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10 - Ontogenetic and Genetic Influences on Bone’s Responsiveness to Mechanical Signals

Published online by Cambridge University Press:  25 March 2017

By
Ian J. Wallace ,
Brigitte Demes  and
Stefan Judex
Edited by
Christopher J. Percival  and
Joan T. Richtsmeier
Christopher J. Percival
Affiliation:
University of Calgary
Joan T. Richtsmeier
Affiliation:
Pennsylvania State University
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Type
Chapter
Information
Building Bones: Bone Formation and Development in Anthropology , pp. 233 - 253
Publisher: Cambridge University Press
Print publication year: 2017

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References

Akhter, M. P., Cullen, D. M., Pedersen, E. A., Kimmel, D. B. and Recker, R. R. (1998). Bone response to in vivo mechanical loading in two breeds of mice. Calcified Tissue International, 63, 442–449.CrossRefGoogle ScholarPubMed
Aldinger, K. A., Sokoloff, G., Rosenberg, D. M., Palmer, A. A. and Millen, K. J. (2009). Genetic variation and population substructure in outbred CD-1 mice: implications for genome-wide association studies. PLoS ONE, 4, e4729.Google Scholar
Amblard, D., Lafage-Proust, M. H., Laib, A., et al. (2003). Tail suspension induces bone loss in skeletally mature mice in the C57BL/6J strain but not in the C3H/HeJ strain. Journal of Bone and Mineral Research, 18, 561–569.Google Scholar
Arnsdorf, E. J., Tummala, P., Kwon, R. Y. and Jacobs, C. R. (2009). Mechanically induced osteogenic differentiation – the role of RhoA, ROCKII and cytoskeletal dynamics. Journal of Cell Science, 122, 546–553.CrossRefGoogle ScholarPubMed
Barak, M. M., Lieberman, D. E. and Hublin, J.-J. (2011). A Wolff in sheep’s clothing: trabecular bone adaptation in response to changes in joint loading orientation. Bone, 49, 1141–1151.CrossRefGoogle Scholar
Batra, N. and Jiang, J. X. (2012). “INTEGRINating” the connexin hemichannel function in bone osteocytes through the action of integrin α5. Communicative and Integrative Biology, 5, 516–518.Google Scholar
Beck, J. A., Lloyd, S., Hafezparast, M., et al. (2000). Genealogies of mouse inbred strains. Nature Genetics, 24, 23–25.CrossRefGoogle ScholarPubMed
Behringer, M., Gruetzner, S., McCourt, M. and Mester, J. (2013). Effects of weight-bearing activities on bone mineral content and density in children and adolescents: a meta-analysis. Journal of Bone and Mineral Research, 29, 467–478.CrossRefGoogle Scholar
Bertram, J. E. A. and Swartz, S. M. (1991). The “law of bone transformation”: a case of crying Wolff? Biological Reviews, 66, 245–273.Google Scholar
Biewener, A. A. and Bertram, J. E. A. (1993). Skeletal strain patterns in relation to exercise training during growth. Journal of Experimental Biology, 185, 51–69.Google Scholar
Biewener, A. A. and Bertram, J. E. A. (1994). Structural response of growing bone to exercise and disuse. Journal of Applied Physiology, 72, 946–955.Google Scholar
Biewener, A. A., Swartz, S. M. and Bertram, J. E. A. (1986). Bone modeling during growth: dynamic strain equilibrium in the chick tibiotarsus. Calcified Tissue International, 39, 390–395.Google Scholar
Bonewald, L. F. (2006). Mechanosensation and transduction in osteocytes. Bonekey Osteovision, 3, 7–15.Google Scholar
Bonjour, J.-P., Chevalley, T., Rizzoli, R. and Ferrari, S. (2007). Gene–environment interactions in the skeletal response to nutrition and exercise during growth. Medicine and Sport Science, 51, 64–80.CrossRefGoogle ScholarPubMed
Bridges, P. S. (1989). Changes in activities with the shift to agriculture in the southeastern United States. Current Anthropology, 30, 385–394.CrossRefGoogle Scholar
Brodt, M. D. and Silva, M. J. (2010). Aged mice have enhanced endocortical response and normal periosteal response compared with young-adult mice following 1 week of axial tibial compression. Journal of Bone and Mineral Research, 25, 2006–2015.Google Scholar
Burger, E. H. and Klein-Nulend, J. (1999). Mechanotransduction in bone – role of the lacunocanalicular network. FASEB Journal, 13, S101–S112.CrossRefGoogle Scholar
Burr, D. B., Milgrom, C., Fyhrie, D., et al. (1996). In vivo measurement of human tibial strains during vigorous activity. Bone, 18, 405–410.CrossRefGoogle ScholarPubMed
Case, N. and Rubin, J. (2010). Beta-catenin – a supporting role in the skeleton. Journal of Cellular Biochemistry, 110, 545–553.Google Scholar
Chen, Z., Qi, L., Beck, T. J., et al. (2011). Stronger bone correlates with African admixture in African-American women. Journal of Bone and Mineral Research, 26, 2307–2316.CrossRefGoogle ScholarPubMed
Chia, R., Achilli, F., Festing, M. F. W. and Fisher, E. M. C. (2005). The origins and uses of mouse outbred stocks. Nature Genetics, 37, 1181–1186.Google Scholar
Conrad, D. F., Jakobsson, M., Coop, G., et al. (2006). A worldwide survey of haplotype variation and linkage disequilibrium in the human genome. Nature Genetics, 38, 1251–1260.Google Scholar
Dalsky, G. P., Stocke, K. S., Ehsani, A. A., et al. (1988). Weight-bearing exercise training and lumbar bone mineral content in postmenopausal women. Annals of Internal Medicine, 108, 824–828.CrossRefGoogle ScholarPubMed
Daly, R. M. (2007). The effect of exercise on bone mass and structural geometry during growth. Medicine and Sport Science, 51, 33–49.CrossRefGoogle Scholar
Danielson, M. E., Beck, T. J., Lian, Y., et al. (2013). Ethnic variability in bone geometry as assessed by hip structure analysis: findings from the hip strength across the menopausal transition study. Journal of Bone and Mineral Research, 28, 771–779.Google Scholar
Demes, B., Stern, J. T. Jr., Hausman, M. R., et al. (1998). Patterns of strain in the macaque ulna during functional activity. American Journal of Physical Anthropology, 106, 87–100.Google Scholar
Demes, B., Qin, Y.-Z., Stern, J. T. Jr., Larson, S. G. and Rubin, C. T. (2001). Patterns of strain in the macaque tibia during functional loading. American Journal of Physical Anthropology, 116, 257–265.Google Scholar
Demissie, S., Dupuis, J., Cupples, L. A., et al. (2007). Proximal hip geometry is linked to several chromosomal regions: genome-wide linkage results from the Framingham Osteoporosis Study. Bone, 40, 743–750.Google Scholar
Devlin, M. J. (2011). Estrogen, exercise, and the skeleton. Evolutionary Anthropology, 20, 54–61.CrossRefGoogle ScholarPubMed
Devlin, M. J. and Lieberman, D. E. (2007). Variation in estradiol level affects cortical bone growth in response to mechanical loading in sheep. Journal of Experimental Biology, 210, 602–613.Google Scholar
Devlin, M. J., Stetter, C. M., Lin, H.-M., et al. (2010). Peripubertal estrogen levels and physical activity affect femur geometry in young adult women. Osteoporosis International, 21, 609–617.CrossRefGoogle ScholarPubMed
Dhamrait, S. S., James, L., Brull, D. J., et al. (2003). Cortical bone resorption during exercise is interleukin-6 genotype-dependent. European Journal of Applied Physiology, 89, 21–25.Google Scholar
Doecke, J. D., Day, C. J., Stephens, A. S., et al. (2006). Association of functionally different RUNX2 P2 promoter alleles with BMD. Journal of Bone and Mineral Research, 21, 265–273.Google Scholar
Donahue, S. W., Jacobs, C. R. and Donahue, H. J. (2001). Flow-induced calcium oscillations in rat osteoblasts are age, loading frequency, and shear stress dependent. American Journal of Physiology, 281, C1635–1641.Google Scholar
Duncan, R. L. (1998). Mechanotransduction and mechanosensitive ion channels in osteoblasts. In: Van Duijn, B. and Wiltink, A. (eds.) Signal Transduction: Single Cell Techniques. Berlin: Springer, pp. 125–134.CrossRefGoogle Scholar
Fenner, J. N. (2005). Cross-cultural estimation of the human generation interval for use in genetics-based population divergence studies. American Journal of Physical Anthropology, 128, 415–423.CrossRefGoogle ScholarPubMed
Forwood, M. R. (1996). Inducible cyclo-oxygenase (COX-2) mediates the induction of bone formation by mechanical loading in vivo. Journal of Bone and Mineral Research, 11, 1688–1693.Google Scholar
Forwood, M. R. (2013). Growing a healthy skeleton. In: Rosen, C. J. (ed.) Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Ames, IA: Wiley-Blackwell, pp. 149–155.Google Scholar
Green, R. E., Krause, J., Briggs, A. W., et al. (2010). A draft sequence of the Neandertal genome. Science, 328, 710–722.CrossRefGoogle ScholarPubMed
Haapasalo, H., Kontulainen, S., Sievänen, H., et al. (2000). Exercise-induced bone gain is due to enlargement in bone size without a change in volumetric bone density: a peripheral quantitative computed tomography study of the upper arms of male tennis players. Bone, 27, 351–357.Google Scholar
Hamrick, M. W., Skedros, J. G., Pennington, C. and McNeil, P. L. (2006). Increased osteogenic response to exercise in metaphyseal versus diaphyseal cortical bone. Journal of Musculoskeletal and Neuronal Interactions, 6, 258–263.Google Scholar
Han, Y., Cowin, S. C., Schaffler, M. B. and Weinbaum, S. (2004). Mechanotransduction and strain amplification in osteocyte cell processes. Proceedings of the National Academy of Sciences USA, 101, 16689–16694.CrossRefGoogle ScholarPubMed
Havill, L. M., Mahaney, M. C., Binkley, T. L. and Specker, B. L. (2007). Effects of genes, sex, age, and activity on BMC, bone size, and areal and volumetric BMD. Journal of Bone and Mineral Research, 22, 737–746.Google Scholar
Hoey, D. A., Chen, J. C. and Jacobs, C. R. (2012). The primary cilium as a novel extracellular sensor in bone. Frontiers in Endocrinology, 3, 75.Google Scholar
Holt, B. M. (2003). Mobility in Upper Paleolithic and Mesolithic Europe: evidence from the lower limb. American Journal of Physical Anthropology, 122, 200–215.Google Scholar
Hrdlička, A. (1937). Human typogeny. Proceedings of the American Philosophical Society, 78, 79–95.Google Scholar
Hung, C. T., Pollack, C. R., Reilly, T. M. and Brighton, C. T. (1995). Real-time calcium response of cultured bone cells to fluid flow. Clinical Orthopaedics and Related Research, 313, 256–269.Google Scholar
Ioannidis, J. P., Ng, M. Y., Sham, P. C., et al. (2007). Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass. Journal of Bone and Mineral Research, 22, 173–183.Google Scholar
Jacobs, C. R., Temiyasathit, S. and Castillo, A. B. (2010). Osteocyte mechanobiology and pericellular mechanics. Annual Review of Biomedical Engineering, 12, 369–400.CrossRefGoogle ScholarPubMed
Joo, Y. I., Sone, T., Fukunaga, M., Lim, S. G. and Onodera, S. (2003). Effects of endurance exercise on three-dimensional trabecular bone microarchitecture in young growing rats. Bone, 33, 485–493.Google Scholar
Judex, S., Gross, T. S. and Zernicke, R. F. (1997). Strain gradients correlate with sites of exercise-induced bone-forming surfaces in the adult skeleton. Journal of Bone and Mineral Research, 12, 1737–1745.Google Scholar
Judex, S., Donahue, L. R. and Rubin, C. (2002). Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton. FASEB Journal, 16, 1280–1282.Google Scholar
Judex, S., Garman, R., Squire, M., et al. (2004). Genetically linked site-specificity of disuse osteoporosis. Journal of Bone and Mineral Research, 19, 607–613.Google Scholar
Judex, S., Zhang, W., Donahue, L. R. and Ozcivici, E. (2013). Genetic loci that control the loss and regain of trabecular bone during unloading and reambulation. Journal of Bone and Mineral Research, 28, 1537–1549.CrossRefGoogle ScholarPubMed
Karinkanta, S., Heinonen, A., Sievänen, H., et al. (2007). A multi-component exercise regimen to prevent functional decline and bone fragility in home-dwelling elderly women: randomized, controlled trial. Osteoporosis International, 18, 453–462.Google Scholar
Karlsson, M. K., Linden, C., Karlsson, C., et al. (2000). Exercise during growth and bone mineral density and fractures in old age. Lancet, 355, 469–470.CrossRefGoogle ScholarPubMed
Karsenty, G. (2003). The complexities of skeletal biology. Nature, 423, 316–318.Google Scholar
Karsenty, G., Kronenberg, H. M. and Settembre, C. (2009). Genetic control of bone formation. Annual Review of Cell and Developmental Biology, 25, 629–648.Google Scholar
Kesavan, C., Mohan, S., Srivastava, A. K., et al. (2006). Identification of genetic loci that regulate bone adaptive response to mechanical loading in C57BL/6J and C3H/HeJ mice intercross. Bone, 39, 634–643.Google Scholar
Klein-Nulend, J., Semeins, C. M., Ajubi, N. E., Nijweide, P. J. and Burger, E. H. (1995). Pulsating fluid flow increases nitric oxide (NO) synthesis by osteocytes but not periosteal fibroblasts – correlation with prostaglandin upregulation. Biochemical and Biophysical Research Communications, 217, 640–648.Google Scholar
Kodama, Y., Dimai, H. P., Wergedal, J., et al. (1999). Cortical tibial bone volume in two strains of mice: effects of sciatic neurectomy and genetic regulation of bone response to mechanical loading. Bone, 25, 183–190.Google Scholar
Kodama, Y., Umemura, Y., Nagasawa, S., et al. (2000). Exercise and mechanical loading increase periosteal bone formation and whole bone strength in C57BL/6J mice but not C3H/Hej mice. Calcified Tissue International, 66, 298–306.CrossRefGoogle Scholar
Kontulainen, S., Kannus, P., Haapasalo, H., et al. (2001). 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. Journal of Bone and Mineral Research, 16, 195–201.Google Scholar
Kwon, R. Y., Hoey, D. A. and Jacobs, C. R. (2011). Mechanobiology of primary cilia. In: Gefen, A. (ed.) Cellular and Biomolecular Mechanics and Mechanobiology. Heidelberg: SpringerLink, pp. 99–124.Google Scholar
Lanyon, L. E. (1987). Functional strain in bone tissue as an objective, and controlling stimulus for adaptive bone remodeling. Journal of Biomechanics, 20, 1083–1093.CrossRefGoogle Scholar
Lanyon, L. E. (1992). The success and failure of the adaptive response to functional load-bearing in averting bone fracture. Bone, 13, S17–21.Google Scholar
Lanyon, L. E. and Rubin, C. T. (1984). Static vs dynamic loads as an influence on bone remodelling. Journal of Biomechanics, 17, 897–906.Google Scholar
Lanyon, L. E., Armstrong, V., Ong, D., Zaman, G. and Price, J. (2004). Is estrogen receptor α key to controlling bones’ resistance to fracture? Journal of Endocrinology, 182, 183–191.Google Scholar
Laugier, P., Novikov, V., Elmann-Larsen, B. and Berger, G. (2000). Quantitative ultrasound imaging of the calcaneus: precision and variation during a 120-day bed rest. Calcified Tissue International, 66, 16–21.CrossRefGoogle ScholarPubMed
Leppänen, O. V., Sievänen, H., Jokihaara, J., et al. (2008). Pathogenesis of age-related osteoporosis: impaired mechano-responsiveness of bone is not the culprit. PLoS ONE, 3, e2540.Google Scholar
Li, J. Z., Absher, D. M., Tang, H., et al. (2008). Worldwide human relationships inferred from genome-wide patterns of variation. Science, 319, 1100–1104.Google Scholar
Lieberman, D. E. (1996). How and why humans grow thin skulls: experimental evidence for systemic cortical robusticity. American Journal of Physical Anthropology, 101, 217–236.Google Scholar
Lieberman, D. E., Devlin, M. J. and Pearson, O. M. (2001). Articular surface area responses to mechanical loading: effects of exercise, age, and skeletal location. American Journal of Physical Anthropology, 116, 266–277.Google Scholar
Lieberman, D. E., Pearson, O. M., Polk, J. D., Demes, B. and Crompton, A. W. (2003). Optimization of bone growth and remodeling in response to loading in tapered mammalian limbs. Journal of Experimental Biology, 206, 3125–3138.Google Scholar
Lieberman, D. E., Polk, J. D. and Demes, B. (2004). Predicting long bone loading from cross-sectional geometry. American Journal of Physical Anthropology, 123, 156–171.Google Scholar
Litzenberger, J. B., Kim, J. B., Tummala, P. and Jacobs, C. R. (2010). Beta1 integrins mediate mechanosensitive signaling pathways in osteocytes. Calcified Tissue International, 86, 325–332.Google Scholar
Liu, D., Genetos, D. C., Shao, Y., et al. (2008). Activation of extracellular-signal regulated kinase (ERK1/2) by fluid shear is Ca2+- and ATP-dependent in MC3T3-E1 osteoblasts. Bone, 42, 644–652.Google Scholar
Liu, Y.-Z., Wilson, S. G., Wang, L., et al. (2008). Identification of PLCL1 gene for hip bone size variation in females in a genome-wide association study. PLoS ONE, 3, e3160.Google Scholar
Lovejoy, C. O., McCollum, M. A., Reno, P. L. and Rosenman, B. A. (2003). Developmental biology and human evolution. Annual Review of Anthropology, 32, 85–109.Google Scholar
Luu, Y. K., Capilla, E., Rosen, C. H., et al. (2009). Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. Journal of Bone and Mineral Research, 24, 50–61.Google Scholar
Macdonald, H. M., Cooper, D. M. L. and McKay, H. A. (2009) Anterior–posterior bending strength at the tibial shaft increases with physical activity in boys: evidence for non-uniform geometric adaptation. Osteoporosis International, 20, 61–70.CrossRefGoogle ScholarPubMed
Maggiano, I. S., Schultz, M., Kierdorf, H., et al. (2008). Cross-sectional analysis of long bones, occupational activities and long-distance trade of the Classic Maya from Xcambó – archaeological and osteological evidence. American Journal of Physical Anthropology, 136, 470–477.Google Scholar
Manolagas, S. C. and Almeida, M. (2007). Gone with the Wnts: β-catenin, T-cell factor, forkhead box O, and oxidative stress in age-dependent diseases of bone, lipid, and glucose metabolism. Molecular Endocrinology, 21, 2605–2614.CrossRefGoogle Scholar
Marchi, D., Sparacello, V. S., Holt, B. M. and Formicola, V. (2006). Biomechanical approach to the reconstruction of activity patterns in Neolithic Western Liguria, Italy. American Journal of Physical Anthropology, 131, 447–455.Google Scholar
Martin, R. B., Burr, D. B. and Sharkey, N. A. (1998). Skeletal Tissue Mechanics. New York, NY: Springer.Google Scholar
Meiring, R. M., Avidon, I., Norris, S. A. and McVeigh, J. A. (2013). A two-year history of high bone loading physical activity attenuates ethnic differences in bone strength and geometry in pre-/early pubertal children from a low-middle income country. Bone, 57, 522–530.Google Scholar
Morimoto, N., Ponce de León, M. S. and Zollikofer, C. P. E. (2011). Exploring femoral diaphyseal shape variation in wild and captive chimpanzees by means of morphometric mapping: a test of Wolff’s Law. Anatomical Record, 294, 589–609.Google Scholar
Nicolella, D. P., Moravits, D. E., Gale, A. M., Bonewald, L. F. and Lankford, J. (2006). Osteocyte lacunae tissue strain in cortical bone. Journal of Biomechanics, 39, 1735–1743.Google Scholar
O’Connor, J. A., Lanyon, L. E. and MacFie, H. (1982). The influence of strain rate on adaptive bone remodelling. Journal of Biomechanics, 15, 767–781.Google Scholar
Ozcivici, E., Luu, Y. K., Adler, B., et al. (2010). Mechanical signals as anabolic agents in bone. Nature Reviews Rheumatology, 6, 50–59.Google Scholar
Pahlavani, M. A. and Vargas, D. M. (2000). Influence of aging and caloric restriction on activation of Ras/MAPK, calcineurin, and CaMK-IV activities in rat T cells. Proceedings of the Society for Experimental Biology and Medicine, 223, 163–169.Google ScholarPubMed
Pearson, O. M. and Lieberman, D. E. (2004). The aging of Wolff’s “Law”: ontogeny and responses to mechanical loading in cortical bone. Yearbook of Physical Anthropology, 47, 63–99.Google Scholar
Rawlinson, S. C. F., El Haj, A. J., Minter, S. L., et al. (1991). Loading-related increases in prostaglandin production in cores of adult canine cancellous bone in vitro: a role for prostacyclin in adaptive bone remodeling? Journal of Bone and Mineral Research, 6, 1345–1351.Google Scholar
Rawlinson, S. C. F., Mosley, J. R., Suswillo, R. F. L., Pitsillides, A. A. and Lanyon, L. E. (1995). Calvarial and limb bone cells in organ and monolayer culture do not show the same early responses to dynamic mechanical strain. Journal of Bone and Mineral Research, 10, 1225–1232.Google Scholar
Reich, D., Thangaraj, K., Patterson, N., Price, A. L. and Singh, L. (2009). Reconstructing Indian population history. Nature, 461, 489–494.Google Scholar
Richards, J. B., Zheng, H.-F. and Spector, T. D. (2012). Genetics of osteoporosis from genome-wide association studies: advances and challenges. Nature Reviews Genetics, 13, 577–588.Google Scholar
Riddle, R. C. and Donahue, H. J. (2009). From streaming potentials to shear stress: 25 years of bone cell mechanotransduction. Journal of Orthopaedic Research, 27, 143–149.Google Scholar
Robling, A. G. and Turner, C. H. (2002). Mechanotransduction in bone: genetic effects on mechanosensitivity in mice. Bone, 31, 562–569.Google Scholar
Robling, A. G., Li, J., Shultz, K. L., Beamer, W. G. and Turner, C. H. (2003). Evidence for a skeletal mechanosensitivity gene on mouse chromosome 4. FASEB Journal, 17, 324–326.Google Scholar
Robling, A. G., Warden, S. J., Shultz, K. L., Beamer, W. G. and Turner, C. H. (2007). Genetic effects on bone mechanotransduction in congenic mice harboring bone size and strength quantitative trait loci. Journal of Bone and Mineral Research, 22, 984–991.Google Scholar
Rubin, C. T. and Lanyon, L. E. (1982). Limb mechanics as a function of speed and gait: a study of functional strains in the radius and tibia of horse and dog. Journal of Experimental Biology, 101, 187–211.Google Scholar
Rubin, C. T. and Lanyon, L. E. (1984). Regulation of bone formation by applied dynamic loads. Journal of Bone and Joint Surgery, 66A, 397–402.Google Scholar
Rubin, C. T. and Lanyon, L. E. (1985). Regulation of bone mass by mechanical strain magnitude. Calcified Tissue International, 37, 411–417.Google Scholar
Rubin, C. T., McLeod, K. J. and Bain, S. D. (1990). Functional strains and cortical bone adaptation: epigenetic assurance of skeletal integrity. Journal of Biomechanics, 23, 43–54.Google Scholar
Rubin, C. T., Bain, S. D. and McLeod, K. J. (1992). Suppression of the osteogenic response in the aging skeleton. Calcified Tissue International, 50, 306–313.Google Scholar
Rubin, C., Turner, A. S., Bain, S., Mallinckrodt, C. and McLeod, K. (2001). Anabolism: low mechanical signals strengthen long bones. Nature, 412, 603–604.Google Scholar
Rubin, C. T., Seeherman, H., Qin, Y.-X. and Gross, T. S. (2013). The mechanical consequences of load bearing in the equine third metacarpal across speed and gait: the nonuniform distributions of normal strain, shear strain, and strain energy density. FASEB Journal, 27, 1887–1894.Google Scholar
Rubin, J., Schwartz, Z., Boyan, B. D., et al. (2007). Caveolin-1 knockout mice have increased bone size and stiffness. Journal of Bone and Mineral Research, 22, 1408–1418.Google Scholar
Ruff, C. B. (2005). Mechanical determinants of bone form: insights from skeletal remains. Journal of Musculoskeletal and Neuronal Interactions, 5, 202–212.Google Scholar
Ruff, C. B., Larsen, C. S. and Hayes, W. C. (1984). Structural changes in the femur with the transition to agriculture on the Georgia coast. American Journal of Physical Anthropology, 64, 124–136.CrossRefGoogle ScholarPubMed
Ruff, C. B., Trinkaus, E., Walker, A. and Larsen, C. S. (1993). Postcranial robusticity in Homo. I: temporal trends and mechanical interpretation. American Journal of Physical Anthropology, 91, 21–53.Google Scholar
Ruff, C. B., Holt, B. and Trinkaus, E. (2006). Who’s afraid of the big bad Wolff?: “Wolff’s Law” and bone functional adaptation. American Journal of Physical Anthropology, 129, 484–498.Google Scholar
Ruff, C. B., Holt, B., Niskanen, M., et al. (2015). Gradual decline in mobility with the adoption of food production in Europe. Proceedings of the National Academy of Sciences USA, 112, 7147–7152.Google Scholar
Salingcarnboriboon, R., Tsuji, K., Komori, T., et al. (2006). Runx2 is a target of mechanical unloading to alter osteoblastic activity and bone formation in vivo. Endocrinology, 147, 2296–2305.Google Scholar
Saxon, L. K., Jackson, B. F., Sugiyama, T., Lanyon, L. E. and Price, J. S. (2011). Analysis of multiple bone responses to graded strains above functional levels, and to disuse, in mice in vivo show that the human Lrp5 G171V High Bone Mass mutation increases the osteogenic response to loading but that lack of Lrp5 activity reduces it. Bone, 49, 184–193.Google Scholar
Schmitt, D., Zumwalt, A. C. and Hamrick, M. W. (2010). The relationship between bone mechanical properties and ground reaction forces in normal and hypermuscular mice. Journal of Experimental Zoology, 313A, 339–351.Google Scholar
Shaw, C. N. and Stock, J. T. (2009). Intensity, repetitiveness, and directionality of habitual adolescent mobility patterns influence the tibial diaphysis morphology of athletes. American Journal of Physical Anthropology, 140, 149–159.Google Scholar
Shaw, C. N. and Stock, J. T. (2013). Extreme mobility in the Late Pleistocene? Comparing limb biomechanics among fossil Homo, varsity athletes and Holocene foragers. Journal of Human Evolution, 64, 242–249.CrossRefGoogle ScholarPubMed
Simons, K. and Toomre, D. (2000). Lipid rafts and signal transduction. Nature Reviews Molecular Cell Biology, 1, 31–39.Google Scholar
Sládek, V., Berner, M. and Sailer, R. (2006). Mobility in Central European Late Eneolithic and Early Bronze Age: tibial cross-sectional geometry. Journal of Archaeological Science, 33, 470–482.Google Scholar
Snow-Harter, C., Bouxsein, M. L., Lewis, B. T., Carter, D. R. and Marcus, R. (1992). Effects of resistance and endurance exercise on bone mineral status of young women: a randomized exercise intervention trial. Journal of Bone and Mineral Research, 7, 761–769.Google Scholar
Srinivasan, S., Agans, S. C., King, K. A., et al. (2003). Enabling bone formation in the aged skeleton via rest-inserted mechanical loading. Bone, 33, 946–955.Google Scholar
Srinivasan, S., Ausk, B. J., Poliachik, S. L., et al. (2007). Rest-inserted loading rapidly amplifies the response of bone to small increases in strain and load cycles. Journal of Applied Physiology, 102, 1945–1952.CrossRefGoogle ScholarPubMed
Srinivasan, S., Gross, T. S. and Bain, S. D. (2012). Bone mechanotransduction may require augmentation in order to strengthen the senescent skeleton. Ageing Research Reviews, 11, 353–360.Google Scholar
Styrkarsdottir, U., Halldorsson, B. V., Gudbjartsson, D. F., et al. (2010). European bone mineral density loci are also associated with BMD in East-Asian populations. PLoS ONE, 5, e13217.Google Scholar
Suuriniemi, M., Mahonen, A., Kovanen, V., et al. (2004). Association between exercise and pubertal BMD is modulated by estrogen receptor α genotype. Journal of Bone and Mineral Research, 19, 1758–1765.Google Scholar
Tajima, O., Ashizawa, N., Ishii, T., et al. (2000). Interaction of the effects between vitamin D receptor polymorphism and exercise training on bone metabolism. Journal of Applied Physiology, 88, 1271–1276.Google Scholar
Tan, V. P., Macdonald, H. M., Kim, S., et al. (2014). Influence of physical activity on bone strength in children and adolescents: a systematic review and narrative synthesis. Journal of Bone and Mineral Research, 29, 2161–2181.Google Scholar
Thompson, W. R., Rubin, C. T. and Rubin, J. (2012). Mechanical regulation of signaling pathways in bone. Gene, 503, 179–193.Google Scholar
Trinkaus, E. (1997). Appendicular robusticity and the paleobiology of modern human emergence. Proceedings of the National Academy of Sciences USA, 94, 13367–13373.Google Scholar
Trinkaus, E., Ruff, C. B., Churchill, S. E. and Vandermeersch, B. (1998). Locomotion and body proportions of the Saint-Césaire 1 Châtelperronian Neandertal. Proceedings of the National Academy of Sciences USA, 95, 5836–5840.Google Scholar
Turner, C. H., Takano, Y. and Owan, I. (1995). Aging changes mechanical loading thresholds for bone formation in rats. Journal of Bone and Mineral Research, 10, 1544–1549.Google Scholar
Turner, C. H., Takano, Y., Owan, I. and Murrell, G. A. (1996). Nitric oxide inhibitor L-NAME suppresses mechanically induced bone formation in rats. American Journal of Physiology, 270, E634–639.Google Scholar
Vashishth, D. (2007). The role of the collagen matrix in skeletal fragility. Current Osteoporosis Reports, 5, 62–66.Google Scholar
Vaughan, T., Reid, D. M., Morrison, N. A. and Ralston, S. H. (2004). RUNX2 alleles associated with BMD in Scottish women; interaction of RUNX2 alleles with menopausal status and body mass index. Bone, 34, 1029–1036.Google Scholar
Vico, L., Collet, P., Guignandon, A., et al. (2000). Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet, 355, 1607–1611.Google Scholar
Wallace, I. J. (2013). Physical activity and genetics as determinants of limb bone structure. PhD dissertation, Stony Brook University. Available at: www.paleoanthro.org/dissertations/download/Google Scholar
Wallace, I. J., Middleton, K. M., Lublinsky, S., et al. (2010). Functional significance of genetic variation underlying limb bone diaphyseal structure. American Journal of Physical Anthropology, 143, 21–30.Google Scholar
Wallace, I. J., Tommasini, S. M., Judex, S., Garland, T. Jr. and Demes, B. (2012). Genetic variations and physical activity as determinants of limb bone morphology: an experimental approach using a mouse model. American Journal of Physical Anthropology, 148, 24–35.Google Scholar
Wallace, I. J., Demes, B., Mongle, C., et al. (2014). Exercise-induced bone formation is poorly linked to local strain magnitude in the sheep tibia. PLoS ONE, 9, e99108.Google Scholar
Wallace, I. J., Judex, S. and Demes, B. (2015). Effects of load-bearing exercise on skeletal structure and mechanics differ between outbred populations of mice. Bone, 72, 1–8.Google Scholar
Wang, N., Butler, J. P. and Ingber, D. E. (1993). Mechanotransduction across the cell surface and through the cytoskeleton. Science, 260, 1124–1127.CrossRefGoogle ScholarPubMed
Wang, Y. L., McNamara, L. M., Schaffler, M. B. and Weinbaum, S. (2007). A model for the role of integrins in flow induced mechanotransduction in osteocytes. Proceedings of the National Academy of Sciences USA, 104, 15941–15946.CrossRefGoogle Scholar
Warden, S. J., Mantila Roosa, S. M., Kersh, M. E., et al. (2014). Physical activity when young provides lifelong benefits to cortical bone size and strength in men. Proceedings of the National Academy of Sciences USA, 111, 5337–5342.Google Scholar
Wesselius, A., Bours, M. J., Agrawal, A., et al. (2011). Role of purinergic receptor polymorphisms in human bone. Frontiers in Bioscience, 16, 2572–2585.Google Scholar
West-Eberhard, M. J. (2003). Developmental Plasticity and Evolution. Oxford: Oxford University Press.Google Scholar
Wetzsteon, R. J., Zemel, B. S., Shults, J., et al. (2011). Mechanical loads and cortical bone geometry in healthy children and young adults. Bone, 48, 1103–1108.Google Scholar
Wolff, J. (1892). Das Gesetz der Transformation der Knochen. Berlin: A. Hirschwald.Google Scholar
Yalcin, B., Nicod, J., Bhomra, A., et al. (2010). Commercially available outbred mice for genome-wide association studies. PLoS Genetics, 6, e1001085.Google Scholar
Yellowley, C. E., Li, Z., Zhou, Z., Jacobs, C. R. and Donahue, H. J. (2000). Functional gap junctions between osteocytic and osteoblastic cells. Journal of Bone and Mineral Research, 15, 209–217.Google Scholar
Ziros, P. G., Basdra, E. K. and Papavassiliou, A. G. (2008). Runx2: of bone and stretch. International Journal of Biochemistry and Cell Biology, 40, 1659–1663.Google Scholar

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