Diabetes Bone Paradox in Type 2 Diabetes

Diabetes bone paradox: why having a high bone mineral density may not always decrease the risk of fractures. 

Patients with type 1 diabetes are known for having low bone mineral density (BMD), putting them at an increased risk for bone fractures. In contrast, patients with type 2 diabetes typically present with a higher BMD, yet these patients have been found to also be at an increased risk for bone fractures. This leads to the “diabetes bone paradox” in which data has yet to provide reasoning for the fractures with normal or high BMD. Increased frailty has shown to put patients at higher risk for adverse outcomes. Measuring frailty in patients with diabetes may help us to understand the diabetes bone paradox.

The current study used data from the Canadian Multicentre Osteoporosis Study (CaMos). It was a prospective cohort study to determine the association between frailty and the risk of incident fractures in patients with type 2 diabetes. 3,149 patients were included in the study, with 138 patients with diabetes. Patients were to complete interview questionnaires and physical examinations at baseline, year 5, and year 10. Annually, questionnaires were mailed to record reported fractures, hospitalizations, and use of bone health medications. Those who reported incident fractures were asked for documentation of proof and data. Frailty status was measured by a Frailty Index (FI) of deficit accumulation. The higher the score the higher the frailty. The primary outcome was defined as the time to the first incident nontraumatic fragility fracture, defined as a fracture of the hip, spine, forearm, pelvis, ribs, and other sites after a fall from standing height or less. Any fractures in the face, fingers and toes were excluded. Secondary outcomes assessed the time to an incident hip fracture and to clinical spine fracture during follow-up.

Linear regression models were used to compare difference in FIs between the groups. To determine the effect of diabetes on the risk of fractures, Cox models compared fracture risk between the groups. To further assess frailty and the association to the risk of fractures and if it can change the effect of diabetes on the risk of fractures, the Cox models included an interaction term (frailty x diabetes). And lastly, a subgroup analysis by sex was performed to determine the risk of fragility fractures.

From the patients included, patients with diabetes were found to be significantly older, male, consumed alcohol, and had a higher BMI. They also had higher lumbar spine and femoral neck T-scores compared to the others (P < 0.001) and a higher FI (P < 0.001). Similar results were displayed by multivariable linear regressions with a mean difference in FIs to be 0.05 (P < 0.001). Upon follow-up, fragility fractures were reported in 611 patients, 35 of those in patients with diabetes. Patients with diabetes presented with higher incidences of fragility (25.4%), hip (4.4%), and spine fractures (2.2%). Diabetes was significantly associated with an increased risk of all fragility fractures (P = 0.019), and with the risk of hip fractures (P = 0.032), but not spinal fractures (P = 0.35). 

Both basic and adjusted Cox models presented a significant relationship between the FI and the risk of incident fragility fractures (P < 0.001 for each). As the FI increased, HRs for diabetes also increased. To further support the data presented thus far, the researchers then compared the cumulative fracture risk between patients with and without diabetes. Additionally, patients were grouped based on their frailty status by the mean of the FI into either the robust or frail subgroup. Upon comparison, patients in the frail group with diabetes were consistently found to have higher cumulative fracture risks.

In terms of secondary outcomes, a significant association was found between FI and an increased risk of hip fractures (P = 0.003), but not spine (P = 0.069). However, no association was found between frailty and diabetes for risk of hip and spine fractures. After a post hoc analysis, FI was significantly associated to risk of hip and spine fractures. While there was an association between diabetes and increased risk of fractures, the increase was not statistically significant. Lastly, the subgroup analysis by sex showed an increased risk of fragility fractures in women and not men, but only for the FI and interaction, not between fragility fracture risk and FI or fracture risk and the interaction.

While patients with type 2 diabetes were found to have significantly higher BMD values, they were also found to be frailer than patients without diabetes. What the authors believe is, the fracture risk in a patient with diabetes might depend on their frailty status. Frailty might change the effect diabetes has on fracture risk and measuring its status might help determine the fracture risk in a patient with diabetes. With future studies, measuring the degree of frailty has the potential to be assessed in primary and community care settings. In this study, the fluctuation of frailty status was not able to be assessed but might help us to further understand the diabetes bone paradox and provide better care in patients with diabetes. Furthermore, data in terms of glycemic control was not accessible and could not be analyzed. Diabetes status was self-reported and not all patients with diabetes may have specifically been diagnosed with type 2 diabetes. This may affect the results, even though the authors acknowledged it would have been a very small proportion of patients who may have type 1 diabetes versus type 2 (~2%).

Practice Pearls:

• Measuring BMD alone in patients with type 2 diabetes is not enough to assess their risk of fractures.
• In patients already presenting as frail, diabetes is a risk factor for fragility fractures and should be properly assessed for need of treatment.
• Measuring the degree of frailty is recommended to improve quality of care in patients with diabetes.

Li, Guowei, et al. Frailty and Risk of Fractures in Patients With Type 2 Diabetes. Diabetes Care. 2019 April  

Emma Kammerer, L|E|C|O|M Bradenton School of Pharmacy, PharmD Candidate