Bone histomorphometry before and after long-term treatment with cinacalcet in dialysis patients with secondary hyperparathyroidism

Geert J Behets, Goce Spasovski, Lulu R Sterling, William G Goodman, David M Spiegel, Marc E De Broe, Patrick C D'Haese, Geert J Behets, Goce Spasovski, Lulu R Sterling, William G Goodman, David M Spiegel, Marc E De Broe, Patrick C D'Haese

Abstract

The multicenter, single-arm BONAFIDE study characterized the skeletal response to cinacalcet in adult dialysis patients with plasma parathyroid hormone (PTH) levels of 300 pg/ml or more, serum calcium of 8.4 mg/dl or more, bone-specific alkaline phosphatase over 20.9 ng/ml and biopsy-proven high-turnover bone disease. Of 110 enrolled patients, 77 underwent a second bone biopsy with quantitative histomorphometry after 6-12 months of cinacalcet treatment. The median PTH decreased from 985 pg/ml at baseline to 480 pg/ml at the end of study (weeks 44-52). Bone formation rate/tissue area decreased from 728 to 336 μm(2)/mm(2)/day, osteoblast perimeter/osteoid perimeter decreased from 17.4 to 13.9%, and eroded perimeter/bone perimeter decreased from 12.7 to 8.3%. The number of patients with normal bone histology increased from none at baseline to 20 at 12 months. Two patients had adynamic bone at the end of study with a PTH under 150 pg/ml, and one patient with overt hypophosphatemia at baseline that reoccurred during follow-up developed osteomalacia. Thus, long-term treatment with cinacalcet substantially reduced PTH, diminished the elevated bone formation rate/tissue area, lowered several biochemical markers of high-turnover bone disease toward normal, and generally improved bone histology. Twenty patients had normal bone histology at follow-up, whereas most had mild hyperparathyroidism or mixed uremic osteodystrophy.

Figures

Figure 1
Figure 1
Study design and treatment schema.
Figure 2
Figure 2
Subject disposition by treatment phase.
Figure 3
Figure 3
Comparison of PTH level at baseline and efficacy assessment phase (median-IQR-range).P-value: Wilcoxon-signed rank test.
Figure 4
Figure 4
Primary efficacy end point: comparison of BFR/T.Ar (median-IQR-range) at baseline and end of study.P-value: Wilcoxon signed-rank test. BFR, bone formation rate; T.Ar, tissue area.
Figure 5
Figure 5
Evolution of type of renal osteodystrophy after cinacalcet treatment.

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