Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease: An Overview

George R. Bailie, PharmD, PhD, FCCP; Shaul G. Massry, MD

Disclosures

Pharmacotherapy. 2005;25(12):1687-1707. 

In This Article

Types of Bone Disease in Chronic Kidney Disease

One outcome of longstanding disturbances in mineral metabolism is the development of different types of bone disease, which can vary from one patient with CKD to another. The most commonly encountered are enhanced bone resorption (high-turnover bone disease [osteitis fibrosa]), adynamic bone disease, and mixed bone disease. Mild forms of these derangements in bone metabolism may be observed in the early stages of CKD (stage 2, glomerular filtration rate [GFR] 60-89 ml/min/1.73 m2) and become more severe as kidney function deteriorates. In high-turnover bone disease, elevated blood concentrations of PTH are responsible for an enhanced number and activity of osteoclasts, leading to increased bone resorption. A consequence of this is the release of calcium and phosphorus into the systemic circulation. Ongoing absorption of calcium from the gastrointestinal tract during treatment with calcium-based drugs leads to the propensity for metastatic calcification in soft tissues.

Adynamic bone disease is associated with oversuppression of parathyroid gland activity with high calcium intake (from diet, dialysate, calcium-containing phosphorus binders) and/or overzealous administration of vitamin D analogs, such as 1,25-dihydroxyvitamin D3 (calcitriol), 25-norvitamin D2 (paricalcitol), or 1α-hydroxyvitamin D2 (doxercalciferol), resulting in low blood concentrations of PTH. Whether this may be associated with the use of cinacalcet (a calcimimetic agent for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease) is unclear because of limited experience with this drug. Patients with adynamic bone disease have lower blood concentrations of PTH that may fall below the recommended target range (intact PTH [iPTH] 150-300 pg/ml), resulting in a bone turnover rate that is less than normal. (Note: since the publication of these K/DOQI guidelines, a different PTH assay has become widely used—the biointact PTH [biPTH] assay. This assays different parts of the PTH molecule, resulting in a target range of 50% of that for iPTH [i.e., 75-150 pg/ml]). In these circumstances, bone may not take up calcium for incorporation into new bone, and any excess calcium may be predisposed to result in calcification in soft tissues. Currently in the United States, about 25% of patients undergoing dialysis have a PTH concentration above the target range (high-turnover disease), about 25% have a PTH within the target range, and about 50% have a PTH less than the target range (adynamic bone disease). Osteosclerosis and osteoporosis may also be encountered. Also, adynamic bone disease may develop after the long-term use of aluminum-based phosphorus-binding agents. Under those circumstances, aluminum accumulates in the mineralization front and prevents osteoid mineralization.

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