Diabetes a Risk Factor for Fractures; Screening Methods Inadequate

Norra MacReady

December 13, 2016

Physicians should be alert to an increased risk of fracture in patients with diabetes and to the limitations of standard methods of assessing bone health in this population, the authors of a new review warn.

The heightened risk is seen with both type 1 and type 2 diabetes. G Isanne Schacter, MD, and William D Leslie, MD, from the University of Manitoba, Winnipeg, write in an article published online in Calcified Tissue International & Musculoskeletal Research.

The prevalence of osteoporosis and diabetes, particularly type 2, is expected to increase as the world's population ages and gets more obese.

In their paper, Drs Schacter and Leslie reviewed several common skeletal parameters derived from dual X-ray absorptiometry (DXA) scanning to determine whether they could account for the excess fracture risk in people with type 1 and type 2 diabetes.

When possible, they recommended ways in which the parameters could be adjusted to provide a better estimate of a patient's risk.

They also studied the Fracture Risk Assessment Tool (FRAX), which is incorporated into modern DXA scanners. FRAX is already known to underestimate fracture risk in people with type 2 diabetes, due to their general higher body mass index (BMI) as well as their risk of falling and subsequent changes in bone density.

"It is our hope that doctors can use the adjustments outlined in our paper to approximate the true fracture risks of someone with diabetes," Dr Leslie told Medscape Medical News.

Effects of Diabetes on Bone Composition

Bone specialists have long known about the relationship between diabetes and fracture risk, but this is often overlooked by many primary-care physicians and even some endocrinologists, Dr Leslie said.

Historically, doctors have tended to downplay the risk of osteoporosis among people with diabetes, especially type 2 diabetes, because these patients often are overweight, which usually is correlated with higher bone-mineral density (BMD), he explained.

"But the fracture risk is higher than you would expect, given their level of bone density."

"So one of the messages in our paper is to make people aware that diabetes is a risk factor for fractures," said Dr Leslie.

One reason for the increased fracture risk is that the other complications of diabetes, such as impaired vision, balance, and neurological function, put these patients at an increased risk for falling, which "will increase the possibility of fractures even if the bone itself is unaffected," he explains.

And a growing body of data suggest that the metabolic alterations characteristic of diabetes take a toll on bone composition too, just as they do on other organs, Dr Leslie noted.

"There is accumulating evidence that the advanced glycosylated end products [AGES] seen with diabetes interfere with normal bone renewal and bone strength, and there is evidence suggesting that the bones of people with diabetes are probably softer. There is also evidence that bone porosity is increased, especially within the dense cortex of the bone, which makes the bone much weaker than one might predict, relative to the amount of bone."

In addition, among people with type 1 diabetes, poor metabolic control may lead to "increased bone resorption and bone loss in young adults, coupled with decreased bone formation retarding bone accumulation during growth, ultimately leading to the development of osteopenia," the doctors state in their review.

When combined with the effects of AGES, people with type 1 diabetes have a relative increase in the risk of hip fracture of 6.4- to 6.9-fold, compared with individuals without diabetes, "which vastly exceeds the relative risk of 1.42 expected from the magnitude of the BMD reduction," they write.

Among people with type 2 diabetes, a lower BMD correlates with a higher fracture risk, just as it does in the general population, they add.

"However, the increased fracture risk associated with type 2 diabetes is not fully captured by BMD that is paradoxically higher, even after adjustment for the BMI."

In short, "type 2 diabetes up-shifts the BMD-fracture relationship such that there is an increase in fracture risk above that predicted from BMD alone, resulting in the additional fracture burden attributable to type 2 diabetes."

Can DXA-Based Measurements Account for the Increased Risk?

DXA scanning is the standard method of measuring BMD and is readily available in most developed nations, Dr Leslie said.

But "while the tools we have to assess fracture risk in the general population, such as DXA, are good, they're not well-tuned to the needs of people with diabetes. There are work-arounds, and this is an area that is a work in progress."

In type 1 diabetes, for example, BMD and FRAX (when secondary osteoporosis is included without BMD) only partially account for the excess risk of fracture. And it is uncertain whether bone geometry, trabecular bone score (TBS), vertebral fracture assessment (VFA), or body composition account for excess fracture risk in those with type 1 diabetes, the review notes.

Similarly, BMD and FRAX can be used to stratify fracture risk in those with type 2 diabetes but do not account for the increased risk of fracture.

But primary-care doctors can use certain adjustments to the FRAX scores to help more accurately predict the fracture risk in type 2 diabetes — for example, they can use the rheumatoid arthritis input (as a proxy for type 2 diabetes) or lower the hip T-score — which compares the patient's BMD with that of a young, healthy adult — by 0.5 units.

DXA-Based Parameters (Techniques) and Associated Fracture Risk in Diabetes

DXA parameter (technique) Does the technique differ between those with or without diabetes? Is the technique associated with fracture risk in those with diabetes? Does the technique account for excess fracture risk in those with diabetes?
  T1D T2D T1D T2D T1D T2D
BMD Yes Yes Yes Yes Partially No
Bone geometry Uncertain Uncertain Uncertain Uncertain Uncertain Uncertain
TBS Uncertain Yes Uncertain Yes Uncertain Partially
VFA Uncertain Uncertain Uncertain Uncertain Uncertain Uncertain
Body composition Uncertain Uncertain Uncertain Uncertain Uncertain Uncertain
FRAX (no adjustments) Yes Yes Uncertain Yes Partially No
Adapted from Tables 2 and 3, Calcif Tissue Int. 2016. Available here.
Source: International Osteoporosis Foundation
BMD=bone-mineral density
TBS=trabecular bone score
VFA=vertebral fracture assessment
FRAX=Fracture Risk Assessment Tool

Effects of Glucose-Lowering Treatment Unknown

It is also still unclear whether good glycemic control will help lower fracture risk, Dr Leslie told Medscape Medical News.

"It is appealing to think that poor glycemic control would accentuate the adverse effects on the bone, and there is evidence to support that idea. However, we do not know to what extent that can be avoided with tight glycemic control."

One of the paradoxical dangers of excessively strict glucose control is that it could cause hypoglycemia and thus increase the risk of falling, he pointed out. "That's part of the challenge of diabetes management: to find that 'safe' zone of glycemic control."

Also unknown is whether diabetes medications interact with agents normally prescribed to treat osteoporosis, such as bisphosphonates.

"There is some evidence showing that those medications have the same effect on increasing bone density in those with and without diabetes — that makes me think that they probably work similarly in both populations," Dr Leslie said.

"There is also no evidence that the medications used for diabetes control affect the action of bisphosphonates."

Nor do insulin or metformin have adverse effects on bone, he added. However, there is "pretty clear evidence" that thiazolidinediones do increase the risk of osteoporosis and fractures.

In conclusion, "diabetes is characterized by an increased fracture risk that is only partially explained by the BMD reductions seen in type 1 diabetes and is underestimated in type 2 diabetes where BMD is increased," he and Dr Schacter state.

"While BMD from DXA still stratifies fracture risk in those with diabetes, additional measures that can be obtained from DXA help to identify patients at increased risk of fracture. Incorporating this additional information into risk-prediction models may help to avoid systematically underestimating the risk of osteoporosis-related fractures in subjects with diabetes," they conclude.

The authors disclosed no relevant financial relationships.

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Calcif Tissue Int. 2016; Published online September 3, 2016. Abstract

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