Age-Related Changes in Bone: Variation and Factors Influencing Bone Fragility

Humans have a unique evolutionary trajectory that allows life past reproductive viability. Antagonistic pleiotropy and resource economics lead to the deterioration of physiological processes once beyond years in which natural selection is effective. As individuals age, bone becomes increasingly fragile and prone to fracture. Due to heterogeneity in human aging patterns, bone aging is a highly variable process. The ability to predict, diagnose, and treat age-related bone fragility has become an area of major focus in medical research, however, there is little consensus in the field as to the mechanisms behind bone aging. The lack of clarity in the causes of bone aging makes individualized medical approaches difficult. Studies of these mechanisms are complicated by the inherent variability in human biology and environment. The use of murine models provides greater experimental control but has previously not recognized the presence of variability in aging.

This work provides evidence for the utility of multiple inbred mouse strains in aging research. This approach provides high level of control but also allows investigation into the causes behind variable aging outcomes. The first aim of this project establishes differences in bone aging in the femora of four inbred mouse strains to demonstrate the range of intraspecies variability in bone aging. The BALB/c and C57Bl/6 strains lose mechanical functionality with age but in different ways. The CBA/J and DBA/2 strains maintain mechanical integrity with aging using different strategies. Different rates of remodeling, as well as mineralization, lead to the variation in mechanical function changes with age in the four strains. The second aim investigates the applicability of comparative mouse models of aging to humans. This aim applies modern theories of aging to the variable bone outcomes. The third aim demonstrates the potential influence age-related changes in mechanoresponse have on bone aging using a tibial axial loading model. The data in this thesis demonstrate the variability in bone aging in a mouse model, providing potential insight into human inter-individual aging variations. The work presented also provides a platform for future aging experimentation investigating factors that influence how well bone ages.

Year	Entry
2006	Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M, .Peterson JM, Melton LJ III. Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res. January 2006;21(1):124-131.
2003	Ahlborg HG, Johnell O, Turner CH, Rannevik G, Karlsson MK. Bone loss and bone size after menopause. NEJM. July 24, 2003;349(4):327-334.
2010	Willinghamm MD, Brodt MD, Lee KL, Stephens AL, Ye J, Silva MJ. Age-related changes in bone structure and strength in female and male BALB/c mice. Calcif Tiss Int. June 2010;86(6):470-483.
2001	Lanyon L, Skerry T. Postmenopausal osteoporosis as a failure of bone's adaptation to functional loading: a hypothesis. J Bone Miner Res. November 2001;16(11):1937-1947.
1996	Aspray TJ, Prentice A, Cole TJ, Sawo Y, Reeve J, Francis RM. Low bone mineral content is common but osteoporotic fractures are rare in elderly rural Gambian women. J Bone Miner Res. July 1996;11(7):1019-1025.
2010	Boskey AL, Coleman R. Aging and bone. J Dent Res. December 2010;89(2):1333-1348.
2014	Birkhold AI, Razi H, Duda GN, Weinkamer R, Checa S, Willie BM. The influence of age on adaptive bone formation and bone resorption. Biomaterials. November 2014;35(34):9290-9301.
1977	Martin RB, Atkinson PJ. Age and sex-related changes in the structure and strength of the human femoral shaft. J Biomech. 1977;10(4):223-231.
2014	Meakin LB, Galea GL, Sugiyama T, Lanyon LE, Price JS. Age-related impairment of bones' adaptive response to loading in mice is associated with sex-related deficiencies in osteoblasts but no change in osteocytes. J Bone Miner Res. August 2014;29(8):1859-1871.
2006	McNamara LM, Ederveen AGH, Lyons CG, Price C, Schaffler MB, Weinans H, Prendergast PJ. Strength of cancellous bone trabecular tissue from normal, ovariectomized and drug-treated rats over the course of ageing. Bone. August 2006;39(2):392-400.
2010	Lynch ME, Main RP, Xu Q, Walsh DJ, Schaffler MB, Wright TM, van der Meulen MCH. Cancellous bone adaptation to tibial compression is not sex dependent in growing mice. J Appl Physiol. September 2010;109(3):685-691.
2010	Soves CP. The Potential Role of Megakaryocytes in Mechanically Mediated Bone Adaptation [PhD thesis]. University of Michigan; 2010.
2005	Price C, Herman BC, Lufkin T, Goldman HM, Jepsen KJ. Genetic variation in bone growth patterns defines adult mouse bone fragility. J Bone Miner Res. November 2005;20(11):1983-1991.
2007	Nyman JS, Roy A, Tyler JH, Acuna RL, Gayle HJ, Wang X. Age‐related factors affecting the postyield energy dissipation of human cortical bone. J Orthop Res. May 2007;25(7):646-655.
1994	Bouxsein ML, Myburgh KH, van der Meulen MCH, Lindenberger E, Marcus R. Age-related differences in cross-sectional geometry of the forearm bones in healthy women. Calcif Tiss Int. February 1994;54(2):113-118.
2003	Currey JD. The many adaptations of bone. J Biomech. 2003;36(10):1487-1495.
2012	Silva MJ, Brodt MD, Lynch MA, Stephens AL, Wood DJ, Civitelli R. Tibial loading increases osteogenic gene expression and cortical bone volume in mature and middle-aged mice. PLoS One. April 2012;7(4):e34980.
2005	Fritton JC, Myers ER, Wright TM, van der Meulen MCH. Loading induces site-specific increases in mineral content assessed by microcomputed tomography of the mouse tibia. Bone. June 2005;36(6):1030-1038.
1996	Fox SW, Chambers TJ, Chow JW. Nitric oxide is an early mediator of the increase in bone formation by mechanical stimulation. Am J Physiol Endocrinol Metab. June 1996;270(6):E955-E960.
1995	Klein-Nulend J, Semeins CM, Ajubi NE, Nijweide P, Burger EH. Pulsating fluid flow increases nitric oxide (NO) synthesis by osteocytes but not periosteal fibroblasts - correlation with prostaglandin upregulation. Biochem Biophys Res Commun. December 14, 1995;217(2):640-648.
1995	Turner CH, Takano Y, Owan I. Aging changes mechanical loading thresholds for bone formation in rats. J Bone Miner Res. October 1995;10(10):1544-1549.
2014	Holguin N, Brodt MD, Sanchez ME, Silva MJ. Aging diminishes lamellar and woven bone formation induced by tibial compression in adult C57BL/6. Bone. August 2014;65:83-91.
1995	Pitsillides AA, Rawlinson SCF, Suswillo RFL, Bourrin S, Zaman G, Lanyon LE. Mechanical strain‐induced NO production by bone cells: a possible role in adaptive bone (re)modeling? FASEB J. December 1995;9(15):1614-1622.
2005	De Souza RL, Matsuura M, Eckstein F, Rawlinson SCF, Lanyon LE, Pitsillides AA. Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. Bone. December 2005;37(6):810-818.
2002	Cummings SR, Melton LJ III. Epidemiology and outcomes of osteoporotic fractures. Lancet. May 18, 2002;359(9319):1761-1767.
2002	Wang X, Shen X, Li X, Agrawal CM. Age-related changes in the collagen network and toughness of bone [published correction appears in Bone. 2003;32(1):107]. Bone. 2002;31(1):1-7.
2004	Riggs BL, Melton LJ III, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, Rouleau PA, McCollough CH, Bouxsein ML, Khosla S. Population-based study of age and sex differences in bone volumetricdensity, size, geometry, and structure at different skeletal sites. J Bone Miner Res. December 2004;19(12):1945-1954.
1993	Felson DT, Zhang Y, Hannan MT, Anderson JJ. Effects of weight and body mass index on bone mineral density in men and women: the Framingham Study. J Bone Miner Res. May 1993;8(5):567-573.
2005	Schriefer JL, Warden SJ, Saxon LK, Robling AG, Turner CH. Cellular accommodation and the response of bone to mechanical loading. J Biomech. September 2005;38(9):1838-1845.
2003	Jepsen KJ, Akkus OJ, Majeska RJ, Nadeau JH. Hierarchical relationship between bone traits and mechanical properties in inbred mice. Mamm Genome. February 2003;14(2):97-104.
1993	McCalden RW, McGeough JA, Barker MB, Court-Brown CM. Age-related changes in the tensile properties of cortical bone: the relative importance of changes in porosity, mineralization, and microstructure. J Bone Joint Surg. 1993;75A(8):1193-1205.
1996	Turner CH, Takano Y, Owan I, Murrell GA. Nitric oxide inhibitor L-NAME suppresses mechanically induced bone formation in rats. Am J Physiol Endocrinol Metab. April 1996;270(4):E634-E639.
2010	Brodt MD, Silva MJ. Aged mice have enhanced endocortical response and normal periosteal response compared with young-adult mice following 1 week of axial tibial compression. J Bone Miner Res. September 2010;25(9):2006-2015.
2001	Cheng B, Zhao S, Luo J, Sprague E, Bonewald LF, Jiang JX. Expression of functional gap junctions and regulation by fluid flow in osteocyte-like MLO-Y4 cells. J Bone Miner Res. February 2001;16(2):249-259.
1988	Ruff CB, Hayes WC. Sex differences in age‐related remodeling of the femur and tibia. J Orthop Res. November 1988;6(6):886-896.
2007	Glatt V, Canalis E, Stadmeyer L, Bouxsein ML. Age‐related changes in trabecular architecture differ in female and male C57BL/6J mice. J Bone Miner Res. August 2007;22(8):1197-1207.
2003	Akkus O, Polyakova‐Akkus A, Adar F, Schaffler MB. Aging of microstructural compartments in human compact bone. J Bone Miner Res. June 2003;18(6):1012-1019.
2010	Isaksson H, Malkiewicz M, Nowak R, Helminen HJ, Jurvelin JS. Rabbit cortical bone tissue increases its elastic stiffness but becomes less viscoelastic with age. Bone. December 2010;47(6):1030-1038.
2001	Donahue SW, Jacobs CR, Donahue HJ. Flow-induced calcium oscillations in rat osteoblasts are age, loading frequency, and shear stress dependent. Am J Physiol Cell Physiol. November 2001;281(5):C1635-C1641.
1998	Singer BR, McLauchlan GJ, Robinson CM, Christie J. Epidemiology of fractures in 15 000 adults: the influence of age and gender. J Bone Joint Surg. March 1998;80B(2):243-248.
1999	Zaman G, Pitsillides AA, Rawlinson SCF, Suswillo RFL, Mosley JR, Cheng MZ, Platts LAM, Hukkanen M, Polak JM, Lanyon LE. Mechanical strain stimulates nitric oxide production by rapid activation of endothelial nitric oxide synthase in osteocytes. J Bone Miner Res. July 1999;14(7):1123-1131.
2003	Srinivasan S, Agans SC, King KA, Moy NY, Poliachik SL, Gross TS. Enabling bone formation in the aged skeleton via rest-inserted mechanical loading. Bone. December 2003;33(6):946-955.
2002	Halloran BP, Ferguson VL, Simske SJ, Burghardt A, Venton LL, Majumdar S. Changes in bone structure and mass with advancing age in the male C57BL/6J mouse. J Bone Miner Res. June 2002;17(6):1044-1050.
2003	Seeman E. Periosteal bone formation: a neglected determinant of bone strength. NEJM. July 24, 2003;349(4):320-323.
1990	Leblanc AD, Schneider VS, Evans HJ, Engelbretson DA, Krebs JM. Bone mineral loss and recovery after 17 weeks of bed rest. J Bone Miner Res. August 1990;5(8):843-850.
2000	Heaney RP, Abrams S, Dawson-Hughes B, Looker A, Marcus R, Matkovic V, Weaver C. Peak bone mass. Osteoporos Int. December 2000;11(12):985-1009.
2002	Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet. June 1, 2002;359(9321):1929-1936.
2003	Ferguson VL, Ayers RA, Bateman TA, Simske SJ. Bone development and age-related bone loss in male C57BL/6J mice. Bone. March 2003;32(3):387-398.
1998	Zioupos P, Currey JD. Changes in the stiffness, strength, and toughness of human cortical bone with age. Bone. January 1998;22(1):57-66.
2003	Frost HM. Bone's mechanostat: a 2003 update. Anat Rec. 2003;275A(2):1081-1101.
2000	Fyhrie DP, Vashishth D. Bone stiffness predicts strength similarly for human vertebral cancellous bone in compression and for cortical bone in tension. Bone. February 2000;26(2):169-173.
2006	Szulc P, Seeman E, Duboeuf F, Sornay-Rendu E, Delmas PD. Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women. J Bone Miner Res. December 2006;21(12):1856-1863.
1976	Burstein AH, Reilly DT, Martens M. Aging of bone tissue: mechanical properties. J Bone Joint Surg. 1976;58A(1):82-86.
2005	Johnell O, Kanis JA, Oden A, Johansson H, De Laet C, Delmas P, Eisman JA, Fujiwara S, Kroger H, Mellstrom D, Meunier PJ, Melton LJ III, O'Neill T, Pols H, Reeve J, Silman A, Tenenhouse A. Predictive value of BMD for hip and other fractures. J Bone Miner Res. July 2005;20(7):1185-1194.
2007	LeBlanc AD, Spector ER, Evans HJ, Sibonga JD. Skeletal responses to space flight and the bed rest analog: a review. J Musculoskel Neuron Interact. 2007;7(1):33-47.
2006	Robling AG, Castillo AB, Turner CH. Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng. 2006;8:455-498.

Year

Entry

2006

Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M, .Peterson JM, Melton LJ III. Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res. January 2006;21(1):124-131.

2003

Ahlborg HG, Johnell O, Turner CH, Rannevik G, Karlsson MK. Bone loss and bone size after menopause. NEJM. July 24, 2003;349(4):327-334.

2010

Willinghamm MD, Brodt MD, Lee KL, Stephens AL, Ye J, Silva MJ. Age-related changes in bone structure and strength in female and male BALB/c mice. Calcif Tiss Int. June 2010;86(6):470-483.

2001

Lanyon L, Skerry T. Postmenopausal osteoporosis as a failure of bone's adaptation to functional loading: a hypothesis. J Bone Miner Res. November 2001;16(11):1937-1947.

1996

Aspray TJ, Prentice A, Cole TJ, Sawo Y, Reeve J, Francis RM. Low bone mineral content is common but osteoporotic fractures are rare in elderly rural Gambian women. J Bone Miner Res. July 1996;11(7):1019-1025.

2010

Boskey AL, Coleman R. Aging and bone. J Dent Res. December 2010;89(2):1333-1348.

2014

Birkhold AI, Razi H, Duda GN, Weinkamer R, Checa S, Willie BM. The influence of age on adaptive bone formation and bone resorption. Biomaterials. November 2014;35(34):9290-9301.

1977

Martin RB, Atkinson PJ. Age and sex-related changes in the structure and strength of the human femoral shaft. J Biomech. 1977;10(4):223-231.

2014

Meakin LB, Galea GL, Sugiyama T, Lanyon LE, Price JS. Age-related impairment of bones' adaptive response to loading in mice is associated with sex-related deficiencies in osteoblasts but no change in osteocytes. J Bone Miner Res. August 2014;29(8):1859-1871.

2006

McNamara LM, Ederveen AGH, Lyons CG, Price C, Schaffler MB, Weinans H, Prendergast PJ. Strength of cancellous bone trabecular tissue from normal, ovariectomized and drug-treated rats over the course of ageing. Bone. August 2006;39(2):392-400.

2010

Lynch ME, Main RP, Xu Q, Walsh DJ, Schaffler MB, Wright TM, van der Meulen MCH. Cancellous bone adaptation to tibial compression is not sex dependent in growing mice. J Appl Physiol. September 2010;109(3):685-691.

2010

Soves CP. The Potential Role of Megakaryocytes in Mechanically Mediated Bone Adaptation [PhD thesis]. University of Michigan; 2010.

2005

Price C, Herman BC, Lufkin T, Goldman HM, Jepsen KJ. Genetic variation in bone growth patterns defines adult mouse bone fragility. J Bone Miner Res. November 2005;20(11):1983-1991.

2007

Nyman JS, Roy A, Tyler JH, Acuna RL, Gayle HJ, Wang X. Age‐related factors affecting the postyield energy dissipation of human cortical bone. J Orthop Res. May 2007;25(7):646-655.

1994

Bouxsein ML, Myburgh KH, van der Meulen MCH, Lindenberger E, Marcus R. Age-related differences in cross-sectional geometry of the forearm bones in healthy women. Calcif Tiss Int. February 1994;54(2):113-118.

2003

Currey JD. The many adaptations of bone. J Biomech. 2003;36(10):1487-1495.

2012

Silva MJ, Brodt MD, Lynch MA, Stephens AL, Wood DJ, Civitelli R. Tibial loading increases osteogenic gene expression and cortical bone volume in mature and middle-aged mice. PLoS One. April 2012;7(4):e34980.

2005

Fritton JC, Myers ER, Wright TM, van der Meulen MCH. Loading induces site-specific increases in mineral content assessed by microcomputed tomography of the mouse tibia. Bone. June 2005;36(6):1030-1038.

1996

Fox SW, Chambers TJ, Chow JW. Nitric oxide is an early mediator of the increase in bone formation by mechanical stimulation. Am J Physiol Endocrinol Metab. June 1996;270(6):E955-E960.

1995

Klein-Nulend J, Semeins CM, Ajubi NE, Nijweide P, Burger EH. Pulsating fluid flow increases nitric oxide (NO) synthesis by osteocytes but not periosteal fibroblasts - correlation with prostaglandin upregulation. Biochem Biophys Res Commun. December 14, 1995;217(2):640-648.

1995

Turner CH, Takano Y, Owan I. Aging changes mechanical loading thresholds for bone formation in rats. J Bone Miner Res. October 1995;10(10):1544-1549.

2014

Holguin N, Brodt MD, Sanchez ME, Silva MJ. Aging diminishes lamellar and woven bone formation induced by tibial compression in adult C57BL/6. Bone. August 2014;65:83-91.

1995

Pitsillides AA, Rawlinson SCF, Suswillo RFL, Bourrin S, Zaman G, Lanyon LE. Mechanical strain‐induced NO production by bone cells: a possible role in adaptive bone (re)modeling? FASEB J. December 1995;9(15):1614-1622.

2005

De Souza RL, Matsuura M, Eckstein F, Rawlinson SCF, Lanyon LE, Pitsillides AA. Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. Bone. December 2005;37(6):810-818.

2002

Cummings SR, Melton LJ III. Epidemiology and outcomes of osteoporotic fractures. Lancet. May 18, 2002;359(9319):1761-1767.

2002

Wang X, Shen X, Li X, Agrawal CM. Age-related changes in the collagen network and toughness of bone [published correction appears in Bone. 2003;32(1):107]. Bone. 2002;31(1):1-7.

2004

Riggs BL, Melton LJ III, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, Rouleau PA, McCollough CH, Bouxsein ML, Khosla S. Population-based study of age and sex differences in bone volumetricdensity, size, geometry, and structure at different skeletal sites. J Bone Miner Res. December 2004;19(12):1945-1954.

1993

Felson DT, Zhang Y, Hannan MT, Anderson JJ. Effects of weight and body mass index on bone mineral density in men and women: the Framingham Study. J Bone Miner Res. May 1993;8(5):567-573.

2005

Schriefer JL, Warden SJ, Saxon LK, Robling AG, Turner CH. Cellular accommodation and the response of bone to mechanical loading. J Biomech. September 2005;38(9):1838-1845.

2003

Jepsen KJ, Akkus OJ, Majeska RJ, Nadeau JH. Hierarchical relationship between bone traits and mechanical properties in inbred mice. Mamm Genome. February 2003;14(2):97-104.

1993

McCalden RW, McGeough JA, Barker MB, Court-Brown CM. Age-related changes in the tensile properties of cortical bone: the relative importance of changes in porosity, mineralization, and microstructure. J Bone Joint Surg. 1993;75A(8):1193-1205.

1996

Turner CH, Takano Y, Owan I, Murrell GA. Nitric oxide inhibitor L-NAME suppresses mechanically induced bone formation in rats. Am J Physiol Endocrinol Metab. April 1996;270(4):E634-E639.

2010

Brodt MD, Silva MJ. Aged mice have enhanced endocortical response and normal periosteal response compared with young-adult mice following 1 week of axial tibial compression. J Bone Miner Res. September 2010;25(9):2006-2015.

2001

Cheng B, Zhao S, Luo J, Sprague E, Bonewald LF, Jiang JX. Expression of functional gap junctions and regulation by fluid flow in osteocyte-like MLO-Y4 cells. J Bone Miner Res. February 2001;16(2):249-259.

1988

Ruff CB, Hayes WC. Sex differences in age‐related remodeling of the femur and tibia. J Orthop Res. November 1988;6(6):886-896.

2007

Glatt V, Canalis E, Stadmeyer L, Bouxsein ML. Age‐related changes in trabecular architecture differ in female and male C57BL/6J mice. J Bone Miner Res. August 2007;22(8):1197-1207.

2003

Akkus O, Polyakova‐Akkus A, Adar F, Schaffler MB. Aging of microstructural compartments in human compact bone. J Bone Miner Res. June 2003;18(6):1012-1019.

2010

Isaksson H, Malkiewicz M, Nowak R, Helminen HJ, Jurvelin JS. Rabbit cortical bone tissue increases its elastic stiffness but becomes less viscoelastic with age. Bone. December 2010;47(6):1030-1038.

2001

Donahue SW, Jacobs CR, Donahue HJ. Flow-induced calcium oscillations in rat osteoblasts are age, loading frequency, and shear stress dependent. Am J Physiol Cell Physiol. November 2001;281(5):C1635-C1641.

1998

Singer BR, McLauchlan GJ, Robinson CM, Christie J. Epidemiology of fractures in 15 000 adults: the influence of age and gender. J Bone Joint Surg. March 1998;80B(2):243-248.

1999

Zaman G, Pitsillides AA, Rawlinson SCF, Suswillo RFL, Mosley JR, Cheng MZ, Platts LAM, Hukkanen M, Polak JM, Lanyon LE. Mechanical strain stimulates nitric oxide production by rapid activation of endothelial nitric oxide synthase in osteocytes. J Bone Miner Res. July 1999;14(7):1123-1131.

2003

Srinivasan S, Agans SC, King KA, Moy NY, Poliachik SL, Gross TS. Enabling bone formation in the aged skeleton via rest-inserted mechanical loading. Bone. December 2003;33(6):946-955.

2002

Halloran BP, Ferguson VL, Simske SJ, Burghardt A, Venton LL, Majumdar S. Changes in bone structure and mass with advancing age in the male C57BL/6J mouse. J Bone Miner Res. June 2002;17(6):1044-1050.

2003

Seeman E. Periosteal bone formation: a neglected determinant of bone strength. NEJM. July 24, 2003;349(4):320-323.

1990

Leblanc AD, Schneider VS, Evans HJ, Engelbretson DA, Krebs JM. Bone mineral loss and recovery after 17 weeks of bed rest. J Bone Miner Res. August 1990;5(8):843-850.

2000

Heaney RP, Abrams S, Dawson-Hughes B, Looker A, Marcus R, Matkovic V, Weaver C. Peak bone mass. Osteoporos Int. December 2000;11(12):985-1009.

2002

Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet. June 1, 2002;359(9321):1929-1936.

2003

Ferguson VL, Ayers RA, Bateman TA, Simske SJ. Bone development and age-related bone loss in male C57BL/6J mice. Bone. March 2003;32(3):387-398.

1998

Zioupos P, Currey JD. Changes in the stiffness, strength, and toughness of human cortical bone with age. Bone. January 1998;22(1):57-66.

2003

Frost HM. Bone's mechanostat: a 2003 update. Anat Rec. 2003;275A(2):1081-1101.

2000

Fyhrie DP, Vashishth D. Bone stiffness predicts strength similarly for human vertebral cancellous bone in compression and for cortical bone in tension. Bone. February 2000;26(2):169-173.

2006

Szulc P, Seeman E, Duboeuf F, Sornay-Rendu E, Delmas PD. Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women. J Bone Miner Res. December 2006;21(12):1856-1863.

1976

Burstein AH, Reilly DT, Martens M. Aging of bone tissue: mechanical properties. J Bone Joint Surg. 1976;58A(1):82-86.

2005

Johnell O, Kanis JA, Oden A, Johansson H, De Laet C, Delmas P, Eisman JA, Fujiwara S, Kroger H, Mellstrom D, Meunier PJ, Melton LJ III, O'Neill T, Pols H, Reeve J, Silman A, Tenenhouse A. Predictive value of BMD for hip and other fractures. J Bone Miner Res. July 2005;20(7):1185-1194.

2007

LeBlanc AD, Spector ER, Evans HJ, Sibonga JD. Skeletal responses to space flight and the bed rest analog: a review. J Musculoskel Neuron Interact. 2007;7(1):33-47.

2006

Robling AG, Castillo AB, Turner CH. Biomechanical and molecular regulation of bone remodeling. Annu Rev Biomed Eng. 2006;8:455-498.

Year	Entry
2020	Mumtaz H, Dallas M, Begonia M, Lara-Castillo N, Scott JM, Johnson ML, Ganesh T. Age-related and sex-specific effects on architectural properties and biomechanical response of the C57BL/6N mouse femur, tibia and ulna. Bone Rep. June 2020;12:100266.

Year

Entry

2020

Mumtaz H, Dallas M, Begonia M, Lara-Castillo N, Scott JM, Johnson ML, Ganesh T. Age-related and sex-specific effects on architectural properties and biomechanical response of the C57BL/6N mouse femur, tibia and ulna. Bone Rep. June 2020;12:100266.