Iron dysregulation, ferroptosis, and oxidative stress in diabetic osteoporosis: Mechanisms, bone metabolism disruption, and therapeutic strategies

Table 1 Effects of diabetes on bone metabolism

Cell type	Mechanism of action	Influencing factors	Specific manifestations	Ferroptosis-related mechanisms	Ref.
Osteoblasts	High-glucose environments inhibit osteoblast proliferation and differentiation	High glucose, AGEs, oxidative stress	Decreased ALP activity, reduced mineralization capacity	High glucose induces ferroptosis via lipid peroxidation and GPX4 inhibition; AGEs promote ferroptosis, disrupting osteoblast function and mineralization	Wu et al[4], Hygum et al[18]
Osteoclasts	Osteoclast formation and function are suppressed in high-glucose conditions	High glucose, inflammatory factors	Reduced number of osteoclasts, diminished bone resorption function	Iron overload in diabetic conditions enhances osteoclast activity through ferroptosis-associated pathways, increasing bone resorption in some contexts	Bao et al[5], Kim et al[21]
Osteocytes	High glucose and inflammatory environments impair osteocyte function	High glucose, inflammatory factors	Decreased osteocyte activity, reduced bone matrix quality	Ferroptosis induced by high glucose and lipid peroxidation leads to osteocyte death; upregulation of HO-1 and intracellular iron overload exacerbate bone matrix deterioration	Bao et al[5], Saadi et al[25], Yang et al[68]

AGEs: Advanced glycation end products. Metabolic byproducts formed in a hyperglycemic environment that can impair cellular function; ALP: Alkaline phosphatase. An enzyme associated with bone mineralization; GPX4: Glutathione peroxidase 4; HO-1: Heme oxygenase-1; Hyperglycemia: A state of elevated blood glucose levels commonly observed in diabetic patients; Oxidative stress: A condition in which high-glucose environments increase oxidative stress levels, leading to cellular damage.