Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Epidemiology and Biostatistics

Supervisor

Garg, Amit X

Abstract

Patients with chronic kidney disease (CKD) face increased fracture risk yet our understanding and management of this risk remains poor. We conducted three studies using retrospective cohort analysis in Ontario, Canada. We developed a 3-year fracture prediction model for patients receiving dialysis. Secondly, we contrasted fracture rates among patients on SGLT2i or DPP4i medications, stratified by kidney function. Lastly, we examined hypocalcemia incidence post-denosumab prescription, stratified by kidney function.

Findings: The fracture risk tool, incorporating demographic and lab data, performed well (AUC 0.72). SGLT2i did not elevate fracture risk vs. DPP4i (HR 0.95 [95% CI 0.79,1.13]). In those prescribed denosumab, hypocalcemia occurred in 0.6% overall but increased to 24.1% in those with eGFR/min/1.73m². These studies contribute to our understanding of the causes and prediction of fractures in patients with CKD. Further validation of the risk score and research into the efficacy of denosumab and management of hypocalcemia are warranted.

Summary for Lay Audience

People with chronic kidney disease are at higher risk of breaking a bone than people with normal kidney function. However, we do not have an easy way of predicting those people with the highest risk so that they can receive treatments or be included in studies. Furthermore, once a person is identified as being at a high risk of breaking a bone, the treatments we have available may have side effects.

We conducted three studies to help answer questions in this area. First, we developed a calculator that will predict the 1- and 3-year risk of breaking a bone for a person receiving dialysis, based on information that is already collected as a part of dialysis care. This calculator did a good job of separating those who will have a fracture and those who will not particularly over the next year.

Then, we examined the effect that a group of diabetes medications called sodium glucose cotransporter-2 inhibitors (SGLT2i) has on the risk of fracture, as some studies have suggested they may increase the risk. We found that SGLT2i were not associated with an increased risk of fracture compared to another group of commonly used diabetes medication called dipeptidyl peptidase 4 inhibitors. This risk did not change when examined over the spectrum of kidney function.

Finally, we looked at the risk of low blood calcium after using a medication called denosumab which is commonly used to decrease the risk of fracture but has been associated with case reports of low blood calcium. We found that although the number of people who had low calcium levels was low, (0.6% of the total group) this risk increased as kidney function decreased. In the group with the lowest level of kidney function, (those on or approaching dialysis) 24% had a measured low calcium level.

The intersection between bone disease, fractures and chronic kidney disease is an understudied one. These three studies help to improve the prediction and prevention of fractures in this population.

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