Gudrun Leidig-Bruckner

Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study

BACKGROUND Osteoporosis and related fractures are a major complication after organ transplantation. The aim of this study was to find out the frequency and predictors of osteoporotic fractures after cardiac or liver transplantation. METHODS 235 consecutive patients who had a cardiac transplant (n=105; 88 men, 17 women) or a liver transplant (130; 75 men, 55 women) were followed. Vertebral fractures were assessed by a standardised analysis of spinal radiographs before and annually after transplantation. Clinical and non-vertebral fracture data were noted from hospital records. FINDINGS In the first and second years after transplantation, the proportion of patients (Kaplan-Meier estimates) who had at least one vertebral fracture was slightly higher in the cardiac group (first year 21%, second year 27%) than in the liver group (first year 14%, second year 21%). In the third and fourth years, one third of patients from both groups had had one or more vertebral fractures. Non-vertebral fractures occurred in nine patients (7%) after liver transplantation and avascular necrosis of the hip head in three patients (3%) after cardiac transplantation. In both groups, no dose-dependent effect of immunosuppressive therapy on fracture development could be identified. Independent predictors assessed by multivariate analysis were age (hazard ratio [95% CI] increase of 5 years, 1.71 [1.1-2.7]) and lumbar bone-mineral density (decrease of 1 SD t score, 1.97 [1.2-3.2]) in cardiac transplantation patients, and vertebral fractures before transplantation (6.07 [1.7-21.7]) in the liver group. INTERPRETATION The high frequency of osteoporotic fractures in the 2 years after transplantation and the limitations of reliable fracture-risk predictions, show the need to investigate preventive therapies.

Elevated plasma endothelin-1 levels in diabetes mellitus ☆

BACKGROUND This study compares plasma endothelin-1 (ET-1) levels in patients with diabetes mellitus or hypertension with healthy controls, and investigates whether ET-1 levels are correlated with glycemic control, metabolic parameters, and vascular complications. METHODS The study population consisted of 103 patients with type 1 diabetes, 124 patients with type 2 diabetes, 35 hypertensive patients without diabetes mellitus, and 99 controls. RESULTS Plasma ET-1 concentrations were significantly higher in patients with type 1 diabetes (0.28 +/- 0.34 fmol/mL, P =.001), type 2 diabetes (0.31 +/- 0.32 fmol/mL, P <.0001), and hypertension (0.35 +/- 0.26 fmol/mL, P <.0001) compared to controls (0.08 +/- 0.13 fmol/mL). Diabetic patients taking angiotensin converting enzyme (ACE) inhibitors had significantly lower plasma ET-1 levels than patients without (0.22 +/- 0.20 fmol/mL v 0.38 +/- 0.39 fmol/mL, P =.029). There were significant associations between ET-1 levels and age (r = 0.38, P <.05) and systolic blood pressure (BP) (r = 0.27, P <.05) in healthy controls. In diabetes we found only nonsignificant associations between ET-1 levels and age or vascular complications and a weak association between plasma ET-1 levels and glycemic control. CONCLUSIONS Patients with diabetes or hypertension have elevated ET-1 levels, but do not exhibit positive correlations between ET-1 levels and BP, which was observed in healthy controls. Increased ET-1 levels do not induce hypertension in diabetes, but were lower in diabetic patients taking ACE inhibitors compared to those without ACE inhibitors. There is no significant association between ET-1 levels and vascular complications. These findings suggest that the plasma ET-1 level is not a marker of endothelial dysfunction but changes in plasma ET-1 levels may precede vascular complications associated with hypertension and diabetes.

What Is a Vertebral Fracture

Vertebral deformities may be caused by a variety of conditions, such as osteoporosis, severe trauma, congenital deformities, Scheuermanns disease, osteoarthritis, and multiple myeloma. For the individual patient, the correct diagnosis of an osteoporotic fracture is a prerequisite for the choice of optimal treatment and will be ensured by careful differential diagnosis based on a spinal radiograph and additional diagnostic procedures. Evaluation of radiographs by experienced radiologists is crucial for the correct diagnosis of vertebral fractures. For clinical trials and epidemiological studies of osteoporosis, qualitative radiological evaluation of radiographs has proven to be insufficient, since results lack reproducibility. Therefore, objective morphometric methods based on vertebral height measurements have been developed for fracture identification and quantification in scientific settings. Satisfactory sensitivity of these methods is usually reached at the expense of specificity, leading to a high number of false positives. With some differences in methodology, most of the morphometric approaches are of comparable validity. However, none of the morphometric methods allows any subclassification of vertebral deformities with respect to etiology. A combined approach based on morphometry as well as standardized radiological evaluation by experts appears to be the most promising solution to the problem. Further efforts are needed to standardize radiological criteria to yield comparable results between individual readers and different studies. It has to be evaluated whether the combined approach (clinical reading and morphometry) is necessary during follow-up evaluation, as morphometry may be sufficient for monitoring once the diagnosis has been established at baseline.

Sex Difference in the Validity of Vertebral Deformities as an Index of Prevalent Vertebral Osteoporotic Fractures: A Population Survey of Older Men and Women

Abstract: Morphometric methods have been developed for standardized assessment of vertebral deformities in clinical and epidemiologic studies of spinal osteoporosis. However, vertebral deformity may be caused by a variety of other conditions. To examine the validity of morphometrically assessed vertebral deformities as an index of osteoporotic vertebral fractures, we developed an algorithm for radiological differential classification (RDC) based on a combination of quantitative and qualitative assessment of lateral spinal radiographs. Radiographs were obtained in a population of 50- to 80-year-old German women (n= 283) and men (n = 297) surveyed in the context of the European Vertebral Osteoporosis Study (EVOS). Morphometric methods (Eastell 3 SD and 4 SD criteria, McCloskey) were validated against RDC and against bone mineral density (BMD) at the femur and the lumbar spine. According to RDC 36 persons (6.2%) had at least one osteoporotic vertebral fracture; among 516 (88.9%) nonosteoporotics 154 had severe spondylosis, 132 had other spinal disease and 219 had normal findings; 14 persons (2.4%) could not be unequivocally classified. The prevalence of morphometrically assessed vertebral deformities ranged from 7.3% to 19.2% in women and from 3.5% to 16.6% in men, depending on the stringency of the morphometric criteria. The agreement between RDC and morphometric methods was poor. In men, 62–86% of cases with vertebral deformities were classified as nonosteoporotic (severe spondylosis or other spinal disease) by RDC, compared with 31–68% in women. Among these, most had wedge deformities of the thoracic spine. On the other hand, up to 80% of osteoporotic vertebral fractures in men and up to 48% in women were missed by morphometry, in particular endplate fractures at the lumbar spine. In the group with osteoporotic vertebral fractures by RDC the proportion of persons with osteoporosis according to the WHO criteria (T-score <−2.5 SD) was 90.0% in women and 86.6% in men, compared with 67.9–85.0% in women and 20.8–50.0% in men with vertebral deformities by various methods. Although vertebral deformities by most definitions were significantly and inversely related to BMD as a continuous variable in both sexes [OR; 95% CI ranged between (1.70; 1.07–2.70) and (3.69; 1.33–10.25)], a much stronger association existed between BMD and osteoporotic fractures defined by RDC [OR; 95% CI between (4.85; 2.30–10.24) and (15.40; 4.65–51.02)]. In the nonosteoporotic group individuals with severe spondylosis had significantly higher BMD values at the femoral neck (p <0.01) and lumbar spine (p <0.0004) compared with the normal group. On the basis of internal (RDC) and external (BMD) validation, we conclude that assessment of vertebral osteoporotic fracture by quantitative methods alone will result in considerable misclassification, especially in men. Criteria for differential diagnosis as used within RDC can be helpful for a standardized subclassification of vertebral deformities in studies of spinal osteoporosis.

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

Abstract 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.

Prevalence and determinants of osteoporosis in patients with type 1 and type 2 diabetes mellitus

BackgroundIncreased risk of osteoporosis and its clinical significance in patients with diabetes is controversial. We analyze osteoporosis prevalence and determinants of bone mineral density (BMD) in patients with type 1 and 2 diabetes.MethodsThree hundred and ninety-eight consecutive diabetic patients from a single outpatient clinic received a standardized questionnaire on osteoporosis risk factors, and were evaluated for diabetes-related complications, HbA1c levels, and lumbar spine (LS) and femoral neck (FN) BMD. Of these, 139 (71 men, 68 women) type 1 and 243 (115 men, 128 women) type 2 diabetes patients were included in the study. BMD (T-scores and values adjusted for age, BMI and duration of disease) was compared between patient groups and between patients with type 2 diabetes and population-based controls (255 men, 249 women).ResultsFor both genders, adjusted BMD was not different between the type 1 and type 2 diabetes groups but was higher in the type 2 group compared with controls (p < 0.0001). Osteoporosis prevalence (BMD T-score < −2.5 SD) at FN and LS was equivalent in the type 1 and type 2 diabetes groups, but lower in type 2 patients compared with controls (FN: 13.0% vs 21.2%, LS: 6.1% vs 14.9% men; FN: 21.9% vs 32.1%, LS: 9.4% vs 26.9% women). Osteoporosis prevalence was higher at FN-BMD than at LS-BMD. BMD was positively correlated with BMI and negatively correlated with age, but not correlated with diabetes-specific parameters (therapy, HbBA1c, micro- and macrovascular complications) in all subgroups. Fragility fracture prevalence was low (5.2%) and not different between diabetes groups. Fracture patients had lower BMDs compared with those without fractures; however, BMD T-score was above −2.5 SD in most patients.ConclusionsDiabetes-specific parameters did not predict BMD. Fracture occurrence was similar in both diabetes groups and related to lower BMD, but seems unrelated to the threshold T-score, <−2.5 SD. These results suggest that osteoporosis, and related fractures, is a clinically significant and commonly underestimated problem in diabetes patients.

Evaluation of thyroid nodules – combined use of 99mTc‐methylisobutylnitrile scintigraphy and aspiration cytology to assess risk of malignancy and stratify patients for surgical or nonsurgical therapy – a retrospective cohort study

Objective  Thyroid nodules are a common clinical problem, and differentiation between benign and malignant nodules is essential. The aim of this study was to evaluate an approach for cold thyroid nodules including 99mTc‐methylisobutylnitrile (MIBI) scintigraphy to assess risk of malignancy and stratify patients for therapy.

Low serum concentrations of insulin‐like growth factor I are associated with femoral bone loss in a population‐based sample of postmenopausal women

OBJECTIVE Cross‐sectional studies suggest that the decline in insulin‐like growth factor‐I (IGF‐1) levels with age may contribute to age‐associated bone loss. However, prospective data on the relation between circulating IGF‐I and bone loss in old age have not yet been reported.

Inactivating calcium-sensing receptor mutations in patients with primary hyperparathyroidism

Objective  Primary hyperparathyroidism (HPT) is characterised by autonomous secretion of PTH from enlarged parathyroid glands leading, in most patients, to asymptomatic hypercalcaemia. Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder caused by inactivating mutations in the calcium‐sensing receptor (CaSR) gene; it is characterised by lifelong and usually asymptomatic hypercalcaemia. Establishing the correct diagnosis is important because surgery can be curative in HPT, but ineffective in FHH. There is overlap in the diagnostic criteria for the two disorders and some patients carrying inactivating mutations in the CaSR gene, which is suggestive of FHH, also have HPT with hyperplastic parathyroid glands or adenomas.

Vertebrale Deformität als Index der osteoporotischen Wirbelfraktur — eine externe Konstruktvalidierung anhand von Knochendichtemeßdaten

BACKGROUND In order to test the validity of vertebral morphometry for the assessment of prevalent vertebral osteoporotic fractures, we examined the association between vertebral deformities and bone mineral density (BMD). METHOD The study population consisted of 595 postmenopausal women and 581 men aged 50 to 82 years who participated in the baseline survey of the European Vertebral Osteoporosis Study (EVOS) in Germany and received BMD measurements by dual-X-ray-absorptiometry (DXA) at the femur and the lumbar spine. RESULTS In both sexes only vertebral deformities defined by more stringent morphometric criteria (McCloskey; Eastell 4 SD criterion) were significantly and inversely related to BMD (odds ratios 1.42 to 3.21 for a 1 SD [standard deviation] reduction in BMD; p < 0.05). The strength of the association depended on the stringency of the morphometric algorithm applied, and on the site of BMD measurement. The strongest associations were observed with femoral neck BMD in women and with BMD at the lumbar spine in men. In contingency analyses between vertebral deformities and osteoporosis (WHO criteria; European young female BMD reference values), vertebral deformities proved to be highly specific by all methods, even slightly more so in men (87.8 to 97.5%) than in women (86.3 to 96.7%). The predictive value of a positive test with respect to vertebral osteoporosis reached a maximum value of about 50% in both sexes. It further increased up to 72%, when the definition of osteoporosis was based on low BMD values at either the spine or the femoral neck, but only in women. CONCLUSIONS In conclusion, for both men and women the likelihood of vertebral deformities to be related to osteoporosis increases with the stringency of the morphometric method, with a similar probability of major deformities to represent vertebral osteoporotic fractures in men as in women. Nevertheless, even the most stringent morphometric criteria are not sufficiently valid instruments for the assessment of the prevalence of vertebral osteoporotic fractures in epidemiological studies.Summary□Background: In order to test the validity of vertebral morphometry for the assessment of prevalent vertebral osteoporotic fractures, we examined the association between vertebral deformities and bone mineral density (BMD).□Method: The study population consisted of 595 postmenopausal women and 581 men aged 50 to 82 years who participated in the baseline survey of the European Vertebral Osteoporosis Study (EVOS) in Germany and received BMD measurements by dual-X-ray-absorptiometry (DXA) at the femur and the lumbar spine.□Results: In both sexes only vertebral deformities defined by more stringent morphometric criteria (McCloskey; Eastell 4 SD criterion) were significantly and inversely related to BMD (odds ratios 1.42 to 3.21 for a 1 SD [standard deviation] reduction in BMD; p<0.05). The strength of the association depended on the stringency of the morphometric algorithm applied, and on the site of BMD measurement. The strongest associations were observed with femoral neck BMD in women and with BMD at the lumbar spine in men. In contingency analyses between vertebral deformities and osteoporosis (WHO criteria; European young female BMD reference values), vertebral deformities proved to be highly specific by all methods, even slightly more so in men (87.8 to 97.5%) than in women (86.3 to 96.7%). The predictive value of a positive test with respect to vertebral osteoporosis reached a maximum value of about 50% in both sexes. It further increased up to 72%, when the definition of osteoporosis was based on low BMD values at either the spine or the femoral neck, but only in women.□ Conclusions: In conclusion, for both men and women the likelihood of vertebral deformities to be related to osteoporosis increases with the stringency of the morphometric method, with a similar probability of major deformities to represent vertebral osteoporotic fractures in men as in women. Nevertheless, even the most stringent morphometric criteria are not sufficiently valid instruments for the assessment of the prevalence of vertebral osteoporotic fractures in epidemiological studies.