Bone Abstracts

Diabetes mellitus results in increased skeletal fragility through reduced bone mineral density and altered collagen structure. How these changes affect bone mechanics at the tissue level remains largely unclear. Anti-osteoporosis medications improve bone mass, but whether they can fully restore tissue strength in diabetic bone, where collagen quality is compromised, has not been fully elucidated. The objective of this study was to determine the effect of type 2 diabetes mellitus and bone-anabolic treatment on bone tissue mechanics in Zucker diabetic fatty (ZDF) rats. We hypothesized that diabetic rats have inferior tissue mechanics, which cannot be fully restored with anabolic treatment due to diabetic changes in the organic phase of the bone.

Ten-week old ZDF diabetic and non-diabetic rats were given 75 μg/kg PTH(1–84) or vehicle 5 days/week over 12 weeks (four groups, n=7 per group). Right femora and L₄ vertebrae were excised, micro-CT scanned, and tested to failure in three points bending and compression, respectively. The force-displacement data were converted into stress-strain using the micro-CT geometry of the specimen cross-sections. In a second approach using linear finite element models of the vertebrae, failure was set to occur when 2% of the elements reached a critical value of stress or strain. Ultimate stress and strain were determined through back-calculation by setting the failure load to that of the mechanical test.

Diabetic rats had significantly lower femoral mid-shaft yield stress (−36%), and significantly lower vertebral yield and ultimate strain (−17 and −22% respectively), and modulus of resilience and toughness (−34 and −46% respectively). After accounting for tissue mineral density, all differences at the vertebra remained significant (P<0.05). PTH treatment increased vertebral ultimate strain (+19%) but not stress, and had no effect at the femur.

Diabetes reduced bone tissue strength and toughness in ZDF rats, independent of mineral density. PTH treatment resulted in limited improvement at the vertebra and none at the femur mid-shaft. These data support the hypothesis that type 2 diabetes mellitus reduces bone tissue mechanics through both collagen and mineral alterations, which cannot be fully restored with bone anabolic agents.