Characteristics of Bone Metabolism in Postmenopausal Women With Newly Diagnosed Type 2 Diabetes Mellitus

Huijuan Li; Yuhua Wen; Peipei Liu; Liya Zhang; Xiaoya Zhang; Yichen Liu; Bin Ma; Haidong Kuang; Jianxin Wang; Lige Song

Disclosures

Clin Endocrinol. 2021;95(3):430-438. 

In This Article

Abstract and Introduction

Abstract

Objective: The characteristics of bone metabolism in T2DM are still controversial. This study aims to recognize bone turnover features in patients with newly diagnosed T2DM who have never been treated with anti-diabetic drugs and further explore the possible factors contributing to their impaired bone turnover.

Materials and Methods: An analytic sample of 88 patients with newly diagnosed T2DM and 152 non-diabetic control individuals were studied. All the participants were postmenopausal women. Demographics variables and clinical history were recorded. We measured lipid profile, glucose metabolism, bone turnover markers indices as well as their related hormones, serum calcium and phosphorus. Bone mineral density was detected by dual-energy X-ray absorptiometry. We compared the differences in bone turnover markers and their regulating hormones between two groups and further analysed the factors related to bone turnover in T2DM.

Results: Compared with the control group, patients with T2DM had a higher level of bone alkaline phosphatase (BALP), lower levels of procollagen type I intact N-terminal (P1NP), osteocalcin (OC) and parathyroid hormone (PTH). Multiple linear regression analysis showed that in patients with T2DM, HbA1c was negatively correlated with P1NP and OC. For patients without diabetes, HbA1c was negatively related to BALP and OC.

Conclusions: Patients with newly diagnosed T2DM may have impaired osteoblastic maturation and bone formation, which may be mainly attributed to hyperglycaemia.

Introduction

Diabetes mellitus (DM) is one of the major chronic diseases worldwide. The prevalence of diabetes in adults is assumed to be 8.4% in 2017,[1] and type 2 diabetes (T2DM) makes up a significant portion. In addition to the well-known chronic complications of T2DM such as diabetic microangiopathy, neuropathy and cardiovascular diseases, accumulating evidence has revealed that the skeleton is another target organ of T2DM.[2] Thus, diabetic bone disease is considered one of the chronic complications of diabetes mellitus. Patients with T2DM tend to have a higher risk of fractures which contribute to high disability and mortality.[3] A previous study showed that patients with T2DM had a 38% increased risk of hip fracture compared with non-diabetics.[4] Another study from Women's Health Initiative Observational Cohort also found a higher rate of fractures in postmenopausal women with T2DM. The risk of any fractures during the follow-up period increased by 29%, which was independent of age.[5] However, the bone mineral density (BMD) of T2DM patients was equal or even higher than that in non-diabetic patients.[6] Therefore, clarifying the characteristics of bone metabolism in T2DM may help us better understand the pathophysiology of diabetic bone disease.

Many previous studies have revealed that bone metabolism in patients with T2DM is unique with lower bone turnover than non-diabetic patients.[7] A meta-analysis showed procollagen type I intact N-terminal (P1NP), osteocalcin (OC) and C-terminal cross-linking telopeptide of type I collagen (CTX) were all lower in patients with T2DM.[8] A cross-sectional study showed that the levels of P1NP and OC were lower in T2DM[9] and some studies found that the levels of CTX and tartrate-resistant acid phosphatase-5b (TRACP-5b) were lower in T2DM.[10] However, the results are still controversial. Some studies found no differences in OC[11] and P1NP[12] between T2DM and non-diabetics and a revealed higher level of CTX[12] and TRACP[13] in T2DM.

Following the increasing T2DM duration, bone metabolism will be influenced by blood and nerve nourishment changes related to chronic complications, including microangiopathy[14] and neuropathy.[15] Anti-diabetic agents can also affect bone metabolism, such as metformin, thiazolidinediones (TZD), glucagon-like peptide 1 receptor agonist (GLP-1 RA) and sodium-glucose co-transporter 2 (SGLT2) inhibitor.[16] For example, metformin has a positive effect on osteogenesis through different signal pathways[17] but TZD can inhibit bone formation and increase bone loss.[16] A novel anti-diabetic agent like canagliflozin may increase the level of bone turnover.[16] And, according to a meta-analysis,[18] liraglutide could significantly reduce bone fracture risks, which indicated a potential benefit to bone metabolism. Thus, to better understand the pathophysiological changes of diabetic bone disease, it is crucial to explore the characteristics of bone metabolism in T2DM patients who have very short duration of diabetes and have not been treated with anti-diabetic drugs.

In this cross-sectional study, 88 postmenopausal women with newly diagnosed T2DM and 152 non-diabetic control patients were enrolled. Demographics and clinical history were recorded. Glucose and lipid metabolism, bone turnover markers and related hormones were detected. The relationships between various metabolic indices (glucose and lipid) with bone metabolism were further evaluated.

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