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Biomedical subjects

J Bollerslev

Publications and source records attributed to J Bollerslev.

At least 55 records · Page 3Linked to original sources
PubMed1995

Collagen metabolism in two types of autosomal dominant osteopetrosis during stimulation with thyroid hormones.

In order to investigate collagen metabolism in two different types of autosomal dominant osteopetrosis (ADO), eight patients with type I (aged 23-61 years, mean 40.4 years) and nine patients with type II ADO (aged 20-49 years, mean 32.8 years) were compared with ten normal controls (aged 22-54 years, mean 35.4 years). The subjects were treated with 100 micrograms of triiodothyronine (T3) daily for 7 days and followed for a total of 4 weeks. Serum T3 increased in all subjects and a corresponding suppression of thyroid-stimulating hormone (TSH) was observed. Serum carboxy-terminal propeptide of type I collagen (S-PICP) in the control and type I groups showed no difference at baseline, whereas type II was lower than controls (p < 0.01). No significant alterations following stimulation were observed in any of the groups. Serum BGP (osteocalcin) values in the two patient groups were insignificantly lower than controls both at baseline and throughout the study. Following stimulation, a significant response was seen in the three groups (p < 0.001). The increases during the treatment period (delta values) for controls, type I and type II were 47.6% (p < 0.01), 51.7% (p = 0.05) and 34.8% (NS), respectively, with no difference between the groups. Serum bone-specific alkaline phosphatase (S-ALP) was not different between the groups and no alterations were observed in relation to treatment. The serum N-terminal propeptide of type III collagen (S-PIIINP) showed no difference at baseline between type I and controls but was significantly higher (p < 0.003) in type II than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Body composition in active acromegaly during treatment with octreotide: a double-blind, placebo-controlled cross-over study.

OBJECTIVE: In active acromegaly body composition is characteristically altered by an increase in lean body mass and a corresponding reduction in fat mass. These changes are induced by an excessive secretion of GH and insulin-like growth factor I (IGF-I). Growth hormone is an anabolic hormone and leads to stimulation of protein synthesis and an increased lipolysis in adipose tissue. Treatment with the somatostatin analogue, octreotide, has been shown to reduce GH levels causing reduced hormonal effects on target tissues. We have studied changes in body composition during short-term reduction in GH level by octreotide in active acromegaly. DESIGN: Octreotide was compared to placebo in a double-blind, cross-over trial. Dual-energy X-ray absorptiometry scanning was employed to calculate body composition. Relations between body composition parameters and clinical signs of acromegaly (finger circumference and foot volume) were studied. PATIENTS: Twelve patients with active acromegaly, confirmed by lack of GH suppression during oral glucose loading, were included. All had pituitary adenomas diagnosed by computed tomography. MEASUREMENTS: Serum GH and IGF-I. Lean body mass, fat mass and total weight, foot volume and finger circumference. RESULTS: Four weeks of octreotide treatment caused a 75% decrease in GH levels (n = 10), a reduction in IGF-I from 476 +/- 51.9 (mean +/- SEM) to 233 micrograms/l +/- 46.3 (P < 0.005) and a corresponding decrease in both body weight (2.51 kg +/- 0.41) (P < 0.005) and lean body mass (2.44 kg +/- 0.48) (P < 0.005). No significant changes in fat mass were observed. These findings were paralleled by significant reductions in foot volume (44.50 ml +/- 17) (P < 0.05) and finger circumference (1.3 mm +/- 0.3) (P < 0.05). CONCLUSIONS: Short-term octreotide therapy reduces growth hormone levels leading to a significant reduction in lean body mass as assessed by dual-energy X-ray absorptiometry. Alterations in lean body mass were positively correlated with reductions in foot volume. Thus, simple clinical tests may be valuable in judging the effects of treatment in active acromegaly.

Absorptiometry, Photon↗
PubMed1994

Cortical bone osteocalcin content and matrix composition in autosomal dominant osteopetrosis type I.

Several bone matrix protein constituents, including the major component collagen type I and the hydroxyapatite binding protein, osteocalcin, have been implicated in the regulation of bone turnover. Cortical bone osteocalcin, collagen and mineral content were studied in autosomal dominant osteopetrosis type I (ADO), a disorder characterized by diffuse symmetrical osteosclerosis. Iliac crest bone biopsies were obtained from eight patients (mean age 43.0 years, range 17-63 years) and compared with 16 age- and sex-matched normal controls (mean age 44.1 years, range 20-61 years). The osteocalcin level in cortical bone was increased (p < 0.03) in ADO (51.4 +/- 3.9 mg/kg bone) compared with controls (38.0 +/- 3.6 mg/kg bone). Total collagen, protein and calcium expressed per kilogram bone dry weight were without significant difference between patients and controls. The pathogenesis of ADO is most likely not related to cortical bone osteocalcin content, a protein implicated in osteoclast ontogeny and activation. These observations are in contrast to recent observations of reduced bone osteocalcin levels in osteopetrotic mutations in the rat and underscore the interspecies heterogeneity of this disorder.

Adolescent↗
PubMed1994

Primary hyperparathyroidism: incidence and clinical and biochemical characteristics. A demographic study.

OBJECTIVE: To give a demographic description of primary hyperparathyroidism (pHPT) in a region in which the incidence of operative treatment was low (2/100,000 inhabitants/year) and to describe the association between histology, biochemistry, and morbidity among the patients. DESIGN: Retrospective study. PATIENTS: 107 consecutive patients who were operated on for pHPT referred for surgery during an 11 year period in a population comprising one million people. RESULTS: The median weight of adenomas was 1,300 mg (range 200-13,500), weight o hyperplastic tissue removed was median 1,500 mg (range 100-23,800). Weight of abnormal parathyroid tissue correlated significantly with preoperative serum calcium concentration (r = 0.50, p < 0.001). Preoperatively serum immunoreactive parathyroid hormone concentration was correlated with serum calcium concentration (r = 0.39, p < 0.001) and with serum creatinine concentration (r = 0.52 p < 0.001). In a quarter of the patients the serum calcium concentration fell below 2.0 mmol/l after operation. In this subgroup the weight of pathological parathyroid tissue was significantly higher than among those who did not develop hypocalcaemia. Preoperative serum calcium concentration was unrelated to postoperative hypocalcaemia. CONCLUSION: Patients from an area in which few operations are done for pHPT had biochemically and clinically advanced disease compared with patients from comparable areas in which more operations are performed. There is a good correlation between biochemistry, organ involvement, and histology. The serum concentration of calcium preoperatively seems to underestimate the presence of advanced disease in patients in whom the bones are affected.

Adenoma↗
PubMed1993

Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium, bone and citrate metabolism.

Urinary acidification, bone metabolism and urinary excretion of calcium and citrate were evaluated in 10 recurrent stone formers with incomplete renal tubular acidosis (iRTA), 10 recurrent stone formers with normal urinary acidification (NUA) and 10 normal controls (NC). Patients with iRTA had lower plasma standard bicarbonate after fasting (P < 0.01) and lower urinary excretion of titratable acid (P < 0.05) and citrate (P < 0.01) compared with NUA patients and NC, and higher urinary excretion of ammonia (P < 0.05) compared with NC (P < 0.05). Hypercalciuria was found in 6 of 10 patients with iRTA compared with 3 of 10 with NUA, and 0 of 10 NC. The citrate/calcium ratio in urine was significantly reduced in iRTA compared with the value in NUA (P < 0.01), and in NUA compared with NC (P < 0.05). Biochemical markers of bone formation (serum osteocalcin) and bone resorption (urinary hydroxyproline) were significantly increased in iRTA compared with NUA and NC (P < 0.01), indicating increased bone turnover in stone formers with iRTA. Stone formers with iRTA thus presented with disturbed calcium, bone and citrate metabolism--the same metabolic abnormalities which characterize classic type 1 RTA. Mild non-carbonic acidosis during fasting may be a pathophysilogical factor of both nephrolithiasis and disturbed bone metabolism in stone formers with iRTA.

Acid-Base Equilibrium↗
PubMed1993

Relation between phenotype and intra-cellular thyroid hormone effect in patients with altered peripheral thyroid hormone sensitivity.

OBJECTIVE: We wished to ascertain whether different phenotypic appearances in patients with altered cellular sensitivity to thyroid hormones were related to the type of altered intra-cellular thyroid hormone effect. DESIGN: Blood samples were obtained from two members of a family suffering from generalized thyroid hormone resistance (GTHR) for hormone assays and examination of the cellular thyroid hormone effect, and the results compared with results from other families with signs of altered peripheral thyroid hormone sensitivity. PATIENTS: Two members of a family with thyroid hormone resistance and nine normal persons were studied. MEASUREMENTS: Basal thyroid hormone function tests were measured. The thyroid hormone effect on mononuclear blood cells was determined by measuring the thyroid hormone stimulated oxygen consumption and glucose uptake. RESULTS: The two family members appeared phenotypically normal except for nodular goitre. Thyroid hormone stimulated glucose uptake was depressed whereas thyroid hormone stimulated oxygen consumption was normal. CONCLUSION: Comparison of the present results of the cellular examination in two patients with GTHR, with the results obtained in other families with altered peripheral thyroid hormone sensitivity, suggest that the classic GTHR (phenotype: normal or with goitre) is linked to impaired thyroid hormone stimulated glucose uptake, whereas in patients with osteopetrosis, the thyroid hormone insensitivity seems located at the mitochondrial level (impaired thyroid hormone stimulated oxygen consumption.

Adult↗
PubMed1993

Autosomal dominant osteopetrosis.

Autosomal dominant osteopetrosis is radiographically characterized by universal osteosclerosis, primarily involving the axial skeleton, and by symmetrical affections of the long bones without modeling defects. Based on standard radiographs, it is possible to describe two different subtypes with different clinical, biochemical, and histologic manifestations. Type I is radiographically characterized by pronounced osteosclerosis of the cranial vault, whereas Type II has end-plate thickening of the vertebrae (Rugger-Jersey spine) and endobones in the pelvis. Both types are strictly family related and seen in childhood. Combined radiogrammetric, biochemical, and histologic investigations indicate states of defective bone resorption, whereas bone formation seems to be normal in both types of patients. Patients with autosomal dominant osteopetrosis are often asymptomatic, and the diagnosis may be reached by chance. However, by systematic investigations, nearly all patients have manifestations related to the disorder. Symptoms are progressive with age, and correlated with osteosclerosis. The fracture frequency is increased in Type II patients, and normal in Type I, where biomechanical investigations have shown normal, or even increased trabecular bone strength. Treatment has been symptomatic. A rational treatment consists of stimulation of bone resorption, in combination with inhibition of bone formation if possible.

Bone Resorption↗
PubMed1992

Serum levels of fetal antigen 2 in hyperthyroidism and primary hyperparathyroidism.

Serum concentration of fetal antigen 2 (FA2) in patients with hyperthyroidism (n = 18) (median: 12.9 mAU/l; range: 3.2-22.4 mAU/l) was significantly (p < 0.002) higher than in age- and sex-matched healthy controls (median: 4.1 mAU FA2/l; range: 2.4-10.0 mAU FA2/l). Serum FA2 was positively correlated with thyroxine (T4) (Rs = 0.51; p < 0.05), triiodothyronine (T3) (Rs = 0.64; p < 0.01), bone-Gla protein (BGP) (Rs = 0.70; p < 0.01), total alkaline phosphatase (total-AP) (Rs = 0.62; p < 0.01), bone isoenzyme alkaline phosphatase (bone-AP) (Rs = 0.63; p < 0.01), N-terminal procollagen type III (PIIINP) (Rs = 0.65; p < 0.01) and urine OH-proline (OHP) (Rs = 0.79; p < 0.01). In patients with hyperparathyroidism the pretreatment levels of FA2 (n = 8) (median: 17.6 mAU/l; range: 5.2-35.0 mAU/l) were significantly (p < 0.001) higher than those of age- and sex-matched controls (median: 3.7 mAU FA2/l; range: 3.4-9.0 mAU/l). The pretreatment level of FA2 was positively correlated with the parathyroid hormone (PTH) (Rs = 0.80; p < 0.05). Following surgical treatment the serum concentrations of FA2, PTH, and BGP decreased compared to pretreatment levels and the fall in these three parameters revealed parallelism. These data indicate that serum FA2 can be used as a marker in the evaluation of metabolic bone diseases.

Adult↗
PubMed1991

Elevated serum levels of creatine kinase BB in autosomal dominant osteopetrosis type II.

Serum levels of creatine kinase isoenzyme BB (CK-BB) were measured spectrophotometrically and by electrophoresis in 17 patients with autosomal dominant osteopetrosis (ADO) and compared with those of age- and sex-matched controls. Eight patients had ADO type 1 and nine patients had ADO type II. CK-BB was significantly increased (p less than 0.002) in type II but normal in type I compared with controls. This finding supports heterogeneity of ADO, and it may indicate a potential role for CK-BB as a marker of immature osteoclasts.

Adult↗
PubMed1991

Decreased thyroid hormone-stimulated oxygen consumption and glucose uptake in mononuclear blood cells from patients with autosomal dominant osteopetrosis type I.

Nine patients, from four different families, with autosomal dominant osteopetrosis were investigated. They all had roentgenological type I disease, characterized by universal, symmetrical osteosclerosis and enlarged thickness of the cranial vault. All patients appeared clinically euthyroid. Thyroxine (T4) and tri-iodothyronine (T3) induced oxygen consumption and glucose uptake were studied in vitro in mononuclear blood cells from patients and control persons. Unstimulated oxygen consumption from patients and controls did not differ, and no difference in unstimulated glucose uptake was observed. The increase in T4 and T3 stimulated oxygen consumption was significantly lower in cells from patients with osteopetrosis (T4: 0.007 +/- 0.004 mumol/mg DNA per h, T3: 0.011 +/- 0.004 mumol/mg DNA per h) compared with controls (T4: 0.017 +/- 0.003 mumol/mg DNA per h, T3: 0.023 +/- -0.013 mumol/mg DNA per h; p less than 0.05, p less than 0.05). Cellular glucose uptake after T4 and T3 stimulation was significantly lower in patients (T4: 0.032 +/- 0.017 mmol/l per mg DNA per h, T3: 0.02 +/- 0.017 mmol/l per mg DNA per h) compared with controls (T4: 0.09 +/- 0.017 mmol/l per mg DNA per h, T3: 0.08 +/- 0.01 mmol/l per mg DNA per h; p less than 0.05, p less than 0.01). The reduced oxygen consumption and glucose uptake indicate thyroid hormone resistance which may be of pathogenetic importance for the development of autosomal dominant osteopetrosis type I.

Adult↗
PubMed1991

Down-regulation of monocyte functions by treatment of healthy adults with 1 alpha,25 dihydroxyvitamin D3.

A number of in vitro studies suggest an immunoregulatory role of 1 alpha,25 Dihydroxyvitamin D3 (1,25-(OH)2D3). The hormone inhibits production of interleukin-2 and immunoglobulin, and it blocks lymphocyte proliferation. Diverse effects on monocyte functions have been reported. However, immunological effects of 1,25-(OH)2D3 have not been substantiated in vivo. Six healthy male volunteers, aged 28-45 yr, were treated orally with 1,25-(OH)2D3 (tabl. Rocaltrol), 1 microgram twice daily for 7 days. Blood and urine samples were collected before and 7 days after initiation of treatment. Blood mononuclear cells from individuals treated with 1,25-(OH)2D3 showed a significantly reduced production of both interleukin-1 alpha (45%) and tumor necrosis factor-alpha (58%) (both measured by ELISA). Interleukin-6, production, measured by the B9 cell assay, was reduced in five individuals (78%), and unchanged in one. There was no effect on the release of interleukin-1 beta. There was no measurable effect on interleukin-2, interferon gamma or immunoglobulin production, or on mitogen-induced proliferation of blood mononuclear cells. Serum-osteocalcin and urine excretion of calcium were increased to 131 and 173%, respectively. The serum-calcium and serum-phosphate levels were unchanged.

Administration, Oral↗
PubMed1991

Effect of a short course of 1,25-dihydroxyvitamin D3 on biochemical markers of bone remodeling in adult male volunteers.

To investigate the stimulatory effect of vitamin D on biochemical markers of bone remodeling, 15 normal men (aged 26-45 years, mean 33.2) were treated orally with 1,25-dihydroxyvitamin D3, 2 micrograms daily for 7 days, and followed for a total of 16 weeks. Serum concentrations of 1,25-dihydroxyvitamin D3 rose 43% during the first week (p less than 0.01), with no significant alteration in the level of 25-hydroxyvitamin D3. Serum level of immunoreactive parathyroid hormone (1-84) (iPTH) decreased markedly (p less than 0.02), and the maximal renal reabsorption capacity of phosphate (TmP/GFR) increased (p less than 0.05), both indicating the impact of the raised vitamin D level on target tissues. Serum phosphate and serum calcium increased during the treatment week (p less than 0.05), as did the fasting renal excretion of phosphate and calcium (p less than 0.01). However, a gradual fall in the excretion of hydroxyproline was seen in the observation period. The serum activity of acid phosphatase increased in the first weeks after vitamin D treatment, reaching significance at the end of week 2 (p less than 0.05). Acid phosphatase activity was still increased at the end of the observation period (p less than 0.02). These observations suggest a synchronization and recruitment of new bone resorptive cells. The immediate response to 1,25-dihydroxyvitamin D administration on the biochemical markers of formative bone cells was a marked increase in the serum level of osteocalcin (BGP), (p less than 0.002) with a gradually fall during the next weeks. A secondary increase, however, was observed in the last two months of the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Increased serum concentrations of type I procollagen C-terminal propeptide and osteocalcin during a short course of calcitriol administration to adult male volunteers.

To investigate bone collagen metabolism during vitamin D treatment, 15 healthy males (aged 28-45 years, median 34) were treated orally with calcitriol, 2 micrograms daily for 7 days and followed for a total of 2 weeks. The serum concentration of calcitriol rose markedly (median difference and 95% confidence limits: 49% (5-82), p less than 0.005) during treatment, whereas serum levels of calcidiol, and calcium remained unchanged. The serum level of procollagen type I C-terminal propeptide rose 15% (7-33, p less than 0.003), whereas no alterations were observed concerning serum procollagen type III N-terminal propeptide, and serum hyaluronan. The serum concentration of osteocalcin rose concomitantly (26% (12-45), p less than 0.003). All values returned to baseline levels within seven days after the treatment week. The serum levels of osteocalcin and procollagen type I C-terminal propeptide were positively correlated (rs = 0.71, p less than 0.004) during the study. Serum procollagen type I C-terminal propeptide and serum osteocalcin did not correlate with serum procollagen type III N-terminal propeptide or serum hyaluronan either at baseline or after treatment. It is concluded that a short course of calcitriol administration to healthy males stimulates the biosynthesis of bone-related matrix proteins. By contrast, connective tissue components of predominantly extraosseous origin are not affected.

Administration, Oral↗
PubMed1990

The effect of carbonic anhydrase inhibition on calcium and bone homeostasis in healthy postmenopausal women.

Carbonic anhydrase localized in bone resorptive cells generates the protons necessary for bone resorption. Inhibition of the enzyme is a potential mechanism for decreasing bone resorption. Eight healthy post-menopausal women received oral acetazolamide 250 mg twice daily for 28 d. Bone resorption, evaluated by serum acid phosphatase activity and the renal excretion of hydroxyproline, was unaltered, as was bone formation estimated by serum levels of alkaline phosphatase and osteocalcin. The fasting renal excretion of calcium was increased, whereas serum ionized calcium was unchanged. The maximal renal reabsorption of phosphate decreased, but it was not an effect of PTH as it decreased significantly during the treatment period. In conclusion, no significant effect on biochemical markers of bone remodelling could be detected during the study period. The observed changes in calcium and phosphate metabolism may be secondary to the renal effect of acetazolamide.

Acetazolamide↗
PubMed1989

Biomechanical competence of iliac crest trabecular bone in autosomal dominant osteopetrosis type I.

Cylindrical horizontal iliac crest trabecular bone biopsies were obtained from 9 patients with autosomal dominant osteopetrosis type I and 18 normal controls of comparable age/sex match. Maximum compressive stress, maximum stiffness, energy absorption capacity and maximum strain were calculated from load-deformation curves after a compression test. Ash density of the bone samples was measured after incineration. The maximum compressive stress was significantly increased in the patient group (12.6 +/- 2.6 (SE) MPa vs. 3.3 +/- 0.4 MPa, p less than 0.01), as was the ash density (0.61 +/- 0.05 g/cm3 versus 0.27 +/- 0.02 g/cm3, p less than 0.01). After correction for ash density (normalized maximum stress) the strength of the trabecular bone samples was still significantly increased in the patients (19.7 +/- 6.4 MPa x cm3/g versus 12.0 +/- 1.2 MPa x cm3/g, p less than 0.01). The maximum stiffness and energy absorption capacity were higher in the patients (p less than 0.01), with a corresponding lower maximum strain value (p less than 0.05). The maximum compressive stress correlated closely to the maximum stiffness and energy absorption capacity in both patients and controls, whereas no correlation to maximum strain was found. The maximum compressive stress thus seems to be representative for the two other biomechanical parameters. No significant correlations between age and maximum compressive stress (R = 0.38), ash density (R = 0.08), or normalized maximum stress (R = 0.45) were observed in type I osteopetrosis, whereas significant age-dependent decreases in maximum compressive stress (R = -0.65, p less than 0.02) and in ash density (R = -0.57, p less than 0.02) were observed in normal individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Structural and histomorphometric studies of iliac crest trabecular and cortical bone in autosomal dominant osteopetrosis: a study of two radiological types.

Cylindrical iliac crest biopsies were obtained from 16 patients with autosomal dominant osteopetrosis after intravital double labeling with tetracycline, and compared with normal age- and sex-matched controls. Ten patients had the radiological type I (5 women, 5 men, aged 17-62 years, mean 42) characterized by diffuse, symmetrical osteosclerosis and enlarged thickness of the cranial vault. Six patients had type II (2 women, 4 men, aged 22-44 years, mean 36), where "Rugger Jersey Spine" and endobone are characteristic findings. Structural studies of cortical and trabecular bone were performed, and trabecular bone resorption and formation rates were studied using dynamic histomorphometry. The total biopsy length (C. Wi) were increased in type I (p less than 0.05), and unchanged in type II. Both types showed increased cortical width (Ct. Wi) (p less than 0.01 and p less than 0.05, respectively), and decreased fractional width of cancellous bone (Cn.Wi/C.Wi) (p less than 0.01 and p less than 0.05). The fractional trabecular bone volume (BV/TV) and trabecular thickness (Tb. Th) were both significantly increased in type I (p less than 0.05), while resorptive and formative indices of trabecular bone remodeling were normal. No difference was found in trabecular bone balance, which was slightly positive in both patients and controls. In type II osteopetrosis the eroded surfaces (OS/BS) were significantly increased (p less than 0.01), as was the total resorptive period RP) (p less than 0.05). The resorption depth (R.D.) was normal, while the resorption rate (MRR) was insignificantly decreased. Many big multinucleated osteoclasts were seen in this type suggesting defective resorptive function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗