FINDINGS FROM TWO LARGE DATABASE STUDIES ON FRACTURE RISK IN CKD PATIENTS INCLUDING DIALYSIS

The number of patients with chronic kidney disease (CKD; stages G3–G5D) is increasing in Japan. They are reported to have a high risk of fractures, and criteria for osteoporosis treatment interventions in dialysis patients (G4–G5D) have been proposed in Europe. However, no comparable consensus exists in Japan, and large-scale evidence on fracture risk and the current status of osteoporosis treatment is limited. We assessed fracture risk and the status of osteoporosis treatment in pre-dialysis CKD and maintenance dialysis patients using nationwide claims databases in Japan.

This report consists of two studies in different CKD populations. Study A (UMIN000051620) used the Medical Data Vision database and included CKD patients aged ≥18 years with two or more eGFR measurements (April 2009–April 2023), with CKD defined as eGFR <60 mL/min/1.73 m^2. The CKD group was matched 1:1 with control patients with baseline eGFR ≥60 mL/min/1.73 m^2. Study B (UMIN000054749) used the DeSC–IQVIA Integrated Claims database to identify ≥20-year-old patients on continuous dialysis for ≥2 years (April 1, 2014–August 31, 2022) and classified them based on osteoporosis treatment history (treated or untreated). The primary endpoints in both studies were all and hip fracture incidences relative to the control group. Key secondary endpoints included bone mineral density (BMD) measurement rates and osteoporosis treatment rates. Study B also evaluated risk factors for all-cause mortality and incident cardiovascular disease (CVD), estimating hazard ratios (HRs) with 95% confidence intervals (CIs).

In Study A, comparing the CKD and control group (n=38,299 each), the incidence of all fractures did not differ (HR 1.022, 95% CI 0.952-1.098; P=0.542), but hip fracture incidence was significantly higher in the CKD group (HR 1.415, 95% CI 1.234–1.622; P<0.001). The HRs for hip fracture increased with advancing CKD stage and were more pronounced in younger subgroups. The BMD measurement and osteoporosis treatment rates were 5.3% and 10.0% in the CKD group, and 4.4% and 4.4% in the control group, respectively. In Study B, the treated group (n=1,095) was older, had a higher proportion of women, and included more patients with a history of fractures than the untreated group (n=37,188). The incidence of all fractures tended to be higher in the treated group, but the difference was not significant (HR 1.135, 95% CI 0.994–1.296; P=0.062), as well as hip (HR 0.944, 95% CI 0.721-1.236; P=0.680). Overall, 40.1% of dialysis patients underwent BMD measurement, and 7.8% received osteoporosis drugs. Age, male sex, history of fracture, diabetes, and chronic obstructive pulmonary disease were risk factors for both mortality and CVD. Dementia was an additional risk factor for mortality. Dyslipidemia, hyperuricemia, and rheumatoid arthritis were additional risk factors for CVD.

Advanced CKD was associated with increased hip fracture risk in Japan. In addition, dialysis patients with a history of fractures had increased risks of mortality and CVD onset. These findings highlight the importance of fracture risk assessments (e.g. BMD measurement) for patients with CKD, including dialysis patients, which consider comorbidities, and of timely osteoporosis treatment.