Title of project

Safety and Efficacy of ALendronate for Osteoporosis with Nephropathy (SEAL-ON): A randomized, double-blinded, placebo-controlled trial

Abstract

The lifetime risk of sustaining an osteoporotic fracture after age 50 is nearly one in five for men and one in two for women. Renal function declines with age, and impaired renal function is common among fracture patients. Currently, osteoporosis treatments are not recommended in patients with chronic kidney disease (CKD), partly because clinical trials demonstrating efficacy and safety are lacking. Therefore, patients with severe osteoporosis and CKD remain without treatment despite their very high fracture risk.

This randomized, double-blinded, placebo-controlled national trial will evaluate the efficacy and safety of alendronate in 514 men and women with severe osteoporosis (T-score < -2.5 and a fragility fracture) and impaired renal function (eGFR < 30 ml/min/1.73 m²). The primary outcome is cumulative fracture incidence after three years. Secondary outcomes include changes in bone turnover markers, bone mineral density, microarchitecture, bone formation and resorption (assessed by bone turnover markers), DXA, HR-pQCT, dynamic bone histomorphometry, and bone material properties, as well as quality of life assessed by questionnaires. Treatment safety will be monitored through adverse effects, blood pressure, and renal function.

The trial is conducted across multiple endocrine units with support from nephrology units and involves local and international experts in clinical endocrinology and nephrology, and bone histology, bone turnover markers, and bone material properties. If effective and safe, alendronate could become the first evidence-based therapy for patients with severe osteoporosis and CKD. Thus, this study has the potential to provide a treatment option in an area of unmet medical need that would easily and within a short timeframe be implemented into clinical practice. The project is supported with a grant (9.751.980 DKK) from Novo Nordisk Foundation (NNF20OC0065760) to cover operating expenses and salary for technicians but not the applicant.