Osteoporosis and diabetes are relatively common age-related diseases that affect a large percentage of the elderly population. As the population ages, the prevalence of diabetes and osteoporosis is increasing. Diabetic patients have a higher risk of hip fracture, as well as an increased risk of fracture at other sites such as the humerus, and foot. Fracture risk in older women with diabetes has been found to be more representative than in older men in many studies . Strotmeyer et al studied 67 premenopausal women with type 1 diabetes mellitus and 237 nondiabetic women aged 35-55 years and found that the risk of fracture occurrence after the age of 20 years was increased in women with type 1 diabetes mellitus[1].

There are many factors that contribute to the increased risk of fracture such as insulin administration, falls, functional impairment, progression of diabetes mellitus and vision loss. Due to the variability of data across studies, the relative risk of hip fracture varied between 1.7 and 12.3 for type 1 diabetes. There found 2.8-fold increased risk of hip fracture [CI 1.2 to 6.6] in patients with type 2 diabetes, mainly due to increased age, physical activity, and body mass index as potential confounders. Yamamoto et al noted an increase in vertebral fractures in female diabetic patients independently of BMD and therefore suggested defining their bone mass as fragile bone in type 2 diabetic patients[2].

There is a clear correlation between bone density and risk of fracture. It has been concluded that when BMD decreases by 10%, there is a 1.6- to 2.6-fold relative increase in the risk of hip fracture, as well as a 1.7- to 2.3-fold increase in the relative risk of vertebral fracture. It has been found that in patients with type 1 diabetes mellitus, low bone formation reduces accumulation during bone growth. Poor glycemic control leads to increased bone resorption and bone loss in youth. A cross-sectional study in adults with type 1 diabetes showed that men with diabetes had reduced hip, femoral neck and spinal BMD compared to non-diabetic groups of the same age [3].

Bone strength depends on bone density and bone mass. Models of diabetes in rodents have shown that a decrease in bone mass is not accompanied by a decrease in bone density, but is often accompanied by a spontaneous decrease in bone strength. Possible underlying mechanisms include the effects of insulin, homeostatic changes in insulin-like growth factor (IGF)-1 and the end product AGE. The anabolic effects of insulin on bone in patients with type 1 and type 2 diabetes mellitus are consistent with the respective insulin secretion status (i.e., hypoinsulinemic versus hyperinsulinemic). However, the potential for elevated fracture risk exists in patients with type 2 diabetes. Despite the potential impact of hyperinsulinemia, various studies have shown the influence of many other potential factors, including hyperglycemia, diabetic complications, and lifestyle factors[4].

AGEs are produced by non-enzymatic glycosylation of the protein aminoglycosome and accumulate in a variety of tissues, including the kidneys and coronary arteries, and can cause further development of diabetic vascular complications. Accumulation of AGEs can be observed in bone and is associated with disruption of bone mineralization. AGEs accumulation can accelerate osteoblast apoptosis leading to inhibition of bone formation, and the binding of AGEs to their receptor RAGE is one of the key factors in the function of AGEs. It was also found that osteoclast-like cells expressed RAGE, indicating that RAGE can act as a positive regulator in osteoclast formation and that RAGE has a regulatory effect on bone reconstruction. Therefore, the adverse effects of AGE on bone also include an increased risk of fracture[5].

Reference:

1. Strotmeyer ES, Cauley JA, Orchard TJ, Steenkiste AR, Dorman JS. Middle-aged premenopausal women with type 1 diabetes have lower bone mineral density and calcaneal quantitative ultrasound than nondiabetic women. Diabetes Care. 2006 Feb;29(2):306-11.

2. Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T. Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res. 2009 Apr;24(4):702-9.

3. Hamilton EJ, Rakic V, Davis WA, Chubb SA, Kamber N, Prince RL, Davis TM. Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes. Diabet Med. 2009 Jan;26(1):45-52.

4. Jensen RB, Bytoft B, Lohse Z, Johnsen SK, Nielsen MF, Oturai PS, Højlund K, Damm P, Clausen TD, Jensen DM. Impact of Lean Body Mass and Insulin Sensitivity on the IGF-1-Bone Mass Axis in Adolescence: the EPICOM Study. J Clin Endocrinol Metab. 2021 Jan 23;106(2):e772-e781.

5. Zhu J, Wang Z, Lv C, Li M, Wang K, Chen Z. Advanced Glycation End Products and Health: A Systematic Review. Ann Biomed Eng. 2024 May 5.