Determinants of skeletal fragility

doi:10.1016/j.berh.2005.07.004

Best Practice & Research Clinical Rheumatology

Volume 19, Issue 6, December 2005, Pages 897-911

https://doi.org/10.1016/j.berh.2005.07.004 Get rights and content

Strategies to reduce fracture risk must be based on a sound understanding of the mechanisms that underline the increased incidence of fractures with age and with certain diseases. There is evidence that in addition to bone minerals density, other factors influence bone strength. The chapter reviews the biomechanical aspects of age-related fractures, including the interacting roles of traumatic loading and bone strength, and the factors that determine a bones resistances to fracture. Also discussed are the mechanisms by which anti-catabolic and anabolic therapies for osteoporosis may affect bone strength. Finally, several current and future methodologies for improving assessment of bone strength in patients are evaluated.

Section snippets

Biomechanics of age-related fractures

From a mechanical perspective, fractures represent a structural failure of the bone, whereby the forces applied to the bone exceed its load-bearing capacity (Figure 1). The forces applied to the bone will depend on the specific activity, and will vary with the rate and direction of the applied loads. For example, the loads applied to the proximal femur during a fall will depend on the height of the fall, the direction of the fall (forwards, backwards, sideways), the impact surface, the extent

Determinants of whole bone strength

The ability of a bone to resist fracture (or ‘whole bone strength’) depends on the amount of bone (i.e. mass), the spatial distribution of the bone mass (i.e. shape and microarchitecture), and the intrinsic properties of the materials that comprise the bone (Figure 3). Bone remodeling—specifically the balance between formation and resorption—is the biologic process that mediates changes in the traits that influence bone strength. Thus, diseases and drugs that impact bone remodeling will

Material versus structural properties of bone

In any discussion of bone strength, it is important to distinguish between the material and structural properties of bone. During any activity, a complex distribution of forces (or loads) is applied to the skeleton. With the imposition of these forces, bones undergo deformations. This relationship between the forces applied to the bone and the resulting deformations characterizes the structural behavior, or structural properties, of the whole bone. Thus, structural properties are influenced by

Role of bone geometry

With regard to whole bone biomechanical behavior, the overall size of the bone (i.e. mass) as well as its shape (i.e. distribution of mass) play important roles. Consistently, laboratory testing of the strength of human cadaveric vertebrae, distal radii and proximal femora has shown, not surprisingly, that larger bones are stronger than smaller bones.5, 28, 29, 30, 31 Moreover, clinical observations support the importance of bone size. For example, a decreased cross-sectional area of the radius

Trabecular microarchitecture

Although bone density is among the strongest predictors of the mechanical behavior of trabecular bone, both empirical observations and theoretical analyses show that aspects of the trabecular microarchitecture influence trabecular bone strength as well.14, 15, 44 Trabecular architecture can be described by the shape of the basic structural elements and their orientation. The trabecular structure is generally characterized by the number of trabeculae in a given volume, their average thickness,

Role of bone matrix properties

In addition to macro- and microarchitecture, features of the bone matrix itself influence bone mechanical properties. Thus, characteristics that affect bone mechanical properties include the composition of the matrix, include (but are not limited to) the relative ratio of inorganic (i.e. mineral) to organic (i.e. water, collagen and non-collagenous proteins); the degree of matrix mineralization; mineral crystal size and maturation; the extent and nature of collagen cross-links; and the amount

Summary

In summary, this chapter reviews several concepts related to the biomechanical aspects of skeletal fragility. First, fractures occur when the loads applied to bone exceed its strength. Therefore, strategies to reduce fractures should consider interventions aimed at reducing the loads applied to bone as well as to maintaining or increasing bone strength. Second, whole bone strength is determined by the amount of bone (i.e. size or mass), the spatial distribution of the bone mass (i.e. shape or

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Bone deconditioning during partial weight-bearing in rodents – A systematic review and meta-analysis
2022, Life Sciences in Space Research
Space agencies are preparing to send humans to the Moon (16% Earth's gravity) and Mars (38% Earth's gravity), however, there is limited evidence regarding the effects of hypogravity on the skeletal system. A novel rodent partial weight-bearing (PWB) model may provide insight into how human bone responds to hypogravity. The aim of this study was to perform a systematic review investigating the effect of PWB on the structure and function of rodent bone. Five online databases were searched with the following inclusion criteria: population (rodents), intervention (PWB for ≥1-week), control (full weight-bearing), outcomes (bone structure/function), and study design (animal intervention). Of the 2,993 studies identified, eight were included. The main findings were that partial weight-bearing exposure for 21–28 days at 20%, 40%, and 70% of full loading causes: (1) loss of bone mineral density, (2) loss of trabecular bone volume, thickness, number, and increased separation, (3) loss of cortical area and thickness, and 4) reduced bone stiffness and strength. These findings predominately relate the tibia/femur of young/mature female mice, however, their deconditioning response appeared similar, but not identical, to male rats. A dose-response trend was frequently observed between the magnitude of deconditioning and PWB level. The deconditioning patterns in PWB resembled those in rodents and humans exposed to microgravity and microgravity analogs. The present findings suggest that countermeasures against bone deconditioning may be required for humans exploring the Lunar and Martian surfaces.
A computational insight on damage-based constitutive modelling in femur mechanics
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Citation Excerpt :
Nevertheless, actual clinical standards suffer from a lack of specificity, resulting uneffective in a number of cases actually characterized by a high risk of fracture (Damron et al., 2016; Mac Niocaill et al., 2011; Seeman and Delmas, 2006; Stone et al., 2003; Damron et al., 2003). This limitation is essentially due to the fact that actual clinical assessment strategies disregard a number of subject-specific mechanical determinants, strictly related to specific loading characteristics, bone morphology, and dominant biomechanical features at both macro- and microscale (Bouxsein, 2005). Personalized finite-element (FE) modelling approaches, based on diagnostic imaging techniques, have been widely employed to investigate the mechanical behaviour of femurs, proving to be effective for tracing some quantitative and reliable estimates of femur fracture risk (Eggermont et al., 2020; Damron et al., 2016; Yosibash et al., 2014; Keyak et al., 2005).
The present paper addresses femur failure mechanics, by numerically investigating the influence of brittle/ quasi-brittle bone constitutive description when combined with several failure criteria and different descriptions of bone ultimate parameters. Starting from computed tomography images of an experimentally-tested cadaveric femur, the bone geometry has been reconstructed through a semi-automatic segmentation procedure, and patient-specific material properties have been derived. Loading-induced loss of structural integrity has been simulated through a progressive thermodynamically-based damage model, by introducing different strain- and stress-based damage evolution laws. An in-house displacement-driven incremental approach has been implemented in a finite element framework to mimic the in-vitro experimental procedure. An energy-based regularization technique allowed to obtain results which are mesh independent and therefore physically meaningful. Depending on the adopted modelling strategy, significant differences in terms of yield and failure load, as well as in fracture patterns, have been numerically experienced. Comparisons between the proposed numerical results and the available experimental outcomes have been carried out. For the femur model herein analysed, an elastic quasi-brittle bone description combined with strain-based failure criteria seems to be more effective in predicting the mechanical behaviour up to the fracture. Presented mesh-independent results therefore contribute to justify the need of damage-based approaches for predicting in an effective way failure mechanisms of femurs.
Local and global microarchitecture is associated with different features of bone biomechanics
2020, Bone Reports
Beside areal bone mineral density (aBMD), evaluation of fragility fracture risk mostly relies on global microarchitecture. However, microarchitecture is not a uniform network. Therefore, this study aimed to compare local structural weakness to global microarchitecture on whole vertebral bodies and to evaluate how local and global microarchitecture was associated with bone biomechanics.
From 21 human L3 vertebrae, aBMD was measured using absorptiometry. Parameters of global microarchitecture were measured using HR-pQCT: trabecular bone volume fraction (Tb.BV/TV_global), trabecular number, structure model index and connectivity density (Conn.D). Local minimal values of aBMD and Tb.BV/TV were identified in the total (Tt) or trabecular (Tb) area of each vertebral body. “Two dimensional (2D) local structural weakness” was defined as Tt.BMD_min, Tt.BV/TV_min and Tb.BV/TV_min. Mechanical testing was performed in 3 phases: 1/ initial compression until mild vertebral fracture, 2/ unloaded relaxation, and 3/ second compression until failure.
Initial and post-fracture mechanics were significantly correlated with bone mass, global and local microarchitecture. Tt.BMD_min, Tt.BV/TV_min, Tb.BV/TV_min, and initial and post-fracture mechanics remained significantly correlated after adjustment for aBMD or Tb.BV/TV_global (p < 0.001 to 0.038). The combination of the most relevant parameter of bone mass, global and local microarchitecture associated with failure load and stiffness demonstrated that global microarchitecture explained initial and post-fracture stiffness, while local structural weakness explained initial and post-fracture failure load (p < 0.001).
Local and global microarchitecture was associated with different features of vertebral bone biomechanics, with global microarchitecture controlling stiffness and 2D local structural weakness controlling strength. Therefore, determining both localized low density and impaired global microarchitecture could have major impact on vertebral fracture risk prediction.
Composition and characteristics of trabecular bone in osteoporosis and osteoarthritis
2020, Bone
Citation Excerpt :
Pathologies known to enlarge the HA crystal size in animal studies (i.e., ovariectomized mice, rachitic rats, and osteopontin-null mice) have been found to increase bone fragility, ductility, and brittleness [30]. Nevertheless, conditions which decrease the crystal size (i.e., Osteogenesis imperfecta mice, hypophosphatemic mice, osteopetrotic rats) have also been found to have a detrimental effect on the mechanical properties of bone causing brittleness and reduced ductility [30–32]. This relation between mechanical properties and the grain size of poly crystalline materials is well explained by the Hall-Petch model that stipulates that above a critical crystal size an inverse correlation exists between material toughness and crystal size while this relation is reversed when the crystal size falls beneath the optimal critical size.
Bone strength depends on multiple factors such as bone density, architecture and composition turnover. However, the role these factors play in osteoporotic fractures is not well understood.
The aim of this study was to analyze trabecular bone architecture, and its crystal and organic composition in humans, by comparing samples taken from patients who had a hip fracture (HF) and individuals with hip osteoarthritis (HOA).
The study included 31 HF patients and 42 cases of HOA who underwent joint replacement surgery between 1/1/2013 and 31/12/2013. Trabecular bone samples were collected from the femoral heads and analyzed using a dual-energy X-ray absorptiometry, micro-CT, and solid-state high-resolution magic-angle-spinning nuclear magnetic resonance (MAS-NMR) spectroscopy.
No differences in proton or phosphorus concentration were found between the two groups using ¹H single pulse, ³¹P single pulse, ³¹P single pulse with proton decoupling NMR spectroscopy, in hydroxyapatite (HA) c-axis or a-axis crystal length. Bone volume fraction (BV/TV), trabecular number (Tb.N), and bone mineral density (BMD) were higher in the HO group than in the HF group [28.6% ± 10.5 vs 20.3% ± 6.6 (p = 0.026); 2.58 mm⁻¹ ± 1.57 vs 1.5 mm⁻¹ ± 0.79 (p = 0.005); and 0.39 g/cm² ± 0.10 vs. 0.28 g/cm² ± 0.05 (p = 0.002), respectively]. The trabecular separation (Tp.Sp) was lower in the HO group 0.42 mm ± 0.23 compared with the HF group 0.58 mm ± 0.27 (p = 0.036). In the HO group, BMD was correlated with BV/TV (r = 0.704, p < 0.001), BMC (r = 0.853, p < 0.001), Tb.N (r = 0.653, p < 0.001), Tb.Sp (−0.561, p < 0.001) and ¹H concentration (−0.580, p < 0.001) in the HO group. BMD was not correlated with BV/TV, Tb.Sp, Tb.Th, Tb.N, Tb.PF, ¹H concentration or HA crystal size in the HF group.
Patients with HO who did not sustain previous hip fractures had a higher femoral head BMD, BV/TV, and Tb.N than HF patients. In HO patients, BMD was positively correlated with the BV/TV and Tb.N and negatively correlated with the femoral head organic content and trabecular separation. Interestingly, these correlations were not found in HF patients with relatively lower bone densities. Therefore, osteoporotic patients with similar low bone densities could have significant microstructural differences. No differences were found between the two groups at a HA crystal level.
Increasing fluoride content deteriorates rat bone mechanical properties
2020, Bone
Citation Excerpt :
Thus, we aimed to investigate how increased fluoride content affects bone mechanical properties. Among the factors that can affect whole bone mechanical behavior are bone density, geometry, microarchitecture, and inherent tissue mechanical properties [28]. Although the influences of bone geometry and microarchitecture on whole bone strength and fracture risk are well documented, the contribution of bone tissue material properties is less well understood [29,30].
Elevation of bone fluoride levels due to drinking beverages with high fluoride content or other means such as inhalation can result in skeletal fluorosis and lead to increased joint pain, skeletal deformities, and fracture. Because skeletal fluorosis alters bone's mineral composition, it is likely to affect bone's tissue-level mechanical properties with consequent effects on whole bone mechanical behavior. To investigate this, we determined whether incubation with in vitro sodium fluoride (NaF) altered bone's mechanical behavior at both the tissue- and whole bone-levels using cyclic reference point indentation (cRPI) and traditional 3-point bending, respectively. Forty-two ulnas from female adult rats (5–6 months) were randomly divided into 5 groups (vehicle, 0.05 M NaF, 0.25 M NaF, 0.75 M NaF, and 1.5 M NaF). Bones were washed in a detergent solution to remove organic barriers to ion exchange and incubated in respective treatment solutions (12 h, 23 °C). Cortical tissue mineral density (TMD) and geometry at the mid-diaphysis were determined by microCT. cRPI was performed on the distal diaphysis (9 N, 2 Hz, 10 cycles), and then bones were tested in 3-point bending to assess whole bone mechanical properties. The incubations in vehicle (0 M) up to 1.5 M in vitro NaF concentrations achieved bone fluoride levels ranging from approximately 0.70 to 15.8 ppm. NaF-incubated bones had significantly greater indentation distances, higher displacement-to-maximum force, and lower estimated elastic modulus, ultimate stress, and bending rigidity with increasing NaF concentration compared to vehicle-incubated bones. cRPI variables were moderately correlated to whole bone mechanical properties such that higher indentation distances were associated with lower estimated elastic modulus, ultimate stress, and bending rigidity. In conclusion, in vitro NaF incubation mostly has a deleterious effect on bone mechanical behavior with increasing NaF levels that is independent of bone turnover and reflected, in part, by less resistance of the tissue to cRPI-based indentation.
Trabecular bone score and bone quantitative ultrasound in Spanish postmenopausal women. The Camargo Cohort Study
2020, Maturitas
To evaluate trabecular bone score (TBS) in Spanish postmenopausal women from our area. To analyze its relationship with bone mineral density (BMD), bone quantitative ultrasound (QUS) and serum concentrations of 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (PTH) and bone turnover markers.
A total of 1450 postmenopausal women aged 44–94 (62 ± 10) participated in this cross-sectional study nested in a population-based cohort. BMD and TBS were assessed by DXA. QUS measurements were performed using a Sahara Clinical Sonometer. Serum 25(OH)D, PTH, P1NP, β-CTX were determined by electrochemiluminescence.
Mean TBS of postmenopausal women in our region was 1.341 ± 0.111. Nearly 50 % of them had normal values. Only 11 % had scores compatible with a clearly degraded microarchitecture. TBS decreased with age, correlated negatively with BMI and was lower in current smokers than in non-smokers. An association was observed between TBS and QUS, although the association was weak and lower than that found between TBS and BMD or QUS and BMD. No association was found between TBS and 25(OH)D, PTH or bone turnover markers.
Half of postmenopausal women in our region have TBS values that indicate a preserved microarchitecture. Only about 10 % have scores compatible with a clearly degraded microarchitecture. A weak association was observed between TBS and QUS, suggesting that the two techniques capture different aspects of bone microarchitecture. The absence of association with 25(OH)D, PTH, and bone turnover markers may be due to the fact that TBS assesses a specific (mostly trabecular) part of the skeleton, whilst the three serum factors are related to the whole skeleton.

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2Determinants of skeletal fragility

Section snippets

Biomechanics of age-related fractures

Determinants of whole bone strength

Material versus structural properties of bone

Role of bone geometry

Trabecular microarchitecture

Role of bone matrix properties

Summary

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Journal of Biomechanics

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Osteoporosis prevention, diagnosis, and therapy

The Journal of the American Medical Association

Biomechanics of age-related fractures

Stress distributions within the proximal femur during gait and falls: implications for osteoporotic fracture

Osteoporosis International

Prediction of femoral fracture load using automated finite element modeling

Journal of Biomechanics

Type of fall and risk of hip and wrist fractures: the study of osteoporotic fractures

Journal of the American Geriatrics Society

Fall severity and bone mineral density as risk factors for hip fracture in ambulatory elderly

The Journal of the American Medical Association

Humeral hypertrophy in response to exercise

The Journal of Bone and Joint Surgery

A murine skeletal adaptation that significantly increases cortical bone mechanical properties

The Journal of Clinical Investigation

Bone quality: where do we go from here?

Osteoporosis International

Bone compressive strength: the influence of density and strain rate

Science

The compressive behavior of bone as a two-phase porous structure

The Journal of Bone and Joint Surgery

Biomechanics of trabecular bone

Annual Reviews in Biomedical Engineering

Effects of porosity and mineral content on the Young's modulus of bone

European Society of Biomechanics

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Determinants of skeletal fragility