Association of Bone Mineral Density, Bone Turnover Markers, and Vertebral Fractures with All-Cause Mortality in Type 2 Diabetes Mellitus

Abstract

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fracture. However, the association between diabetes-related osteoporosis and mortality in T2DM remains unknown. This historical cohort study assessed the endpoint of all-cause mortality in patients with T2DM. According to our hospital record, bone parameters were examined in 797 patients from 1997 to 2009. We excluded 78 because of diseases affecting bone metabolism and could not follow-up 308 patients. Finally, in 411 patients, the associations of bone turnover markers, bone mineral density (BMD), and the prevalence of vertebral fractures with mortality were investigated by Cox regression analyses adjusted for confounding factors. Of 411 patients, 56 died during the follow-up period of almost 7 years. Cox regression analyses showed that reduced BMD at the lumbar spine (LS) and femoral neck (FN) (T-score ≤ -2.5) and severe vertebral fractures were associated with higher mortality (hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.48-7.16, p = 0.003 for LS-T score ≤ -2.5; HR 5.19, 95% CI 1.83-14.75, p = 0.002 for FN-T score ≤ -2.5; HR 2.93, 95% CI 1.42-6.02, p = 0.004 for multiple vertebral fractures; HR 7.64, 95% CI 2.13-27.42, p = 0.002 for grade 3 vertebral fracture). Separate analysis in men and women showed that decreased serum osteocalcin was associated with mortality in women (HR 3.82, 95% CI 1.01-14.46 per SD decrease, p = 0.048). The present study is the first to show the association of reduced BMD and severe vertebral fractures with increased all-cause mortality in patients with T2DM. Moreover, higher serum osteocalcin was significantly associated with decreased mortality in women with T2DM.

Comparison of FRAX in postmenopausal Asian women with and without type 2 diabetes mellitus: a retrospective observational study

“…With the increasing prevalence of T2DM and osteoporosis, the relationship between T2DM and bone metabolism has increasingly become the focus of research. 2,4 Metabolic disorders induced by T2DM tend to affect bone metabolism in different ways. 4,26 However, there is no consensus about the changes in BMD in patients with T2DM.…”

“…Type 2 diabetes mellitus (T2DM) tends to be associated with higher bone mineral density (BMD) and, illogically, with an increase in bone fragility. [1][2][3] It is increasingly recognized that postmenopausal women with T2DM have a high fracture risk that is associated with osteoporosis 1,4 and that previously established methods for predicting fracture events can be very variable in patients with T2DM because a higher BMD is associated with increased fracture events in these patients. 5 Conceptually, osteoporosis is defined as a systemic skeletal disease that is characterized by bone mass impairment and micro-architectural deterioration of bone tissue with a consequent decrease in bone strength and susceptibility to fracture.…”

Management of fracture risk in patients with diabetes—Chinese Expert Consensus

“…In recent years, the risk of fracture in T2D patients has attracted increasing attention . For T2D patients, severe vertebral fractures may even be related to all‐cause mortality . Bone mineral densities (BMDs) measured with dual‐energy X‐ray absorptiometry (DXA) indicate the risk of fractures for non‐diabetic patients, but may underestimate fracture risk in T2D patients because T2D patients may experience fractures at relative elevated BMDs compared with non‐diabetics .…”

“…4,5 For T2D patients, severe vertebral fractures may even be related to all-cause mortality. 6 Bone mineral densities (BMDs) measured with dualenergy X-ray absorptiometry (DXA) indicate the risk of fractures for non-diabetic patients, but may underestimate fracture risk in T2D patients because T2D patients may experience fractures at relative elevated BMDs compared with non-diabetics. 7 Moreover, various diabetes therapies may affect bone metabolism, 8 which poses a huge challenge to the clinical management of fracture risk in T2D patients.…”

Volumetric bone mineral density of the spine predicts mortality in African-American men with type 2 diabetes

“…Many confounding factors are present, including those relating to the measurement of areal BMD (aBMD), and the complex interactions that exist between bone, body weight, and metabolism in T2D. A cohort study including 222 men and 189 women with T2D reported an inverse association between lumbar spine and femoral neck aBMD measured by Dual X-ray Absorptiometry (DXA) and all-cause mortality, and a positive association of severe vertebral fractures and mortality [6]. These observations require confirmation in larger cohorts and using more specific measures including volumetric BMD (vBMD) measured with Quantitative Computed Tomography (QCT).…”