Effect of 1,25-Dihydroxyvitamin D 3 and Calcium Carbonate on Bone Loss Associated With Long-Term Renal Transplantation Alfonso M. Cueto-Manzano, MD, Shaikh Konel, MD, Anthony J. Freemont, MD, Judith E. Adams, MD, Barbara Mawer, MD, Ram Gokal, MD, and Alastair J. Hutchison MD ● To investigate the effect of calcitriol plus calcium carbonate on the bone loss associated with long-term renal transplantation, 30 patients with serum creatinine levels less than 2.0 mg/dL were randomly allocated to a control (n  14) or treatment group (n  16) and studied with bone biopsy and densitometry at baseline and after 1 year of follow-up. Calcitriol (0.25 g/d) plus calcium carbonate (500 mg/d of elemental calcium) were administered to patients in the treatment group. Comparing the baseline and final data of each group at a time, no change in bone mineral density (BMD) z score was observed at the distal radius (control, –0.8  0.8 versus –0.6  0.9; treatment, –1.0  1.0 versus –1.0  1.1). However, a significant increase (P F 0.05) was found at the lumbar spine in both groups (control, 0.1  1.6 versus 0.4  1.6; treatment, –0.1  1.5 versus 0.3  1.5) and only in the treatment group at the femoral neck (control, –0.9  1.0 versus –0.8  1.0; treatment, –0.5  0.9 versus –0.3  1.1). When BMD was compared between groups, no significant differences were observed at the evaluated anatomic sites at baseline or after 1 year of follow-up. After 1 year of follow-up, adjusting for age and sex (z score), the control group showed a trend to reduce the value of several histomorphometric parameters, including osteoblast surface (–2.2  6.1 versus –3.4  3.9), osteoid surface (–2.3  3.5 versus –3.1  3.9), and osteoclast surface (0.2  5.0 versus –1.3  3.3). Consequently, there was a significant reduction (P F 0.05) in mineralizing surface (–9.8  11.0 versus –15.8  12.3) and appositional rate (–5.8  2.7 versus –7.6  2.2). In the treatment group, a significant reduction (P F 0.05) in osteoclast surface was observed at the end of the study (3.9  6.8 versus –1.2  4.1), and although a trend to reduce osteoblast surface (–2.5  2.6 versus –3.2  5.7) and osteoid surface (–2.1  2.5 versus –3.2  2.8) was also found, patients maintained approximately the same level of wall thickness (–5.2  5.3 versus –5.3  3.3) and bone volume (–2.7  1.8 versus 2.5  1.7). However, there was no improvement in mineralizing surface (–4.2  2.9 versus –10.4  3.6) or appositional rate (–5.8  3.1 versus –8.1  2.6). No significant differences in bone histomorphometric variables were observed between groups after 1 year of follow-up. In conclusion, 1,25-dihydroxyvitamin D 3 and calcium carbonate did not significantly improve bone loss in long-term renal transplant recipients. However, significant osteoclast suppression and a trend to maintain trabecular bone volume and wall thickness as well as improve the axial BMD were observed in the treatment group.  2000 by the National Kidney Foundation, Inc. INDEX WORDS: 1,25-Dihydroxyvitamin D 3 ; calcium carbonate; bone loss; bone densitometry; bone histomorphom- etry; renal transplantation. K IDNEY transplantation restores many of the excretory, metabolic, and hormonal abnormalities of chronic renal failure implicated in the development of renal osteodystrophy. 1,2 Notwithstanding, renal transplant recipients de- velop considerable bone loss within the first 6 to 18 months after grafting. 3-5 Cross-sectional data suggest that beyond 3 years after transplantation, the bone mineral density (BMD) does not change or may increase slightly but remains less than the normal population reference values. 6 Others have recently suggested a continuous demineraliza- tion process in long-term renal transplant recipi- ents. 7 In renal transplant recipients, as well as the risk factors for bone loss present in the healthy population, other abnormalities could negatively affect bone metabolism, including the previous renal osteodystrophy, hyperparathyroidism, and use of immunosuppressive drugs. The role of glucocorticoids in inducing osteoporosis is well known, 8,9 and evidence suggests that cyclospo- rine A causes in vivo high-turnover osteopenia in animals. 10,11 In humans, most studies have shown a decrease in BMD with several immunosuppres- sive regimens, including cyclosporine A and pred- nisolone. 3-5,12-15 From the Department of Renal Medicine, Manchester Royal Infirmary; and Departments of Osteopathology, Diag- nostic Radiology, and Medicine, School of Medicine, Univer- sity of Manchester, Manchester, UK. Received December 23, 1998; accepted in revised form September 17, 1999. A.M.C-M. had an International Society of Nephrology fellowship award from December 1996 to June 1998 and was in the Department of Renal Medicine, Manchester Royal Infirmary. Address reprint requests to Alfonso M. Cueto-Manzano, MD, Depto de Nefrologı ´a y M M, Instituto Nal de la Nutricio ´n Salvador Zubira ´n, Vasco de Quiroga No. 15, Deleg, Tlalpan 14000, Me ´xico, DF, Mexico. E-mail: acueto@jal1.telmex.net.mx  2000 by the National Kidney Foundation, Inc. 0272-6386/00/3502-0023$3.00/0 American Journal of Kidney Diseases, Vol 35, No 2 (February), 2000: pp 227-236 227