title: Can deterministic mechanical size effects contribute to fracture and microdamage accumulation in trabecular bone?
abstract: Failure of bone under monotonic and cyclic loading is related to the bone mineral density, the quality of the bone matrix, and the evolution of microcracks. The theory of linear elastic fracture mechanics has commonly been applied to describe fracture in bone. Evidence is presented that bone failure can be described through a non-linear theory of fracture. Thereby, deterministic size effects are introduced. Concepts of a non-linear theory are applied to discern how the interaction among bone matrix constituents (collagen and mineral), microcrack characteristics, and trabecular architecture can create distinctively differences in the fracture resistance at the bone tissue level. The non-linear model is applied to interpret pre-clinical data concerning the effects of anti-osteoporotic agents on bone properties. The results show that bisphosphonate (BP) treatments that suppress bone remodeling will change trabecular bone in ways such that the size of the failure process zone relative to the trabecular thickness is reduced. Selective estrogen receptor modulators (SERMs) that suppress bone remodeling will change trabecular bone in ways such that the size of the failure process zone relative to the trabecular thickness is increased. The consequences of these changes are reflected in bone mechanical response and predictions are consistent with experimental observations in the animal model which show that BP treatment is associated with more brittle fracture and microcracks without altering the average length of the cracks, whereas SERM treatments lead to a more ductile fracture and mainly increase crack length with a smaller increase in microcrack density. The model suggests that BPs may be more effective in cases in which bone mass is very low, whereas SERMS may be more effective when milder osteoporotic symptoms are present.
authors.affiliation: School of Mechanical Engineering, Purdue University, 585 Purdue Mall, West Lafayette, IN 47907, USA. siegmund@purdue.edu
authors.forename: Thomas
authors.initials: T
authors.lastname: Siegmund
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Allen
authors.forename: David B
authors.initials: DB
authors.lastname: Burr
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology; D004285:Dogs; D005260:Female; D050723:Fractures, Bone / Q000473:pathology* / Q000503:physiopathology*; D008954:Models, Biological; D009929:Organ Size / Q000187:drug effects; D015203:Reproducibility of Results; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology
chemical_list: D004164:Diphosphonates; D020845:Selective Estrogen Receptor Modulators; D003094:Collagen
references.citation: J Biomed Mater Res A. 2006 Dec 1;79(3):747-51
references.pmid: 17013865
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17741-6
references.pmid: 17095608
references.citation: J Biomech. 2003 Sep;36(9):1343-53
references.pmid: 12893043
references.citation: Bone. 2006 Aug;39(2):289-99
references.pmid: 16540385
references.citation: J Biomech. 2008;41(3):603-9
references.pmid: 18023446
references.citation: Proc Natl Acad Sci U S A. 2003 May 13;100(10):5597-600
references.pmid: 12732735
references.citation: J Biomech. 2008;41(7):1427-35
references.pmid: 18406410
references.citation: J Biomech Eng. 2003 Dec;125(6):785-93
references.pmid: 14986402
references.citation: Comput Methods Biomech Biomed Engin. 2010 Oct;13(5):605-15
references.pmid: 20077238
references.citation: Bone. 1996 Aug;19(2):89-95
references.pmid: 8853850
references.citation: J Mech Behav Biomed Mater. 2008 Jan;1(1):59-67
references.pmid: 19627772
references.citation: J Biomech. 2009 Jan 5;42(1):22-8
references.pmid: 19056085
references.citation: Bone. 1993 Jul-Aug;14(4):595-608
references.pmid: 8274302
references.citation: Bone. 2006 Nov;39(5):1130-1135
references.pmid: 16814622
references.citation: Endocrinology. 2007 Aug;148(8):3908-13
references.pmid: 17478550
references.citation: J Theor Biol. 2000 Sep 21;206(2):299-306
references.pmid: 10966766
references.citation: Biophys J. 2000 Oct;79(4):1737-46
references.pmid: 11023882
references.citation: J Biomech. 2008;41(2):259-66
references.pmid: 17981285
references.citation: Bone. 1994 Jan-Feb;15(1):105-9
references.pmid: 8024844
references.citation: J Biomech. 2006;39(16):2974-82
references.pmid: 16375909
references.citation: Osteoporos Int. 2008 Mar;19(3):329-37
references.pmid: 18094911
references.citation: Bone. 2004 May;34(5):790-8
references.pmid: 15121010
references.citation: Biomaterials. 2006 Mar;27(9):2095-113
references.pmid: 16271757