Bone Metabolism and Diabetes Mellitus

Bone is a dynamic tissue maintained by the balanced activities of osteoblasts, which form new matrix, and osteoclasts, which resorb old bone. This remodelling process is regulated by a network of hormonal signals, mechanical cues and local growth factors. In diabetes mellitus, chronic hyperglycaemia and insulin deficiency or resistance disrupt bone turnover and microarchitecture. High glucose levels promote the formation of advanced glycation end-products in collagen, reducing matrix quality and increasing fragility. Impaired insulin signalling compromises osteoblast function and attenuates the production of osteocalcin, a bone-derived hormone that also modulates glucose homeostasis. Simultaneously, diabetes-associated inflammation and local acidosis enhance osteoclast activation, accelerating bone loss. The net result is an elevated risk of osteopenia, delayed fracture healing and increased fracture incidence in both type 1 and type 2 diabetes. Understanding these interwoven pathways is critical for developing targeted interventions to preserve skeletal health in a growing population affected by diabetes worldwide.

Research from Nature Portfolio

Recent studies have uncovered a pivotal role for local acidosis in diabetic bone marrow as a driver of excessive osteoclast activation. Acidification of the marrow microenvironment sensitises transient receptor potential cation channel subfamily V member 1 (TRPV1) on osteoclasts, promoting resorption that is not corrected by insulin alone. Blocking TRPV1 in experimental models restores normal osteoclast numbers and ameliorates bone loss, suggesting a novel therapeutic avenue to protect skeletal integrity in diabetes.

Another investigation has focused on the Wnt signalling inhibitor Dickkopf-1 (Dkk1) produced by osteogenic cells. Mice lacking Dkk1 in late osteoblasts and osteocytes are largely protected from cortical bone loss induced by type 1 diabetes. Although trabecular bone formation remains compromised, ablation of Dkk1 prevents the diabetes-driven increase in osteoclast numbers at the cortical compartment. These findings highlight Dkk1 as a key mediator of skeletal deterioration in diabetes and a potential target for preserving bone strength.

Bone Metabolism and Diabetes Mellitus publication trend

The graph below shows the total number of articles in bone metabolism and diabetes mellitus across all publications each year (not limited to Nature Index journals).

Technical terms

Osteoblast: A specialised cell responsible for producing bone matrix and initiating mineralisation.

Osteoclast: A multinucleated cell that degrades mineralised bone matrix, facilitating remodelling.

Wnt/β-catenin signalling: A molecular pathway that promotes osteoblast differentiation and bone formation.

TRPV1: A pH-sensitive ion channel on osteoclasts that mediates acid-induced bone resorption.

Dickkopf-1 (Dkk1): A secreted inhibitor of Wnt signalling that limits osteoblast activity.

Advanced glycation end-products (AGEs): Non-enzymatic modifications of proteins by glucose, impairing collagen quality and bone strength.

References

1. Differential effects of type 1 diabetes mellitus and subsequent osteoblastic β-catenin activation on trabecular and cortical bone in a mouse model. Experimental & Molecular Medicine (2018).
2. Mechanisms involved in altered bone metabolism in diabetes: a narrative review. Journal of Diabetes & Metabolic Disorders (2016).
3. Diabetes Stimulates Osteoclastogenesis by Acidosis-Induced Activation of Transient Receptor Potential Cation Channels. Scientific Reports (2016).
4. Role of osteogenic Dickkopf-1 in bone remodeling and bone healing in mice with type I diabetes mellitus. Scientific Reports (2021).
5. miR-26a Attenuated Bone-Specific Insulin Resistance and Bone Quality in Diabetic Mice. Molecular Therapy - Nucleic Acids (2020).