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

Guideline 13: Treatment of Bone Disease in Chronic Kidney Disease

This guideline has three distinct subsections, each dealing with specific types of bone disease. Two of the subsections are discussed here.

Guideline 13A: Hyperparathyroid (high-turnover) and Mixed (high-turnover with mineralization defect) Bone Disease

Guideline Statements

13A.1 - In stages 3 and 4 CKD with plasma iPTH concentrations above 70 pg/ml (7.7 pmol/L, biPTH > 35 pg/ml [stage 3]) or above 110 pg/ml (12.1 pmol/L, biPTH > 55 pg/ml [stage 4]) on more than two consecutive measurements, dietary phosphorus intake should be restricted. If this is ineffective in lowering plasma PTH concentrations, calcitriol (E) or one of its analogs (alfacalcidol [E] or doxercalciferol [O]) should be given to prevent or ameliorate bone disease.

13A.2 - In patients with stage 5 CKD who have elevated plasma iPTH concentrations (> 300 pg/ml [33.0 pmol/L]), calcitriol (E) or one of its analogs (doxercalciferol, alfacalcidol, or paricalcitol [O]) should be used to reverse the bone features of PTH overactivity (i.e., high-turnover bone disease) and to treat defective mineralization.

It is difficult to predict bone activity accurately from PTH concentrations. Although high-turnover bone disease is often associated with plasma iPTH concentrations above 400 pg/ml (44.0 pmol/L, biPTH > 200 pg/ml), lesions may be seen at lower PTH concentrations, and low-turnover bone disease may occur at plasma iPTH concentrations above 400 pg/ml (44.0 pmol/L). The definitive test for bone histology is from a bone biopsy. However, because of the difficulty and expense of performing a bone biopsy, most clinical studies of osteodystrophy used PTH concentrations as a marker for bone turnover. Thus, the newer vitamin D analogs have largely obtained FDA approval for use in the control of iPTH concentration, and few data are available to document their effect on bone histology. Since iPTH concentrations correlate to some extent with bone turnover, it is assumed that avoidance of very high or very low iPTH concentrations would prevent either the hyperactive osteitis fibrosa or the hypoactive adynamic disorder, although no convincing outcome studies have proved this.

Guideline 13C: Adynamic Bone Disease

Guideline Statements

13C.1 - Adynamic bone disease in stage 5 CKD (determined by bone biopsy or iPTH concentrations < 100 pg/ml [11.0 pmol/L, biPTH < 50 pg/ml]) should be treated by allowing plasma iPTH concentrations to increase in order to increase bone turnover (O).

13C.1a - This can be accomplished by decreasing dosages of calcium-based phosphorus binders and vitamin D or eliminating such therapy (O).

Adynamic bone disease has become increasingly frequent and may be due to overzealous suppression of PTH by vitamin D analogs or calcium-containing phosphorus binders. The effects of cinacalcet in this situation are not yet clear because of limited experience to date. Being relatively inert, adynamic bone does not modulate calcium and phosphorus concentrations appropriately. With this regulatory function impaired, calcium is neither released from nor taken up by the bone normally. One result is that minimal calcium loading often leads to marked hypercalcemia. In addition, with the failure of the bone to accrue calcium, other tissues become vulnerable to its accumulation in the form of metastatic calcification. Adynamic bone disease is associated with increased morbidity, such as an increased risk of hip fracture and vertebral collapse fracture. Age, duration of dialysis, female sex, diabetes mellitus, and decreased PTH concentrations appear to confer an increased risk of fracture.

Adynamic bone disease is treated by increasing bone turnover through an increase in PTH concentration. This can best be accomplished by lowering dosages of calcium-based phosphorus binders or replacing them with non-calcium-containing agents and by lowering or stopping vitamin D therapy or calcimimetics. The lowering of dialysate calcium concentration (to 1.0-2.0 mEq/L) may also be appropriate.

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