Contributions of Material Properties and Structure to Increased Bone Fragility for a Given Bone Mass in the UCD-T2DM Rat Model of Type 2 Diabetes

Claire Acevedo, Meghan Sylvia, Eric Schaible, James L. Graham, Kimber Stanhope, Lionel N. Metz, Bernd Gludovatz, Ann V. Schwartz, Robert O. Ritchie, Tamara N. Alliston, Peter J Havel, Aaron J. Fields

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Adults with type 2 diabetes (T2D) have a higher fracture risk for a given bone quantity, but the mechanisms remain unclear. Using a rat model of polygenic obese T2D, we demonstrate that diabetes significantly reduces whole-bone strength for a given bone mass (μCT-derived BMC), and we quantify the roles of T2D-induced deficits in material properties versus bone structure; ie, geometry and microarchitecture. Lumbar vertebrae and ulnae were harvested from 6-month-old lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM rats (diabetic for 69 ± 7 days; blood glucose >200 mg/dL). Both obese rats and those with diabetes had reduced whole-bone strength for a given BMC. In obese rats, this was attributable to structural deficits, whereas in UCD-T2DM rats, this was attributable to structural deficits and to deficits in tissue material properties. For the vertebra, deficits in bone structure included thinner and more rod-like trabeculae; for the ulnae, these deficits included inefficient distribution of bone mass to resist bending. Deficits in ulnar material properties in UCD-T2DM rats were associated with increased non-enzymatic crosslinking and impaired collagen fibril deformation. Specifically, small-angle X-ray scattering revealed that diabetes reduced collagen fibril ultimate strain by 40%, and those changes coincided with significant reductions in the elastic, yield, and ultimate tensile properties of the bone tissue. Importantly, the biomechanical effects of these material property deficits were substantial. Prescribing diabetes-specific tissue yield strains in high-resolution finite element models reduced whole-bone strength by a similar amount (and in some cases a 3.4-fold greater amount) as the structural deficits. These findings provide insight into factors that increase bone fragility for a given bone mass in T2D; not only does diabetes associate with less biomechanically efficient bone structure, but diabetes also reduces tissue ductility by limiting collagen fibril deformation, and in doing so, reduces the maximum load capacity of the bone.

Original languageEnglish (US)
Pages (from-to)1066-1075
Number of pages10
JournalJournal of Bone and Mineral Research
Volume33
Issue number6
DOIs
StatePublished - Jun 1 2018

Fingerprint

Type 2 Diabetes Mellitus
Bone and Bones
Ulna
Collagen
Sprague Dawley Rats
Lumbar Vertebrae
Blood Glucose
Spine
X-Rays

Keywords

  • BIOMECHANICS
  • BONE μCT
  • COLLAGEN
  • METABOLISM
  • PRECLINICAL STUDIES

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Contributions of Material Properties and Structure to Increased Bone Fragility for a Given Bone Mass in the UCD-T2DM Rat Model of Type 2 Diabetes. / Acevedo, Claire; Sylvia, Meghan; Schaible, Eric; Graham, James L.; Stanhope, Kimber; Metz, Lionel N.; Gludovatz, Bernd; Schwartz, Ann V.; Ritchie, Robert O.; Alliston, Tamara N.; Havel, Peter J; Fields, Aaron J.

In: Journal of Bone and Mineral Research, Vol. 33, No. 6, 01.06.2018, p. 1066-1075.

Research output: Contribution to journalArticle

Acevedo, C, Sylvia, M, Schaible, E, Graham, JL, Stanhope, K, Metz, LN, Gludovatz, B, Schwartz, AV, Ritchie, RO, Alliston, TN, Havel, PJ & Fields, AJ 2018, 'Contributions of Material Properties and Structure to Increased Bone Fragility for a Given Bone Mass in the UCD-T2DM Rat Model of Type 2 Diabetes', Journal of Bone and Mineral Research, vol. 33, no. 6, pp. 1066-1075. https://doi.org/10.1002/jbmr.3393
Acevedo, Claire ; Sylvia, Meghan ; Schaible, Eric ; Graham, James L. ; Stanhope, Kimber ; Metz, Lionel N. ; Gludovatz, Bernd ; Schwartz, Ann V. ; Ritchie, Robert O. ; Alliston, Tamara N. ; Havel, Peter J ; Fields, Aaron J. / Contributions of Material Properties and Structure to Increased Bone Fragility for a Given Bone Mass in the UCD-T2DM Rat Model of Type 2 Diabetes. In: Journal of Bone and Mineral Research. 2018 ; Vol. 33, No. 6. pp. 1066-1075.
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