title: Bone and skeletal muscle: neighbors with close ties.
abstract: The musculoskeletal system evolved in mammals to perform diverse functions that include locomotion, facilitating breathing, protecting internal organs, and coordinating global energy expenditure. Bone and skeletal muscles involved with locomotion are both derived from somitic mesoderm and accumulate peak tissue mass synchronously, according to genetic information and environmental stimuli. Aging results in the progressive and parallel loss of bone (osteopenia) and skeletal muscle (sarcopenia) with profound consequences for quality of life. Age-associated sarcopenia results in reduced endurance, poor balance, and reduced mobility that predispose elderly individuals to falls, which more frequently result in fracture because of concomitant osteoporosis. Thus, a better understanding of the mechanisms underlying the parallel development and involution of these tissues is critical to developing new and more effective means to combat osteoporosis and sarcopenia in our increasingly aged population. This perspective highlights recent advances in our understanding of mechanisms coupling bone and skeletal muscle mass, and identify critical areas where further work is needed.
authors: Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287‐0882, USA. ddigiro2@jhmi.edu
authors: Douglas J
authors: DJ
authors: DiGirolamo
authors: Douglas P
authors: DP
authors: Kiel
authors: Karyn A
authors: KA
authors: Esser
mesh_terms: D000058:Accidental Falls; D000375:Aging; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000503:physiopathology*; D001842:Bone and Bones / Q000503:physiopathology*; D006801:Humans; D018482:Muscle, Skeletal / Q000503:physiopathology*; D004856:Postural Balance; D055948:Sarcopenia / Q000503:physiopathology*
references: J Bone Miner Res. 1999 Dec;14(12):2150-8
references: 10620075
references: Cell Tissue Res. 2012 Mar;347(3):521-44
references: 22327483
references: Anat Rec A Discov Mol Cell Evol Biol. 2003 Dec;275(2):1081-101
references: 14613308
references: J Clin Endocrinol Metab. 1984 Oct;59(4):701-4
references: 6384252
references: Gerontology. 2010;56(2):157-66
references: 19851058
references: Obesity (Silver Spring). 2009 May;17(5):1062-9
references: 19165157
references: Nature. 1997 May 1;387(6628):83-90
references: 9139826
references: Nat Rev Rheumatol. 2012 Nov;8(11):674-83
references: 23045255
references: Med Sci Sports Exerc. 2005 Oct;37(10):1741-7
references: 16260975
references: J Bone Miner Res. 2003 Mar;18(3):561-9
references: 12619942
references: Physiology (Bethesda). 2007 Aug;22:269-78
references: 17699880
references: Proc Natl Acad Sci U S A. 2008 May 13;105(19):7082-7
references: 18460605
references: J Bone Miner Res. 2009 Sep;24(9):1608-17
references: 19419307
references: Nature. 2012 Jan 11;481(7382):463-8
references: 22237023
references: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15842-6
references: 14671324
references: Am J Physiol Endocrinol Metab. 2006 Sep;291(3):E506-16
references: 16621900
references: J Bone Miner Res. 2009 Apr;24(4):710-8
references: 19063671
references: Bone. 2004 May;34(5):771-5
references: 15121007
references: Acta Neurol Scand. 2001 May;103(5):320-2
references: 11328209
references: Clin Biochem. 2012 Aug;45(12):863-73
references: 22465238
references: Cell Stem Cell. 2009 Nov 6;5(5):527-39
references: 19896443
references: J Gerontol A Biol Sci Med Sci. 2006 Oct;61(10):1059-64
references: 17077199
references: Bone. 2000 Aug;27(2):319-26
references: 10913929
references: Pediatr Int. 2001 Apr;43(2):157-60
references: 11285068
references: Eur Cell Mater. 2012 Sep 12;24:197-209; discussion 209-10
references: 22972510
references: Annu Rev Cell Dev Biol. 2000;16:191-220
references: 11031235
references: J Clin Endocrinol Metab. 1987 Jan;64(1):51-8
references: 3782436
references: Pediatr Endocrinol Rev. 2005 Sep;3(1):5-10
references: 16369208
references: J Physiol. 1983 May;338:37-49
references: 6875963
references: Dis Model Mech. 2013 Jan;6(1):25-39
references: 23268536
references: Cold Spring Harb Perspect Biol. 2012 Dec 01;4(12):
references: 23209148
references: J Appl Physiol (1985). 2000 Aug;89(2):823-39
references: 10926670
references: J Clin Endocrinol Metab. 2003 Jan;88(1):358-62
references: 12519877
references: Cell. 2007 Jan 26;128(2):325-39
references: 17254970
references: J Bone Miner Res. 2001 Feb;16(2):195-201
references: 11204418
references: J Bone Joint Surg Am. 1977 Mar;59(2):204-8
references: 845205
references: Biomed Sci Instrum. 2005;41:128-34
references: 15850093
references: Curr Osteoporos Rep. 2011 Jun;9(2):60-6
references: 21404001
references: Endocrinology. 2010 Sep;151(9):4289-300
references: 20573726
references: Nature. 2002 Nov 28;420(6914):418-21
references: 12459784
references: Scand J Rehabil Med. 1986;18(2):51-8
references: 3775302
references: Nature. 2005 Mar 24;434(7032):514-20
references: 15724149
references: J Appl Physiol (1985). 1995 May;78(5):1733-9
references: 7649906
references: J Gravit Physiol. 2002 Jul;9(1):P7-10
references: 14703663
references: Nature. 2003 May 15;423(6937):332-6
references: 12748651
references: Prog Clin Biol Res. 1982;101:553-7
references: 7156158
references: J Gerontol A Biol Sci Med Sci. 2004 Nov;59(11):1099-110
references: 15602055
references: Neuromuscul Disord. 2008 Jul;18(7):521-9
references: 18502640
references: J Pediatr Orthop. 2000 Jan-Feb;20(1):71-4
references: 10641693
references: Hum Mol Genet. 2011 Dec 15;20(24):4891-902
references: 21920942
references: Nat Rev Endocrinol. 2012 Apr 03;8(8):457-65
references: 22473333
references: J Appl Physiol (1985). 1999 Jan;86(1):350-8
references: 9887150
references: Development. 2010 Sep 1;137(17):2807-17
references: 20699295
references: Trends Genet. 2008 Dec;24(12):604-12
references: 18992957
references: Am J Phys Anthropol. 2004;Suppl 39:63-99
references: 15605390
references: Nat Med. 2011 Oct 30;17(11):1481-9
references: 22037645
references: Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20405-10
references: 19918075
references: Curr Opin Genet Dev. 2009 Oct;19(5):444-53
references: 19762225
references: Osteoporos Int. 2000;11(1):31-5
references: 10663356
references: Nature. 2008 Feb 28;451(7182):1069-75
references: 18305538
references: J Am Geriatr Soc. 2010 Nov;58(11):2085-91
references: 21054288
references: Science. 2007 Aug 10;317(5839):807-10
references: 17690295
references: J Bone Miner Res. 2010 Dec;25(12):2633-46
references: 20533325
references: Anat Rec A Discov Mol Cell Evol Biol. 2003 May;272(1):388-91
references: 12704695
references: J Nutr Health Aging. 2008 Mar;12(3):202-6
references: 18309443
references: Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18117-22
references: 16330774
references: J Clin Endocrinol Metab. 2001 Oct;86(10):4576-84
references: 11600506
references: J Intern Med. 2012 Oct;272(4):317-29
references: 22702419
references: J Exp Biol. 2001 Sep;204(Pt 18):3201-8
references: 11581335
references: Osteoporos Int. 2008 Nov;19(11):1517-25
references: 18392663
references: Exp Cell Res. 2010 Nov 1;316(18):3059-66
references: 20406633
references: J Orthop Res. 2003 Nov;21(6):1025-32
references: 14554215
references: Am J Clin Nutr. 2009 Jun;89(6):1895-900
references: 19369381
references: J Bone Joint Surg Am. 1988 Aug;70(7):1052-60
references: 3403574
references: J Bone Miner Res. 2011 Feb;26(2):229-38
references: 21254230
references: J Bone Miner Res. 2009 Feb;24(2):338-45
references: 18847322
references: Virchows Arch B Cell Pathol. 1976 Aug 11;21(2):113-8
references: 822576
references: Tissue Eng Part C Methods. 2013 Apr;19(4):316-25
references: 22992043
references: Cell Mol Life Sci. 2009 Apr;66(7):1135-9
references: 19234809
references: Scand J Med Sci Sports. 2003 Feb;13(1):40-7
references: 12535316
references: Development. 2011 Aug;138(15):3247-59
references: 21750035
references: Biochem Biophys Res Commun. 2007 Dec 14;364(2):358-65
references: 17950246
references: Am J Clin Nutr. 2004 May;79(5):874-80
references: 15113728
references: J Clin Invest. 1985 Jul;76(1):149-55
references: 3894418
references: J Endocrinol Invest. 2011 Jul;34(7 Suppl):3-7
references: 21985972
references: Bone. 2000 Sep;27(3):351-7
references: 10962345
references: J Clin Invest. 2010 Nov;120(11):4007-20
references: 20921627
references: Cold Spring Harb Symp Quant Biol. 2011;76:101-11
references: 21960527
references: Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16876-81
references: 17075068
references: Nat Rev Mol Cell Biol. 2011 Jun;12(6):349-61
references: 21602905
references: Recent Pat Biotechnol. 2012 Dec;6(3):223-9
references: 23092433
references: Essays Biochem. 2006;42:75-88
references: 17144881
references: Biochem Biophys Res Commun. 2003 Jan 24;300(4):965-71
references: 12559968
references: Dev Biol. 2011 Aug 15;356(2):486-95
references: 21683695
references: Am J Physiol. 1989 Jun;256(6 Pt 1):C1262-6
references: 2735398
references: Endocr Rev. 2002 Jun;23(3):279-302
references: 12050121
references: Neuroscience. 1992;46(1):197-207
references: 1594103
references: J Gerontol A Biol Sci Med Sci. 2003 May;58(5):M436-40
references: 12730253
references: J Bone Miner Res. 1996 Mar;11(3):337-49
references: 8852944
references: Science. 2003 Nov 28;302(5650):1575-7
references: 14645852
references: FASEB J. 2008 Aug;22(8):2676-89
references: 18390925
references: Aging Cell. 2011 Apr;10(2):191-7
references: 21210937
references: Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5124-9
references: 20194748
references: Bone. 2010 Apr;46(4):1082-8
references: 20080223
references: Spinal Cord. 2000 Jan;38(1):26-32
references: 10762194
references: J Cell Biol. 1970 Feb;44(2):459-62
references: 5411085
references: J Gerontol A Biol Sci Med Sci. 2008 Oct;63(10):1076-81
references: 18948558
references: Bone. 2008 May;42(5):837-40
references: 18295563
references: Nature. 2005 Feb 17;433(7027):760-4
references: 15716955
references: Development. 2011 Sep;138(17):3657-66
references: 21828094
references: Bone. 2007 Aug;41(2):223-30
references: 17543594
references: Exp Cell Res. 2010 Nov 1;316(18):3081-6
references: 20828559
references: Neurobiol Aging. 2006 Aug;27(8):1145-54
references: 16085338
references: Calcif Tissue Int. 1988 Dec;43(6):335-9
references: 3146421
references: Bone Res. 2013 Mar 29;1(1):85-97
references: 26273494
references: Osteoporos Int. 1994;4 Suppl 1:7-13
references: 8081064
references: Trends Cell Biol. 2012 Nov;22(11):602-9
references: 22944199
references: J Biol Chem. 2007 Oct 26;282(43):31666-74
references: 17698843
references: J Clin Endocrinol Metab. 2012 Aug;97(8):2693-8
references: 22593587
references: FASEB J. 2011 May;25(5):1474-85
references: 21248241
references: Bone. 2013 May;54(1):98-105
references: 23388417
references: J Appl Physiol (1985). 2007 Jul;103(1):48-54
references: 17303707
references: Dev Cell. 2009 May;16(5):734-43
references: 19460349
references: Angle Orthod. 2004 Feb;74(1):3-15
references: 15038485
references: J Clin Endocrinol Metab. 2004 Aug;89(8):3864-71
references: 15292319
references: J Bone Miner Res. 2006 Sep;21(9):1464-74
references: 16939405
references: Bone. 2010 Jan;46(1):64-71
references: 19781677
references: Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15111-6
references: 20713720
references: Arch Dis Child. 1994 Sep;71(3):235-8
references: 7979497
references: Curr Opin Clin Nutr Metab Care. 2013 May;16(3):272-7
references: 23481148
references: Scand J Rehabil Med. 1993 Jun;25(2):57-62
references: 8341992