Neuropathy Contributes, But Not Entirely Responsible for Fracture Risk in Type 1 Diabetes

April 7, 2021
Patrick Campbell

A case-controlled study of 60 patients in the United Kingdom found presence neuropathy contributes to fracture risk in patients with type 1 diabetes but found other factors play a role in the increased risk among these patients.

New research from investigators at the University of Sheffield is providing insight into the impact of type 1 diabetes and diabetic neuropathy on bone health.

While patients with type 1 diabetes were found to be at a greater risk of fracture, results of the 60-person case-control study indicate having diabetes and diabetic neuropathy did not fully explain the increased risk in this patient population.

"It is important to investigate what leads to an increased risk of fractures in type 1 diabetes. Our results suggest that in addition to bone features, balance and muscle strength also play a role," said lead investigator Tatiane Vilaca, MD, PhD, of the University of Sheffield, in a statement. "These findings could help improve approaches to fracture prevention."

Unable to identify prior studies examining the effect of diabetic retinopathy on bone health and fracture risk, Vilaca and a team of colleagues designed the current study to fill this knowledge gap. For their study, investigators enrolled 60 patients aged 18 years and older from Sheffield, UK-based diabetes clinics or research lists to undergo assessments related to bone health and impact of neuropathy between October 2017-October 2018.

Investigators recruited 3, 20-patient cohorts for the study. These cohorts included 20 patients with type1 diabetes with distal symmetric sensorimotor polyneuropathy, 20 patients with type 1 diabetes but without neuropathy, and 20 healthy controls. All patients with type 1 diabetes had diabetes for at least 5 years and all patients in the study had an eGFR greater than 60 mL/min/1.73m2.

To assess bone health, all participants underwent assessments of areal bone mineral density (aBMD) and appendicular muscle mass by dual‐energy X‐ray absorptiometry, microarchitecture by high‐resolution peripheral quantitative tomography at the standard ultra‐distal site and at an exploratory 14% bone length site at the tibia and radius, and bone turnover markers. Assessments of neuropathy were performed using the Toronto Clinical Neuropathy Score (TCNS) and patients also underwent assessments of muscle strength, gait, and balance through the Short Physical Performance Battery (SPPB).

Upon analysis, investigators found tibial cortical porosity at the standard ultra-distal site was 56% greater among patients with diabetes with neuropathy compared to those with diabetes and without neuropathy. Additionally, this was positively correlated with severity of neuropathy (TCNS; R=.347, P=.028) and negatively with nerve conduction amplitude and velocity (R=−0.386, P=.015 and R=−.358, P=.025, respectively). Investigators pointed out similar negative correlations were also observed at the radius (R=−.484, P=.006 and R=−.446, P=.012, respectively).

When comparing those with diabetes but without neuropathy to the healthy controls, assessment at the exploratory 14% offset site indicated greater trabecular volumetric BMD (tibia 25%, P=024; radius 46%, P=.017), trabecular bone volume (tibia 25%, P=.023; radius 46%, P=.017), and trabecular number (tibia 22%, P=.014; radius 30%, P=.010) in those with diabetes.

Investigators also pointed out serum levels of carboxy‐terminal cross‐linking telopeptides of type I collagen and N‐terminal propeptide of type I collagen were lower in patients with diabetes compared to controls. No differences were observed in aBMD and appendicular muscle mass between the groups, but investigators did not those with neuropathy had worse performance in the SPPB than those with diabetes but without neuropathy and the healthy controls.

Additionally, histories of previous fracture were more common among both groups of patients with type 1 diabetes (Diabetes with neuropathy: 13 of 20; Diabetes without neuropathy: 10 of 20) than the healthy controls (5 of 20).

This study, “The Effects of Type 1 Diabetes and Diabetic Peripheral Neuropathy on the Musculoskeletal System: A Case– Control Study,” was published in the Journal of Bone and Mineral Research.