Search PubMed⌕ Search

Biomedical subjects

P Burckhardt

Publications and source records attributed to P Burckhardt.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Prevention of osteoporosis and role of densitometry].

Osteoporosis is a major public health problem in countries with aging populations, resulting in excess morbidity and mortality. Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with the consequent increase in bone fragility and susceptibility to fractures. Therefore, the bone loss that precedes fractures is a continuous process that is often mostly irreversible in the aging. The most efficient method of preventing fractures is the prevention of bone loss. The measurement of bone mass and other skeletal characteristics can effectively identify women at high risk for fractures. The measurement of bone mass which can be carried out by osteo-densitometry is now widely available. It is the only clinical data that can provide accurate assessment of individual fracture risk. Treatments exist that will preserve bone mass and presumably reduce fracture risk; therefore there is a place for screening of patients at high risk of fractures. Many studies have shown recently that a reduced bone mass (at least 1 standard deviation below normal) was associated with a more than 100% increased risk of fracture. Thus the initial assessment of bone mass can be used to estimate future fracture risk and to start prevention measures for high risk patients. Primary prevention can be initiated during the adolescence to optimize peak bone mass. Later in life, secondary prevention can prevent excessive bone loss and more specific treatments can prevent postmenopausal and age related bone demineralization. Strategies of prevention should be promoted and validated as general health care strategies.

Absorptiometry, Photon↗
PubMed1994

[Hypercalcemia as incidental finding--what should be done?].

The discovery of a hypercalcemia validated by exclusion of hemoconcentration and follow-up calcium determinations opens the differential diagnosis of a malignancy and of hyperthyroidism whereas drug-induced causes can be recognized easily. A single determination of plasmatic parathyroid hormone (PTH) allows to safely distinguish between PTH-induced or PTH-independent, most often tumor-associated hypercalcemia. In both instances the patient may be free of symptoms particularly the very old one. Therapeutic measures are indicated in both instances: Treatment of malignancy-associated hypercalcemia is clinically effective and treatment of asymptomatic hyperthyroidism is likewise recommended, mainly to preserve bone mass and cerebral performance.

Calcium↗
PubMed1994

Effects of treatment of malignancy-associated hypercalcemia on serum parathyroid hormone-related protein.

Parathyroid hormone-related protein (PTHrP) is the primary mediator of hypercalcemia in patients with malignancy-associated hypercalcemia. We conducted this study to examine the effects of treatment with a bisphosphonate on serum PTHrP. We analyzed 41 episodes of hypercalcemia occurring in 38 patients: 22 patients received alendronate, and 16 were treated with pamidronate. At baseline, 29 patients had an increased serum PTHrP (group I) and 9 had low or undetectable levels (group II). The two groups did not differ significantly in baseline hypercalcemia (3.26 versus 3.41 mM) or the response of serum calcium to therapy. Serum calcium was normalized in 88% of group I and 70% of group II patients. Lowering of the mean calcium level was not associated with a change in the level of PTHrP in group I patients (40.2 versus 36.7 pgEq/ml) or group II patients. We also analyzed data on serum PTH and 1,25-(OH)2D in 20 of the patients. Serum PTH rose with treatment in group I patients (9.7-40.2 pg/ml, p < 0.05), as did the serum 1,25-(OH)2D (19.1-32.4 pg/ml, p < 0.001). Similarly, treatment of group II patients was associated with an increase in serum PTH (9.8-37.2 pg/ml) and serum 1,25-(OH)2D (22.9-40.2 pg/ml). The individual increases in 1,25-(OH)2D levels associated with therapy could not be predicted from the level of PTHrP or the changes in levels of serum calcium or PTH. Our data show that effective treatment of malignancy-associated hypercalcemia is not associated with a consistent change in serum levels of PTHrP. Therapy is associated with a variable increase in the serum levels of PTH and 1,25-(OH)2D.

Alendronate↗
PubMed1994

Regulation of collagen type I and biglycan mRNA levels by hormones and growth factors in normal and immortalized osteoblastic cell lines.

Growth factors, such as transforming growth factor beta (TGF-beta) and insulin-like growth factors (IGF) I and II, have been shown to exert anabolic effects on bone cells in vitro. Hormones, such as PTH and probably insulin and growth hormone, were recently shown to stimulate bone formation in vivo as well. The aim of the present study was to assess by northern blots, which were quantitated by densitometry, the effects of these anabolic growth factors and hormones in two osteogenic cell populations: CRP 10/30 cells, a clonal cell population derived from primary rat calvarial cells, and IRC 10/30-myc cells, which were established from CRP 10/30 by immortalization. Transcripts for alpha 1(I) collagen, biglycan, osteonectin, osteopontin, and osteocalcin were detected in both cell populations, which is consistent with the phenotype expressed by mature osteoblasts. There were no difference in the basal expression of bone matrix mRNAs between the two cell populations. PTH increased alpha 1(I) collagen mRNA levels in both osteoblastic cells but had no effect on the biglycan transcripts. Neither insulin nor growth hormone affected mRNA levels of either matrix protein after 24 h exposure. All three growth factors, TGF-beta, IGF-I, and IGF-II, increased alpha 1(I) collagen transcripts in a time- and dose-dependent manner in both cell populations. Biglycan mRNA levels were enhanced in both osteoblastic lines only by IGF-I and IGF-II, but not TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Two years' effectiveness of intravenous pamidronate (APD) versus oral fluoride for osteoporosis occurring in the postmenopause.

Bisphosphonates seem to be effective as antiresorptive agents in the prevention and treatment of osteoporosis. However, the optimal dose and route of administration as well as the specific effects on cortical or trabecular bone have not been clarified. To compare pamidronate (APD) with fluoride (F) in the therapy of postmenopausal osteoporosis, 32 osteoporotic women were treated for 2 years either with APD (30 mg as a single intravenous infusion over 1 h every 3 months, n = 16, mean age 65 years) or with fluoride orally (20-30 mg F/day, n = 16, mean age 67 years) in an open study. Both groups received 1 g calcium and 1000 U vitamin D per day, but no estrogens or other drugs acting on bone. Both groups showed the same initial mean number of fractures per patient (2.8 and 2.7). Bone densitometry was performed every 6 months at three sites: lumbar spine and hip with dual-energy X-ray absorptiometry (BMD), distal forearm with single photon absorptiometry and lumbar spine with quantitative computed tomography. Biochemical assessment was performed in blood and urine every 3 months. Lumbar BMD (g/cm2, mean +/- SEM) increased from 0.632 (+/- 0.030) at time 0 to 0.696 (+/- 0.028) at 24 months in the APD group (p < 0.001), and from 0.684 (+/- 0.025) to 0.769 (+/- 0.028) in the fluoride group (p < 0.001). Femoral neck BMD increased significantly from 0.558 (+/- 0.025) to 0.585 (+/- 0.025) (p < 0.01) in the APD group, whereas it did not change in the fluoride group.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

The effect of treatment with calcitonin on vertebral fracture rate in osteoporosis.

The efficacy of treatments for osteoporosis does not become evident when evaluated by fracture incidence (FI). Vertebral FI decreased in all controlled studies on calcitonin, but not significantly. Small sample sizes and short periods of treatment may have masked a possible therapeutic benefit, but longer, controlled studies with sodium fluoride or etidronate in larger groups of patients also failed to show a decrease in FI. The present analysis of nine published, therapeutic studies which indicate the FI per year and the initial prevalence of vertebral fractures, examines the question of whether the initial prevalence of fractures has an effect on the subsequent incidence of new fractures and whether the therapeutic effects have to be evaluated as a function of the initial prevalence of fractures. Bearing in mind the differences in roentgenological evaluation and in the size and quality of the various studies, the analysis revealed (1) that in the control groups there was a higher FI in patients with more than three vertebral fractures at baseline (estimated odds ratio (OR) = 49, p = 0.011); (2) that a similar trend, although not statistically significant, was observed in treated patients; (3) that the groups of control patients treated for more than 1 year showed in general an increase in FI beyond the first year and that the reverse was true in treated patients. In conclusion, failure to allow for the initial prevalence of vertebral fractures at the individual level in therapeutic trials of calcitonin to treat osteoporosis and prevent new fractures might have contributed to the absence of a demonstrable benefit of the treatment in those studies.

Calcitonin↗
PubMed1993

Direct evidence of a parathyroid related protein gradient between the mother and the newborn in humans.

Umbilical cord plasma has increased parathormone (PTH)-like bioactivity in comparison with that in maternal plasma, but suppressed PTH levels. Previous attempts to detect elevated levels of PTHrP(1-34) in the umbilical cord were unsuccessful, whereas PTHrP was detected by immunohistochemistry in both fetal parathyroid glands and placental membranes. At the time of delivery, plasma samples were drawn simultaneously from 47 normal mothers (mean age, 26 years) and from the umbilical cord of 25 female and 22 male newborns and assessed for calcium adjusted for albumin, magnesium, creatinine, intact PTH and PTHrP. PTHrP was measured using a new 2-site immunoradiometric assay recognizing separately 1-40 and 60-72 residues with a sensitivity of 0.3 pmol/l. Mean (+/- S.D.) plasma calcium values were 2.35 +/- 0.10 in the mothers versus 2.63 +/- 0.12 mmol/l in the newborns (P < 0.001). PTH values were significantly higher in the mothers, as expected (22.3 +/- 14.8 vs. 6.2 +/- 0.9 pg/ml). In contrast, PTHrP values were significantly higher in the newborns (1.50 +/- 0.39 versus 0.84 +/- 0.28 pmol/l, P < 0.001). Only 1/47 mother had a PTHrP level higher than her child (0.9 vs. 0.8 pmol/l). Only 10/47 mothers had PTHrP higher than 1 pmol/l whereas only 1/47 newborn had a value below 1 pmol/l. There was no correlation between Ca and PTHrP in either group. Serum creatinine values were all within the normal range. Serum magnesium levels were not different between the mothers and the children.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1992

[Moderate Paget's disease treated with pamidronate (APD): experience in 43 patients with a single 60 mg infusion of varying duration of 1-to-24 hours].

Pamidronate disodium (APD) given as a single 60 mg intravenous infusion over 24 hours was shown to be an effective treatment for Paget's disease of bone. To further improve the feasibility of a simple treatment that ensures compliance in elderly outpatients (pts), we investigated the effectiveness of a single 60 mg APD intravenous infusion given over 8 hours (12 pts), 4 hours (9 pts) and 1 hour (10 pts) compared with that over 24 hours (12 pts). Infusion rate of APD was 7.5, 15 and 60 mg/h respectively, in comparison with 2.5 mg/h previously. Clinical improvement and biochemical remission were observed in all patients. Side effects, limited to mild transient fever and local transient increase in bone pain, occurred in 9 patients (2-3 pts in each group). There was no difference in the fall of plasma alkaline phosphatase and of urinary hydroxyproline between the 4 infusion rates. Plasma alkaline phosphatase (U/l, mean +/- SEM) decreased from 263 +/- 34 to 110 +/- 8 (1 h infusion), from 251 +/- 26 to 102 +/- 9 (4 h), from 237 +/- 23 to 95 +/- 9 (8 h) and from 256 +/- 29 to 97 +/- 7 (24 h), from day 0 to day 180 respectively (all p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Pharmacokinetics of pamidronate in patients with bone metastases.

BACKGROUND: Pamidronate is a second-generation bisphosphonate used in the treatment of tumor-induced hypercalcemia and in the management of bone metastases from breast cancer, myeloma, or prostate cancer. The pharmacokinetics of pamidronate is unknown in cancer patients. PURPOSE: To determine the influence of the rate of administration and of bone metabolism, we studied the pharmacokinetics of pamidronate at three different infusion rates in 37 patients with bone metastases. METHODS: Three groups of 11-14 patients were given 60 mg pamidronate as an intravenous infusion over a period of 1, 4, or 24 hours. Urine samples were collected in the three groups of patients. Plasma samples were obtained only in the 1-hour infusion group. The assay of pamidronate in plasma and urine was performed by high-performance liquid chromatography with fluorescence detection after the derivatization of pamidronate with fluorescamine. RESULTS: The body retention (BR) at 0-24 hours of pamidronate represented 60%-70% of the administered dose and was not significantly modified by the infusion rate. In particular, the BR at 0-24 hours was not reduced at the fastest infusion rate. Among patients, a threefold variability in BR at 0-24 hours occurred, which was related directly to the number of bone metastases and, to some extent, to creatinine clearance. At 60 mg/hour, the plasma kinetics followed a multiexponential course characterized by a short distribution phase. The mean (+/- SD) half-life of the distribution phase was 0.8 hour (+/- 0.3), the mean (+/- SD) of the area under the curve for drug concentration in plasma x time at 0-24 hours was 22.0 +/- 8.8 mumol/L x hours, and the mean (+/- SD) of the maximum plasma concentration was 9.7 mumol/L (+/- 3.2). Pharmacokinetic variables remained unchanged after repeated infusions applied to four patients. Clinically, the three infusion rates were equally well tolerated without significant toxicity. CONCLUSIONS: The 1-hour infusion rate could be proposed as kinetically appropriate for the administration of pamidronate to patients with metastatic bone diseases.

Aged↗
PubMed1992

Comparison of a rapid (2-h) versus a slow (24-h) infusion of alendronate in the treatment of hypercalcemia of malignancy.

Alendronate (aminohydroxybutylidene bisphosphonate) is a potent inhibitor of bone resorption but the role of the duration of intravenous infusion in its efficacy profile is unclear. In a two-centre, parallel, randomized, double-blind study, 20 patients with tumoral hypercalcemia received a single 10-mg i.v. infusion over either 2 h (group A, n = 10) or 24 h (group B, n = 10). Recurrences (n = 6) were retreated using the same regimen. Pretreatment plasma calcium (Ca) was 3.32 +/- 0.08 mM (mean +/- SEM) for all patients. Treatment A and B were associated with similar temporal profiles for onset, time to reach normocalcemia, (6 vs 5 days), nadir (day 6: 2.45 +/- 0.06 vs 2.43 +/- 0.08 mM) and time to relapse (day 21). Normocalcemia (2.15-2.55 mM) was achieved in seven (A) and nine (B) patients with other cases being partial responders (Ca: 2.65-2.76 mM). A significant decrease of urinary calcium and hydroxyproline excretion and a significant increase of PTH accompanied Ca normalization in both groups. Ca response was 50% lower on 2nd treatment with alendronate. Both treatments were well tolerated with transient mild fever being the most common adverse experience. In conclusion, whether infused over 2 or over 24 h, a single dose of 10 mg alendronate led to normalization of tumoral hypercalcemia in a large majority of cases.

Aged↗
PubMed1992

Serum 25-hydroxyvitamin D: distribution and determinants in the Swiss population.

The serum 25-hydroxyvitamin D [25(OH)D] concentration was measured in a representative sample of the general adult population in Switzerland (n = 3276). The median concentration was 46 nmol/L and no significant difference was found between men and women. Between the ages of 25 and 74 y, 25(OH)D was not significantly correlated with age (r2 = 0.01). Six percent of the population was vitamin D deficient [ie, 25(OH)D less than or equal to 20 nmol/L] and between 34% and 95% had a relatively low concentration of vitamin D (ie, less than 38 or less than 95 nmol/L, respectively). Among the determinants of low 25(OH)D were indicators of little sunshine exposure, such as the winter season [odds ratio (OR) 2.4, 1.5-3.7 (95% confidence interval)] and less than 30 min of time spent outdoors daily by individuals greater than 65 y of age (OR 5.6, 1.5-21.2), as well as indicators of low nutritional intake of vitamin D, such as the absence of regular intake of butter or margarine (OR 2.0, 1.3-3.1) and the consumption of few dairy products (OR 1.7, 1.2-2.4).

25-Hydroxyvitamin D 2↗
PubMed1992

Treatment of osteoporosis.

No new compounds were tested in 1991, but more results on available therapeutic options were accumulated. Bisphosphonates and calcitonins appeared to increase bone density when used for a period of 1 to 3 years and to decrease vertebral fracture rate. Estrogen replacement therapy is still the most effective prevention of postmenopausal bone loss. Various studies revealed that the risk of inducing breast cancer has not been established and that estrogen has a strong protective effect against cardiovascular mortality. Screening for osteoporosis at menopause to target estrogen replacement therapy to women at increased fracture risk is recommended. Calcium and vitamin D supplements proved to be of significant value, especially in elderly people, in whom they even decreased fracture incidence. Fluoride demonstrated variable bioavailability. This might explain why certain fluoride studies showed fast increases in bone density with heavy side effects but no effect on fracture rate, whereas fluoride preparations of lower bioavailability were better tolerated and decreased fracture incidence. For almost all drugs, some dose dependence was demonstrated and maximally tolerated doses were established, but minimal effective doses are still unknown. Vertebral fracture rate was more often included as the final criterion in therapeutic trials, whereas long-term effects on hip fracture incidence still need more attention.

Humans↗
PubMed1991

[Prevalence of risk factors for osteoporosis and distribution of calciuria and hydroxyprolinuria in an elderly population of a general practice. Results of a survey among 32 practitioners of the Vaud and Fribourg districts].

169 postmenopausal women and 84 male patients aged over 59 years from the outpatient consultations of 32 general practitioners were examined. The most frequently encountered risk factors for osteoporosis were low physical activity (41% of women, 27% of men), low intake of dairy products (37%/21%), smoking (11%/22%), while the particularly relevant risk factors were more rare, such as corticotherapy (7%/9%) and early menopause (17%). The risk factors were not more frequent than in 550 persons of the same age screened among the Swiss general population in another study. The same group of persons also yielded reference values for urinary calcium and hydroxyproline in the fasting urine, which are both considered as markers of bone turnover and as potential tools for screening osteoporosis. The urinary values were independent of age, body mass index, calcium intake, and the duration of the postmenopausal period. They were different from those found in 38 patients with Paget's disease, 66 patients with malignant hypercalcemia and 25 with bone metastasis from breast cancer. Calcium and hydroxyproline excretion are expressed as a ratio of urinary creatinine. Percentiles 10 and 90 of urinary calcium are 0.058 and 0.363 mmol/mmol (male) and 0.062 and 0.523 mmol/mmol (women). Percentiles 10 and 90 for urinary hydroxyproline are 0.006 and 0.024 mmol/mmol (male) and 0.010 and 0.025 mmol/mmol (women).

Aged↗