Abstract
Fracture repair, which aims at regaining the functional competence of a bone, is a complex and multifactorial process. For the success of fracture repair biology and mechanics are of immense importance. The biological and mechanical environments must be compatible with the processes of cell and tissue proliferation and differentiation. The biological environment is characterized by the vascular supply and by many biochemical components, the biochemical milieu. A good vascular supply is a prerequisite for the initiation of the fracture repair process. The biochemical milieu involves complex interactions among local and systemic regulatory factors such as growth factors or cytokines. The mechanical environment is determined by the local stress and strain within the fracture. However, the local stress and strain is not accessible, and the mechanical environment, therefore, is described by global mechanical factors, e.g., gap size or interfragmentary movement. The relationship between local stress and strain and the global mechanical factors can be obtained by numerical models (Finite Element Model). Moreover, there is considerable interaction between biological factors and mechanical factors, creating a biomechanical environment for the fracture healing process. The biomechanical environment is characterized by osteoblasts and osteocytes that sense the mechanical signal and express biological markers, which effect the repair process. This review will focus on the effects of biomechanical factors on fracture repair as well as the effects of age and osteoporosis.
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References
Einhorn TA (1995) Enhancement of fracture healing. J Bone Joint Surg Am 77:940–956
Buckwalter JA, Einhorn TA, Bolander ME, Cruess RL (1996) Healing of the musculoskeletal tissues. In: Heckman JD (ed) Fractures in adults. Lippincott–Raven, Philadelphia, New York, pp 261–304
Buckwalter JA, Woo SL, Goldberg VM, Hadley EC, Booth F, Oegema TR, Eyre DR (1993) Soft-tissue aging and musculoskeletal function. J Bone Joint Surg Am 75:1533–1548
Kawai T, Murakami S, Hiranuma H, Sakuda M (1997) Radiographic changes during bone healing after mandibular fractures. Br J Oral Maxillofac Surg 35:312–318
Claes L, Grass R, Schmickal T, Kisse B, Eggers C, Gerngross H, Mutschler W, Arand M, Wintermeyer T, Wentzensen A (2002) Monitoring and healing analysis of 100 tibial shaft fractures. Langenbecks Arch Surg 387:146–152
Meyer RA Jr, Tsahakis PJ, Martin DF, Banks DM, Harrow ME, Kiebzak GM (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
Meyer RA Jr, Meyer MH, Tenholder M, Wondracek S, Wasserman R, Garges P (2003) Gene expression in older rats with delayed union of femoral fractures. J Bone Joint Surg Am 85:1243–1254
Ekeland A, Engesoeter LB, Langeland N (1982) Influence of age on mechanical properties of healing fractures and intact bones in rats. Acta Orthop Scand 53:527–534
Barrios C, Brostrom LA, Stark A, Walheim G (1993) Healing complications after internal fixation of trochanteric hip fractures: the prognostic value of osteoporosis. J Orthop Trauma 7:438–442
Cobey JC, Cobey JH, Conant L, Weil UH, Greenwald WF, Southwick WO (1976) Indicators of recovery from fractures of the hip. Clin Orthop 14:258–262
Moffett JD, Einhorn TA (1999) General orthopedic principles. In: Rosen CJ, Glowacki J, Bilezikian JP (eds) The aging skeleton. Academic Press, San Diego, pp 383–397
Nieminen S, Nurmi M, Satokari K (1981) Healing of femoral neck fractures; influence of fracture reduction and age. Ann Chir Gynaecol 70:26–31
Hee HT, Wong HP, Low YP, Myers L (2001) Predictors of outcome of floating knee injuries in adults: 89 patients followed for 2–12 years. Acta Orthop Scand 72:385–394
Kubo T, Shiga T, Hashimoto J, Yoshioka M, Honjo H, Urabe M, Kitajima I, Semba I, Hirasawa Y (1999) Osteoporosis influences the late period of fracture healing in a rat model prepared by ovariectomy and low calcium diet. J Steroid Biochem Mol Biol 68:197–202
Wheeler DL, Eschbach EJ, Montfort MJ, Maheshwari P, McLoughlin SW (2000) Mechanical strength of fracture callus in osteopenic bone at different phases of healing. J Orthop Trauma 14:86–92
Cao Y, Mori S, Mashiba T, Westmore MS, Ma L, Sato M, Akiyama T, Shi L, Komatsubara S, Miyamoto K, Norimatsu H (2002) Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats. J Bone Miner Res 17:2237–2246
Waters RV, Gamradt SC, Asnis P, Vickery BH, Avnur Z, Hill E, Bostrom M (2000) Systemic corticosteroids inhibit bone healing in a rabbit ulnar osteotomy model. Acta Orthop Scand 71:316–321
Lill CA, Hesseln J, Schlegel U, Eckhardt C, Goldhahn J, Schneider E (2003) Biomechanical evaluation of healing in a non-critical defect in a large animal model of osteoporosis. J Orthop Res 21:836–842
Pankovic AM, Tarabishy IE, Yelda S (1981) Flexible intramedullary nailing of tibial-shaft fractures. Clin Orthop 160:185–195
Koch PP, Gross DF, Gerber C (2002) The results of functional (Sarmiento) bracing of humeral shaft fractures. J Shoulder Elbow Surg 11:143–150
Aro HT, Wahner HT, Chao EY (1991) Healing patterns of transverse and oblique osteotomies in the canine tibia under external fixation. J Orthop Trauma 5:351–364
Augat P, Margevicius K, Simon J, Wolf S, Suger G, Claes L (1998) Local tissue properties in bone healing: influence of size and stability of the osteotomy gap. J Orthop Res 16:475–481
Augat P, Merk J, Genant HK, Claes L (1997) Quantitative assessment of experimental fracture repair by peripheral computed tomography. Calcif Tissue Int 60:194–199
Claes L, Augat P, Suger G, Wilke HJ (1997) Influence of size and stability of the osteotomy gap on the success of fracture healing. J Orthop Res 15:577–584
Claes LE, Wilke H-J, Augat P, Rübenacker S, Margevicius KJ (1995) Effect of dynamization on gap healing of diaphyseal fractures under external fixation. Clin Biomech 10:227–234
Kenwright J, Goodship AE (1989) Controlled mechanical stimulation in the treatment of tibial fractures. Clin Orthop 241:36–47
Claes LE, Heigele CA, Neidlinger-Wilke C, Kaspar D, Seidl W, Margevicius KJ, Augat P (1998) Effects of mechanical factors on the fracture healing process. Clin Orthop 355:S132–147
Augat P, Rapp S, Claes L (2002) A modified hip screw incorporating injected cement for the fixation of osteoporotic trochanteric fractures. J Orthop Trauma 16:311–316
Gerich T, Blauth M, Witte F, Krettek C (2001) [Osteosynthesis of fractures of the head of the tibia in advanced age. A matched-pair analysis]. Unfallchirurg 104:50–56
Kenwright J, Richardson JB, Cunningham JL, White SH, Goodship AE, Adams MA, Magnussen PA, Newman JH (1991) Axial movement and tibial fractures. A controlled randomised trial of treatment. J Bone Joint Surg Br 73:654–659
Larsson S, Kim W, Caja VL, Egger EL, Inoue N, Chao EY (2001) Effect of early axial dynamization on tibial bone healing: a study in dogs. Clin Orthop 388:240–251
Augat P, Merk J, Wolf S, Claes L (2001) Mechanical stimulation by external application of cyclic tensile strains does not effectively enhance bone healing. J Orthop Trauma 15:54–60
Augat P, Burger J, Schorlemmer S, Henke T, Peraus M, Claes L (2003) Shear movement at the fracture site delays healing in a diaphyseal fracture model. J Orthop Res 21:1011–1017
Sarmiento A, McKellop HA, Llinas A, Park SH, Lu B, Stetson W, Rao R (1996) Effect of loading and fracture motions on diaphyseal tibial fractures. J Orthop Res 14:80–84
Park SH, O’Connor K, McKellop H, Sarmiento A (1998) The influence of active shear or compressive motion on fracture-healing. J Bone Joint Surg Am 80:868–878
Bishop NE, Tami I, van Rhijn MJ, Corveleijn R, Schneider E, Ito K (2002) Effects of volumetric vs. shear deformation on tissue differentiation during secondary bone healing. Trans Orthop Res Soc 27:O114
Stedtfeld HW (1993) [Fracture management in elderly patients. A technically and ethically challenging responsibility]. Fortschr Med 111:102–106
Claes LE, Heigele CA (1999) Magnitudes of local stress and strain along bony surfaces predict the course and type of fracture healing. J Biomech 32:255–266
Simon U, Augat P, Utz M, Claes L (2003) Simulation of tissue development and vascularisation in the callus healing process. Trans Orthop Res Soc 28:O299
Gardner TN, Mishra S (2003) The biomechanical environment of a bone fracture and its influence upon the morphology of healing. Med Eng Phys 25:455–464
Glowacki J (1998) Angiogenesis in fracture repair. Clin Orthop 355 [Suppl]: S82–89
Rhinelander FW (1979) Vascular proliferation and blood supply during fracture healing. In: Brooker AF, Edwards CC (eds) External fixation: the current state of the art. Williams and Wilkins, Baltimore, pp 9–14
Schweiberer L, Schenk R (1977) Histomorphologie und Vaskularisation der sekundären Knochenbruchheilung unter besonderer Berücksichtigung der Tibiaschaftfraktur. Unfallheilkunde, 80:275–286
Claes L, Eckert-Hubner K, Augat P (2002) The effect of mechanical stability on local vascularization and tissue differentiation in callus healing. J Orthop Res 20:1099–1105
Claes L, Eckert-Hubner K, Augat P (2003) The fracture gap size influences the local vascularization and tissue differentiation in callus healing. Langenbecks Arch Surg 388:316–322
Wallace AL, Draper ER, Strachan RK, McCarthy ID, Hughes SP (1994) The vascular response to fracture micromovement. Clin Orthop 301:281–290
Kirchen ME, O’Connor KM, Gruber HE, Sweeney JR, Fras IA, Stover SJ, Sarmiento A, Marshall GJ (1995) Effects of microgravity on bone healing in a rat fibular osteotomy model. Clin Orthop 318:231–242
Reed MJ, Edelberg JM (2004) Impaired angiogenesis in the aged. Sci Aging Knowl Environ 2004:pe 7
Edelberg JM, Reed MJ (2003) Aging and angiogenesis. Front Biosci 8:s1199–1209
Bostrom MP (1998) Expression of bone morphogenetic proteins in fracture healing. Clin Orthop 355 [Suppl]:S116–123
Joyce ME, Roberts AB, Sporn MB, Bolander ME (1990) Transforming growth factor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur. J Cell Biol 110:2195–2207
Reddi AH (2001) Bone morphogenetic proteins: from basic science to clinical applications. J Bone Joint Surg Am 83 [Suppl 1]: S1–6
Valentin-Opran A, Wozney J, Csimma C, Lilly L, Riedel GE (2002) Clinical evaluation of recombinant human bone morphogenetic protein-2. Clin Orthop 395:110–120
Sciadini MF, Dawson JM, Banit D, Juliao SF, Johnson KD, Lennington WJ, Schwartz HS (2000) Growth factor modulation of distraction osteogenesis in a segmental defect model. Clin Orthop 381:266–277
Yudell RM, Block MS (2000) Bone gap healing in the dog using recombinant human bone morphogenetic protein-2. J Oral Maxillofac Surg 58:761–766
Mizumoto Y, Moseley T, Drews M, Cooper VN, 3rd, Reddi AH (2003) Acceleration of regenerate ossification during distraction osteogenesis with recombinant human bone morphogenetic protein-7. J Bone Joint Surg Am 85 [Suppl 3]:124–130
Boden SD, Joyce ME, Oliver B, Heydemann A, Bolander ME (1989) Estrogen receptor mRNA expression in callus during fracture healing in the rat. Calcif Tissue Int 45:324–325
Monaghan BA, Kaplan FS, Lyttle CR, Fallon MD, Boden SD, Haddad JG (1992) Estrogen receptors in fracture healing. Clin Orthop 280:277–280
Nomura S, Takano-Yamamoto T (2000) Molecular events caused by mechanical stress in bone. Matrix Biol 19:91–96
Mikuni-Takagaki Y (1999) Mechanical responses and signal transduction pathways in stretched osteocytes. J Bone Miner Metab 17:57–60
Kusec V, Jelic M, Borovecki F, Kos J, Vukicevic S, Korzinek K (2003) Distraction osteogenesis by Ilizarov and unilateral external fixators in a canine model. Int Orthop 27:47–52
Ilizarov GA (1989) The tension-stress effect on the genesis and growth of tissues: part II. The influence of the rate and frequency of distraction. Clin Orthop 239:263–285
Carter DR, Beaupre GS, Giori NJ, Helms JA (1998) Mechanobiology of skeletal regeneration. Clin Orthop 355 [Suppl]:S41–55
Sato M, Yasui N, Nakase T, Kawahata H, Sugimoto M, Hirota S, Kitamura Y, Nomura S, Ochi T (1998) Expression of bone matrix proteins mRNA during distraction osteogenesis. J Bone Miner Res 13:1221–1231
Yeung HY, Lee KM, Fung KP, Leung KS (2002) Sustained expression of transforming growth factor-beta1 by distraction during distraction osteogenesis. Life Sci 71:67–79
Holbein O, Neidlinger-Wilke C, Suger G, Kinzl L, Claes L (1995) Ilizarov callus distraction produces systemic bone cell mitogens. J Orthop Res 13:629–638
Lammens J, Liu Z, Aerssens J, Dequeker J, Fabry G (1998) Distraction bone healing versus osteotomy healing: a comparative biochemical analysis. J Bone Miner Res 13:279–286
Weiss S, Baumgart R, Jochum M, Strasburger CJ, Bidlingmaier M (2002) Systemic regulation of distraction osteogenesis: a cascade of biochemical factors. J Bone Miner Res 17:1280–1289
Banes AJ, Tsuzaki M, Yamamoto J, Fischer T, Brigman B, Brown T, Miller L (1995) Mechanoreception at the cellular level: the detection, interpretation, and diversity of responses to mechanical signals. Biochem Cell Biol 73:349–365
Pavalko FM, Norvell SM, Burr DB, Turner CH, Duncan RL, Bidwell JP (2003) A model for mechanotransduction in bone cells: the load-bearing mechanosomes. J Cell Biochem 88:104–112
Rawlinson SC, Pitsillides AA, Lanyon LE (1996) Involvement of different ion channels in osteoblasts’ and osteocytes’ early responses to mechanical strain. Bone 19:609–614
Schmidt C, Pommerenke H, Durr F, Nebe B, Rychly J (1998) Mechanical stressing of integrin receptors induces enhanced tyrosine phosphorylation of cytoskeletally anchored proteins. J Biol Chem 273:5081–5085
Chiquet M (1999) Regulation of extracellular matrix gene expression by mechanical stress. Matrix Biol 18:417–426
Braddock M, Schwachtgen JL, Houston P, Dickson MC, Lee MJ, Campbell CJ (1998) Fluid shear stress modulation of gene expression in endothelial cells. News Physiol Sci 13:241–246
Neidlinger-Wilke C, Stalla I, Claes L, Brand R, Hoellen I, Rubenacker S, Arand M, Kinzl L (1995) Human osteoblasts from younger normal and osteoporotic donors show differences in proliferation and TGF beta-release in response to cyclic strain. J Biomech 28:1411–1418
Klein-Nulend J, Sterck JG, Semeins CM, Lips P, Joldersma M, Baart JA, Burger EH (2002) Donor age and mechanosensitivity of human bone cells. Osteoporos Int 13:137–146
Joldersma M, Burger EH, Semeins CM, Klein-Nulend J (2000) Mechanical stress induces COX-2 mRNA expression in bone cells from elderly women. J Biomech 33:53–61
Todd JA, Robinson RJ (2003) Osteoporosis and exercise. Postgrad Med J 79:320–323
Marcus R (2001) Role of exercise in preventing and treating osteoporosis. Rheum Dis Clin North Am 27:131–141, vi
Kemmler W, Lauber D, Weineck J, Hensen J, Kalender W, Engelke K (2004) Benefits of 2 years of intense exercise on bone density, physical fitness, and blood lipids in early postmenopausal osteopenic women: results of the Erlangen Fitness Osteoporosis Prevention Study (EFOPS). Arch Intern Med 164:1084–1091
Chien MY, Wu YT, Hsu AT, Yang RS, Lai JS (2000) Efficacy of a 24-week aerobic exercise program for osteopenic postmenopausal women. Calcif Tissue Int 67:443–448
Iwamoto J, Takeda T, Ichimura S (2001) Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis. J Orthop Sci 6:128–132
Joldersma M, Klein-Nulend J, Oleksik AM, Heyligers IC, Burger EH (2001) Estrogen enhances mechanical stress-induced prostaglandin production by bone cells from elderly women. Am J Physiol Endocrinol Metab 280:E436–442
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Augat, P., Simon, U., Liedert, A. et al. Mechanics and mechano-biology of fracture healing in normal and osteoporotic bone. Osteoporos Int 16 (Suppl 2), S36–S43 (2005). https://doi.org/10.1007/s00198-004-1728-9
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DOI: https://doi.org/10.1007/s00198-004-1728-9