Search Results

You are looking at 1 - 10 of 23 items for

  • Author: Leif Mosekilde x
Clear All Modify Search
Restricted access

Leif Mosekilde and Flemming Melsen

ABSTRACT

Histomorphometric analysis of iliac crest biopsies was performed after tetracycline double-labelling in 22 hyperthyroid patients before and after medical antithyroid treatment for an average period of 4 months. The initially increased cortical porosity was normalized during treatment whereas the amount of trabecular bone was unchanged. The osteoclastic resorption in cortical bone decreased but was still elevated. The osteocytic osteolysis remained slightly increased. In trabecular bone, however, the bone turn-over decreased to a subnormal level following treatment and the surfaces were inactive in bone resorption and bone formation. An increase was observed in the amount, extent and width of osteoid seams due to an increase in the lifespan of bone forming sites and a prolongation of the maturity period of osteoid. The observed increased deposition of cortical bone after antithyroid treatment may explain the positive calcium balance in this period.

Restricted access

Leif Mosekilde and Merete Sanvig Christensen

ABSTRACT

Serum immunoreactive parathyroid hormone (S-iPTH) was measured together with serum and urinary calcium and phosphorus in 45 hyperthyroid patients in order to assess parathyroid function. Serum calcium and phosphorus were increased and positively correlated to the degree of hyperthyroidism. The prevalence of hypercalcaemia was 51.1 % using serum calcium values corrected for individual variations in serum albumin concentration compared to 15.6% using the uncorrected calcium values. S-iPTH was decreased and inversely correlated to serum calcium (corrected). Subnormal levels of S-iPTH were found in 28.9 % of the patients. The urinary excretion of calcium and phosphorus was increased and positively correlated to the degree of hyperthyroidism. The tubular reabsorption of calcium (TRCa %) was decreased, positively correlated to S-iPTH and inversely correlated to serum calcium. Increased mobilisation of bone mineral in hyperthyroidism is suggested mainly to be responsible for the elevated serum levels and increased urinary excretion of calcium and phosphorus and for the decreased parathyroid function.

Restricted access

Johan Halse, Flemming Melsen and Leif Mosekilde

Abstract.

Iliac crest bone biopsies from 18 patients with active acromegaly, of whom 11 had received tetracycline double-labelling, were evaluated by quantitative histomorphometry and compared with age- and sex-matched normal controls. A significant increase (P < 0.01) was found in both cortical (175%) and trabecular (130%) bone mass. In trabecular bone, resorption surfaces and active (tetracycline-labelled) and total formation surfaces were increased (P < 0.05 and P < 0.01, respectively) causing an enhanced bone turn-over at tissue level (P < 0.01). The increased trabecular bone mass indicates a positive net balance per remodelling cycle and, therefore, larger than normal bone remodelling units, which in part may explain the increased bone turn-over at tissue level. The activity of the osteoblasts active in mineralization (the appositional rate) was increased (P < 0.01) and positively related to the fasting serum growth hormone levels (Rs = 0.69, P < 0.05). The average activity of active and inactive osteoblasts (bone formation rate at basic metabolic unit (BMU) level) was insignificantly increased. The proportion of active (tetracycline labelled) to non-active formation surfaces was normal. The bone changes were unrelated to serum levels and urinary excretions of calcium and phosphorus or to renal excretion of total and non-dialyzable hydroxyproline or cAMP.

Restricted access

Moustapha Kassem, Leif Mosekilde and Erik F Eriksen

Kassem M, Mosekilde L, Eriksen EF. Effects of fluoride on human bone cells in vitro: differences in responsiveness between stromal osteoblast precursors and mature osteoblasts. Eur J Endocrinol 1994;130:381–6. ISSN 0804–4643

The cellular effects of sodium fluoride (NaF) on human bone cells in vitro have been variable and dependent on the culture system used. Variability could be attributed to differences in responsiveness to NaF among different populations of cells at various stages of differentiation in the osteoblastic lineage. In this study we compared the effects of NaF in serum-free medium on cultures of more differentiated human osteoblast-like (hOB) cells derived from trabecular bone explants and on osteoblast committed precursors derived from human bone marrow, i.e. human marrow stromal osteoblast-like (hMS(OB)) cells. Sodium fluoride (10−5 mol/l) increased proliferation of hMS(OB) cells (p<0.05, N = 10) but was not mitogenic to hOB cells (p>0.05, N= 10). Alkaline phosphatase (AP) production increased in both hMS(OB) (p<0.05, N=9) and hOB cells (p<0.05, N=9). No significant effects on procollagen type I propeptide production were obtained in either culture. In the presence of 1,25-dihydroxycholecalciferol (10−9 mol/l), NaF enhanced alkaline phosphatase (p<0.05, N=8), procollagen type I propeptide (p<0.05, N=7) and osteocalcin (p<0.05, N=7) production by hMS(OB) cells but not by hOB cells. Our results suggest that osteoblast precursors are more sensitive to NaF action than mature osteoblasts and that the in vivo effects of NaF on bone formation may be mediated by stimulating proliferation and differentiation of committed osteoblast precursors in bone marrow.

M Kassem, Mayo Clinic, Endocrine Research Unit, W-Joseph 5-164, Rochester, MN 55904, USA

Restricted access

Jørgen Rungby, Leif Mosekilde and Jørgen Hjelm Poulsen

Abstract.

The ability of the human body to store substantiable amounts of not only inactive vitamin D metabolites but also the bioactive 1,25-hydroxylated metabolite was demonstrated in a patient suffering from renal hydroxylase deficiency.

Free access

Anne Kristine Amstrup, Lars Rejnmark and Leif Mosekilde

Objective

Primary hyperparathyroidism (PHPT) is associated with feelings of fatigue and depression, as well as limitation to physical and mental functioning. These quality of life (QoL) characteristics improve after parathyroidectomy. However, whether former patients fully regain QoL compared with healthy controls is largely unknown.

Design and patients

Cross-sectional study. Fifty-one former PHPT patients, successfully treated by surgery (mean time since parathyroidectomy 7.4 (range 5–15) years), and 51 sex- and age-matched healthy controls.

Methods

The 36-item Short-Form Health Survey version 2 and the WHO-Five Well-being Index. The surveys included questions on overall physical and mental health, functioning, and limitation in daily life activities.

Results

Former patients scored significantly lower compared with controls in physical functioning (P=0.01), role limitation caused by emotional problems (P=0.01), vitality (P<0.001), and general health (P=0.01). Compared with the controls, cases had a lower median (interquartile range) score of physical component summary (PCS; 54.9 (47.9–58.7) vs 49.6 (45.2–55.9), P=0.03) and mental component summary (MCS; 55.4 (49.7–58.1) vs 52.5 (44.7–55.5), P=0.04). There was no association between time since operation and PCS or MCS. Compared with controls, cases had higher body mass index (BMI; 26.0±4.7 vs 28.8±6.0 kg/m2, P<0.001) and a higher frequency of cardiovascular diseases (CVD; 41.2 vs 62.7%, P=0.03). After adjustment for differences in BMI and CVD, PCS did no longer differ between groups. However, adjustments did not change the finding of a lower MCS in cases compared with controls.

Conclusion

Even though QoL may improve substantially after surgery, former PHPT patients still have reduced QoL compared with healthy controls.

Free access

Lars Rejnmark, Peter Vestergaard, Lene Heickendorff and Leif Mosekilde

Objective

Although calcitriol (1,25(OH)2D) is considered the biologically active vitamin D metabolite, several studies have shown that calcidiol (25OHD) is the vitamin D metabolite that is most closely linked to parathyroid function and indices of calcium homeostasis. Moreover, low levels of 25OHD have been associated with increased risk of different diseases including cancer, diabetes, and myopathy.

Design

Cross-sectional study.

Methods

We studied relations between plasma concentrations of 25OHD, 1,25(OH)2D, and parathyroid hormone (PTH) in fasting plasma samples from 315 healthy postmenopausal women randomly selected from the local background population.

Results

P-1,25(OH)2D levels varied in a concentration-dependent manner with P-25OHD levels (P<0.001). Thus, P-1,25(OH)2D levels were the lowest in women with vitamin D insufficiency, i.e., P-1,25(OH)2D levels were reduced by approximately one-third in subjects with P-25OHD levels below 25 nmol/l compared with levels above 80 nmol/l (P<0.01). The association was most pronounced at P-25OHD concentrations below 80 nmol/l, whereas no major increase in P-1,25(OH)2D was observed at P-25OHD concentrations above 80 nmol/l. In multiple regression analysis, PTH was a minor although significant predictor of P-1,25(OH)2D levels.

Conclusions

In normal postmenopausal women, the conversion of 25OHD to active vitamin D depends on the substrate concentration. Our data support that vitamin D insufficiency should be considered at P-25OHD levels below 80 nmol/l.

Restricted access

Leif Mosekilde, Merete Sanvig Christensen, Flemming Melsen and Niels Schwartz Sørensen

ABSTRACT

The effect of antithyroid treatment on the disturbed calcium-phosphorus metabolism in hyperthyroidism was studied in 16 patients. Elevated serum concentrations and urinary excretions of calcium and phosphorus were almost normalized 4 weeks after the start of medical treatment. Serum immunoreactive parathyroid hormone was decreased in the hyperthyroid state and became normal after medical treatment. Serum alkaline phosphatase levels were elevated throughout the study with an increase to a maximum peak after 8 weeks of antithyroid treatment. Urinary hydroxyproline excretion was initially markedly increased and fell rapidly during therapy. The observed changes suggest decreased bone resorption and increased bone formation with deposition of bone mineral after antithyroid treatment.

Alterations in the serum albumin concentration during the investigation period influenced the total serum calcium concentration. Using albumin adjusted serum calcium values no hypocalcaemia was found during medical treatment or after a subsequent subtotal thyroidectomy.

Restricted access

Henning Kaspersen Nielsen, Peter Laurberg, Kim Brixen and Leif Mosekilde

Abstract.

Serum osteocalcin varies in a diurnal rhythm, with peak values during the night and minimum levels before noon, but the factors controlling this rhythm are unknown. In this study, we evaluated the temporal relations between the osteocalcin rhythm and variations in serum concentrations of cortisol, intact parathyroid hormone (PTH(1-84)), and ionized calcium (Ca2+) in 15 normal volunteers, aged 22-46 years. Serum cortisol varied in a typical way preceding inverse changes in serum osteocalcin by about 4 h (r=0.78, p<0.0001). Changes in serum osteocalcin following the early morning increase in serum cortisol were statistically indistinguishable from the changes seen after oral administration of 2.5 or 10 mg of prednisone. Serum PTH (1-84) showed a diurnal rhythm (p<0.01) with peak values (4.06±0.42 pmol/l) at 20.30 h and nadir (2.81±0.10 pmol/l) around 10.30 h, preceding changes in serum osteocalcin in the same direction by 5 h (r=0.55, p<0.02). Prednisone at a dose of 10 mg did not change the time course significantly. Serum Ca2+ varied in an almost bi-phasic pattern (p<0.01) with maximal mean levels around 16.30 and 09.30 h and minimal levels around 05.30 and 14.30 h. Serum Ca2+ correlated inversely with PTH (1-84) (r=0.53, p<0.01), and serum osteocalcin was inversely related to Ca2+ at concurrent time points (r=0.59, p<0.005). Prednisone caused a 2-3 h lasting increase in serum Ca2+ 3-5 h after ingestion (p<0.001). In conclusion, our results suggest that cortisol is strongly associated to the diurnal rhythm in serum osteocalcin. The biological relevance of the reported relation between serum osteocalcin and PTH (1-84) and serum Ca2+ is uncertain.

Restricted access

Jens Bollerslev, Sandy C Marks Jr, Lis Mosekilde, Jane B Lian, Gary S Stein and Leif Mosekilde

Bollerslev J, Marks SC, Mosekilde L, Lian JB, Stein GS, Mosekilde L. Cortical bone osteocalcin content and matrix composition in autosomal dominant osteopetrosis type I. Eur J Endocrinol 1994;130:592–4. ISSN 0804–4643

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. Corticol 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.

Jens Bollerslev, Dept. of Med. Endocrinology, National Hospital, Pilestredet 32, N-0027 Oslo, Norway