Bones provide mechanical and protective function, while also serving as housing for marrow and a site for regulation of calcium ion homeostasis. The properties of bones do not remain constant with age; rather, they change throughout life, in some cases improving in function, but in others, function deteriorates. Here we review the modifications in the mechanical function and shape of bones, the bone cells, the matrix they produce, and the mineral that is deposited on this matrix, while presenting recent theories about the factors leading to these changes.
AaronJEMakinsNBSagreiyaK (1987). The microanatomy of trabecular bone loss in normal aging men and women. Clin Orthop Relat Res215:260-271.
2.
AdachiTAonumaYItoSTanakaMHojoMTakano-YamamotoT. (2009). Osteocyte calcium signaling response to bone matrix deformation. J Biomech42:2507-2512.
3.
AkkusOPolyakova-AkkusAAdarFSchafflerMB (2003). Aging of microstructural compartments in human compact bone. J Bone Miner Res18:1012-1019.
4.
AlmeidaMHanLMartin-MillanMPlotkinLIStewartSARobersonPK. (2007a). Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem282:27285-27297.
5.
AlmeidaMHanLMartin-MillanMO’BrienCAManolagasSC (2007b). Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription. J Biol Chem282:27298-27305.
6.
AmmannPRizzoliR (2003). Bone strength and its determinants. Osteoporos Int14(Suppl 3):13-18.
7.
BaileyAJSimsTJEbbesenENMansellJPThomsenJSMosekildeL (1999). Age-related changes in the biochemical properties of human cancellous bone collagen: relationship to bone strength. Calcif Tissue Int65:203-210.
8.
BanksEReevesGKBeralVBalkwillALiuBRoddamA (Million Women Study Collaborators) (2009). Hip fracture incidence in relation to age, menopausal status, and age at menopause: prospective analysis. PLoS Med6:e1000181.
9.
BanseXDevogelaerJPLafosseASimsTJGrynpasMBaileyAJ (2002). Cross-link profile of bone collagen correlates with structural organization of trabeculae. Bone31:70-76.
10.
BarerMJowseyJ (1967). Bone formation and resorption in normal human rib. A study of persons from 11 to 88 years of age. Clin Orthop Relat Res52:241-247.
11.
BennettCNLongoKAWrightWSSuvaLJLaneTFHankensonKD. (2005). Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci USA102:3324-3329.
12.
Binte AnwarRTanakaMKohnoSIkegameMWatanabeNNowazesh AliM. (2007). Relationship between porotic changes in alveolar bone and spinal osteoporosis. J Dent Res86:52-57.
13.
BlackALaneMA (2002). Nonhuman primate models of skeletal and reproductive aging. Gerontology48:72-80.
14.
BlairHCCarringtonJL (2006). Bone cell precursors and the pathophysiology of bone loss. Ann NY Acad Sci1068:244-249.
15.
BlairHCSimonetSLaceyDLZaidiM (2007). Osteoclast biology. In: Osteoporosis. 3rd ed.MarcusRFeldmanDNelsonDRosenCJ, editors. New York, NY: Academic Press, Chapter 7, pp. 151-168.
16.
BlascoMALeeHWHandeMPSamperELansdorpPMDePinhoRA. (1997). Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell91:25-34.
17.
BonewaldLF (2007). Osteocytes. In: Osteoporosis. 3rd ed.MarcusRFeldmanDNelsonDRosenCJ, editors. New York, NY: Academic Press, Chapter 8, pp. 169-190.
18.
BonewaldLFJohnsonML (2008). Osteocytes, mechanosensing and Wnt signaling. Bone42:606-615.
19.
BoskeyA (2007). Mineralization of bones and teeth. Elements Magazine3:385-391.
20.
BoskeyAPleshko CamachoN (2007). FT-IR imaging of native and tissue-engineered bone and cartilage. Biomaterials28:2465-2478.
21.
BoskeyALMooreDJAmlingMCanalisEDelanyAM (2003). Infrared analysis of the mineral and matrix in bones of osteonectin-null mice and their wildtype controls. J Bone Miner Res18:1005-1011.
22.
BoskeyALDiCarloEPaschalisEWestPMendelsohnR (2005a). Comparison of mineral quality and quantity in iliac crest biopsies from high- and low-turnover osteoporosis: an FT-IR microspectroscopic investigation. Osteoporos Int16:2031-2038.
23.
BoskeyALYoungMFKiltsTVerdelisK (2005b). Variation in mineral properties in normal and mutant bones and teeth. Cells Tissues Organs181:144-153.
24.
BoskeyALSpevakLWeinsteinRS (2009). Spectroscopic markers of bone quality in alendronate-treated postmenopausal women. Osteoporos Int20:793-800.
25.
BoyceBFYaoZXingL (2009). Osteoclasts have multiple roles in bone in addition to bone resorption. Crit Rev Eukaryot Gene Expr19:171-180.
26.
BrackASConboyMJRoySLeeMKuoCJKellerC. (2007). Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science317:807-810.
27.
BurgerCZhouHWWangHSicsIHsiaoBSChuB. (2008). Lateral packing of mineral crystals in bone collagen fibrils. Biophys J95:1985-1992.
28.
BurnellJMTeubnerEJMillerAG (1980). Normal maturational changes in bone matrix, mineral, and crystal size in the rat. Calcif Tissue Int31:13-19.
29.
BursteinAHReillyDTMartensM (1976). Aging of bone tissue: mechanical properties. J Bone Joint Surg Am58:82-86.
30.
CaladoRT (2009). Telomeres and marrow failure. Hematology Am Soc Hematol Educ Program2009:338-343.
31.
CampagnolaPJLoewLM (2003). Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms. Nat Biotechnol21:1356-1360.
32.
CaoJJWronskiTJIwaniecUPhlegerLKurimotoPBoudignonB. (2005). Aging increases stromal/osteoblastic cell-induced osteoclastogenesis and alters the osteoclast precursor pool in the mouse. J Bone Miner Res20:1659-1668.
33.
CaoJJKurimotoPBoudignonBRosenCLimaFHalloranBP (2007). Aging impairs IGF-I receptor activation and induces skeletal resistance to IGF-I. J Bone Miner Res22:1271-1279.
34.
CardenAMorrisMD (2000). Application of vibrational spectroscopy to the study of mineralized tissues. J Biomed Opt5:259-268.
35.
CarringtonJL (2005). Aging bone and cartilage: cross-cutting issues. Biochem Biophys Res Commun328:700-708.
36.
CerroniAMTomlinsonGATurnquistJEGrynpasMD (2000). Bone mineral density, osteopenia, and osteoporosis in the rhesus macaques of Cayo Santiago. Am J Phys Anthropol113:389-410.
37.
ChanGKDuqueG (2002). Age-related bone loss: old bone, new facts. Gerontology48:62-71.
38.
ChangSMultaniASCabreraNGNaylorMLLaudPLombardD. (2004). Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat Genet36:877-882.
ChenJHLiuCYouLSimmonsCA (2009). Boning up on Wolff’s Law: mechanical regulation of the cells that make and maintain bone. J Biomech43:108-118.
41.
ChoGWuYAckermanJL (2003). Detection of hydroxyl ions in bone mineral by solid-state NMR spectroscopy. Science300:1123-1127.
42.
ChungHYCesariMAntonSMarzettiEGiovanniSSeoAY. (2009). Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev8:18-30.
43.
ColmanRJLaneMABinkleyNWegnerFHKemnitzJW (1999). Skeletal effects of aging in male rhesus monkeys. Bone24:17-23.
44.
CurreyJD (1969). The relationship between the stiffness and the mineral content of bone. J Biomech2:477-480.
45.
CurreyJDButlerG (1975). The mechanical properties of bone tissue in children. J Bone Joint Surg Am57:810-814.
46.
CurreyJDBrearKZiouposP (1996). The effects of ageing and changes in mineral content in degrading the toughness of human femora. J Biomech29:257-262; erratum in J Biomech 30:1001, 1997.
47.
DaniellHW (1983). Postmenopausal tooth loss. Contributions to edentulism by osteoporosis and cigarette smoking. Arch Intern Med143:1678-1682.
48.
DeCarolisNAWhartonKAJrEischAJ (2008). Which way does the Wnt blow? Exploring the duality of canonical Wnt signaling on cellular aging. Bioessays30:102-106.
49.
Denisov-NikolskiiYIZhilkinBADoktorovAAMatveĭchukIV (2002). (Ultrastructural organization of the human lamellar bone tissue mineral component in aged and elderly). Morfologiia122:79-83 [in Russian].
50.
DennisonEHindmarshPFallCKellingraySBarkerDPhillipsD. (1999). Profiles of endogenous circulating cortisol and bone mineral density in healthy elderly men. J Clin Endocrinol Metab84:3058-3063.
51.
DonnellyEBoskeyALBakerSPvan der MeulenMC (2009). Effects of tissue age on bone tissue material composition and nanomechanical properties in the rat cortex. J Biomed Mater Res A92:1048-1056.
52.
DuqueGRivasDLiWLiAHendersonJEFerlandG. (2009). Age-related bone loss in the LOU/c rat model of healthy ageing. Exp Gerontol44:183-189.
53.
EarnshawSAKeatingNHoskingDJChilversCERavnPMcClungM. (1998). Tooth counts do not predict bone mineral density in early postmenopausal Caucasian women. EPIC study group. Int J Epidemiol27:479-483.
54.
EppellSJTongWKatzJLKuhnLGlimcherMJ (2001). Shape and size of isolated bone mineralites measured using atomic force microscopy. J Orthop Res19:1027-1034.
55.
FedarkoNSVetterUKWeinsteinSRobeyPG (1992). Age-related changes in hyaluronan, proteoglycan, collagen, and osteonectin synthesis by human bone cells. J Cell Physiol151:215-227.
FuchsRKAllenMRRuppelMEDiabTPhippsRJMillerLM. (2008). In situ examination of the time-course for secondary mineralization of Haversian bone using synchrotron Fourier transform infrared microspectroscopy. Matrix Biol27:34-41.
58.
GoldmanHMMcFarlinSCCooperDMThomasCDClementJG (2009). Ontogenetic patterning of cortical bone microstructure and geometry at the human mid-shaft femur. Anat Rec (Hoboken)292:48-64.
59.
Gourion-ArsiquaudSBurketJCHavillLMDiCarloEDotySBMendelsohnR. (2009a). Spatial variation in osteonal bone properties relative to tissue and animal age. J Bone Miner Res24:1271-1281.
60.
Gourion-ArsiquaudSFaibishDMyersESpevakLCompstonJHodsmanA. (2009b). Use of FTIR spectroscopic imaging to identify parameters associated with fragility fracture. J Bone Miner Res24:1565-1571.
61.
Gourion-ArsiquaudSAllenMRBurrDBVashishthDTangSYBoskeyAL (2010). Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone46:666-672.
62.
GrynpasM (1993a). Age and disease-related changes in the mineral of bone. Calcif Tissue Int53(Suppl 1):57-64.
63.
GrynpasMDHancockRGGreenwoodCTurnquistJKesslerMJ (1993b). The effects of diet, age, and sex on the mineral content of primate bones. Calcif Tissue Int52:399-405.
64.
GrynpasMDTupyJHSodekJ (1994). The distribution of soluble, mineral-bound, and matrix-bound proteins in osteoporotic and normal bones. Bone15:505-513.
65.
GrzesikWJFrazierCRShapiroJRSponsellerPDRobeyPGFedarkoNS (2002). Age-related changes in human bone proteoglycan structure. Impact of osteogenesis imperfecta. J Biol Chem277:43638-43647.
66.
HanschinRGSternWB (1995). X-ray diffraction studies on the lattice perfection of human bone apatite (Crista iliaca). Bone16(4 Suppl):355S-363S.
67.
HavillLM (2004). Osteon remodeling dynamics in Macaca mulatta: normal variation with regard to age, sex, and skeletal maturity. Calcif Tissue Int74:95-102.
HiranoTTurnerCHForwoodMRJohnstonCCBurrDB (2000). Does suppression of bone turnover impair mechanical properties by allowing microdamage accumulation?Bone27:13-20.
70.
HuttnerEAMachadoDCde OliveiraRBAntunesAGHeblingE (2009). Effects of human aging on periodontal tissues. Spec Care Dentist29:149-155.
71.
IkedaTNagaiYYamaguchiAYokoseSYoshikiS (1995). Age-related reduction in bone matrix protein mRNA expression in rat bone tissues: application of histomorphometry to in situ hybridization. Bone16:17-23.
72.
JayoMJJeromeCPLeesCJRankinSEWeaverDS (1994). Bone mass in female cynomolgus macaques: a cross-sectional and longitudinal study by age. Calcif Tissue Int54:231-236.
73.
JepsenKJ (2009). Systems analysis of bone. Wiley Interdiscip Rev Syst Biol Med1:73-88.
74.
JiangYMishimaHSakaiSLiuYKOhyabuYUemuraT (2008). Gene expression analysis of major lineage-defining factors in human bone marrow cells: effect of aging, gender, and age-related disorders. J Orthop Res26:910-917.
75.
JilkaRLWeinsteinRSTakahashiKParfittAMManolagasSC (1996). Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence. J Clin Invest97:1732-1740.
76.
JilkaRLWeinsteinRSParfittAMManolagasSC (2007). Quantifying osteoblast and osteocyte apoptosis: challenges and rewards. J Bone Miner Res22:1492-1501.
77.
JonassonGJonassonLKiliaridisS (2006). Changes in the radiographic characteristics of the mandibular alveolar process in dentate women with varying bone mineral density: a 5-year prospective study. Bone38:714-721.
78.
JowseyJ (1966). Studies of Haversian systems in man and some animals. J Anat100(Pt 4):857-864.
79.
KanisJA (2002). Diagnosis of osteoporosis and assessment of fracture risk. Lancet359:1929-1936.
80.
KashimaTGNishiyamaTShimazuKShimazakiMKiiIGrigoriadisAE. (2009). Periostin, a novel marker of intramembranous ossification, is expressed in fibrous dysplasia and in c-Fos–overexpressing bone lesions. Hum Pathol40:226-237.
81.
KasteSCKasowKAHorwitzEM (2007). Quantitative bone mineral density assessment in malignant infantile osteopetrosis. Pediatr Blood Cancer48:181-185.
82.
KavukcuogluNBDenhardtDTGuzelsuNMannAB (2007). Osteopontin deficiency and aging on nanomechanics of mouse bone. J Biomed Mater Res A83:136-144.
83.
KawashimaYFrittonJCYakarSEpsteinSSchafflerMBJepsenKJ. (2009). Type 2 diabetic mice demonstrate slender long bones with increased fragility secondary to increased osteoclastogenesis. Bone44:648-655.
84.
KennedyBKKaeberleinM (2009). Hot topics in aging research: protein translation, 2009. Aging Cell8:617-623.
85.
KrallEAGarciaRIDawson-HughesB (1996). Increased risk of tooth loss is related to bone loss at the whole body, hip and spine. Calcif Tissue Int59:433-437.
86.
KribbsPJChestnutCH3rdOttSMKilcoyneRF (1989). Relationships between mandibular and skeletal bone in an osteoporotic population. J Prosthet Dent62:703-707.
87.
KuhnLTGrynpasMDReyCCWuYAckermanJLGlimcherMJ (2008). A comparison of the physical and chemical differences between cancellous and cortical bovine bone mineral at two ages. Calcif Tissue Int83:146-154.
88.
Kuro-oM (2009). Klotho and aging. Biochim Biophys Acta1790:1049-1058.
89.
Kuro-oMMatsumuraYAizawaHKawaguchiHSugaTUtsugiT. (1997). Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature390:45-51.
90.
LaMotheJMHeppleRTZernickeRF (2003). Selected contribution: bone adaptation with aging and long-term caloric restriction in Fischer 344 x Brown-Norway F1-hybrid rats. J Appl Physiol95:1739-1745.
91.
LeeCCFletcherMDTarantalAF (2005). Effect of age on the frequency, cell cycle, and lineage maturation of rhesus monkey (Macaca mulatta) CD34+ and hematopoietic progenitor cells. Pediatr Res58:315-322.
92.
LeeHWBlascoMAGottliebGJHornerJWGreiderCWDePinhoRA (1998). Essential role of mouse telomerase in highly proliferative organs. Nature392:569-574.
93.
LeemingDJHenriksenKByrjalsenIQvistPMadsenSHGarneroP. (2009). Is bone quality associated with collagen age?Osteoporos Int20:1461-1470.
LianJBSteinGS (2008). Osteoblast biology. In: Osteoporosis. 3rd ed.MarcusRFeldmanDNelsonDRosenCJ, editors. New York, NY: Academic Press, Chapter 6, pp. 93-128.
96.
LiangSHosurKBDomonHHajishengallisG (2010). Periodontal inflammation and bone loss in aged mice. J Periodontal Res(Epub ahead of print, March 9, 2010) (in press).
97.
LingYRiosHFMyersERLuYFengJQBoskeyAL (2005). DMP1 depletion decreases bone mineralization in vivo: an FTIR imaging analysis. J Bone Miner Res20:2169-2177.
98.
LoongCKReyCKuhnLTCombesCWuYChenS. (2000). Evidence of hydroxyl-ion deficiency in bone apatites: an inelastic neutron-scattering study. Bone26:599-602.
99.
LuCHansenESapozhnikovaAHuDMiclauTMarcucioRS (2008). Effect of age on vascularization during fracture repair. J Orthop Res26:1384-1389.
100.
ManolagasSC (2010). From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev, 31:266-300.
101.
ManolagasSCParfittAM (2010). What old means to bone. Trends Endocrinol Metab21:369-374
102.
MartinGM (2005). Genetic modulation of senescent phenotypes in Homo sapiens. Cell120:523-532.
103.
MartinGMSpragueCAEpsteinCJ (1970). Replicative life-span of cultivated human cells. Effects of donor’s age, tissue, and genotype. Lab Invest23:86-92.
104.
MasudaHChikudaHSugaTKawaguchiHKuro-oM (2005). Regulation of multiple ageing-like phenotypes by inducible klotho gene expression in klotho mutant mice. Mech Ageing Dev126:1274-1283.
105.
MatsuoK (2009). Cross-talk among bone cells. Curr Opin Nephrol Hypertens18:292-297.
106.
McCaldenRWMcGeoughJABarkerMBCourt-BrownCM (1993). Age-related changes in the tensile properties of cortical bone. The relative importance of changes in porosity, mineralization, and microstructure. J Bone Joint Surg Am75:1193-1205.
107.
MellibovskyLBustamanteMLluchPNoguesXGrinbergDBalcellsS. (2007). Bone mass of a 113-year-old man. J Gerontol A Biol Sci Med Sci62:794-795.
108.
MeltonLJ3rd (1996). Epidemiology of hip fractures: implications of the exponential increase with age. Bone18(3 Suppl):121S-125S.
109.
MeneghiniCDalconiMCNuzzoSMobilioSWenkRH (2003). Rietveld refinement on x-ray diffraction patterns of bioapatite in human fetal bones. Biophys J84:2021-2029.
110.
MeyerRAJrTsahakisPJMartinDFBanksDMHarrowMEKiebzakGM (2001). Age and ovariectomy impair both the normalization of mechanical properties and the accretion of mineral by the fracture callus in rats. J Orthop Res19:428-435.
111.
MillerLMLittleWSchirmerASheikFBusaBJudexS (2007). Accretion of bone quantity and quality in the developing mouse skeleton. J Bone Miner Res22:1037-1045.
112.
MohajeryMBrooksSL (1992). Oral radiographs in the detection of early signs of osteoporosis. Oral Surg Oral Med Oral Pathol73:112-117.
113.
MohammadARBauerRLYehCK (1997). Spinal bone density and tooth loss in a cohort of postmenopausal women. Int J Prosthodont10:381-385.
114.
MohsinSO’BrienFJLeeTC (2006). Microcracks in compact bone: a three-dimensional view. J Anat209:119-124.
115.
MoriyaYItoKMuraiS (1998). Effects of experimental osteoporosis on alveolar bone loss in rats. J Oral Sci40:171-175.
116.
MullerM (2009). Cellular senescence: molecular mechanisms, in vivo significance, and redox considerations. Antioxid Redox Signal11:59-98.
117.
NagarajaSLinASGuldbergRE (2007). Age-related changes in trabecular bone microdamage initiation. Bone40:973-980.
118.
NaikAAXieCZuscikMJKingsleyPSchwarzEMAwadH. (2009). Reduced COX-2 expression in aged mice is associated with impaired fracture healing. J Bone Miner Res24:251-264.
119.
NakanishiRShimizuMMoriMAkiyamaHOkudairaSOtsukiB. (2006). Secreted frizzled-related protein 4 is a negative regulator of peak BMD in SAMP6 mice. J Bone Miner Res21:1713-1721.
120.
NegriAL (2005). The klotho gene: a gene predominantly expressed in the kidney is a fundamental regulator of aging and calcium/phosphorus metabolism. J Nephrol18:654-658.
121.
NievesJWBilezikianJPLaneJMEinhornTAWangYSteinbuchM. (2009). Fragility fractures of the hip and femur: incidence and patient characteristics. Osteoporos Int29:399-408.
122.
NovakADedharS (1999). Signaling through beta-catenin and Lef/Tcf. Cell Mol Life Sci56:523-537.
123.
NymanJSRoyAAcunaRLGayleHJReyesMJTylerJH. (2006). Age-related effect on the concentration of collagen crosslinks in human osteonal and interstitial bone tissue. Bone39:1210-1217.
124.
NymanJSRoyATylerJHAcunaRLGayleHJWangX (2007). Age-related factors affecting the postyield energy dissipation of human cortical bone. J Orthop Res25:646-655.
125.
O’BrienFJBrennanOKennedyODLeeTC (2005). Microcracks in cortical bone: how do they affect bone biology?Curr Osteoporos Rep3:39-45.
126.
O’DriscollSWSarisDBItoYFitzimmonsJS (2001). The chondrogenic potential of periosteum decreases with age. J Orthop Res19:95-103.
127.
PaschalisEPDiCarloEBettsFShermanPMendelsohnRBoskeyAL (1996). FTIR microspectroscopic analysis of human osteonal bone. Calcif Tissue Int59:480-487.
128.
PaschalisEPBettsFDiCarloEMendelsohnRBoskeyAL (1997). FTIR microspectroscopic analysis of normal human cortical and trabecular bone. Calcif Tissue Int61:480-486.
129.
PellegrinoEDBiltzRM (1972). Mineralization in the chick embryo. I. Monohydrogen phosphate and carbonate relationships during maturation of the bone crystal complex. Calcif Tissue Res10:128-135.
130.
PietschmannPSkalickyMKneisselMRaunerMHofbauerGStupphannD. (2007). Bone structure and metabolism in a rodent model of male senile osteoporosis. Exp Gerontol42:1099-1108.
131.
PlantalechLGuillaumontMVergnaudPLeclercqMDelmasPD (1991). Impairment of gamma carboxylation of circulating osteocalcin (bone gla protein) in elderly women. J Bone Miner Res6:1211-1216.
132.
PłudowskiPLebiedowskiMOlszanieckaMMarowskaJMatusikHLorencRS (2006). Idiopathic juvenile osteoporosis—an analysis of the muscle-bone relationship. Osteoporos Int17:1681-1690.
133.
ProvotSSchipanniEWuJKronenbergH (2008). Development of the skeleton. In: Osteoporosis. 3rd ed.MarcusRFeldmanDNelsonDRosenCJ, editors. New York, NY: Academic Press, Chapter 10, pp. 241-270.
134.
PurnellJQBrandonDDIsabelleLMLoriauxDLSamuelsMH (2004). Association of 24-hour cortisol production rates, cortisol-binding globulin, and plasma-free cortisol levels with body composition, leptin levels, and aging in adult men and women. J Clin Endocrinol Metab89:281-287.
135.
RamanadhamSYarasheskiKESilvaMJWohltmannMNovackDVChristiansenB. (2008). Age-related changes in bone morphology are accelerated in group VIA phospholipase A2 (iPLA2beta)-null mice. Am J Pathol172:868-881.
136.
RauchF (2005). Bone growth in length and width: the Yin and Yang of bone stability. J Musculoskelet Neuronal Interact5:194-201.
137.
RauchFTraversRNormanMETaylorAParfittAMGlorieuxFH (2002). The bone formation defect in idiopathic juvenile osteoporosis is surface-specific. Bone31:85-89.
138.
RaunerMSiposWPietschmannP (2008). Age-dependent Wnt gene expression in bone and during the course of osteoblast differentiation. Age (Dordr)30:273-282.
139.
ReyCRenugopalakrishnanVCollinsBGlimcherMJ (1991a). Fourier transform infrared spectroscopic study of the carbonate ions in bone mineral during aging. Calcif Tissue Int49:251-258.
140.
ReyCShimizuMCollinsBGlimcherMJ (1991b). Resolution-enhanced Fourier transform infrared spectroscopy study of the environment of phosphate ion in the early deposits of a solid phase of calcium phosphate in bone and enamel and their evolution with age: 2. Investigations in the nu3PO4 domain. Calcif Tissue Int49:383-388.
141.
ReyCHinaATofighiAGlimcherMJ (1995a). Maturational of poorly crystalline apatites – chemical and structural aspects in vivo and in vitro. Cells Materials5:345-356.
142.
ReyCMiquelJLFacchiniLLegrandAPGlimcherMJ (1995b). Hydroxyl groups in bone mineral. Bone16:583-586.
143.
ReynoldsRMDennisonEMWalkerBRSyddallHEWoodPJAndrewR. (2005). Cortisol secretion and rate of bone loss in a population-based cohort of elderly men and women. Calcif Tissue Int77:134-138.
144.
RichardsJBKavvouraFKRivadeneiraFStyrkársdóttirUEstradaKHalldórssonBV. (2009). Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann Intern Med151:528-537.
145.
RitchieCSJoshipuraKHungHCDouglassCW (2002). Nutrition as a mediator in the relation between oral and systemic disease: associations between specific measures of adult oral health and nutrition outcomes. Crit Rev Oral Biol Med13:291-300.
146.
RochefortGYPalluSBenhamouCL (2010). Osteocyte: the unrecognized side of bone tissue. Osteoporos Int(Epub ahead of print, March 4, 2010) (in press).
147.
SahinEDePinhoRA (2010). Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature464:520-528.
148.
SaitoMMarumoK (2010). Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int21:195-214.
149.
SalihDABrunetA (2008). FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol20:126-136.
150.
SanfilippoFBianchiAE (2003). Osteoporosis: the effect on maxillary bone resorption and therapeutic possibilities by means of implant prostheses—a literature review and clinical considerations. Int J Periodontics Restorative Dent23:447-457.
151.
SarajlicNTopicBBrkicHAlajbegIZ (2009). Aging quantification on alveolar bone loss. Coll Antropol33:1165-1170.
152.
SchafflerMBChoiKMilgromC (1995). Aging and matrix microdamage accumulation in human compact bone. Bone17:521-552.
153.
SchneiderSBreitSMGramppSKünzelWWLiesegangAMayrhoferE. (2004). Comparative assessment of bone mineral measurements obtained by use of dual-energy x-ray absorptiometry, peripheral quantitative computed tomography, and chemical-physical analyses in femurs of juvenile and adult dogs. Am J Vet Res65:891-900.
154.
SeemanE (2003). The structural and biomechanical basis of the gain and loss of bone strength in women and men. Endocrinol Metab Clinic North Am32:25-38.
155.
SeemanE (2009). Bone modeling and remodeling. Crit Rev Eukaryot Gene Expr9:219-233.
156.
SomervilleJMAspdenRMArmourKEArmourKJReidDM (2004). Growth of C57BL/6 mice and the material and mechanical properties of cortical bone from the tibia. Calcif Tissue Int74:469-475.
157.
SouthardKASouthardTESchlechteJAMeisPA (2000). The relationship between the density of the alveolar process and that of post-cranial bone. J Dent Res89:964-969.
158.
StreckfusCFParsellDEStreckfusJEPenningtonWJohnsonRB (1999). Relationship between oral alveolar bone loss and aging among African-American and Caucasian individuals. Gerontology45:110-114.
159.
SuzukiHAmizukaNOdaKLiMYoshieHOhshimaH. (2005). Histological evidence of the altered distribution of osteocytes and bone matrix synthesis in klotho-deficient mice. Arch Histol Cytol68:371-381.
160.
SzulcPSeemanE (2009). Thinking inside and outside the envelopes of bone: dedicated to PDD. Osteoporos Int20:1281-1288.
161.
TaguchiASueiYOhtsukaMOtaniKTanimotoKHollenderLG (1999). Relationship between bone mineral density and tooth loss in elderly Japanese women. Dentomaxillofac Radiol28:219-223.
162.
TanakaMEjiriSToyookaEKohnoSOzawaH (2002). Effects of ovariectomy on trabecular structures of rat alveolar bone. J Periodontal Res37:161-165.
163.
TanakaMToyookaEKohnoSOzawaHEjiriS (2003). Long-term changes in trabecular structure of aged rat alveolar bone after ovariectomy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod95:495-502.
164.
TangSYZeenathUVashishthD (2007). Effects of non-enzymatic glycation on cancellous bone fragility. Bone40:1144-1151.
165.
TarnowskiCPIgnelziMAJrMorrisMD (2002). Mineralization of developing mouse calvaria as revealed by Raman microspectroscopy. J Bone Miner Res17:1118-1126.
166.
TommasiniSMNasserPSchafflerMBJepsenKJ (2005). Relationship between bone morphology and bone quality in male tibias: implications for stress fracture risk. J Bone Miner Res20:1372-1380.
167.
TommasiniSMNasserPJepsenKJ (2007). Sexual dimorphism affects tibia size and shape but not tissue-level mechanical properties. Bone40:498-505.
168.
TongWGlimcherMJKatzJLKuhnLEppellSJ (2003). Size and shape of mineralites in young bovine bone measured by atomic force microscopy. Calcif Tissue Int72:592-598.
169.
TosiLLBoyanBDBoskeyAL (2005). Does sex matter in musculoskeletal health? The influence of sex and gender on musculoskeletal health. J Bone Joint Surg Am87:1631-1647.
170.
Van CauterELeproultRKupferDJ (1996). Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol. J Clin Endocrinol Metab81:2468-2473.
171.
VashishthD (2007). Hierarchy of bone microdamage at multiple length scales. Int J Fatigue29:1024-1033.
172.
VashishthDGibsonGJKhouryJISchafflerMBKimuraJFyhrieDP (2001). Influence of nonenzymatic glycation on biomechanical properties of cortical one. Bone28:195-201.
173.
VerborgtOGibsonGJSchafflerMB (2000). Loss of osteocyte integrity in association with microdamage and bone remodelling after fatigue in vivo. J Bone Miner Res15:60-67.
174.
Viguet-CarrinSFolletHGineytsERouxJPMunozFChapurlatR. (2010). Association between collagen cross-links and trabecular microarchitecture properties of human vertebral bone. Bone46:342-347.
175.
Von WowernNStoltzeK (1978). Histoquantitation on small jaw specimens. Scand J Dent Res86:193-199.
176.
WallaceJMRajacharRMAllenMRBloomfieldSARobeyPGYoungMF. (2007). Exercise-induced changes in the cortical bone of growing mice are bone- and gender-specific. Bone40:1120-1127.
177.
WangQSeemanE (2008). Skeletal growth and peak bone strength. Best Pract Res Clin Endocrinol Metab22:687-700.
178.
WeinerSTraubW (1989). Crystal size and organization in bone. Connect Tissue Res21:259-265.
179.
WesterbeekZWHeppleRTZernickeRF (2008). Effects of aging and caloric restriction on bone structure and mechanical properties. J Gerontol A Biol Sci Med Sci63:1131-1136.
180.
WhiteSCRudolphDJ (1999). Alterations of the trabecular pattern of the jaws in patients with osteoporosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod88:628-635.
181.
WilliamsBOInsognaKL (2009). Where Wnts went: the exploding field of Lrp5 and Lrp6 signaling in bone. J Bone Miner Res24:171-178.
182.
WooSLKueiSCAmielDGomezMAHayesWCWhiteFC. (1981). The effect of prolonged physical training on the properties of long bone: a study of Wolff’s Law. J Bone Joint Surg Am63:780-787.
183.
WuMFanninJRiceKMWangBBloughER (2010). Effect of aging on cellular mechanotransduction. Ageing Res Rev(Epub ahead of print, November 20, 2009) (in press).
184.
WuYAckermanJLKimHMReyCBarrougAGlimcherMJ (2002). Nuclear magnetic resonance spin-spin relaxation of the crystals of bone, dental enamel, and synthetic hydroxyapatites. J Bone Miner Res17:472-480.
185.
YatesLBKarasikDBeckTJCupplesLAKielDP (2007). Hip structural geometry in old and old-old age: similarities and differences between men and women. Bone41:722-732.
186.
YerramshettyJSLindCAkkusO (2006). The compositional and physicochemical homogeneity of male femoral cortex increases after the sixth decade. Bone39:1236-1243.
187.
ZhouSGreenbergerJSEpperlyMWGoffJPAdlerCLeboffMS. (2008). Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell7:335-343.
188.
ZhuWRobeyPGBoskeyAL (2008). The regulatory role of matrix proteins in mineralization of bone. In: Osteoporosis. 3rd ed.MarcusRFeldmanDNelsonDRosenCJ, editors. New York, NY: Academic Press, Chapter 9, pp. 191-240.
189.
ZuscikMJHiltonMJZhangXChenDO’KeefeRJ (2008). Regulation of chondrogenesis and chondrocyte differentiation by stress. J Clin Invest118:429-438.