Search PubMed⌕ Search

Biomedical subjects

J Foldes

Publications and source records attributed to J Foldes.

At least 19 recordsLinked to original sources
PubMed1997

Serum interleukin-6 and bone metabolism in patients with thyroid function disorders.

To determine the possible involvement of interleukin-6 (IL-6) in the bone loss of hyperthyroidism, relationships between thyroid status, biochemical and densitometric parameters of bone metabolism, and IL-6 were studied in female subjects. Patients with hyperthyroidism caused by either toxic nodular goiter or Graves' disease had significantly higher serum IL-6 concentrations than normal controls. Within the control group, serum IL-6 was higher in postmenopausal than in premenopausal women, but this influence of menopausal status was not seen in the hyperthyroid patients. The production of IL-6 by blood mononuclear cells was higher in cells from the hyperthyroid women. Bone turnover was increased in the hyperthyroid patients based on serum osteocalcin and urinary deoxypyridinoline excretion, and the hyperthyroid group also had reduced radius bone mineral content (BMC). A subgroup of hyperthyroid patients who had the lowest BMC (values more than 1 SD below normal age-matched controls) also had serum IL-6 concentrations significantly greater than those of hyperthyroid patients showing less reduction of BMC. The correlations observed in this study support the possibility that IL-6 plays a role in mediating the bone loss that results from excess thyroid hormone.

Adult↗
PubMed1995

Replacement therapy with imiglucerase for type 1 Gaucher's disease.

Gaucher's disease, the most common sphingolipidosis, is caused by deficiency of the lysosomal enzyme glucocerebrosidase. Therapy with alglucerase (the placental enzyme) is safe and effective at various dosing regimens. We report the use of low-dose imiglucerase (the recombinant enzyme) at two dosing schedules: 15 u/kg once fortnightly or 2.5 u/kg thrice weekly. Mean reductions in spleen and liver volumes achieved (in all ten patients) by imiglucerase at 12 months were 36.4% and 14.5%, respectively; mean increase in haemoglobin and platelet counts were 13.4% and 25.7%. There were no serious side-effects. No significant differences were observed between the two schedules. Low-dose low-frequency imiglucerase may be an alternative cost-effective approach with satisfactory clinical response and uncompromised quality of life.

Adolescent↗
PubMed1995

Relations between histologic indices of bone formation: implications for the pathogenesis of spinal osteoporosis.

Wall thickness, a major determinant of trabecular thickness, falls with age and falls further in osteoporosis. To estimate the importance of defective osteoblast recruitment in the pathogenesis of this defect, we compared various histologic indices of bone formation in iliac bone biopsies in three groups of subjects--healthy premenopausal women, healthy postmenopausal women, and patients with postmenopausal osteoporosis and at least one non-traumatic vertebral compression fracture. Indices that reflect the frequency of activation of bone remodeling and consequent birth rate of new teams of osteoblasts (osteoid surface, mineralizing surface, osteoblast surface, and bone formation rate, all expressed per unit of bone surface) were each higher in healthy subjects who were postmenopausal than in those who were premenopausal, but lower in osteoporotic than in normal postmenopausal women. In each group, the primary surface measurements were significantly correlated with each other, but the correlation was less close in those with osteoporosis. Indices that reflect the average collective performance of individual teams of osteoblasts (mineralizing surface and osteoblast surface per unit of osteoid surface, mineral apposition rate, adjusted apposition rate, and wall thickness) were all lower in postmenopausal than in premenopausal normal subjects, and even lower in those with postmenopausal osteoporosis. The parameters of the regression lines relating bone formation rate to osteoblast surface were essentially the same in each group, indicating that bone formation rate per unit of osteoblast surface was unaffected by age or menopause, and was the same in osteoporosis as in healthy subjects of similar age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Alfacalcidol (alpha D3) and calcium in osteoporosis.

In a prospective, randomized study, 66 osteoporotic postmenopausal women (mean age, 67 years) were scheduled to receive either alfacalcidol 0.25 microgram twice daily together with calcium 500 mg twice daily (treatment group, n = 24) or placebo twice daily with calcium 500 mg twice daily (control group, n = 42) for three years. In the treatment group, bone mineral content at the distal radius may have increased by 2% compared to a significant decrease of 7.8% in the control group. The difference between the two groups was also significant. Since the dose of alfacalcidol and calcium remained unadjusted, frequent hypercalciuria, as well as occasional mild, transient elevations of serum calcium, were observed in the treatment group. No changes in serum creatinine levels or creatinine clearance throughout the study were observed. The two groups did not differ with respect to the frequency of clinical side effects, which were mainly gastrointestinal and probably related to the calcium supplementation. Alfacalcidol and calcium may prevent further bone loss in women suffering from postmenopausal osteoporosis.

Absorptiometry, Photon↗
PubMed1992

Calcium homeostasis, bone metabolism and safety aspects during long-term treatment with a GnRH agonist.

Thirty-five women with symptomatic fibroids were treated with monthly injections of 3.2 mg microcapsulated D-Trp-6-LHRH for 6 months. During treatment serum 17 beta-oestradiol levels decreased, falling to castration levels associated with a reduction in the volume of the fibroids. In 16 patients a complete calcium homeostasis and bone metabolism work-up was carried out during treatment and subsequently for a 6-month follow-up period. Bone mineral content (BMC) and Compton bone densitometry readings remained unchanged. There were significant increases in serum calcium phosphate and alkaline phosphatase concentrations. A slight although not significant increase was observed in osteocalcin and parathyroid hormone (PTH) serum levels. Serum 1,25(OH)2D3 values decreased significantly after 3 months of treatment. Urinary hydroxyproline/creatinine and calcium/creatinine ratios as well as 24-h urinary calcium values increased significantly during the treatment period but decreased rapidly to pretreatment values after 3 months in the follow-up period. The endocrine changes induced by the GnRH-agonist treatment were associated with reversible biochemical signs of increased bone turnover and no significant changes in bone mass, suggesting that the treatment can be administered safely for a period of 6 months in patients with oestrogen-dependent diseases.

Adult↗
PubMed1992

Parathyroid stimulation after bleeding in man.

A role for the PTH-calcium axis in the normal bone-marrow response to bleeding or erythropoietin administration has been demonstrated in rats. We studied 20 autologous blood donors, each donating two units of blood, who served as a human bleeding model. Fifteen patients completed the study. Blood donations were followed by a significant increase in serum intact PTH (2.15 +/- 0.67 to 2.81 +/- 0.84 pmol/l; p = 0.0003) and protein-corrected total calcium (2.43 +/- 0.09 to 2.49 +/- 0.08 mmol/l; p = 0.2). All the individual values remained within the normal range. PTH weakly correlated with the reticulocyte count, but not with the corrected serum calcium. We conclude that moderate bleeding in humans is followed by a physiological increase in serum PTH and calcium.

Adolescent↗
PubMed1992

Bone structure and calcium metabolism in obese Zucker rats.

Obesity is associated with altered bone mass. However, reports on bone status in obesity are inconsistent. Increased or normal bone mass was reported in obese adults but decreased bone mineral content was described in obese children. Therefore we evaluated the obese fa/fa rat as a possible model to assist in studies of bone metabolism in obesity. Obese and lean 14-week-old male rats underwent 24 h balance studies for calcium, magnesium and phosphate. Plasma calcium, magnesium, phosphate, immunoreactive parathyroid hormone, urinary cAMP (cyclic adenosine monophosphate) and femur bone histomorphometry were also analysed. Obese rats were heavier and had higher plasma insulin, cholesterol and triglycerides levels (P less than 0.05). A comparable positive balance for calcium, magnesium and phosphate was found in obese and lean rats. Total plasma calcium was higher in the obese, but albumin corrected calcium and plasma magnesium, phosphate and glucose were similar to the lean. In contrast to human obesity, obese rats were hypercalciuric, hypermagnisuric and hyperphosphaturic (P less than 0.05). iPTH and urinary cAMP were higher in the obese. Femora of fa/fa rats were shorter and lighter. Their bone osteoid surface and bone calcium content were similar to controls. Femora metaphysis in the obese had increased number of trabeculae, decreased trabecular width and higher erosion surface/bone surface ratio. Their diaphysis had increased cortical area/bone area and cortical width/bone width ratios and decreased medullary area. In summary, obese rats have higher iPTH, are hypercalciuric and have decreased bone mass. These last two observations differ from what is described in adult human obesity. Therefore, the obese fa/fa rat is of limited assistance in studies of bone status in adult human obesity. It might be of help in studies of bone metabolism in juvenile obesity.

Animals↗
PubMed1991

Structural and geometric changes in iliac bone: relationship to normal aging and osteoporosis.

We measured indices of bone volume (cancellous and cortical) and bone surface (cancellous, endocortical, and intracortical) in intact, full-thickness transiliac bone biopsies obtained from 47 healthy white women (23 premenopausal and 24 postmenopausal) and 82 patients with postmenopausal osteoporosis. In the normal subjects there was the expected loss of cancellous bone with age, best shown by a reduction in bone surface/tissue volume, but no fall in cortical thickness with age despite a significant reduction in forearm bone density measured by single-photon absorptiometry. Bone surface/bone volume was about four times higher in cancellous than in cortical bone, and cancellous bone contributed about one-third of the total bone volume and about two-thirds of the bone surface when related to the core volume referent. In the osteoporotic patients, core width, an index of iliac bone thickness at the biopsy site, was reduced by 10%, but we could not determine whether this was the result of compaction of the core or of bone slenderness. All indices of bone volume, cortical as well as cancellous, were significantly smaller, as were the values for forearm bone densitometry; the relative deficits at different sites depended on whether they were expressed as percentages or as zeta scores. Bone surface/bone volume was increased in both cancellous and cortical bone, but bone surface/tissue volume was reduced in cancellous bone and increased in cortical bone. The proportions of total bone volume and surface contributed by cancellous and cortical bone were almost the same as in normal postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Difference in label length between demethylchlortetracycline and oxytetracycline: implications for the interpretation of bone histomorphometric data.

We measured the individual lengths of fluorescent labels on the three subdivisions of the endosteal envelope in iliac bone biopsy specimens produced by the administration of both oxytetracycline and demethylchlortetracycline. Fifty-one healthy subjects and 53 patients with postmenopausal osteoporosis were labeled in the stated order, and 8 osteopenic patients were labeled in the reverse order. Whatever the order of administration, the demethylchlortetracycline label was longer than the oxytetracycline label. We conclude: (1) the difference in label lengths reflects a difference between the two compounds in some intrinsic property, whether physical, chemical, or pharmacokinetic. (2) If the calculation of extent of mineralizing surface is based on the mean length of the two labels, a suitable correction should be applied to the shorter label; alternatively, the length of the longer label alone should be used. (3) Unlabeled osteoid not due to label escape probably results from slow terminal mineralization after cessation of matrix synthesis during which too few tetracycline molecules are incorporated to exceed the threshold for visible fluorescence, rather than from the temporary interruption of mineralization followed by its resumption.

Adult↗
PubMed1991

Hypophosphatemic rickets with hypocalciuria following long-term treatment with aluminum-containing antacid.

We present what we believe is the first case of rickets following prolonged treatment with aluminum containing antacids that bind phosphate, in an 18-year-old mentally retarded boy with cerebral palsy and spastic quadriplegia. As expected, serum calcitriol was increased and urinary phosphate excretion was very low. However, in contrast to all published cases of antacid induced hypophosphatemic osteomalacia in adults, despite a substantial increase in bone resorption reflected by urinary total hydroxyproline excretion, urinary calcium excretion was low rather than high, and significant hypocalcemia occurred after antacids were ceased and a phosphate salt administered. We suggest that the skeleton was so under-mineralized because of growth during prolonged phosphate deficiency, possibly augmented by anticonvulsant administration and immobilization, that increased bone resorption did not release enough calcium to cause hypercalciuria, or to prevent hypocalcemia during resumption of normal mineralization.

Adolescent↗
PubMed1991

The ambiguity of interstitial bone thickness: a new approach to the mechanism of trabecular thinning.

The assumption that a change in interstitial bone thickness reflects a converse change in resorption depth was recently found to be incorrect. Accordingly, we re-examined previously published data concerning trabecular thickness and wall thickness in 15 patients with nonosteomalacic osteopenia following intestinal bypass surgery for obesity. The average number of remodeling cycles completed since the operation was calculated according to two assumptions: First, that the measured activation frequency had been present since the operation; second, that activation frequency had increased in the first two years after operation because of secondary hyperparathyroidism. In comparison with mean wall thickness in 40 normal subjects (38.6 microns), resorption depth calculated in accordance with the first assumption was significantly increased (54.1 microns; p less than 0.001), but calculated in accordance with the second assumption was unchanged (42.1 microns; NS). Reasons are given for believing that the second assumption is more likely to be correct than the first. Mean trabecular thickness and mean wall thickness were significantly correlated (r = 0.68; p less than 0.005). We conclude: 1) Mean resorption depth cannot be inferred from interstitial bone thickness, but can be calculated if the number of remodeling cycles corresponding to the observed structural changes is known. 2) Even though interstitial bone thickness is reduced, trabecular thinning following intestinal bypass surgery is mainly due to decreased wall thickness, as the result of defects in the recruitment and/or function of osteoblasts. The same probably applies to cancellous osteopenia in various other gastrointestinal and hepatobiliary disorders. 3) The study of intestinal bone disease may shed light on the pathogenesis of other, more common, forms of osteoporosis.

Bone Density↗
PubMed1991

HLA-D antigens and Paget's disease of bone.

HLA-A, -B, -C, -DR, and -DQ antigens were determined in 25 Ashkenazi Jews with Paget's disease of bone. HLA-DR2 was more frequent in the Pagetic patients compared with 57 healthy controls of the same ethnic origin. This finding concurs with a previous report and raises the possibility that HLA-DR2 may be associated with Paget's disease of bone, probably by predisposing the bone cells to viral infection.

Female↗
PubMed1990

Zinc excretion in osteoporotic women.

The relation of zinc to the aging skeleton was investigated in 140 women aged 36-85 years, mostly postmenopausal, who attended the Jerusalem Osteoporosis Center. Osteoporosis was determined by lumbar spine radiograms (Smith index). Bone density (BD) of the distal radius was assessed by Compton spectroscopy and bone mineral content (BMC) at the same site by single-photon absorptiometry. Urine samples (24 h) were analyzed for zinc (UZn), hydroxyproline (UHP), calcium (UCa), magnesium (UMg), and phosphorus (UP) and expressed per gram creatinine. Patients with definite osteoporosis (n = 94) compared to subjects with borderline or no osteoporosis (n = 34) had a significantly higher mean age (67.4 versus 58.6 years), postmenopausal age (PMA, 19.9 versus 11.0), UZn (811 versus 581), UHP (23.5 versus 18.2), and UMg (90.4 versus 74.3). Urinary calcium UCa and phosphorus UP were similar in both groups. The bone mass measurements BD, BMC, and CI were lower in the osteoporotic group. Hyperzincuria (UZn above 800 micrograms/g creatinine) was found in 41 osteoporotic patients (45%) compared to 6 subjects in the control group (17%). In view of the positive correlation between UZn and age (r = 0.35, p = 0.001) and to eliminate the effect of age, a separate analysis was performed for 66 subjects under the age of 65 in whom the mean age was similar for the osteoporosis patients (n = 38) and control group (n = 28). Nevertheless, the osteoporosis patients still had a significantly higher mean UZn and UHP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Frequency distributions of tetracycline-based measurements: implications for the interpretation of bone formation indices in the absence of double-labeled surfaces.

The frequency distributions of mineral apposition rate (MAR) and mineralizing surface (MS), measured separately on the intracortical, endocortical, and cancellous surfaces in 46 normal subjects and 79 patients with postmenopausal osteoporosis, indicated that MAR has a finite lower limit of 0.3 mu/day (uncorrected for section obliquity) but that MS has no finite lower limit. We conclude that in the absence of labels MAR, and indices derived from it, must be treated as missing values, but that MS and indices with MS in the numerator should be allowed to take values of zero. To avoid infinite values for indices with MS in the denominator, we propose that osteoid mineralization rate (the reciprocal of mineralization lag time) and osteoblast vigor (the reciprocal of formation period) be used instead. For surfaces with genuine single labels (SL) but no double labels, we propose that MS is calculated as SL/2 and that for MAR either the lower limit of 0.3 or the mean measured value from other surfaces be used for calculating derived indices.

Adult↗
PubMed1989

Osteogenic response to marrow aspiration: increased serum osteocalcin and alkaline phosphatase in human bone marrow donors.

It has been shown recently in experimental animals that regeneration of bone marrow after ablation is associated with enhanced osteogenic growth factor activity and a systemic increase in bone formation. To assess the possible occurrence of a similar phenomenon in humans, serum markers of bone formation, osteocalcin and alkaline phosphatase, were measured in marrow donors before the aspiration of large amounts of iliac marrow and 1 day to 5 weeks thereafter. Both osteocalcin and alkaline phosphatase showed significant increases, with peak values 1-3 and 2-4 weeks postaspiration, respectively. The absolute maximal increase in osteocalcin was significantly higher in adolescent and child donors than in adults. When evaluated together with studies on systemic changes during fracture healing and marrow regeneration, these findings suggest that marrow aspiration in humans evokes a systemic osteogenic response.

Adolescent↗