Canadian Contributions to the understanding of physiology: a focus on bone
January 10, 2017
A look back: Exercise Physiology and CSEP's first 50 years
The Canadian Society for Exercise Physiology will be celebrating its 50th anniversary in 2017.
A signature initiative is a celebration of the contributions of Canadian researchers to exercise physiology over the past 50 years. The objective is to highlight significant Canadian contributors and their contributions to exercise physiology, health and fitness, nutrition and gold standard publications globally as well as provide insights on future research directions in these areas. These achievements have been organized into a series of short historical communiqués on prominent Canadian contributors and will be published on a monthly basis.
The fourth article focuses on bone and looks at some of the key Canadians contributions to the research on exercise and bone; this review aims to provide an overview of that history.
Canadian Contributions to the understanding of physiology: a focus on bone
Chilibeck, P.D.1 and Giangregorio,
1College of Kinesiology,
University of Saskatchewan, Saskatoon SK, S7N 5B2
Kinesiology, University of Waterloo, Waterloo, ON, N2L 3G1, and the Schlegel-UW
Research Institute for Aging
Canadians have made substantial contributions to the research on exercise and bone; this review aims to provide an overview of that history. The first section covers the evolution of imaging techniques used to assess bone and how they have been used to understand the effect of physical activity on bone. Subsequent sections cover important Canadian contributions to research on the influence of physical activity on bone across the lifespan, throughout growth and maturation, and in older individuals at risk of fracture. The final sections cover contributions to basic science on the influence of loading on bone in animal models and at the cellular level, and directions for future research.
Evolution of imaging techniques
Raphael Chow and Joan Harrison from the University of Toronto were some of the first researchers to assess the influence of exercise on bone mass in humans by relating physical fitness (i.e., maximal aerobic power and muscular strength) to the amount of calcium in the body using neutron activation analysis in a group of postmenopausal women (Chow et al. 1986). Their research group went on to develop some of the first exercise programs for people with osteoporosis, showing that loss of whole body calcium could be attenuated with an appropriate exercise program (Chow et al. 1989).
Exercise and bone research evolved with the increased use of imaging techniques to assess bone mineral density (BMD). Don Bailey at the University of Saskatchewan was one of the first to identify a relationship between BMD, as assessed at the calcaneus by computed tomography (CT), and level of childhood physical activity in young women (aged 20-35y) (McCulloch et al. 1990). His work suggested that bone health could be largely influenced by lifestyle factors during growth. Research at McMaster University, led by Duncan MacDougall, Joe Blimkie, Colin Webber, and Chris Gordon used dual photon absorptiometry, which allowed assessment of BMD at more clinically relevant bone sites (e.g., lumbar spine, hip), to assess the relationship between running mileage and BMD in long-distance runners and also used CT scanning to assess bone cross-sectional area in the lower legs (MacDougall et al. 1992). The use of the latter technique was in recognition that the strength of bone is dependent not only on its density but also on its geometry, with a greater cross-sectional area allowing for a greater dissipation of forces applied to bone. They showed that running a moderate distance (i.e., 24-32 km per week) was associated with higher BMD in the legs, and that running greater distances (i.e., 64-88 km per week) was associated with increased cross-sectional area of the tibia and fibula.
A limitation of dual photon absorptiometry was its poor reproducibility, and a limitation of repeat CT scanning is its relatively high radiation exposure. The McMaster group (including Joe Blimkie, Digby Sale and Phil Chilibeck) were some of the first in Canada to use dual energy X-ray absorptiometry (DXA) to measure BMD, which has greater reproducibility (Chilibeck et al. 1994), to assess the relationship between BMD and physical activity level or changes in BMD during exercise training interventions in adolescent girls or young women (Rice et al. 1993; Blimkie et al. 1996; Chilibeck et al. 1996).
A limitation of DXA is that it assesses only “areal” BMD (i.e. in two dimensions as g/cm2). Further, although DXA assessments can be performed at clinically-relevant bone sites (i.e. those susceptible to osteoporotic fracture) at the lumbar spine, hip, and forearm, they were not able to provide information about bone geometric properties. Peripheral quantitative tomography (pQCT) was developed to overcome these limitations, allowing assessment of volumetric BMD (i.e., in three dimensions; g/cm3) and bone geometric properties in the forearm or lower limb, with relatively low radiation exposure. Joe Blimkie, Shawn Davison, Jonathan Adachi, and Colin Webber used pQCT to show that pre-adolescent gymnasts have superior trabecular and cortical volumetric BMD at the forearm compared to healthy non-gymnasts (Dyson et al. 1997). Maureen Ashe and colleagues Karim Khan and Heather McKay at UBC refined the interpretation of pQCT measures by exploring the validity of pQCT measures (i.e. total bone content at the distal radius and cortical thickness at the mid-shaft of the radius) to predict bone strength by scanning radial specimens from older females and directly determining bone strength (Ashe et al. 2006).
More advanced pQCT analysis has been used to assess micro-architectural properties of bone. Norma MacIntyre, Jonathan Adachi, and Colin Webber were some of the first in the world to explore alternative analysis methods to assess the influence of physical activity on micro-architectural properties of bone, showing that maximal hole size was smaller and connectivity larger in trabecular bone of the dominant forearm, exposed to a greater amount of loading on a daily basis, compared to the non-dominant forearm (MacIntyre et al. 1999).
Influence of Physical Activity on Bone during Growth
Don Bailey’s group from the University of Saskatchewan (along with Alan Martin, Heather McKay, Bob Faulkner, and Bob Mirwald) conducted prospective analyses of changes in bone during growth in boys and girls, and they discovered that a substantial portion of adult skeletal bone mass (26%) is accumulated in the 2 years surrounding peak growth velocity during adolescence (Bailey et al. 2000). They identified that this was an important time period to influence overall bone mass accumulation through lifestyle factors such as nutrition and physical activity. The most active boys and girls from their cohort accumulated 9% and 17% greater total body bone mineral content, respectively, over inactive adolescents one year after attainment of peak velocity of skeletal growth (Bailey et al. 1999). Adam Baxter-Jones and Saija Kontulainen later joined this research group and followed these adolescents into young adulthood. They showed that the benefits of high physical activity levels during adolescence carried over into young adulthood, in that children/adolescents who were the most active (at ages 8-15y) had 8-10% greater bone mineral content at the femoral neck or lumbar spine at age 23-30y compared to their less active counterparts (Baxter-Jones et al. 2008). Later they used hip structural analysis software to assess geometric changes around the hip and found those who were active during their growing years were able to maintain superior geometric properties (predicting greater bone strength at the hip) into young adulthood (Jackowski et al. 2014).
Brief, high-impact or novel loading patterns appear to be effective for improving bone health in children. Heather McKay (UBC) and her research group (including Karim Khan, Moira Petit, Heather MacDonald, and Saija Kontulainen) showed that a simple school-based intervention that involved 10 countermovement jumps three times per day was effective for improving bone mineral content at the hip and lumbar spine, and improving some geometric properties around the hip and tibia (McKay et al. 2005; MacDonald et al. 2007, 2008).
Given that high-impact and unusual loading patterns are thought to be the most beneficial for stimulating bone formation, a number of Canadian researchers have investigated the impact of gymnastics training on bone health. Bob Faulkner at the University of Saskatchewan found that hip bone density and geometric properties were substantially higher in premenarcheal gymnasts compared to controls (Faulkner et al. 2003) and these benefits were maintained well into retirement, as assessed by Marta Erlandson in a 10-year follow-up study (Erlandson et al. 2012). Dr. Erlandson also showed that the benefits of gymnastics were not restricted to elite gymnasts – children aged 4-10y who participated in recreational gymnastics programs (i.e., 1-2 hours per week) had 7% greater bone mineral content at the femoral neck over a four year period (Erlandson et al. 2011). The benefits of gymnastics have also been assessed by the McMaster group (led by Joe Blimkie) who showed enhanced geometric properties at the wrist with gymnastics training in 7-11 yr-old gymnasts (Dyson et al. 1997), and Bareket Falk from Brock University who showed enhanced bone architecture as evaluated by ultrasound in the wrists of prepubertal and early pubertal gymnasts (Falk et al. 2003). However, athletes and recreationally active women with low energy availability may experience estrogen deficiency and bone loss, which has been demonstrated in research led by Mary Jane De Souza (De Souza et al. 2008; Mallinson et al. 2013). More recently, she was involved in a consensus on how to oversee the treatment and return to play of the female athlete triad (De Souza et al. 2014; Joy et al. 2014).
Older or at-risk populations
Canadian researchers were among the first to assess the effectiveness of exercise on bone outcomes among people at high risk of fracture (i.e. those diagnosed with osteoporosis) and have led the development of physical activity recommendations for individuals with osteoporosis. Panagiota (Nota) Klentrou’s group from Brock University compared hospital-based and home-based aerobic and strength training exercise for women with osteoporosis and found similar changes in BMD, and standing height was stable over time (Walker et al. 2000). Heather McKay and Karim Khan showed that a community-based exercise program in osteoporotic women, despite having no effect on BMD, was effective for improving balance, important for the prevention of falls which is a leading cause of fracture (Carter et al. 2002). Along with Theresa Liu-Ambrose, they found resistance training and agility training were effective for improving cortical BMD at the radial shaft and lower leg, respectively, in women with low bone mass (Liu-Ambrose et al. 2004). At McMaster, a longitudinal study led by Neil McCartney and Audrey Hicks revealed that despite promising effects on exercise capacity and muscle strength, resistance training and aerobic training did not have a significant effect on whole body bone mineral content in older adults (McCartney et al. 1995). Similarly, Alexandra Papaioannou and Neil McCartney showed that home-based exercise involving stretching, strength training, and walking improved quality of life in women with vertebral fractures, despite having no effect on BMD (Papaioannou et al. 2004). However, the latter trial included women on bisphosphonate therapy, which may have limited the potential for benefit.
Lora Giangregorio (University of Waterloo), Norma MacIntyre, Lehana Thabane, Carly Skidmore, and Alexandra Papaioannou led a Cochrane review on exercise for improving outcomes after osteoporotic vertebral fracture. Dr. Giangregorio also led a team including Alexandra Papaioannou, Maureen Ashe, Norma MacIntyre, Angela Cheung, and Stuart McGill to publish evidence-based expert consensus statements on physical activity (including activities of leisure and daily living) and exercise for people with different degrees of osteoporosis (i.e. with and without vertebral fracture). Their Too Fit To Fracture recommendations state that people with osteoporosis should participate in a multicomponent exercise program including moderate to vigorous aerobic physical activity, strength training and balance training, consistent with Canada’s Physical Activity guidelines, and also include exercises to improve back extensor muscle endurance. Individuals with a history of vertebral fracture should emphasize moderate over vigorous physical activity (Giangregorio et al. 2014b; 2015). Dr. Giangregorio has translated these findings into on-line modules on exercise and osteoporosis for CSEP-certified members and along with Nota Klentrou and Phil Chilibeck assisted with development of workshops for exercise professionals working with clients who have osteoporosis (www.bonefit.ca). The development of these workshops was led by
Dr. Judi Laprade from the University of Toronto. Tools for patients and physicians were also created by the Too Fit To Fracture team in partnership with Osteoporosis Canada (http://www.osteoporosis.ca/osteoporosis-and-you/too-fit-to-fracture/).
Basic science for the development of exercise programs
Canadian researchers have also led basic science studies of bone and exercises, using proof-of-concept trials using bone markers in humans, animal models or studying the effects of loading at the cellular level to derive recommendations for effective exercise programs. Ron Zernicke (University of Calgary and later University of Michigan) and Jo Welch (Dalhousie University) used animal models to provide support of for the recommendation that strains applied to bone should be of high impact, high frequency, or high rate (i.e. applied quickly) but interspersed with rest periods, rather than being continuous in nature (Judex and Zernicke 2000; Lamothe and Zernicke 2004; Welch et al. 2008). This type of loading includes impact loading by dropping animals from heights (i.e. drop jumps) or applying high frequency loads to bone. Bone appears to respond well to high impact, high frequency or high rate strains, but bone loses its sensitivity to loading the longer loads are applied. Work in animals has been confirmed in human studies and programs, such as “jump at the bell” developed by Heather McKay from UBC during which small bouts of jumping exercise interspersed throughout the day were effective for improving parameters of bone health in children (McKay et al. 2005). Similarly, researchers at Brock University (including Nota Klentrou, Bareket Falk, and Wendy Ward) found that a single session of this type of loading (i.e. plyometric jumping) was effective for stimulating bone formation in men and boys, but more so in boys (Kish et al. 2015), providing support for the notion that physical activity during childhood may have the greatest impact on bone health (Bailey et al. 1999).
Lidan You’s lab at the University of Toronto provides insight on how different patterns of loading are effective for appropriately activating bone cells to induce bone formation and inhibit bone resorption. Her work has shown that osteocytes are the primary bone cell involved in sensing mechanical strain – activation of these cells causes inhibition of maturation and activation of osteoclasts, the cells involved in bone resorption (You et al. 2008). Her work gives support to the recommendation that loads that are high frequency and intermittent (i.e. loading interrupted by short periods of recovery) are optimal for stimulating osteoblasts, the cells involved in bone formation (Batra et al. 2005; Lau et al. 2010), and that one of the mechanisms by which strain on bone causes increased bone formation is through the induction of oscillatory fluid flow through interstitial regions of bone to activate osteoblasts or de-activate osteoclasts (Kim et al. 2006). The latter finding indicates that dynamic loading of bone is more important than static loading (i.e. dynamic muscle contractions would be more effective than isometric efforts for stimulating positive adaptation in bone).
Directions for future research
High-resolution pQCT is relatively new and allows assessment of bone at the micro-architectural level. Canadian researchers including Steve Boyd (University of Calgary) have assessed elite athletes (i.e. alpine skiers) and determined that micro-architectural properties of bone, and therefore bone strength, is enhanced in athletes compared to non-athletes despite no differences in BMD (Liphardt et al. 2015). Along with Heather McKay, Dr. Boyd has also determined that high impact physical activity in adolescents is predictive of bone micro-architectural properties (McKay et al. 2011). Heather McKay and Heather MacDonald (UBC) have also used HR-pQCT to assess the effect of sedentary behavior on bone microarchitecture in children, finding no relationship between sedentary behavior and bone architecture or estimated bone strength at the distal tibia (Gabel et al. 2015). There is currently a lack of human clinical trials (i.e., randomized controlled trials) examining the effects of exercise on outcomes measured using HR-pQCT; therefore, this is an avenue for future research.
As it is difficult to improve BMD with exercise interventions in older populations, Darren Candow (University of Regina) along with Phil Chilibeck and Saija Kontulainen (University of Saskatchewan) have explored using novel pharmaceutical (i.e. ibuprofen) or nutritional (creatine monohydrate, soy isoflavone) interventions in conjunction with exercise training to enhance BMD (Chilibeck et al. 2013, 2015; Duff et al. 2016). A small pilot study indicated creatine supplementation during exercise training may be of benefit for bone health (Chilibeck et al. 2015), but larger randomized controlled trials are needed to verify if this is an intervention that is truly effective.
Lora Giangregorio’s working group on appropriate exercise for people at high risk of fracture has developed guidelines based on feedback from experts (Giangregorio et al. 2015); however, they have indicated there is a lack of large randomized controlled trials using these exercise interventions in people at high risk of fracture (Giangregorio et al. 2014a). They have identified this as another important future research priority. A multicentre trial of exercise in women with osteoporotic vertebral fractures is ongoing, and will complete follow-up in 2016; Canadians leading the trial include Drs. Giangregorio, Papaioannou, Cheung, Adachi, Ashe, Kendler, Gibbs, Bleakney, Thabane, Braun and several other international researchers (Giangregorio et al. 2014). As with the vast majority of exercise research, there is a dearth of studies exploring how to increase uptake of exercise research by health care providers or individuals with osteoporosis. Given the large body of evidence of the efficacy of exercise for improving bone health in Canada alone, here’s hoping the next generation of scientists and exercise physiologists establish effective strategies to translate research to practice.
Ashe, M.C,, Khan, K.M., Kontulainen, S.A., Guy, P., Liu, D., Beck, T.J., and McKay, H.A. 2006. Accuracy of pQCT for evaluating the aged human radius: an ashing, histomorphometry and failure load investigation. Osteoporos Int. 17(8): 1241-51.
Bailey, D.A., Martin, A.D., McKay, H.A., Whiting, S., and Mirwald, R. 2000. Calcium accretion in girls and boys during puberty: a longitudinal analysis. J. Bone Miner. Res. 15(11): 2245-50.
Bailey, D.A., McKay, H.A., Mirwald, R.L., Crocker, P.R., and Faulkner, R.A. 1999. 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. 14(10): 1672-9.
Batra, N.N., Li, Y.J., Yellowley, C.E., You, L., Malone, A.M., Kim, C.H., and Jacobs, C.R. 2005. Effects of short-term recovery periods on fluid-induced signaling in osteoblastic cells. J. Biomech. 38(9): 1909-17.
Baxter-Jones, A.D., Kontulainen, S.A., Faulkner, R.A., and Bailey, D.A. 2008. A longitudinal study of the relationship of physical activity to bone mineral accrual from adolescence to young adulthood. Bone 43(6): 1101-7.
Blimkie, C.J., Rice, S., Webber, C.E., Martin, J., Levy, D., and Gordon, C.L. 1996. Effects of resistance training on bone mineral content and density in adolescent females. Can. J. Physiol. Pharmacol. 74(9): 1025-33.
Carter, N.D., Khan, K.M., McKay, H.A., Petit, M.A., Waterman, C., Heinonen, A., Janssen, P.A., Donaldson, M.G., Mallinson, A., Riddell, L., Kruse, K., Prior, J.C., and Flicker, L. 2002. Community-based exercise program reduces risk factors for falls in 65- to 75-year-old women with osteoporosis: randomized controlled trial. Can. Med. Assoc. J. 167(9): 997-1004.
Chilibeck, P.D., Candow, D.G., Landeryou, T., Kaviani, M., and Paus-Jenssen, L. 2015. Effects of Creatine and Resistance Training on Bone Health in Postmenopausal Women. Med. Sci. Sports Exerc. 47(8): 1587-95.
Chilibeck, P.D., Vatanparast, H., Pierson, R., Case, A., Olatunbosun, O., Whiting, S.J., Beck, T.J., Pahwa, P., and Biem, H.J. 2013. Effect of exercise training combined with isoflavone supplementation on bone and lipids in postmenopausal women: a randomized clinical trial. J. Bone Miner. Res. 28(4):780-93.
Chilibeck, P., Calder, A., Sale, D.G., and Webber, C. 1994. Reproducibility of dual-energy x-ray absorptiometry. Can. Assoc. Radiol. J. 45(4): 297-302.
Chilibeck, P.D., Calder, A., Sale, D.G., and Webber, C.E. 1996. Twenty weeks of weight training increases lean tissue mass but not bone mineral mass or density in healthy, active young women. Can J Physiol Pharmacol. 74: 1180-5.
Chow, R.K., Harrison, J.E., Brown, C.F., and Hajek, V. 1986. Physical fitness effect on bone mass in postmenopausal women. Arch. Phys. Med. Rehabil. 67(4): 231-4.
Chow, R., Harrison, J., and Dornan, J. 1989. Prevention and rehabilitation of osteoporosis program: exercise and osteoporosis. Int. J. Rehabil. Res. 12(1): 49-56.
De Souza, M.J., Nattiv, A., Joy, E., Misra, M., Williams, N.I., Mallinson, R.J., Gibbs, J.C., Olmsted, M., Goolsby, M., Matheson, G.; Expert Panel. 2014. Br. J. Sports Med. 48(4):289.
De Souza, M.J., West, S.L., Jamal, S.A., Hawker, G.A., Gundberg, C.M., Williams, N.I. 2008. The presence of both an energy deficiency and estrogen deficiency exacerbate alterations of bone metabolism in exercising women. Bone. 243(1): 140-8.
Duff, W.R.D., Kontulainen, S.A., Candow, D.G., Gordon, J.J., Mason, R.S., Taylor-Gjevre, R., Nair, B., Szafron, M., Baxter-Jones, A.D., Zello, G.A., Chilibeck, P.D. 2016. Effects of low-dose ibuprofen supplementation and resistance training on bone and muscle in postmenopausal women: A randomized controlled trial. Bone Reports 5: 96–103.
Dyson, K., Blimkie, C.J., Davison, K.S., Webber, C.E., and Adachi, J.D. 1997. Gymnastic training and bone density in pre-adolescent females. Med. Sci. Sports Exerc. 29(4): 443-50.
Erlandson, M.C., Kontulainen, S.A., Chilibeck, P.D., Arnold, C.M., and Baxter-Jones, A.D. 2011. Bone mineral accrual in 4- to 10-year-old precompetitive, recreational gymnasts: a 4-year longitudinal study. J Bone Miner. Res. 26(6): 1313-20.
Erlandson, M.C., Kontulainen, S.A., Chilibeck, P.D., Arnold, C.M., Faulkner, R.A., and Baxter-Jones, A.D. 2012. 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. 27(1): 104-10.
Falk, B., Bronshtein, Z., Zigel, L., Constantini, N.W., and Eliakim, A. 2003. Quantitative ultrasound of the tibia and radius in prepubertal and early-pubertal female athletes. Arch. Pediatr. Adolesc. Med. 157(2): 139-43.
Faulkner, R.A., Forwood, M.R., Beck, T.J., Mafukidze, J.C., Russell, K., and Wallace, W. 2003. Strength indices of the proximal femur and shaft in prepubertal female gymnasts. Med. Sci. Sports Exerc. 35(3): 513-8.
Gabel, L., McKay, H.A., Nettlefold, L., Race, D., and Macdonald, H.M. 2015. Bone architecture and strength in the growing skeleton: the role of sedentary time. Med. Sci. Sports Exerc. 47(2):363-72.
Giangregorio, L.M., MacIntyre, N.J., Heinonen, A., Cheung, A.M., Wark, J.D., Shipp, K., McGill, S., Ashe, M.C., Laprade, J., Jain, R., Keller, H., and Papaioannou A. 2014a. Too Fit To Fracture: a consensus on future research priorities in osteoporosis and exercise. Osteoporos Int. 25(5): 1465-72.
Giangregorio, L.M., Macintyre, N.J., Thabane, L., Skidmore, C.J., and Papaioannou, A. 2013. Exercise for improving outcomes after osteoporotic vertebral fracture. Cochrane Database Syst. Rev. Jan 31;(1):CD008618.
Giangregorio, L.M., McGill, S., Wark, J.D., Laprade, J., Heinonen, A., Ashe, M.C., MacIntyre, N.J., Cheung, A.M., Shipp, K., Keller, H., Jain, R., and Papaioannou A. 2015. Too Fit To Fracture: outcomes of a Delphi consensus process on physical activity and exercise recommendations for adults with osteoporosis with or without vertebral fractures. Osteoporos Int. 26(3):891-910.
Giangregorio, L.M., Papaioannou, A., Macintyre, N.J., Ashe, M.C., Heinonen, A., Shipp, K., Wark, J., McGill, S., Keller, H., Jain, R., Laprade, J., and Cheung, A.M. 2014b. Too Fit To Fracture: exercise recommendations for individuals with osteoporosis or osteoporotic vertebral fracture. Osteoporos Int. 25(3): 821-35.
Giangregorio, L.M., Thabane, L., Adachi, J.D., Ashe, M.C., Bleakney, R.R., Braun, E.A., Cheung, A.M., Fraser, L.A., Gibbs, J.C., Hill, K.D., Hodsman, A.B., Kendler, D.L., Mittmann, N., Prasad, S., Scherer, S.C., Wark, J.D., and Papaioannou, A. 2014. Build better bones with exercise: protocol for a feasibility study of a multicenter randomized controlled trial of 12 months of home exercise in women with a vertebral fracture. Phys. Ther. 94(9): 1337-52.
Jackowski, S.A., Kontulainen, S.A., Cooper, D.M., Lanovaz, J.L., Beck, T.J., and Baxter-Jones, A.D. 2014. Adolescent physical activity and bone strength at the proximal femur in adulthood. Med. Sci. Sports Exerc. 46(4): 736-44.
Joy E., De Souza M.J., Nattiv A., Misra M., Williams N.I., Mallinson R.J., Gibbs J.C., Olmsted M., Goolsby M., Matheson G., Barrack M., Burke L., Drinkwater B., Lebrun C., Loucks A.B., Mountjoy M., Nichols J., Borgen J.S. 2014 female athlete triad coalition consensus statement on treatment and return to play of the female athlete triad. Curr. Sports Med. Rep. 13(4): 219-32.
Judex, S., and Zernicke, R.F. 2000. High-impact exercise and growing bone: relation between high strain rates and enhanced bone formation. J. Appl. Physiol. 88(6): 2183-91.
Kim, C.H., You, L., Yellowley, C.E., and Jacobs, C.R. 2006. Oscillatory fluid flow-induced shear stress decreases osteoclastogenesis through RANKL and OPG signaling. Bone 39(5): 1043-7.
Kish, K., Mezil, Y., Ward, W.E., Klentrou, P., and Falk, B. 2015. Effects of plyometric exercise session on markers of bone turnover in boys and young men. Eur. J. Appl. Physiol. 115(10): 2115-24.
LaMothe, J.M., and Zernicke, R.F. 2004. Rest insertion combined with high-frequency loading enhances osteogenesis. J. Appl. Physiol. 96(5): 1788-93.
Lau, E., Al-Dujaili, S., Guenther, A., Liu, D., Wang, L., and You, L. 2010. Effect of low-magnitude, high-frequency vibration on osteocytes in the regulation of osteoclasts. Bone 46(6): 1508-15.
Liphardt, A.M., Schipilow, J.D., Macdonald, H.M., Kan, M., Zieger, A., and Boyd, S.K. 2015. Bone micro-architecture of elite alpine skiers is not reflected by bone mineral density. Osteoporos Int. 26(9): 2309-17.
Liu-Ambrose, T.Y., Khan, K.M., Eng, J.J., Heinonen, A., and McKay, H.A. 2004. Both resistance and agility training increase cortical bone density in 75- to 85-year-old women with low bone mass: a 6-month randomized controlled trial. J. Clin. Densitom. 7(4): 390-8.
MacDonald, H.M., Kontulainen, S.A., Khan, K.M., and McKay, H.A. 2007. Is a school-based physical activity intervention effective for increasing tibial bone strength in boys and girls? J Bone Miner Res. 22(3): 434-46.
MacDonald, H.M., Kontulainen, S.A., Petit, M.A., Beck, T.J., Khan, K.M., and McKay, H.A. 2008. Does a novel school-based physical activity model benefit femoral neck bone strength in pre- and early pubertal children? Osteoporos Int. 19(10): 1445-56.
MacDougall, J.D., Webber, C.E., Martin, J., Ormerod, S., Chesley, A., Younglai, E.V., Gordon, C.L., and Blimkie, C.J. 1992. Relationship among running mileage, bone density, and serum testosterone in male runners. J. Appl. Physiol. 73(3): 1165-70.
MacIntyre, N.J., Adachi, J.D., and Webber, C.E. 1999. In vivo detection of structural differences between dominant and nondominant radii using peripheral quantitative computed tomography. J. Clin. Densitom. 2(4): 413-22.
Mallinson R.J., Williams N.I., Hill B.R., De Souza M.J.. 2013. Body composition and reproductive function exert unique influences on indices of bone health in exercising women. Bone 56(1):91-100. McCartney, N., Hicks, A.L., Martin, J., and Webber, C.E. 1995. Long-term resistance training in the elderly: effects on dynamic strength, exercise capacity, muscle, and bone. J. Gerontol. A Biol. Sci. Med. Sci. 50(2): B97-104.
McCulloch, R.G., Bailey, D.A., Houston, C.S., and Dodd, B.L. 1990. Effects of physical activity, dietary calcium intake and selected lifestyle factors on bone density in young women. Can. Med. Assoc. J. 142: 221-7.
McKay, H., Liu, D., Egeli, D., Boyd, S., and Burrows, M. 2011. Physical activity positively predicts bone architecture and bone strength in adolescent males and females. Acta Paediatr. 100(1): 97-101.
McKay, H.A., MacLean, L., Petit, M., MacKelvie-O'Brien, K., Janssen, P., Beck, T., Khan, K.M. 2005. "Bounce at the Bell": a novel program of short bouts of exercise improves proximal femur bone mass in early pubertal children. Br. J. Sports Med. 39(8): 521-6.
Papaioannou, A., Adachi, J.D., Winegard, K., Ferko, N., Parkinson, W., Cook, R.J., Webber, C., and McCartney, N. 2003. Efficacy of home-based exercise for improving quality of life among elderly women with symptomatic osteoporosis-related vertebral fractures. Osteoporos Int. 14(8): 677-82.
Rice, S., Blimkie, C.J., Webber, C.E., Levy, D., Martin, J., Parker, D., and Gordon, C.L. 1993. Correlates and determinants of bone mineral content and density in healthy adolescent girls. Can. J. Physiol. Pharmacol. 71(12): 923-30.
Walker, M., Klentrou, P., Chow, R., and Plyley, M. 2000. Longitudinal evaluation of supervised versus unsupervised exercise programs for the treatment of osteoporosis. Eur. J. Appl. Physiol. 83(4 -5): 349-55.
Welch, J.M., Turner, C.H., Devareddy, L., Arjmandi, B.H., and Weaver, C.M. 2008. High impact exercise is more beneficial than dietary calcium for building bone strength in the growing rat skeleton. Bone 42(4): 660-8.
You, L., Temiyasathit, S., Lee, P., Kim, C.H., Tummala, P., Yao, W., Kingery, W., Malone, A.M., Kwon, R.Y., and Jacobs, C.R. 2008. Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading. Bone 42(1): 172-9.
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