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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The etiology of diabetic osteopenia has not been established. The value of serum osteocalcin (BGP) as a marker of the bone abnormalities and the possible role of the polyol pathway in diabetic osteopenia were investigated. Three groups of rats were studied over 7 weeks: group D (n = 12), rats with streptozotocin (55 mg/kg)-induced diabetes given saline by gavage; group DS (n = 12), rats with streptozotocin-induced diabetes given the aldose reductase inhibitor sorbinil (25 mg/kg) daily by gavage; and group C (n = 6), saline-injected controls. Circulating levels of ionized calcium, BGP, amino-terminal PTH, and glucose were measured on days 0, 7, 14, 28, and 49. Tibial bone specimens were examined for the presence of aldose reductase by immunocytochemistry and by histomorphometry after tetracycline labeling. Diabetic rats with or without sorbinil treatment failed to gain weight [group D, 234 +/- 26 g; group DS, 217.0 +/- 40 g; group C, 310 +/- 33 g (mean +/- SD)]. Serum BGP levels decreased significantly in the diabetic rats within 7 days and remained lower throughout the study. BGP values on day 7 were: group D, 47.7 +/- 4.9 ng/ml; group DS, 65.9 +/- 5.5 ng/ml; and group C, 90.4 +/- 4 ng/ml (mean +/- SEM). Serum PTH levels were similar in all groups, except for day 49, when an increase in the D group was observed. Bone histomorphometry showed decreased bone remodeling in the D group, which confirmed the serum BGP findings. Aldose reductase was detectable in the small blood vessels and in bone itself. Sorbinil failed to influence the biochemical or bone histomorphometric abnormalities associated with diabetes. Serum BGP may be a valuable marker for the decreased bone remodeling in insulinopenic diabetes.
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PMID:Bone mineral metabolism in experimental diabetes mellitus: osteocalcin as a measure of bone remodeling. 313 94

Forty-eight chronic hemodialysis patients were divided comparably into two groups (24 patients in each). Two micrograms of 1 alpha(OH)D3 was administered to one group for 3 months and its placebo to the other group. In the 1 alpha(OH)D3-treated group, serum total calcium increased from 7.82 +/- 0.11 (mean +/- SEM) to 9.70 +/- 0.27 mg/dl (p less than 0.001) which was significantly higher (p less than 0.001) than control values of 8.86 +/- 0.06 mg/dl from normal volunteers. Systolic, diastolic and mean blood pressures, however, did not change significantly throughout the study. Even in the 9 patients who had a substantial increment of serum calcium of more than 2 mg/dl with hypercalcemia (greater than 10 mg/dl) at 3 months, no significant changes in blood pressure were found. Serum iPTH decreased from 2.83 +/- 0.28 to 0.98 +/- 0.23 ng/ml (p less than 0.001) at 3 months of treatment. Furthermore, a significant inverse correlation was obtained between the changes in serum calcium and iPTH. In the placebo group there were no significant changes in serum calcium, iPTH and blood pressure during the 3-month treatment period. The present study indicates that a substantial increase in serum calcium or a chronic hypercalcemia induced by 1 alpha(OH)D3 treatment in maintenance hemodialysis patients does not accompany a rise in blood pressure, probably due to a concomitant suppression of PTH. The results also suggest that the hypocalcemic state found in hemodialysis patients is not associated with any significant change in blood pressure. The importance of PTH in blood pressure regulation was discussed.
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PMID:Does 1 alpha(OH)D3 treatment affect blood pressure levels in maintenance hemodialysis patients? 321 60

In order to evaluate the role of calcium regulating hormones in the pathogenesis of mitral ring calcification, we have studied the serum levels of PTH and vitamin D metabolites in aged females both with and without mitral ring calcification (MRC). In the patients with MRC (n = 17), significantly lower levels of serum total protein (6.6 +/- 0.2 in the MRC group vs 7.1 +/- 0.1 g/dl in the control group, mean +/- SEM), BUN (15.7 +/- 0.9 vs 18.3 +/- 0.9 mg/dl), creatinine (0.7 +/- 0.02 vs 0.9 +/- 0.02 mg/dl) and calcium (8.4 +/- 0.1 vs 9.2 +/- 0.1 mg/ml) were observed as compared with those in the controls (n = 32). Significantly higher PTH levels (0.57 +/- 0.07 vs 0.38 +/- 0.04 ng/ml) were found in the MRC group. Levels of all three vitamin D metabolites in the MRC group were significantly lower than those in the control group (25-OHD; 11.2 +/- 1.4 vs 19.6 +/- 1.2 ng/ml, 24,25(OH)2D; 0.7 +/- 0.1 vs 1.3 +/- 0.1 ng/ml and 1,25(OH)2D; 12.5 +/- 2.4 vs 43.0 +/- 3.5 pg/ml). The correlation coefficient between PTH and 1,25(OH) 2D was -0.382(n = 49, p less than 0.01). Thus, the significantly higher PTH levels in the MRC group might result in hypovitaminosis D. In conclusion, evidence of hypovitaminosis D in the patients with mitral ring calcification was demonstrated.
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PMID:Evidence of hypovitaminosis D in patients with mitral ring calcification. 324 33

Administration of the antifungal drug ketoconazole reduces serum 1,25-dihydroxyvitamin D (1,25-D) levels in normal subjects. To determine whether a similar effect occurs in hypercalcemic patients, ketoconazole (200 mg every 8 h for 7 days) was given to nine patients with confirmed primary hyperparathyroidism, three patients with probable primary hyperparathyroidism who were awaiting surgery, and three patients with mild hypercalcemia of uncertain etiology who were being followed. Ketoconazole administration led to a significant reduction in mean serum 1,25-D levels in the hypercalcemic patients [basal, 64 +/- 7 (+/- SEM) pg/mL (154 +/- 17 pmol/L) vs. 36 +/- 5 pg/mL (86 +/- 12 pmol/L) after ketoconazole; P less than 0.001]. Serum total calcium fell slightly but significantly [basal, 11.05 +/- 0.17 mg/dL (2.76 +/- 0.04 mmol/L) vs. 10.77 +/- 0.16 (2.69 +/- 0.04 mmol/L) after ketoconazole; P less than 0.02], but the falls in total serum calcium and serum 1,25-D after ketoconazole treatment were not correlated with one another. Ketoconazole administration did not alter serum ionized calcium, 25-hydroxyvitamin D, phosphate, alkaline phosphatase, or PTH concentrations or urinary cAMP excretion. The responses to ketoconazole were similar in all three patient subgroups. We conclude that short term administration of ketoconazole to hypercalcemic patients causes a substantial fall in serum 1,25-D and a small fall in total serum calcium. These effects render ketoconazole a potentially useful agent for investigation of the importance of 1,25-D in patients with hypercalcemic disorders and for their treatment.
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PMID:Ketoconazole-induced reduction in serum 1,25-dihydroxyvitamin D and total serum calcium in hypercalcemic patients. 336 Sep 1

Amino-hydroxypropylidene bisphosphonic acid (AHPrBP, previously APD) is a potent inhibitor of bone resorption. Since it remains in bone for a long time, and since it was not found to impair bone mineralization, it could be administered at high dose over a short period of time. Therefore, 11 patients with symptomatic Paget's disease received AHPrBP orally at 1200 mg/day over 5 consecutive days. Controls were performed after 1 month in all patients, 6 months in 8 patients, and one year in 4 patients. Clinical improvement and biochemical remission was observed in all patients, except one with severe disease. Side effects were negligible. Disease activity at bone scintigram decreased over 6 months. Plasma alkaline phosphatase activity fell progressively and significantly from 210 +/- 26 U/l (means +/- SEM) to 103 +/- 10 U/l after 6 months (nl less than 120 U/l). Urinary excretion of hydroxyproline decreased immediately and became normal (nl less than 2.3 mumol/lGF) as a mean at day 5 (from 4.6 +/- 0.4 mumol/lGF to 2.1 +/- 0.3 mumol/lGF). Thereafter it remained within the normal range (2.0 +/- 0.2 mumol/l at day 180). Plasma calcium and phosphate concentrations fell transiently between day 4 and 15, whereas plasma PTH levels increased over this period of time. In conclusion, a short course of AHPrBP given per os at high dose induces a rapid decline in activity and remission of moderate Paget's disease, without significant side effects.
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PMID:Paget's disease of bone treated in five days with AHPrBP (APD) per Os. 345 56

The bone histology in patients with chronic renal failure and aluminum-related bone disease does not always show the excess accumulation of unmineralized osteoid (matrix) characteristic of osteomalacia. Frequently, bone aluminum accumulation is associated with normal or reduced amounts of unmineralized osteoid and low bone formation and is referred to as aplastic bone disease. In this study, we compared static and dynamic bone histomorphometric parameters and plasma PTH and aluminum levels in 12 patients with osteomalacia and 18 patients with aplastic bone disease who had been receiving dialysis for the same duration to determine if the difference in osteoid accumulation in these 2 lesions might be explained by differences in aluminum accumulation or PTH levels. The stainable bone surface aluminum level was significantly higher in the patients with osteomalacia compared to that in the group with aplastic bone [61 +/- 5% (+/- SEM) vs. 43 +/- 4%; P less than 0.02]. The rates of bone apposition and bone formation were lower in the group with osteomalacia (P less than 0.01). Plasma amino-terminal PTH was not significantly different in the 2 groups. The increment in plasma aluminum levels after a single infusion of deferoxamine was higher in the osteomalacic group than in the aplastic group, suggesting that the patients with osteomalacia accumulated more total body chelatable aluminum than did those with aplastic bone disease during a comparable length of time on dialysis. We conclude that the excess unmineralized osteoid in aluminum-related osteomalacia results from the high rate of total body aluminum accumulation, which directly causes uncoupling of matrix mineralization and matrix production, independent of PTH levels. Patients with aplastic bone disease who have accumulated lesser amounts of total body aluminum fail to develop excess unmineralized osteoid because production and mineralization of matrix are more closely coupled than in the osteomalacic lesion, despite a decline in osteoblast numbers.
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PMID:Osteomalacia and aplastic bone disease in aluminum-related osteodystrophy. 358 92

This paper highlights some observations made by the authors in SEM studies of hard tissue resorption and considers their significance in relation to current concepts. All mammalian mineralised tissues may undergo physiological resorption, the resulting surface reflecting the density of mineralisation and the organic matrix chemistry, organisation and orientation. Resorption-repair coupling may follow the resorption of any tissue, but SEM studies first noted this process in the case of the dental tissues. The difference between fetal and adult bone formation and resorption provided evidence against the concept of osteocytic osteolysis. SEM stereophotogrammetric methods for the quantitation of individual resorption lacunae are now much quicker and have been extended to the study of in vitro resorption by mammalian and avian osteoclasts isolated from bone and seeded into new substrates. Experimental studies using SEM were first conducted on the osteotropic hormonal effects on bones forming in vivo and extended to the in vitro situation. The effects observed underlined the several actions of PTH on osteoblasts and indicated their important role in the control of bone resorption. Immunological marking techniques monitored by SEM first established that osteoclasts had no Fc or C3 receptors, although other cells in the vicinity did. The study of osteoclasts resorbing substrates other than bone in vitro has increased our understanding of the essential components of a resorbable substrate. Experiments growing separated bone cells and marrow cells on calcified substrates have shown that such cells will continue to resorb for at least six weeks.
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PMID:Early scanning electron microscopic studies of hard tissue resorption: their relation to current concepts reviewed. 358 11

The antimycotic agent ketoconazole is known to inhibit several cytochrome P450-dependent enzymes involved in the biosynthesis of steroid hormones from cholesterol. Since 1,25-dihydroxyvitamin D is also a sterol synthesized by cytochrome P450-dependent enzymes, we assessed whether ketoconazole would lower serum 1,25-dihydroxyvitamin D levels. In nine normal men, administration of ketoconazole for 1 week in doses of 300-1200 mg/day led to a dose-dependent reduction in serum 1,25-dihydroxyvitamin D levels (r = -0.64; P less than 0.001). At the highest dose taken by each man (1200 mg/day in six, 900 mg/day in one, and 600 mg/day in two), serum levels of 1,25-dihydroxyvitamin D fell significantly compared to baseline [14 +/- 1 (+/- SEM) vs. 39 +/- 3 pg/ml; P less than 0.001), but there was no change in serum levels of 25-hydroxyvitamin D, PTH, calcium, phosphate, or alkaline phosphatase. Ketoconazole may be potentially useful in exploring the pathogenetic role of 1,25-dihydroxyvitamin D in disorders of calcium metabolism and in treatment of patients with hypercalcemic disorders or renal stone disease.
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PMID:Ketoconazole-induced reduction in serum 1,25-dihydroxyvitamin D. 375 45

In the course of characterizing monoclonal antibodies (MAbs) recognizing cell surface antigens on dispersed human parathyroid cells (dPTCs), we identified one MAb (4F2) that bound avidly to parathyroid cells and had marked effects on parathyroid function. The binding of MAb 4F2 to human adenomatous dPTCs resulted in a marked [53.8 +/- 7.9% (+/- SEM)] reduction in low calcium (Ca)-stimulated PTH secretion to levels equivalent to those in cell suppressed by high extracellular Ca (1.5 mM). Typically, these functional effects were optimal at antibody dilutions of 1:10(4) to 1:10(5). Cell viability was confirmed at the conclusion of each experiment by trypan blue exclusion (greater than 90-95%) and cell surface immunofluorescence. Parallel studies using the Ca-sensitive dye Quin-2 showed that inhibition of PTH secretion in 4F2-treated cells was associated with a concomitant increase in cytosolic Ca (Cai) of 188% in 0.5 mM Ca; these values also approached Cai levels in control cells incubated in high Ca. Mab controls, P3 X 63, which do not bind to dPTCs, and Mab LC7-2, which recognizes a different epitope of the same antigen as 4F2 on dPTCs, did not alter PTH secretion or Cai. Immunoprecipitation of 125I-labeled parathyroid cell extracts with MAb 4F2 demonstrated proteins with mol wt of approximately 145, 85, and 45 under nonreducing conditions and 85 and 45 kilodaltons after reduction with 5% mercaptoethanol. These studies suggest that 1) Mab-4F2 binding to its cell surface antigen inhibits PTH secretion by human adenomatous parathyroid cells in vitro; 2) the alterations in secretory function could be related to by an attendant increase in Cai; 3) the 4F2 antigen on dPTCs is a heterodimeric protein of (approximately) 85K and 45K; and 4) the 4F2 antigen may be an important component of the Ca-sensing and/or signal-transducing mechanism in this cell.
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PMID:Binding of monoclonal antibody (4F2) to its cell surface antigen on dispersed adenomatous parathyroid cells raises cytosolic calcium and inhibits parathyroid hormone secretion. 378 35

Patients with acromegaly have alterations in mineral metabolism. To determine the effect of correction of excess GH secretion on calcium metabolism, we studied 12 acromegalic patients before and 3-4 weeks after pituitary adenomectomy. Treatment of acromegaly resulted in significant decreases in both serum calcium [from 9.3 +/- 0.2 to 8.7 +/- 0.1 mg/dl (mean +/- SEM); P less than 0.01] and urinary calcium excretion (from 200 +/- 24 to 88 +/- 12 mg/24 h; P less than 0.0002). Serum phosphate also decreased significantly (P less than 0.01) from 4.8 +/- 0.2 to 4.3 +/- 0.2 mg/dl. Both serum immunoreactive PTH and calcitonin levels were normal initially and did not change after surgery. The mean serum 25-hydroxyvitamin D (25OHD) level was significantly (P less than 0.01) lower and the 1,25-dihydroxyvitamin D [1,25-(OH)2D] level was significantly (P less than 0.0001) higher in acromegaly compared with measurements in 25 normal subjects. After surgery, the serum 25OHD level did not change; however, the serum 1,25-(OH)2D concentration fell significantly (P less than 0.0001) from 60 +/- 4 to 43 +/- 2 pg/ml. A positive correlation was found between the decrements in urinary calcium excretion and the serum 1,25-(OH)2D level when the comparison was made between the decrements as percentages of pretreatment values (r = 0.64; P less than 0.05). The accumulated data suggest that the hypercalciuria in acromegaly might be due to intestinal calcium hyperabsorption, which could be attributed to the elevated circulating 1,25-(OH)2D level. Excessive GH secretion might stimulate the production of 1,25-(OH)2D and might also directly stimulate calcium absorption.
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PMID:Changes in calcium homeostasis in acromegaly treated by pituitary adenomectomy. 383


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