A controlled study of vitamin D3 to prevent bone loss in renal-transplant patients receiving low doses of steroids

BACKGROUND: New and potent immunosuppressive regimens allow for reduced doses of corticosteroids after renal transplantation. The aims of our study were to investigate whether the use of low-dose corticosteroids is associated with a reduction in posttransplant bone loss and to assess the ability of cholecalciferol supplementation to further decrease bone loss in this setting. METHODS: Ninety patients admitted for renal transplantation and scheduled to be treated per protocol with low doses of prednisolone were randomized to receive either 400 mg daily oral calcium (Ca group, n=44) or the same dose of calcium in association with a monthly dose of 25,000 IU of vitamin D3 (CaVitD group, n=46). Bone mineral density (BMD) was measured by dual energy absorptiometry at baseline and at 1 year. RESULTS: The overall population experienced a moderate but significant -2.3+/-0.9% loss of lumbar spine BMD (P<0.01) but no bone loss at the femoral neck and shaft during the first posttransplant year. Bone loss tended to be slightly higher in the CaVitD group, but the difference did not reach statistical significance. Patients in the CaVitD group had significantly higher 25(OH) but not 1,25(OH)2 vitamin D levels. We observed a highly significant negative correlation between 25(OH) vitamin D and intact parathyroid hormone (iPTH) serum levels. CONCLUSIONS: Kidney-transplant recipients receiving modern immunosuppressive regimens with low doses of corticosteroids experience only minimal loss of BMD during the first posttransplant year. Cholecalciferol supplementation did not prevent posttransplant bone loss but contributed to the normalization of iPTH levels after renal transplantation.     

Comparison of calcitonin versus calcitonin + resistance exercise as prophylaxis for osteoporosis in heart transplant recipients

BACKGROUND: Rapid bone loss occurs early after heart transplantation. There is no standard therapeutic intervention to prevent osteoporosis in heart transplant recipients (HTR). The purpose of this study was to determine the effectiveness of a regimen combining the antiresorptive properties of nasal calcitonin with the osteogenic stimulus of resistance exercise. METHODS: Eighteen candidates for heart transplantation were randomly assigned either to a group that received calcitonin and participated in 6 months of resistance exercise (n=10) or to a group that received only calcitonin (n=8). Calcitonin therapy (200 IU daily for 8 months) was initiated 48 hr after transplantation. Resistance exercise was initiated 2 months after transplantation. Bone mineral density (BMD) of the total body, femur neck, and lumbar vertebra (L2-3) were assessed before, and at 2 and 8 months after transplantation. RESULTS: Total body and femur neck BMD did not decrease (P>or=0.05) below pretransplantation values at 2 months after transplantation in either group. BMD of the lumbar spine was significantly (P相似文献   

Clodronate treatment of established bone loss in cardiac recipients: a randomized study

BACKGROUND: Bone loss has been reported as a complication after heart transplantation (HTx), and the increase in bone fractures is an effective problem. Treatment of osteoporosis has obtained mixed results. In this study we evaluate the effect of treatment with an oral bisphosphonate. METHODS: Sixty-four patients with low mineral density 6 months after HTx were randomized as follows: Group A received oral clodronate (1600 mg/day in two divided doses), and Group B received placebo. Every patient was also treated with 2000 mg/day of oral calcium carbonate. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry at the lumbar spine, 1/3 and 1/10 of the distal nondominant forearm before and after 12 months of treatment. Laboratory tests were performed at 3, 6, and 12 months of treatment. RESULTS: All patients demonstrated manifest bone loss 6 months after HTx compared with normal non-HTx controls (P=0.0001). After 1 year of clodronate therapy, BMD at the lumbar spine increased from 0.77+/-1.4 g/cm(2) to 0.86 g/cm(2) (P=0.02). Laboratory tests did not show any significant variation, except for the bone isoenzyme of alkaline phosphatase, which showed a significant decrease after 1 year of treatment. The incidence of new fractures was 9.3% in the placebo group and 0% in the clodronate group. Therapy was well tolerated without impact on graft function. CONCLUSIONS: One year of clodronate therapy induced a significant increase in BMD at the lumbar spine in our HTx patients. Treatment was well tolerated without onset of new bone fractures.     

Quantitative ultrasound of the calcaneus and dual X-ray absorptiometry of the lumbar spine in assessment and follow-up of skeletal status in patients after kidney transplantation

Bone loss after kidney transplantation is a significant complication of immunosuppressive treatment leading to a high prevalence of bone fracture in these patients. The purpose of this study was to determine the usefulness of quantitative ultrasound (QUS) of the calcaneus in comparison with dual X-ray absorptiometry (DXA) of the lumbar spine in determining bone status and mineral changes in patients in the first 6 months after transplantation. Forty-six patients participated in the study (25 men and 21 women; age range 26-62 years, 102+/-66 months previously on dialysis). They were treated with cyclosporine, methylprednisolone, mycophenolate mofetil, and basiliximab. The 6-month cumulative steroid dose was 24.9+/-3.7 mg/kg body weight. Calcaneal QUS (Sahara, Hologic, Waltham, Mass.) and DXA (Hologic QDR 4500) of the lumbar spine were done in all patients within 3 weeks after transplantation and 6 months thereafter. Bone mineral density (BMD) of the lumbar spine measured by DXA decreased from 0.892+/-0.137 to 0.837+/-0.126 g/cm2 (p<0.0001) and the T score decreased from 1.84+/-1.29 standard deviation (SD) to 2.35+/-1.19 SD (p<0.0001) in the first 6 months after transplantation. The QUS parameters of the calcaneus were broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI). The QUS parameters did not change significantly after the first 6 months. All QUS parameters correlated significantly with DXA BMD of the lumbar spine immediately after transplantation and 6 months thereafter. Significant decrease of the lumbar spine BMD in the first 6 months after transplantation was not accompanied by significant changes of calcaneal QUS parameters. The calcaneal QUS does not reflect bone mineral changes occurring in the lumbar spine and could not be a substitute for a direct-site DXA of the lumbar spine in the early period after kidney transplantation.     

Bisphosphonates are effective prophylactic of early bone loss after renal transplantation

INTRODUCTION: Rapid bone loss and fractures occur early after solid organ transplantation. We examined the preliminary results of a prospective study evaluating the efficacy of prophylactic use of bisphosphonates in renal allograft recipients. METHODS: Bone mineral density (BMD) was measured at the lumbar spine and the hip by dual energy X-ray absorptiometry at 1, 6, 12 months. Alendronian or risedronian were initiated for patients with osteopenia or osteoporosis at 1 month who had no contraindications to bisphosphonates. The treatment lasted at least 6 months. Sixty-six patients were included in the study; 39 were treated with bisphosphonates (A), and 27 were drug-free (B). Presently, 24 group A and 13 group B patients have completed the 12-month observation period. RESULTS: In group A 53.8% (21) subjects had osteoporosis and 46.2% (18), osteopenia. Mean T-score L(2)-L(4) in group A at 1, 6, and 12 months were: (-)2.22 +/- 1.06; (-)2.07 +/- 1.25; (-)1.89 +/- 1.07, respectively. The T-score increase between 6 and 12 months was significant (P = 0.0014). The relative rise in BMD L(2)-L(4) between 1 and 12 months was 2.26%. In group B mean T-score L(2)-L(4) at 1, 6, and 12 months were: (-)0.26 +/- 1.34; (-)0.80 +/- 1.19; (-)1.2 +/- 1.59, respectively. The T-score decrease between 1 and 12 months in group B was significant (P = .0082). The 12-month relative decrease in femoral neck and trochanter BMD in group B was (-)2.1% and (-)2.75%, respectively. CONCLUSION: Bisphosphonates are effective for prophylaxis of rapid bone loss early after renal transplantation.     

Lumbar bone mineral density after kidney transplantation: a three-year prospective study

Osteopenia is a common complication after transplantation. However, prospective long-term studies are scarce and most were performed in patients on cyclosporine and high-dose steroids. In 65 patients with functioning grafts, 41 males and 24 females, 50 on tacrolimus-based immunosuppression and 15 on cyclosporine-based immunosuppression, bone mineral density (BMD) was measured in the lumbar spine (L2-L4) and femoral neck (FN) using dual X-ray absorptiometry (DEXA) in the first month after transplantation (baseline) and at 1, 2, and 3 years. At baseline, BMD was similar to the control population both in L2-L4 (z score = -0.421) and in FN (z score = -0.518). During the follow-up, 3 types of patterns were identified: BMD increased in L2-L4 in 25 patients (38.5%), remained stable in 20 patients (30.8%), and decreased in 20 patients (30.8%). BMD losses appeared mainly during the first year (0.964 +/- 0.162 baseline; 0.904 +/- 0.161 at 1 year, 0.886 +/- 0.140 at 3 years; analysis of variance [ANOVA] P < .001). However, the improvement was maintained throughout the follow-up (0.860 +/- 0.176 g/cm2 at baseline; 0.901 +/- 0.161 at 1 year; 0.954 +/- 0.178 at 3 years; ANOVA P < .001) and there was a parallel increase of BMD in FN (0.712 +/- 0.144 at baseline; 0.744 +/- 0.249 at 1 year; 0.826 +/- 0.184 at 3 years; ANOVA P < .01). There were no differences between both groups in graft function, intact parathyroid hormone (iPTH) levels, number of postmenopausal women, or steroid doses. About one third of patients had bone loss during the first year after transplantation. We were unable to identify any risk factor for this complication in patients on low-dose steroids.     

Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

BACKGROUND: Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. METHODS: Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. RESULTS: Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). CONCLUSIONS: Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.     

Long-term follow-up study on bone mineral density and fractures after simultaneous pancreas-kidney transplantation

BACKGROUND: In type 1 diabetic patients with end-stage renal failure, low bone mass is prevalent and the incidence of fractures high after simultaneous pancreas kidney transplantation (SPK). Data are scarce on preexisting skeletal morbidity or the long-term effects of SPK on bone mass and risk of fractures. METHODS: We conducted a prospective study addressing these issues in 19 consecutive SPK recipients before and at 3, 6, and 12 months, and 2.5 to 4 years after establishment of graft function. RESULTS: Prior to transplantation, 13 patients (68%) had hyperparathyroidism, 7 of whom had osteoporosis. Mean bone mineral density (BMD) was significantly lower at the femoral neck than at the lumbar spine (T-scores -2.0 +/- 0.89 vs. -0.66 +/- 0.84). There was a significant decrease in BMD at both lumbar spine and femoral neck at 6 months post-transplantation (-6.0 +/- 5.4% and -6.9 +/- 4.3%, respectively). No further loss was observed in the following 6 months. At 1 year post-transplantation, 9 patients had osteoporosis associated with hyperparathyroidism in 8, and none had sustained a clinical fracture. A significant albeit small increase in BMD was observed 6 months after start of alfacalcidol 0.25 microg/day. At end-evaluation, osteoporosis and hyperparathyroidism persisted in the patients in whom it was documented at 1 year. Five patients who had lower BMD at the femoral neck pretransplantation sustained a clinical fracture. CONCLUSION: Cortical osteoporosis is prevalent in SPK recipients at the time of transplantation, progresses early post-transplantation, and is associated with relatively high incidence of fractures. Reversal of persistent hyperparathyroidism with the use of alfacalcidol may contribute to a decrease in skeletal morbidity.     

Resistance exercise training and alendronate reverse glucocorticoid-induced osteoporosis in heart transplant recipients.

BACKGROUND: Immunosuppression therapy with bolus glucocorticoids causes regional osteoporosis in the axial skeleton of heart transplant recipients (HTR). No preventive strategy is generally accepted for steroid-induced bone loss. METHODS: To determine the efficacy of an anti-osteoporosis regimen that combined a bisphosphonate agent (alendronate sodium) with the osteogenic stimulus of mechanical loading, 25 HTRs were randomly assigned either to a group that received alendronate (10 mg/day) for 6 months (ALEN; n = 8), a group that received alendronate (10 mg/day) and performed specific resistance exercises for 6 months (ALEN + TRN; n = 8) or to a non-intervention control group (CONTR; n = 9). Alendronate was initiated at 2 months after transplantation. Bone mineral density (BMD) of the total body, femur neck and lumbar spine (L-2 and L-3) was measured by dual-energy X-ray absorptiometry before and 2, 5 and 8 months after transplantation. Resistance training consisted of lumbar extension exercise (MedX) performed 1 day/week and 8 variable resistance exercises (MedX) performed 2 days/week. RESULTS: Pre-transplantation BMD values did not differ among the 3 groups. BMD of the total body, femur neck and lumbar vertebra were significantly decreased below baseline at 2 months after transplantation in CONTR (-2.6 +/- 0.9%, -5.1 +/- 1.8%, -12.5 +/- 4.2%, respectively), ALEN (-2.8 +/- 0.8%, -5.3 +/- 1.6%, -12.0 +/- 3.9%) and ALEN + TRN groups (-2.7 +/- 1.0%, -5.6 +/- 2.1%, -11.2 +/- 3.7%). CONTR had further significant losses of BMD after 3 and 6 months. ALEN had no further regional BMD losses after initiation of alendronate therapy. ALEN + TRN restored BMD of the whole body, femur neck and lumbar vertebra to within 0.9%, 2.1%, and 3.4% of pre-transplantation levels, respectively. CONCLUSIONS: Resistance exercise plus alendronate was more efficacious than alendronate alone in restoring BMD in HTRs. Our results indicate that anti-osteoporosis therapy in this population should include both an anti-resorptive agent as well as an osteogenic stimulus, such as mechanical loading.     

Bone Mineral Density in the Long Term after Liver Transplantation

Hepatic osteodystrophy is a complication of chronic liver disease and bone mass is known to decline further in the first year after liver transplantation. The present study focused on bone mineral density (BMD) between 1 and 15 years after liver transplantation under a prednisolone- and azathioprine-based immunosuppressive regimen. Three groups of adult patients were studied: group 1, 45 patients with a follow-up of 5–9 years after transplantation, had BMD measurements done at 1, 2 and 5 years after transplantation; group 2, 17 patients with a follow-up of 10–14 years, had BMD measurements done at 5 and 10 years; group 3, 4 patients with a follow-up of more than 15 years, had BMD measurements done at 10 and 15 years. BMD of lumbar spine (L1–L4) and proximal femur was measured using dual-energy X-ray absorptiometry, and at the same time radiographs of the spine and hips were made. Spinal BMD increased significantly, during the second post-transplant year; subsequently no significant changes were seen. Proximal femur BMD decreased slightly, but significantly during the second year, and remained stable afterwards. About one-third of patients had a BMD below the fracture threshold (= 0.798 g/cm² for the lumbar spine and 0.675 g/cm² for the hip) during the follow-up. In 5 of the 66 patients studied, new vertebral fractures occurred. No fractures or avascular necrosis of the hips were seen. Furthermore, after transplantation lower Z-scores of the hip were found in patients with pre-transplant cholestatic liver diseases, and lower Z-scores of the lumbar spine were found in men compared with women. Long-term follow-up of BMD up to 15 years after transplantation revealed an improvement mainly in the second postoperative year with no deterioration afterwards. Nevertheless a substantial number of patients (around one-third) kept a BMD below the fracture threshold, and new fractures may occasionally occur. The overall outcome appeared somewhat less favorable in men and patients transplanted for cholestatic liver diseases. Received: 15 July 1999 / Accepted: 11 January 2000     

No important influence of limited steroid exposure on bone mass during the first year after renal transplantation: a prospective, randomized, multicenter study

BACKGROUND: Steroid-related bone loss is a recognized complication after renal transplantation. In a prospective, randomized, multicenter study we compared the influence of a steroid-free immunosuppressive regimen with a regimen with limited steroid exposure on the changes in bone mass after renal transplantation. METHODS: A total of 364 recipients of a renal transplant were randomized to receive either daclizumab (1 mg/kg on days 0 and 10 after transplantation; steroid-free group n=186) or prednisone (0.3 mg/kg per day tapered to 0 mg at week 16 after transplantation; steroids group n=178). All patients received tacrolimus, mycophenolate mofetil, and, during the first 3 days, 100 mg prednisolone intravenously. Changes in bone mineral density (BMD) were evaluated in 135 and 126 patients in the steroid-free and steroids group, respectively. RESULTS: The mean (+/- SD) BMD of the lumbar spine decreased slightly in both groups during the first 3 months after transplantation (steroid-free -1.3 +/- 4.0% [P<0.01]; steroids -2.3 +/-4.2% [P<0.01]). In the following months, lumbar BMD recovered in both groups (P<0.01), resulting in a lumbar BMD at 12 months after transplantation comparable with the baseline value. No difference between the groups was found at 3 months (steroid-free versus steroids +1.0%; 95% confidence interval -0.0%-+2.0%, P=0.060) and at 12 months after transplantation (steroid-free versus steroids +0.9%; 95% confidence interval -0.8%-+2.6%, NS). CONCLUSION: The use of a moderate dose of steroids during 4 months after transplantation has no important influence on bone mass during the first year after renal transplantation. On average, both regimens prevented accelerated bone loss.     

Parameters of high bone-turnover predict bone loss in renal transplant patients: a longitudinal study

BACKGROUND: Osteoporosis is a serious complication of kidney transplantation. Various factors have been postulated to contribute to posttransplant bone loss, among them treatment with corticosteroids, the use of cyclosporine and cyclosporine-like agents, and persistent hyperparathyroidism. In a previous cross-sectional study of long-term renal transplant recipients, we observed that osteoporosis or osteopenia was present in 88% of patients. Because biochemical markers of bone formation (serum osteocalcin) and bone resorption (urine pyridinoline, PYD, and deoxypyridinoline, DPD) were elevated in the majority of study subjects, we hypothesized that elevated rates of bone-turnover contribute to posttransplant bone loss in long-term renal transplant patients. This study was performed to examine this hypothesis. METHODS: The study population was composed of 62 patients who were more than 1-year postrenal transplantation and who had preserved renal function. They were followed prospectively for 1 year. Biochemical markers of bone-turnover were measured at study entry, and patients were classified as having high bone-turnover based on elevated urinary levels of at least one marker of bone resorption (i.e., PYD or DPD) and/or serum osteocalcin (group 1). If none of these were present, they were classified as having normal bone-turnover (group 2). Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DEXA) at time of entry into the study and again after 1 year of follow-up. The changes in BMD at the lumbar spine, hip, and wrist over the period of the study were compared between the high and normal bone-turnover groups. RESULTS: Forty-three patients (69%) were classified as having high bone-turnover (Group 1), and 19 patients (31%) were classified as having normal bone-turnover (Group 2). There was a statistically significant difference in change in BMD between the two groups at the lumbar spine (-1.11+/-0.42%, high bone-turnover, vs. 0.64+/-0.54%, normal bone-turnover; P=0.02) and the hip (-0.69+/-0.38%, high bone-turnover, vs. 1.36+/-0.66%, normal bone-turnover; P=0.006). Whereas group 2 had stable bone mass, group 1 exhibited bone loss at these skeletal sites. CONCLUSIONS: Our results indicate that bone loss is greater in renal transplant recipients with elevated biochemical markers of bone-turnover, suggesting that these markers may be useful in identifying patients at risk for continued bone loss. These data support the hypothesis that continued bone loss in long-term renal transplant recipients is associated with high bone-turnover. If accelerated bone resorption does play a role in posttransplant bone loss, this would provide a strong rationale for use of antiresorptive therapy for the prevention and treatment of this complication.     

Bone loss and fracture after lung transplantation.

BACKGROUND: Osteoporosis is very common in patients with end-stage pulmonary disease. However, there are few prospective data on fracture incidence after lung transplantation. METHODS: We prospectively evaluated changes in bone mass, fracture incidence, and biochemical indices of bone and mineral metabolism in 30 patients who completed 1 year of observation after lung transplantation. All received calcium, vitamin D, and therapy with one or more agents that inhibit bone resorption, initiated shortly after transplantation. RESULTS: Before transplantation, only 20% of the patients had normal lumbar spine (LS) and femoral neck bone mineral density (BMD). After transplantation, 15 patients (50%) sustained significant bone loss at either the LS (-8.6+/-1.0%) or the femoral neck (-11.3+/-2.2%). Eleven (37%) patients (10 women) sustained a total of 54 atraumatic fractures. Pretransplantation LS BMD and T scores were significantly lower in those who sustained fractures (-2.809+/-0.32 versus -1.569+/-0.29; P<0.01). Fracture patients were more likely to have had pretransplantation glucocorticoid therapy (chi-square 5.687; P<0.02). The duration of pretransplantation glucocorticoid therapy was also longer in fracture patients (4.9+/-0.8 versus 1.3+/-0.4 years; P<0.001). Biochemical markers of bone resorption were significantly higher in patients who sustained bone loss and/or fractures. CONCLUSIONS: We conclude that fractures are a significant problem in the first year after lung transplantation, even in patients who receive therapy to prevent bone loss. Women with low pretransplantation BMD and a history of pretransplantation glucocorticoid therapy are at greatest risk.     

Resistance training prevents vertebral osteoporosis in lung transplant recipients

BACKGROUND: Osteoporosis and vertebral fractures are a consequence of glucocorticoid immunosuppression therapy in lung transplant recipients (LTR). The purpose of this study was to determine the therapeutic efficacy of a 6-month program of specific resistance exercise designed to reverse glucocorticoid-induced vertebral osteoporosis. METHODS: Sixteen lung transplant candidates were randomly and prospectively assigned to a group (n=8) that performed 6 months of exercise on a lumbar extensor machine or to a control group (n=8). Resistance exercise was initiated at 2 months after transplantation. Bone mineral density (BMD) of the lumbar vertebra (L2-3) was assessed using a dual-energy X-ray absorptiometer (DXA). DXA scans were performed before and 2 months after transplantation and after 6 months of lumbar extensor training or control period. RESULTS: Lumbar BMD did not differ (P>0.05) between the two groups at study entry. Both the trained (0.63 to 0.54 g/cm2 of hydroxyapatite) and control groups (0.62 to 0.53 g/cm2 of hydroxyapatite) lost significant and comparable amounts (-14.5%) of BMD between study entry and 2 months posttransplantation. The control group lost further (P相似文献   

Areal and volumetric bone mineral density changes after renal transplantation in children: a longitudinal study

INTRODUCTION: The effect of renal transplantation on areal bone mineral density (aBMD) in children has previously been studied. However, most previous reports did not include estimation of volumetric bone mineral density (vBMD) or analyze longitudinal data in these patients. In addition, updated reference standards for aBMD in children have recently been made available. METHODS: This retrospective study describes the longitudinal effect of renal transplantation on aBMD and vBMD in a cohort of 40 pediatric kidney transplant recipients. Lumbar spine aBMD measurements were obtained using dual-energy X-ray absorptiometry prior to transplant and yearly thereafter. vBMD values and z-scores were estimated as described in the most recently published references. RESULTS: A significant decrease in average aBMD and vBMD z-scores was observed within 1 year posttransplant, which did not recover during follow-up. The negative effect of transplantation on vBMD was blunted and vBMD z-scores were higher compared to aBMD. Linear mixed-effects model analysis demonstrated that lumbar spine aBMD and vBMD z-scores were inversely related to yearly prednisone dose (g/m2) but this effect was diminished as glomerular filtration rate was increased. CONCLUSIONS: Bone mineral density was negatively affected by renal transplantation in this cohort of pediatric patients. Estimation of vBMD appears to be appropriate for interpretation of the BMD changes occurring after renal transplant in children. The inverse relation between BMD z-scores and yearly prednisone dose suggests that ongoing posttransplant corticosteroid therapy may be responsible for the negative effect of transplantation on bone mineral density in this cohort.     

Bone mass after long-term euthyroidism in former hyperthyroid women treated with (131)I influence of menopausal status.

The objective of this study was to assess bone mineral density (BMD) and bone markers in former hyperthyroid females after long-term euthyroidism (>4 yr) following (131)I therapy, as well as the potential influence of the timing of menopause. Twenty-six females ages 57 +/- 8 yr previously diagnosed with hyperthyroidism and treated with (131)I who were euthyroid for a minimum of the last 4 yr (10 +/- 5 yr) were studied. Eighteen patients (69%) were on levothyroxine (LT(4)) replacement therapy for 9 +/- 4 yr. BMD (g/cm(2) and Z-score) was measured by dual X-ray absorptiometry in the lumbar spine, femoral neck, and Ward's triangle. BMD (Z-score) was lower than the normal reference values for the Spanish population in all sites (lumbar spine: -0.65 +/- 1.13; femoral neck: -0.47 +/- 0.95; Ward's triangle: -0.37 +/- 0.88). No differences were found between BMD values according to the etiology of the hyperthyroidism or current LT(4) therapy. Current postmenopausal patients (n = 21) showed lower BMD than current premenopausal patients in the lumbar spine and femoral neck (p < 0.05). Those women who were postmenopausal at the time of the (131)I therapy (n = 15) also had lower lumbar spine BMD than premenopausal patients (p = 0.01), while no significant difference in BMD was seen according to the menopausal status when hyperthyroidism was diagnosed. Former hyperthyroid patients after long-term euthyroidism following (131)I therapy showed reduced BMD at the lumbar spine and proximal femur. Menopausal women showed a greater reduction in bone density. The menopausal status at the time of diagnosis did not seem to have long-term effects in bone density; nevertheless, an early therapeutic intervention in premenopause is suggested to reduce bone loss.     

Treatment with vitamin D and calcium reduces bone loss after renal transplantation: a randomized study

A decrease in bone mineral density (BMD) is a major complication of renal transplantation (RTx), predominantly occurring within the first 6 mo after RTx. The most important causative factor is the use of corticosteroids, but persisting hyperparathyroidism and abnormalities in vitamin D metabolism play a role too. This study examines the effect of treatment with calcium and active vitamin D on the loss of BMD in the first 6 mo after RTx. A total of 111 renal transplant recipients (65 men, 46 women; age, 47 +/- 13 yr) were randomized to either treatment with active vitamin D (0.25 microg/d) plus calcium (1000 mg/d) (CaD group), or to no treatment (NoT group). Immunosuppressive therapy consisted of cyclosporine, prednisone, and mycophenolate mofetil. Laboratory parameters and BMD (lumbar spine and hip) were measured at 0, 1 (laboratory only), 3, and 6 mo after RTx. Lumbar BMD was nearly normal at the time of RTx. In both groups, a significant decrease in lumbar BMD was observed during the first 3 mo (CaD, -3.3 +/- 4.3%; P < 0.0001; NoT, -4.1 +/- 4.8%; P < 0.0001). Between the third day and sixth month, lumbar BMD slightly recovered in the CaD group, but it decreased further in the NoT group (total loss 0 to 6 mo: CaD, -2.6 +/- 5.0% [P < 0.001]; NoT, -5.0 +/- 4.7% [P < 0.0001]). As a result, the amount of bone loss at 6 mo was significantly lower in the CaD group (P = 0.02). Loss of BMD at the different femoral sites was also significantly reduced in the CaD group. Apart from a trend toward more frequent hypercalcemia in the CaD group, no clinical or biochemical differences existed between the groups. 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 mo after RTx.     

Effect of nutrition and body composition on bone density after liver transplantation

We investigated the relationship between nutrition, body composition, and bone mineral density (BMD) in young adults after liver transplantation. METHOD: A cross-sectional study involving bone densitometry, anthropometry, and detailed food and lifestyle questionnaires. RESULTS: Of 37 patients recruited, 26 were male. The mean age was 38.8 (+/-12.3) years, and the posttransplant period was 7.5 (+/-5.1) years (range 1.3-16.4). A significant proportion of patients (23 [62%]) were overweight (BMI 25-29.9) or obese (BMI>or=30). A total of 20 (54%) patients were osteopenic, and four (11%) had osteoporosis (lumbar spine or total body BMD). Lean mass showed a statistically significant correlation with lumbar spine and total body BMD in men and women, the most significant being bone mineral content, r=0.66, P=.01. The correlation was stronger in females (r=0.81, P<.01) than in males (r=0.56, P<.01). The average daily intake of vitamin D, total protein, and phosphorus was greater than 100% of the American Dietary Reference recommendations, calcium was 90%, and magnesium 56%. There was no significant relationship between any nutritional parameter and BMD nor history of fractures, steroid use, or length of time from transplantation. CONCLUSION: Osteopenia determined by lumbar spine BMD underestimates poor BMD in our population of young adults after liver transplant. Maintaining muscle mass may be helpful in preserving BMD. The effect of a limited intake of magnesium needs further investigation.     

The prevention of bone fractures after liver transplantation: experience with alendronate treatment

OBJECTIVE: The aim of this study was to prevent fractures in the first postoperative year. METHODS AND PATIENTS: We studied 59 patients (48 men, 11 women) aged 42.6+/-11.4 years, who underwent liver transplantation. All patients received oral alendronate 70 mg weekly and calcium 1 g and calcitriol 0.5 mug daily. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the lumbar spine and proximal femur at baseline as well as at 6 and 12 months after transplantation for comparison with an historical control group (n=31). Spinal radiographs were obtained to assess vertebral fractures at the same time. Additionally, serum osteocalcin, serum parathyroid hormone (PTH), urinary deoxypyridinoline (DPD), and biochemical parameters were determined every 3 months. RESULTS: At baseline, femoral total BMD of men was significantly greater than that of women (P<.05, .85+/-.1 vs .74+/-.1). A significant increase in BMD was observed at 12 months (P<.05), no patient developed a bone fracture. Comparison analysis of genders showed that there was a significant difference in favor of men (P<.05). The lumbar BMD, neck T-, and Z-scores were significantly higher among patients treated with alendronate than historical controls (P<.05). After 3 months, serum PTH was increased and serum osteocalcin and urinary DPD were reduced. No severe side effects from alendronate treatment were observed during the study. CONCLUSION: A direct sign of the success of our study was no fracture observed during the first postoperative year. Alendronate should be considered for patients with low bone mass after liver transplantation.     

Prevention of osteoporosis after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol.

BACKGROUND: Accelerated bone loss is a well-recognized complication after cardiac transplantation (HTx) due to immunosuppressive therapy. The purpose of this prospective, longitudinal, randomized, placebo-controlled, double-blind study was to investigate the effect of calcitriol (1,25-dihydroxyvitamin D3) in the prevention of bone loss and fracture rate after HTx. METHODS: Basic therapy included 1000 mg of calcium daily and sex hormone replacement in hypogonadal patients. A total of 132 patients (111 male, 21 female; mean age: 51+/-10 years; 35+/-25 months after HTx) were randomized to 0.25 microg of calcitriol or placebo. Bone mineral density (BMD, g/cm2; T score, %) of the lumbar spine and x-rays for the assessment of vertebral fractures were performed at baseline and after 12, 24, and 36 months. Biochemical indexes of mineral metabolism were measured every 3 months. RESULTS: Overall BMD was significantly decreased after HTx (T score 87+/-13%). BMD increased continuously within the study period in the calcitriol group (1 year: 2.2+/-4.8%; 2 years: 3.9+/-5.4%; 3 years: 5.7+/-4.4%) as well as in the placebo group (1 year: 1.8+/-4.9%; 2 years: 3.7+/-6.5%; 3 years: 6.1+/-7.8%) without statistical difference between the groups. Fracture incidence was low during the study interval (1 year: 2.0%; 2 years: 3.4%; 3 years: 0%). Hypogonadism (20%) was associated with a lower BMD (78+/-12% vs. 88+/-12%; P<0.01) and a higher increase (35%) after hormone replacement in comparison to normogonadal patients. Increased intact parathyroid hormone and bone resorption markers decreased significantly during therapy. CONCLUSIONS: Calcium supplementation and sex hormone replacement in hypogonadism proved a sufficient long-term prevention therapy to improve decreased BMD and to prevent fractures after HTx. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role in the long-term bone loss and should therefore be monitored and treated adequately. Low-dose calcitriol demonstrated no significant extra benefit regarding BMD and fracture rate in the long-term period after HTx.