Run, Jump and Be Merry: How Much Exercise is Needed for Building Young Bones?

Regular weight-bearing physical activity is essential for the development of a strong and healthy skeleton. This concept is of particular importance during childhood and adolescence, as over half of peak bone mass is accrued during the teenage years, accompanying development of secondary sexual characteristics and the pubertal growth spurt.⁽¹⁾ The skeletal loading associated with exercise has also been shown in both animal and human models to augment bone size and strength, thus facilitating the development of a structurally optimized skeleton,^(2–4) and data from clinical trials support the skeletal benefits of exercise, particularly during the periods of growth. ^(5–7) However, the exercise prescription that yields optimal bone accrual and skeletal strength for the pediatric skeleton is unknown. Thus, the article of Detter et al.⁽⁸⁾ in this issue of the Journal of Bone and Mineral Research is timely and of high interest.

The study of Detter et al.⁽⁸⁾ was elegantly designed, utilizing data from a prospective, population-based, controlled exercise intervention study with incident fractures, and bone mass and structureas outcomes. The Malmo Pediatric Osteoporosis Prevention (POP) Study captured data from 417 girls and 500 boys in their intervention group and 835 girls and 869 boys in the control group, each age 6–9 years at study entry. The children were enrolled in four neighboring elementary schools in Sweden, from a middle-class socioeconomic status, and each school was government funded, necessitating utilization of a compulsory standard Swedish physical education curriculum. While representing a convenience sample, these aspects of the study are noteworthy as there was less variability at baseline with respect to physical activity. The four schools were also similar in size, important given how the treatment was assigned in the current exercise intervention trial. One of the 4 schools was offered to participate as the intervention school, with the other 3 serving as controls. Fracture incidence was assessed in all participants. Importantly, a sophisticated surveillance system was employed with all fractures verified radiographically. Fractures during the 6-year period were registered in radiological archives from the hospital and a computerized database that included all radiographs obtained in southern Sweden. As there was only one emergency hospital in the city, virtually all fractures were captured, a unique system that has been previously shown to miss less than 3% of all sustained fractures.⁽⁹⁾ This feature of the study is a remarkable one, as fracture verification can be tedious and time-consuming, with efforts often yielding inaccurate data. In a study of children, documentation of fractures is critically important as the International Society for Clinical Densitometry and American Society for Bone and Mineral Research recently convened international experts for the second Pediatric Position Development Conference and deemed that in a child or adolescent, the diagnosis of osteoporosis cannot be established “without clinical evidence of skeletal fragility.”⁽¹⁰⁾

In addition fracture data, anthropometric and skeletal traits were obtained in a subset of participants. Multiple skeletal assessment tools were employed to assess bone density, and skeletal geometry and strength before and after a 6-year physical activity intervention: a 40 minute session every school day (200 min/week) vs. the Swedish standard of 60 min/week provided in 1–2 classes per week. The intervention included ball games, jumping, running and other play. This is a noteworthy feature of the study as the authors tested a feasible and sustainable intervention, including activities and games that children generally enjoy. Seventy-eight girls and 111 boys were in the intervention group, and 52 girls and 54 boys, the control group. All underwent dual-energy X-ray absorptiometry (DXA) measures (hip, spine, whole body) at baseline and annually; 221 adolescents underwent radial and tibial pQCT measurements at the study’s conclusion; 133 underwent QUS calcaneal measures at the six-year follow-up visit; and 248 agreed to wear an accelerometer for 4 consecutive days, 2 and 4 years after study initiation, to verify reported physical activity.

In addition to strengths, there are limitations of this study that merit discussion. DXA was the tool used to obtain measures of bone mass, which can be confounded by bone size, relevant to note in a study of growing children.⁽¹⁾ Additionally, DXA provides little information about bone strength, and no information on bone geometry or microarchitecture which are informative outcomes to consider in determining fracture risk. Another assessment tool, peripheral quantitative computed tomography (pQCT) was employed, but only at the study’s conclusion, which provided information on bone structure, geometry, and volumetric BMD. While the authors acknowledge that it was not possible, valuable information would have been afforded by an evaluation of changes in bone structure and geometry after the intervention, as captured by pQCT. At the six-year follow-up visit, right calcaneal bone traits were also measured by qualitative ultrasound (QUS). This modality has been used in pediatrics much less frequently than in adults, as there is continued debate as to which skeletal properties are captured by QUS. Finally, high-resolution pQCT (HR-pQCT) measurements were not obtained in this trial, and would be needed to explore whether bone geometry or microarchitecture changes in children who have engaged in weight-bearing exercise are sustained as peak bone mass is approached.

Children in this study were assessed during a ‘critical window’ for bone health, with all participants entering the protocol during elementary school.. The skeleton appears to be highly impressionable during late childhood and early adolescence, and thus, more sensitive to an exercise intervention when initiated during this period. This ‘sensitivity’ may relate to skeletal loads introduced to surfaces undergoing fast apposition,^(11–12) a critical concept to consider during adolescence as over half of bone accrual occurs during the teenage years.⁽¹⁾ The current results, including an intervention initiated during late childhood and skeletal benefits noted 6 years later, illustrate this point. An important clinical take-home message is that that any osteogenic intervention begun during these formative years has the potential to enhance peak bone mass. Perhaps most importantly, exercise initiated when an individual is young may augment bone size and strength more dramatically than bone mass, and these ultimate changes in skeletal dimensions and strength may confer long-term benefits for bone health.^(2–4)

Sexually dimorphic results were seen in the current study. Among girls in the intervention group, a higher annual bone accrual rate was observed in femoral neck bone mineral content (BMC), spine bone mineral density (BMD), and a larger gain noted in femoral neck area. A higher tibial cortical BMC was also seen at follow-up, as well as larger tibial cross-sectional area and polar strength strain index (SSI). In fact, there was evidence of skeletal benefit in the girls on measures from all 3 bone assessment tools employed. In boys from the intervention group, only a higher annual accrual rate was seen in spine BMD. No differences were observed in the boys on either pQCT or QUS assessments. Per the rigorous design of the study, sexually dimorphic differences were also seen in the both the axial vs. appendicular skeleton. However, some of the findings may have been due to the reduced physical activity levels in the female participants at baseline as opposed to intrinsic differences between gender groups. Because of lower physical activity levels, the female participates were exposed to greater differences between their habitual and the new loading associated with the intervention, with the differential potentially being a strong predictor of the magnitude of bone adaptation. Nonetheless, the article leaves the reader considering the possibility that the female skeleton may be more receptive to the effects of weight-bearing activity, especially when initiated during pre-pubertal and peri-pubertal years.

What is novel about the study of Detter et al.?⁽⁸⁾ First, many previous studies that have explored the response of the pediatric skeleton to exercise have utilized a cross-sectional design and documented solely measures of bone density, without considering bone size or skeletal strength. The current study examined youth over age 6 years, allowing for repeated measures of multiple bone traits. Most studies have only used DXA, with its inherent limitations, as mentioned, in growing children. The current study used not only DXA, but also pQCT and QUS to afford measures of the appendicular skeleton, important as children typically fracture extremity bones vs. the axial skeleton. There is current consensus that bone strength is the most informative variable to follow to capture skeletal health.⁽¹³⁾ Those studies that have employed tools that afford three-dimensional measures of bone density (e.g., volumetric BMD from pQCT) and estimated strength parameters (such as polar SSI derived from pQCT) are regarded as more informative assessment tools. On a structural level, intense physical activity has also been shown to be associated with high bone mass and larger bone size.^(14–15) Importantly, both in mice and humans, it has been shown that the maintenance of bone size, but not mass are sustained following cessation of exercise.^(2–3) Thus, the most important benefits of exercise may be conferred through changes in bone size. The longitudinal design of the current study afforded some insight into whether sustained exercise during adolescence garners skeletal benefits. However, further observation would have been needed to determine whether the changes were sustained after stopping the intervention.

With any exercise intervention, risks and benefits must be assessed, especially with regard to fracture risk. Safety endpoints included documented fractures over the 6-year study period, and efficacy endpoints, the change in bone mass accrual and gains in bone size. Why would one consider the safety of a running and jumping routine in children and young adolescents? Khosla et al. have shown that that the young adolescent skeleton is particularly vulnerable to fracture during periods of rapid growth, including the early years of puberty, prior to completion of bone accrual and consolidation.⁽¹⁶⁾ The same investigative group used HR-pQCT to explain the microarchitectural basis for the observation of increased fracture frequency among young adolescents.⁽¹⁷⁾ The fractures observed in the current study, with the highest percentage occurring at the distal forearm, replicate findings from other studies of children and adolescents.^(18–19) While the title and take-home message of the current article is that a six-year exercise program improves skeletal traits without affecting fracture risk, each of the above points is important to consider.⁽⁸⁾

Are there public health implications that stem from the data of Detter et al.?⁽⁸⁾ The investigators were clever in the design of their intervention as they chose activities that children generally enjoy as part of routine play (i.e., running and jumping). Thus, the current intervention is one that could be widely adopted by healthy children and adolescents on a population level. Likely more than adults, a child must be engaged to remain compliant with any type of physical intervention. Among contemporary youth, there are concerning trends of inactivity.⁽²⁰⁾ There are also disturbing trends within school systems, with fewer funds being allocated towards physical education classes compared to other activities, with inherent threats to optimal bone accretion and other aspects of health. Additionally, the authors highlight the point that girls tend to reduce their level of activity during puberty.⁽²¹⁾ In fact, the authors hypothesized that they would identify more robust benefits from an exercise program among the girls whom they studied (vs. boys), a finding that bore out. At baseline, school-age girls in the current study were documented to be less physically active than their male peers, which in itself merits reflection regarding accompanying negative health ramifications. Public health efforts should particularly target girls in campaigns to encourage school children and teenagers to become more physically active.

In summary, considering which exercise regimen provides the optimal osteogenic stimulus for bone is a question of high interest and fervent investigation in the skeletal health field. While the study of Detter et al. focused on growing children,⁽⁸⁾ the data are likely to be of interest to pediatric bone clinicians and investigators, as well as those whose focus is the adult skeleton. The amount of bone accrued by skeletal maturity is the primary contributor to peak bone mass, which, in turn, is a major determinant of osteoporosis and fractures later in life.^(1,10) Physical activity introduced during growth has the potential to reduce the burden of fractures during the elderly years.⁽¹⁵⁾ In fact, some experts consider osteoporosis to be a “pediatric disease” given that the underpinnings of this disease appear to occur during early to late adolescence. Paraphrasing the charge in Ecclesiastes to “eat, drink and be merry,”⁽²²⁾ the study by Detter et al. provides data to suggest that children should run and jump, as well! For growing children and adolescents, endorsement of this practice appears to be safe and may eventually lead to optimized peak bone mass, augmented bone size, and gains in skeletal strength, which in turn, may lower their future risk of osteoporosis and fractures as adults.