For many older adults, especially women or those with type 2 diabetes, the risk of fracturing bones is real, and it has a significant impact on quality of life. Understanding more about why bone might become more fragile is the first step in preventing it or reducing the risks, whether it is for yourself or for helping a client or family member. 


We need to think about ways to prevent bone fragility associated with type 2 diabetes and better management strategies, says Pharmacist and PreKure Faculty member, Dr Catherine Crofts.  


Dr Catherine Crofts has just published a paper on this subject – Rethinking Fragility Fractures in Type 2 Diabetes: The Link between Hyperinsulinaemia and Osteofragilitas. Catherine and her co-authors were facing a mystery – people with type 2 diabetes have a greater risk of fragility fractures. But, this could not be due to osteoporosis, because people with type 2 diabetes typically have a higher bone mineral density. So what was the cause?

Dr Catherine Crofts explains more below.


What is bone?

Bone is made up of minerals, especially calcium and phosphate, with smaller amounts of  magnesium, sodium and bicarbonate. These minerals, mostly in a calcium-phosphate complex called hydroxyapatite, are placed around a collagen scaffold by osteoblast cells (bone “builders”).  These osteoblasts are entombed by the minerals, but during the process, evolve into another bone cell called osteocytes. Osteocytes are special as they have now formed long, thin dendritic processes that touch and communicate with other osteocytes.  This is important as the osteocytes use these dendrites to communicate with other osteocytes, coordinating regular bone remodelling. This involves small amounts of bone, in particular weakened or damaged parts, that are broken down by osteoclasts (cleaners) and rebuilt by the osteoblasts. 

A hormone called osteocalcin is released by osteoblasts and osteocytes, and ensures the hydroxyapatite crystals are aligned correctly. The correct combination and amounts of collagen and aligned hydroxyapatite is required for optimal bone strength. 


The sad reality is that people with type 2 diabetes have a greater risk of fragility fractures.


What is osteoporosis?

Osteoporosis or “thin bones” can affect up to 34% of older adults, especially women. It’s believed to occur when more bone breakdown happens than regrowth. There are many reasons for this – age and, for women, menopause, as oestrogen is an important factor for simulating osteoblastic activity.

Osteoporosis by itself is not necessarily an issue, the problems arise when people fall and suffer ‘low energy fractures’ – falls from a standing height or less. These fractures, in particular hip fractures, have high morbidity and mortality rates and place a significant burden on the economy. Fracture risk is generally assessed by scanning bone mineral density. This scan assesses the bone mineral density with lower mineral densities (osteoporosis) being associated with a higher risk of fractures. 


Type 2 diabetes – protective against osteoporosis?

For many years, we believed that obesity and type 2 diabetes was protective against osteoporosis because people with obesity and/or type 2 diabetes have greater bone mineral density. However, the sad reality is people with type 2 diabetes have a greater risk of fragility fractures. Yet, this could not be osteoporosis, because of the higher bone mineral density – so what was the cause?

This question had been bugging Dr Kenneth Brooker, an otolaryngologist surgeon and colleague of Dr Joseph Kraft, for some years. He believed it was due to high insulin levels causing a change in a particular bone factor called osteoprotegerin. During the first level 4 covid-19 lockdown in New Zealand in March 2020, we decided to try and figure out the process, and invited Isabella Cooper, a biochemistry PhD candidate to join us.

What we thought would be a simple process turned out to be anything but simple. Over the last nearly 18 months we have created an argument that people with type 2 diabetes have fragile bones from a very distinct mechanism to osteoporosis.  We have called this state “osteofragalitis” meaning “fragile bones”. 



What we think is happening is as follows:

  • Bone is important not just for structural integrity, but bone is also an important store of minerals, such as calcium.  We know that insulin is critical for bone mineral deposition as people with type 1 diabetes (insulin deficiency) are at a higher risk of osteopenia (thin, but not fragile bones). 
  • We also know times of high insulin levels, such as autumn, are important to ensure the body has adequate energy and micronutrients, especially calcium, to manage times of famine (e.g. winter). The problem is high insulin levels leads to lower osteocalcin levels, which means that the minerals may not be aligned correctly in the bone leading to increased bone fragility. This is not normally a problem as long as periods of feasting are aligned with periods of famine. If the feasting periods are relatively short, only smaller areas of bone may be weaker, then during times of famine, these weaker areas remodelled first to allow the release of the minerals. If performed in a normal physiological manner, i.e., in the presence of low insulin, more osteocalcin is released, which allows the new bone to be rebuilt in a stronger manner. 
  • Poorly aligned bone minerals are less of a problem when you have good quantity and quantity of bone collagen. Bone cells, especially osteoblasts need a lot of ATP (the cell’s energy unit) to make collagen. This should come from fatty acid oxidation. When people have high insulin levels, fatty acids are not broken down to be available for energy production. There is also more glucose than normal in the bloodstream. Combining these factors means the bone cells switch from burning fatty acids for fuel to burning glucose.  This doesn’t create as much energy for the bone cells, plus creates more waste products in the form of reactive oxidative species. This leads to less and/or poor-quality collagen being made, creating a poorer quality bone scaffold to which the minerals adhere. To make things worse, collagen glycates easily and has a slow turnover. As HbA1c increases, the amount of glycated collagen will also increase. Glycated collagen further compromises bone structure and integrity.  So, the poorer the collagen quality/quantity, the increased risk of fragility fractures, no matter the bone mineral density.


Dense, but fragile bones

So, high insulin levels lead to an inadequate collagen scaffolding for bones and poorly aligned mineral structure – leading to increased bone fragility. This is acceptable over short periods of time, but over longer periods of time, the person may develop dense, but fragile bones. Unfortunately, this fragility will not be detected on the bone mineral density scans, as these  scans will simply record normal to high bone mineral density, so the patient is told they are not at risk of fractures until one occurs. 

Overall, this means that all people with type 2 diabetes are at a relatively high risk of fragility fractures. People with hyperinsulinaemia, but normal glucose levels, are at a moderately high risk. Because collagen is a long-lived protein, and bone turnover in some bones may take 7-10 years, these fracture risks are cumulative over time. The earlier the hyperinsulinaemia develops, the greater the risk over time. Theoretically, the risk is greatest if the hyperinsulinaemia and/or type 2 diabetes develops before puberty. 

Currently, diagnostic tests to detect bone fragility are in very early experimental phases.  This means that for osteofragalitis, prevention is cure.