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Osteoporosis After Kidney Transplantation: Preliminary Report From a Single Center
Osteoporosis After Kidney Transplantation: Preliminary Report From a Single Center H.-H. Wang, P.-C. Chang, S.-H. Chu, K.-L. Liu, P.-C. Lai, J.-Y. Huang, and Y.-J. Chiang ABSTRACT Objective. One of the major adverse effects of kidney transplantation is osteoporosis, which is mainly related to steroid use. Only limited data are available on calcitonin therapy for posttransplantation osteoporosis. Method. From March 2007 to August 2007, 67 kidney recipients agreed to enter this study. Dual energy X-ray absorptiometry (DEXA) was performed to evaluate bone mineral density (BMD) in the lumbar (L) spine and left femoral neck. We prescribed calcitonin nasal spray to osteoporosis patients (DEXA T ⬍⫺2.5 SD) who agreed with the treatment. A second and a third DEXA were performed at 3-month subsequent intervals later to evaluate the therapeutic effects. Results. The incidence of osteoporosis in our kidney recipients was 46.26% (31/67 patients). Osteopenia accounted for 38.81% (26/67 patients) and only 14.93% (10/67 patients) were normal. Calcitonin inhalation seemed to improve the BMD with 61% showing improvement on the second DEXA study in our preliminary data. Conclusion. Our preliminary data suggested that calcitonin may help to restore bone mass in kidney recipients with osteoporosis. Steroid elimination may prevent the onset of osteoporosis and might even enhance calcitonin efficacy. In the future we need a longer study period to confirm the results and compare it with the outcomes of bisphosphonates therapy.
O
NE of the major adverse effects of kidney transplantation is osteoporosis, which may be mainly related to steroid use.1 Other risk factors include immunosuppressants, loop-diuretics, pre-existing hyperparathyroidism, long waiting time, immobility, lower body mass index (BMI), diabetes, and impaired graft function.2 Treatments with calcitrol or bisphosphonates have been reported to be successful.2 However, data on calcitonin therapy for posttransplantation osteoporosis are scarce. The aims of this cross-sectional study were to measure the severity of bone loss and to longitudinally evaluate the efficacy of calcitonin on osteoporosis. METHODS From March 2007 to August 2007, there were 67 kidney recipients who agreed to enter this study. Dual energy X-ray absorptiometry (DEXA) was performed to evaluate bone mineral density (BMD) in the lumbar (L) spine and left hip/femoral head. World Health Organization (WHO) criteria were used to evaluate the severity of bone loss. We prescribed calcitonin nasal spray to osteoporosis patients (DEXA T ⬍⫺2.5 SD) if they agreed to the treatment. A
second and a third DEXA were performed subsequently at 3-month intervals to evaluate the therapeutic effects.
RESULTS
The incidence of osteoporosis (DEXA T ⬍⫺2.5 SD) in our kidney recipients was 46.26% (31/67 patients). Osteopenia (DEXA T between ⫺1.0 and ⫺2.5 SD) accounted for 38.81% (26/67 patients) and only 10 (14.93%) patients were normal. The standard immunosuppressants in our center included a calcineurin inhibitor (CNI), a mycophenolate derivative (MPA), and steroids. Some patients were sucFrom the Departments of Urology (H.-H.W., P.-C.C., S.-H.C., K.-L.L., Y.-J.C.) and Nephrology (P.-C.L., J.-Y.H.), Chang-Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan. Address reprint requests to Yang-Jen Chiang, MD, Department of Urology, Chang-Gung Memorial Hospital, No. 5, FuHsing St., Gueishan, Taoyuan 333, Taiwan. E-mail: zorro@ cgmh.org.tw
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.06.042
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2412
Transplantation Proceedings, 40, 2412–2413 (2008)
OSTEOPOROSIS
cessfully reduced on and eliminated from steroids. Of 15 patients free of steroids in this study, and only 6 (40%) had osteoporosis. The type of CNI or MPA did not alter the risk of osteoporosis. In the 31 osteoporosis patients, 22 agreed to nasal calcitonin (200 IU spray every other day) to increase bone mass. We repeated DEXA 3 months after treatment. In the 18 patients who completed the 3-month treatment, 12 showed L-spine BMD and 6 femoral neck BMD improvements. To determine the overall effect, we observed that 11 of the 18 patients had net increased DEXA T values. For those not responding well, we added bisphosphonates; they needed further DEXA follow-up to evaluate their outcomes. No patient had a fracture during the study period. There was no adverse effect reported with calcitonin nasal spray use. A further randomized study comparing this with bisphosphonates therapy may give us more clues on the management of osteoporosis in recipients.
DISCUSSION
Bone mass loss is a well-recognized adverse effect after kidney transplantation. Our cross-sectional study demonstrated that 46.26% experienced osteoporosis, 38.81% experienced osteopenia, and 14.93% were normal. We have somehow seen a higher incidence of low bone density compared with Durieux et al,3 Parker et al,4 and Gallego et al.5 This may relate to the longer waiting period in Taiwan, which has been described as a risk factor for posttransplantation bone loss. Most studies have shown that bone density loss is mainly related to cumulative steroid dose.5,6 Our data showed less osteoporosis in the steroid-elimination recipients (6/15 [40%] compared with 25/52 [48.1%]). All 3 patients who used calcitonin had improved bone density. This result suggested that steroid minimization or elimination may be one option for osteoporosis management and that it might increase the efficacy of calcitonin. However, we have to enroll more cases to confirm this finding. The roles of CNI, MPA, and rapamycin are controversial.2 In our study the different type of CNI or MPA did not alter the risk of osteoporosis. Among other risk factors, no significant difference between normal and osteoporosis recipients was found based on BMI, diabetes, waiting time, and graft function. Our case number was limited; we need
2413
for accumulate more patients to affirm a solid conclusion on risk factors. Considering therapy for posttransplantation bone loss, calcitriol or bisphosphonates have been reported to be effective.2 There is a limited report on the effect of calcitonin on osteoporosis after kidney transplantation. Grotz et al reported increased L-spine BMD but no improvement in femoral neck BMD after calcitonin nasal spray use.7 Our protocol for osteoporosis recipients used calcitonin intranasal (200 IU every other day for 3 months). Among the 18 patients who completed the 3-month therapy, 12 had increased L-spine BMD and 6 had increased femoral neck BMD. There were 11 (61%) patients who showed a net gain of BMD. Our data also revealed a better effect on the L-spine, probably due to a greater trabecular component in the spine and more cortical bone in the femoral neck. More evidence on calcitonin effects on bone homeostasis are required to confirm this theory. This preliminary result suggested that calcitonin nasal spray improved bone mass in 61% of posttransplantation osteoporosis patients. In conclusion, our preliminary data suggested that calcitonin might help to restore bone mass in kidney recipients with osteoporosis. Steroid elimination may prevent the onset of osteoporosis and even enhance calcitonin effectiveness. In the future we need a longer study period to confirm the results and compare them with the effects of bisphosphonate therapy. REFERENCES 1. Julian BA, Laskow DA, Dubovsky J, et al: Rapid loss of vertebral mineral density after transplantation. N Engl J Med 325:544, 1991 2. Kodras K, Haas M: Effect of kidney transplantation on bone. Eur J Clin Invest 36:63, 2006 3. Durieux S, Mercadal L, Orcel P, et al: Bone mineral density and fractures prevalence in long-term kidney graft recipients. Transplantation 74:496, 2002 4. Parker CR, Freemont AJ, Blackwell PJ, et al: Cross-sectional analysis of renal transplantation ostroporosis. J Bone Miner Res 4:1943, 1999 5. Gallego R, Oliva E, Vega N, et al: Steroids and bone density in patients with functioning kidney allografts. Transplant Proc 38:2434, 2006 6. Pichette V, Bonnardeux A, Prudhomme L, et al: Long-term bone loss in kidney transplant recipients: a cross-sectional and longitudinal study. Am J Kidney Dis 28:105, 1996 7. Grotz WH, Rump LC, Niesssn A, et al: Treatment of osteopenia and osteoporosis after kidney transplantation. Transplantation 66:1004, 1998
O
NE of the major adverse effects of kidney transplantation is osteoporosis, which may be mainly related to steroid use.1 Other risk factors include immunosuppressants, loop-diuretics, pre-existing hyperparathyroidism, long waiting time, immobility, lower body mass index (BMI), diabetes, and impaired graft function.2 Treatments with calcitrol or bisphosphonates have been reported to be successful.2 However, data on calcitonin therapy for posttransplantation osteoporosis are scarce. The aims of this cross-sectional study were to measure the severity of bone loss and to longitudinally evaluate the efficacy of calcitonin on osteoporosis. METHODS From March 2007 to August 2007, there were 67 kidney recipients who agreed to enter this study. Dual energy X-ray absorptiometry (DEXA) was performed to evaluate bone mineral density (BMD) in the lumbar (L) spine and left hip/femoral head. World Health Organization (WHO) criteria were used to evaluate the severity of bone loss. We prescribed calcitonin nasal spray to osteoporosis patients (DEXA T ⬍⫺2.5 SD) if they agreed to the treatment. A
second and a third DEXA were performed subsequently at 3-month intervals to evaluate the therapeutic effects.
RESULTS
The incidence of osteoporosis (DEXA T ⬍⫺2.5 SD) in our kidney recipients was 46.26% (31/67 patients). Osteopenia (DEXA T between ⫺1.0 and ⫺2.5 SD) accounted for 38.81% (26/67 patients) and only 10 (14.93%) patients were normal. The standard immunosuppressants in our center included a calcineurin inhibitor (CNI), a mycophenolate derivative (MPA), and steroids. Some patients were sucFrom the Departments of Urology (H.-H.W., P.-C.C., S.-H.C., K.-L.L., Y.-J.C.) and Nephrology (P.-C.L., J.-Y.H.), Chang-Gung Memorial Hospital and Chang-Gung University College of Medicine, Taoyuan, Taiwan. Address reprint requests to Yang-Jen Chiang, MD, Department of Urology, Chang-Gung Memorial Hospital, No. 5, FuHsing St., Gueishan, Taoyuan 333, Taiwan. E-mail: zorro@ cgmh.org.tw
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.06.042
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2412
Transplantation Proceedings, 40, 2412–2413 (2008)
OSTEOPOROSIS
cessfully reduced on and eliminated from steroids. Of 15 patients free of steroids in this study, and only 6 (40%) had osteoporosis. The type of CNI or MPA did not alter the risk of osteoporosis. In the 31 osteoporosis patients, 22 agreed to nasal calcitonin (200 IU spray every other day) to increase bone mass. We repeated DEXA 3 months after treatment. In the 18 patients who completed the 3-month treatment, 12 showed L-spine BMD and 6 femoral neck BMD improvements. To determine the overall effect, we observed that 11 of the 18 patients had net increased DEXA T values. For those not responding well, we added bisphosphonates; they needed further DEXA follow-up to evaluate their outcomes. No patient had a fracture during the study period. There was no adverse effect reported with calcitonin nasal spray use. A further randomized study comparing this with bisphosphonates therapy may give us more clues on the management of osteoporosis in recipients.
DISCUSSION
Bone mass loss is a well-recognized adverse effect after kidney transplantation. Our cross-sectional study demonstrated that 46.26% experienced osteoporosis, 38.81% experienced osteopenia, and 14.93% were normal. We have somehow seen a higher incidence of low bone density compared with Durieux et al,3 Parker et al,4 and Gallego et al.5 This may relate to the longer waiting period in Taiwan, which has been described as a risk factor for posttransplantation bone loss. Most studies have shown that bone density loss is mainly related to cumulative steroid dose.5,6 Our data showed less osteoporosis in the steroid-elimination recipients (6/15 [40%] compared with 25/52 [48.1%]). All 3 patients who used calcitonin had improved bone density. This result suggested that steroid minimization or elimination may be one option for osteoporosis management and that it might increase the efficacy of calcitonin. However, we have to enroll more cases to confirm this finding. The roles of CNI, MPA, and rapamycin are controversial.2 In our study the different type of CNI or MPA did not alter the risk of osteoporosis. Among other risk factors, no significant difference between normal and osteoporosis recipients was found based on BMI, diabetes, waiting time, and graft function. Our case number was limited; we need
2413
for accumulate more patients to affirm a solid conclusion on risk factors. Considering therapy for posttransplantation bone loss, calcitriol or bisphosphonates have been reported to be effective.2 There is a limited report on the effect of calcitonin on osteoporosis after kidney transplantation. Grotz et al reported increased L-spine BMD but no improvement in femoral neck BMD after calcitonin nasal spray use.7 Our protocol for osteoporosis recipients used calcitonin intranasal (200 IU every other day for 3 months). Among the 18 patients who completed the 3-month therapy, 12 had increased L-spine BMD and 6 had increased femoral neck BMD. There were 11 (61%) patients who showed a net gain of BMD. Our data also revealed a better effect on the L-spine, probably due to a greater trabecular component in the spine and more cortical bone in the femoral neck. More evidence on calcitonin effects on bone homeostasis are required to confirm this theory. This preliminary result suggested that calcitonin nasal spray improved bone mass in 61% of posttransplantation osteoporosis patients. In conclusion, our preliminary data suggested that calcitonin might help to restore bone mass in kidney recipients with osteoporosis. Steroid elimination may prevent the onset of osteoporosis and even enhance calcitonin effectiveness. In the future we need a longer study period to confirm the results and compare them with the effects of bisphosphonate therapy. REFERENCES 1. Julian BA, Laskow DA, Dubovsky J, et al: Rapid loss of vertebral mineral density after transplantation. N Engl J Med 325:544, 1991 2. Kodras K, Haas M: Effect of kidney transplantation on bone. Eur J Clin Invest 36:63, 2006 3. Durieux S, Mercadal L, Orcel P, et al: Bone mineral density and fractures prevalence in long-term kidney graft recipients. Transplantation 74:496, 2002 4. Parker CR, Freemont AJ, Blackwell PJ, et al: Cross-sectional analysis of renal transplantation ostroporosis. J Bone Miner Res 4:1943, 1999 5. Gallego R, Oliva E, Vega N, et al: Steroids and bone density in patients with functioning kidney allografts. Transplant Proc 38:2434, 2006 6. Pichette V, Bonnardeux A, Prudhomme L, et al: Long-term bone loss in kidney transplant recipients: a cross-sectional and longitudinal study. Am J Kidney Dis 28:105, 1996 7. Grotz WH, Rump LC, Niesssn A, et al: Treatment of osteopenia and osteoporosis after kidney transplantation. Transplantation 66:1004, 1998