Loss of Bone Flexibility Linked to Increased Hip Fracture Risk

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A new study reveals that bone flexibility, as well as density, in bone nanostructure is an important factor in assessing the likelihood that someone will suffer a hip fracture. The findings, published in Scientific Reports, suggest that doctors should look more closely at bone flexibility when deciding on a treatment to prevent bone fractures.

Clinicians often use DEXA scans, which look at how porous or dense bones are, to assess the likelihood of a fracture. DEXA scans detect bone weakness in osteoporosis, a condition that causes weakened bones, when deciding on treatments, like prescribing bisphosphonate drugs, to help prevent fractures.

However, some people whose bones seem healthy on DEXA scans are more likely than others to suffer fractures.

To find out why the researchers looked to the building blocks of bones: stiff minerals surrounding flexible collagen fibrils, which are responsible for our bones’ resistance to fracture during trips and falls.

Using high energy intense beams of X-rays to examine the flexibility of hip bone samples the researchers were able to assess how collagen and minerals within the bones flexed and then broke apart when pressure was applied.

They compared the behavior of the bone tissue samples under pressure between three groups of donors: those who had not suffered a hip fracture; those who were never treated with a bisphosphonate who suffered a fractured hip; and those treated with bisphosphonates who had suffered a fractured hip.

The team found that donors without fractures were more likely to have flexible collagen and mineral nanostructure than those with who had suffered fractures.

Irrespective of bisphosphonate treatment, the collagen and minerals were less flexible under load in patients with fractures, meaning the mineral broke away from the collagen at much lower forces.

The researchers say the bones may have fractured because the tissue was too inflexible and could not deform to absorb energy during a bump or fall – highlighting the importance of flexibility in the collagen and minerals of bone.

Therefore, flexibility at the nanoscale could be important in predicting future bone fractures and a target for new treatments – a finding that could inform future preventative treatment of bone fractures.

Study co-author Dr Ulrich Hansen, of Imperial’s Department of Mechanical Engineering, said: “We tend to think of our bones as solid, hard support structures, but flexibility appears to be extremely important in bone health. If bones are too hard, they are less able to absorb impact and more likely to break. Our study suggests that flexibility could be just as important as density in preventing fractures.”

Osteoporosis Link

One of the main risk factors for age-related hip fractures is osteoporosis, a disease where bone density is lost leaving patients prone to fractures. Usually, old bone tissue is broken down and replaced with new tissue. Osteoporosis occurs when the breaking down of bone outpaces its replacement.

44 million people in the US, and over 200 million worldwide live with osteoporosis. Patients are often treated with bisphosphonates to address the condition by binding to the surface of bones and blocking bone removal.

In this study the researchers found that donors with hip fractures who had received bisphosphonates for between one and 13 years had lower tissue strength and nanoscale flexibility than the untreated fracture donors and a control group.

The researchers say their results could be because in some bisphosphonate users, the drug might bind itself to and harden the mineral crystals that surround the collagen fibers within bone. The hardening could make bone less flexible and therefore less able to absorb impact.

However, the findings could also be a result of the patients’ bones being more osteoporotic in the first place, and these results could be because the researchers couldn’t control for additional factors like initial disease severity.

Co-author Dr Richard Abel from the Department of Surgery and Cancer said:

“We were surprised to see that bisphosphonate users seemed to have less flexible bone nanostructures.”

Perhaps after a long period of treatment in some patients, there is a loss of flexibility at the nanoscale that offsets some of the strength benefits from increases in bone density. More research is needed to determine exactly why this is and how this could affect clinical practice in long-term users.

Lead author Dr Shaocheng Ma from the Department of Mechanical Engineering said: “It’s possible that the amount of mineral strain is key in setting off the fracture process. However, in patients who have taken bisphosphonates for a long time the mineral could become too stiff, causing it to break away from the collagen. This releases the collagen and allows it to stretch uncontrollably, which then results in a fracture.”

Currently, the diagnosis, treatment and follow up for fragility focuses on the mineral in bone, but this study highlights the role of other factors like collagen, and the interaction between mineral and collagen at the nanoscale.

Source: Shaocheng Ma, En Lin Goh, Tabitha Tay, Crispin C. Wiles, et al. Nanoscale mechanisms in age-related hip-fractures. Scientific Reports, 2020; 10 (1) DOI: 10.1038/s41598-020-69783-5

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