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Microdamage repair and remodeling requires mechanical loading

  1. Erik I Waldorff1,
  2. Katya B Christenson1,
  3. Laura A Cooney2,
  4. Steven A Goldstein1,*

Article first published online: 14 DEC 2009

DOI: 10.1359/jbmr.091016

Issue

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Volume 25, Issue 4, pages 734–745, April 2010

Additional Information

How to Cite

Waldorff, E. I., Christenson, K. B., Cooney, L. A. and Goldstein, S. A. (2010), Microdamage repair and remodeling requires mechanical loading. J Bone Miner Res, 25: 734–745. doi: 10.1359/jbmr.091016

Author Information

  1. 1

    Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA

  2. 2

    Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA

*Orthopaedic Research Laboratories, University of Michigan, 2001 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.

Publication History

  1. Issue published online: 9 APR 2010
  2. Article first published online: 14 DEC 2009
  3. Accepted manuscript online: 27 JAN 2010 12:00AM EST
  4. Manuscript Accepted: 9 OCT 2009
  5. Manuscript Revised: 14 JUL 2009
  6. Manuscript Received: 25 NOV 2008

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References

  • 1
    Riggs BL, Melton LJ 3rd. The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone. 1995; 17: 505–511S.
  • 2
    Verborgt O, Gibson GJ, Schaffler MB. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J Bone Miner Res. 2000; 15: 60–67.
    Direct Link:
  • 3
    Verborgt O, Tatton NA, Majeska RJ, Schaffler MB. Spatial distribution of Bax and Bcl-2 in osteocytes after bone fatigue: complementary roles in bone remodeling regulation? J Bone Miner Res. 2002; 17: 907–914.
    Direct Link:
  • 4
    Burr DB, Martin RB, Schaffler MB, Radin EL. Bone remodeling in response to in vivo fatigue microdamage. J Biomech. 1985; 18: 189–200.
  • 5
    Bentolila V, Boyce TM, Fyhrie DP, Drumb R, Skerry TM, Schaffler MB. Intracortical remodeling in adult rat long bones after fatigue loading. Bone. 1998; 23: 275–281.
  • 6
    Mori S, Burr DB. Increased intracortical remodeling following fatigue damage. Bone. 1993; 14: 103–109.
  • 7
    Burr DB, Martin RB. Calculating the probability that microcracks initiate resorption spaces. J Biomech. 1993; 26: 613–616.
  • 8
    Lee TC, Staines A, Taylor D. Bone adaptation to load: microdamage as a stimulus for bone remodelling. J Anat. 2002; 201: 437–446.
    Direct Link:
  • 9
    Cardoso L, Herman BC, Verborgt O, Laudier D, Majeska RJ, Schaffler MB. Osteocyte apoptosis controls activation of intracortical resorption in response to bone fatigue. J Bone Miner Res. 2009; 24: 597–605.
    Direct Link:
  • 10
    Burr DB, Forwood MR, Fyhrie DP, Martin RB, Schaffler MB, Turner CH. Bone microdamage and skeletal fragility in osteoporotic and stress fractures. J Bone Miner Res. 1997; 12: 6–15.
    Direct Link:
  • 11
    Waldorff EI, Goldstein SA, McCreadie BR. Age-dependent microdamage removal following mechanically induced microdamage in trabecular bone in vivo. Bone. 2007; 40: 425–432.
  • 12
    Inoue M, Tanaka H, Moriwake T, Oka M, Sekiguchi C, Seino Y. Altered biochemical markers of bone turnover in humans during 120 days of bed rest. Bone. 2000; 26: 281–286.
  • 13
    Kim H, Iwasaki K, Miyake T, Shiozawa T, Nozaki S, Yajima K. Changes in bone turnover markers during 14-day 6 degrees head-down bed rest. J Bone Miner Metab. 2003; 21: 311–315.
  • 14
    Vico L, Collet P, Guignandon A, et al. Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet. 2000; 355: 1607–1611.
  • 15
    Caillot-Augusseau A, Vico L, Heer M, et al. Space flight is associated with rapid decreases of undercarboxylated osteocalcin and increases of markers of bone resorption without changes in their circadian variation: observations in two cosmonauts. Clin Chem. 2000; 46: 1136–1143.
  • 16
    Morey-Holton ER, Globus RK. Hindlimb unloading rodent model: technical aspects. J Appl Physiol. 2002; 92: 1367–1377.
  • 17
    Morey-Holton ER, Globus RK. Hindlimb unloading of growing rats: a model for predicting skeletal changes during space flight. Bone. 1998; 22: 83–88S.
  • 18
    Wronski TJ, Morey-Holton ER. Skeletal response to simulated weightlessness: a comparison of suspension techniques. Aviat Space Environ Med. 1987; 58: 63–68.
  • 19
    Bloomfield SA, Allen MR, Hogan HA, Delp MD. Site- and compartment-specific changes in bone with hindlimb unloading in mature adult rats. Bone. 2002; 31: 149–157.
  • 20
    Sakata T, Halloran BP, Elalieh HZ, et al. Skeletal unloading induces resistance to insulin-like growth factor I on bone formation. Bone. 2003; 32: 669–680.
  • 21
    Sakata T, Wang Y, Halloran BP, Elalieh HZ, Cao J, Bikle DD. Skeletal unloading induces resistance to insulin-like growth factor-I (IGF-I) by inhibiting activation of the IGF-I signaling pathways. J Bone Miner Res. 2004; 19: 436–446.
    Direct Link:
  • 22
    Bloomfield SA. Does altered blood flow to bone in microgravity impact on mechanotransduction? J Musculoskelet Neuronal Interact. 2006; 6: 324–326.
  • 23
    Stevens HY, Meays DR, Frangos JA. Pressure gradients and transport in the murine femur upon hindlimb suspension. Bone. 2006; 39: 565–572.
  • 24
    Knothe Tate ML, Knothe U, Niederer P. Experimental elucidation of mechanical load-induced fluid flow and its potential role in bone metabolism and functional adaptation. Am J Med Sci. 1998; 316: 189–195.
  • 25
    Knothe Tate ML, Niederer P, Knothe U. In vivo tracer transport through the lacunocanalicular system of rat bone in an environment devoid of mechanical loading. Bone. 1998; 22: 107–117.
  • 26
    Smith SM, Davis-Street JE, Fesperman JV, et al. Evaluation of treadmill exercise in a lower body negative pressure chamber as a countermeasure for weightlessness-induced bone loss: a bed rest study with identical twins. J Bone Miner Res. 2003; 18: 2223–2230.
    Direct Link:
  • 27
    Zwart SR, Hargens AR, Lee SM, et al. Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins. Bone. 2007; 40: 529–537.
  • 28
    Zhang LF, Sun B, Cao XS, et al. Effectiveness of intermittent –Gx gravitation in preventing deconditioning due to simulated microgravity. J Appl Physiol. 2003; 95: 207–218.
  • 29
    Ballas MT, Tytko J, Cookson D. Common overuse running injuries: diagnosis and management. Am Fam Physician. 1997; 55: 2473–2484.
  • 30
    Knobloch K, Schreibmueller L, Jagodzinski M, Zeichen J, Krettek C. Rapid rehabilitation programme following sacral stress fracture in a long-distance running female athlete. Arch Orthop Trauma Surg. 2007; 127: 809–813.
  • 31
    Turner CH, Akhter MP, Raab DM, Kimmel DB, Recker RR. A noninvasive, in vivo model for studying strain adaptive bone modeling. Bone. 1991; 12: 73–79.
  • 32
    Midura RJ, Su X, Androjna C. A simulated weightlessness state diminishes cortical bone healing responses. J Musculoskel Neuronal Interact. 2006; 6: 327–328.
  • 33
    Waldorff EI. Effects of aging and disuse on bone remodeling in response to microdamage. PhD dissertation, Department of Biomedical Engineering, University of Michigan, Ann Arbor, 2008: 33–77 Available at http://hdl.handle.net/2027.42/61648.
  • 34
    Aicher A, Rentsch M, Sasaki K, et al. Nonbone marrow-derived circulating progenitor cells contribute to postnatal neovascularization following tissue ischemia. Circ Res. 2007; 100: 581–589.
  • 35
    Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest. 2003; 111: 1221–1230.
  • 36
    Burr DB, Hooser M. Alterations to the en bloc basic fuchsin staining protocol for the demonstration of microdamage produced in vivo. Bone. 1995; 17: 431–433.
  • 37
    Herman BC, Berman D, Majeska RJ, Jepsen KJ, Schaffler MB. Activation of Bone Remodeling after Fatigue: Differential Response to Linear Microcracks and Diffuse Damage. San Francisco: Orthopaedic Research Society, 2008: 898.
  • 38
    Filgueira L. Fluorescence-based staining for tartrate-resistant acidic phosphatase (TRAP) in osteoclasts combined with other fluorescent dyes and protocols. J Histochem Cytochem. 2004; 52: 411–414.
  • 39
    Sweat F, Puchtler H, Rosenthal SI. Sirius red F3ba as a stain for connective tissue. Arch Pathol. 1964; 78: 69–72.
  • 40
    Puchtler H, Meloan SN, Waldrop FS. Are picro-dye reactions for collagens quantitative? Chemical and histochemical considerations. Histochemistry. 1988; 88: 243–256.
  • 41
    Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992; 119: 493–501.
  • 42
    Strange R, Friis RR, Bemis LT, Geske FJ. Programmed cell death during mammary gland involution. Methods Cell Biol. 1995; 46: 355–368.
  • 43
    Tami AE, Nasser P, Schaffler MB, Knothe Tate ML. Noninvasive fatigue fracture model of the rat ulna. J Orthop Res. 2003; 21: 1018–1024.
    Direct Link:
  • 44
    Uthgenannt BA, Kramer MH, Hwu JA, Wopenka B, Silva MJ. Skeletal self-repair: stress fracture healing by rapid formation and densification of woven bone. J Bone Miner Res. 2007; 22: 1548–1556.
    Direct Link:
  • 45
    Uthgenannt BA, Silva MJ. Use of the rat forelimb compression model to create discrete levels of bone damage in vivo. J Biomech. 2007; 40: 317–324.
  • 46
    Matsuzaki H, Wohl GR, Novack DV, Lynch JA, Silva MJ. Damaging fatigue loading stimulates increases in periosteal vascularity at sites of bone formation in the rat ulna. Calcif Tissue Int. 2007; 80: 391–399.
  • 47
    Silva MJ, Touhey DC. Bone formation after damaging in vivo fatigue loading results in recovery of whole-bone monotonic strength and increased fatigue life. J Orthop Res. 2007; 25: 252–261.
    Direct Link:
  • 48
    Silva MJ, Uthgenannt BA, Rutlin JR, Wohl GR, Lewis JS, Welch MJ. In vivo skeletal imaging of 18F-fluoride with positron emission tomography reveals damage- and time-dependent responses to fatigue loading in the rat ulna. Bone. 2006; 39: 229–236.
  • 49
    Cao JJ, Kurimoto P, Boudignon B, Rosen C, Lima F, Halloran BP. Aging impairs IGF-I receptor activation and induces skeletal resistance to IGF-I. J Bone Miner Res. 2007; 22: 1271–1279.
    Direct Link:
  • 50
    Hsieh YF, Silva MJ. In vivo fatigue loading of the rat ulna induces both bone formation and resorption and leads to time-related changes in bone mechanical properties and density. J Orthop Res. 2002; 20: 764–771.
    Direct Link:
  • 51
    Delahunty KM, Horton LG, Coombs HF 3rd, et al. Gender- and compartment-specific bone loss in C57BL/6J mice: correlation to season? J Clin Densitom. 2009; 12: 89–94.
  • 52
    Isotupa K, Koski K. Trabecular architecture of the mandibular condyle of the rat as revealed by vital staining. Proc Finn Dent Soc. 1991; 87: 59–67.
  • 53
    Kogianni G, Mann V, Noble BS. Apoptotic bodies convey activity capable of initiating osteoclastogenesis and localized bone destruction. J Bone Miner Res. 2008; 23: 915–927.
    Direct Link:
  • 54
    Tatsumi S, Ishii K, Amizuka N, et al. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 2007; 5: 464–475.
  • 55
    Follet H, Li J, Phipps RJ, Hui S, Condon K, Burr DB. Risedronate and alendronate suppress osteocyte apoptosis following cyclic fatigue loading. Bone. 2007; 40: 1172–1177.
  • 56
    Aguirre JI, Plotkin LI, Stewart SA, et al. Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. J Bone Miner Res. 2006; 21: 605–615.
    Direct Link:
  • 57
    Basso N, Heersche JN. Effects of hind limb unloading and reloading on nitric oxide synthase expression and apoptosis of osteocytes and chondrocytes. Bone. 2006; 39: 807–814.
  • 58
    Hefferan TE, Evans GL, Lotinun S, Zhang M, Morey-Holton E, Turner RT. Effect of gender on bone turnover in adult rats during simulated weightlessness. J Appl Physiol. 2003; 95: 1775–1780.
  • 59
    Allen MR, Bloomfield SA. Hindlimb unloading has a greater effect on cortical compared with cancellous bone in mature female rats. J Appl Physiol. 2003; 94: 642–650.
  • 60
    Vico L, Bourrin S, Very JM, Radziszowska M, Collet P, Alexandre C. Bone changes in 6-month-old rats after head-down suspension and a reambulation period. J Appl Physiol. 1995; 79: 1426–1433.
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