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Clinical tools for evaluating fracture risk, such as dual energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS), focus on bone mineral and cannot detect changes in the collagen matrix that affect bone mechanical properties. However, the mechanical response tissue analyzer (MRTA) directly measures a whole bone mechanical property. The aims of our study were to investigate the changes in fatigue resistance after collagen degradation and to determine if clinical tools can detect changes in bone mechanical properties due to fatigue. Male and female emu tibiae were endocortically treated with 1 M KOH for 1–14 days and then either fatigued to failure or fatigued to induce stiffness loss without fracture. Partial fatigue testing caused a decrease in modulus measured by mechanical testing even when not treated with KOH, which was detected by MRTA. At high stresses, only KOH-treated samples had a lower fatigue resistance compared to untreated bones for both sexes. No differences were observed in fatigue behavior at low stresses for all groups. KOH treatment is hypothesized to have changed the collagen structure in situ and adversely affected the bone. Cyclic creep may be an important mechanism in the fast deterioration rate of KOH-treated bones, as creep is the major cause of fatigue failure for bones loaded at high stresses. Therefore, collagen degradation caused by KOH treatment may be responsible for the observed altered fatigue behavior at high stresses, since collagen is responsible for the creep behavior in bone. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:197–203, 2011

Young adults are at risk of stress fractures. Risk is higher in younger and female individuals. Stress fractures occur due to repeated loading of the bone (fatigue). We modeled this with rabbit tibiae. Age increased fatigue resistance which correlated with bone mineral density. A sex difference was not detected.Younger adults who engage in intense physical activity with a sudden increase in intensity level (military recruits/college athletes) are at risk of bone stress fractures. Risk is greater in females and diminishes with aging. Stress fractures may be the result of fatigue damage, which is not repaired rapidly enough to avoid fracture. It was hypothesized that the fatigue resistance of whole rabbit tibiae would be less in female specimens but greater as animal age increased.Rabbit tibiae were harvested from three age groups (4, 7, and ≥ 12 months (females only)). The tibiae were scanned with dual energy X-ray absorptiometry to determine bone mineral density (BMD), computed tomography to quantify geometry, and then fatigue tested in three-point bending.In the ≥ 12-month group, BMD was approximately 20% higher, while the fatigue resistance was found to be approximately ten times higher than the other age groups. Sex was not a factor in the 4- and 7-month groups. Multiple linear regression revealed that fatigue life was negatively correlated with applied stress range and positively correlated with BMD (adjusted r (2) = 0.69).A difference in fatigue behavior due to sex was not detected, but there was a large increase in fatigue resistance with age. This correlated with increased BMD and parallels a reduced risk of stress fracture due to age in military recruits. Skeletal "maturation" may play an important role in determining stress fracture risk. Increased risk in females may be due to mechanisms other than those that determine material behavior.