SEARCH

SEARCH BY CITATION

Keywords:

  • Bone disease;
  • children;
  • renal transplantation;
  • vitamin D

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

The effect of treatment with alfacalcidol on post-transplantation bone loss in children and adolescents was investigated.

Of the 63 young patients who received renal transplant and were subjected to dual-energy x-ray absorptiometry (DEXA), 30 patients had low-bone mineral density (BMD) (z-score ≤−1) and were enrolled into the study. Their mean age at the time of transplantation was 14.5 ± 4.0 years and the mean duration after transplantation was 48 ± 34 months. Patients with low BMD were randomized into two equal homogeneous groups: group 1 (control) received placebo and group 2 received daily alfacalcidol 0.25 μg by mouth. Parameters of bone metabolism (intact parathyroid hormone, serum osteocalcin and urinary deoxypyridinoline) and BMD were assessed before and after the study period.

After 12 months of treatment BMD at the lumber spine decreased from −2.2 to −2.5 in group 1 while it increased from −2.1 to −0.6 in group 2 (p < 0.001). Serum intact parathyroid hormone level decreased significantly in group 2 (p = 0.042). Apart from transient hypercalcemia in 1 patient in group 2, no other significant adverse effects were noted.

This study suggested the value of alfacalcidol in the treatment of bone loss in young renal transplant recipients.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

Kidney transplantation corrects most of the metabolic abnormalities that cause renal osteodystrophy. However, many transplanted patients develop osteoporosis and other bone lesions that are related, at least in part, to their immunosuppressive regimen (1). Other abnormalities could negatively affect the bone metabolism including the pre-transplant renal osteodystrophy and persistent hyperparathyroidism (2).

Many studies were interested in the value of preventive and therapeutic interventions for post-transplant bone disease in adults; but studies in children are scarce. Most pharmacologic agents available for therapy of osteoporosis have not been subjected to prospective controlled studies in organ transplant recipients. This prompted us to enroll our patients with post-transplant bone loss in a prospective randomized study to demonstrate the value of alfacalcidol on post-transplant bone disease. Treatment with a low dose of active vitamin D and calcium partially prevents bone loss at the lumbar spine and proximal femur during the first 6 months after renal transplantation (3). The beneficial effects of active vitamin D could be partially explained in renal transplant recipients due to the unique presence of secondary hyperparathyroidism and renal osteodystrophy in these patients (4). However, the respective role of hyperparathyroidism on post-transplant bone disease remains controversial. Julian et al. (5) did not find a significant correlation between PTH (parathyroid hormone) levels and lumbar bone loss, and Kim et al. (6) obtained similar results. Other studies were consistent with the classical deleterious effect of hyperparathyroidism on bone (2,7).

We aimed to evaluate the effects of 12 months of alfacalcidol therapy on bone mass and some biochemical parameters in pediatric renal transplant recipients in a prospective randomized study.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

We prospectively studied 30 young patients with low BMD (z-score ≤−1 by DEXA) who received live related renal allotransplants at the age of 17 years or less. Inclusion criteria were a first kidney transplant performed more than 1 year previously, stable graft function at entry (serum creatinine <2.0 mg/dL), normal dietary intake and informed consent. The presence of previous vertebral or hip fracture, intake of drugs (other than immunosuppressive drugs) affecting bone metabolism were considered exclusion criteria. The Human Research Subjects Committee in our institution approved this study.

The underlying kidney diseases were hypoplastic kidney (n = 10), glomerulonephritis (n = 7), tubulointerstitial nephritis (n = 8) and hereditary nephritis (n = 5). While patients were on dialysis 18 patients had mild-to-moderate secondary hyperparathyroidism. Phosphate binding was achieved with calcium salts alone (n = 14) or in combination with aluminum-containing phosphate binders (n = 4). Fifteen patients had been treated with calcitriol at a dose ranging from 0.25 to 0.5 μg/day prior to transplantation.

We blindly randomized our patients into two groups, group 1 (control group), group 2 received oral alfacalcidol 0.25 μg daily. Every patient was supplemented with daily 500 mg oral elemental calcium as calcium carbonate. Parameters of bone turnover (intact parathyroid hormone, serum osteocalcin and urinary deoxypyridinoline) and calcium metabolism were measured before and after 12 months of treatment. BMD was measured by DEXA using lunar DFXMD 7517 machine, Madison, WI. All patients were evaluated by the same apparatus. Quality assurance was performed daily. Body composition was measured by total body DEXA. The bone, fat and lean mass of the total body were assessed by means of DEXA. The BMD results were expressed as gm/cm2. BMD was measured on the lumbar spine at L2–4, femoral neck and for the whole body. Age- and ethnicity-specific standard deviations (z-scores) were determined for all bone mineral measurements from the normative data collected from a cohort of 423 ethnically diverse, healthy youths (8). Assessment of pubertal maturity using Tanner staging was performed by transplant pediatricians within 1 month of the DEXA. Pubertal development was labeled advanced, normal or delayed based on the 3rd and 97th percentiles of published standards (9). Three patients were stage 1 Tanner, 4 were stage 2, 7 were stage 3, 8 were stage 4 and 8 were stage 5.

Serum creatinine, creatinine clearance, calcium, phosphorus, albumin and alkaline phosphatase were measured monthly using a synchron CX7 system (Beckman auto analyzer instruments, Inc, Brea, CA). The creatinine clearance was calculated from Schwartz formula for children up to 18 years (10) and using Cockroft-Gault formula in adults more than 18 years old (11). Intact parathyroid hormone was measured by a two-site radioimmunoassay for intact PTH (Diagnostic Product Corp., Los Angeles, CA). To assess bone turnover, we measured serum osteocalcin as a marker of bone formation and urine deoxypyridinoline as a marker of bone resorption. Serum osteocalcin was measured by polyclonal radioimmunoassay (12). Urine concentration of deoxypyridinoline was assayed by high-performance liquid chromatography and normalized to urinary creatinine excretion (13). Intact PTH and markers of bone turnover were measured at baseline and after 12 months of treatment.

Statistical analysis

The results are presented as means with standard deviation (SD) for nominally distributed data, or medians with percentiles for non-normal distributions. Nominally distributed continuous variables were compared using t-tests. Paired sample t-test was performed for comparison before and after treatment in the same group and repeated measures analysis was performed for comparison between both groups. Categorical variables were compared using chi-square tests. All statistical tests are two-sided, with a p-value of < 0.05 taken to indicate statistical significance. SPSS statistics package (SPSS V11.0, SPSS Inc., Chicago, IL) was used for these analyses (14).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

Patient characteristics

The mean age of patients at the time of transplantation was 14.5 ± 4.0 years and the mean duration after transplantation was 48 ± 34 months, range 12–192 months. All patients completed the study and had functioning grafts at the end of the study. Baseline patient characteristics are shown in Table 1 and there were no statistically significant differences between both groups. Of the 30 participants, 25 had a pubertal stage consistent with chronological age, whereas 5 were delayed. Four of the delayed patients had glucocorticoid exposure before transplantation, in view of their glomerular disease. There was no statistically significant difference between both groups regarding height z-scores and Tanner stage in both sexes (Table 1).

Table 1.  Base line characteristics at study entry
VariablesGroup (1)Group (2)
  1. No statistically significant differences were found between both groups.

Age (mean ± SD in years)14.6 ± 4.314.5 ± 3.8
Sex (male/female)11/412/3
Original kidney disease
 Hypoplastic kidney55
 Glomerular disease43
 Tubulointerstitial disease44
 Hereditary nephritis23
Mean duration of renal failure before transplantation (years)2.2 ± 2.12.4 ± 2.3
Pre-transplant renal replacement therapy
 No (pre-emptive)34
 Hemodialysis910
 Peritoneal dialysis31
Years since transplantation3.2 ± 2.94.1 ± 3.8
Height SD score−1.4 (−3.4 to 1.1)−1.5 (−2.9 to 0.2)
Pubertal status (advanced/normal/delayed)0/13/20/12/3
Tanner stages (1/2/3/4/5)1/2/4/4/42/2/3/4/4
Cmulative steroid dose
 15 g or less89
 More than 15 g76

Medications

Patients transplanted before 1989 (n = 3) were treated conventionally with a maintenance immunosuppressive regimen comprising daily prednisolone between 0.1 and 0.15 mg/kg and azathioprine 2 mg/kg. A triple regimen with prednisolone, cyclosporine A and azathioprine has been introduced since 1989 (n = 20). Cyclosporine A was administered so that whole-blood trough levels were maintained between 100 and 150 ng/mL. Tacrolimus was introduced as a primary therapy since 1997 (n = 7). The cmulative steroid dose was 12 ± 4 g with a maintenance daily dose of 0.1 mg/kg and there was no difference in the mean cmulative steroid dose at the baseline and after treatment in both groups (p = 0.342 and 0.248, respectively). The incidence of acute rejections in the first year of transplantation was comparable in both study groups (36% vs. 33%) and there were no rejection episodes during the study period.

Laboratory investigations

High proportions of patients in both groups (62% and 61% in both treatment and control groups, respectively) demonstrated elevated intact PTH levels at baseline. In fact, more than one third of patients demonstrated baseline intact PTH values exceeding twice the upper limit of normal (0.8–5.2 pmol/L). In contrast, the baseline osteocalcin values were below the lower limit of normal in 12 patients (40%) with non-statistical difference between groups (p = 0.18).Values of alkaline phosphatase were above upper limit of normal in 47% of patients. Average serum calcium levels were found in most of the patients in both groups; however, the values were near the lower limit of normal in 11 patients (37%). In case of creatinine clearance values, although, a trend of gradual decrease was observed throughout the study period till the end of the study after 12 months this difference did not reach statistical significance (p = 0.18). There were no statistically significant differences seen between the two groups with respect to all laboratory investigations (Table 2). After 12 months of treatment, serum calcium was significantly higher and intact PTH was significantly lower in group 2. To simplify data presentation, only the initial and final results of all variables are shown in Table 2.

Table 2.  Laboratory characteristics before and after treatment
VariablesGroup (1)Group (2)p value
BaselineAfterBaselineAfter
  1. NS = Non-significant.

  2. aThe difference in group 1 before and after treatment.

  3. bThe difference in group 2 before and after treatment.

  4. cThe difference between both groups before treatment.

  5. dThe difference between both groups after treatment.

S.cr. (mg/dL)1.5 ± 0.31.6 ± 0.31.6 ± 0.31.7 ± 0.2NS
Cr.cl. (mL/min/1.73m2)79.8 ± 10.973.6 ± 10.880.4 ± 10.872.3 ± 9.3NS
S. calcium (mg/dL)8.9 ± 0.89.0 ± 0.78.8 ± 0.89.9 ± 0.9NSa, 0.018b, NSc, 0.023d
S. phosphorus (mg/dL)3.9 ± 1.04.1 ± 1.04.0 ± 1.24.0 ± 1.2NS
S. albumin (g/dL)4.0 ± 0.53.9 ± 0.43.8 ± 0.43.7 ± 0.4NS
Alkaline phosphatase (IU/L)140.8 ± 85.3143.8 ± 66.9141.6 ± 86.3101.8 ± 86.6NSa, 0.007b, NSc, 0.006d
Intact PTH (pmol/L)6.7 ± 8.66.9 ± 8.66.5 ± 8.65.2 ± 8.7NSa, 0.044b, NSc, 0.042d
Osteocalcin (ng/mL)44.8 ± 20.645.8 ± 21.646.8 ± 23.547.9 ± 22.7NS
Urine deoxypyridinoline81.3 ± 64.383.9 ± 61.283.9 ± 61.283.9 ± 61.2NS
Urine Ca/cr.0.05 ± 0.070.04 ± 0.060.04 ± 0.080.04 ± 0.05NS

Body composition

There was no statistically significant difference in the mean values of total body composition and fat and lean mass in both groups. Table 3 shows that at the end of the study, the control group had significant bone loss at the lumbar spine, femoral neck and whole body BMD, while alfacalcidol group had significant improvement in the BMD.

Table 3.  Parameters of DEXA before and after treatment
VariablesGroup (1)Group (2)p value
BaselineAfterBaselineAfter
  1. NS = Non-significant.

  2. aThe difference in group 1 before and after treatment.

  3. bThe difference in group 2 before and after treatment.

  4. cThe difference between both groups before treatment.

  5. dThe difference between both groups after treatment.

BMD (z-score)
 Lumbar 2–4 spine−2.2 ± 2.0−2.5 ± 2.2−2.1 ± 2.1−0.6 ± 0.7NSa, <0.001b, NSc, <0.001d
 Femoral neck−2.4 ± 2.1−2.6 ± 2.3−2.3 ± 2.1−0.9 ± 0.8NSa, <0.001b NSc, <0.001d
 Whole body−1.3 ± 1.4−1.8 ± 1.7−1.2 ± 1.20.3 ± 0.2NSa, <0.001b, NSc, <0.001d
Body composition (kg)
 Total bone calcium0.717 ± 0.2060.710 ± 0.2030.716 ± 0.2090.727 ± 0.206NS
 Bone mineral content1.893 ± 0.5501.868 ± 0.5391.897 ± 0.5431.913 ± 0.547NS
 Lean body mass33.1 ± 8.134.1 ± 8.234.5 ± 8.236.1 ± 8.1NS
 Fat body mass17.2 ± 12.718.2 ± 12.117.5 ± 12.818.2 ± 12.7NS

There were no significant correlations found between BMD z-scores and time interval after transplantation or age at transplantation. Similarly, there was no significant correlation between height SD score and BMD z-scores at any site for the combined group of all transplant recipients. The improvement in bone mass in the alfacalcidol group did not correlate with an improvement in the height or weight

After 12 months of treatment all patients had functioning graft. No adverse effects related to calcium intake were recorded. Apart from transient hypercalcemia in 1 patient in group 2, which necessitated decrease of alfacalcidol dose, alfacalcidol was well tolerated and no other clinical side effects were registered. Only 1 patient in the control group had traumatic fracture humerus and no fractures were reported in the other group. The patient who experienced fracture had low BMD (z-score −2.1).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

The occurrence of bone loss is independent of the organ transplanted and has been frequently diagnosed after heart, lung, liver, bone marrow and kidney transplantation (15). The onset of bone loss has been attributed mainly to immunosuppression therapy and in particular to corticosteroids (5,16). Animal studies strongly suggest that cyclosporine has independent effects on bone and mineral metabolism that contribute to bone loss after organ transplantation (17). Moreover, Monegal et al. suggested that cyclosporine may have a deleterious effect on bone after liver transplantation (18). In renal transplant recipients, post-transplant bone loss is more complex (19). Pre-transplant renal osteodystrophy and persistent hyperparathyroidism are still risk factors for post-transplant bone loss. The diagnosis of persistent hyperparathyroidism is merely based on histomorphological data. Serum intact PTH levels are found to be increased until 6 months after renal transplantation and may persist in more than 50% of patients at 1 year (15).

Because osteoporosis remains a well known risk factor for bony fractures, and on the other hand corticosteroids and CsA could not always be avoided in immunosuppression protocols, specific antiosteoporotic treatment is necessary to preserve or restore bone mass. Specific treatment modalities include supplemental calcium, antiresorptive drugs and drugs, which exhibit a direct effect on bone formation (3,20–25). However, the use of different methods for treatment has not been well defined, especially in children.

The role of vitamin D on bone remodeling is complex because of the dual effects of the steroid, increasing both bone formation and resorption. Although osteoclasts are responsible for resorbing bone, both actions of 1, 25-(OH)2D3 on bone remodeling are mediated through the osteoblast (26).

We chose to include only those recipients who had received transplantation more than 1 year ago to avoid the period when most rapid changes in bone mineral have been shown to occur in adult recipients. After 1 year of treatment with 1-hydroxycholecalciferol (alfacalcidol) there was an improvement in BMD compared to the non-treated control group. These results are in agreement with many other studies, which could demonstrate substantial improvement of bone mass after transplantation (27–31). The high percentage of patients with mildly elevated PTH and alkaline phosphatase levels may be related to persistence of secondary hyperparathyroidism, which started prior to transplantation and present in some patients with mildly impaired graft function. Moreover, patients in the alfacalcidol group clearly had suppression of intact PTH accompanied by an increase of calcium level, which may be inconsistent with the suppression of persistent hyperparathyroidism, which is a known risk factor for bone loss in renal transplant recipients compared to other organ transplant recipients (32,33). The transplanted kidney begins to synthesize calcitriol, often within hours of transplantation, which affects parathyroid activity, reducing PTH concentration substantially but never enough to reach normal levels; so even transplant patients with best outcome in terms of renal function fail to manifest full suppression of PTH. A mild vitamin D deficiency might have contributed to the aggravation of secondary hyperparathyroidism (34). Treatment with active vitamin D could result in suppression of PTH and subsequent improvement of hypophosphatemia (30,35,36).

Despite improvement in BMD there was no change in the serum osteocalcin and urinary deoxypyridinoline in alfacalcidol group; this may be explained by the limitations of these markers in predicting BMD. Cohen and Shane reported that the current assays of osteocalcin measure both intact molecule and osteocalcin degradation products that accmulate with renal dysfunction. The development of new assays, which detect only intact serum osteocalcin, is likely to improve the utility of osteocalcin in the evaluation of renal osteodystrophy. Also, considerable biological and diurnal variations exist in deoxypyridinoline assay and this can lead to difficulties in interpreting the results (37).

The trend of decrease in BMD in the control group after 1 year of follow-up suggests that in the long term, patients may retain some of the BMD lost during the first years after transplantation. This finding is in keeping with previous reports of Pichette et al. (34) but contrasts with the data reported by Cueto-Manzano et al. (38) and those reported by Grotz et al. (7).

A gradual decline in creatinine clearance was observed in both the control and treatment groups. A reduced creatinine tubular secretion caused by calcitriol (as proposed by Bertoli et al. 39) does not seem the most feasible explanation because patients had reasonably preserved renal function, and its decrease was observed even in the control group. Hence, we believe that this effect may be caused by a natural decline in graft function.

Many studies suggested the benefit of prophylaxis with antiresorptive agents early after renal transplantation (7,23,40). In our study identification of low BMD and treatment of high-risk individuals after renal transplantation may be an alternate strategy to prophylaxis for all patients.

The findings of bone health of pediatric renal transplant recipients remain controversial. One prospective study showed a marked decrease in size-adjusted spine BMD during the first 2 years after transplantation (41). A second study found continuing losses in spine BMD even after transplantation in those patients receiving methylprednisolone (42). In contrast to the above studies, three cross-sectional studies proposed that deficits in BMD in renal transplant recipients could be attributed to the decreased height of this population (43–45). Bone density of patients was similar to controls when they were matched by height rather than chronologic age. This approach has been challenged, however, because the shorter renal transplant patients were compared with younger controls (46).

We recognize several limitations of this study. The major limitation is the relatively small number of patients. However, we intended to exclude early renal transplants and patients with normal BMD in our study to decrease the bias caused by the effect of delayed graft function and to avoid any extra factors as initial rapid bone loss after transplantation that could superimpose the treatment effect. Also BMD z-scores were calculated on the basis of chronologic age rather than skeletal or pubertal maturity. Finally, the cross-sectional design precluded calculation of rates of loss or recovery of BMD at various points after transplantation.

Despite these limitations, we believe this study adds to the existing scarce literature on the effects of alfacalcidol on post-renal transplantation bone loss in children. Although we did not correct for pubertal maturation, we found that 25 of 30 patients had Tanner pubertal stages consistent with chronologic age. Further studies are warranted to better define the effect of various treatment modalities on bone disease in pediatric renal transplantations. Larger prospective studies are needed.

In conclusion, treatment of post-renal transplantation bone loss in young population using alfacalcidol seems to be effective and safe.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References
  • 1
    Monier-Faugere MC, Mawad H, Qi Q, Friedler RM, Malluche HH. High prevalence of low bone turnover and occurrence of osteomalacia after kidney transplantation. J Am Soc Nephrol 2000; 11: 10931099.
  • 2
    Messa P, Sindici C, Cannella G, Miotti V, Risaliti A, Gropuzzo M. Persistent hyperparathyroidism after renal transplantation. Kidney Int 1998; 54: 17041713.
  • 3
    De Sevaux RG, Hoitsma AJ, Corstens FH, Wetzels JF. Treatment with vitamin D and calcium reduces bone loss after renal transplantation: a randomized study. J Am Soc Nephrol 2002; 13: 16081614.
  • 4
    Jehle PM. Steroid-induced osteoporosis, how it can be prevented? Nephrol Dial Transplant 2003; 8: 861864.
  • 5
    Julian BA, Laskow DA, Dubovsky J, Curtis J, Quarles D. Rapid loss of vertebral mineral density after renal transplantation. N Engl J Med 1991; 325: 544550.
  • 6
    Kim H, Chang K, Lee T, Kwon J, Park S. Bone mineral density after renal transplantation. Transplant Proc 1998; 30: 30293030.
  • 7
    Grotz WH, Mundinger FA, Rasenack J et al. Bone loss after kidney transplantation: a longitudinal study in 115 graft recipients. Nephrol Dial Transplant 1995; 10: 20962100.
  • 8
    Bachrach LK, Hastie T, Wang MC, Narasimhan B, Marcus R. Bone mineral acquisition in healthy Asian, Hispanic, black, and Caucasian youth: a longitudinal study. J Clin Endocrinol Metab 1999; 84: 47024712.
  • 9
    Tanner JM, Davies PS. Clinical longitudinal standards for height and height velocity for North American Children. J Pediatr 1985; 107: 317329.
  • 10
    Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children and adolescents. Pediatr Clin North Am 1987; 34: 571576.
  • 11
    Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 3135.
  • 12
    Gundberg CM, Hauschka PV, Lian JB. Osteocalcin—isolation, characterization and detection. Methods Enzymol 1984; 107: 526530.
  • 13
    Black D, Duncan A, Robins SP. Quantitative analysis of the pyridine crosslinks of collagen in urine using non-paired reversed phase high-performance liquid chromatography. Anal Biochem 1988; 169: 197204.
  • 14
    Everitt BS. Statistical Methods for Medical Investigators, 2nd Edn. New York , NY , USA : John Wiley & Sons Inc.; 1994.
  • 15
    Sperschneider H, Stein G. Bone disease after renal transplantation. Nephrol Dial Transplant 2003; 18: 874877.
  • 16
    Almond MK, Kwan JTC, Evans K, Cunningham J. Loss of regional bone mineral density in the first 12 months following renal transplantation. Nephron 1994; 66: 5257.
  • 17
    Epstein S. Post-transplantation bone disease: the role of immunosuppressive agents on the skeleton. J Bone Miner Res 1996; 11: 17.
  • 18
    Monegal A, Navasa M, Guanabens N et al. Bone mass and mineral metabolism in liver transplant patients treated with FK506 or cyclosporine A. Calcif Tissue Int 2001; 68: 8386.
  • 19
    Van-Cleemput J, Doenen W, Geusens P, Dequeker Patients, Van Der Werf F, Van Hoecke J. Prevention of bone loss in cardiac transplant recipients: a comparison of bisphosphonates and vitamin D. Transplantation 1996; 61: 14951499.
  • 20
    El-Agroudy A, El-Husseini A, El-Sayed M, Ghoneim M. Preventing bone loss in renal transplant recipients with vitamin D: a prospective randomized study. J Am Soc Nephrol 2003; 14: 29752979.
  • 21
    Cruz DN, Brickel HM, Wysolmerski JJ et al. Treatment of osteoporosis and osteopenia in long-term renal transplant patients with alendronate. Am J Transplant 2002; 2: 6267.
  • 22
    Arlen DJ, Lambert K, Ioannidis G, Adachi JD. Treatment of established bone loss after renal transplantation with etidronate. Transplantation 2001; 71: 669673.
  • 23
    Giannini S, Dangel A, Carraro G et al. Alendronate prevents further bone loss in renal transplant recipients. J Bone Miner Res 2001; 16: 21112117.
  • 24
    Grotz WH, Rump LC, Niessen A et al. Treatment of osteopenia and osteoporosis after kidney transplantation. Transplantation 1998; 66: 10041008.
  • 25
    Grotz W, Nagel C, Poeschel D et al. Effect of ibandronate on bone loss and renal function after kidney transplantation. J Am Soc Nephrol 2001; 12: 15301537.
  • 26
    Jane LF, Adriana SD, Tricia P, Eduardo AS. Relative potencies of 1,25-(OH)2D3 and 19-Nor-1,25-(OH)2D2 on inducing differentiation and markers of bone formation in MG-63 cells. J Am Soc Nephrol 2001; 12: 14681474.
  • 27
    Reginster JY, Kuntz D, Verdickt W. Prophylactic use of alfacalcidol in corticosteroid-induced osteoporosis. Osteoporos Int 1999; 9: 7581.
  • 28
    Ring JD, Coster A, Meng T, Schacht E, Umbach R. Treatment of glucocorticoids-induced osteoporosis with alfacalcidol/calcium versus vitamin D/calcium. Calcif Tissue Int 1999; 65: 337340.
  • 29
    Garcia-Delgado I, Prieto S, Fil-Fraguns L, Robles E, Rufillanchas J, Hawkins F. Calcitonin, etidronate, and calcidiol treatment in bone loss after cardiac transplantation. Calcif Tissue Int 1997; 60: 155159.
  • 30
    Talalaj M, Gradowska L, Marcinowska-Suchowierska E, Durlik M, Gaciana Z, Lao M. Efficiency of preventive treatment of glucocorticoids-induced osteoporosis with 1, 25-dihydroxyvitamin D3 and calcium in kidney transplant recipients. Transplant Proc 1996; 28: 34853487.
  • 31
    Sambrook P, Birmingham J, Kelly P et al. Prevention of corticosteroid induced osteoporosis: a comparison of calcium, calcitriol and calcitonin. N Engl J Med 1993; 328: 17471752.
  • 32
    Dissanayake IR, Epstein S. The fate of bone after renal transplantation. Curr Opin Nephrol Hypertens 1998; 7: 389395.
  • 33
    Berczi C, Asztalos L, Kincses Z et al. Comparison of calcium and alfacalcidol supplement in the prevention of osteopenia after kidney transplantation. Osteoporos Int 2003; 14: 412417.
  • 34
    Pichette V, Bonnardeaux A, Prudhomme L, Gagne M, Cardicnal J, Ouimet D. Long-term bone loss in kidney transplant recipients: a cross-sectional and longitudinal study. Am J Kidney Dis 1996; 28: 105111.
  • 35
    Steiner RW, Ziegler M, Halasz NA, Catherwood BD, Manolagas S, Deftos LJ. Effect of daily oral vitamin D and calcium therapy, hypophosphatemia, and endogenous 1-25, dihydroxycholecalciferol on parathyroid hormone and phosphate wasting in renal transplant recipients. Transplantation 2003; 56: 843846.
  • 36
    Lobo PI, Cortez MS, Stevenson W. Normocalcemic hyperparathyroidism associated with relatively low 1-25 vitamin D levels post-renal transplant can be successfully treated with oral calcitriol. Clin Transplant 1995; 9: 277281.
  • 37
    Cohen A, Shane E. Transplantation osteoporosis. Curr Opin Endocrinol Diabetes 2001; 8: 283290.
  • 38
    Cueto-Manzano MA, Konel S, Freemont JA et al. Effect of 1,25- dihydroxyvitamin D3 and calcium carbonate on bone loss associated with long-term renal transplantation. Am J Kidney Dis 2000; 35: 227236.
  • 39
    Bertoli M, Luisetto G, Ruffatti A, Urso M, Romagnoli G. Renal function during calcitriol therapy in chronic renal failure. Clin Nephrol 1990; 33: 98102.
  • 40
    Fan LS, Almond MK, Ball E, Evans K, Cunningham J. Pamidronate therapy as prevention of bone loss following renal transplantation. Kidney Int 2000; 57: 684689.
  • 41
    Feber J, Cochat P, Braillon P et al. Bone mineral density after renal transplantation in children. J Pediatr 1994; 125: 870875.
  • 42
    Ferraris JR, Pasqualini T, Legal S et al. Effect of deflazacort versus methylprednisone on growth, body composition, lipid profile, and bone mass after renal transplantation. The Deflazacort Study Group. Pediatr Nephrol 2000; 14: 682688.
  • 43
    Reusz GS, Szabo AJ, Peter F et al. Bone metabolism and mineral density following renal transplantation. Arch Dis Child 2000; 83: 146151.
  • 44
    Klaus G, Paschen C, Wuster C et al. Weight-/height-related bone mineral density is not reduced after renal transplantation. Pediatr Nephrol 1998; 12: 343348.
  • 45
    Sanchez CP, Salusky IB, Kuizon BD et al. Bone disease in children and adolescents undergoing successful renal transplantation. Kidney Int 1998; 53: 13581364.
  • 46
    Leonard MB, Bachrach LK. Assessment of bone mineralization following renal transplantation in children: limitations of DXA and the confounding effects of delayed growth and development. Am J Transplant 2001; 1: 193196.