The Role of Matrix Composition in the Mechanical Behavior of Bone

Ünal, Mustafa; Creecy, Amy; Nyman, Jeffry S.

doi:10.1007/s11914-018-0433-0

Cited by 102 publications

(74 citation statements)

References 100 publications

(111 reference statements)

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“…The positive correlation between DXA z ‐score and the 8680 cm −1 peak indicates that water is associated with BMD. Water has been shown to play a major role in the interface of the mineral and organic components of the bone matrix, contributing to bone quality and resistance to fractures . For example, water detection using magnetic resonance imaging has been associated with fracture risk in a study with cadaveric arms .…”

Section: Discussionmentioning

confidence: 99%

Clinical application of near infrared fiber optic spectroscopy for noninvasive bone assessment

Shanas

Querido

Dumont

et al. 2020

Journal of Biophotonics

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Section: Discussionmentioning

confidence: 99%

Clinical application of near infrared fiber optic spectroscopy for noninvasive bone assessment

Shanas

Querido

Dumont

et al. 2020

Journal of Biophotonics

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“…Fifth, the free plate model used for cortical bone characteristics identification was parametrized in terms of Ct.Th and Ct.Po, assuming universal material properties of the tissue matrix. Fixed matrix properties did not take into account the inevitable interindividual variability of bone tissue properties . However, such a hypothesis has been found to yield reasonably accurate ex vivo identification of Ct.Th and Ct.Po of human radius and tibia specimens .…”

Section: Discussionmentioning

confidence: 99%

“…Fixed matrix properties did not take into account the inevitable interindividual variability of bone tissue properties. (74) However, such a hypothesis has been found to yield reasonably accurate ex vivo identification of Ct.Th and Ct.Po of human radius and tibia specimens. (40) This model simplification can be avoided using a model parametrized in terms of thickness and stiffness (ie., including four independent stiffness coefficients to account for the generally accepted transverse isotropy of cortical long bones measured axially).…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-Based Estimates of Cortical Bone Thickness and Porosity Are Associated With Nontraumatic Fractures in Postmenopausal Women: A Pilot Study

Minonzio

Bochud

Vallet

et al. 2019

Journal of Bone and Mineral Research

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Recent ultrasound (US) axial transmission techniques exploit the multimode waveguide response of long bones to yield estimates of cortical bone structure characteristics. This pilot cross‐sectional study aimed to evaluate the performance at the one‐third distal radius of a bidirectional axial transmission technique (BDAT) to discriminate between fractured and nonfractured postmenopausal women. Cortical thickness (Ct.Th) and porosity (Ct.Po) estimates were obtained for 201 postmenopausal women: 109 were nonfractured (62.6 ± 7.8 years), 92 with one or more nontraumatic fractures (68.8 ± 9.2 years), 17 with hip fractures (66.1 ± 10.3 years), 32 with vertebral fractures (72.4 ± 7.9 years), and 17 with wrist fractures (67.8 ± 9.6 years). The areal bone mineral density (aBMD) was obtained using DXA at the femur and spine. Femoral aBMD correlated weakly, but significantly with Ct.Th (R = 0.23, p < 0.001) and Ct.Po (R = ‐0.15, p < 0.05). Femoral aBMD and both US parameters were significantly different between the subgroup of all nontraumatic fractures combined and the control group (p < 0.05). The main findings were that (1) Ct.Po was discriminant for all nontraumatic fractures combined (OR = 1.39; area under the receiver operating characteristic curve [AUC] equal to 0.71), for vertebral (OR = 1.96; AUC = 0.84) and wrist fractures (OR = 1.80; AUC = 0.71), whereas Ct.Th was discriminant for hip fractures only (OR = 2.01; AUC = 0.72); there was a significant association (2) between increased Ct.Po and vertebral and wrist fractures when these fractures were not associated with any measured aBMD variables; (3) between increased Ct.Po and all nontraumatic fractures combined independently of aBMD neck; and (4) between decreased Ct.Th and hip fractures independently of aBMD femur. BDAT variables showed comparable performance to that of aBMD neck with all types of fractures (OR = 1.48; AUC = 0.72) and that of aBMD femur with hip fractures (OR = 2.21; AUC = 0.70). If these results are confirmed in prospective studies, cortical BDAT measurements may be considered useful for assessing fracture risk in postmenopausal women. © 2019 American Society for Bone and Mineral Research.

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“…2). These proteins were chosen due to their association with osteoblasts and bone matrix remodeling [39,[69][70][71][72], or osteoblasts and bone metastatic cancer [32,33,73]. We observed the largest differences between conditioned and vehicle-treated osteoblast protein expression in late (20 days) differentiated osteoblasts, which are shown in Fig.…”

Section: Crosstalk Occurs Between Osteoblasts and Breast Cancer Cellsmentioning

confidence: 99%

Osteoblasts are “educated” by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment

et al. 2019

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Introduction: In a cancer-free environment in the adult, the skeleton continuously undergoes remodeling. Boneresorbing osteoclasts excavate erosion cavities, and bone-depositing osteoblasts synthesize osteoid matrix that forms new bone, with no net bone gain or loss. When metastatic breast cancer cells invade the bone, this balance is disrupted. Patients with bone metastatic breast cancer frequently suffer from osteolytic bone lesions that elicit severe bone pain and fractures. Bisphosphonate treatments are not curative. Under ideal circumstances, osteoblasts would synthesize new matrix to fill in erosion cavities caused by osteoclasts, but this is not what occurs. Our prior evidence demonstrated that osteoblasts are diverted from laying down bone matrix to producing cytokines that facilitate breast cancer cell maintenance in late-stage disease. Here, we have new evidence to suggest that there are subpopulations of osteoblasts in the tumor niche as evidenced by their protein marker expression that have distinct roles in tumor progression in the bone. Methods: Tumor-bearing tibia of mice was interrogated by immunofluorescent staining for the presence of osteoblasts and alterations in niche protein expression. De-identified tissue from patients with bone metastatic breast cancer was analyzed for osteoblast subpopulations via multi-plex immunofluorescent staining. Effects of breast cancer cells on osteoblasts were recapitulated in vitro by osteoblast exposure to breast cancer-conditioned medium. Triplenegative and estrogen receptor-positive breast cancer proliferation, cell cycle, and p21 expression were assessed upon contact with "educated" osteoblasts. Results: A subpopulation of osteoblasts was identified in the bone tumor microenvironment in vivo of both humans and mice with bone metastatic breast cancer that express RUNX2/OCN/OPN but is negative for IL-6 and alpha-smooth muscle actin. These tumor "educated" osteoblasts (EOs) have altered properties compared to "uneducated" osteoblasts and suppress both triple-negative and estrogen receptor-positive breast cancer cell proliferation and increase cancer cell p21 expression. EO effects on breast cancer proliferation were mediated by NOV and decorin. Importantly, the presence of EO cells in the tibia of mice bearing tumors led to increased amounts of alkaline phosphatase and suppressed the expression of inflammatory cytokines in vivo. Conclusions: Our work reveals that there is a subpopulation of osteoblasts in the bone tumor microenvironment that demonstrate a functional role in retarding breast cancer cell growth.

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The Role of Matrix Composition in the Mechanical Behavior of Bone

Cited by 102 publications

References 100 publications

Clinical application of near infrared fiber optic spectroscopy for noninvasive bone assessment

Clinical application of near infrared fiber optic spectroscopy for noninvasive bone assessment

Ultrasound-Based Estimates of Cortical Bone Thickness and Porosity Are Associated With Nontraumatic Fractures in Postmenopausal Women: A Pilot Study

Osteoblasts are “educated” by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment

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