Heterogeneity of bone tissue properties is emerging as a potential indicator of altered bone quality in pathologic tissue. The objective of this study was to compare the distributions of tissue properties in women with and without histories of fragility fractures using Fourier transform infrared (FTIR) imaging. We extended a prior study that examined the relationship of the mean FTIR properties to fracture risk by analyzing in detail the widths and the tails of the distributions of FTIR properties in biopsies from fracture and non-fracture cohorts. The mineral and matrix properties of cortical and trabecular iliac crest tissue were compared in biopsies from women with a history of fragility fracture (+Fx; n = 21, age: mean 54 ± SD 15 y) and with no history of fragility fracture (−Fx; n = 12, age: 57 ± 5 y). A subset of the patients included in the −Fx group were taking estrogen-plusprogestin hormone replacement therapy (HRT) (−Fx + HRT n = 8, age: 58 ± 5 y) and were analyzed separately from patients with no history of HRT (−Fx − HRT n = 4, age: 56 ± 7 y). When the FTIR parameter mean values were examined by treatment group, the trabecular tissue of −Fx−HRT patients had a lower mineral:matrix ratio (M:M) and collagen maturity (XLR) than that of −Fx + HRT patients (−22% M:M, −18% XLR) and +Fx patients (−17% M:M, −18% XLR). Across multiple FTIR parameters, tissue from the −Fx − HRT group had smaller lowtail (5th percentile) values than that from the −Fx + HRT or +Fx groups. In trabecular collagen maturity and crystallinity (XST), the −Fx − HRT group had smaller low-tail values than those in the –Fx + HRT group (−16% XLR, −5% XST) and the + Fx group (−17% XLR, −7% XST). The relatively low values of trabecular mineral:matrix ratio and collagen maturity and smaller low-tail values of collagen maturity and crystallinity observed in the −Fx − HRT group are characteristic of younger tissue. Taken together, our data suggest that the presence of newly formed tissue that includes small/imperfect crystals and immature crosslinks, as well as moderately mature tissue, is an important characteristic of healthy, fracture-resistant bone. Finally, the larger mean and low-tail values of mineral:matrix ratio and collagen maturity noted in our −Fx + HRT vs. −Fx−HRT biopsies are consistent with greater tissue age and greater BMD arising from decreased osteoclastic resorption in HRT-treated patients.
Heather Hunt will present an invited talk entitled, “Mechanical and Biochemical Assessment of Bone Quality in Type 2 Diabetics” at the NSF-sponsored 6th Advanced Study Institute on Global Healthcare Challenges held June 22-26 2015 in Izmir, Turkey.
Heterogeneity of material properties is an important potential contributor to bone fracture resistance because of its putative contribution to toughness, but establishing the contribution of heterogeneity to fracture risk is still in an incipient stage. Experimental studies have demonstrated changes in distributions of compositional and nanomechanical properties with fragility fracture history, disease, and pharmacologic treatment. Computational studies have demonstrated that models with heterogeneous material properties predict apparent stiffness moderately better than homogeneous models and show greater energy dissipation. Collectively, these results suggest that microscale material heterogeneity affects not only microscale mechanics but also structural performance at larger length scales.
The American Society for Bone and Mineral Research has awarded PhD student Ashley Lloyd a 2014 Young Investigator Award for her abstract “Cortical Tissue from Postmenopausal Women with Atypical Fractures Shows Reduced Heterogeneity in Nanomechanical Properties.” She will accept the award at the ASBMR Annual Meeting in Houston, TX September 11-15 2014.
PhD student Ashley Lloyd was selected to participate in the Endocrine Fellows Foundation/American Society for Bone and Mineral Research (ASBMR) Eighth Fellows Forum on Metabolic Bone Diseases. She will attend the forum prior to the 2014 ASBMR annual meeting at the at the Hilton Americas Houston, Houston, TX, September 10-11, 2014.
Michelle Chin was awarded an Engineering Learning Initiatives Undergraduate Research Award for her proposal entitled, “Effect of bisphosphonates on bone tissue composition in postmenopausal women with fragility fractures.” The ELI grant provides support for research expenses for her senior thesis work this fall. Congratulations Michelle!
The American Society for Bone and Mineral Research has awarded Prof. Donnelly the Harold M. Frost Young Investigator Award. She will accept the award at the Sun Valley Workshop on Skeletal Biology in Sun Valley, ID August 4-7 2013. More information is available at the ASBMR award announcement.
Michelle Chin was awarded an Engineering Learning Initiatives Undergraduate Research Award for her proposal entitled, “Effect of bisphosphonates on bone tissue composition in postmenopausal women with fragility fractures.” The ELI grant will support her work in the lab this summer. Congratulations Michelle!
Despite having higher than average bone density, patients with type 2 diabetes paradoxically have increased risk of fracture relative to individuals without diabetes. NIH/NIAMS has awarded Prof. Donnelly a career development grant to investigate the changes in collagen properties that occur in bone tissue with type 2 diabetes and their relationship to fracture risk. Key collaborators include Prof. Deepak Vashishth at Rensselaer Polytechnic Institute and Dr. Joseph Lane at the Hospital for Special Surgery.
The American Society for Bone and Mineral Research has awarded Prof. Donnelly the 2012 Junior Faculty Osteoporosis Research (JFOR) Award to support her proposal, “Spectroscopic and Biochemical Markers of Bone Quality in Patients with Atypical Femoral Fractures.” She will accept the award at the ASBMR annual meeting on 14 October 2012.