Early rapid loss followed by long-term consolidation characterizes the development of lumbar bone mineral density after kidney transplantation

BACKGROUND: Bone mineral density (BMD) decreases significantly early after renal transplantation. This prospective study was designed to evaluate the long-term lumbar BMD development. METHODS: Sixty-three renal-transplant recipients (mean age 44 +/- 12 years, 37 [59%] male) underwent serial yearly posttransplant laboratory parameter and BMD measurements of the lumbar spine (dual energy x-ray absorptiometry). Combined maintenance immunosuppression included prednisolone in 95% of patients. The minimum number of consecutive scans was three; the maximum number seven (n = 15). Examinations were performed between 3 +/- 2 and 68 +/- 4 months posttransplant. RESULTS: BMD was significantly lower compared with healthy controls at all times after transplantation. t scores were below -1. BMD development revealed a biphasic pattern: between 3 +/- 2 and 10 +/- 2 months, a significant BMD decrease of -0.016 +/- 0.055 g/cm2 (-1.6%, P = 0.024) occurred. Later, a moderate increase resulting in BMD stability until the sixth year posttransplant was detected. Within the first year, posttransplant osteocalcin (from 19 +/- 15 to 32 +/- 23 microg/L) and calcitriol (from 24 +/- 15 to 43 +/- 24 ng/L) displayed a significant increase. Compared with patients with a pronounced decrease, patients with a substantial increase in early posttransplant BMD had a lower baseline BMD (0.989 +/- 0.131 vs. 1.149 +/- 0.202 g/cm2 [P = 0.0122]) and lower creatinine levels (105 +/- 23 vs. 141 +/- 53 mmol/L [P = 0.0227]). CONCLUSION: Our study confirms a significant decrease of lumbar BMD early after renal transplantation. Bone loss was less pronounced than previously described. The longitudinal follow-up verifies a previously assumed biphasic lumbar BMD development: after the first year, no further significant bone loss occurred, and bone density remained relatively stable at significantly lower levels compared with healthy controls.     

High Prevalence of Osteoporosis in Patients with Chronic Liver Disease Prior to Liver Transplantation

Osteoporosis is a common complication of liver transplantation. Its pathogenesis is multifactorial, but preexisting bone disease in patients with chronic liver disease is likely to play an important role. The aim of this study was to evaluate bone mineral density in adult patients with chronic liver disease prior to liver transplantation. A total of 243 consecutive patients (128 male, 115 female; mean age 51.1years) with chronic liver disease undergoing assessment for transplantation, were recruited over a 4-year period. BMD measurements were made using dual energy X-ray absorptiometry in the lumbar spine (L1-L4) and femoral neck (FN). Osteoporosis and osteopenia were defined by WHO criteria. Osteoporosis at either L1-L4 or FN was present in 36.6%, osteopenia in 48.1%, and normal BMD in only 15.2% of patients. There was no difference in prevalence of osteoporosis between males and females (P = 0.442). Women with osteoporosis were on average 10 years older (56.2 +/- 1.4 years) than those with normal bone density (46.4 +/- 2.3 years) P = 0.002; in men, no statistically significant age effect was found. Patients with osteoporosis had on average lower body weight than those with normal bone density (64.9 +/- 1.8 kg vs 74.2 +/- 2.2 kg) P = 0.003. T-scores in patients with cholestatic liver disease were lower than in non-cholestatic disease and the lowest BMD values were found in patients with cystic fibrosis. Logistic regression revealed that in women, increasing age (P = 0.004; OR = 1.12; CI 1.04-1.21) and lower body weight (P = 0.01; OR = 0.95; CI 0.91-0.99) were significant independent risk factors for osteoporosis but menopausal status (P = 0.1; OR = 0.24; CI 0.05-1.32) and presence or absence of cholestasis (P = 0.326; OR = 1.54; CI 0.65-3.67) were not. There were no independent risk factors in men. This study demonstrates a high prevalence of osteoporosis in patients with chronic liver disease prior to liver transplantation, men and women being equally affected. With the exception of increasing age and lower body weight in women, no independent risk factors were found, emphasizing the importance of BMD measurements in these patients and the need for prophylactic measures to optimize bone health.     

Parathyroidectomy can improve bone mineral density in patients with symptomatic secondary hyperparathyroidism

HYPOTHESIS: The recovery of osteoporosis or bone mineral density (BMD) after parathyroidectomy and autotransplantation can be improved in patients with symptomatic secondary hyperparathyroidism. DESIGN: Case series. SETTING: Tertiary referral center. PATIENTS: Forty-five patients with symptomatic secondary hyperparathyroidism who underwent total parathyroidectomy and autotransplantation were included. They were divided into an osteoporotic group (n = 20) and a nonosteoporotic group (n = 25) according to preoperative T scores less than -2.5 at either the lumbar spine (L1-L4) or the femoral neck (FN). INTERVENTIONS: Serum levels of calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone were checked before surgery and 1 day, 1 week, and 3 months after surgery. The BMDs of the FN and L1-L4 were measured using dual-energy x-ray absorptiometry before surgery and 6 months after surgery. RESULTS: Patients with osteoporosis were older (mean +/- SD, 50.2 +/- 14.0 years) than those without osteoporosis (42.7 +/- 9.1 years) (P =.04). Except for bone fractures found in 2 women in the osteoporotic group, there were no significant differences between the 2 groups in sex, clinical manifestations, duration of dialysis, weight of removed parathyroid tissue, and types of dialysis. Also, serum levels of calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone were similar in both groups. Both 1 day and 1 week after total parathyroidectomy and autotransplantation, serum levels of calcium and intact parathyroid hormone decreased rapidly and then gradually increased 3 months later; however, serum levels of alkaline phosphatase increased rapidly and then gradually decreased 3 months later. Six months after parathyroidectomy, BMD, T score, and Z score at L1-L4 and the FN increased significantly (P<.001). The increment was much better in the osteoporotic group than in the nonosteoporotic group (P<.001). Also, osteopenia or osteoporosis improved significantly after parathyroidectomy at both L1-L4 and the FN (P<.001 for both). CONCLUSION: Parathyroidectomy and autotransplantation can improve BMD of symptomatic secondary hyperparathyroidism at L1-L4 and the FN.     

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.     

The role of tacrolimus (FK506)-based immunosuppression on bone mineral density and bone turnover after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol

BACKGROUND: Tacrolimus (FK506) is a new immunosuppressive drug in organ transplantation that has demonstrated experimentally to be more deleterious on bone mineral metabolism than cyclosporine. The purpose of this clinical study was to evaluate the effects of a tacrolimus-based immunosuppression on the skeleton and to investigate in a prospective, longitudinal, randomized, double-blind, study the effect of 0.25 microg calcitriol (1,25-dihydroxyvitamin D3) versus placebo in the prevention of bone loss and fracture rate after heart transplantion (HTx). METHODS: A total of 53 patients (5 female, 48 male, mean age: 53+/-11 years) were randomized to the study medication. Basic therapy included calcium and sex hormone replacement in hypogonadism. Bone mineral density of the lumbar spine (LS) and femoral neck (FN) were performed at baseline, after 12 and 24 months. Biochemical indexes of mineral metabolism were measured every 3 months. RESULTS: Overall bone mineral density (BMD) was significantly decreased after HTx (T-score-LS: 89+/-13%; FN: 88+/-14%). LS-BMD (% change in g/cm2) increased significantly within the study period in the calcitriol group (12 months: 7.1+/-8.1%, P<0.01; 24 months: 14.0+/-10.1%, P<0.01) and showed a positive trend in the placebo group (12 months: 4.5+/-9.3%, NS; 24 months: 6.2+/-8.0%, NS). FN-BMD in the calcitriol group was stable (12 months: -2.1+/-4.2%; NS; 24 months: -0.9+/-3.2%, NS). FN-BMD in the placebo group decreased significantly within the first 12 month follow-up period (-7.3+/-5.4; P<0.05) and stabilized within 2 years (-8.0+/-4.1%; P < 0.05). Fracture incidence was low during the study interval (first year: 5.0%, second year: 0%). Bone resorption markers decreased significantly during calcitriol therapy. CONCLUSIONS: High dose tacrolimus-based immunosuppressive regimen is associated with a rapid bone loss early after cardiac transplantation. Beyond the first 6 months after HTx, calcium, vitamin D, and hormone supplementation in hypogonadism lead sufficiently to bone mineral recovery. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role for the bone loss and should be therefore monitored and treated adequately. Low dose calcitriol should be substituted for at least 2 years as additional antiresorptive therapy.     

Evidence of continuing bone recovery at a mean of 7 years after liver transplantation.

Patients with end-stage liver disease have low bone-turnover osteoporosis, and there is often further bone loss of 20% to 30% after orthotopic liver transplantation (OLT). Bone recovery after OLT has been reported, but data are limited. We undertook studies to determine whether bone recovery continues in the long term. Twenty-eight adult patients alive at least 5 years after OLT were studied (14 men, 14 women). Bone mineral density (BMD), serum parathyroid hormone (PTH), osteocalcin, and vitamin D levels were measured pretransplantation, at 3 months, 12 months, a mean of 46 months, and a mean of 85 months (range, 63 to 117 months) after transplantation. When BMD is expressed as a z score, the results were as follows: x0.82 +/- 0.22 pre-OLT; -2.04 +/- 0.27 at 3 months; -1.68 +/- 0.24 at 12 months; -1.23 +/- 0.24 at a mean of 46 months; and -1.0 +/- 0.26 at a mean of 85 months after OLT. The results at 46 and 85 months were significantly greater than the measurement at 3 months after OLT (P <.05). Furthermore, mean BMD (expressed as a z score) returns to the pre-OLT level at a mean of 85 months. At final follow-up, 9 of 28 patients had elevated PTH levels, and 14 of 27 patients had elevated osteocalcin levels. Five patients had spontaneous fractures in the first 12 months after transplantation, and 5 more patients had fractures by final follow-up. Even at 7 years after OLT, there was a significant increase in BMD (expressed as a z score) compared with 3 months after transplantation. Elevation of serum PTH and osteocalcin levels in some patients suggests continuing bone remodeling.     

Reduced training is associated with increased loss of BMD.

This 8-year controlled, follow-up study in 66 Swedish soccer women evaluated the effect of training and reduced training on BMD. The players who retired during the follow-up lost BMD in the femoral neck, whereas the controls did not. INTRODUCTION: Physical activity during adolescence increases BMD, but whether the benefits are retained with reduced activity is controversial. MATERIALS AND METHODS: At baseline, DXA evaluated BMD in 48 active female soccer players with a mean age of 18.2 +/- 4.4 (SD) years, in 18 former female soccer players with a mean age of 43.2 +/- 6.2 years and retired for a mean of 9.4 +/- 5.3 years, and in 64 age- and sex-matched controls. The soccer women were remeasured after a mean of 8.0 +/- 0.3 years, when 35 of the players active at baseline had been retired for a mean of 5.3 +/- 1.6 years. RESULTS AND CONCLUSIONS: The players still active at follow-up had a higher BMD at baseline than the matched controls in the femoral neck (FN; 1.13 +/- 0.19 versus 1.00 +/- 0.13 g/cm2; p = 0.02). The yearly gain in BMD during follow-up was higher in the active players than in the controls in the leg (0.015 +/- 0.006 versus 0.007 +/- 0.012 g/cm2, p = 0.04). The soccer players who retired during follow-up had a higher BMD at baseline than the matched controls in the FN (1.13 +/- 0.13 versus 1.04 +/- 0.13 g/cm2; p = 0.005). The players that retired during follow-up lost BMD, whereas the controls gained BMD during the study period in the FN (-0.007 +/- 0.01 versus 0.003 +/- 0.02 g/cm2 yearly; p = 0.01). The soccer players already retired at baseline had higher BMD at study start than the matched controls in the leg (1.26 +/- 0.09 versus 1.18 +/- 0.10 g/cm2; p = 0.01). The former players who were retired at study start lost BMD, whereas the controls gained BMD during the study period in the trochanter (-0.006 +/- 0.01 versus 0.004 +/- 0.014 g/cm2 yearly; p = 0.01). This study shows that, in girls, intense exercise after puberty is associated with higher accrual of BMD, and decreased physical activity in both the short-term and long-term perspective is associated with higher BMD loss than in controls.     

Bone mineral density in lung-transplant recipients before and after graft: prevention of lumbar spine post-transplantation-accelerated bone loss by pamidronate.

BACKGROUND: Lung-transplant recipients are at risk of osteoporosis. They may have low bone mass even before posttransplantation immunosuppressive therapy. We studied bone mineral density (BMD) before and after lung transplantation and compared the efficacy of antiresorptive therapies to calcium and vitamin D supplementation. METHODS: Areal BMD was assessed in 42 patients awaiting lung transplantation and measured again after surgery at 6 (n = 29), and at 12 months (n = 20). Nineteen patients received antiresorptive therapy (30 mg pamidronate IV every 3 months (n = 14), or hormonal replacement therapy (n = 5)), and 10 patients received only calcium and vitamin D supplements.RESULTS: Mean age- and gender-adjusted lumbar spine (LS) and femoral neck (FN) BMD was significantly decreased prior to transplantation (- 0.6 +/- 0.2, p< 0.01, and - 1.5 +/- 0.2 standard deviation, p < 0.001, respectively). At that time, 29% were osteoporotic (T-score < - 2.5 below the peak bone mass), while 55% were below - 1.0 T-score. Antiresorptive therapy decreased the rate of LS bone loss during the first 6 months and led to a significant increase of BMD at 1 year, with LS changes of + 0.2 +/- 0.1 vs - 0.4 +/- 0.1 Z-score in the calcium-vitamin D group (p< 0.002), and + 0.2 +/- 0.1 vs - 0.04 +/- 0.1 for FN (NS). One out of 20 patients experienced clinically evident fractures during antiresorptive therapy, and 3 out of 12 in the calcium-vitamin D group. CONCLUSION: A significant proportion of patients awaiting lung transplantation was osteoporotic or osteopenic. Antiresorptive therapy (pamidronate or hormone-replacement therapy (HRT)) prevented accelerated LS bone loss after graft.     

COL1A1 Sp1 polymorphism predicts perimenopausal and early postmenopausal spinal bone loss.

Genetic factors play an important role in the pathogenesis of osteoporosis but the genes that determine susceptibility to poor bone health are defined incompletely. Previous work has shown that a polymorphism that affects an Spl binding site in the COLIA1 gene is associated with reduced bone mineral density (BMD) and an increased risk of osteoporotic fracture in several populations. Data from cross-sectional studies have indicated that COLIA1 Sp1 alleles also may be associated with increased rates of bone loss with age, but longitudinal studies, which have examined bone loss in relation to COLIA1 genotype, have yielded conflicting results. In this study, we examined the relationship between COLIA1 Sp1 alleles and early postmenopausal bone loss measured by dual-energy X-ray absorptiometry (DXA) in a population-based cohort of 734 Scottish women who were followed up over a 5- to 7-year period. The distribution of genotypes was as expected in a white population with 484 "SS" homozygotes (65.9%); 225 "Ss" heterozygotes (30.7%), and 25 "ss" homozygotes (3.4%). Women taking hormone-replacement therapy (HRT; n = 239) had considerably reduced rates of bone loss at the spine (-0.40 +/- 0.06%/year) and hip (-0.56 +/- 0.06%/year) when compared with non-HRT users (n = 352; spine, -1.36 +/- 0.06%/year; hip, -1.21 +/- 0.05%/year; p < 0.001 for both sites). There was no significant difference in baseline BMD values at the lumbar spine (LS) or femoral neck (FN) between genotypes or in the rates of bone loss between genotypes in HRT users. However, in non-HRT users (n = 352), we found that ss homozygotes (n = 12) lost significantly more bone at the lumbar site than the other genotype groups in which ss = -2.26 +/- 0.31%/year compared with SS = -1.38 +/- 0.07%/year and Ss = -1.22 +/- 0.10%/year (p = 0.004; analysis of variance [ANOVA]) and a similar trend was observed at the FN in which ss = -1.78 +/- 0.19%/year compared with SS = -1.21 +/- 0.06%/year and Ss = -1.16 +/- 0.08%/year (p = 0.06; ANOVA). The differences in spine BMD loss remained significant after correcting for confounding factors. Stepwise multiple regression analysis showed that COLIA1 genotype independently accounted for a further 3.0% of the variation in spine BMD change after age (4.0%), weight (5.0%), and baseline BMD (2.8%). We conclude that women homozygous for the Sp1 polymorphism are at significantly increased risk of excess rates of bone loss at the spine, but this effect may be nullified by the use of HRT.     

Better late than never? Experience with intravenous pamidronate treatment in patients with low bone mass or fractures following cardiac or liver transplantation

 Organ transplantation is associated with a high turnover of bone metabolism, and an increased loss of bone mass and incidence of osteoporotic fractures. Established therapies for osteoporosis after organ transplantation are still lacking, however. We report on an intravenous bisphosphonate therapy initiated in transplant patients because of a high rate of bone loss or incident osteoporotic fractures. Twenty-one patients after liver transplantation and 13 patients after heart transplantation received 30 mg pamidronate intravenously every 3 months, combined with 1000 mg calcium and 1000 IU vitamin D per day. The median time interval between transplantation and start of pamidronate treatment was 1.9 years in cardiac patients and 2.3 years in liver patients. Lumbar spine bone mineral density (LS BMD) and femoral neck BMD (FN BMD) were measured before and every 6 months after pamidronate therapy was initiated. Spinal radiographs were performed annually. Biochemical markers of bone metabolism were determined every 3 months, immediately before pamidronate administration. From a previous observational study, 58 patients treated only with calcium and vitamin D were matched for age, sex, pretransplantation LS BMD and time interval between transplantation and the first pamidronate treatment. In the pamidronate-treated patients, the mean increase in LS BMD adjusted for baseline values amounted to 0.080 ± 0.038 g/cm² (8.6 ± 4.0 %) after 1 year and 0.091 ± 0.058 g/cm² (10.4 ± 6.1%) after 2 years compared with 0.001 ± 0.037 g/cm² (0.26 ± 4.0%) after 1 year and 0.015 ± 0.057 g/cm² (1.8 ± 6.0%) after 2 years in the historical control group (absolute LS BMD changes pamidronate group vs historical group p < 0.0001 after 1 and 2 years). The changes of FN BMD were 0.024 ± 0.043 g/cm² (3.2 ± 6.1%) after 1 year and 0.046 ± 0.052 g/cm² (7.0 ± 6.1%) after 2 years in the pamidronate group compared with −0.012 ± 0.043 g/cm² (−1.6 ± 6.1%) after 1 year and −0.013 ± 0.052 g/cm² (−1.1 ± 6.1%) after 2 years in the historical control group (absolute FN BMD changes pamidronate group vs historical group p=0.003 after 1 year and p=0.001 after 2 years). From a total of 287 application cycles of pamidronate treatment, no severe side effects were observed and non-severe side effects were seen in only 39 cycles (13.6%). We conclude that cyclic intravenous pamidronate treatment is beneficial to patients with low bone mass or osteoporotic fractures following transplant, even when not immediately initiated. Received: 5 March 2002 / Accepted: 27 August 2002     

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.     

Natural history and risk factors for bone loss in postmenopausal Caucasian women: a 15-year follow-up population-based study

SUMMARY: In this 15-year follow-up study, we found that the estimated rate of bone loss at the femoral neck (FN) for women aged 45-68 was linear at a rate of 1.67% per year, but quadratic for lumbar spine (LS) at a rate of 3.12% initially, and slowing down with age. We also confirmed the protective role of HRT, increasing weight, and lean mass in long-term bone loss. INTRODUCTION: The objective was to describe the natural history of bone loss and explore the role of environmental factors in postmenopausal women over a 15-year period. METHODS: Bone mineral density (BMD) at the FN and the LS were measured in postmenopausal women from the Chingford Study. Height, weight, HRT status, and calcium/vitamin D supplement were assessed at each visit. Osteoarthritis of hip and spine was assessed by X-ray at baseline and at year 8. RESULTS: A total of 955 postmenopausal women with an average age of 54.7 at baseline were included. Both FN and LS BMD decreased significantly with age (p<0.0001). The decline was larger in the LS (-3.12% per year), which showed a quadratic relationship, than in the FN (-1.67% per year) with a linear relationship. The rate of bone loss was reduced by one third annually for the FN and LS respectively in current HRT users. Change in weight was positively associated with both DeltaFN and DeltaLS BMD (beta=0.16% and 0.09% change in DeltaFN and DeltaLS BMD per kilogramme change in weight respectively, p<0.0001 for both sites). Spine OA and progression were positively associated with DeltaLS BMD (beta=1.22% change in DeltaLS BMD per grade in spine OA and 0.45% change in DeltaLS BMD for patients who progressed, p<0.0001 for spine OA and p=0.002 for spine OA progression). Spine OA (beta=0.54% change in DeltaFN BMD per grade, p<0.0001), but not progression, and hip OA were positively associated with DeltaFN BMD. Furthermore, both age and body weight at baseline were positively associated with both DeltaFN and DeltaLS BMD (beta=0.02-0.04% change in DeltaFN and DeltaLS BMD per year increase in age at baseline and 0.004-0.007% change in DeltaFN and DeltaLS BMD per kilogramme increase in weight at baseline, all p<0.0001). CONCLUSION: This large population-based longitudinal study demonstrated that the decline of BMD over 15 years is linear with age for the FN, but quadratic for the LS. The study confirmed the protective role of HRT, increased weight and lean mass in long-term bone loss.     

Longitudinal Changes in BMD and Fracture Risk in Orthotopic Liver Transplant Recipients Not Using Bone‐Modifying Treatment

Osteoporosis is prevalent in end‐stage liver disease, but data on long‐term changes in bone mineral density (BMD) and related fracture incidence after orthotopic liver transplantation (OLT) are scarce. We evaluated BMD changes up to 5 years in consecutive recipients of a successful OLT at the Leiden University Medical Centre between 2000 and 2011, in whom sequential BMD data were available. Spinal radiographs were available at time of screening and at 6 and 12 months post‐OLT and were assessed for vertebral fractures by two independent observers using Genant's semiquantitative method. Patients were excluded from the study when started on bisphosphonates. A total of 201 patients (71% men), median age 53 years (range, 18–70 years) were included in the study. Most common liver pathology was viral (27%) or alcoholic liver disease (25%). All patients received prednisone for at least 6 months after transplantation and the majority received either tacrolimus or cyclosporine for immunosuppression. At time of screening for OLT, osteoporosis and osteopenia were found in 18% and 36% of patients at the lumbar spine (LS), respectively, and in 9% and 42% at the femoral neck (FN), respectively. T‐scores declined significantly at both sites 6 months after OLT, but increased thereafter at the LS, reaching pretransplantation values at 2 years and remaining stable thereafter. FN T‐scores remained consistently lower than pretransplantation values. The prevalence of vertebral fractures increased from 56% at screening to 71% at 1 year after OLT, with a fracture incidence of 34%. BMD changes did not predict fracture risk. Osteoporosis, osteopenia, and vertebral fractures are prevalent in patients with end‐stage liver disease. An overall decline in BMD is observed within the first 6 months after OLT, with subsequent recovery to pretransplantation values at the LS, but not at the FN. Vertebral fracture risk is high after OLT regardless of changes in BMD. © 2014 American Society for Bone and Mineral Research.     

Skipping breakfast and less exercise are risk factors for bone loss in young Japanese adults: a 3-year follow-up study

Although bone loss contributes to osteoporosis (OP) in the elderly, little is known about changes in bone mineral density (BMD) in young adults that lead to bone loss. Here, we evaluated the rate of bone change and risk factors for bone loss in young men and women using data from a 3-year prospective study of Japanese medical students. The study included a self-administrated questionnaire survey, anthropometric measurements, and BMD measurements of the spine (L2–L4) and femoral neck (FN). After 3 years, the BMD of the participants was again measured at the same sites. In all, 458 students (95.4 %; 298 men and 160 women; age range, 18–29 years; mean age, 20.2 years) completed both the baseline and follow-up surveys. The mean L2–L4 BMD value at baseline increased significantly within 3 years. This tendency was also observed for the FN in men but not in women. The annual changes at L2–L4 were 1.78 % in men and 0.97 % in women per year; those for FN were 1.08 % in men and 0.08 % in women per year. However, 20.3 % and 38.5 % of the total freshmen lost BMD in the lumbar spine and FN, respectively. After adjustment for age and body mass index, logistic regression analysis revealed that bone loss in men at L2–L4 at the baseline was affected by skipping breakfast. In contrast, exercise (>2 h/week) increased lumbar spine BMD in both genders. These findings indicate that breakfast and exercise are important for maintaining BMD in young men and women.     

Evaluation of bone mineral density and fat-lean distribution in patients with multiple myeloma in sustained remission.

To study the usefulness of bone mineral density (BMD) in the follow-up of myeloma (MM) patients, BMD was evaluated in 44 MM patients in sustained remission for at least 2 years (35.4 +/- 10.5 months) after high-dose or conventional chemotherapy in a retrospective study. Patients never received bisphosphonates before or during the follow-up. Patients underwent lumbar spine (LS) BMD and a whole body (WB) BMD testing before therapy and at least once in the remission period. At baseline, mean LS BMD was 0.863 +/- 0.026 g/cm2, mean lumbar Z-score was -1.45 SD. LS BMD significantly increased from baseline by 5 +/- 1.8%, 9.3 +/- 1.7%, and 14 +/- 1.9% at 1, 2, and 3 years, respectively. The percentage of patients with a T-score below 2.5 SD decreased from 39% at baseline to 18.5% at 3 years. Compared with baseline, WB BMD decreased by -2.8 +/- 0.5%, -2.6 +/- 0.7%, and -1.7 +/- 0.6% at 1, 2, and 3 years, respectively. Mean percentage change of the fat compartment increased from baseline by +28.4 +/- 7.1% at the trunk, and +17.1 +/- 5% in peripheral areas at 3 years. In conclusion, in MM patients in remission after chemotherapy, LS BMD progressively increased after a mean follow-up of 3 years. These patients never received bisphosphonates, so this increase was related to the anti-myeloma treatment. The major effect on BMD was observed at the LS, which is primarily composed of trabecular bone containing the bone marrow. Interestingly, a drastic increase of the fat content was also observed. These results underlined that BMD and fat-lean evaluation could be of interest in the follow-up of MM patients.     

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.     

Bone mineral density and height gain in children with chronic cholestatic liver disease undergoing transplantation

BACKGROUND: Osteodystrophy is a well-described complication of chronic liver disease. Previous reports in adults and children undergoing liver transplantation (LT) were discordant, with the former showing no improvement of bone disease in the first year after transplantation and the latter demonstrating remarkable benefit from it. Our aim was to perform a pilot study on osteodystrophy in children undergoing LT and evaluate the contribution of growth on bone mineral density (BMD) changes. METHODS: We studied six patients (two male), with a median age at transplantation of 8.8 (range 3.8-16.6) years. Indications for transplantation were biliary atresia and progressive familial intrahepatic cholestasis (three patients each). BMD was studied with dual-energy x-ray absorptiometry and biochemical markers of liver and bone function in patients before and at 3, 6, and 12 months after LT. RESULTS: Median L2-L4 spinal BMD was 0.54 g/cm2 (range 0.29-0.87) before LT, and 0.58 g/cm2 (0.27-0.86) at 3 months, 0.66 g/cm2 (0.36-1.00) at 6 months, and 0.76 g/cm2 (0.44-1.02) at 12 months after LT (P=0.005). Median height was 133 (range 93-167) cm before LT, and 134 (93-167) at 3 months, 136 (97-167) at 6 months, and 139 (102-167) at 12 months after LT. There was direct correlation between height gain and total body BMD improvement (r=0.929, P=0.007). CONCLUSION: BMD in children with chronic cholestatic liver disease improves remarkably by 12 months after LT. Catch-up growth in children can account for the different effect of LT on bone density between adult and pediatric populations in the first year after surgery.     

Increase in Bone Mineral Density after Successful Parathyroidectomy for Tertiary Hyperparathyroidism after Renal Transplantation

BACKGROUND: Few studies have reported changes of bone mineral density (BMD) after parathyroidectomy in patients with persistent hyperparathyroidism after renal transplantation (3 HPT). PATIENTS AND METHODS: We retrospectively analyzed 14 patients who underwent successful parathyroidectomy for 3 HPT and who had available BMD data before and after parathyroidectomy. RESULTS: Median follow-up time was 26 months (IQR: 16.8-40.2). Serum calcium levels decreased significantly after parathyroidectomy (2.32 +/- 0.09 versus 2.66 +/- 0.16 mmol/l; p < 0.01), as did PTH levels (5.1 +/- 3.0 versus 27.8 +/- 23.7 pmol/l; p < 0.01). Nine patients (64%) had a steroid-free immunosuppression at follow-up. Mean increase in BMD was 9.5 +/- 8.0% for the spine and 9.5 +/- 7.9% for the hip (p < 0.01 for both sites). Patients with osteoporosis (T-score 相似文献   

Prevalence of osteoporosis, osteopenia, and vertebral fractures in long-term renal transplant recipients

BACKGROUND: Osteopenia and osteoporosis are frequent complications early after transplantation. Their long-term prevalences and associations with the risk of fractures are not well known. The objective of the present work was to determine the incidence of osteopenia and osteoporosis versus vertebral fractures in renal transplant recipients with stable graft function and with a follow-up of at least 10 years. PATIENTS AND METHODS: Forty renal transplant recipients, 24 men and 16 women, were included in the study. The mean age was 41.8 years and the follow-up was 130 +/- 14 months. Initial immunosuppression consisted of cyclosporine with or without an antiproliferative agent. Measurements of bone mass density (BMD) were performed by dual-energy X-ray absorptiometry (DEXA). The assessment of vertebral fracture using conventional radiography was evaluated by semiquantitative criteria. RESULTS: Eleven patients (27.5%) displayed lumbar spine osteoporosis (T-score < -2.5); 21 (52.5%), osteopenia (T-score > -2.5 and < -1) and 8 (20.0%), normal BMD. However, BMD was better preserved at the femoral neck: 14 patients (35.0%) had normal BMD; 20 (50.0%) osteopenia, and 6 (15.0%), osteoporosis. When analyzed together, patients with osteoporosis or osteopenia showed worse graft function at 1 and 8 years compared with normal BMD patients (1.75 +/- 0.634 vs 1.32 +/- 0.33 mg/dL at 1 year; P < .014) and (1.7 +/- 0.4 vs 1.2 +/- 0.2 mg/dL at 5 years; P < .01) and a greater number were prescribed vitamin D (50% vs 23%). Mild vertebral fractures were observed in 60.0% patients with osteoporosis; 70% with osteopenia; and 43% with normal lumbar BMD. Peripheral fractures were more common in patients with osteoporosis (P = .053). CONCLUSIONS: Osteoporosis and osteopenia are common among long-term renal transplant recipients are associated with poorer graft function. Lumbar spine BMD osteoporosis is associated with peripheral fractures. However, mild vertebral deformities are not associated with the presence of osteopenia or osteoporosis.     

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.