Diuretics May Increase Fracture Risk – Renal and Urology News

Diuretic treatment may increase the risk of bone fractures, a new study finds.

In a nationwide study of 863,339 US veterans, initiation of diuretics was significantly associated with a 14% increased risk of a first vertebral or nonvertebral fracture compared with nonuse, Csaba P. Kovesdy, MD, of Memphis VA Medical Center in Tennessee, and colleagues reported in Mayo Clinic Proceedings. Fractures occurred in 7.79 per 1000 patient-years over a median 7.7 years. Hip fracture was specifically associated with diuretic use.

In multivariable adjusted models, only loop and thiazide diuretic users had a significant 39% and 8% increased risk for fracture, whereas potassium-sparing diuretic users did not.

In subgroup analyses, patients 60 years of age and younger, corticosteroid users, and patients with serum sodium levels less than 140 mEq/L had significant fracture risks. Patients with an estimated glomerular filtration rate (eGFR) less than 30 mL/min per 1.73 m² did not. At baseline, the mean eGFR of veterans in the Therapeutic Interventions to Assess Outcomes and Disparities in CKD cohort was 84.4 mL/min/1.73 m².

“Hyponatremia, one of the major adverse effects of long-term use of diuretics (particularly of thiazides), has recently been recognized as a risk factor for osteoporotic fractures, potentially through hyponatremia-induced osteoclastic activity and bone loss,” Dr Kovesdy’s team pointed out.

The investigators used an intent-to-treat approach and temporal matching, comparing new diuretic users with nonusers enrolled within the same 180-day period. They adjusted models for patients’ socioeconomic factors, comorbidities, eGFR, systolic blood pressure, and body mass index. They also adjusted for multiple medications and supplements, such as calcium channel blockers, calcium and vitamin D supplements, bisphosphonates, parathyroid hormone analogs, denosumab, calcitonin, estrogen, corticosteroids, proton pump inhibitors, phenytoin, aromatase inhibitors, tamoxifen, raloxifene, medroxyprogesterone, and thyroxine.

Previous studies have found associations between diuretic use and fracture risk in specific populations, such as older adults or postmenopausal women. This veteran population was 93.5% men, limiting the generalizability of these results to women. Diabetes affected 27.1%. Mean age was 63.3 years. Half of the veterans initiated diuretics, of whom 77.4%, 22.5%, and 0.1% used thiazide, loop, and potassium-sparing diuretic users, respectively.

“Our findings suggest distinct pathophysiologic contributions of diuretics to bone metabolism and the need for careful attention to skeletal outcomes when initiating diuretics independent of known osteoporosis and fracture risk factors,” Dr Kovesdy’s team wrote.