• 1
    Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, Garry PJ, Lindeman RD. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol. 1998; 147(8): 75563.
  • 2
    Looker AC, Orwoll ES, Johnston CC, Lindsay RL, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP. Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res. 1997; 12(11): 17618.
  • 3
    Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007; 22(3): 46575.
  • 4
    Janssen I, Shepard DS, Katzmarzyk PT, Roubenoff R. The healthcare costs of sarcopenia in the United States. J Am Geriatr Soc. 2004; 52(1): 805.
  • 5
    Janssen I, Heymsfield SB, Wang ZM, Ross R. Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr. J Appl Physiol. 2000; 89(1): 818.
  • 6
    Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med. 1988; 319(26): 17017.
  • 7
    Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB. Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med. 1995; 332(9): 55661.
  • 8
    Studenski S, Perera S, Wallace D, Chandler JM, Duncan PW, Rooney E, Fox M, Guralnik JM. Physical performance measures in the clinical setting. J Am Geriatr Soc. 2003; 51(3): 31422.
  • 9
    Newman AB, Kupelian V, Visser M, Simonsick EM, Goodpaster BH, Kritchevsky SB, Tylavsky FA, Rubin SM, Harris TB. Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. J Gerontol A Biol Sci Med Sci. 2006; 61(1): 727.
  • 10
    Newman AB, Simonsick EM, Naydeck BL, Boudreau RM, Kritchevsky SB, Nevitt MC, Pahor M, Satterfield S, Brach JS, Studenski SA, Harris TB. Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability. JAMA. 2006; 295(17): 201826.
  • 11
    Studenski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M, Brach J, Chandler J, Cawthon P, Connor EB, Nevitt M, Visser M, Kritchevsky S, Badinelli S, Harris T, Newman AB, Cauley J, Ferrucci L, Guralnik J. Gait speed and survival in older adults. JAMA. 2011; 305(1): 508.
  • 12
    Hamrick MW. A role for myokines in muscle-bone interactions. Exerc Sport Sci Rev. 2011; 39(1): 437.
  • 13
    Romero-Suarez S, Mo C, Lara N, Jaehn K, Johnson M, Bonewald L, Brotto M. The β-catenin activating factor, Wnt3a, stimulates skeletal myogenesis. J Bone Miner Res. 2011; 26(Suppl 1):Available at
  • 14
    Proctor DN, Melton LJ, Khosla S, Crowson CS, O'Connor MK, Riggs BL. Relative influence of physical activity, muscle mass and strength on bone density. Osteoporos Int. 2000; 11(11): 94452.
  • 15
    Khosla S, Atkinson EJ, Riggs BL, Melton LJ 3rd. Relationship between body composition and bone mass in women. J Bone Miner Res. 1996; 11(6): 85763.
  • 16
    Riggs BL, Melton LJ, Robb RA, Camp JJ, Atkinson EJ, McDaniel L, Amin S, Rouleau PA, Khosla S. A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men. J Bone Miner Res. 2008; 23(2): 20514.
  • 17
    Lamberts SW, van den Beld AW, van der Lely AJ. The endocrinology of aging. Science. 1997; 278(5337): 41924.
  • 18
    Khosla S, Melton LJ 3rd, Riggs BL. Clinical review 144: estrogen and the male skeleton. J Clin Endocrinol Metab. 2002; 87(4): 144350.
  • 19
    Khosla S, Melton LJ 3rd, Riggs BL. The unitary model for estrogen deficiency and the pathogenesis of osteoporosis: is a revision needed?. J Bone Miner Res. 2011; 26(3): 44151.
  • 20
    Walsh M, Hunter G, Livingstone M. Sarcopenia in premenopausal and postmenopausal women with osteopenia, osteoporosis and normal bone mineral density. Osteoporos Int. 2006; 17(1): 617.
  • 21
    Joseph C, Kenny AM, Taxel P, Lorenzo JA, Duque G, Kuchel GA. Role of endocrine-immune dysregulation in osteoporosis, sarcopenia, frailty and fracture risk. Mol Aspects Med. 2005; 26(3): 181201.
  • 22
    Greenlund LJS, Nair KS. Sarcopenia—consequences, mechanisms, and potential therapies. Mech Ageing Dev. 2003; 124(3): 28799.
  • 23
    Patrick G, Elisabeth SR, Pierre DD. Low serum IGF-1 and occurrence of osteoporotic fractures in postmenopausal women. Lancet. 2000; 355(9207): 8989.
  • 24
    Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, Glass DJ. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol. 2001; 3(11): 100913.
  • 25
    Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, Ooi GT, Setser J, Frystyk J, Boisclair YR, LeRoith D. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest. 2002; 110(6): 77181.
  • 26
    Amin S, Riggs BL, Atkinson EJ, Oberg AL, Melton LJ 3rd, Khosla S. A potentially deleterious role of IGFBP-2 on bone density in aging men and women. J Bone Miner Res. 2004; 19(7): 107583.
  • 27
    Amin S, Riggs BL, Melton LJ 3rd, Achenbach SJ, Atkinson EJ, Khosla S. High serum IGFBP-2 is predictive of increased bone turnover in aging men and women. J Bone Miner Res. 2007; 22(6): 799807.
  • 28
    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 volumetric density, size, geometry, and structure at different skeletal sites. J Bone Miner Res. 2004; 19: 194554.
  • 29
    Melton LJ III. History of the Rochester Epidemiology Project. Mayo Clin Proc. 1996; 71(3): 26674.
  • 30
    Melton LJ 3rd, Khosla S, Riggs BL. Epidemiology of sarcopenia. Mayo Clin Proc. 2000; 75(Suppl): S102; discussion S12-3.
  • 31
    Camp JJ, Karwoski RA, Stacy MC, Atkinson EJ, Khosla S, Melton LJ, Riggs BL, Robb RA. A system for the analysis of whole-bone strength from helical CT images. Proc SPIE. 2004; 5369: 7488.
  • 32
    Cann CE. Quantitative CT for determination of bone mineral density: a review. Radiology. 1988; 166(2): 50922.
  • 33
    Kalender WA, Felsenberg D, Genant HK, Fischer M, Dequeker J, Reeve J. The European spine phantom: a tool for standardization and quality control in spinal bone mineral measurements by DXA and QCT. Eur J Radiol. 1995; 20: 8392.
  • 34
    Keaveny TM, Kopperdahl DL, Melton LJ 3rd, Hoffmann PF, Amin S, Riggs BL, Khosla S. Age-dependence of femoral strength in white women and men. J Bone Miner Res. 2010; 25(5): 9941001.
  • 35
    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. 2006; 21(1): 12431.
  • 36
    Muller R, Hahn M, Vogel M, Delling G, Ruegsegger P. Morphometric analysis of noninvasively assessed bone biopsies: comparison of high-resolution computed tomography and histologic sections. Bone. 1996; 18: 21520.
  • 37
    Laib A, Hilderbrand T, Hauselmann HJ, Ruegsegger P. Ridge number density: a parameter for in vivo bone structure analysis. Bone. 1997; 21(6): 5416.
  • 38
    Laib A, Hauselmann HJ, Ruegsegger P. In vivo high resolution 3D-QCT of the human forearm. Technol Health Care. 1998; 6(5–6): 32937.
  • 39
    Laib A, Ruegsegger P. Calibration of trabecular bone structure measurements of in vivo three-dimensional peripheral quantitative computed tomography with 28-micron-resolution microcomputed tomography. Bone. 1999; 24(1): 359.
  • 40
    Parfitt AM, Mathews CHE, Villaneuva AR, Kleerekoper M, Frame B, Rao DS. Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. J Clin Invest. 1983; 72: 1396409.
  • 41
    Khosla S, Amin S, Singh RJ, Atkinson EJ, Melton LJ, Riggs BL. Comparison of sex steroid measurements in men by immunoassay versus mass spectroscopy and relationships with cortical and trabecular volumetric bone mineral density. Osteoporos Int. 2008; 19: 146571.
  • 42
    Khosla S, Melton LJ III, Atkinson EJ, O'Fallon WM, Klee GG, Riggs BL. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab. 1998; 83(7): 226674.
  • 43
    Melton LJ 3rd, Riggs BL, Achenbach SJ, Amin S, Camp JJ, Rouleau PA, Robb RA, Oberg AL, Khosla S. Does reduced skeletal loading account for age-related bone loss?. J Bone Miner Res. 2006; 21(12): 184755.
  • 44
    Ainsworth BE, Haskell WL, Leon AS, Jacobs DR Jr, Montoye HJ, Sallis JF, Paffenbarger RS Jr. Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc. 1993; 25(1): 7180.
  • 45
    Blain H, Jaussent A, Thomas E, Micallef JP, Dupuy AM, Bernard PL, Mariano-Goulart D, Cristol JP, Sultan C, Rossi M, Picot MC. Appendicular skeletal muscle mass is the strongest independent factor associated with femoral neck bone mineral density in adult and older men. Exp Gerontol. 2010; 45(9): 67984.
  • 46
    Melton LJ 3rd, Riggs BL, van Lenthe GH, Achenbach SJ, Muller R, Bouxsein ML, Amin S, Atkinson EJ, Khosla S. Contribution of in vivo structural measurements and load/strength ratios to the determination of forearm fracture risk in postmenopausal women. J Bone Miner Res. 2007; 22(9): 14428.
  • 47
    Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD. Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res. 2007; 22(3): 42533.
  • 48
    Riggs BL, Khosla S, Melton LJ 3rd. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002; 23(3): 279302.
  • 49
    Brodsky IG, Balagopal P, Nair KS. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men—a clinical research center study. J Clin Endocrinol Metab. 1996; 81(10): 346975.
  • 50
    Hamrick MW, McNeil PL, Patterson SL. Role of muscle-derived growth factors in bone formation. J Musculoskelet Neuronal Interact. 2010; 10(1): 6470.
  • 51
    Andreassen M, Raymond I, Kistorp C, Hildebrandt P, Faber J, Kristensen LØ. IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population. Eur J Endocrinol. 2009; 160(1): 2531.
  • 52
    Hu D, Pawlikowska L, Kanaya A, Hsueh WC, Colbert L, Newman AB, Satterfield S, Rosen C, Cummings SR, Harris TB, Ziv E. Serum insulin-like growth factor-1 binding proteins 1 and 2 and mortality in older adults: the Health, Aging, and Body Composition Study. J Am Geriatr Soc. 2009; 57(7): 12138.
  • 53
    Sandhu MS, Heald AH, Gibson JM, Cruickshank JK, Dunger DB, Wareham NJ. Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study. Lancet. 2002; 359(9319): 17405.
  • 54
    Rodier F, Coppe JP, Patil CK, Hoeijmakers WA, Munoz DP, Raza SR, Freund A, Campeau E, Davalos AR, Campisi J. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol. 2009; 11(8): 9739.
  • 55
    Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, Kirkland JL, van Deursen JM. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011; 479(7372): 2326.
  • 56
    Clemmons DR, Snyder DK, Busby WH. Variables controlling the secretion of insulin-like growth factor binding protein-2 in normal human subjects. J Clin Endocrinol Metab. 1991; 73(4): 72733.
  • 57
    Münzer T, Rosen CJ, Harman SM, Pabst KM, Clair CS, Sorkin JD, Blackman MR. Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men. Am J Physiol Endocrinol Metab. 2006; 290(5): E100613.
  • 58
    Meier C, Nguyen TV, Center JR, Seibel MJ, Eisman JA. High IGFBP-2 levels are associated with an increased risk of osteoporotic fractures in elderly men. J Bone Miner Res. 2005; 20(S1; S36). Available at:
  • 59
    van den Beld AW, Blum WF, Pols HA, Grobbee DE, Lamberts SW. Serum insulin-like growth factor binding protein-2 levels as an indicator of functional ability in elderly men. Eur J Endocrinol. 2003; 148(6): 62734.