Patients with chronic kidney disease (CKD) experience an increased fracture risk due to impaired bone quality and quantity. Low bone mineral density (BMD) predicts fracture risk in all CKD stages, including advanced CKD (CKD G4-5D). Pharmacological therapy improves BMD and reduces fracture risk in moderate CKD. Its efficacy in advanced CKD remains to be determined, although pilot studies suggest a positive effect on BMD. Currently, antiresorptive agents are the most commonly prescribed drugs for prevention and therapy of osteoporosis. Their use in advanced CKD has been limited by lack of large clinical trials and fear of causing kidney dysfunction and adynamic bone disease (ABD). In recent decades, ABD has evolved as the most predominant form of renal osteodystrophy, commonly associated with poor outcomes, including premature mortality and progression of vascular calcification. Evolving evidence indicates that reduction of bone turnover by parathyroidectomy or pharmacological therapies, such as calcimimetics and antiresorptive agents, are not associated with premature mortality or accelerated vascular calcification in CKD. In contrast, chronic inflammation, oxidative stress, malnutrition, and diabetes can induce low bone turnover and associate with poor prognosis. Thus, the conditions causing suppression of bone turnover rather than the low bone turnover per se may account for the perceived association with outcomes. Anabolic treatment, in contrast, has been suggested to improve turnover and bone mass in patients with advanced CKD and low bone turnover, however, uncertainty about safety even exceeds that of antiresorptive agents. Here, we critically review the pathophysiologic concept of ABD and discuss the impact of low bone turnover on safety and efficacy of anti-osteoporosis pharmacotherapy in advanced CKD.
Copyright © 2021. Published by Elsevier Inc.

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