Improvement of adynamic bone disease after renal transplantation

Brazilian Journal of Medical and Biological Research (2006) 39: 31-41 Adynamic bone disease after transplantation ISSN 0100-879X 31 Improvement of adynamic bone disease after renal transplantation K.A. Abdallah4, V. Jorgetti2, R.C. Pereira2, L.M. dos Reis2, L.M. Pereira1,2, P.H.S. Corrêa3, A. Borelli3, L.E. Ianhez1,2, R.M.A. Moysés2 and E. David-Neto1,2 Unidade de Transplante Renal, 1Divisão de Urologia, 2Nefrologia, 3Endocrinologia, 4Alergia e Imunologia Clínica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil Abstract Correspondence E. David-Neto Unidade de Transplante Renal Hospital das Clínicas, FM, USP Rua Ferdinando Laboriau, 263 01250-040 São Paulo, SP Brasil E-mail: Research supported by FAPESP (No. 95/02431-9). R.M.A. Moysés was also supported by FAPESP (No. 98/06352-4). Received December 1, 2004 Accepted August 19, 2005 Low bone remodeling and relatively low serum parathyroid hormone (PTH) levels characterize adynamic bone disease (ABD). The impact of renal transplantation (RT) on the course of ABD is unknown. We studied prospectively 13 patients with biopsy-proven ABD after RT. Bone histomorphometry and bone mineral density (BMD) measurements were performed in the 1st and 12th months after RT. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and osteocalcin were measured regularly throughout the study. Serum PTH levels were slightly elevated at transplantation, normalized at the end of the third month and remained stable thereafter. Bone biopsies performed in the first month after RT revealed low bone turnover in all patients, with positive bone aluminum staining in 5. In the 12th month, second biopsies were performed on 12 patients. Bone histomorphometric dynamic parameters improved in 9 and were completely normalized in 6, whereas no bone mineralization was detected in 3 of these 12 patients. At 12 months post-RT, no bone aluminum was detected in any patient. We also found a decrease in lumbar BMD and an increase in femoral BMD. Patients suffering from ABD, even those with a reduction in PTH levels, may present partial or complete recovery of bone turnover after successful renal transplantation. However, it is not possible to positively identify the mechanisms responsible for the improvement. Identifying these mechanisms should lead to a better understanding of the physiopathology of ABD and to the development of more effective treatments. Introduction Renal transplantation (RT) typically corrects most mineral metabolism abnormalities that can lead to renal osteodystrophy. However, pre-existing bone diseases may not be completely resolved by RT, especially if the recovery of renal function is not Key words • Adynamic bone disease • Aluminum bone disease • Bone biopsy • Parathormone • Renal osteodystrophy • Renal transplantation adequate. In addition, the immunosuppressive drugs commonly used to prevent rejection have significant effects on bone remodeling and are also responsible for RT-related bone loss. As a consequence, there is a significant decrease in bone mineral density (BMD) in the first year after RT, which has been confirmed by various prospective studBraz J Med Biol Res 39(1) 2006 32 K.A. Abdallah et al. ies (1). In some cases, bone loss has been as high as 10%. However, these studies were not able to determine the various patterns of renal osteodystrophy (high or low bone turnover) because they were based on BMD findings. Currently, renal osteodystrophy is differentiated solely by means of a bone biopsy and histomorphometric analysis (2) and few prospective studies have evaluated this parameter (3-6). For example, mild to moderate hyperparathyroidism is spontaneously reversed during the first 1 or 2 years after a successful RT (3). We have previously demonstrated that successful kidney transplantation clears the aluminum on the mineralizing surface and restores normal bone remodeling in patients with aluminumrelated osteomalacia (4). However, there are no data regarding the outcome of adynamic bone disease (ABD) following kidney transplantation. In the present study, we have examined the natural course of ABD after kidney transplantation and the effect of previous low bone remodeling activity on bone mass. Material and Methods Patients and study design In order to identify patients with ABD, all patients who lacked clear signs of moderate or severe hyperparathyroidism (parathyroid hormone (PTH) >800 pg/mL or radiologic features of hyperparathyroidism) at admission for RT were considered. The study was approved by the Hospital Ethics Committee and only those who agreed to participate in the study were enrolled. After giving informed written consent, the patients were submitted to a bone biopsy during the first month after transplantation. The 13 patients in whom ABD was confirmed remained in the study. The BMD of the lumbar spine (L1-L4) and of the total femoral neck was also measured. After following the patients for 1 year, Braz J Med Biol Res 39(1) 2006 BMD and bone biopsies were repeated. Hormonal and biochemical markers related to bone metabolism were routinely measured. Signs and symptoms related to bone disease were investigated. Laboratory measurements The first blood sample obtained from patients undergoing cadaver kidney transplantation was collected immediately prior to surgery. All other blood samples were collected in the morning after an overnight fast. Serum calcium (normal range = 9.011.0 mg/dL), phosphorus (normal range = 2.3-4.6 mg/dL), alkaline phosphatase (normal range = 60-170 U/L), and creatinine (normal range <1.4 mg/dL) were measured with a Cobas-Integra autoanalyzer (Roche Diagnostics Corporation, Indianapolis, IN, USA). Osteocalcin (normal range = 6-37 pg/ mL) and intact PTH (normal range = 8-76 pg/mL) were measured by radioimmunoassay using Cis-Bio assays (CIS-BIO International, Gif-sur-Yvette, France). Levels of 1,25-dihydroxyvitamin D (1,25-(OH)2D3, normal range = 16-55 pg/mL) were determined by radioimmunoassay (Nichols Institute, San Juan Capistrano, CA, USA). Radioimmunometric assay (INCSTAR, Rohm and Haas Company, Dietzenbach, Germany) was used to measure 25-hydroxyvitamin D (25-(OH)D3, normal range = 16-74 ng/mL). Blood samples were collected and kept at 20ºC until analysis. Analysis was carried out in duplicate. Bone mineral densitometry Vertebral and femoral bone density was measured by dual-energy X-ray absorptiometry (Hologic QDR-4500, Waltham, MA, USA). The results are reported as BMD (g/ cm2) and as percentage of the value for an age- and sex-matched population. For serial measurements, the position and the region of interest were carefully determined. The 33 Adynamic bone disease after transplantation coefficient of variation for a phantom spine evaluation was 0.5%. Bone histomorphometry Biopsy specimens were obtained from the anterior superior iliac crest after double labeling with tetracycline, with a 10-day interval betwee (...truncated)