Microdamage caused by fatigue loading in human cancellous bone: relationship to reductions in bone biomechanical performance

Abstract

Vertebral fractures associated with osteoporosis are often the result of tissue damage accumulated over time. Microscopic tissue damage (microdamage) generated in vivo is believed to be a mechanically relevant aspect of bone quality that may contribute to fracture risk. Although the presence of microdamage in bone tissue has been documented, the relationship between loading, microdamage accumulation and mechanical failure is not well understood. The aim of the current study was to determine how microdamage accumulates in human vertebral cancellous bone subjected to cyclic fatigue loading. Cancellous bone cores (n = 32) from the third lumbar vertebra of 16 donors (10 male, 6 female, age 76 ± 8.8, mean ± SD) were subjected to compressive cyclic loading at σ/E0 = 0.0035 (where σ is stress and E0 is the initial Young's modulus). Cyclic loading was suspended before failure at one of seven different amounts of loading and specimens were stained for microdamage using lead uranyl acetate. Damage volume fraction (DV/BV) varied from 0.8 ± 0.5% (no loading) to 3.4 ± 2.1% (fatigue-loaded to complete failure) and was linearly related to the reductions in Young's modulus caused by fatigue loading (r(2) = 0.60, p<0.01). The relationship between reductions in Young's modulus and proportion of fatigue life was nonlinear and suggests that most microdamage generation occurs late in fatigue loading, during the tertiary phase. Our results indicate that human vertebral cancellous bone tissue with a DV/BV of 1.5% is expected to have, on average, a Young's modulus 31% lower than the same tissue without microdamage and is able to withstand 92% fewer cycles before failure than the same tissue without microdamage. Hence, even small amounts of microscopic tissue damage in human vertebral cancellous bone may have large effects on subsequent biomechanical performance.

Figure 1. Fatigue loading of cancellous bone.

(A) A creep-fatigue curve is shown. Lines represent minimum and maximum strain per cycle, as indicated in the inset. The creep-fatigue curve consists of three phases: the primary phase where the strain accumulation per cycle decreases, the secondary phase where the strain accumulation per cycle is constant, and the tertiary phase where the strain accumulation per cycle increases. (B) Stress-strain plots for the first load cycle (N₁) and a later load cycle (N_i) are shown. Mechanical properties measured within the loading cycle include the Young’s modulus (E, shown in red), energy dissipation (U, measured as the area labeled in blue), maximum strain_i = creep strain_i+cyclic strain_i.

Figure 2. Reduction in Young’s modulus with fatigue loading.

(A) Reduction in Young’s modulus for 6 samples loaded to failure is shown. Each color represents a different specimen. (B) The average reduction in Young’s modulus of all samples loaded to failure is shown relative to the proportion of fatigue life used. The numbers and colored ranges on the curve indicate the points where fatigue loading was stopped for each group (the range shown in the inset).

Figure 3. The distribution of DV/BV and mechanical properties for each of the groups.

Colors represent different donors. Female donors are shown as circles, male donors as squares. Lines connect specimens from the same donor. (A) Reduction in Young’s modulus (r² = 0.96, p<0.01), (B) Damage volume fraction (r² = 0.71, p<0.01), (C) Maximum strain (r² = 0.93, p<0.01), and (D) Maximum energy dissipation (r² = 0.65, p<0.01) were increased in groups experiencing more fatigue loading.

Figure 4. Visualization of microdamage in cancellous bone.

Red represents microdamage and transparent white represents bone. Shown are two specimens from the same donor subjected to (A) No loading (Group 1) and (B) Fatigue loading in group 5 (Young’s modulus was reduced by 42%). (C) An enlarged view of a damage site in the cancellous bone is shown.

Figure 5. Changes in mechanical properties with fatigue loading.

(A) The proportion of creep strain to maximum strain is shown for the six specimens fatigue loaded to failure. Each color represents a different specimen. (B) The alterations in modulus and energy dissipation in one specimen fatigue loaded to failure is shown. Modulus reduction increased progressively throughout fatigue loading, with a rapid loss in stiffness close to failure. Energy dissipation remained relatively constant until in the tertiary phase, where it increased rapidly.

Figure 6. The relationships between DV/BV and mechanical properties.

A positive relation between DV/BV and (A) reduction in Young’s modulus (r² = 0.60, p<0.01); and (B) maximum strain applied during cyclic loading (r² = 0.61, p<0.01) was observed. Dotted lines indicate the 95% confidence interval of the regression line.

Figure 7. The estimated relationship between the amount of microdamage (DV/BV) and the proportion of fatigue life used (N/N_f).

The relationship is derived from the average reduction in Young’s modulus in Fig. 2B and regression model in Fig. 6A. Error bars in blue indicate the 95% confidence intervals at specified points.