Effects of Diabetes on Bone Material Properties
- 102 Downloads
Purpose of Review
Individuals with type 1 and type 2 diabetes mellitus (T1DM, T2DM) have an increased risk of bone fracture compared to non-diabetic controls that is not explained by differences in BMD, BMI, or falls. Thus, bone tissue fracture resistance may be reduced in individuals with DM. The purpose of this review is to summarize work that analyzes the effects of T1DM and T2DM on bone tissue compositional and mechanical properties.
Studies of clinical T2DM specimens revealed increased mineralization and advanced glycation endproduct (AGE) concentrations and significant relationships between mechanical performance and composition of cancellous bone. Specifically, in femoral cancellous tissue, compressive stiffness and strength increased with mineral content; and post-yield properties decreased with AGE concentration. In addition, cortical resistance to in vivo indentation (bone material strength index) was lower in patients with T2DM vs. age-matched non-diabetic controls, and this resistance decreased with worsening glycemic control. Recent studies on patients with T1DM and history of a prior fragility fracture found greater mineral content and concentrations of AGEs in iliac trabecular bone and correspondingly stiffer, harder bone at the nanosacle.
Recent observational data showed greater AGE and mineral content in surgically retrieved bone from patients with T2DM vs. non-DM controls, consistent with reduced bone remodeling. Limited data on human T1DM bone tissue also showed higher mineral and AGE content in patients with prior fragility fractures compared to non-DM and non-fracture controls.
KeywordsBone material properties Type 1 diabetes mellitus (T1DM) Type 2 diabetes mellitus (T2DM) Advanced glycation end products (AGEs) Diabetic murine models In vitro glycation
Funding for this work was provided in part by NIH K01 AR064314 to ED.
Compliance with Ethical Standards
Conflict of Interest
Sashank Lekkala, Erik A. Taylor, Heather B. Hunt, and Eve Donnelly declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human participants or animals performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 9.Napoli N, Chandran M, Pierroz DD, Abrahamsen B, Schwartz AV, Ferrari SL. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol. Nat Publ Group. 2017;13:208–19.Google Scholar
- 11.•• Hunt H, Torres A, Palomino P, Marty E, Saiyed R, Cohn M, et al. Altered tissue composition, microarchitecture, and mechanical performance in cancellous bone from men with type 2 diabetes mellitus. J Bone Miner Res. 2019; This study relating compositional and mechanical properties found increased pentosidine and mineralization in men with T2DM, and showed that high concentrations of AGEs can increase fragility, especially for T2DM patients with low BV/TV.Google Scholar
- 15.Yamagishi S-I. Role of advanced glycation end products (AGEs) and receptor for AGEs (RAGE) in vascular damage in diabetes. EXG. 2011;46:217–24.Google Scholar
- 17.Nilsson AG, Sundh D, Johansson L, Nilsson M, Mellström D, Rudäng R, et al. Type 2 diabetes mellitus is associated with better bone microarchitecture but lower bone material strength and poorer physical function in elderly women: a population-based study. J Bone Miner Res. 2017;32:1062–71.PubMedCrossRefPubMedCentralGoogle Scholar
- 19.• Hygum K, Starup-Linde J, Harsløf T, Vestergaard P, Langdahl BL. Diabetes mellitus, a state of low bone turnover-a systematic review and meta-analysis. Eur J Endocrinol. 2017;176:R137–57 This extensive review of biochemical markers of bone formation and resorption in diabetes and found that low bone turnover is observed in both T1DM and T2DM conditions. PubMedCrossRefPubMedCentralGoogle Scholar
- 20.Zhukouskaya VV, Eller-Vainicher C, Shepelkevich AP, Dydyshko Y, Cairoli E, Chiodini I. Bone health in type 1 diabetes: focus on evaluation and treatment in clinical practice. J Endocrinol Invest. Springer International Publishing. 2015;38:941–50.Google Scholar
- 22.•• Farlay D, Armas LAG, Gineyts E, Akhter MP, Recker RR, Boivin G. Nonenzymatic glycation and degree of mineralization are higher in bone from fractured patients with type 1 diabetes mellitus. J Bone Miner Res. 2016;31:190–5 This is the only study to our knowledge to have assessed compositional properties in patients with T1DM and found increased AGE accumulation in patients with T1DM.PubMedCrossRefPubMedCentralGoogle Scholar
- 31.Silva MJ, Brodt MD, Lynch MA, McKenzie JA, Tanouye KM, Nyman JS, et al. Type 1 diabetes in young rats leads to progressive trabecular bone loss, cessation of cortical bone growth, and diminished whole bone strength and fatigue life. J Bone Miner Res. 2009;24:1618–27.PubMedPubMedCentralCrossRefGoogle Scholar
- 35.Makowski AJ, Patil CA, Mahadevan-Jansen A, Nyman JS. Polarization control of Raman spectroscopy optimizes the assessment of bone tissue. J Biomed Opt International Society for Optics and Photonics. 2013;18:055005.Google Scholar
- 39.Rubin MR, Paschalis EP, Poundarik A, Sroga GE, McMahon DJ, Gamsjaeger S, et al. Correction: advanced glycation endproducts and bone material properties in type 1 diabetic mice. PLoS ONE. 2016;11:1–14.Google Scholar
- 43.•• Karim L, Moulton J, Van Vliet M, Velie K, Robbins A, Malekipour F, et al. Bone microarchitecture, biomechanical properties, and advanced glycation end-products in the proximal femur of adults with type 2 diabetes. Bone. Elsevier. 2018;114:32–9 This is the first study to examine compositional and mechanical properties of bone from humans with T2DM and found reduced resistance to creep indentation in cortical bone from patients with T2DM. CrossRefGoogle Scholar
- 44.Bucknell A, King KB, Oren TW, Botolin S, Williams A. Arthroplasty in veterans: analysis of cartilage, bone, serum, and synovial fluid reveals differences and similarities in osteoarthritis with and without comorbid diabetes. J Rehabil Res Dev. 2012;48:1195.Google Scholar
- 45.Pritchard JM, Papaioannou A, Tomowich C, Giangregorio LM, Atkinson SA, Beattie KA, et al. Bone mineralization is elevated and less heterogeneous in adults with type 2 diabetes and osteoarthritis compared to controls with osteoarthritis alone. Bone. Elsevier Inc. 2013;54:76–82.PubMedPubMedCentralCrossRefGoogle Scholar
- 47.•• Farr JN, Drake MT, Amin S, Melton LJ, McCready LK, Khosla S. In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res. 2014;29:787–95 This comprehensive assessment of geometric and microarchitectural properties in women with T2DM demonstrated that bone material strength index decreased with 10-year HbA1c.PubMedPubMedCentralCrossRefGoogle Scholar
- 54.Marin C, Papantonakis G, Sels K, Van Lenthe GH, Falgayrac G, Vangoitsenhoven R, et al. Unraveling the compromised biomechanical performance of type 2 diabetes- and Roux-en-Y gastric bypass bone by linking mechanical-structural and physico-chemical properties. Sci Rep Springer US. 2018;8:1–12.Google Scholar
- 56.Kerckhofs G, Durand M, Vangoitsenhoven R, Marin C, Van Der Schueren B, Carmeliet G, et al. Changes in bone macro-and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography. Sci Rep Nature Publishing Group. 2016;6:1–13.Google Scholar
- 63.Hamann C, Goettsch C, Mettelsiefen J, Henkenjohann V, Rauner M, Hempel U, et al. Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function. Am J Physiol Metab. 2011;301:E1220–8.Google Scholar
- 69.Huang L, You YK, Zhu TY, Zheng LZ, Huang XR, Chen HY, et al. Validity of leptin receptor-deficiency (db/db) type 2 diabetes mellitus mice as a model of secondary osteoporosis. Sci Rep Nature Publishing Group. 2016;6:1–7.Google Scholar