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Bisphosphonates in Chronic Kidney Disease; Balancing Potential Benefits and Adverse Effects on Bone and Soft Tissue

Nigel D. Toussaint^*, Grahame J. Elder, and Peter G. Kerr^*

^* Department of Nephrology, Monash Medical Centre and Monash University, Clayton, Victoria, Australia; and Centre for Transplant and Renal Research, Westmead Millennium Institute and Bone and Mineral Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia

Correspondence: Dr. Nigel Toussaint, Department of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia. Phone: (w) +61 3 9594 3072, (m) + 61 418 560 198; E-mail: Nigel.Toussaint{at}med.monash.edu.au

Cardiovascular disease is highly prevalent in chronic kidney disease (CKD) and is often associated with increased vascular stiffness and calcification. Recent studies have suggested a complex interaction between vascular calcification and abnormalities of bone and mineral metabolism, with an inverse relationship between arterial calcification and bone mineral density (BMD). Although osteoporosis is recognized and treated in CKD 1 to 3, the interpretation of BMD levels in the osteoporotic range is controversial in CKD 4, 5, and 5D when renal osteodystrophy is generally present. In addition, there is a paucity of data for patients with CKD mineral and bone disorder (MBD), because studies using bisphosphonates in postmenopausal and glucocorticoid-induced osteoporosis have generally excluded patients with significant CKD. For these patients, treatment of low BMD using standard therapies for osteoporosis is not without potential for harm due to the possibility of worsening low bone turnover, osteomalacia, mixed uraemic osteodystrophy, and of exacerbated hyperparathyroidism; and bisphosphonates should only be used selectively and with caution. Some experimental and clinical studies have also suggested that bisphosphonates may reduce progression of extra-osseous calcification and inhibit the development of atherosclerosis. The authors review the potential benefits and risks associated with bisphosphonate use for bone protection in CKD, and assess their effect on vascular calcification and atherosclerosis.