Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation.
BACKGROUND
Bone loss occurs during the first 6 months after renal transplantation (RT), and corticosteroid therapy plays an important role. Although calcium plus vitamin D administration prevents corticosteroid-induced osteoporosis, its use in RT recipients is limited by the risk of hypercalcemia.


METHODS
This double-blind, randomized, and controlled prospective intervention trial examined the effect of intermittent calcitriol (0.5 microg/48 h) during the first 3 months after RT, plus oral calcium supplementation (0.5 g/day) during 1 year with calcium supplementation alone. The primary outcome measure was the change in bone mineral density (BMD) at 3 and 12 months after RT; we also explored whether the effect of calcitriol on BMD was different among vitamin D receptor (VDR) genotypes (BsmI). Forty-five recipients were randomized to calcitriol therapy (CT) and 41 were randomized to placebo (PL).


RESULTS
Both groups had a similar degree of pre-existing hyperparathyroidism (197 +/- 229 vs. 191 +/- 183 pg/mL), but a more pronounced decrease of parathyroid hormone (PTH) levels after RT was observed in CT patients (at 3 months: 61.4 +/- 42.2 vs. 85.7 +/- 53.1 pg/mL, P= 0.02; at 12 months: 67.3 +/- 33.7 vs. 82.6 +/- 37 pg/mL; P= 0.08). CT patients preserved their BMD at the total hip significantly better than those on PL (3 months: 0.04 +/- 3.3 vs. -1.93 +/- 3.2%, P= 0.01; 12 months: 0.32 +/- 4.8 vs. -2.17 +/- 4.4%, P= 0.03); significant differences were noted at the intertrochanter, trochanter, and Ward's triangle. Differences did not reach significance at the femoral neck. Two CT patients (4.4%) and 4 PL patients (9.8%) developed a hypercalcemic episode during the first 3 months after RT. The effect of CT on BMD at 3 months was more prominent in recipients with the at-risk allele of the VDR gene (P= 0.03).


CONCLUSIONS
Therapy with low-dose calcium supplements during 1 year, plus intermittent calcitriol for 3 months after RT, is safe, decreases PTH levels more rapidly, and prevents bone loss at the proximal femur; a more pronounced effect is seen in recipients with at least one at-risk allele of the VDR genotype.
Torres
Armando
A
Nephrology Section, Hospital Universitario de Canarias, University of La Laguna, Tenerife, Canary Islands, Spain. atorres@ull.es
García
Sagrario
S
Gómez
Angeles
A
González
Antonieta
A
Barrios
Ysamar
Y
Concepción
María Teresa
MT
Hernández
Domingo
D
García
José J
JJ
Checa
María Dolores
MD
Lorenzo
Victor
V
Salido
Eduardo
E
D000284:Administration, Oral; D000328:Adult; D015519:Bone Density / Q000187:drug effects; D002117:Calcitriol / Q000008:administration & dosage*; D002118:Calcium / Q000008:administration & dosage*; D002120:Calcium Channel Agonists / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018167:Receptors, Calcitriol / Q000235:genetics; D012307:Risk Factors
D002120:Calcium Channel Agonists; D018167:Receptors, Calcitriol; D002117:Calcitriol; D002118:Calcium