A biomechanical perspective on bone quality

Abstract

Observations that dual-energy X-ray absorptiometry (DXA) measures of areal bone mineral density cannot completely explain fracture incidence after anti-resorptive treatment have led to renewed interest in bone quality. Bone quality is a vague term but generally refers to the effects of skeletal factors that contribute to bone strength but are not accounted for by measures of bone mass. Because a clinical fracture is ultimately a mechanical event, it follows then that any clinically relevant modification of bone quality must change bone biomechanical performance relative to bone mass. In this perspective, we discuss a framework for assessing the clinically relevant effects of bone quality based on two general concepts: (1) the biomechanical effects of bone quality can be quantified from analysis of the relationship between bone mechanical performance and bone density; and (2) because of its hierarchical nature, biomechanical testing of bone at different physical scales (<1 mm, 1 mm, 1 cm, etc.) can be used to isolate the scale at which the most clinically relevant changes in bone quality occur. As an example, we review data regarding the relationship between the strength and density in excised specimens of trabecular bone and highlight the fact that it is not yet clear how this relationship changes during aging, osteoporosis development, and anti-resorptive treatment. Further study of new and existing data using this framework should provide insight into the role of bone quality in osteoporotic fracture risk.

Figure 1

In the current discussion bone quality is defined as the effects of characteristics of bone that influence bone’s ability to resist fracture but are not explained by measures of bone mass (the arrow on the right side). Others have proposed that bone quality refers to all the characteristics of bone that influence resistance to fracture (the rectangle at the bottom of the image).

Figure 2

A hypothetical biomechanical analysis of the strength-density relationships for bone from a normal control group compared to that from bone from two different treatment groups. Both treatment groups show the same increase in bone strength. (A) The relationship between bone strength and density in bone exposed to Treatment 1 has an increased slope, indicating improved bone quality. Bone exposed to Treatment 2 shows a similar relationship between bone strength and density as compared to the normal control group suggesting that it is not different in terms of bone quality. (B) The ratio of bone strength to density in samples exposed to Treatment 1 is greater than that in the other groups suggesting that bone quality has been improved.

Figure 3

A conceptual diagram illustrating the relationship between the hierarchical nature of aspects of bone quality is shown. Mechanical testing at the scale of 5 mm (indicated by the horizontal line) will characterize the net effects of lower scale factors such as microarchitecture, bone volume fraction and the mechanical properties of the mineralized tissue (strength, toughness, fatigue, etc.) that are all determined at even lower scales. If changes in bone quality cannot be detected through mechanical testing at the scale of 5 mm then any net changes in whole bone quality must originate at a higher scale or not at all.

Figure 4

The relationships between trabecular bone ultimate strength in compression (σ_ult) and apparent density (ρ) in various regions of the skeleton are shown (A, B). The strength:density ratio in each of these regions was also found to vary with density (C, D). Significant linear regressions for each region are shown (p <0.05). Regions are noted as follows: VB – vertebral body (199 specimens taken from 3 males aged 70, 77 and 84 years), VB*-vertebral body (30 specimens from 16 males and 9 females aged 20-90), FN – femoral neck (29 specimens from 15 males and 8 females age range 49–101), DF – distal femur (average value per donor from 255 samples among a cohort including 25 males and 19 females aged 20–102), GT- greater trochanter (10 specimens from 16 males and 5 females aged 49–87), PT – Proximal Tibia (15 samples from 15 males aged 40–84). Data marked DF is taken from McCalden [24]. Data marked VB is from a set of samples reported by Keller [23]. Data marked with a * was collected in our laboratory [25] and was converted from measured yield strength values (σ_ult = 1.2(σ_y) [64]. Vertebral body data has been pooled.

Figure 5

Strength:density ratios (mean ± SD) for the data in Figure 3 are shown. Significant differences in the strength:density ratio exist between sites indicate differences in bone quality (ANOVA with Tukey post-hoc). Groups having the same lower case letters are not significantly different from one another. See key to Figure 3.

Figure 6

Aging effects on the strength:density ratio for vertebral trabecular bone are shown. VB - Data converted from reported measures of ultimate load/ash density [40] assuming a constant degree of mineralization (ash mass/total mass = 0.67 [18]) and normalized by average strength/average apparent density (27 females, 15 males). VB* - Data from our laboratory (30 specimens from 16 males and 9 females) using ultimate strength calculated from measured yield properties ((σ_ult = 1.2(σ_y) [64]. Both groups show significant declines with age (p<0.05). The pooled r² value is shown.