Late Low-Dose Steroid Withdrawal in Renal Transplant Recipients Increases Bone Formation and Bone Mineral Density

Corticosteroids have been the most widely used immunosuppressive agents since the first clinical transplantation in the 1950s. There are few studies of late steroid withdrawal in renal transplantation and none have prospectively assessed bone mineral density (BMD). The study aim was to assess the impact of corticosteroid withdrawal, in stable renal transplant recipients, on BMD and bone turnover. BMD, osteocalcin (OC) and cross-linked telopeptide of type I collagen (CTx) were measured in 92 patients randomized into a trial of steroid withdrawal. Patients with functioning renal transplants for more than 1 year with a serum creatinine below 200 micromol/L entered the trial. All patients were on triple immunosuppression (Cyclosporin microemulsion, Azathioprine and prednisolone), corticosteroids were withdrawn at 1 mg/month. BMD was measured twice annually with serum CTx and OC. One year following withdrawal of glucocorticoids there was no significant difference in creatinine. BMD increased in the withdrawal group (2.54% per year L1-L4, p < 0.01), there was a slight reduction in the control group. Mean OC increased from 5.3 to 12.2 ng/mL (p < 0.05) in the withdrawal group, but was unchanged in the controls. No change was seen in CTx. Corticosteroid withdrawal in renal transplant recipients results in an increase in BMD with a corresponding increase in serum OC.     

Mineral and Bone Disease in Kidney Transplant Recipients

Purpose of Review

Despite metabolic improvements following kidney transplantation, transplant recipients still often suffer from complex mineral and bone disease after transplantation.

Recent Findings

The pathophysiology of post-transplant disease is unique, secondary to underlying pre-transplant mineral and bone disease, immunosuppression, and changing kidney function. Changes in modern immunosuppression regimens continue to alter the clinical picture. Modern management includes reducing cumulative steroid exposure and correcting the biochemical abnormalities in mineral metabolism. While bone mineral density screening appears to help predict fracture risk and anti-osteoporotic therapy appears to have a positive effect on bone mineral density, more data regarding specific treatment is necessary.

Summary

Patients with mineral and bone disease after kidney transplantation require special care in order to properly manage and mitigate their mineral and bone disease. Recent changes in clinical management of transplant patients may also be changing the implications on patients’ mineral and bone disease.

     

The Impact of Smoking on Bone Metabolism,Bone Mineral Density and Vertebral Fractures in Postmenopausal Women

Background: Smoking is recognized among the risk factors for osteoporosis, but only few studies have comprehensively explored its influence on bone metabolism and strength. We aimed to evaluate smoking effects on calcium-phosphate metabolism, bone mineral density (BMD) and fracture risk in postmenopausal women. Methods: Our sample included 1067 postmenopausal women who arrived to our osteoporosis outpatient clinic. Anamnestic data, smoking habits (categorized as never, former, and current; and by smoking intensity and duration), biochemical parameters, lumbar/femoral BMD, and presence of vertebral fractures were recorded. In a subsample of 357 women, the changes in BMD after a 2-yr follow-up period were also assessed. Results: Current smokers had shorter reproductive age, lower body mass index, and higher prevalence of heavy alcohol consumption than former/never smokers. They also had lower PTH values and weaker linear association between serum vitamin D and parathyroid hormone (current β = −0.11[SE = 0.004]; former β = −0.14[SE = 0.01]; never β = −0.20[SE = 0.003]; p < 0.01 for all). Baseline BMD did not reflect differences based on smoking habits, duration or intensity. However, after 2 years, only current smokers significantly worsened in femural BMD. After adjustment for confounders, the chance of having sustained vertebral fractures at the first evaluation increased by 74% (95% confidence interval:1.07–2.83) in current compared with never smokers, especially among heavy smokers. Conclusions: Smoking may negatively affect bone by inhibiting vitamin D-parathyroid hormone axis, reducing estrogen exposure, promoting risky health behaviors, and accelerating bone loss, especially at the femur. No significant differences were observed in these outcomes among former smokers, suggesting that quitting smoking has beneficial effects on bone health.     

Impact of Enterococcal Bacteremia in Liver Transplant Recipients

BackgroundEnterococcus species are a common cause of bacteremia in liver transplant recipients. Vancomycin-resistant enterococci (VRE) have become an important cause of nosocomial infection. In this study, we analyzed the incidence, antibiotic resistance, and outcomes of enterococcal bacteremia in living donor liver transplant recipients and the risk factors for VRE.Patients and MethodsThis single-center, retrospective review included 536 patients who underwent liver transplant between January 2008 and December 2017.ResultsAmong 536 patients, 42 (7.8%) experienced a total of 58 enterococcal bacteremic episodes (37 Enterococcus faecium, 17 Enterococcus faecalis, 2 Enterococcus casseliflavus, 1 Enterococcus. avium, and 1 Enterococcus raffinosus). Most cases of enterococcal bacteremia (46/58, 79.3%) occurred within 6 months after transplant; among the 26 cases of VRE bacteremia, 50% occurred within 1 month after transplant. E. faecium isolates had the highest rate of vancomycin resistance (25/37, 67.5%), whereas all E. faecalis isolates were susceptible to vancomycin. According to multivariate analysis, post-transplant dialysis (odds ratio, 3.95; 95% CI, 1.51–10.34; P = .005) and length of post-transplant hospital stay (odds ratio, 1.03; 95% CI, 1.009–1.04; P = .004) were significantly associated with VRE bacteremia. One-year mortality was 31% (13/42) among recipients with enterococcal bacteremia, 5.0% (20/384) among nonbacteremic patients, and 11.1% (10/90) among patients with nonenterococcal bacteremia (P < .001).ConclusionIn this study, enterococcal bacteremia showed high incidence in liver transplant recipients, especially with vancomycin resistance, occurred in early period after transplant, and was associated with increased mortality. High rates of resistance to vancomycin warrant further efforts to manage enterococcal infection in liver transplant recipients at our center.     

Bone Mineral Density and Vertebral Fractures in Men

In women, many studies indicate that the risk of vertebral fragility fractures increases as bone mineral density (BMD) declines. In contrast, few studies are available for BMD and vertebral fractures in men. It is uncertain that the strength of the relationship between BMD and fractures is similar in magnitude in middle-aged men and in postmenopausal women. In the present study, 200 men (mean age 54.7 years) with lumbar osteopenia (T-score <−1.5) were recruited to examine the relationships between spine BMD and hip BMD and the associations of BMD with vertebral fractures. Lumbar BMD was assessed from L2 to L4, in the anteroposterior view, using dual-energy X-ray densitometry. At the upper left femur, hip BMD was measured at five regions of interest: femoral neck, trochanter, intertrochanter, Ward’s triangle and total hip. Spinal radiographs were analyzed independently by two trained investigators and vertebral fracture was defined as a reduction of at least 20% in the anterior, middle or posterior vertebral height. Spinal radiographs evidenced at least one vertebral crush fracture in 119 patients (59.5%). The results of logistic regression showed that age, femoral and spine BMDs were significant predictors of the presence of a vertebral fracture. Odds ratios for a decrease of 1 standard deviation ranged from 1.8 (1.3–2.8) for spine BMD to 2.3 (1.5–3.6) for total hip BMD. For multiple fractures odds ratios ranged from 1.7 (1.1–2.5) for spine BMD to 2.6 (1.7–4.3) for total hip BMD. In all models, odds ratios were higher for hip BMD than for spine BMD, particularly in younger men, under 50 years. A T-score <−2.5 in the femur (total femoral site) was associated with a 2.7-fold increase in the risk of vertebral fracture while a T-score <−2.5 in the spine was associated with only a 2-fold increase in risk. This study confirms the strong association of age and BMD with vertebral fractures in middle-aged men, shows that the femoral area is the best site of BMD measurement and suggests that a low femoral BMD could be considered as an index of severity in young men with lumbar osteopenia. Received: 27 October 1998 / Accepted: 22 February 1999     

Impact of Pretransplant Infections on Clinical Course in Liver Transplant Recipients

Background

Uncontrolled infections are known to be an absolute contraindication for liver transplantation; however, the posttransplant prognosis of recipients treated for pretransplant infection is unclear. The aim of this study was to analyze pretransplant infections among liver transplant recipients and to determine their impact on posttransplant clinical outcomes.

Bone Mineral Density Predicts Fractures in Chronic Kidney Disease

Fractures are common in chronic kidney disease (CKD). The optimal methods by which to assess fracture risk are unknown, in part, due to a lack of prospective studies. We determined if bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA), and/or high‐resolution peripheral quantitative computed tomography (HRpQCT) could predict fractures in men and women ≥18 years old with stages 3 to 5 CKD. BMD was measured by DXA (at the total hip, lumbar spine, ultradistal, and 1/3 radius) and by HRpQCT (at the radius), and subjects were followed for 2 years for incident morphometric spine fractures and low‐trauma clinical fractures. The mean age of the subjects was 62 years with equal numbers having stages 3, 4, and 5 CKD. Over 2 years there were 51 fractures in 35 subjects. BMD by DXA at baseline was significantly lower at all sites among those with incident fractures versus those without. For example, the mean BMD at the total hip in those with incident fractures was 0.77 g/cm² (95% confidence interval [CI], 0.73 to 0.80) and in those without fracture was 0.95 g/cm² (95% CI, 0.92 to 0.98). Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without. For example, volumetric BMD in those with incident fractures was 232 mg HA/cm³ (95% CI, 213 to 251) and in those without fracture was 317.6 mg HA/cm³ (95% CI, 306 to 329.1). Bone loss occurred in all subjects, but was significantly greater among those with incident fractures. Our data demonstrate that low BMD (by DXA and HRpQCT) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD. © 2014 American Society for Bone and Mineral Research.     

Bone Mineral Density Deficits and Fractures in Survivors of Childhood Cancer

Although substantial increases in survival rates among children diagnosed with cancer have been observed in recent decades, survivors are at risk of developing therapy-related chronic health conditions. Among children and adolescents treated for cancer, acquisition of peak bone mass may be compromised by cancer therapies, nutritional deficiencies, and reduced physical activity. Accordingly, failure to accrue optimal bone mass during childhood may place survivors at increased risk for deficits in bone density and fracture in later life. Current recommendations for the treatment of bone density decrements among cancer survivors include dietary counseling and supplementation to ensure adequate calcium and vitamin D intake. Few strategies exist to prevent or treat bone loss. Moving forward, studies characterizing the trajectory of changes in bone density over time will facilitate the development of interventions and novel therapies aimed at minimizing bone loss among survivors of childhood cancer.     

Impact of Vitamin D,Bisphosphonate, and Combination Therapy on Bone Mineral Density in Kidney Transplant Patients

Background

Osteoporosis can develop and become aggravated in kidney transplant patients; however, the best preventive options for post-transplantation osteoporosis remain controversial.

Methods

We retrospectively analyzed cohort of 182 renal transplant recipients of mean age 46.7 ± 12.1 years including 47.3% women. Seventy-three patients received neither vitamin D nor bisphosphonate after transplantation (group 1). The other patients were classified into the following 3 groups: calcium plus vitamin D (group 2; n = 40); bisphosphonate (group 3; n = 18); and both regimens (group 4; n = 51). Bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry at baseline and at 1 year after transplantation.

Results

At 1 year after transplantation, T-scores of the femoral neck and entire femur were significantly decreased in group 1 (−0.23 ± 0.65 [P = .004] and −0.21 ± 0.74 [P = .018], respectively), whereas the lumbar spine was significantly increased in group 4 (0.27 ± 0.79; P = .020). Post hoc analysis demonstrated that the delta T-score was significantly lower in group 1 than in group 4 (P = .009, 0.035, and 0.031 for lumbar spine, femoral neck, and entire femur, respectively). In a multivariate analysis adjusted by age, sex, body mass index, dialysis duration, diabetes, calcineurin inhibitors, estimated glomerular filtration rate, and persistent hyperparathyroidism, both group 2 and group 4 showed protective effects on BMD reduction (odds ratio [OR], 0.165; 95% confidence interval [CI] 0.032–0.845 [P = .031]; and OR, 0.169; 95% CI, 0.045–0.626 [P = .008]; respectively). However, group 3 did not show a protective effect (OR, 0.777; 95% CI, 0.198–3.054; P = .718), because their incidence of persistent hyperparathyroidism after transplantation was significantly higher (50.0%) than the other groups (P < .001). The incidence of bone fractures did not differ among the groups.

Conclusions

Combination therapy with vitamin D and bisphosphonate was the most effective regimen to improve BMD among kidney recipients.     

The Impact of Bone Mineral Density on Bone Metabolism and the Fracture Healing Process in Elderly Chinese Patients With Osteoporotic Vertebral Compression Fractures

Background: The aim of this study was to investigate the effect of bone mineral density (BMD) on bone histomorphological parameters and bone turnover markers (BTMs) following osteoporotic vertebral compression fracture (OVCF) and to determine the correlation between BMD and the percentage of middle height compression during the healing process. Methods: A total of 206 patients with OVCFs were included in this study. Bone biopsy specimens were acquired during surgery. Blood samples were obtained to determine the serum concentrations of BTMs. The patients were divided into 2 groups according to BMD.Results: The concentrations of N-terminal propeptide of type I collagen (PINP) in the T-score ≤ ?2.5 group (50.92 ± 12.78 ng/ml) were significantly lower than those in the T-score > ?2.5 group (68.75 ± 28.66 ng/ml, p = 0.025) 3–6 mo after fracture. Moreover, the volume of necrotic bone in the T-score ≤ ?2.5 group (15.15 ± 5.44%) was higher than that (1.67 ± 0.79%, p < 0.001) in the T-score > ?2.5 group during the same period. BMD was statistically correlated with cancellous bone content (R_S = 0.761, p <0.001), PMHC (R_S = 0.85, p < 0.001), fibrous tissue volume (R_S = ?0.376, p < 0.001), and necrotic bone content (R_S = ?0.487, p < 0.001).Conclusions: The healing process of OVCFs in the setting of low bone mass frequently occurs in the presence of decreased bone formation abilities, severe vertebral body height loss and a large amount of necrotic bone.     

Bone Mineral Density and Bone Size in Men With Primary Osteoporosis and Vertebral Fractures

The bone mineral density (BMD) at the lumbar spine, proximal femur, and total skeleton was evaluated in 38 men with primary osteoporosis and vertebral fractures. BMD of the patients was significantly reduced over all skeletal areas compared with controls. The Z-score of the lumbar spine (−2.8 ± 0.9) was less than that of the other areas (P < 0.001) except the legs (−2.5 ± 1.1) (p.n.s.) showing that bone loss had a tendency to be greater over the axial skeleton. Vertebral dimensions compared with age-matched controls were as follows: projected L2–L4 area (cm 2): 45.7 ± 5.6 versus 53.7 ± 3.6 (P < 0.001); vertebral width (cm): 4.37 ± 0.44 versus 4.90 ± 0.36 (P < 0.001). Serum biochemical parameters and testosterone levels were similar between osteoporotic and control men. We conclude that men with vertebral osteoporotic fractures have reduced vertebral BMD and vertebral dimensions compared with age-matched controls. Thus, these findings indicate that the achievement of a reduced bone size at the end of the growth period or a failure of periosteal increase during adult life is likely to contribute to the pathogenesis of the vertebral fractures observed in older men. Received: 31 January 1997 / Accepted: 2 July 1997     

Comparison of Femoral Morphology and Bone Mineral Density between Femoral Neck Fractures and Trochanteric Fractures

Background  

Many studies that analyzed bone mineral density (BMD) and skeletal factors of hip fractures were based on uncalibrated radiographs or dual-energy xray absorptiometry (DXA).     

Low Bone Mineral Density and Fragility Fractures in Permanent Vegetative State Patients

Disuse of the musculoskeletal system causes bone loss. Whether patients in vegetative state, a dramatic example of immobilization after severe brain injury, suffer from bone loss and fractures is currently unknown. Serum markers of bone turnover, bone mineral density (BMD) measurements, and clinical data were cross‐sectionally analyzed in 30 consecutive vegetative state patients of a dedicated apallic care unit between 2003 and 2007 and compared with age‐ and sex‐matched healthy individuals. Vegetative state patients showed low calcium levels and vitamin D deficiency compared with healthy controls. Serum bone turnover markers revealed high turnover as evidenced by markedly elevated carboxy‐terminal telopeptide of type I collagen (β‐crosslaps) and increased levels of alkaline phosphatase. BMD measured by dual‐energy X‐ray absorptiometry (DXA) scanning showed strongly decreased T‐ and Z‐scores for hip and spine. Over a period of 5 years, 8 fragility fractures occurred at peripheral sites in 6 of 30 patients (n = 3 femur, n = 2 tibia, n = 2 fibula, n = 1 humerus). In conclusion, high bone turnover and low BMD is highly prevalent in vegetative state patients, translating into a clinically relevant problem as shown by fragility fractures in 20% of patients over a time period of 5 years. © 2014 American Society for Bone and Mineral Research.     

Increased Bone Mineral Density in a Man with Known Compression Fractures

A 70-yr-old man was referred for bone mineral density because of a history of vertebral and hip fracture. His past history included prednisone-treated rheumatoid arthritis and stroke resulting in hemiparesis and expressive aphasia. He had received injections for back pain at another hospital. The overall spine T-score was +3.40 with L3 at +10.92. The overall hip T-score was -1.09 with the femoral neck at -1.75 and Ward's triangle at -2.94. Radiographs of the spine revealed increased densities of L2-4. The patient's wife provided information the aphasic patient could not. The back injections were part of a vertebroplasty for stabilization. The patient had such great pain relief that he ambulated too soon, fell, and suffered a right hip fracture. Injection of polymethylmethyacrylate is a new addition to the treatment of spinal osteoporosis. The case demonstrates the importance of acquiring a complete medical history.     

Betel Nut Chewing Is Associated With Reduced Tacrolimus Concentration in Taiwanese Liver Transplant Recipients

Purpose

Studies have shown that arecoline, the major alkaloid component of betel nuts, alters the activity of enzymes in the cytochrome P450 (CYP-450) family. Tacrolimus, an immunosuppressant that protects against organ rejection in transplant recipients, not only is mainly metabolized by CYP3A enzymes but also has a narrow therapeutic range. We aimed to investigate whether dose-adjusted blood trough levels of tacrolimus differed over time between betel nut-chewing and non–betel nut-chewing liver transplant recipients.

Impact of Donor Age and Year of Transplant on Graft Survival in Liver Transplant Recipients with Chronic Hepatitis C

Studies suggest donor age and year of transplantation are associated with low graft survival in liver transplant recipients with hepatitis C. We sought to determine if advanced donor age and recent year of transplantation are associated with graft survival in hepatitis C recipients and to determine if the effect of donor age on graft survival is specific to hepatitis C. We analyzed the United Network for Organ Sharing liver transplant database from 1994 to 2002. Six thousand four hundred and four subjects transplanted for end-stage liver disease from chronic hepatitis C met our criteria. One-year graft survival in hepatitis C recipients with organs from donors <40 years old and >or=60 years old was 84% and 73%, p = 0.003, respectively. These rates in recipients with cholestatic liver disease and alcoholic liver disease were 85% and 82%, respectively, p = 0.11 and 82% and 78%, respectively, p = 0.14. Three-year graft survival in hepatitis C recipients transplanted from 1994 to 1995 and 1996 to 1999 was 67% and 69%, respectively, p = 0.10. Graft survival in hepatitis C recipients has not declined in recent years. Older donor age is associated with lower short-term graft survival in recipients with hepatitis C, but not in recipients with cholestatic or alcoholic liver disease.