Differences in sensitivity to microstructure between cyclic- and impact-based microindentation of human cortical bone

Uppuganti, Sasidhar; Granke, Mathilde; Manhard, Mary Kate; Does, Mark D.; Perrien, Daniel S.; Lee, Donald H.; Nyman, Jeffry S.

doi:10.1002/jor.23392

Cited by 21 publications

(10 citation statements)

References 34 publications

(46 reference statements)

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“…The determinants of BMSi are poorly understood, (23) though reports indicate that BMSi is negatively associated with intracortical porosity and positively associated with the ultimate bending stress of cortical bone, (24) factors which would be expected to also relate to fracture risk. Similar to prior reports we found a weak negative association between BMSi and age, (15) and a weak positive association between BMSi and aBMD by DXA.…”

Section: Discussionmentioning

confidence: 99%

Bone Material Strength Index as Measured by Impact Microindentation in Postmenopausal Women With Distal Radius and Hip Fractures

Rozental

Walley

Demissie

et al. 2017

Journal of Bone and Mineral Research

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We tested whether cortical bone tissue properties assessed by in vivo impact microindentation would distinguish postmenopausal women with recent distal radius (DRF) or hip fracture (HF) from nonfracture controls (CONT). We enrolled postmenopausal women with recent DRF (n = 57), HF (n = 41), or CONT (n = 93), and used impact microindentation to assess bone material strength index (BMSi) at the anterior surface of the mid-tibia diaphysis. Areal bone mineral density (aBMD) (g/cm ) of the femoral neck (FN), total hip (TH), and lumbar spine (LS) were measured by dual-energy X-ray absorptiometry (DXA). HF and DRF subjects had significantly lower BMD than CONT at all sites (-5.6% to -8.2%, p < 0.001 for all). BMSi was 4% lower in DRF compared to CONT (74.36 ± 8.77 versus 77.41 ± 8.79, p = 0.04). BMSi was similarly lower in HF versus CONT, but the difference did not reach statistical significance (74.62 ± 8.47 versus 77.41 ± 8.79, p = 0.09). Lower BMSi was associated with increased risk of DRF (unadjusted OR, 1.43; 95% CI, 1.02 to 2.00, per SD decrease, p = 0.04), and remained statistically significant after adjustment for age, age and BMI, and age, BMI, and FN BMD (OR = 1.48 to 1.55). Lower BMSi tended to be associated with HF, but only reached borderline significance (unadjusted OR = 1.39; 95% CI, 0.96 to 2.01, p = 0.08). These results provide strong rationale for future investigations aimed at assessing whether BMSi can predict fracture in prospective studies and improve identification of women at risk for fragility fractures. © 2017 American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 99%

Bone Material Strength Index as Measured by Impact Microindentation in Postmenopausal Women With Distal Radius and Hip Fractures

Rozental

Walley

Demissie

et al. 2017

Journal of Bone and Mineral Research

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“…Traditional microindentation was additionally used to test our specimens. This is an established method to investigate elastic deformation properties of bone at the microscale . Results indicated that ribose‐treated specimens had lower maximum force and stiffness, contributing to the observed 75% and 77% lower elastic modulus on the OLT and IR surfaces, respectively, compared with vehicles.…”

Section: Discussionmentioning

confidence: 99%

In Vitro‐Induced High Sugar Environments Deteriorate Human Cortical Bone Elastic Modulus and Fracture Toughness

Merlo

Aaronson

Vaidya

et al. 2019

Journal Orthopaedic Research

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Advanced glycation end-products (AGEs) have been suggested to contribute to bone fragility in type 2 diabetes (T2D). AGEs can be induced through in vitro sugar incubations but there is limited data on the effect of total fluorescent AGEs on mechanical properties of human cortical bone, which may have altered characteristics in T2D. Thus, to examine the effect of AGEs on bone directly in T2D patients with uncontrolled sugar levels, it is essential to first understand the fundamental mechanisms by studying the effects of controlled in vitro-induced AGEs on cortical bone mechanical behavior. Here, human cortical bone specimens from female cadaveric tibias (ages 57-87) were incubated in an in vitro 0.6 M ribose or vehicle solution (n = 20/group) for 10 days at 37°C, their mechanical properties were assessed by microindentation and fracture toughness tests, and induced AGE levels were quantified through a fluorometric assay. Results indicated that ribose-incubated bone had significantly more AGEs (+81%, p ≤ 0.005), lower elastic modulus assessed by traditional microindentation, and lower fracture toughness compared with vehicle controls. Furthermore, based on pooled data, increased AGEs were significantly correlated with deteriorated mechanical properties. The findings presented here show that the accumulation of AGEs allows for lower stiffness and increased ability to initiate a crack in human cortical bone. Statement of clinical significance: High sugar levels as in T2D results in deteriorated bone quality via AGE accumulation with a consequent weakening in bone's mechanical integrity.

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“…In the same study, IDI and BMSi correlated with tissue mineral density roughly to the same degree (r = −0.390; r = 0.430, respectively). Uppuganti et al have also found correlations between quasi-static apparent level mechanical behavior in bending to be correlated with BMSi 55 , while Abraham et al 33 did not 33 (Table 3). Yet whole bone mechanical behavior appears to be correlated with IDI 51 , and Granke et al 56 found moderate correlations between IDI and femoral cortical beam bending parameters.…”

Section: Studies Comparing Osteoprobe Biodent and Whole-bone Behaviormentioning

confidence: 92%

“…However, cadaver studies provide the opportunity to compare the BioDent and Osteoprobe with other mechanical testing modalities 33,54,55 . Karim and co-authors suggest BioDent measures creep or fatigue crack growth from cyclic loading, whereas OsteoProbe is sensitive to energy dissipated from rapid loading 54 .…”

Section: Studies Comparing Osteoprobe Biodent and Whole-bone Behaviormentioning

confidence: 99%

“…Although Biodent and Osteoprobe measurements appear to be correlated in some cases, these measures appear to be differentially sensitive to various aspects of bone composition. For example, Uppuganti and colleagues 55 found cyclic RPI to be sensitive to tissue mineral density (r = −0.89), and OsteoProbe to be sensitive to cortical porosity (r = −0.90; Table 2). Abraham et al 33 found that BMSi was more strongly correlated with advanced glycation end product (AGEs) content (r = −0.613) than IDI (r = 0.281).…”

Section: Studies Comparing Osteoprobe Biodent and Whole-bone Behaviormentioning

confidence: 99%

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Clinical Measurements of Bone Tissue Mechanical Behavior Using Reference Point Indentation

Chang

Easson

Tang

2018

Clinic Rev Bone Miner Metab

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Over the last thirty years, it has become increasingly clear the amount of bone (e.g. ‘bone quantity’) and the quality of the bone matrix (e.g. ‘bone quality’) both critically contribute to bone’s tissue-level mechanical behavior and the subsequent ability of bone to resist fracture. Although determining the tissue-level mechanical behavior of bone through mechanical testing is relatively straightforward in the laboratory, the destructive nature of such testing is unfeasible in humans and in animal models requiring longitudinal observation. Therefore, surrogate measurements are necessary for quantifying tissue-level mechanical behavior for the pre-clinical and clinical evaluation of bone strength and fracture risk in vivo. A specific implementation of indentation known as reference point indentation (RPI) enables the mechanical testing of bone tissue without the need to excise and prepare the bone surface. However, this compromises the ability to carefully control the specimen geometry that is required to define the bone tissue material properties. Yet the versatility of such measurements in clinical populations is provocative, and to date there are a number of promising studies that have utilized this tool to discern bone pathologies and to monitor the effects of therapeutics on bone quality. Concurrently, on-going efforts continue to investigate the aspects of bone material behavior measured by RPI, and the compositional factors that contribute to these measurements. There are currently two variants, cyclic- and impact- RPI, that have been utilized in pre-clinical and clinical studies. This review surveys clinical studies that utilize RPI, with particular emphasis on the clinical instrument, as well as the endeavors to understand the fundamental mechanisms of such measurements. Ultimately, an improved awareness in the tradeoffs and limitations of in vivo RPI is critical towards the effective and successful utilization of this tool for the overall improvement of fragility determination in the clinic.

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Differences in sensitivity to microstructure between cyclic- and impact-based microindentation of human cortical bone

Cited by 21 publications

References 34 publications

Bone Material Strength Index as Measured by Impact Microindentation in Postmenopausal Women With Distal Radius and Hip Fractures

Bone Material Strength Index as Measured by Impact Microindentation in Postmenopausal Women With Distal Radius and Hip Fractures

In Vitro‐Induced High Sugar Environments Deteriorate Human Cortical Bone Elastic Modulus and Fracture Toughness

Clinical Measurements of Bone Tissue Mechanical Behavior Using Reference Point Indentation

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