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Bone disease in patients with chronic renal failure (CRF) is thought to be the consequence primarily of the interplay of several factors, including the serum levels of parathyroid hormone (PTH), vitamin D, calcium, and phosphorus, and exposure to bone toxins such as aluminum or amyloid. Recently the metabolic acidosis noted with CRF has been implicated as an additional factor contributing to the genesis of bone disease. Although metabolic acidosis might be the dominant factor in the cause of bone disease in some instances, more commonly this acid-base disturbance interacts with other factors contributing to the development of bone disease. The following article summarizes the data in support of an important role for metabolic acidosis in the genesis of bone disease in patients with CRF and presents our recommendations for treatment of uremic acidosis to prevent or treat the bone disease.