The amount of bone remodeling in the skeleton has been associated with fracture risk independent of clinical measures of bone mineral density. This has led to the suggestion that bone remodeling can influence bone fragility independent of bone mass. Although many explanations have been proposed, it is currently not known how bone remodeling alone can influence bone strength independent of bone mass. In this work we evaluate the most commonly cited explanation for the effect of bone remodeling on bone strength: that cavities formed during the remodeling process (resorption cavities) act as microstructural flaws or stress risers. Resorption cavities may influence cancellous bone stiffness and strength under a single load or may lead to reductions in cancellous bone strength or stiffness by promoting the initiation and/or propagation of microscopic cracks and other tissue damage. This project is based on the hypothesis that resorption cavities impair bone stiffness and strength independent of bone mass.
The specific aims are to 1) determine how the number and morphology of resorption cavities influence the bone stiffness and strength of human cancellous bone and the degree to which resorption cavities are associated with microscopic tissue damage caused by a single loading event;2) determine if microscopic tissue damage caused by a single overloading event impairs cancellous bone strength under reloading;3) determine how microscopic tissue damage formed during cyclic loading is associated with reductions in cancellous bone stiffness;and 4) determine if resorption cavities promote the initiation or propagation of microscopic cracks during cyclic loading. Completing these aims will provide a quantitative evaluation of the most commonly cited explanation for the relationship between bone turnover and fracture risk.

Public Health Relevance

This project addressed the problem of osteoporosis-related fractures in the elderly by determining how measures of biological activity in the skeleton (bone remodeling) are related to the ability of bone to resist fracture. The proposed research has the potential to influence clinical decisions regarding the treatment and prevention of osteoporosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR057362-05
Application #
8438426
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Lester, Gayle E
Project Start
2010-03-01
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2015-02-28
Support Year
5
Fiscal Year
2013
Total Cost
$290,890
Indirect Cost
$85,690
Name
Cornell University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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Hernandez, C J; Lambers, F M; Widjaja, J et al. (2014) Quantitative relationships between microdamage and cancellous bone strength and stiffness. Bone 66:205-13
Hernandez, C J; Lopez, H K; Lane, J M (2014) Theoretical consideration of the effect of drug holidays on BMD and tissue age. Osteoporos Int 25:1577-84
Matheny, J B; Slyfield, C R; Tkachenko, E V et al. (2013) Anti-resorptive agents reduce the size of resorption cavities: a three-dimensional dynamic bone histomorphometry study. Bone 57:277-83
Goff, M G; Slyfield, C R; Kummari, S R et al. (2012) Three-dimensional characterization of resorption cavity size and location in human vertebral trabecular bone. Bone 51:28-37
Slyfield, C R; Tkachenko, E V; Fischer, S E et al. (2012) Mechanical failure begins preferentially near resorption cavities in human vertebral cancellous bone under compression. Bone 50:1281-7