High prevalence of low bone mineral density in pre-dialysis chronic kidney disease patients: bone histomorphometric analysis.

UNLABELLED: Chronic kidney disease (CKD) leads to reduced bone mineral density (BMD) in pre-dialysis and dialysis patients. A few studies have used dual-energy x-ray absorptiometry (DEXA) to assess BMD in pre-dialysis CKD patients and have shown low BMD to be highly prevalent. Until now there have been no studies reporting the histological features of low BMD in pre-dialysis CKD patients. AIM: To determine the prevalence and histological features of low BMD in pre-dialysis CKD patients. METHOD: Pre-dialysis CKD patients (n = 103, 46 females/57 males), median creatinine clearance of 29 (10 - 78) ml/min/ 1.73 m2, were evaluated using biochemical analysis and DEXA. Bone biopsies were obtained from those with low BMD. RESULTS: Fifty (48.5%) out of the 103 patients had low BMD (LBD group) and 53 (51.5%) had normal BMD (NBD group). The risk for low BMD was increased in those patients with alkaline phosphatase levels above 190 U/l and intact-PTH (iPTH) below 70 pg/ml (p < 0.05). Demographic and biochemical parameters from both groups were comparable, except for lower body mass index (BMI) in LBD subjects (p = 0.04). Women who had been post-menopausal for at least 1 year comprised 65% (13/20) and 50% (13/26) of the LBD and NBD groups, respectively (p = NS). In 40 LBD patients, bone histomorphometry revealed adynamic bone disease (ABD, 52.5%), osteomalacia (OM, 42.5%) and mixed bone disease (MBD, 5%). Trabecular bone volume (BV/TV) was lower in ABD and OM patients. A nearly significant association was found between ABD and iPTH < or = 150 pg/ml (p = 0.056), whereas higher values of iPTH were associated with OM. Total alkaline phosphatase < or = 190 U/l was significantly associated with ABD, whereas higher values were associated with OM. No correlation was observed between BV/TV and BMD. CONCLUSION: Low BMD is frequent in pre-dialysis CKD patients, and low turnover bone disease, manifesting as ABD and OM, was the hallmark of this bone loss.

Parathyroid hormone changes during phosphorus load in patients with chronic renal insufficiency with low serum parathyroid hormone or adynamic bone disease.

UNLABELLED: Adynamic bone disease (ABD) is frequently associated with low serum parathyroid hormone (PTH) concentrations. Many clinical and therapeutic conditions have been associated with ABD, and recently, a low phosphorus intake accompanied by low serum concentration of phosphorus and PTH has been described. AIM: To evaluate the parathyroid gland response of chronic renal insufficiency patients (CRI) with low serum PTH or ABD to a phosphorus load. METHODS: We examined the effects of 0.5 and 1.0 g/d of phosphorus load over a period of 60 days in 18 patients with mild CRI with a bone biopsy showing ABD (n = 7) or with low serum PTH (serum intact PTH < or = 40 ng/l) and serum phosphorus < 4.5 mg/dl (n = 11). RESULTS: Serum intact PTH increased significantly only after 1 g of phosphorus (58.5 to 83 ng/l) with a median percent increase of 72%. PTH secretion increased more in patients with lower basal PTH levels (81%). Serum phosphorus did not change significantly and urinary phosphorus increased from 487 to 1,062 mg/dl (p < 0.05). Significant decreases in serum ionized calcium (from 1.26 to 1.19 mmol/l) and calcitriol (from 34.5 to 24.9 pg/ml) were observed. Changes in PTH were inversely correlated with changes in serum ionized calcium (r = -0.54, p < 0.05) and the final PTH concentrations were positively correlated with changes in serum phosphorus (r= 0.52, p < 0.05). CONCLUSIONS: The parathyroid glands of chronic renal insufficiency patients with "relative hypoparathyroidism" or ABD responded to a phosphorus load with an increase in serum PTH levels. The decrease in serum ionized calcium and calcitriol as well as minimal changes in serum phosphorus appeared to be involved in this response.

Effect of etidronate treatment on bone mass of male nephrolithiasis patients with idiopathic hypercalciuria and osteopenia.

Osteopenia is frequently found among calcium stone forming (CSF) patients with hypercalciuria. We investigated the effect of a 2-year therapeutic course of etidronate, a bone-sparing agent, in 7 young male CSF patients. The treatment consisted of a cyclic intermittent administration of phosphate followed by sodium etidronate and calcium supplementation every 74 days. Bone mineral density (BMD) measured at 12-month intervals and bone biopsies performed at baseline and after 2 years were the primary efficacy parameters. Mean lumbar spine BMD increased significantly after the 1st year by 2.6 +/- 1.0% (mean +/- SE, p < 0.05) and nonsignificantly after the 2nd year by 5.6 +/- 2.6%. Nonsignificant changes were observed for femoral neck mean BMD after either the 1st or the 2nd year (decrease of 2.0 +/- 1.0% and 2.0 +/- 3.0%, respectively). Mean histomorphometric parameters showed that bone volume, osteoid volume, and eroded surfaces did not differ from baseline (13.9 +/- 2.2 vs. 12.2 +/- 1.1%, 1.2 +/- 0.7 vs. 2.6 +/- 0.7%, and 20.7 +/- 6.2 vs. 13. 7 +/- 1.3%, respectively). Osteoid surface was significantly lower than baseline values (9.5 +/- 5.2 vs. 18.8 +/- 5.3%, p < 0.05). These data suggest that etidronate given to young male CSF patients presenting with hypercalciuria and osteopenia led to a significant amelioration of BMD, evident only in the lumbar spine after 1 year of treatment. There was no histological evidence of long-term improvement in bone remodeling.