Rethinking Bone Disease in Kidney Disease

Abstract

Renal osteodystrophy (ROD) is the bone component of chronic kidney disease mineral and bone disorder (CKD-MBD). ROD affects bone quality and strength through the numerous hormonal and metabolic disturbances that occur in patients with kidney disease. Collectively these disorders in bone quality increase fracture risk in CKD patients compared with the general population. Fractures are a serious complication of kidney disease and are associated with higher morbidity and mortality compared with the general population. Furthermore, at a population level, fractures are at historically high levels in patients with end-stage kidney disease (ESKD), whereas in contrast the general population has experienced a steady decline in fracture incidence rates. Based on these findings, it is clear that a paradigm shift is needed in our approach to diagnosing and managing ROD. In clinical practice, our ability to diagnose ROD and initiate antifracture treatments is impeded by the lack of accurate noninvasive methods that identify ROD type. The past decade has seen advances in the noninvasive measurement of bone quality and strength that have been studied in kidney disease patients. Below we review the current literature pertaining to the epidemiology, pathology, diagnosis, and management of ROD. We aim to highlight the pressing need for a greater awareness of this condition and the need for the implementation of strategies that prevent fractures in kidney disease patients. Research is needed for more accurate noninvasive assessment of ROD type, clinical studies of existing osteoporosis therapies in patients across the spectrum of kidney disease, and the development of CKD-specific treatments. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Keywords: BONE DISEASE; CKD; CKD‐MBD; ESKD; FRACTURES; OSTEOPOROSIS.

Figure 1

Adjusted hospitalized fracture rates per 1000 person‐years in Medicare point‐prevalent hemodialysis and non‐ESKD patients aged 66 years or older. Reprinted with permission from Arneson et al.73

Figure 2

HR‐pQCT provides detailed images of bone microarchitecture at the radius (left) and tibia (right). Scout view (A) reference line position (solid line) and the measurement site (dotted line). Images from healthy, postmenopausal white female (B). Images from female with CKD, no fractures (C). Images from female with CKD and prevalent fractures (D). Reprinted with permission from Nickolas et al.103

Figure 3

Algorithm for fracture risk screening and initiation of antifracture strategies in patients with CKD. DXA = dual‐energy X‐ray absorptiometry; CKD‐MBD = chronic kidney disease‐mineral and bone disorder; PTH = parathyroid hormone; BSAP = bone‐specific alkaline phosphatase; LLN = lower limit of the normal reference range; ULN = upper limit of the normal reference range. Lifestyle factors include weight‐bearing exercise, cessation of smoking, adequate nutrition, moderate alcohol intake, and fall prevention strategies. Management of CKD‐MBD includes phosphate lowering, vitamin D supplementation (nutritional and active), calcimimetics, and parathyroidectomy. Anabolic agents include teriparatide and abaloparatide. Antiresorptive agents include bisphosphonate and denosumab.