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Multiscale Predictors of Femoral Neck In Situ Strength in Aging Women: Contributions of BMD, Cortical Porosity, Reference Point Indentation, and Nonenzymatic Glycation.

ABSTRACT: The diagnosis of fracture risk relies almost solely on quantifying bone mass, yet bone strength is governed by factors at multiple scales including composition and structure that contribute to fracture resistance. Furthermore, aging and conditions such as diabetes mellitus alter fracture incidence independently of bone mass. Therefore, it is critical to incorporate other factors that contribute to bone strength in order to improve diagnostic specificity of fracture risk. We examined the correlation between femoral neck fracture strength in aging female cadavers and areal bone mineral density, along with other clinically accessible measures of bone quality including whole-bone cortical porosity (Ct.Po), bone material mechanical behavior measured by reference point indentation (RPI), and accumulation of advanced glycation end-products (AGEs). All measurements were found to be significant predictors of femoral neck fracture strength, with areal bone mineral density (aBMD) being the single strongest correlate (aBMD: r?=?0.755, p?

SUBMITTER: Abraham AC

PROVIDER: S-EPMC4673035 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Multiscale Predictors of Femoral Neck In Situ Strength in Aging Women: Contributions of BMD, Cortical Porosity, Reference Point Indentation, and Nonenzymatic Glycation.

Abraham Adam C AC Agarwalla Avinesh A Yadavalli Aditya A McAndrew Christopher C Liu Jenny Y JY Tang Simon Y SY

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20150714 12

The diagnosis of fracture risk relies almost solely on quantifying bone mass, yet bone strength is governed by factors at multiple scales including composition and structure that contribute to fracture resistance. Furthermore, aging and conditions such as diabetes mellitus alter fracture incidence independently of bone mass. Therefore, it is critical to incorporate other factors that contribute to bone strength in order to improve diagnostic specificity of fracture risk. We examined the correlat ...[more]

PMID: 26060094

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Project description:The assessment of fracture risk often relies primarily on measuring bone mineral density, thereby accounting for only a single pathology: the loss of bone mass. However, bone's ability to resist fracture is a result of its biphasic composition and hierarchical structure that imbue it with high strength and toughness. Reference point indentation (RPI) testing is designed to directly probe bone mechanical behavior at the microscale in situ, although it remains unclear which aspects of bone composition and structure influence the results at this scale. Therefore, our goal in this study was to investigate factors that contribute to bone mechanical behavior measured by cyclic reference point indentation, impact reference point indentation, and three-point bending. Twenty-eight female cadavers (ages 57-97) were subjected to cyclic and impact RPI in parallel at the unmodified tibia mid-diaphysis. After RPI, the middiaphyseal tibiae were removed, scanned using micro-CT to obtain cortical porosity (Ct.Po.) and tissue mineral density (TMD), then tested using three-point bending, and lastly assayed for the accumulation of advanced glycation end-products (AGEs). Both the indentation distance increase from cyclic RPI (IDI) and bone material strength index from impact RPI (BMSi) were significantly correlated with TMD (r=-0.390, p=0.006; r=0.430, p=0.002; respectively). Accumulation of AGEs was significantly correlated with IDI (r=0.281, p=0.046), creep indentation distance (CID, r=0.396, p=0.004), and BMSi (r=-0.613, p<0.001). There were no significant relationships between tissue TMD or AGEs accumulation with the quasi-static material properties. Toughness decreased with increasing tissue Ct.Po. (r=-0.621, p<0.001). Other three-point bending measures also correlated with tissue Ct.Po. including the bending modulus (r=-0.50, p<0.001) and ultimate stress (r=-0.56, p<0.001). The effects of Ct.Po. on indentation were less pronounced with IDI (r=0.290, p=0.043) and BMSi (r=-0.299, p=0.037) correlated modestly with tissue Ct.Po. These results suggest that RPI may be sensitive to bone quality changes relating to collagen.

Project description:Antiresorptive denosumab is known to improve the quality and strength of cortical bone in the proximal femurs of osteoporotic women, but its efficacy in preventing periprosthetic bone loss and reducing femoral stem migration has not been studied in women undergoing cementless total hip arthroplasty. We conducted a single-center, randomized, double-blinded, placebo-controlled trial of 65 postmenopausal women with primary hip osteoarthritis and Dorr type A or B proximal femur anatomy. The patients randomly received subcutaneous injections of denosumab 60?mg or placebo once every 6 months for 12 months, starting 1 month before surgery. The primary endpoint was the change in bone mineral density (BMD) of the proximal femur (Gruen zone 7) at week 48, and the secondary endpoint was stem subsidence measured by radiostereometric analysis (RSA) at week 48. Exploratory endpoints included changes in BMDs of the contralateral hip, lumbar spine and distal radius, serum levels of bone turnover markers, walking speed, walking activity, patient-reported outcome measures, and radiographic assessment of stem osseointegration. The participants underwent vertebral-fracture assessment in an extension safety study at 3 years. Denosumab significantly decreased bone loss in the medial femoral neck (zone 7) and increased periprosthetic BMD in the greater trochanteric region (zone 1) and lesser trochanteric region (zone 6). Denosumab did not reduce temporary femoral stem migration. The migration occurred mainly during the settling period (0 to 12 weeks) after implantation of the prosthesis. All of the stems osseointegrated, as evaluated by RSA and radiographs. There were no intergroup differences in functional recovery. Discontinuation of denosumab did not lead to any adverse events. In conclusion, denosumab increased periprosthetic BMD in the clinically relevant regions of the proximal femur, but the treatment response was not associated with any reduction of initial stem migration. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Dataset Information

Multiscale Predictors of Femoral Neck In Situ Strength in Aging Women: Contributions of BMD, Cortical Porosity, Reference Point Indentation, and Nonenzymatic Glycation.

Publications

Multiscale Predictors of Femoral Neck In Situ Strength in Aging Women: Contributions of BMD, Cortical Porosity, Reference Point Indentation, and Nonenzymatic Glycation.

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