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Reducing the Risk of Re‐Fracture in the Dialysis Population: Is it Time to Consider Therapy with PTH Analogues?

Dialysis patients are at high risk for fracture, with published rates in excess of a 20% probability of fracture over the next 10 years of dialysis. Unfortunately, there is no accepted methodology for quantifying this risk in advance of the first fracture; conventional bone densitometry performs unreliably in this role, in contrast to its utility in elderly patients with osteoporosis. The KDIGO clinical guidelines emphasize the importance of bone turnover in the development of renal osteodystrophy with high bone turnover strongly associated with uncontrolled secondary hyperparathyroidism, and adynamic bone disease (ABD) defined as a very low bone turnover state associated with functional hypoparathyroidism. It is likely that fractures occur in association with both extremes of uremic bone turnover, in addition to the known risk factors for developing osteoporosis prior to an individual developing end‐stage renal failure. No systematic evidence has been forthcoming on therapy to reduce the risk of re‐fracture after a dialysis patient presents with a first fracture. Anti‐resorptive therapy might be effective in high turnover uremic bone disease and has been demonstrably effective in reducing fracture risk in osteoporotic patients, but there is only post hoc evidence that cinacalcet might reduce the incidence of fractures, and almost no evidence on outcomes from the use of bisphosphonates in dialysis patients. Fractures associated with ABD present a particular challenge. Although aluminum intoxication has been an important cause of skeletal fracturing in the past, this is a rare event today, when nonaluminum containing dietary phosphate binders are routinely prescribed. We suggest that the use of an anabolic agent would be a more plausible approach to the management of ABD (rather than anti‐resorptive agents) and propose that a “proof‐of‐concept” trial with a PTH analogue such as teriparatide should be considered for these patients.