Diabetes and complications related to it are common, and most people know about them. Diabetes harms blood vessels and nerves, which causes heart problems, problems with peripheral nerves, and weakens eyesight. The need for foot and eye care, and the evaluation of heart and kidney health, are all well-recognized in diabetic care.
Whenever a person living with diabetes goes to a doctor for a particular reason or just for their usual check-up, they are evaluated for various complications. However, quarterly or half-yearly evaluations often neglect bone health.
In fact, the relationship between diabetes and complications related to bones is one of the least appreciated subjects. Researchers warn that the danger is real and can often lead to acute complications. Worst of all, many regular tests like bone mineral density (BMD) scores are of little help in assessing the risk. People with diabetes are at much higher risk of fracture despite the seemingly normal BMD scores.
The risk of complications related to bones is poorly recognized in the guidelines. European guidelines practically say nothing about it, while American Diabetes Association guidelines just mention osteoporosis and bone fragility. None of the guidelines say when and how often should the person be evaluated for bone health.
So why is an evaluation of bone health so tricky in diabetes?
It seems that the mechanism of the weakening of bones in diabetes differs from osteoporosis. So,let us say in post-menopausal women, osteoporosis would be considered if the score is -2.5 or lower. However, specialists warn that, with diabetes, even a person with -1.5 is at a high risk of fracture. Some specialists recommend that there is a need to revise the criteria for osteoporosis and the BMD T-score for people with diabetes.
To understand why in diabetes bones are weakened, even when the density scores are not bad, we need to look at the microscopic levels. High-resolution scans of bones of those living with diabetes show that they have a higher number of tiny pores in the outer layer of bones, which render them weaker and more prone to fractures. In diabetes, it is not so much about low bone density as is the case of classical osteoporosis, but it is more about poor bone quality.
What causes the fragile bones in diabetes?
Research indicates that advanced glycation end-products (AGEs) that are responsible for various vascular complications are also behind the weakened bones. Research has demonstrated the direct relationship between the amount of AGEs in blood and bone health.
However, things are not that straightforward in practice. It is still not known whom to check for bone health and whom not, or whom to prescribe drugs for strengthening the bones. Researchers think that there is a need to include this information in the new guidelines so that doctors or diabetes specialists can provide better care.
BMD T-score cannot be considered as a sole factor in assessing the risk of fracture in diabetes. However, the presence of other complications may indicate the risk, such as the severity of diabetic retinopathy, which is a direct indicator of the severity and duration of diabetes. A person with retinopathy must also go through screening for bone disease, at least once a year.
Similarly, researchers say that those living with type 2 diabetes and taking insulin should be regularly checked for bone conditions. Although insulin is anabolic and is not harmful to the bones, insulin therapy indicates that a person with type 2 diabetes has a long history of diabetes, and that the person is not responding to oral drugs. Moreover, those living with type 2 diabetes are often obese, which increases the risk of fracture and other complications.
New medications may help to protect diabetic bones
Recent research into the subject has indicated that there is a specific relationship between obesity, type 2 diabetes, and fragile bones. In one of the experiments involving an investigational drug called TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine], which helps to reduce obesity and insulin resistance, has also been demonstrated to strengthen the bones and promote the formation of new bones.The effectiveness of TNP has come as a surprise for researchers as most of the anti-diabetic drugs cause the weakening of bones. Researchers think that TNP may, in the future, be used to stimulate bone growth after the fractures.
So what are the relationships between diabetes, obesity, and fragile bones, and how does TNP help? To understand it, investigators consulted stem cell therapy investigators. In the research on mice, researchers found that a high-fat diet not only promoted obesity, but it also resulted in a higher content of fat in the bones. It is probably due to the fact that a single type of stem cells from bone marrow (called mesenchymal stem cells (MSCs)) differentiate and mature into bone tissues and fat cells. So, it seems that high-fat diets promote not only obesity but also an accumulation of more fat in bones.
However, scientists found that in a genetically-modified mouse that was lacking the gene for producing anenzyme called inositol hexakisphosphate kinase 1 (IP6K1), something that is also blocked by TNP, when fed with a high-fat diet, didn’t develop many fat cells and had a higher production of bone cells. Researchers then concluded that TNP would not only help to increase insulin sensitivity and counter obesity, but would also help to strengthen bones. All this happens due to the inhibition of IP6K1 by the experimental drug TNP.
These studies demonstrated that reason of fragile bones in those with diabetes differ than in non-diabetic individuals. Researchers also found that there is a relationship between poor bone health, obesity, and insulin resistance.
Although IP6K1 inhibitor TNP is highly effective in improving bone strength, stimulating its growth, along with helping to counter obesity and insulin resistance, it is still an experimental drug. The issue with the present candidate drug is that it is not selective enough, instead of working just on MSCs it affects the entire body, resulting in adverse side effects.
Researchers, though, are confident that they are working in the right direction and soon they would be able to come up with something safer and efficient.
- Diabetes and Bone Fragility: An Underappreciated Complication. Endocrine News. November 2016. https://endocrinenews.endocrine.org/diabetes-bones-underappreciated-complication/. Accessed February 22, 2018.
- Boregowda SV, Ghoshal S, Booker CN, Krishnappa V, Chakraborty A, Phinney DG. IP6K1 Reduces Mesenchymal Stem/Stromal Cell Fitness and Potentiates High Fat Diet-Induced Skeletal Involution. Stem Cells. 2017;35(8):1973-1983. doi:10.1002/stem.2645
- Marciano DP, Kuruvilla DS, Boregowda SV, et al. Pharmacological repression of PPARγ promotes osteogenesis. Nat Commun. 2015;6:7443. doi:10.1038/ncomms8443
- Ghoshal S, Zhu Q, Asteian A, et al. TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates diet induced obesity and insulin resistance via inhibition of the IP6K1 pathway.Mol Metab. 2016;5(10):903-917. doi:10.1016/j.molmet.2016.08.008