

161.

Misra

Pacaud

Petryk

. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122:398-417.

162.

Weaver

Fleet

. Vitamin D requirements: current and future. Am J Clin Nutr. 2004;80:1735S-1739S.

163.

Bonjour

. Dietary protein: an essential nutrient for bone health. J Am Coll Nutr. 2005;24:526S-536S.

164.

Henry

Fatayerju

Eastell

. Attainment of peak bone mass at the lumbar spine, femoral neck and radius in men and women: relative contributions of bone size and volumetric bone mineral density. Osteoporos Int. 2004;15:263-273.

165.

Vatanparast

Bailey

Baxter-Jones

. The effects of dietary protein on bone mineral mass in young adults may be modulated by adolescent calcium intake. J Nutr. 2007;137:2674-2679.

166.

Alexy

Remer

Manz

. Long-term protein intake and dietary potential renal acid load are associated with bone modeling and remodeling at the proximal radius in healthy children. Am J Clin Nutr. 2005;82:1107-1114.

167.

Vartanian

Schwartz

Brownell

. Effects of soft drink consumption on nutrition and health: a systematic review and meta-analysis. Am J Public Health. 2007;97:667-675.

168.

Ortego-Centeno

Munoz-Torres

Jodar

. Effect of tobacco consumption on bone mineral density in healthy young males. Calcif Tissue Int. 1997;60:496-500.

169.

Ortego-Centeno

Munoz-Torres

Hernandez-Quero

. Bone mineral density, sex steroids, and mineral metabolism in premenopausal smokers. Calcif Tissue Int. 1994;55:403-407.

170.

Lorentzon

Mellstrom

Haug

. Smoking is associated with lower bone mineral density and reduced cortical thickness in young men. J Clin Endocrinol Metab. 2007;92:497-503.

171.

Hernandez

Seco

Cortes-Prieto

. Gynecological factors and body mass index as determinants of bone mass in normal postmenopausal women. A study with peripheral quantitative computed tomography (pQCT). Eur J Obstet Gynecol Reprod Biol. 2000;92:193-198.

172.

Faulkner

Bailey

. Osteoporosis: a pediatric concern? Med Sport Sci. 2007;51:1-12.

173.

Tremblay

Warburton

Janssen

. New Canadian physical activity guidelines. Appl Physiol Nutr Metab. 2011;36:36-46; 47-58.

174.

O’Donovan

Blazevich

Boreham

. The ABC of Physical Activity for Health: a consensus statement from the British Association of Sport and Exercise Sciences. J Sports Sci. 2010;28:573-591.

175.

World Health Organization. Global Recommendations on Physical Activity for Health. Geneva, Switzerland: WHO; 2010.

176.

Physical Activity Guidelines Advisory Committee. Physical Activity Guidelines Advisory Committee Report. Washington, DC: US Department of Health and Human Services; 2008.

177.

Kohrt

Bloomfield

Little

. American College of Sports Medicine Position Stand: physical activity and bone health. Med Sci Sports Exerc. 2004;36:1985-1996.

178.

Kesaniemi

Riddoch

Reeder

. Advancing the future of physical activity guidelines in Canada: an independent expert panel interpretation of the evidence. Int J Behav Nutr Phys Act. 2010;7:41.

Prevention of Osteoporosis and Bone Fragility

Abstract

Keywords

Introduction

Bone Growth Processes

Measuring Bone Mass and Strength in Growing Skeleton

Skeletal Growth and Bone Fragility

Optimizing Bone Mass and Strength Development During Growth

Nonmodifiable Factors

Genetics and Sex

Modifiable Factors

Physical Activity

Muscle and Fat Tissue

Nutrition

Smoking

Recommendations

Footnotes

Acknowledgements

References