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     

Bone mineral density changes in hypercalciuretic osteoporotic men treated with thiazide diuretics

A few studies suggest that thiazide diuretic agents may have modest beneficial effects on bone. Few data are available on the effects of these medications in patients with osteoporosis and hypercalciuria. OBJECTIVE: To evaluate the effects of thiazide diuretic therapy on bone mass and urinary calcium excretion in hypercalciuretic osteoporotic male patients. PATIENTS AND METHODS: Osteoporosis was defined as a greater than 2.5 standard deviation (S.D.) decrease in bone mineral density (BMD) at the lumbar spine or hip (T-score). We used an open-label prospective design to compare 14 patients with hypercalciuretic osteoporosis treated with a thiazide diuretic for 18 months and 13 patients with primary osteoporosis treated with calcium and vitamin D supplementation. Mean age was 53.5 +/- 9.6 years in the thiazide group and 48.7 +/- 8.4 years in the calcium-vitamin D supplementation group. The following serum parameters were assayed at baseline: 25OH-D3, 1,25OH-D3, parathyroid hormone (PTH), and bone turnover markers. Urinary calcium excretion and BMD by dual-energy X-ray absorptiometry at the spine and hip were determined at baseline and after 18 months of treatment. RESULTS: Annual BMD increases were similar in the two groups during the 18-month treatment period: lumbar spine, 0.6 +/- 2.5% (P = 0.47) in the thiazide group and 0.004 +/- 3% (P = 0.78) in the supplementation group; femoral neck, 0.47 +/- 2.6% (P = 0.89) and 1.1 +/- 3.2% (P = 0.22); total hip, 0.65 +/- 2.5% (P = 0.37) and 0.12 +/- 2.1% (P = 0.51). Urinary calcium excretion fell by 45.9% in the thiazide group from baseline to study completion (P = 0.0015). CONCLUSION: We found no evidence that thiazide therapy increased bone mass in patients with hypercalciuria and osteoporosis as compared to calcium-vitamin D supplementation in patients with osteoporosis but no hypercalciuria. In contrast, our results establish the efficacy of thiazide diuretics in reducing urinary calcium excretion, an effect that may decrease the risk of urinary lithiasis. Studies in larger patient cohorts treated for longer periods are needed to confirm or refute our findings.     

Identification of men with reduced bone density at the lumbar spine and femoral neck using BMD of the os calcis.

We assessed the utility of os calcis (OC) bone mineral density (BMD) measurements to identify men with low BMD at the lumbar spine (LS) and femoral neck (FN). BMD was measured by dual X-ray absorptiometry (DXA). Receiver operator characteristics (ROC) analysis was applied to determine the risk of osteoporosis at the lumbar spine or femoral neck. [A total of 230 men with an average age of 59 yr were studied.] The most common reasons for referral were fracture (47%) and steroid use (46%). Twenty-six percent were osteoporotic at the LS, 21% at the FN, and 15% at the OC. Optimal classification with respect to osteoporotic measurements at the LS or FN was obtained at an OC T-score of -1.9 (BMD = 0.45 g/cm2). Osteoporosis was only weakly related to a simple cumulative risk factor score, but was strongly related to a T-score OC categorized into quartiles. Regression analysis of BMD on the major risk factors alone explained only 17% of the variance in BMD at the LS and 5% at the FN. The combination of the T-score at the OC, age, and weight provided the best model. BMD OC is superior to risk factors alone in the clinical evaluation and selection of men referred for axial densitometry.     

Changes in QUS and BMD Measurements with Antiresorptive Therapy: A Two-Year Longitudinal Study

There is lack of consensus on whether quantitative ultrasound (QUS) measurements can be used to monitor response to therapy. The aim of this 2-year longitudinal study was to assess whether calcaneal QUS measurement variables respond to antiresorptive therapy and whether these measurements display adequate long-term precision to be useful for monitoring purposes. The study population consisted of 195 postmenopausal women divided into three groups: Group 1: 39 women treated with antiresorptive therapy who commenced treatment at baseline; Group 2: 25 women treated with antiresorptive therapy who had been on treatment for at least 2 years at baseline; Group 3: 131 women who did not taken estrogen, bisphosphonates, or calcium during the 2-year study period. Subjects had baseline and 12 and 24 months follow-up BMD measurements at the lumbar spine (LS), femoral neck (FN), and total hip (THIP) and calcaneal QUS measurements of broadband ultrasound attenuation (BUA) and speed of sound (SOS). BUA and SOS were combined to provide an estimate of heel BMD (Est heel BMD). For women in Group 1, all BMD and QUS measurement variables increased significantly from baseline after 2 years of treatment. For women in Group 2, only THIP BMD and BUA increased significantly after 2 years and the changes were less than those observed in Group 1 women. The overall treatment effect for each measurement variable, defined as the difference in the mean absolute changes between Groups I and 3 after 2 years, was 0.08, 0.03, and 0.04 g/cm2 for LS, FN, and THIP BMD, and for BUA, SOS, and Est heel BMD it was 5.8 dB/MHz, 13.1 m/sec, and 0.05 g/cm2, respectively. When the overall treatment effect was expressed in T-score units, the effect was greatest for LS BMD (0.65 T-score units) and lowest for FN BMD (0.31 T-score units). QUS measurement variables yielded intermediate values of 0.43- 0.52 T-score units. The average least significant change (LSC) was 0.38 T-score units for BMD measurements, whereas the LSC for QUS measurements was three times greater at approximately 1.20 T-score units. Ninety-four percent of the women in Group 1 showed changes in LS BMD that exceeded the LSC after two years, while the percentage was lower for the other measurement variables ranging from approximately 6% for FN BMD, SOS and Est heel BMD to 50% for THIP BMD. A lower percentage of women in Groups 2 and 3 displayed changes that exceeded the LSC for both BMD and QUS measurement variables. Changes in all QUS variables were significantly correlated with changes in LS BMD, with correlation coefficients ranging from 0.26 to 0.40. In conclusion, calcaneal QUS measurement variables were found to show a highly significant response to antiresorptive therapy. However, the precision of QUS measurements was not good enough to allow QUS to be used for monitoring response to treatment. Future improvements in the precision of calcaneal QUS measurements are required to increase the utility of QUS for monitoring purposes.     

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.     

Impact of Long-Term Cinacalcet, Ibandronate or Teriparatide Therapy on Bone Mineral Density of Hemodialysis Patients: A Pilot Study

Background: Insufficient evidenced-based information is available for the treatment of osteoporosis in hemodialysis (HD) patients. Methods: In 102 HD patients, bone mineral density (BMD) was measured twice 16 ± 3 months apart. In the second BMD measurement 66 of them had a femoral neck (FN) T-score <-2.5. Of these 66 patients, 38 consented to a bone biopsy. Depending on both the bone biopsy findings and parathyroid hormone levels, patients were assigned to treatment groups. Eleven patients with osteitis fibrosa and iPTH >300 pg/ml received cinacalcet, 11 with osteitis fibrosa and iPTH <300 pg/ml received ibandronate, 9 with adynamic bone disease received teriparatide, and 7 with mild abnormalities received no treatment. A third BMD measurement was done after an average treatment period of 13-16 months. We compared the annual percent change of FN and lumbar spine (LS) BMD before and during treatment. Results: FN and LS BMD decreased significantly in the cinacalcet group, with an annual change of 3.6 and 3.4% before treatment to -4.2% (p = 0.04) and -7.7% (p = 0.02) during treatment, respectively. In the teriparatide group, FN and LS BMD increased, although not significantly, with an annual change of -5.4 and -2.6% before treatment to 2.7 and 4.9% during treatment, respectively. In both the ibandronate and the no treatment groups, BMD change rate remained negative during the whole study. Conclusions: Teriparatide administration improved BMD in HD patients with adynamic bone disease, although these results did not reach statistical significance. In HD patients with osteitis fibrosa, ibandronate did not improve BMD while cinacalcet reduced BMD.     

Mechanisms of bone loss following allogeneic and autologous hemopoietic stem cell transplantation.

A significant proportion of patients will be long-term survivors of bone marrow transplantation (BMT) and little is known about their risk of late bony complications. We therefore evaluated bone mineral density (BMD) prior to BMT, post-transplantation changes in BMD, and mechanisms of bone loss in long-term survivors. We performed two analyses. The first was a cross-sectional study of 83 consecutive BMT patients (38 F, 45 M), examining the relationship between BMD and bone turnover, measured immediately prior to transplantation, and a number of disease and patient variables. The second was a prospective study of 39 patients (19F, 20 M) followed for a median of 30 months (range 5-64 months) following either allogeneic (allo, n = 29) or autologous (auto, n = 10) BMT to determine if bone loss was related to treatment of graft versus host disease (GVHD) with glucocorticoids and cyclosporine A, high bone turnover rates, or hypogonadism. Auto BMT recipients acted as a control group for effects of GVHD therapy on BMD. Prior to BMT, spinal and femoral neck (FN) BMDs were 8.6% and 14% lower in female auto BMT recipients than in female allo BMT recipients, respectively (p = 0.12 and p = 0. 003). Urinary bone resorption markers were higher than in normal gender- and age-matched control subjects. Patients treated previously with glucocorticoids also had 8% lower FN BMD. Glucocorticoid-pretreated women with amenorrhoea had lower lumbar spine (LS) and FN BMDs than eumenorrheic women and women receiving HRT. Post-allo BMT, patients lost 11.7% of FN BMD compared with a nonsignificant decrease of 1.1% post-auto BMT (p < 0.001). Spinal BMD and total body bone mineral content (TBBMC) decreased by 3.9% and 3.5%, respectively, post-allo, compared with an increase (1.5%, p = 0.03) or nonsignificant decrease (-3.7%, p = NS), respectively, post-auto BMT. Post-allo BMT bone loss correlated best with the cumulative prednisolone dose at the LS and FN, and with average daily prednisolone dose for TBBMC. At the spine, the rate of bone loss was 4%/10 g of prednisolone, while the rate of bone loss at the FN was greater (9%/10 g of prednisolone). Bone loss was also negatively related to the duration of cyclosporine therapy for GVHD and baseline deoxypyridinoline concentrations. Avascular necrosis of the femoral head occurred in four, and vertebral and rib fractures occurred in one of the allo BMT patients, but in no auto BMT patients. In conclusion, BMT recipients are at risk of osteoporosis secondary to bone loss associated with their underlying illness and/or chemotherapy, particularly in female autograft recipients, and in allograft recipients secondary to GVHD and its treatment.     

Osteoporosis Before Lung Transplantation: Association with Low Body Mass Index, but Not with Underlying Disease

Due to progress in lung transplantation, post-transplantation osteoporosis becomes an important problem. We determined bone mineral density (BMD) in 74 lung transplantation candidates, among them 24 patients with cysticfibrosis, 16 with chronic obstructive pulmonary disease, 14 with pulmonary fibrosis, and 11 with pulmonary hypertension. The mean T score (+/- SD) was -2.6 +/- 1.3 at femoral neck (FN), -2.2 +/- 1.6 at Ward's triangle (WT) and -2.3 +/- 1.5 at lumbar spine (LS). Osteoporosis was found in 61% of the patients at FN, 45% at WT and 50% at LS. Patients with different underlying lung diseases were similarly affected, not only those with cystic fibrosis but also others, including patients with pulmonary hypertension. No association was found between BMD and age, gender, menstrual condition in women and testosterone level in men. A negative correlation was found between chronic glucocorticoid use and T scores. Body mass index correlated positively (p < 0.01) with T scores at any site and the correlation was also significant for the 2 largest subgroups. Loss of lung function (FEV1) also was associated with lower T scores. No correlation was found between BMD and biochemical indices of bone turnover. Multivariate analysis revealed BMI and glucocorticoid use as independent risk factors. We conclude that osteoporosis is a very common condition in patients with end-stage pulmonary disease, independent of the underlying diagnosis. In view of additional bone loss under immunosuppressive treatment after lung transplantation, early diagnosis and prevention of osteoporosis in the pretransplant period should receive high priority.     

Allogeneic Bone Marrow Transplantation is Associated with a Preferential Femoral Neck Bone Loss

Osteoporosis is a major complication of organ transplantation. Little is known about the risk of developing osteoporosis in bone marrow transplant (BMT) recipients. We studied early and late changes in bone mineral density (BMD), as well as biochemical markers of bone remodeling, in patients at the time of allogeneic BMT (alloBMT) and up to 13 years thereafter. In a cross-sectional study, 102 patients (40 women, 62 men, mean age ± SEM, 38.9 ± 1.6 years) were segregated into a first group (A, n= 48) and evaluated before or during the first weeks (mean ± SD 0.3 ± 0.1 month, range –0.5 to 3 months) following alloBMT, and a second group (B, n= 54) studied 60.1 ± 5.6 months (range 6–156 months) following alloBMT. Lumbar spine (LS) BMD was similar in groups A and B and was within normal limits. In contrast, femoral neck (FN) Z- and T-scores were significantly decreased in group B compared with group A (–0.68 ± 0.14 vs –0.03 ± 0.14 SD and –0.84 ± 0.14 vs –0.22 ± 0.14 SD, respectively; p≤0.002). Osteopenia (T-score between –1 and –2.5 SD) was present in 35% of group A and 43% of group B patients (NS). Osteoporosis (T-score <–2.5 SD) was detected in 7% of group B patients, but in none of those in group A (p= 0.05). In a longitudinal study, 56 subjects were evaluated at the time of alloBMT, and 33 and 23 were studied 6 or 12 months later, respectively (13 women, 20 men, 37.5 ± 1.6 years). All were treated with supplements of calcium and vitamin D. Amenorrheic women received hormone replacement therapy (HRT). Three-monthly pamidronate infusions were given to 15 men and 10 non-amenorrheic women who were osteopenic/osteoporotic or had elevated baseline bone turnover markers. Mean baseline LS and FN Z- and T-scores were within normal range. Six months after BMT, FN BMD decreased by 4.2 ± 0.7% (p<0.001), and whole body BMD and bone mineral content by 1.5 ± 0.4% and 3.1 ± 0.6%, respectively (p≤0.0001). Twelve months after the graft, there was no further significant bone loss and only FN BMD decrease remained significantly different compared with baseline (–5.6 ± 1.1%, p≤0.0001). These results indicate that the risk of decreased BMD is higher for the femoral neck than the lumbar spine and whole body levels in patients with allogeneic bone marrow transplantation, and that bone loss occurs mainly during the first 6 months after the graft. Received: 9 February 2001 / Accepted: 23 May 2001     

Hyperparathyroidism and long-term bone loss after renal transplantation

BACKGROUND: While early bone loss after renal transplantation (RT) is well described, factors affecting the long-term fate of bone have received less attention. METHODS: Whole body (WB), lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) was measured using dual energy X-ray absorptionometry in 126 stable RT patients and repeated in 114 survivors after 3 yr. Percentage change per year (%/yr) was correlated to clinical and biochemical markers of bone metabolism. RESULTS: Low bone mass was a marker of increased mortality (FN < 80% normal 6.3%/yr; >80% 2.2%/yr). Percent change was WB -0.7 +/- 1.5 (p < 0.01); LS -0.3 +/- 2.6; FN -1.0 +/- 3.0 (p < 0.01) and, corrected for expected loss for age and sex: WB -0.5 (p < 0.01); LS 0.0; FN -0.8 (p < 0.05). Factors associated with increased loss rates were (LS%): short RT duration [<2 yr: -3.1 (p < 0.01)], high prednisone dose [>9 mg/d: -1.9 (p < 0.01)], high cyclosporine trough concentration [>175 ng/L: -1.9 (p < 0.05)], high hyperparathyroidism (PTH) [>150 ng/L: -1.5 (p < 0.05)], high alkaline phosphatase [>275 U/L: -1.6 (p < 0.05)], high osteocalcin [>75 microg/L: -1.6 (p < 0.05)]. Marginal detrimental effects of uremia, hypoalbuminemia and hyperphosphatemia were noted. Thiazide treatment seemed to protect against, and furosemide to exacerbate, bone loss, but this may have been related to associated uremia. Patients treated with vitamin D gained bone, while untreated patients with low initial 1,25-dihydroxyvitamin D lost bone [FN%-2.1 (p < 0.05)]. The prevalence of PTH (52%) and hypercalcemia (22%) remained unchanged. There was no effect of sex hormone levels, calcium and phosphate excretion, or serum calcium. CONCLUSION: While LS BMD stabilizes after RT, there is a continuing loss of WB and FN BMD. The major causes of bone loss are steroid therapy and continuing PTH, with no tendency towards spontaneous resolution. Increased vitamin D and calcium therapy should be considered for this patient group, and more aggressive therapy, e.g. parathyroidectomy given for patients with resistant PTH of >150 ng/L.     

Effectiveness of alendronate and etidronate in the treatment of osteoporosis in men: a prospective observational study

The prevalence of osteoporosis in men is higher than previously assumed; consequently, numerous therapies are being investigated to treat these patients. The Canadian Database of Osteoporosis and Osteopenia patients (CANDOO) was analyzed to examine changes in bone mineral density (BMD) in consecutively seen osteoporotic men administered alendronate, etidronate or no bone-active drugs (control) over 1 year. A total of 244 men attending six Canadian osteoporosis clinics were included in the study (42 alendronate, 102 etidronate and 100 control). Multiple imputation was used to model missing data to provide a more robust statistical model. The imputed datasets (five) were analyzed using multivariable linear regression to determine differences between groups in the percent change of lumbar spine (LS) and femoral neck (FN) BMD from baseline to 1 year. Differences in the percent change in BMD from baseline were most notable at the LS in favor of alendronate (4.3%; 95% CI: 2.1, 6.6 ) and etidronate (2.1%; 95% CI: 0.3, 4.0) therapy when compared with controls. At the LS, alendronate therapy led to significantly greater (2.2%; 95% CI: 0.2, 4.2) gains in BMD as compared to etidronate therapy. Compared to controls, there were no significant differences in FN BMD with alendronate (2.1%; 95% CI: –0.4, 4.7) or etidronate therapy (0.9%; 95% CI: –1.1, 2.8), nor were there significant differences between bisphosphonate groups (1.3%; 95% CI: –1.1, 3.6, in favor of alendronate). While both alendronate and etidronate significantly increased LS BMD in osteoporotic men after 1 year in real-world settings, alendronate therapy resulted in significantly superior gains in LS BMD. The effect of these two bisphosphonates on fractures and FN BMD in osteoporotic men is likely positive, but requires further study.     

Bone Mineral Density in Male Patients with L-Thyroxine Suppressive Therapy and Graves Disease

Little is known about the effects of thyroid hormone excess in male patients. Our aim was to evaluate bone mineral density (BMD), bone turnover markers, and thyroid function in male patients with treated thyroid cancer on long-term suppressive L-T4 therapy (TC) and in male patients with Graves' disease (GD). We studied 49 male patients (aged 45+/-12 years), 17 with TC (29-288 months on L-T4 suppressive therapy; free T4: 1.9+/-0.6 ng/dl [normal< or =2.0]; TSH: 0.2+/-0.3 microU/ml [Normal 0.5-5.0]) and 32 with recent onset GD (<12 weeks, free T4: 2.0+/-1.4 ng/dl; TSH: 1.07+/-1.8 microU/ml; TSHRAb 53+/-45% [normal < 15]). BMD was measured by dual X-ray absorptiometry (DXA, Hologic QDR1000w) at the lumbar spine (L2-L4, LS), femoral neck (FN), and Ward's triangle (WT). Results were expressed as Z-score (SD compared to national controls). Total alkaline phosphatase (ALP), osteocalcin (BGP), iPTH, serum phosphorus, serum, and 24 h urine calcium were measured as bone markers. Age, weight, and body mass index were comparable in both groups. Patients with TC and with GD showed reduced axial BMD (95% confidence interval: LS: TC (-1.27-0.01)(P = 0.046), GD (-1.06 to-0.38)(P < 0.001); FN: TC (-0.82 to-0.16)(P = 0.007), GD (-0.95 to-0.15)(P = 0.008); WT: TC (-0.82 to -0.18)(P = 0.004), GD (-0.97 to -0.08)(P = 0.024). No significant differences in BMD were found between the groups. Among bone markers, total ALP and osteocalcin levels showed higher levels in Graves' disease (ALP: 139+/-76 vs. 88+/-34, P < 0.01; BGP: 7.5+/-3.7 vs. 4.6+/-1.6; P < 0.001). Our data suggest a mild deleterious effect of thyroid hormone excess in the axial bone mass from male subjects. A skeletal status assessed by BMD in male patients with chronic TSH suppression by L-T4 or history of hyperthyroidism is recommended.     

Prevention of bone loss and fracture after lung transplantation: a pilot study

BACKGROUND: Osteoporotic fracture is a significant source of morbidity after lung transplantation. Therapies to prevent posttransplant fracture are largely untested among lung transplant recipients. METHODS: In this prospective uncontrolled study, lung transplant referrals were assessed for bone health with metabolic, radiographic, and bone mineral density measurements. Transplant recipients were treated with an antiresorptive regimen that included a bisphosphonate starting before or after transplantation. One year after transplantation, the fracture rate and bone density of patients in each group were reassessed and compared to historical controls. Between January 1996 and August 1999, 45/50 (90%) lung transplant referrals underwent bone health assessment. Transplant candidates received calcium, vitamin D, and hormone replacement therapy as indicated for hypogonadism. After July 1998, bisphosphonate therapy was added for candidates with osteopenia or osteoporosis (T score <1). After transplantation, all patients received 90 mg of pamidronate i.v. every 12 weeks, regardless of pretransplant bone density. Radiologic evaluation was performed for clinical suspicion of fracture. Bone density was remeasured 1 year after transplantation. RESULTS: Most transplant referrals suffered from osteopenia or osteoporosis, and 29% of transplant referrals had prevalent vertebral compression fractures. Hypogonadism was untreated in 50% of men and 20% of women, and 15% of patients had hypovitaminosis D. Of the 21 patients assessed 1 year after transplantation, new fractures occurred in 4% of these patients. Lateral lumbar spine and hip bone density remained stable or improved in 65% and 86% of patients, respectively. Most of those who lost bone density had started bisphosphonate therapy after transplantation. CONCLUSIONS: Antiresorptive therapy with a bisphosphonate decreases the fracture rate and preserves bone mass 1 year after lung transplantation. In end-stage lung disease patients with osteopenia or osteoporosis, bisphosphonate therapy should be initiated before transplant surgery is contemplated.     

Estrogen receptor alpha gene polymorphisms and bone mineral density: haplotype analysis in women from the United Kingdom.

Genetic factors are important in the pathogenesis of osteoporosis and the estrogen receptor has been suggested as a possible candidate gene for regulation of bone mineral density (BMD). We investigated the relationship between PvuII, XbaI, and dinucleotide (TA)n repeat polymorphisms of the estrogen receptor alpha (ER-alpha) gene and BMD in a study of women from northeast Scotland in the United Kingdom. No significant association was observed between BMD values at the lumbar spine (LS) and femoral neck (FN) in relation to PvuII and XbaI polymorphisms individually, but haplotype analysis showed that BMD values (Z score) were significantly lower in those who carried the Px haplotype (n = 36) compared with those who did not (n = 170) at both the LS (mean +/- SEM; -0.775 +/- 0.125 vs. -0.285 +/- 0.082;p = 0.002) and the FN (-0.888 +/- 0.130 vs. -0.335 +/- 0.083; p = 0.0006). In keeping with this, the Px haplotype also was found to be an independent predictor of LS BMD (p = 0.019) and FN BMD (p = 0.005) in a multiple regression analysis model that included other possible predictors of BMD including age, years since menopause (YSM), hormone-replacement therapy (HRT) use, weight, and height. This model explained 15.7% and 23.4% of the total observed variance in LS and FN BMD, respectively, with the Px haplotype accounting for approximately 3% of the variance at both sites. Although the TA repeat polymorphism was in strong linkage disequilibrium (LD) with the PvuII (chi2 = 109.8; p < 0.0001) and XbaI (chi2 = 97.2; p < 0.0001) polymorphisms, there was no overall association between TA repeat number and BMD. We conclude that polymorphisms of the ER-alpha gene are significantly related to BMD in our population and that this association is dependent on the Px haplotype, suggesting that it is the Px haplotype, or a linked polymorphism, that confers risk.     

Bone mineral density changes within 11 months of renal transplantation in Iranian patients

BACKGROUND AND AIM: We studied bone mineral density (BMD) changes in Iranian patients with end-stage renal disease (ESRD) within 11 months after renal transplantation. METHODS: Among 68 ESRD candidates for renal transplantation, the BMD at the femur and the spine were assessed using a DEXA Norland scanner. Linear regression analysis was used to identify risk factors associated with low bone density. RESULTS: Mean BMD, T-score and Z-score of femur and spine were significantly reduced (at femur, 0.78 +/- 0.14, -2.4 +/- 1.1, -1.6 +/- 1.0; at spine, 142.25 +/- 105, -1.09 +/- 1.1, -1.07 +/- 0.9). Osteoporosis and osteopenia were found 55.2% and 36.2% at the femur and 8.6% and 58.6% at the spine, respectively. The BMD showed a significant negative association with age (r=0.615), female gender (r=0.394), and corticosteroid intake (r=0.286), and a positive association with weight (r=0.394) and body mass index (r=0.626). There was no significant association between BMD measurements and calcium, phosphorous, or parathyroid hormone levels. At 11 months follow-up, in 20 patients, the subject had lost a mean of 2.4% T-score and 2.8% Z-score at spine (P=.027 and .13, respectively), but did not experience significant declines at the femur. BMD showed a decrease in 80% of recipients in the spine area; there was a 15% BMD increase at the hip. CONCLUSION: Low bone density is common among ESRD Iranian patients. Early screening and treatment of this group is recommended. Significant loss in lumbar density occurred within 11 months of transplantation in more than one third of a prospective cohort of renal transplant recipients.     

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.     

Long-term corticosteroid therapy induces mild changes in trabecular bone texture.

The relative roles of bone mineral density (BMD) decrease and of microarchitectural changes in corticosteroid-induced osteoporosis (CIOP) are debated. Our objective has been to evaluate both bone microarchitecture (by a fractal analysis of texture on radiographs) and BMD in corticosteroid (CS)-treated patients. In this study, 60 patients from a rheumatology unit with a mean age of 60.6+/-14.8 years taking CS therapy for more than 6 months and a cumulative dose of prednisone over 1 g and 57 controls among age-matched patients and hospital staff were recruited. Bone diseases and bone-modifying drugs (except calcium, vitamin D, and hormonal replacement therapy [HRT]) were considered as exclusion criteria. A fractal analysis of trabecular bone texture was performed on calcaneus radiographs after an oriented analysis in 18 directions. The fractal analysis was based on the fractional Brownian motion model. Results were expressed by H parameter (H = 2 - fractal dimension) in each direction, Hmean being the average of 18 directions, Hmini the minimum, and Hmaxi the maximum. BMD was measured by double-energy X-ray absorptiometry (DEXA) at the femoral neck (FN) and lumbar spine (LS). The odds ratios (OR) were calculated for a variation of 1 SD. The mean duration and dose of CS therapy was 5.6+/-6.6 years and 16.9+/-19.7 g. CS therapy was significantly correlated to a decrease in FN or LSBMD: OR = 1.95, 95% confidence interval (CI, 1.29-2.97) and OR = 3.19 (CI, 1.80-5.66), respectively. The Hmean and Hmaxi were significantly lower in the cases than in the controls: P = 0.03 and P = 0.02; OR = 1.67 (CI, 1.10-2.54) and OR = 1.75 (CI, 1.05-2.37). A similar trend was observed with Hmini but the difference did not reach the level of statistical significance: P = 0.06, OR = 1.57 (CI, 1.05-2.37). This study was repeated among cases and controls who had never taken HRT (respectively, n = 40 and n = 39). The results were similar. Among patients taking CS therapy, the presence of nontraumatic fractures was inversely related to BMD values but not to texture parameters. These data have shown that long-term CS therapy induces both BMD decrease and trabecular bone texture changes. The effect of CS therapy was much stronger on BMD than on the fractal H parameter. These results are in accordance with previous studies showing a lower effect of CS therapy on bone microarchitecture than on bone mass. These results can be contrasted with those observed in women with postmenopausal osteoporosis and vertebral crush fractures in which the variations in the fractal parameters are more significant than the BMD variations.     

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   

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.