• 1
    Karasik D, Hannan MT, Cupples LA, Felson DT, Kiel DP 2004 Genetic contribution to biological aging: The Framingham Study. J Gerontol A Biol Sci Med Sci 59: 218226.
  • 2
    Pearson OM, Lieberman DE 2004 The aging of Wolff's “law”: Ontogeny and responses to mechanical loading in cortical bone. Am J Phys Anthropol Suppl 39: 6399.
  • 3
    Manolagas SC 2000 Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21: 115137.
  • 4
    Kiel DP 2000 Adult bone maintenance. In: MarcusR (ed.) Atlas of Clinical Endocrinology. III. Osteoporosis. Current Medicine, Philadelphia, PA, USA, 2939.
  • 5
    Buckey JC 2006 Space Physiology. University Press, Oxford, UK.
  • 6
    Zethraeus N, Borgstrom F, Strom O, Kanis JA, Jonsson B 2007 Cost-effectiveness of the treatment and prevention of osteoporosis–a review of the literature and a reference model. Osteoporos Int 18: 923.
  • 7
    Faulkner KG, Wacker WK, Barden HS, Simonelli C, Burke PK, Ragi S, Del Rio L 2006 Femur strength index predicts hip fracture independent of bone density and hip axis length. Osteoporos Int 17: 593599.
  • 8
    Faulkner KG, Cummings SR, Black D, Palermo L, Gluer CC, Genant HK 1993 Simple measurement of femoral geometry predicts hip fracture: The study of osteoporotic fractures. J Bone Miner Res 8: 12111217.
  • 9
    Melton LJ III, Riggs BL, van Lenthe GH, Achenbach SJ, Muller R, Bouxsein ML, Amin S, Atkinson EJ, Khosla S 2007 Contribution of in vivo structural measurements and load/strength ratios to the determination of forearm fracture risk in postmenopausal women. J Bone Miner Res 22: 14421448.
  • 10
    Lauretani F, Bandinelli S, Bartali B, Iorio AD, Giacomini V, Corsi AM, Guralnik JM, Ferrucci L 2006 Axonal degeneration affects muscle density in older men and women. Neurobiol Aging 27: 11451154.
  • 11
    Tan RS 2005 Aging Men's Health: A Case-Based Approach. Thieme, New York, NY, USA.
  • 12
    Frontera WR, Hughes VA, Fielding RA, Fiatarone MA, Evans WJ, Roubenoff R 2000 Aging of skeletal muscle: A 12-yr longitudinal study. J Appl Physiol 88: 13211326.
  • 13
    Frederiksen H, Gaist D, Petersen HC, Hjelmborg J, McGue M, Vaupel JW, Christensen K 2002 Hand grip strength: A phenotype suitable for identifying genetic variants affecting mid- and late-life physical functioning. Genet Epidemiol 23: 110122.
  • 14
    Rantanen T, Volpato S, Ferrucci L, Heikkinen E, Fried LP, Guralnik JM 2003 Handgrip strength and cause-specific and total mortality in older disabled women: Exploring the mechanism. J Am Geriatr Soc 51: 636641.
  • 15
    Frontera WR, Suh D, Krivickas LS, Hughes VA, Goldstein R, Roubenoff R 2000 Skeletal muscle fiber quality in older men and women. Am J Physiol Cell Physiol 279: C611C618.
  • 16
    Goodpaster BH, Kelley DE, Thaete FL, He J, Ross R 2000 Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content. J Appl Physiol 89: 104110.
  • 17
    Goodpaster BH, Thaete FL, Kelley DE 2000 Composition of skeletal muscle evaluated with computed tomography. Ann N Y Acad Sci 904: 1824.
  • 18
    Hicks GE, Simonsick EM, Harris TB, Newman AB, Weiner DK, Nevitt MA, Tylavsky FA 2005 Trunk muscle composition as a predictor of reduced functional capacity in the health, aging and body composition study: The moderating role of back pain. J Gerontol A Biol Sci Med Sci 60: 14201424.
  • 19
    Hicks GE, Simonsick EM, Harris TB, Newman AB, Weiner DK, Nevitt MA, Tylavsky FA 2005 Cross-sectional associations between trunk muscle composition, back pain, and physical function in the health, aging and body composition study. J Gerontol A Biol Sci Med Sci 60: 882887.
  • 20
    Prendergast P, van der Helm F, Duda G 2005 Analysis of muscles and joint loads. In: MowV, HuiskesR (eds.) Basic Orthopaedic Biomechanics and Mechano-Biology, 3rd ed. Lippincott Williams & Wilkins, Philadelphia, PA, USA, 2989.
  • 21
    Visser M, Kritchevsky SB, Goodpaster BH, Newman AB, Nevitt M, Stamm E, Harris TB 2002 Leg muscle mass and composition in relation to lower extremity performance in men and women aged 70 to 79: The health, aging and body composition study. J Am Geriatr Soc 50: 897904.
  • 22
    Broadwin J, Goodman-Gruen D, Slymen D 2001 Ability of fat and fat-free mass percentages to predict functional disability in older men and women. J Am Geriatr Soc 49: 16411645.
  • 23
    Huygens W, Thomis MA, Peeters MW, Vlietinck RF, Beunen GP 2004 Determinants and upper-limit heritabilities of skeletal muscle mass and strength. Can J Appl Physiol 29: 186200.
  • 24
    Visser M, Harris TB, Langlois J, Hannan MT, Roubenoff R, Felson DT, Wilson PW, Kiel DP 1998 Body fat and skeletal muscle mass in relation to physical disability in very old men and women of the Framingham Heart Study. J Gerontol A Biol Sci Med Sci 53: M214M221.
  • 25
    Visser M, Deeg DJ, Lips P, Harris TB, Bouter LM 2000 Skeletal muscle mass and muscle strength in relation to lower-extremity performance in older men and women. J Am Geriatr Soc 48: 381386.
  • 26
    Solomon AM, Bouloux PM 2006 Modifying muscle mass—the endocrine perspective. J Endocrinol 191: 349360.
  • 27
    Frost HM, Schonau E 2000 The “muscle-bone unit” in children and adolescents: A 2000 overview. J Pediatr Endocrinol Metab 13: 571590.
  • 28
    Frost HM 2003 Bone's mechanostat: A 2003 update. Anat Rec A Discov Mol Cell Evol Biol 275: 1081101.
  • 29
    Sievänen H 2005 Hormonal influences on the muscle-bone feedback system: A perspective. J Musculoskelet Neuronal Interact 5: 255261.
  • 30
    Orestes-Cardoso SM, Nefussi JR, Hotton D, Mesbah M, Orestes-Cardoso MD, Robert B, Berdal A 2001 Postnatal Msx1 expression pattern in craniofacial, axial, and appendicular skeleton of transgenic mice from the first week until the second year. Dev Dyn 221: 113.
  • 31
    Matsuoka T, Ahlberg PE, Kessaris N, Iannarelli P, Dennehy U, Richardson WD, McMahon AP, Koentges G 2005 Neural crest origins of the neck and shoulder. Nature 436: 347355.
  • 32
    Churchill SE 1996 Particulate versus integrated evolution of the upper body in late pleistocene humans: A test of two models. Am J Phys Anthropol 100: 559583.
  • 33
    Wolf JB, Pomp D, Eisen EJ, Cheverud JM, Leamy LJ 2006 The contribution of epistatic pleiotropy to the genetic architecture of covariation among polygenic traits in mice. Evol Dev 8: 468476.
  • 34
    Lovejoy CO, Meindl RS, Ohman JC, Heiple KG, White TD 2002 The Maka femur and its bearing on the antiquity of human walking: Applying contemporary concepts of morphogenesis to the human fossil record. Am J Phys Anthropol 119: 97133.
  • 35
    Carter DR, Orr TE 1992 Skeletal development and bone functional adaptation. J Bone Miner Res 7 (Suppl 2): S389S395.
  • 36
    Nevill AM, Holder RL, Stewart AD 2003 Modeling elite male athletes' peripheral bone mass, assessed using regional dual x-ray absorptiometry. Bone 32: 6268.
  • 37
    Nevill AM, Holder RL, Maffulli N, Cheng JC, Leung SS, Lee WT, Lau JT 2002 Adjusting bone mass for differences in projected bone area and other confounding variables: An allometric perspective. J Bone Miner Res 17: 703708.
  • 38
    Kelly SA, Czech PP, Wight JT, Blank KM, Garland T Jr 2006 Experimental evolution and phenotypic plasticity of hindlimb bones in high-activity house mice. J Morphol 267: 360374.
  • 39
    Wilsman NJ, Farnum CE, Leiferman EM, Fry M, Barreto C 1996 Differential growth by growth plates as a function of multiple parameters of chondrocytic kinetics. J Orthop Res 14: 927936.
  • 40
    Bagge M 2000 A model of bone adaptation as an optimization process. J Biomech 33: 13491357.
  • 41
    Turner CH 2002 Biomechanics of bone: Determinants of skeletal fragility and bone quality. Osteoporos Int 13: 97104.
  • 42
    Nowlan NC, Prendergast PJ 2005 Evolution of mechanoregulation of bone growth will lead to non-optimal bone phenotypes. J Theor Biol 235: 408418.
  • 43
    Ferretti JL, Capozza RF, Cointry GR, Garcia SL, Plotkin H, Alvarez Filgueira ML, Zanchetta JR 1998 Gender-related differences in the relationship between densitometric values of whole-body bone mineral content and lean body mass in humans between 2 and 87 years of age. Bone 22: 683690.
  • 44
    Washburn RA, Smith KW, Jette AM, Janney CA 1993 The Physical Activity Scale for the Elderly (PASE): Development and evaluation. J Clin Epidemiol 46: 153162.
  • 45
    van der Meulen MC, Carter DR 1995 Developmental mechanics determine long bone allometry. J Theor Biol 172: 323327.
  • 46
    Haapasalo H, Kontulainen S, Sievanen H, Kannus P, Jarvinen M, Vuori I 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: 351357.
  • 47
    Bass SL, Saxon L, Daly RM, Turner CH, Robling AG, Seeman E, Stuckey S 2002 The effect of mechanical loading on the size and shape of bone in pre-, peri-, and postpubertal girls: A study in tennis players. J Bone Miner Res 17: 22742280.
  • 48
    Plato CC, Wood JL, Norris AH 1980 Bilateral asymmetry in bone measurements of the hand and lateral hand dominance. Am J Phys Anthropol 52: 2731.
  • 49
    Gilsanz V, Wren TA, Sanchez M, Dorey F, Judex S, Rubin C 2006 Low-level, high-frequency mechanical signals enhance musculoskeletal development of young women with low BMD. J Bone Miner Res 21: 14641474.
  • 50
    McGill SM, Norman RW 1986 Partitioning of the L4-L5 dynamic moment into disc, ligamentous, and muscular components during lifting. Spine 11: 666678.
  • 51
    Cholewicki J, McGill SM 1996 Mechanical stability of the in vivo lumbar spine: Implications for injury and chronic low back pain. Clin Biomech (Bristol, Avon) 11: 115.
  • 52
    Stokes IA, Gardner-Morse M 1999 Quantitative anatomy of the lumbar musculature. J Biomech 32: 311316.
  • 53
    Zumwalt A 2006 The effect of endurance exercise on the morphology of muscle attachment sites. J Exp Biol 209: 444454.
  • 54
    Rubin CT, Sommerfeldt DW, Judex S, Qin Y 2001 Inhibition of osteopenia by low magnitude, high-frequency mechanical stimuli. Drug Discov Today 6: 848858.
  • 55
    Fritton SP, McLeod KJ, Rubin CT 2000 Quantifying the strain history of bone: Spatial uniformity and self-similarity of low-magnitude strains. J Biomech 33: 317325.
  • 56
    Adams DJ, Spirt AA, Brown TD, Fritton SP, Rubin CT, Brand RA 1997 Testing the daily stress stimulus theory of bone adaptation with natural and experimentally controlled strain histories. J Biomech 30: 671678.
  • 57
    Desplanches D, Mayet MH, Ilyina-Kakueva EI, Sempore B, Flandrois R 1990 Skeletal muscle adaptation in rats flown on Cosmos 1667. J Appl Physiol 68: 4852.
  • 58
    Daly RM, Bass SL 2006 Lifetime sport and leisure activity participation is associated with greater bone size, quality and strength in older men. Osteoporos Int 17: 12581267.
  • 59
    Herring S 1994 Development of functional interactions between skeletal and muscular systems. In: HallB (ed.) Bone, vol 9. CRC Press, Boca Raton, FL, USA, 165191.
  • 60
    Hamrick MW 2003 Increased bone mineral density in the femora of GDF8 knockout mice. Anat Rec A Discov Mol Cell Evol Biol 272: 388391.
  • 61
    Benjamin M, Rufai A, Ralphs J 2000 The mechanism of formation of bony spurs (enthesophytes) in the Achilles tendon. Arthritis Rheum 43: 576583.
  • 62
    Hamrick MW, Pennington C, Newton D, Xie D, Isales C 2004 Leptin deficiency produces contrasting phenotypes in bones of the limb and spine. Bone 34: 376383.
  • 63
    Uusi-Rasi K, Sievanen H, Heinonen A, Beck TJ, Vuori I 2004 Determinants of changes in bone mass and femoral neck structure, and physical performance after menopause: A 9-year follow-up of initially peri-menopausal women. Osteoporos Int 15: 909917.
  • 64
    Petit MA, Beck TJ, Lin HM, Bentley C, Legro RS, Lloyd T 2004 Femoral bone structural geometry adapts to mechanical loading and is influenced by sex steroids: The Penn State Young Women's Health Study. Bone 35: 750759.
  • 65
    Bouxsein ML, Uchiyama T, Rosen CJ, Shultz KL, Donahue LR, Turner CH, Sen S, Churchill GA, Muller R, Beamer WG 2004 Mapping quantitative trait loci for vertebral trabecular bone volume fraction and microarchitecture in mice. J Bone Miner Res 19: 587599.
  • 66
    Wallace DC 2005 A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: A dawn for evolutionary medicine. Annu Rev Genet 39: 359407.
  • 67
    Forwood MR, Burr DB 1993 Physical activity and bone mass: Exercises in futility? Bone Miner 21: 89112.
  • 68
    Forwood MR 2001 Mechanical effects on the skeleton: Are there clinical implications? Osteoporos Int 12: 7783.
  • 69
    Schmid K, McSharry W, Pameijer C, Binette J 1980 Chemical and physiochemical studies on the mineral deposits of the human atherosclerotic aorta. Atherosclerosis 37: 199210.
  • 70
    Hirukawa K, Miyazawa K, Maeda H, Kameyama Y, Goto S, Togari A 2005 Effect of tensile force on the expression of IGF-I and IGF-I receptor in the organ-cultured rat cranial suture. Arch Oral Biol 50: 367372.
  • 71
    Kaptoge S, Dalzell N, Jakes RW, Wareham N, Day NE, Khaw KT, Beck TJ, Loveridge N, Reeve J 2003 Hip section modulus, a measure of bending resistance, is more strongly related to reported physical activity than BMD. Osteoporos Int 14: 941949.
  • 72
    Fricke O, Schoenau E 2007 The ‘Functional Muscle-Bone Unit’: Probing the relevance of mechanical signals for bone development in children and adolescents. Growth Horm IGF Res 17: 19.
  • 73
    Huang RP, Rubin CT, McLeod KJ 1999 Changes in postural muscle dynamics as a function of age. J Gerontol A Biol Sci Med Sci 54: B352B357.
  • 74
    Turner CH, Takano Y, Owan I 1995 Aging changes mechanical loading thresholds for bone formation in rats. J Bone Miner Res 10: 15441549.
  • 75
    Melton LJ III, Riggs BL, Achenbach SJ, Amin S, Camp JJ, Rouleau PA, Robb RA, Oberg AL, Khosla S 2006 Does reduced skeletal loading account for age-related bone loss? J Bone Miner Res 21: 18471855.
  • 76
    Karasik D, Cupples LA, Hannan MT, Kiel DP 2004 Genome screen for a combined bone phenotype using principal component analysis: The Framingham study. Bone 34: 547556.
  • 77
    Looker AC, Beck TJ 2002 Maternal history of osteoporosis and femur geometry. 75: 277285.
  • 78
    Karasik D, Ginsburg E, Livshits G, Pavlovsky O, Kobyliansky E 2000 Evidence on major gene control of cortical bone loss in human population. Genet Epidemiol 19: 410421.
  • 79
    Koller DL, Liu G, Econs MJ, Hui SL, Morin PA, Joslyn G, Rodriguez LA, Conneally PM, Christian JC, Johnston CC, Foroud T, Peacock M 2001 Genome screen for quantitative trait loci underlying normal variation in femoral structure. J Bone Miner Res 16: 985991.
  • 80
    Xiong DH, Shen H, Xiao P, Guo YF, Long JR, Zhao LJ, Liu YZ, Deng HY, Li JL, Recker RR, Deng, HW 2006 Genome-wide scan identified QTLs underlying femoral neck cross-sectional geometry that are novel studied risk factors of osteoporosis. J Bone Miner Res 21: 424437.
  • 81
    Peacock M, Koller DL, Lai D, Hui S, Foroud T, Econs MJ 2005 Sex-specific quantitative trait loci contribute to normal variation in bone structure at the proximal femur in men. Bone 37: 467473.
  • 82
    Shen H, Long JR, Xiong DH, Liu YJ, Liu YZ, Xiao P, Zhao LJ, Dvornyk V, Zhang YY, Rocha-Sanchez S, Liu PY, Li JL, Deng HW 2005 Mapping quantitative trait loci for cross-sectional geometry at the femoral neck. J Bone Miner Res 20: 19731982.
  • 83
    Demissie S, Dupuis J, Cupples LA, Beck TJ, Kiel DP, Karasik D 2007 Proximal hip geometry is linked to several chromosomal regions: Genome-wide linkage results from the Framingham Osteoporosis Study. Bone 40: 743750.
  • 84
    Babij P, Zhao W, Small C, Kharode Y, Yaworsky PJ, Bouxsein ML, Reddy PS, Bodine PV, Robinson JA, Bhat B, Marzolf J, Moran RA, Bex F 2003 High bone mass in mice expressing a mutant LRP5 gene. J Bone Miner Res 18: 960974.
  • 85
    Volkman SK, Galecki AT, Burke DT, Miller RA, Goldstein SA 2004 Quantitative trait loci that modulate femoral mechanical properties in a genetically heterogeneous mouse population. J Bone Miner Res 19: 14971505.
  • 86
    Turner CH, Roeder RK, Wieczorek A, Foroud T, Liu G, Peacock M 2001 Variability in skeletal mass, structure, and biomechanical properties among inbred strains of rats. J Bone Miner Res 16: 15321539.
  • 87
    Klein OF, Carlos AS, Vartanian KA, Chambers VK, Turner EJ, Phillips TJ, Belknap JK, Orwoll ES 2001 Confirmation and fine mapping of chromosomal regions influencing peak bone mass in mice. J Bone Miner Res 16: 19531961.
  • 88
    Hamrick MW, Pennington C, Byron CD 2003 Bone architecture and disc degeneration in the lumbar spine of mice lacking GDF-8 (myostatin). J Orthop Res 21: 10251032.
  • 89
    Masinde GL, Wergedal J, Davidson H, Mohan S, Li R, Li X, Baylink DJ 2003 Quantitative trait loci for periosteal circumference (PC): Identification of single loci and epistatic effects in F2 MRL/SJL mice. Bone 32: 554560.
  • 90
    Klein RF, Turner RJ, Skinner LD, Vartanian KA, Serang M, Carlos AS, Shea M, Belknap JK, Orwoll ES 2002 Mapping quantitative trait loci that influence femoral cross-sectional area in mice. J Bone Miner Res 17: 17521760.
  • 91
    Zhai G, Ding C, Stankovich J, Cicuttini F, Jones G 2005 The genetic contribution to longitudinal changes in knee structure and muscle strength: A sibpair study. Arthritis Rheum 52: 28302834.
  • 92
    Seeman E, Hopper JL, Young NR, Formica C, Goss P, Tsalamandris C 1996 Do genetic factors explain associations between muscle strength, lean mass, and bone density? A twin study. Am J Physiol 270: E320E327.
  • 93
    Hsu FC, Lenchik L, Nicklas BJ, Lohman K, Register TC, Mychaleckyj J, Langefeld CD, Freedman BI, Bowden DW, Carr JJ 2005 Heritability of body composition measured by DXA in the diabetes heart study. Obes Res 13: 312319.
  • 94
    Li X, Masinde G, Gu W, Wergedal J, Mohan S, Baylink DJ 2002 Genetic dissection of femur breaking strength in a large population (MRL/MpJ × SJL/J) of F2 Mice: Single QTL effects, epistasis, and pleiotropy. Genomics 79: 734740.
  • 95
    Sun X, Lei SF, Deng FY, Wu S, Papacian C, Hamilton J, Recker RR, Deng HW 2006 Genetic and environmental correlations between bone geometric parameters and body compositions. Calcif Tissue Int 79: 4349.
  • 96
    Deng FY, Xiao P, Lei SF, Zhang L, Yang F, Tang ZH, Liu PY, Liu YJ, Recker RR, Deng HW 2007 Bivariate whole genome linkage analysis for femoral neck geometric parameters and total body lean mass. J Bone Miner Res 22: 808816.
  • 97
    Li R, Tsaih SW, Shockley K, Stylianou IM, Wergedal J, Paigen B, Churchill GA 2006 Structural model analysis of multiple quantitative traits. PLoS Genet 2: e114.
  • 98
    Garland T Jr, Morgan MT, Swallow JG, Rhodes JS, Girard I, Belter JG, Carter PA 2002 Evolution of a small-muscle polymorphism in lines of house mice selected for high activity levels. Evolution Int J Org Evolution 56: 12671275.
  • 99
    Karamichou E, Richardson RI, Nute GR, Gibson KP, Bishop SC 2006 Genetic analyses and quantitative trait loci detection, using a partial genome scan, for intramuscular fatty acid composition in Scottish Blackface sheep. J Anim Sci 84: 32283238.
  • 100
    Schenkel FS, Miller SP, Ye X, Moore SS, Nkrumah JD, Li C, Yu J, Mandell IB, Wilton JW, Williams JL 2005 Association of single nucleotide polymorphisms in the leptin gene with carcass and meat quality traits of beef cattle. J Anim Sci 83: 20092020.
  • 101
    Eisman JA 1999 Genetics of osteoporosis. Endocr Rev 20: 788804.
  • 102
    Ralston SH 2002 Genetic control of susceptibility to osteoporosis. J Clin Endocrinol Metab 87: 24602466.
  • 103
    Ioannidis JP, Ng MY, Sham PC, Zintzaras E, Lewis CM, Deng HW, Econs MJ, Karasik D, Devoto M, Kammerer CM, Spector T, Andrew T, Cupples LA, Duncan EL, Foroud T, Kiel DP, Koller D, Langdahl B, Mitchell BD, Peacock M, Recker R, Shen H, Sol-Church K, Spotila LD, Uitterlinden AG, Wilson SG, Kung AW, Ralston SH 2007 Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass. J Bone Miner Res 22: 173183.
  • 104
    Seeman E 2003 Invited Review: Pathogenesis of osteoporosis. J Appl Physiol 95: 21422151.
  • 105
    Kanis JA 2002 Diagnosis of osteoporosis and assessment of fracture risk. Lancet 359: 19291936.
  • 106
    Deng HW, Mahaney MC, Williams JT, Li J, Conway T, Davies KM, Li JL, Deng H, Recker RR 2002 Relevance of the genes for bone mass variation to susceptibility to osteoporotic fractures and its implications to gene search for complex human diseases. Genet Epidemiol 22: 1225.
  • 107
    Andrew T, Antioniades L, Scurrah KJ, Macgregor AJ, Spector TD 2005 Risk of wrist fracture in women is heritable and is influenced by genes that are largely independent of those influencing BMD. J Bone Miner Res 20: 6774.
  • 108
    van Meurs JB, Schuit SC, Weel AE, van der Klift M, Bergink AP, Arp PP, Colin EM, Fang Y, Hofman A, van Duijn CM, van Leeuwen JP, Pols HA, Uitterlinden AG 2003 Association of 5′ estrogen receptor alpha gene polymorphisms with bone mineral density, vertebral bone area and fracture risk. Hum Mol Genet 12: 17451754.
  • 109
    Villadsen MM, Bunger MH, Carstens M, Stenkjaer L, Langdahl BL 2005 Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with osteoporotic vertebral fractures, but is a weak predictor of BMD. Osteoporos Int 16: 411416.
  • 110
    Schulze TG, McMahon FJ 2004 Defining the phenotype in human genetic studies: Forward genetics and reverse phenotyping. Hum Hered 58: 131138.
  • 111
    Harris TB, Launer LJ, Eiriksdottir G, Kjartansson O, Jonsson PV, Sigurdsson G, Thorgeirsson G, Aspelund T, Garcia ME, Cotch MF, Hoffman HJ, Gudnason V 2007 Age, Gene/Environment Susceptibility-Reykjavik Study: Multidisciplinary applied phenomics. Am J Epidemiol 165: 10761087.
  • 112
    Almasy L, Dyer TD, Blangero J 1997 Bivariate quantitative trait linkage analysis: Pleiotropy versus co- incident linkages. Genet Epidemiol 14: 953958.
  • 113
    Williams JT, Van Eerdewegh P, Almasy L, Blangero J 1999 Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. I. Likelihood formulation and simulation results. Am J Hum Genet 65: 11341147.
  • 114
    Havill LM, Rogers J, Cox LA, Mahaney MC 2006 QTL with pleiotropic effects on serum levels of bone-specific alkaline phosphatase and osteocalcin maps to the baboon ortholog of human chromosome 6p23-21.3. J Bone Miner Res 21: 18881896.
  • 115
    de Bakker PI, Yelensky R, Pe'er I, Gabriel SB, Daly MJ, Altshuler D 2005 Efficiency and power in genetic association studies. Nat Genet 37: 12171223.
  • 116
    Hirschhorn JN, Daly MJ 2005 Genome-wide association studies for common diseases and complex traits. Nat Rev Genet 6: 95108.
  • 117
    Kiel D, Demissie S, Cupples L, Dupuis J, Lunetta K, Murabito JM, Karasik D 2007 Genome-wide association with bone mass and geometry in the Framingham Heart Study. BMC Med Genet 8 (Suppl I): S14.
  • 118
    Giresi PG, Stevenson EJ, Theilhaber J, Koncarevic A, Parkington J, Fielding RA, Kandarian SC 2005 Identification of a molecular signature of sarcopenia. Physiol Genomics 21: 253263.
  • 119
    Gajendran VK, Lin JR, Fyhrie DP 2007 An application of bioinformatics and text mining to the discovery of novel genes related to bone biology. Bone 40: 13781388.
  • 120
    Qureshi A, McGuigan F, Seymour D, Hutchison J, Reid D, Ralston S 2001 Association between COLIA1 Sp1 alleles and femoral neck geometry. Calcif Tissue Int 69: 6772.
  • 121
    Rivadeneira F, Houwing-Duistermaat JJ, Beck TJ, Janssen JA, Hofman A, Pols HA, Van Duijn CM, Uitterlinden AG 2004 The influence of an insulin-like growth factor I gene promoter polymorphism on hip bone geometry and the risk of nonvertebral fracture in the elderly: The Rotterdam Study. J Bone Miner Res 19: 12801290.
  • 122
    van Meurs JB, Rivadeneira F, Jhamai M, Hugens W, Hofman A, van Leeuwen JP, Pols HA, Uitterlinden AG 2006 Common genetic variation of the low-density lipoprotein receptor-related protein 5 and 6 genes determines fracture risk in elderly white men. J Bone Miner Res 21: 141150.
  • 123
    Volkman SK, Galecki AT, Burke DT, Paczas MR, Moalli MR, Miller RA, Goldstein SA 2003 Quantitative trait loci for femoral size and shape in a genetically heterogeneous mouse population. J Bone Miner Res 18: 14971505.
  • 124
    Kiel DP, Ferrari SL, Cupples LA, Karasik D, Manen D, Imamovic A, Herbert AG, Dupuis J 2007 Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men. Bone 40: 587596.
  • 125
    Gennari L, Masi L, Merlotti D, Picariello L, Falchetti A, Tanini A, Mavilia C, Del Monte F, Gonnelli S, Lucani B, Gennari C, Brandi ML 2004 A polymorphic CYP19 TTTA repeat influences aromatase activity and estrogen levels in elderly men: Effects on bone metabolism. J Clin Endocrinol Metab 89: 28032810.
  • 126
    McClung JM, Davis JM, Wilson MA, Goldsmith EC, Carson JA 2006 Estrogen status and skeletal muscle recovery from disuse atrophy. J Appl Physiol 100: 20122023.
  • 127
    Frost HM 1999 On the estrogen-bone relationship and postmenopausal bone loss: A new model. J Bone Miner Res 14: 14731477.
  • 128
    Herbst KL, Bhasin S 2004 Testosterone action on skeletal muscle. Curr Opin Clin Nutr Metab Care 7: 271277.
  • 129
    Shearman AM, Cupples LA, Demissie S, Peter I, Schmid CH, Karas RH, Mendelsohn ME, Housman DE, Levy D 2003 Association between estrogen receptor alpha gene variation and cardiovascular disease. JAMA 290: 22632270.
  • 130
    Shearman AM, Karasik D, Gruenthal KM, Demissie S, Cupples LA, Housman DE, Kiel DP 2004 Estrogen receptor Beta polymorphisms are associated with bone mass in women and men: The Framingham study. J Bone Miner Res 19: 773781.
    Direct Link:
  • 131
    Grundberg E, Ribom EL, Brandstrom H, Ljunggren O, Mallmin H, Kindmark A 2005 A TA-repeat polymorphism in the gene for the estrogen receptor alpha does not correlate with muscle strength or body composition in young adult Swedish women. Maturitas 50: 153160.
  • 132
    Karasik D, Shearman A, Cupples L, Demissie S, Gruenthal K, Housman D, Kiel DP 2003 Association of Aromatase Gene Polymorphisms with Bone Mineral Density in Men and Women: The Framingham Offspring Study. J Bone Miner Res 18: S325.
  • 133
    Herrington DM, Howard TD, Brosnihan KB, McDonnell DP, Li X, Hawkins GA, Reboussin DM, Xu J, Zheng SL, Meyers DA, Bleecker ER 2002 Common estrogen receptor polymorphism augments effects of hormone replacement therapy on E-selectin but not C-reactive protein. Circulation 105: 18791882.
  • 134
    Carling T, Kim KC, Yang XH, Gu J, Zhang XK, Huang S 2004 A histone methyltransferase is required for maximal response to female sex hormones. Mol Cell Biol 24: 70327042.
  • 135
    Grundberg E, Carling T, Brandstrom H, Huang S, Ribom EL, Ljunggren O, Mallmin H, Kindmark A 2004 A deletion polymorphism in the RIZ gene, a female sex steroid hormone receptor coactivator, exhibits decreased response to estrogen in vitro and associates with low bone mineral density in young Swedish women. J Clin Endocrinol Metab 89: 61736178.
  • 136
    Lorentzon M, Eriksson AL, Mellstrom D, Ohlsson C 2004 The COMT val158met polymorphism is associated with peak BMD in men. J Bone Miner Res 19: 20052011.
    Direct Link:
  • 137
    Lorentzon M, Eriksson AL, Nilsson S, Mellstrom D, Ohlsson C 2007 Association between physical activity and BMD in young men is modulated by catechol-O-methyltransferase (COMT) genotype: The GOOD study. J Bone Miner Res 22: 11651172.
  • 138
    Goldspink G 2004 Age-related muscle loss and progressive dysfunction in mechanosensitive growth factor signaling. Ann N Y Acad Sci 1019: 294298.
  • 139
    Langlois JA, Rosen CJ, Visser M, Hannan MT, Harris T, Wilson PW, Kiel DP 1998 Association between insulin-like growth factor I and bone mineral density in older women and men: The Framingham Heart Study. J Clin Endocrinol Metab 83: 42574262.
  • 140
    Karasik D, Rosen CJ, Hannan MT, Broe KE, Dawson-Hughes B, Gagnon DR, Wilson PW, Visser M, Langlois JA, Mohan S, Kiel DP 2002 Insulin-like growth factor binding proteins 4 and 5 and bone mineral density in elderly men and women. Calcif Tissue Int 71: 323328.
  • 141
    Lupu F, Terwilliger JD, Lee K, Segre GV, Efstratiadis A 2001 Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev Biol 229: 141162.
  • 142
    Rosen CJ, Ackert-Bicknell CL, Adamo ML, Shultz KL, Rubin J, Donahue LR, Horton LG, Delahunty KM, Beamer WG, Sipos J, Clemmons D, Nelson T, Bouxsein ML, Horowitz M 2004 Congenic mice with low serum IGF-I have increased body fat, reduced bone mineral density, and an altered osteoblast differentiation program. Bone 35: 10461058.
  • 143
    Vaessen N, Heutink P, Janssen JA, Witteman JC, Testers L, Hofman A, Lamberts SW, Oostra BA, Pols HA, van Duijn CM 2001 A polymorphism in the gene for IGF-I: Functional properties and risk for type 2 diabetes and myocardial infarction. Diabetes 50: 637642.
  • 144
    Goldspink G, Yang SY 2004 The splicing of the IGF-I gene to yield different muscle growth factors. Adv Genet 52: 2349.
  • 145
    Tang LL, Wang YL, Sun CX 2004 The stress reaction and its molecular events: Splicing variants. Biochem Biophys Res Commun 320: 287291.
  • 146
    Schrager MA, Roth SM, Ferrell RE, Metter EJ, Russek-Cohen E, Lynch NA, Lindle RS, Hurley BF 2004 Insulin-like growth factor-2 genotype, fat-free mass, and muscle performance across the adult life span. J Appl Physiol 97: 21762183.
  • 147
    Van Laere AS, Nguyen M, Braunschweig M, Nezer C, Collette C, Moreau L, Archibald AL, Haley CS, Buys N, Tally M, Andersson G, Georges M, Andersson L 2003 A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig. Nature 425: 832836.
  • 148
    Roth SM, Martel GF, Ferrell RE, Metter EJ, Hurley BF, Rogers MA 2003 Myostatin gene expression is reduced in humans with heavy-resistance strength training: A brief communication. Exp Biol Med (Maywood) 228: 706709.
  • 149
    Steelman CA, Recknor JC, Nettleton D, Reecy JM 2006 Transcriptional profiling of myostatin-knockout mice implicates Wnt signaling in postnatal skeletal muscle growth and hypertrophy. FASEB J 20: 580582.
  • 150
    Bischoff HA, Borchers M, Gudat F, Duermueller U, Theiler R, Stahelin HB, Dick W 2001 In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem J 33: 1924.
  • 151
    Bischoff-Ferrari HA, Borchers M, Gudat F, Durmuller U, Stahelin HB, Dick W 2004 Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res 19: 265269.
  • 152
    Uitterlinden AG, Ralston SH, Brandi ML, Carey AH, Grinberg D, Langdahl BL, Lips P, Lorenc R, Obermayer-Pietsch B, Reeve J, Reid DM, Amedei A, Bassiti A, Bustamante M, Husted LB, Diez-Perez A, Dobnig H, Dunning AM, Enjuanes A, Fahrleitner-Pammer A, Fang Y, Karczmarewicz E, Kruk M, van Leeuwen JP, Mavilia C, van Meurs JB, Mangion J, McGuigan FE, Pols HA, Renner W, Rivadeneira F, van Schoor NM, Scollen S, Sherlock RE, Ioannidis JP 2006 The association between common vitamin D receptor gene variations and osteoporosis: A participant-level meta-analysis. Ann Intern Med 145: 255264.
  • 153
    Arai H, Miyamoto KI, Yoshida M, Yamamoto H, Taketani Y, Morita K, Kubota M, Yoshida S, Ikeda M, Watabe F, Kanemasa Y, Takeda E 2001 The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene. J Bone Miner Res 16: 12561264.
  • 154
    Fang Y, van Meurs JB, Rivadeneira F, van Schoor NM, van Leeuwen JP, Lips P, Pols HA, Uitterlinden AG 2007 Vitamin D receptor gene haplotype is associated with body height and bone size. J Clin Endocrinol Metab 92: 14911501.
  • 155
    Windelinckx A, De Mars G, Beunen G, Aerssens J, Delecluse C, Lefevre J, Thomis MA 2007 Polymorphisms in the vitamin D receptor gene are associated with muscle strength in men and women. Osteoporos Int 18: 12351242.
  • 156
    Grundberg E, Brandstrom H, Ribom EL, Ljunggren O, Mallmin H, Kindmark A 2004 Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Eur J Endocrinol 150: 323328.
  • 157
    Ferrari SL, Deutsch S, Choudhury U, Chevalley T, Bonjour JP, Dermitzakis ET, Rizzoli R, Atonarakis SE 2004 Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites. Am J Hum Genet 74: 866875.
  • 158
    Akhter MP, Wells DJ, Short SJ, Cullen DM, Johnson ML, Haynatzki GR, Babij P, Allen KM, Yaworsky PJ, Bex F, Recker RR 2004 Bone biomechanical properties in LRP5 mutant mice. Bone 35: 162169.
  • 159
    Sawakami K, Robling AG, Ai M, Pitner ND, Liu D, Warden SJ, Li J, Maye P, Rowe DW, Duncan RL, Warman ML, Turner CH 2006 The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment. J Biol Chem 281: 2369823711.
  • 160
    Armstrong DD, Esser KA 2005 Wnt/beta-catenin signaling activates growth-control genes during overload-induced skeletal muscle hypertrophy. Am J Physiol Cell Physiol 289: C853C859.
  • 161
    Nordstrom A, Gerdhem P, Brandstrom H, Stiger F, Lerner UH, Lorentzon M, Obrant K, Nordstrom P, Akesson K 2004 Interleukin-6 promoter polymorphism is associated with bone quality assessed by calcaneus ultrasound and previous fractures in a cohort of 75-year-old women. Osteoporos Int 15: 820826.
  • 162
    Ferrari SL, Karasik D, Liu J, Karamohamed S, Herbert AG, Cupples LA, Kiel DP 2004 Interactions of interleukin-6 promoter polymorphisms with dietary and lifestyle factors and their association with bone mass in men and women from the framingham osteoporosis study. J Bone Miner Res 19: 552559.
  • 163
    Roth SM, Schrager MA, Lee MR, Metter EJ, Hurley BF, Ferrell RE 2003 Interleukin-6 (IL6) genotype is associated with fat-free mass in men but not women. J Gerontol A Biol Sci Med Sci 58: B1085B1088.
  • 164
    Barbieri M, Ferrucci L, Ragno E, Corsi A, Bandinelli S, Bonafe M, Olivieri F, Giovagnetti S, Franceschi C, Guralnik JM, Paolisso G 2003 Chronic inflammation and the effect of IGF-I on muscle strength and power in older persons. Am J Physiol Endocrinol Metab 284: E481E487.
  • 165
    Moron FJ, Mendoza N, Vazquez F, Molero E, Quereda F, Salinas A, Fontes J, Martinez-Astorquiza T, Sanchez-Borrego R, Ruiz A 2006 Multilocus analysis of estrogen-related genes in Spanish postmenopausal women suggests an interactive role of ESR1, ESR2 and NRIP1 genes in the pathogenesis of osteoporosis. Bone 39: 213221.
  • 166
    Szulc P, Delmas PD 2007 Bone width is correlated positively with the upper to the lower segment ratio in elderly men–the MINOS study. Bone 40: 194199.
  • 167
    Kamel HK, Maas D, Duthie EH Jr 2002 Role of hormones in the pathogenesis and management of sarcopenia. Drugs Aging 19: 865877.
  • 168
    Vanderschueren D, Venken K, Ophoff J, Bouillon R, Boonen S 2006 Clinical Review: Sex steroids and the periosteum–reconsidering the roles of androgens and estrogens in periosteal expansion. J Clin Endocrinol Metab 91: 378382.
  • 169
    Rivadeneira F, van Meurs JB, Kant J, Zillikens MC, Stolk L, Beck TJ, Arp P, Schuit SC, Hofman A, Houwing-Duistermaat JJ, van Duijn CM, van Leeuwen JP, Pols HA, Uitterlinden AG 2006 Estrogen receptor beta (ESR2) polymorphisms in interaction with estrogen receptor alpha (ESR1) and insulin-like growth factor I (IGF1) variants influence the risk of fracture in postmenopausal women. J Bone Miner Res 21: 14431456.
  • 170
    Kenny AM, Dawson L, Kleppinger A, Iannuzzi-Sucich M, Judge JO 2003 Prevalence of sarcopenia and predictors of skeletal muscle mass in nonobese women who are long-term users of estrogen-replacement therapy. J Gerontol A Biol Sci Med Sci 58: M436M440.
  • 171
    Taaffe DR, Newman AB, Haggerty CL, Colbert LH, de Rekeneire N, Visser M, Goodpaster BH, Nevitt MC, Tylavsky FA, Harris TB 2005 Estrogen replacement, muscle composition, and physical function: The Health ABC Study. Med Sci Sports Exerc 37: 17411747.
  • 172
    Turner CH 2007 Molecular mechanisms of exercise in bone and muscle: The search for an exercise pill. In: CavanaughP (ed.) Bone Loss During Spaceflight: Etiology, Countermeasures, and Implications for Bone Health on Earth. Cleveland Clinic Press, Cleveland, OH, USA, 17.
  • 173
    Bhasin S, Buckwalter JG 2001 Testosterone supplementation in older men: A rational idea whose time has not yet come. J Androl 22: 718731.
  • 174
    Walsh S, Zmuda JM, Cauley JA, Shea PR, Metter EJ, Hurley BF, Ferrell RE, Roth SM 2005 Androgen receptor CAG repeat polymorphism is associated with fat-free mass in men. J Appl Physiol 98: 132137.
  • 175
    Ioannidis JP, Stavrou I, Trikalinos TA, Zois C, Brandi ML, Gennari L, Albagha O, Ralston SH, Tsatsoulis A 2002 Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density and fracture risk in women: A meta-analysis. J Bone Miner Res 17: 20482060.
  • 176
    Lee K, Jessop H, Suswillo R, Zaman G, Lanyon L 2003 Endocrinology: Bone adaptation requires oestrogen receptor-alpha. Nature 424: 389.
  • 177
    Kostek MC, Delmonico MJ, Reichel JB, Roth SM, Douglass L, Ferrell RE, Hurley BF 2005 Muscle strength response to strength training is influenced by insulin-like growth factor 1 genotype in older adults. J Appl Physiol 98: 21472154.
  • 178
    Roth SM, Zmuda JM, Cauley JA, Shea PR, Ferrell RE 2004 Vitamin D receptor genotype is associated with fat-free mass and sarcopenia in elderly men. J Gerontol A Biol Sci Med Sci 59: 1015.
  • 179
    van Rossum EF, Koper JW, van den Beld AW, Uitterlinden AG, Arp P, Ester W, Janssen JA, Brinkmann AO, de Jong FH, Grobbee DE, Pols HA, Lamberts SW 2003 Identification of the BclI polymorphism in the glucocorticoid receptor gene: Association with sensitivity to glucocorticoids in vivo and body mass index. Clin Endocrinol (Oxf) 59: 585592.
  • 180
    van Rossum EF, Voorhoeve PG, te Velde SJ, Koper JW, de Delemarre-van Waal HA, Kemper HC, Lamberts SW 2004 The ER22/23EK polymorphism in the glucocorticoid receptor gene is associated with a beneficial body composition and muscle strength in young adults. J Clin Endocrinol Metab 89: 40044009.
  • 181
    van Schoor NM, Dennison E, Lips P, Uitterlinden AG, Cooper C 2007 Serum fasting cortisol in relation to bone, and the role of genetic variations in the glucocorticoid receptor. Clin Endocrinol (Oxf) 67: 871878.
  • 182
    Dennison EM, Syddall HE, Fall CH, Javaid MK, Arden NK, Phillips DI, Cooper C 2004 Plasma leptin concentration and change in bone density among elderly men and women: The Hertfordshire Cohort Study. Calcif Tissue Int 74: 401406.
  • 183
    Livshits G, Pantsulaia I, Trofimov S, Kobyliansky E 2003 Genetic variation of circulating leptin is involved in genetic variation of hand bone size and geometry. Osteoporos Int 14: 476483.
  • 184
    Li G, Bunn JR, Mushipe MT, He Q, Chen X 2005 Effects of pleiotrophin (PTN) over-expression on mouse long bone development, fracture healing and bone repair. Calcif Tissue Int 76: 299306.
  • 185
    Xing W, Baylink D, Kesavan C, Hu Y, Kapoor S, Chadwick RB, Mohan S 2005 Global gene expression analysis in the bones reveals involvement of several novel genes and pathways in mediating an anabolic response of mechanical loading in mice. J Cell Biochem 96: 10491060.
  • 186
    Oh KW, Lee WY, Rhee EJ, Baek KH, Yoon KH, Kang MI, Yun EJ, Park CY, Ihm SH, Choi MG, Yoo HJ, Park SW 2005 The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men. Clin Endocrinol (Oxf) 63: 131138.
  • 187
    Pistilli EE, Gordish-Dressman H, Seip RL, Devaney JM, Thompson PD, Price TB, Angelopoulos TJ, Clarkson PM, Moyna NM, Pescatello LS, Visich PS, Zoeller RF, Hoffman EP, Gordon PM 2007 Resistin polymorphisms are associated with muscle, bone, and fat phenotypes in white men and women. Obesity (Silver Spring) 15: 392402.
  • 188
    Agoston H, Khan S, James CG, Gillespie JR, Serra R, Stanton LA, Beier F 2007 C-type natriuretic peptide regulates endochondral bone growth through p38 MAP kinase-dependent and -independent pathways. BMC Dev Biol 7: 18.
  • 189
    Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N 1999 VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5: 623628.
  • 190
    Springer ML, Chen AS, Kraft PE, Bednarski M, Blau HM 1998 VEGF gene delivery to muscle: Potential role for vasculogenesis in adults. Mol Cell 2: 549558.