Bone disease in children and adolescents undergoing successful renal transplantation

Abstract

Little is known about the extent and severity of bone disease in children undergoing successful renal transplantation. To address this issue, 47 patients with stable renal function 3.2 +/- 1.7 years after transplantation (Tx) underwent iliac crest bone biopsy. The mean age of patients was 12 +/- 2.0 years; 36 had received cadaveric renal grafts, whereas 11 had undergone living-related Tx. Immunosuppressive drugs included cyclosporine 0.17 +/- 0.4 mg/kg/day, prednisone 7.5 +/- 2.1 mg/kg/day, and either azathioprine 1.6 +/- 0.9 mg/kg/day or mycophenolate mofetil 30 +/- 3 mg/kg/day. In addition to quantitative bone histomorphometry, the bone mineral content (BMC) of the lumbar spine was measured by dual energy X-ray absorptiometry (DXA) in 24/47 patients. Thirty-one transplant recipients had normal bone formation (N-Bfr), 11 had mild hyperparathyroidism (HPT) and 5 had adynamic skeletal lesions (AD). The interval since Tx, duration of dialysis before Tx and cumulative prednisone dose did not differ among groups. Trabecular bone area was highest in subjects with HPT. Unexpectedly, eroded bone perimeter exceeded normal reference values both in patients with AD and in those with N-Bfr; the osteoid area and osteoid perimeter were also elevated in these two groups. Hyperparathyroidism improved or resolved after Tx in all 14 subjects with this skeletal lesion prior to Tx, but one patient developed AD after Tx. Bone histology did not change after Tx in those with N-Bfr during regular dialysis, but bone formation increased after Tx in two of three patients with AD during regular dialysis. Z-scores for height in pre-pubertal patients after Tx were below age-appropriate values in each histologic subgroup, but values did not differ among groups. Z-scores for bone mineral content at the lumbar spine were also less than age-predicted values, -0.67 +/- 1.2. After adjusting for the degree of growth retardation, height-adjusted z-scores for lumbar spine BMC after Tx were above normal in all three histologic groups (0.68 +/- 1.0). The results suggest that reductions in bone mass and post-transplant osteoporosis are not prominent findings in pediatric renal transplant recipients when the influence of growth retardation on bone mass measurements by DXA is carefully considered.

Value of the New Bone Classification System in Pediatric Renal Osteodystrophy

“…Although reports from prior decades demonstrated a prevalence of the mixed lesion of renal osteodystrophy in adult and pediatric dialysis patients (1,14), these lesions were defined primarily by excess osteoid accumulation, which was attributed to aluminum intoxication and/or to the stimulatory effects of PTH on osteoblast matrix secretion. However, in these findings, the mineralization defect was defined as a combination of osteoid accumulation and delayed osteoid maturation-a parameter that would not be expected to be altered by excess PTH alone.…”

“…Derived indices were calculated by formulas displayed in the appendix. Normal values for all histomorphometric parameters were previously obtained from double-tetracycline-labeled iliac crest bone biopsy specimens from 31 pediatric patients with normal kidney function (mean age 12.4 Ϯ 8.9 years, 71% male, 48% Caucasian, and 26% Hispanic) who were undergoing elective orthopedic surgery (14). Bone specimen acquisition, fixation, staining, and measurement for these normal volunteers were performed as described above for study subjects.…”

“…Bone turnover was determined by bone formation rate/bone surface (BFR/BS) after tetracycline labeling and was classified as low, normal, or high on the basis of normal values previously established at our institution (12,14). Biochemical values were evaluated for each bone turnover subgroup.…”

Early Skeletal and Biochemical Alterations in Pediatric Chronic Kidney Disease

“…Patients were admitted to the UCLA General Clinical Research Center and full-thickness bone biopsies (0.5 cm in diameter by 1-2 cm in length) were obtained from the anterior iliac crest using a modified Bordier trephine needle after double tetracycline labeling (13). Specimens were dehydrated in alcohol, cleared with xylene, and embedded in methylmethacrylate.…”

“…Derived indices were calculated as described by Parfitt et al (14). Normal parameters of bone histomorphometry were defined from bone biopsies obtained from a control group of 31 pediatric patients with normal kidney function (mean age, 12.461.5 years; 71% male; 48% Caucasian and 26% Hispanic) undergoing elective orthopedic surgery (13).…”