Biomedical subjects

L Mosekilde

Publications and source records attributed to L Mosekilde.

At least 181 records · Page 10Linked to original sources

PubMed1994

Familial isolated primary hyperparathyroidism.

UNLABELLED: Familial primary hyperparathyroidism (PHPT) is usually encountered in the context of multiple endocrine neoplasia (MEN) syndromes. Few families have been reported in the literature where PHPT was the only abnormality. However, in these families no long-term follow-up data were reported and no genetic linkage studies were performed. OBJECTIVE: We investigated a large family with a familial primary hyperparathyroidism for biochemical and genetic markers of multiple endocrine neoplasia syndromes. DESIGN: A family screening study. PATIENTS: Thirty-seven family members participated in this study including 7 patients who had been previously operated upon for PHPT. MEASUREMENTS: Serum calcium (albumin adjusted), was measured in all family members. Hypercalcaemic subjects and patients who had been operated upon for PHPT were assessed for biochemical markers of MEN syndromes (serum gastrin, prolactin, calcitonin, fasting plasma glucose and 24-hours urinary excretion of adrenaline, noradrenaline and vanillylmandelic acid (VMA)). Genetic linkage analysis was performed using DNA markers linked to chromosome 11q13, the presumed MEN type 1 (MEN-1) locus. RESULTS: Four new patients with PHPT and two with probable PHPT were discovered. No clinical or biochemical evidence of MEN syndromes could be detected. DNA marker pMS51(D11S97) was informative, maximum two-point lodscore of 2.12 at a recombination fraction of 0.05 confirming linkage to chromosome 11q13. CONCLUSIONS: Familial PHPT can exist as a separate clinical entity. Isolated familial PHPT is caused by mutation in a gene located in the MEN-1 region on chromosome 11q13, possibly the MEN-1 locus.

Adult↗

PubMed1994

The positive effect of parathyroid hormone on femoral neck bone strength in ovariectomized rats is more pronounced than that of estrogen or bisphosphonates.

This study elucidates the effect of PTH, estrogen, and the bisphosphonate Risedronate (NE-58095) on femoral neck bone strength in ovariectomized (OVX) rats aged 90 days at the beginning of the investigation. Furthermore, the effects of these monotherapies were compared with those of concurrent treatment with PTH plus estrogen or PTH plus bisphosphonate. Four weeks after surgery the rats were randomized into a sham-operated vehicle-treated group, an OVX vehicle-treated group, and the various treatment groups and followed for 5 and 15 weeks. The proximal one-third of the left femur was then subjected to geometrical measurements and biomechanical testing. Neither ovariectomy nor the different treatment regimens influenced femoral neck geometry. OVX rats exhibited a decrease in femoral neck bone strength compared with control rats. This was most evident after 5 weeks. Treatment of OVX rats with Risedronate or estrogen alone tended to increase bone strength to control level, though these findings were nonsignificant. In contrast, treatment with PTH showed a highly significant increase in femoral neck biomechanical competence. Concurrent treatment with PTH plus estrogen or PTH plus Risedronate also significantly increased the femoral neck bone strength, but neither showed any advantage over treatment with PTH alone. It is concluded that treatment with PTH increases the strength of the femoral neck in estrogen-depleted rats in a highly significant manner, and that this effect is much more pronounced than the effect of the two antiresorptive agents estrogen or Risedronate. Thus, these findings provide further support for the anabolic effect of PTH and add weight to the argument for the promising potential of PTH in the treatment of postmenopausal osteoporosis.

Animals↗

PubMed1994

The effect on vertebral bone mass and strength of long term treatment with antiresorptive agents (estrogen and calcitonin), human parathyroid hormone-(1-38), and combination therapy, assessed in aged ovariectomized rats.

The aim of the study was to assess the long term effect of the antiresorptive agents estrogen and salmon calcitonin, the anabolic drug PTH, and combination therapy on vertebral bone mass and bone biomechanical competence in aged osteopenic ovariectomized (OVX) rats. Seventy-nine 1-yr-old retired breeder Wistar rats were randomized into seven groups: 1) sham-operated, 2) OVX, 3) OVX plus estrogen, 4) OVX plus salmon calcitonin, 5) OVX plus human (h) PTH-(1-38), 6) OVX plus hPTH-(1-38) and estrogen, and finally, 7) OVX plus hPTH-(1-38) and calcitonin. Treatment regimens were initiated 8 weeks after ovariectomy and continued for 24 weeks. Whole body bone mass was measured by dual photon absorptiometry at intervals of 4 weeks and at death. Changes in spinal bone mass (BMC), biomechanical competence, and structure were assessed from the lumbar vertebral bodies. The results revealed a protective effect of both estrogen and calcitonin on ovariectomy-induced loss of whole body bone mass, but only estrogen had a significant effect on spinal BMC. hPTH-(1-38) monotherapy increased vertebral bone mass (BMC and ash content), size, and biomechanical parameters 20-80% over OVX levels. A more rapid effect on vertebral bone mass was seen when hPTH-(1-38) was combined with estrogen or salmon calcitonin. The study has shown that in aged OVX osteopenic rats, hPTH-(1-38) therapy increases vertebral bone mass and bone quality and also maintains trabecular connectivity. Both estrogen and calcitonin reduce the ovariectomy-induced bone loss, but cannot restore bone mass to sham-operated levels. On the basis of this study, it is concluded that PTH therapy seems to hold promise in the management of postmenopausal and age-related osteoporosis.

Absorptiometry, Photon↗

PubMed1994

Effects of fluoride on human bone cells in vitro: differences in responsiveness between stromal osteoblast precursors and mature osteoblasts.

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.

Adult↗

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

No evidence for reduced spontaneous or growth-hormone-stimulated serum levels of insulin-like growth factor (IGF)-I, IGF-II or IGF binding protein 3 in women with spinal osteoporosis.

To test the hypothesis that a dysfunctional growth hormone (GH)-insulin-like growth factor (IGF) axis may play a role in the pathogenesis of osteoporosis, we compared the levels of IGF-I, IGF-II and IGF binding protein 3 (IGFBP-3) in 15 women with spinal osteoporosis (i.e. at least one non-traumatic vertebral fracture) and 15 normal age-matched women. Furthermore, the response to 3 days' treatment with recombinant human GH (r-hGH) (0.2 IU kg-1.day-1) was determined. The basal levels of IGF-I, IGF-II and IGFBP-3 were similar in patients and controls (mean +/- SEM): IGF-I, 16.5 +/- 1.3 versus 16.0 +/- 1.3 nmol/l (NS); IGF-II, 79.9 +/- 3.6 versus 72.5 +/- 4.1 nmol/l (NS); and IGFBP-3, 125.7 +/- 6.5 versus 130.3 +/- 7.8 nmol/l (NS). Stimulation with r-hGH elicited increased levels of IGF-I, IGF-II and IGFBP-3 within both groups (p < 0.001). The maximal values expressed as a percentage of baseline were: IGF-I, 341 +/- 26% versus 369 +/- 22%, IGF-II, 125 +/- 4% versus 119 +/- 5%, IGFBP-3, 141 +/- 5% versus 147 +/- 7% in osteoporotic patients and controls, respectively. No significant differences were observed between patients and controls in either their maximal response or in the area under the response curves. Our results do not support the hypothesis of a dysfunctional GH-IGF axis in women with spinal osteoporosis.

Aged↗

PubMed1994

Growth hormone stimulates proliferation of normal human bone marrow stromal osteoblast precursor cells in vitro.

In this study the effects of growth hormone (GH) in human marrow stromal osteoblast-like [hMS(OB)] cell cultures containing a population of osteoblast precursors, were tested. GH (dose range 0.1-500 ng/ml) stimulated hMS(OB) cell proliferation in a dose-dependent fashion as evidenced by increased 3H-thymidine incorporation into DNA and increased cell number. Maximal stimulation was 173 +/- 35% (P < 0.001, n = 12) and 145 +/- 6% (P < 0.0001, n = 10) of no-treatment controls for 3H-thymidine incorporation and cell number, respectively. GH did not exert major effects on differentiation markers in hMS(OB) cell cultures. 1,25-dihydroxy vitamin D3 (10(-9) M) alone increased cellular production of alkaline phosphatase (AP) and induced expression of osteocalcin. When GH was tested in combination with 1,25(OH)2D3, it tended to inhibit vitamin D-stimulated effects on differentiation markers but these effects were not statistically significant. Our results suggest that GH induces proliferation of less differentiated cells in the osteoblast lineage and this mechanism may in part mediate the in vivo effects of GH on bone formation.

Adult↗

PubMed1993

Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry.

Type I collagen makes up more than 90% of bone matrix. Therefore, analysis of antigens related to collagen formation and degradation in bone should provide good and specific estimates of both bone resorption and bone formation rates. In this study we measured serum levels of the pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) as a marker of bone resorption and serum carboxy-terminal propeptide of type I procollagen (PICP) as a marker of bone formation. Serum levels of the two antigens were correlated to histomorphometric indices of bone resorption and bone formation calculated from iliac crest bone biopsies in a group of 18 individuals with high- and low-turnover bone disease (myxedema, primary hyperparathyroidism, and thyrotoxicosis). After logarithmic transformation the regression of S-ICTP on volume-referent resorption rate (BRs/R/BV) was significant (r = 0.61, p < 0.01, SEM/Y = 56%). S-ICTP also showed a significant regression on the volume-referent cancellous bone balance (r = -0.45, p < 0.05, SEM/Y = 412%). S-PICP was significantly correlated to the mineral appositional rate (r = 0.53, p < 0.05) and volume-referent bone formation rate (r = 0.61, p < 0.01, SEM/Y = 48%). The correlation to bone turnover as expressed in the activation frequency was also highly significant (r = 0.61, p < 0.01, SEM/Y = 51%). No significant correlation with wall thickness or bone balance was demonstrable per remodeling cycle. Thus, assays employing antigens that reflect collagen formation and degradation are useful instruments for the evaluation of rates of bone remodeling in metabolic bone disease.

Adult↗

PubMed1993

Evaluation of the skeletal effects of combined mild dietary calcium restriction and ovariectomy in Sinclair S-1 minipigs: a pilot study.

A pilot study was conducted to investigate the combined effects of ovariectomy (OVX) with preceding and concomitant mild dietary calcium restriction on the minipig skeleton. Minipigs 4 months old were fed diets containing 0.9, 0.75, or 0.5% calcium (Ca). At 10 months, the 0.75 and 0.5% pigs were OVX and the 0.9% were either sham operated or OVX. All pigs were maintained on their respective diets for an additional 6 months. Excised lumbar vertebrae and long bones were evaluated by densitometry and histomorphometry, and vertebral cancellous bone samples were tested biomechanically. In pigs fed the 0.9% Ca diet, OVX alone effected decreases of 6% in vertebral bone mineral density (BMD), 15% in trabecular bone volume (BV/TV), and 13% in trabecular number (Tb.N), an increase of 15% in trabecular separation (Tb.Sp), and a nonsignificant increase (p < 0.056) in vertebral cancellous final erosion depth (F.E.De) compared with the 0.9% Ca sham-operated group. Decreasing dietary Ca to 0.5% in combination with OVX effected an 8% reduction in vertebral BMD that was not associated with any significant alterations in parameters of vertebral cancellous bone microstructure or remodeling compared with the 0.9% Ca sham-operated pigs. Increases in serum PTH noted in the 0.5% Ca OVX group were generally paralleled by increases in calcitriol. In OVX pigs fed a diet containing 0.75% Ca, a 10% reduction in vertebral BMD was observed. This was associated with significant increases in F.E.De and vertebral marrow star volume (Ma.St.V) compared with the 0.9% Ca sham-operated pigs and the other OVX groups. In addition, Tb.Sp was increased and Tb.N decreased compared with the 0.9% Ca sham-operated pigs. Increases in serum PTH in this group were not accompanied by increases in calcitriol. Midradial and midfemoral BMD values were reduced in the 0.75 and 0.5% Ca OVX groups compared with the 0.9% Ca sham-operated pigs. Histomorphometric analyses of cortical bone suggested the reduction in cortical bone mass in the 0.75% Ca OVX group may have been largely due to net loss on the endocortical surface versus possible failure to accrue bone in the 0.5% Ca OVX group. Ash density and biomechanical parameters for vertebral cancellous bone decreased progressively in the 0.9% sham-operated, 0.9% Ca OVX, and 0.75% Ca OVX groups and then increased in the 0.5% Ca OVX group. After normalization for bone mass (ash), mechanical changes were still apparent, particularly for the 0.75% Ca OVX group compared with other OVX groups, reflecting that structural changes had taken place in the trabecular network.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid Phosphatase↗

PubMed1993

1,25-dihydroxyvitamin D3 potentiates fluoride-stimulated collagen type I production in cultures of human bone marrow stromal osteoblast-like cells.

In this study we tested the effects of sodium fluoride (NaF) in serum-free cultures of human marrow stromal osteoblast-like [hMS(OB)] cells. NaF (10(-5) M) stimulated hMS(OB) cell proliferation up to 220% of control cultures. NaF alone did not increase type I collagen production, but in the presence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] (10(-9) M), NaF enhanced type I collagen production in a dose-dependent way to 300% of 1,25-(OH)2D3-treated control cultures. The production of alkaline phosphatase (ALP) and osteocalcin (bone gla protein, BGP) was also enhanced in the presence of 1,25-(OH)2D3 to 170 and 200%, respectively, of 1,25-(OH)2D3-treated controls. Our results suggest that 1,25-(OH)2D3 potentiates fluoride-mediated anabolism in hMS(OB) cell cultures and suggest that osteoblast precursors in bone marrow are targets for fluoride action.

Alkaline Phosphatase↗

PubMed1993

Growth hormone stimulates proliferation and differentiation of normal human osteoblast-like cells in vitro.

In this study we investigated the direct, short-term effects of human growth hormone (hGH) on the biology of normal adult human osteoblast-like (hOB) cells cultured from trabecular bone explants. In Subconfluent cultures, hGH stimulated hOB proliferation in a dose-dependent fashion (P < 0.001, n = 15) with half-maximal effects at a concentration of 10 ng/ml. These mitogenic effects were detectable within 24 hours as shown by bromodeoxyuridine labeling. In confluent cultures containing mainly quiescent cells, hGH increased levels of alkaline phosphatase (P < 0.05, n = 10) and to a lesser degree levels of procollagen type I carboxyterminal propeptide (PICP) (P = 0.07, n = 9). Effects on osteocalcin (bone GLa protein, BGP) levels were highly variable among different cell strains and only 7 of 10 cell strains showed a stimulatory response (P = 0.16). We also studied the effects of hGH on osteoblastic production of insulin-like growth factor I (IGF-I) and IGF-II as well as the production of GH-dependent, insulin-like growth factor binding protein 3 (IGFBP-3). Under basal conditions, human osteoblasts produced IGF-II and IGFBP-3 in the conditioned medium. When stimulated with hGH, minor insignificant increase in both IGF-II and IGFBP-3 (125% and 126% of control, respectively) were detectable. No IGF-I was detectable in the conditioned medium under basal conditions or after stimulation with hGH. In conclusion, the results obtained in this study suggest that GH exerts direct anabolic effects on human osteoblasts.

Alkaline Phosphatase↗

PubMed1993

Cortical bone mass, composition, and mechanical properties in female rats in relation to age, long-term ovariectomy, and estrogen substitution.

The study comprised 12 groups of female rats: 6 groups of intact rats killed at 2, 6, 9, 12, 15, and 24 months of age, 4 groups of rats ovariectomized at 6 months and killed together with the intact rats at 9, 12, 15, and 24 months of age, and 2 groups of rats (one intact and one ovariectomized) treated with estrogen (2 micrograms estradiol valerate/rat/week s.c.) for 8 months before they were killed at 24 months of age. The composition, dimensions, and mechanical strength of intact bone and bone collagen from femoral diaphyses were investigated in relation to age, ovariectomy, and estrogen administration. Up to 6-9 months of age, the axial length, percentage ash, density, and compressive mechanical stress increased, whereas percentage collagen decreased. An age-related increase in bone mass, cross-sectional area, and wall thickness and a decrease in mechanical quality of bone collagen were apparent from 2 to 24 months of age. An age-related periosteal bone formation and the absence of endosteal bone resorption were demonstrated in intact rats. Compared with intact rats, ovariectomy was followed by an increase in body weight, a tendency to reduced percentage ash and a depressed bone mass, cross-sectional area, and wall thickness of femoral diaphyses. The compressive mechanical stress of intact bone and the mechanical quality of bone collagen were unaffected by ovariectomy. Ovariectomy did not influence the periosteal bone formation but induced an endosteal bone resorption not present in the intact rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1993

Vertebral structure and strength in vivo and in vitro.

The incidence of vertebral fragility fractures has increased 2-4-fold during the past 30 years and the rate of increase is the same for both men and women. To arrest or reverse this increase, thorough understanding of normal, age-related changes in bone structure and strength is crucial. The human vertebral body is constructed to provide maximum strength with minimum bone mass. The strength is the sum of bone size, cortical thickness, trabecular architecture, and bone mass. With age, all these factors change due to the remodeling process, but the decline in bone strength is much more pronounced than the decline in mass. In individuals with very low bone mass, this discrepancy between mass and strength is even more marked. Structural studies have all shown a disruption of the trabecular network with age--mainly caused by perforation of horizontal supporting struts. These changes begin in the vertebral center. Later, a decline in cortical thickness is disclosed. The biomechanical consequence of this is a 4-6-fold decrease in vertebral strength during normal aging. As the structural changes cannot be reversed, it is difficult to increase bone strength by therapeutic regimens. Focus should therefore be placed on prevention. Three avenues are suggested: (1) to use the vast amount of existing biological data in a computer model to increase the understanding of the relationship among bone structure, mass, and strength, and to help identify the intervention regimens offering the best prospects of success; (2) to investigate characteristics of load-bearing trabecular bone that does not fracture; and (3) to focus more on life-style factors.

Aged↗

PubMed1993

Distribution of hydroxylated vitamin D metabolites [25OHD3 and 1,25(OH)2D3] in domestic pigs: evidence that 1,25(OH)2D3 is stored outside the blood circulation?

1. The distribution of 25-hydroxycholecalciferol (25OHD3) and 1,25-dihydroxycholecalciferol [1,25(OH)2D3] in various organs from domestic pigs was examined by HPLC. 2. Plasma levels of both metabolites corresponded to those found in healthy human subjects. 3. Tissue concentrations of 25OHD3 in fat, kidney, liver, and intestinal mucosa were low (< 1/3 of plasma levels), whereas tissue concentrations of 1,25(OH)2D3 exceeded plasma levels by factors 3-7, adipose tissue concentrations being the highest. 4. Substantial amounts of activated vitamin D are stored outside the blood-streams and may actively participate in vitamin D and calcium homeostasis.

Animals↗

PubMed1993

The effect of aging and ovariectomy on the vertebral bone mass and biomechanical properties of mature rats.

Ovariectomy has a proven pronounced effect on bone mass, as has been shown in several animal models and in clinical studies. The aim of this study was to investigate the effect of ovariectomy on both vertebral bone mass and biomechanical competence. The study was performed on a long-term mature rat model. One hundred and five, three-month-old female Wistar rats were randomized into seven groups. One group was killed at the start of the study and was used as a baseline group. Three groups were ovariectomized and followed for one, three, or six months after the operation. Three groups were sham-operated and followed for the same periods. At death, three lumbar vertebrae were obtained from each rat, and changes in bone mass (ash content, trabecular bone volume (TBV)), bone structure, and biomechanical competence were assessed from these vertebrae. The results revealed an age-related (three-nine months) increase in bone mass and biomechanical competence in the sham-operated control groups. In the ovariectomized groups, an age-related decrease in TBV was disclosed. The ash content remained constant, whereas the biomechanical parameters--after an initial increase--showed decreasing values with age in the ovariectomized groups. When age-matched control and ovariectomized rats were compared, an increasing difference in both bone mass and bone biomechanical competence was disclosed. The study has shown that ovariectomy has a pronounced effect not only on vertebral bone mass, but also on bone quality, and that this mature rat model forms an excellent basis for evaluating potential therapeutic regimens for the treatment of osteoporosis.

Aging↗

PubMed1993

The effects of growth hormone on fracture healing in rats: a histological description.

Previous biomechanical studies have indicated that growth hormone has a stimulatory effect on fracture healing. This study was designed to give a histological description of the long-term effects of growth hormone on fracture healing in rats. Sixty-four female rats were divided into two groups and were given either biosynthetic human growth hormone (2.7 mg/kg body weight/day) or saline s.c. in two daily injections. This treatment was given for 20 days after a closed tibial fracture with medullary nailing had been performed. Five or six rats were killed from each group after 10, 20, 30, 40, 50, and 80 days of healing. The fracture site was embedded undecalcified in methylmethacrylate, cut into 8 microns thick, mid-frontal sections, and investigated in a normal light microscope after staining with Masson Trichrome and in polarized light after staining with Sirius red. The results revealed that growth hormone had an initially stimulatory effect on external callus formation. However, the callus formed was loosely structured and was not removed by the normal modeling and remodeling process. The callus therefore persisted even after 80 days of healing. In contrast, after only 40 days the saline treated rats showed healing, with a resumption of the normal size and shape of the fractured tibial bone, leaving only a small amount of dense callus tissue. The study also revealed that the hemopoietic system was stimulated by growth hormone, with massive invasion of marrow cells into the external fracture callus. Bone marrow cells dominated the intratrabecular space in growth-hormone treated animals, even after 80 days of healing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effects of intravenous EDTA treatment on serum parathyroid hormone (1-84) and biochemical markers of bone turnover.

Patients with primary hyperparathyroidism have increased bone turnover, but it is less well documented how brief periods of excess parathyroid hormone (PTH) (endogenous or exogenous) affect bone metabolism. In the present double blind study, we examined the effect of either ethylenediaminetetraacetatic acid (EDTA) or placebo on serum levels of PTH and biochemical markers of bone turnover in 15 women and 39 men (aged 41 to 81 years) suffering intermittent claudication due to atherosclerosis. Disodium EDTA was administered as 20 repeated infusions of 3 grams during a period of 5-9 weeks. Serum calcium and serum phosphate decreased following treatment (p < 0.001) and remained unchanged in the placebo group. However, the differences between the groups were insignificant (ANOVA p = 0.13 and p < 0.10, respectively). PTH increased 2 1/2 fold following EDTA treatment (p < 0.001, ANOVA). The change in serum PTH was inversely correlated with the change in serum calcium (r = -0.53, p < 0.01). In the EDTA group, urinary hydroxyproline/creatinine and calcium/creatinine increased after treatment (ANOVA p < 0.001 and p < 0.05, respectively). Serum bone alkaline phosphatase decreased significantly in the EDTA group immediately after treatment (p < 0.001, ANOVA) and returned to baseline level at three months while only an insignificant decrease in serum osteocalcin was seen following treatment. We conclude that EDTA treatment increases endogenous PTH secretion considerably and leads to increased bone resorption. However, no changes in osteoblastic markers indicating increased activation of bone remodeling could be demonstrated. Our findings support that chelation therapy with EDTA is accompanied by bone loss.

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↗