Abstract
The significance of sclerostin for bone and cardiovascular health in patients with chronic kidney disease (CKD) is complex and incompletely understood. Experimental evidence suggests that anti-sclerostin therapy shows diminished efficacy on bone in the setting of CKD. Limited clinical evidence suggests that the osteoanabolic and anti-resorptive activity is attenuated, but hypocalcemia is more prevalent in patients with advanced CKD (eGFR < 30 mL/min) treated with anti-sclerostin (romosozumab) therapy as compared to patients without kidney disease. Furthermore, sclerostin is prominently expressed in uremic arteries. Whether the inhibition of sclerostin has adverse effects on cardiovascular health in CKD is currently unknown. This review summarizes the current understanding of the physiology and pathophysiology of sclerostin in CKD, with a focus on the cardiovascular safety of anti-sclerostin therapy in patients with or without CKD.
Highlights
Renal osteodystrophy (ROD) is a type of secondary osteoporosis which may occur at the early stages of chronic kidney disease (CKD), but typically occurs in patients with advanced CKD (Stage IV, eGFR < 30 mL/min)
For the first sclerostin allele set, which is associated with reduced expression of sclerostin and increased bone mineral density (BMD), no association with cardiovascular disease was identified using the data of two population-based studies of cardiovascular risk (CARDIoGRAMplusC4D and MEGASTROKE) encompassing over 1 million participants
Romosozumab is an anti-sclerostin antibody which was approved for clinical use by the U.S Food and Drug Administration (FDA) as well as the European Medicines Agency (EMA) in 2019
Summary
Renal osteodystrophy (ROD) is a type of secondary osteoporosis which may occur at the early stages of chronic kidney disease (CKD), but typically occurs in patients with advanced CKD (Stage IV, eGFR < 30 mL/min). Patients with renal osteodystrophy may have alterations in bone volume, bone turnover or bone mineralization, which may occur individually or in different constellations. The turnover, mineralization, and volumeclassification (TMV) of renal osteodystrophy was introduced in 2006, with the aim of the harmonization of the reporting of bone histology results for scientific research and clinical patient care [1]. Because ROD comes in different subtypes, with sometimes diametrically different characteristics (e.g., high or low bone turnover), it is not surprising that there is no “one-size-fits-all” treatment for ROD. The current notion is that high bone turnover should be treated with anti-resorptive agents, while low bone turnover should be treated with turnover-activating osteoanabolic therapies.
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