Effects of Treatment of Renal Osteodystrophy on Bone Histology

Abstract

Renal osteodystrophy is characterized by abnormalities in bone turnover, mineralization, and bone volume. The effects of treatment modalities for renal osteodystrophy on bone should be analyzed with respect to these abnormalities. The major treatment modalities for renal osteodystrophy include phosphate binders, vitamin D compounds, and calcimimetics. Aluminum-containing phosphate binders have been shown to be toxic to bone secondary to their effects on bone turnover, mineralization, and bone volume. The use of calcium-based phosphate binders has been associated with the development of adynamic bone disease (low bone turnover), bone loss, and worsening of vascular calcifications. New nonaluminum, noncalcium phosphate binders have been developed (sevelamer hydrochloride and lanthanum carbonate). These agents show a potential for improvement in bone turnover and bone volume. Patients with renal osteodystrophy are deficient in calcitriol and often in calcidiol. Calcidiol deficiency has been underappreciated and deserves to be addressed in the treatment of patients with renal osteodystrophy. Calcitriol replacement therapy by daily oral administration is associated with frequent episodes of hypercalcemia and suppression of bone turnover in patients with stages 3 to 5 chronic kidney disease. Pulse oral or intravenous calcitriol administration induces frequent episodes of hypercalcemia or hyperphosphatemia, respectively, and achieves the same degree of correction of bone abnormalities. There are no data on the effects of paricalcitol or doxercalciferol on human bone. Experimental data, however, show that these two analogues and maxacalcitol may control serum parathyroid hormone levels without suppressing bone turnover. Calcimimetics lower parathyroid hormone levels and bone turnover.Clin J Am Soc Nephrol 3: S157-S163, 2008. doi: 10.2215/CJN.02500607 R enal osteodystrophy (ROD) starts early with loss of kidney function (approximately 50% loss of glomerular infiltration rates [1]). Virtually all patients with advanced chronic kidney disease (CKD) have ROD, and an association between histologic changes in bone turnover and vascular calcifications has been described (2,3). This association underlines the importance of treatment of ROD. The main abnormalities of ROD encompass changes in turnover, mineralization, and bone volume (4,5); therefore, effects of treatment modalities should be analyzed with respect to these three abnormalities. Three major therapeutic groups are available for the management of ROD: phosphate binders (P-binders), vitamin D or vitamin D analogues, and calcimimetics. P-BindersUse of P-binders has evolved in the past 30 yr (6,7). Initially, aluminum-containing P-binders were used during the 1970s to 1980s. They were replaced by calcium-based P-binders in the 1980s because of toxicities associated with aluminum. In the early 1990s, non-calcium-based P-binders were introduced because, again, toxicities were found with high doses of calciumbased binders (2,8 -10). Most recently, new calcium-and aluminum-...

Targeted surgical parathyroidectomy in end‐stage renal disease patients and long‐term metabolic control: A single‐center experience in the current era

“…Elevated parathyroid hormone (PTH) levels are very common among end‐stage renal disease (ESRD) patients and the excessive elevation of PTH is difficult to control with medications alone . Although activated vitamin‐D or analogs (VDA), e.g., calcitriol, paricalcitol, doxelcalciferol lower PTH levels, they do it so at the price of promoting both calcium and phosphorus retention and increasing extra‐osseous calcification with escalating doses . Responsiveness may depend on parathyroid gland size as well .…”

Long-Term Mortality and Bone Safety in Patients with End-Stage Renal Disease Receiving Lanthanum Carbonate

“…Randomized prospective studies of paired bone biopsies also showed that LaC was not associated with bone toxicity or mineralization defects [10,28], and no clinically relevant changes in liver enzymes or bilirubin were noted [29]. In addition, LaC does not cross the blood-brain barrier, unlike aluminum-based binders [5,22], and adverse events reported by patients receiving LaC are comparable to those reported by patients taking other non-aluminum-based binders (including calcium carbonate, sevelamer hydrochloride, or standard therapy), with the exception of hypercalcemia events, which are higher in patients receiving calcium-based binders [3,15,30].…”

Cinacalcet Decreases Bone Formation Rate in Hypercalcemic Hyperparathyroidism after Kidney Transplantation

“…Most therapies for secondary hyperparathyroidism result in a decline of bone formation [23]. For example, calcitriol induced an oversuppression of bone formation rate in 80% of CKD stage 3–4 patients [24].…”