[Metabolic osteopathies. Osteodensitometry methods].
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Absorptiometry, Photon↗
Biomedical subjects
C Wüster
Publications and source records attributed to C Wüster.
Ultrasound velocity of the tibia in normal German women and hip fracture patients.
One of the latest developments in quantitative ultrasound (QUS) is the measurement of the speed of sound (SOS) of cortical bone of the midtibia. To determine the diagnostic validity of this method we measured 150 healthy women aged 22-94 years. Additionally, we report on first results of patients with hip fracture. Precision in vivo of the tibial QUS expressed as the percentage coefficient of variation (CV) was 0.39% for the first day and 0.45% after repositioning the second day (mean CV = 0.42%). No significant dependency of tibial SOS was found with weight, height, and body mass index in pre- and postmenopausal women. There was a significant decline of SOS with age in postmenopausal women (SOS = 4225 - 5.3 age, r = -0.46, P < 0. 001), whereas premenopausal women showed no decline (SOS = 3906 + 1. 3 age, r = 0.13, ns) Mean SOS values of premenopausal women were significantly higher than those of postmenopausal women (3960 +/- 78.7 m/second and 3898 +/- 120 m/second, respectively, P < 0.001). Postmenopausal women on estrogen substitution had significantly higher mean tibial SOS values than age-comparable postmenopausal women without estrogen substitution (3980 +/- 99 m/second and 3869 +/- 100 m/second, respectively, P < 0.001). Significant difference between age-matched healthy women, n = 11, and hip fracture patients, n = 13, expressed as z-score of -1.4 SD was found. In conclusion, tibial QUS declines with age and detects higher values in premenopausal women and postmenopausal women on estrogen substitution and lower values in hip fracture patients. Further prospective studies are needed to clarify its role in fracture risk assessment.
Adult↗
Lower serum 25-hydroxyvitamin D is associated with increased bone resorption markers and lower bone density at the proximal femur in normal females: a population-based study.
Subclinical vitamin D deficiency is considered to be a risk factor for osteoporosis. Therefore, we studied vitamin D status and bone mineral density (BMD) in an age- and sex-stratified population based sample (209 males and 206 females aged between 50 and 80 years). In addition, urinary excretion of pyridinium crosslinks of collagen was determined in order to monitor bone resorption. We found a seasonal variation of serum 25-hydroxyvitamin D (25(OH)D) levels with higher values detected in the summer (27 +/ - 10 ng/ml) and lower values measured in the winter (17 +/- 9 ng/ml). Further analyses were performed separately for winter and summer, respectively. We also excluded subjects taking osteotropic medication. In men, we found no significant relationship between vitamin D status and bone density or pyridinium crosslinks. In women, we found significant positive correlations between 25(OH)D and proximal femur BMD in winter (r = 0.21, p < 0.05) and in summer (r = 0.36, p < 0.01). The association between 25(OH)D and proximal femur BMD persisted after correction for age and body mass index. Serum 25(OH)D and urinary pyridinium crosslinks were inversely correlated in females in winter (r = -0.24, p < 0.02) and in summer (r = -0.32, p < 0.02). Our data support the hypothesis that already moderately low serum levels of 25(OH)D within the "normal" range lead to osteopenia via increased bone resorption.
Age Factors↗
Relationship between circulating insulin-like growth factor components and sex hormones in a population-based sample of 50- to 80-year-old men and women.
There is a large body of evidence that points to a systemic link between the somatotropic axis and sex hormones, but epidemiologic data on the interactions between the two hormonal systems are still missing. We examined here the associations between the plasma levels of insulin-like growth factor (IGF) I, IGF-II, IGF-binding protein 3 (IGFBP-3), and sex hormones in a population-based sample of 486 men and women, aged 50-80 yr. The strongest association was an age-independent inverse correlation between all three circulating IGF components and sex hormone-binding globulin (SHBG), the major testosterone-binding protein in plasma. Consistent with this, bio-available (non-SHBG-bound) but not total testosterone levels were positively associated with the IGF system in men, and 3 alpha-androstanediol glucuronide was positively correlated with circulating IGFs in women. Moreover, part of the correlation between the circulating IGF system and bone mineral density at the femur and the calcaneus could be accounted for by SHBG. Our data suggest that sex hormones and the GH/IGF system are significantly interrelated in the elderly population. These hormonal interactions may play an important role in human aging and the pathogenesis of age-related diseases.
Aged↗
Multicenter German reference data base for peripheral quantitative computer tomography.
The wide spread use of bone densitometers in Germany and other European countries has required the establishment of a validated reference population data base. A semianthropomorphic forearm cross-calibration phantom (EFP), developed during a concerted research action of the European Union's programme in Biomedical Engineering (COMAC-BME), was used to cross-calibrate the peripheral quantitative computer tomography (pQCT) devices at four German centers participating in the multicenter study. In total, 723 women and 208 men were included in the normal data base. No significant regional differences were found between the data of the different centers. In addition to the manufacturers calibration standard, proper calibration of the pQCT devices could be monitored during collection of the normal female and male data base. As a merit of the COMAC-BME study the measurements obtained with all pQCT devices thus ensured an uniform reference data base for distal radius measurements in Germany.
Adult↗
Forearm BMD as measured by peripheral quantitative computed tomography (pQCT) in a German reference population.
Low bone mass as estimated by decreased bone mineral density (BMD) is an established predictor of osteoporotic fractures. One of the latest developments in bone densitometry is peripheral quantitative computed tomography (pQCT) of the forearm. In Germany, the CT bone scanner XCT 900 has already been widely used; however, interpretation of measurements with respect to osteoporosis risk assessment can be improved by better defined and validated reference data. In the present study, this device was used to measure BMD at the distal radius in a well-defined healthy population of 179 German adults (91 men, 88 women) aged 20-79 years. In vivo precision was 1.67% for trabecular and 0.81% for total BMD measurements. Peak values of trabecular and total BMD were observed at the ages 40-50 years in women and 30-40 years in men. Beyond these ages, both trabecular and total BMD showed a linear decline with age, decreasing by 0.85% and 1.08% per year in women and by 0.59% and 0.54% in men, respectively. Measures of BMD were not influenced by weight, height or body mass index (BMI). In both sexes, trabecular and total radial BMD showed a positive and significant correlation with femoral BMD measures obtained by dual X-ray absorptiometry (DXA). Weaker correlations were observed with DXA measures of the lumbar spine. Compared with the 95% reference range provided by the manufacturer, the distribution of age- and sex-specific values of trabecular BMD of the distal radius was shifted to lower values by up to 1 standard deviation.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorptiometry, Photon↗
Outcome of bone mineral density in anorexia nervosa patients 11.7 years after first admission.
Osteopenia is a typical finding in patients suffering from anorexia nervosa. Unfortunately, available longitudinal studies are limited by a relatively short follow-up period. Therefore cross-sectional long-term followup studies may help to determine both the outcome of this bone lesion and variables that influence its subsequent development. Of an initial 66 consecutive patients with anorexia nervosa, 51 (77.3%) could be further evaluated. After an average of 11.7 years following first admission, cross-sectional measurements of lumbar and proximal radial bone mineral density (BMD) were performed. The ability to predict BMD using variables obtained from anamnestic and clinical data was then determined by multiple-regression analysis. The BMD of both radial and lumbar bone in anorexic patients with poor disease outcome (as defined by the Morgan-Russell general outcome categories) deviated by -2.18 and -1.73 SD (Z score), respectively. In patients with a good disease outcome lumbar BMD was significantly less reduced compared with radial BMD (-0.26 versus -0.68 SD). Variables reflecting estrogen deficiency and nutritional status in the course of the disease, that is, relative estrogen exposure (for lumbar BMD) and years of anorexia nervosa (for radial BMD), allowed the best prediction of BMD. A marked reduction in cortical and trabecular BMD in anorexic patients with poor disease outcome suggests a higher risk of fractures in these patients. Furthermore, the finding of a persistently reduced cortical and a slightly reduced trabecular BMD, even in patients with good disease outcome, suggests that a recovery of trabecular BMD might be possible, at least in part. Recovery of cortical bone, if possible at all, seems to proceed more slowly.
Absorptiometry, Photon↗
Methylpentylaminopropylidenebisphosphonate (BM 21.0955): a new potent and safe bisphosphonate for the treatment of cancer-associated hypercalcemia.
Bisphosphonates have been shown to be effective in lowering serum calcium levels in patients with cancer-associated hypercalcemia. 1-Hydroxy-3-(methylpentylamino)propylidenebisphosphonate (BM 21.0955) was developed as a third generation bisphosphonate and has been recently proven effective in animals and in patients with Paget's disease or tumor osteolysis. Thirty-six patients with cancer-associated hypercalcemia were treated with increasing doses (0.2-2.0 mg) of BM 21.0955 by single i.v. infusion over 4 h in a phase I trial. Six patients were rejected from analysis due to concomitant treatment with other bisphosphonates or chemotherapy. After rehydration and infusion of BM 21.0955 the mean serum calcium levels fell significantly (P < 0.001), from 3.29 +/- 0.49 mmol/l to 3.04 +/- 0.44 mmol/l until day 2 and normalized on day 6 (2.66 +/- 0.33 mmol/l). Serum calcium was reduced in all patients and normalized in 16. No symptomatic hypocalcemia occurred. Mean serum creatinine decreased significantly (P < 0.01), from 1.25 +/- 0.58 mg/dl (day 0) to 1.05 +/- 0.37 mg/dl (day 6). The mean urinary calcium/creatinine concentration fell significantly (P < 0.001), from 1.90 +/- 1.16 mM/mM (day 0) to 0.37 +/- 0.34 mM/mM/l (day 6). There were no subjective drug-related side effects during or after the infusion. Thirteen patients had elevations of morning body temperature above 38 degrees C. This was due to confirmed infections in five patients and possibly drug- or tumor-related in the other eight. We conclude from these preliminary results that a single infusion of BM 21.0955 is an effective and safe way to treat cancer-associated hypercalcemia.
Aged↗
Levels of parathyroid hormone-related protein (PTHrP) in hypercalcemia of malignancy are not lowered by treatment with the bisphosphonate BM 21.0955.
Parathyroid hormone-related protein (PTHrP) is a major cause of hypercalcemia in malignancy and serum levels are elevated in many patients suffering from this syndrome. In 10 patients with hypercalcemia of malignancy the levels of the midregional fragment of PTHrP in serum were determined by radioimmunoassay over 7 days during a calcium-lowering treatment with a single dose of the bisphosphonate BM 21.0955. PTHrP concentrations remained unchanged 6 days after administration of the drug as compared with pretherapeutic values, thus apparently excluding an effect of either the drug itself or the rapid fall in serum calcium on the release of PTHrP by the tumors or on its clearance from the circulation. In the patients with elevated midregional PTHrP levels (n = 6), the calcium-lowering effect of the drug was significantly less pronounced than in patients with normal PTHrP (n = 4) (mean serum calcium of 2.89 vs. 2.51 mmol/l at day 6), despite similar pretherapeutic concentrations. Of the six patients with elevated PTHrP, five were still hypercalcemic, whereas in the group with normal PTHrP one out of four patients remained hypercalcemic. In conclusion, PTHrP levels in hypercalcemia of malignancy remained unchanged after calcium-lowering therapy with bisphosphonates. High serum PTHrP levels were, however, predictive of a lesser effectiveness of the drug in lowering serum calcium.
Adult↗
Decreased serum levels of insulin-like growth factors and IGF binding protein 3 in osteoporosis.
OBJECTIVES: The aim of the study was to investigate endogenous growth hormone (GH) secretion in patients with osteoporosis and in patients with degenerative bone diseases or no spinal disease by measuring serum insulin-like growth factors 1 and 2 (IGFs) and their major binding protein 3 (BP-3) as an indirect parameter of GH secretion. DESIGN: A cross-sectional study. SETTING: All patients were seen as out-patients of the Endocrinology Department of the University of Heidelberg where all bone parameters were measured. IGFs and BP-3 serum levels were measured at the Children's Hospital of the University of Tübingen. SUBJECTS: A total number of 310 patients were studied. The group with primary osteoporosis and vertebral fractures (OPO) consisted of 141 patients (98 females, 43 males). Spinal degenerative bone disease or osteoarthritis (DEG) was present in 108 patients (91 females, 17 males). Sixty-one control patients (56 females, 5 males) had no spinal disease on X-ray, but presented with lower back pain. MAIN OUTCOME MEASURES: Serum levels of IGFs, BP-3, PTH and 25-vitamin D3 were measured by radioimmunoassay. Bone mineral density (BMD) was determined using absorptiometry; anthropometric parameters and menopausal status were recorded. RESULTS: There was no difference in age and years after menopause between OPO and DEG, but control individuals were younger. Mean IGFs and BP-3 serum levels in patients with OPO were lower (P < 0.001) than those in patients with DEG or in controls. Patients with DEG had significantly higher BP-3 levels than controls (P < 0.001). There was a significant (P < 0.05) negative correlation of BP-3 with age in females with OPO, but not in controls or in DEG patients. The IGFs did not decrease with age in any of the three groups. Binding protein 3 was positively correlated (P < 0.05) with BMD in postmenopausal women with OPO but not in controls or DEG patients. CONCLUSION: We conclude that systemic IGFs and IGF binding protein 3 are decreased in patients with osteoporosis. Further studies are needed to investigate whether this is as a result of diminished secretion of endogenous GH and whether this reflects the local circumstances of IGFs and IGF binding proteins in bone.
Adult↗
Growth hormone and bone metabolism.
GH is a potent anabolic hormone for bone and calcium metabolism, not only via direct effects but also mediated through other systems. The individual effects on bone metabolism are summarized in Table 1. Some of the signs (low BMD and low serum osteocalcin) and symptoms (increased prevalence of vertebral fractures) seen in patients with GHD may be due to the lack of GH itself, others may be due to secondary hormone deficiencies or changes in body composition induced by GHD. GH treatment can reverse changes of calcium metabolism. Whether it is able to increase bone mass still needs to be determined in larger and longer studies. Some patients with established osteoporosis and vertebral fractures seem to suffer from GHD. Treatment of osteoporosis with GH has not previously been successful, but studies with more patients over several years to investigate the effects of GH treatment on vertebral fracture rates are lacking. As GH seems to reverse some signs of old age, such as muscle weakness and reduced exercise capacity, it is possible to speculate that GH could prevent the occurrence of hip fractures in elderly people.
Bone Density↗
Reduced bone mineral density and low parathyroid hormone levels in patients with the adult form of hypophosphatasia.
Hypophosphatasia is a heritable metabolic bone disease with characteristically reduced levels of alkaline phosphatase (ALP) in the blood, liver, kidney and bone. ALP levels are normal in the intestine and placenta. About 300 patients have been reported so far in the literature. Three kindreds with 52 known subjects are described here, whereby 12 subjects could be examined osteologically. Four subjects were patients and had clinical signs of the disease: spontaneous fractures of the metatarsals or femora and low ALP serum levels ranging between 8 and 23 U/l (normal range 40-170 U/l). Four other members without fractures had reduced ALP levels; they might be carriers of the disease and develop symptoms later in life. The four remaining subjects had normal ALP levels and no signs of the disease. Serum levels of intact parathyroid hormone (iPTH) were found to be in the lower normal range and serum calcium levels in the upper normal range. There was a significant (P less than 0.05) negative correlation between iPTH and serum calcium levels (r = -0.78). Urinary calcium excretion was increased in 3 subjects with fractures. 25-OH-D3 levels were increased in 6 of 8 subjects without any treatment. The bone mineral density (BMD) was measured using dual X-ray absorptiometry of the lumbar spine, representing mainly trabecular bone, and single-photon absorptiometry of the forearm, measuring mainly cortical bone. Z-scores of the spinal bone mass ranged between 0.38 and -1.95 SD; Z-scores of the forearm bone mass ranged between 0.53 and -2.47 SD with the lowest values in patients with fractures.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Bone mass of spine and forearm in osteoporosis and in German normals: influences of sex, age and anthropometric parameters.
We measured forearm bone mineral density (BMD) using single photon absorptiometry (SPA) and bone mineral content (BMC) and BMD of lumbar spine by dual photon absorptiometry (DPA). The population consisted of 463 bone healthy subjects, 346 females and 117 males aged 20-85 years. Any underlying bone disease or other diseases known to affect bone mass were excluded by physical examination, thoracic and lumbar radiographs and laboratory screening. Patients with osteoarthritis of lumbar spine were excluded as well as patients taking drugs known to affect bone mass. All bone mass values declined with age. Body height also declined with age by 1.2 cm and 1.8 cm per 10 years (-0.7% and -1%) in females and males respectively. Main effects of age, body height, -surface, -weight and -mass index on bone mass were calculated using multiple regression models. In males and females lumbar BMC measured in gHA depended primarily on body height and secondarily on age. Spinal BMD as measured in g cm-2 was primarily dependent on age and then on height. In females forearm BMD depended primarily on age and then on body surface, in males on body surface only. Using receiver operating characteristic (ROC) analysis the ROC area increased from 0.81-0.85 (n.s.) including body height into spinal BMD values leading to a higher sensitivity of measurements of spinal bone mass in recognizing 58 patients with spinal postmenopausal osteoporosis. Including body surface into forearm BMD measurements ROC area increased from 0.66-0.69 (P = 0.055).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effects of endogenous and exogenous calcitonin on inflammation-mediated osteopenia in the rat.
Inflammation-mediated osteopenia (IMO) in the rat is characterized by loss of bone mass within 3 weeks after induction of nonspecific inflammation (s.c. talcum injections) in growing rats. Histologically, this shows as marked inhibition of osteoblasts 3 days after the initiation of IMO. The role of calcitonin (CT) was investigated in the present study. A reversible increase of serum CT levels was found after intraperitoneal calcium challenge in rats on day 4 after induction of IMO, which was thought to be a result from calcium efflux from bone. No difference in stimulated serum CT levels between the rats with and without IMO was seen on any other day during 4 weeks after initiation of IMO. Bone loss after IMO was more pronounced in normocalcemic and euthyroid rats with deficiency of endogenous CT (thyroidectomy with parathyroid gland reimplanted) (-12.9%) compared with sham operated controls with IMO (-3.25%). Daily subcutaneous injections of 100 mIU salmon CT in rats with and without IMO did not prevent the development of bone loss. This might have been due to the growing state of rats of this age group. Our results support the hypothesis that endogenous CT physiologically has a bone protective role. They furthermore are consistent with the view that endogenous CT itself is not pathogenetically involved in the development of osteoporosis.
Animals↗
Serum levels of intact parathyroid hormone and alkaline phosphatase correlate with cortical and trabecular bone loss in primary hyperparathyroidism.
We examined the relationship between bone loss and several biochemical indices in 38 patients with primary hyperparathyroidism. Bone mineral density was reduced by 12 +/- 4.0% in the lumbar spine, 18 +/- 4.2% at the distal radius and 21 +/- 2.8% at the proximal radius (mean +/- SEM). There were significant negative correlations between the serum concentrations of intact parathyroid hormone (PTH) and the Z-scores of the bone mineral content at the proximal and distal radius. In the lumbar spine, bone mineral density was greater in patients with mildly elevated PTH and less in patients whose PTH levels exceeded 8.6 pmol/l. We also observed a strong association between increased levels of serum alkaline phosphatase and low bone mineral Z-scores. Our data thus indicate that cortical and, with the exception of mild primary hyperparathyroidism, trabecular bone loss is proportional to the concentration of circulating PTH and the severity of PTH-induced bone turnover. For the individual patient, however, the usefulness of intact PTH and alkaline phosphatase measurements for assessing bone loss associated with primary hyperparathyroidism seems to be only limited.
Aged↗
Long-term excess of endogenous calcitonin in patients with medullary thyroid carcinoma does not affect bone mineral density.
In a cross-sectional study of 39 patients with medullary thyroid carcinoma (MTC), we have investigated the effects of long-term calcitonin excess on bone mineral density. Bone mineral density was measured by dual X-ray absorptiometry at the lumbar spine between the second and fourth vertebra and by single photon absorptiometry at the distal forearm. The mean observation time of each patient between diagnosis of tumour and measurement of bone mineral density was 62.4 months (range 1-158 months). The mean calcitonin serum level was 14.4 micrograms/l at the time of measurement of bone mineral density. All patients were substituted with 150-200 micrograms L-thyroxine daily. At both sites, the mean bone mineral densities of all patients with MTC were not significantly different from controls. Patients with normal calcitonin levels (below 0.2 micrograms/l) after treatment had a normal bone mineral density of the spine but significantly (P less than 0.05) reduced bone mineral density values of the forearm. This was due to the decreased body surface areas of patients in this subgroup. Patients with multiple endocrine neoplasia type IIa had significantly higher bone mineral densities. Other bone-influencing factors, such as postoperative hypoparathyroidism, calcium intake, diarrhoea, menopause, tumour stage, previous anti-tumour treatment, or thyroxine substitution dose, did not affect bone mineral density. We thus conclude that long-term excess of endogenous calcitonin in patients with MTC has no positive effect on bone mineral density.
Absorptiometry, Photon↗
Bone disease after liver transplantation.
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Adult↗
[Hyperparathyroidism: pathology, diagnosis and therapy].
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Humans↗