Increasing duration of type 1 diabetes perturbs the strength–structure relationship and increases brittleness of bone

Abstract

Type 1 diabetes (T1DM) increases the likelihood of a fracture. Despite serious complications in the healing of fractures among those with diabetes, the underlying causes are not delineated for the effect of diabetes on the fracture resistance of bone. Therefore, in a mouse model of T1DM, we have investigated the possibility that a prolonged state of diabetes perturbs the relationship between bone strength and structure (i.e., affects tissue properties). At 10, 15, and 18 weeks following injection of streptozotocin to induce diabetes, diabetic male mice and age-matched controls were examined for measures of skeletal integrity. We assessed 1) the moment of inertia (I MIN ) of the cortical bone within diaphysis, trabecular bone architecture of the metaphysis, and mineralization density of the tissue (TMD) for each compartment of the femur by microcomputed tomography and 2) biomechanical properties by three point bending test (femur) and nanoindentation (tibia). In the metaphysis, a significant decrease in trabecular bone volume fraction and trabecular TMD was apparent after 10 weeks of diabetes. For cortical bone, type 1 diabetes was associated with decreased cortical TMD, I MIN , rigidity, and peak moment as well as a lack of normal age-related increases in the biomechanical properties. However, there were only modest differences in material properties between diabetic and normal mice at both whole bone and tissue-levels. As the duration of diabetes increased, bone toughness decreased relative to control. If the sole effect of diabetes on bone strength was due to a reduction in bone size, then I MIN would be the only significant variable explaining the variance in the maximum moment. However, general linear modeling found that the relationship between peak moment and I MIN depended on whether the bone was from a diabetic mouse and the duration of diabetes. Thus, these Correspondence: Jeffry S. Nyman, Vanderbilt Orthopaedic Institute, Medical Center East, South Tower, Suite 4200, Nashville, TN 37232, jeffry.s.nyman@vanderbilt.edu, (615) 936-6296. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptBone. Author manuscript; available in PMC 2012 April 1.

Biomechanical characteristics of bone in streptozotocin-induced diabetic rats: Anin-vivorandomized controlled experimental study

“…It is possible that subjecting the animals to a longer period of hyperglycaemia would cause further deterioration in the material properties of bone. This has been confirmed by Nyman et al [23] in a mouse model exposed to DM for up to 18 wk, in which further deterioration in mechanical properties was observed with longer exposure.…”

“…However, the changes that occur are probably not only to be result of changes in mechanical properties but are probably also due to inherent detrimental changes which occur in the structural material properties. This theory has been confirmed in a mouse model where significant differences were observed in the strength-structure relationship, with reductions to the tissue mineral density of bone in DM, which became apparent after only 10 wk [23] . Our experimental model subjected the D group of rats to uncontrolled levels of hyperglycaemia.…”

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

“…Specifically, T1DM patients have an absolute deficiency of insulin-like growth factor 1 (IGF1), that results in impaired bone formation and lower peak bone mass. Conversely, T2DM patients may display increased BMD due to both increased mechanical loading and hyperinsulinaemia; however, both T1DM and T2DM patients have microarchitectural bone changes, resulting in bone which has an inferior quality compared with that of the general population (Brown 2004, Yamagishi et al 2005, Melton et al 2008, Milczarczyk 2008, Nyman et al 2011. As DM is beyond the remit of this review, we direct the reader to the review by Jackuliak & Payer (2014).…”

Alteration of the bone tissue material properties in type 1 diabetes mellitus: A Fourier transform infrared microspectroscopy study

“…Several studies using STZ-injected rodent models have been published in the last decade and reported inconsistent data on the effect of T1DM on bone tissue material properties, i.e., the mineral and organic component of the bone matrix [12][13][14][15]. Previous studies seem suggest that bone microarchitecture deterioration appears early, while modification of intrinsic material, as determined by bone toughness, occurs later [16]. Furthermore, an inherent problem with the STZ model is that this compound is often injected around 10 weeks of age, and the general duration of studies is around 10-12 weeks.…”