Critical review of bone health, fracture risk and management of bone fragility in diabetes mellitus

Abstract

The risk of fracture is increased in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). However, in contrast to the former, patients with T2DM usually possess higher bone mineral density. Thus, there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes. Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk. Moreover, some antidiabetic medications further enhance the fragility of the bone. On the other hand, antiosteoporosis medications can affect the glucose homeostasis in these patients. It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk. Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature. With the advancement in imaging technology, newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes. The purpose of this review is to explore the pathophysiology behind poor bone health in diabetic patients. Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.

Keywords: Antidiabetic drugs; Antiosteoporosis therapy; Bone mineral density; Diabetes; Fracture risk; Microarchitecture.

Figure 1

Mechanisms of increased bone fragility in type 1 diabetes mellitus. DKA: Diabetic ketoacidosis; IGF-1: Insulin-like growth factor; PPAR: Peroxisome proliferator-activated receptor; MSC: Mesenchymal stem cell;IL-1: Interleukin 1; TNF: Tumor necrosis factor.

Figure 2

Mechanisms underlying bone fragility in type 2 diabetes mellitus. AGE: Advanced glycated end product; BMSi: Bone material strength index; CTX: C-terminal cross-linked telopeptide; GLP-1: Glucagon-like peptide-1; MSC: Mesenchymal stem cells; P1NP: Procollagen type 1 N-terminal propeptide; PTH: Parathyroid hormone; ROS: Reactive oxygen species; TRAP: Tartrate-resistant acid phosphatase.

Figure 3

Algorithm for evaluation of bone health in type 1 diabetes mellitus. BMI: Body mass index; BMD-DXA: Bone mineral density by dual energy X-ray absorptiometry; F/U: Follow up; FRAX: Fracture Risk Assessment Tool; H/o: History of; T1DM: Type 1 diabetes mellitus; TBS: Trabecular bone score; VFA: Vertebral fracture assessment.

Figure 4

Evaluation of fracture risk in patients with type 2 diabetes mellitus. ¹: ≥ 1 nonvertebral nonhip fragility fracture might be required to initiate therapy; ²: Diabetes-specific clinical risk factors (diabetes duration, antidiabetic medications,, hemoglobin A1c and microvascular complications); ³: In diabetes, fracture risk at T-score < -2 equivalent for nondiabetes at T-score < -2.5; ⁴: See text. CRF: Clinical risk factor; TBS: Trabecular bone score; DXA: Dual energy X-ray absorptiometry; T2DM: Type 2 diabetes mellitus; FRAX: Fracture Risk Assessment Tool; H/o: History of. Modified from Ferrari et al[123]: Ferrari SL, Abrahamsen B, Napoli N, Akesson K, Chandran M, Eastell R, El-Hajj Fuleihan G, Josse R, Kendler DL, Kraenzlin M, Suzuki A, Pierroz DD, Schwartz AV, Leslie WD; Bone and Diabetes Working Group of IOF. Diagnosis and management of bone fragility in diabetes: an emerging challenge. Osteoporos Int 2018; 29:2585-2596.Copyright ©The Author(s) 2018. Published by Springer Nature.

Figure 5

Strategies for treating type 2 diabetes mellitus and concurrent osteoporosis. CKD-MBD: Chronic kidney disease–mineral and bone disorder; DPP-4i: Dipeptidyl-peptidase 4 inhibitor; GLP-1: Glucagon-like peptide-1; T2DM: Type 2 diabetes mellitus.