Effect of sodium etidronate and phenytoin of Pagetic bone.
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Aged↗
Biomedical subjects
L V Avioli
Publications and source records attributed to L V Avioli.
Alkaline phosphatase activity in chronic streptozotocin-induced insulin deficiency in the rat: effect of insulin replacement.
Alterations in circulating alkaline phosphatase have been described in both man and the experimental animal with chronic insulin deficiency. We evaluated plasma and tissue alkaline phosphatase levels in freely-fed control, streptozotocin-induced diabetic and insulin-treated diabetic rats, seven weeks after the induction of diabetes. Circulating alkaline phosphatase activity was markedly elevated in the insulin deficient animal (p less than 0.001) and completely normalized following insulin administration. The elevated plasma alkaline phosphatase activity observed in the insulin deficient animals was heat-resistant and phenylalanine-sensitive, a pattern typical of the intestinal isoenzyme. Small intestinal alkaline phosphatase activity was significantly higher (p less than 0.01) in the diabetic animals, but comparable in the insulin-replaced and control rats. The intestinal isoenzyme activity was found to be strikingly insulin-sensitive; withholding insulin therapy for 36 hr prior to sacrifice resulted in an abrupt rise in both plasma and intestinal alkaline phosphatase values comparable to those observed in the insulin-deficient state. In contrast to these observations, skeletal alkaline phosphatase activity was decreased in the insulin deficient animal (p less than 0.01) and this abnormality was corrected by insulin replacement. Neither insulin deficiency nor insulin replacement resulted in any significant changes in the hepatic alkaline phosphatase isoenzyme.
Alkaline Phosphatase↗
Correction of abnormal bone and mineral metabolism in chronic streptozotocin-induced diabetes mellitus in the rat by insulin therapy.
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Animals↗
Isolated skeletal involvement in Cushing's syndrome: response to therapy.
A 38-yr-old male presented with severe symptomatic osteopenia secondary to adrenal hyperfunction without any clinical expression of Cushing's syndrome. The predominantly axial distribution of his osteopenia and the presence of rib fractures healing with abundant callus formation, despite insignificant elevations in serum alkaline phosphatase, were characteristic of glucocorticoid excess syndromes. The histological features of the pretreatment bone biopsy were typical of those associated with excess glucocorticoids, namely decreased quantities of nonmineralized bone matrix, reflecting sites of bone formation, and an increase in the number of osteoclasts, indicating enhanced bone resorption. Six weeks after adrenalectomy, repeat bone biopsy revealed a marked increase in bone matrix synthesis and a significant decrease in bone resorption. These observations suggest that stimulators of skeletal turnover, like sodium fluoride, may be inappropriate in the initial treatment of steroid-induced osteopenia after surgical cure and that vitamin D and calcium therapy offers a more rational approach. Furthermore, the importance of the routine evaluation of adrenal function in any patient presenting with osteopenia is stressed, as well as the fact that relatively isolated skeletal involvement, classically described in micronodular adrenal disease, is not necessarily peculiar to a specific subset of the syndrome but may potentially attend any cause of glucocorticoid excess.
Adrenal Cortex Function Tests↗
Alterations in circulating vitamin D metabolites in the young insulin-dependent diabetic.
To assess the relationship between the decreased bone mass observed in young insulin-requiring diabetic patients and vitamin D metabolism, we measured serum 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D concentration in 45 white, insulin-dependent diabetic subjects, 7-18 yr of age. Metacarpal cortical thickness in 87% of these diabetics was below the mean for their respective ages, while 16% had a cortical thickness value greater than 2 sDs below the mean. Serum calcium and phosphate concentrations were normal, immunoreactive parathyroid hormone was in the low normal range, and total serum alkaline phosphatase was elevated compared to age- and sex-matched controls. Circulating 24,25-dihydroxyvitamin D concentrations were significantly elevated, and 1,25-dihydroxyvitamin D was significantly decreased. The increase in 24,25-dihydroxyvitamin D was greater in the diabetics with the most severe bone loss and was maximally increased during the first 5 yr of clinical diabetes. No apparent correlation was seen between metabolic control, as measured by hemoglobin A1C and urine and plasma glucose, and the circulating levels of the vitamin D metabolites. Despite appropriate insulin replacement, alterations in vitamin D metabolism occur in the young insulin-dependent diabetic and could relate to the decrease in cortical bone mass observed in these patients.
24,25-Dihydroxyvitamin D 3↗
1,25-dihydroxyvitamin D in male, nonspawning female, and spawning female trout.
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Animals↗
The effect of streptozotocin-induced chronic diabetes mellitus on bone and mineral homeostasis in the rat.
Diabetes mellitus was induced in Lewis rats by streptozotocin, and these animals and control rats fed ad lib were studied after 7 weeks. At the time of sacrifice, nondecalcified histological sections of bone were prepared and subsequently quantitated by micromorphometric techniques. In addition, tibial alkaline phosphatase and mineral ash content were determined. The bones obtained from the diabetic animals are characterized by significant decrements in the quantities of osteoid and osteoclasts and by failure to acquire a tetracycline label. These histological features are attended by reduced quantities of urinary hydroxyproline and tibial alkaline phosphatase. As compared with control animals fed ad lib, diabetic rats are hyperphosphatemic and markedly hypercalciuric. Circulating alkaline phosphatase is also elevated and associated with a parallel increase in intestinal content of this enzyme. Although serum corticosterone levels are increased, diabetes is associated with decrements in both circulating immunoreactive parathyroid hormone and 1,25(OH)2D. We conclude that prolonged streptozotocin-induced diabetes mellitus in the rat results in reduced bone turnover. The relative roles that functional caloric deprivation, low circulating levels of 1,25(OH)2D, hypercalciuria, hypercortisolemia, and decreased blood parathyroid hormone levels play in the genesis of these skeletal abnormalities remain to be determined.
Alkaline Phosphatase↗
Hormonal regulation of mineral metabolism.
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Animals↗
Postmenopausal osteoporosis: prevention versus cure.
Vertebral and femoral neck fracture syndromes and their attendant morbidity still continue to plague the lives of many postmenopausal women. The osteopenia that characterizes the "vertebral collapse" or "hip fracture" syndromes results from the gradual and progressive loss of bone mass the begins early in the fourth decade of life in all individuals and proceeds at an accentuated rate in the female population. A unified hypothesis that effectively explains the pathogenesis of the fracture-prone osteopenia state is still nonexistent, although sedentary life styles, genetic predisposition, hormonal imbalance, vitamin deficiencies, high-protein diets, and cigarette smoking have all been implicated in this regard. One of the most consistent observations, which cannot be ignored, is the inadequate calcium intake of women in the second and third decade of life and the negative calcium balance that characterizes the perimenopausal state. Nutritional adequacy with respect to this most essential skeletal ingredient is considered most appropriate not only in any proposed therapeutic regimen for postmenopausal osteopenic females, but also in the young, active, menstruating female.
Adult↗
The control of phosphate uptake by the isolated renal tubule.
An in vitro isolated tubular model is presented which appears to have many characteristics of an active transport system in that Pi accumulation by the preparation is sodium- and temperature-dependent, stimulated by PTH and cAMP and is also conditioned by the metabolic integrity of the tissue. The relationship between the observations made in the dispersed convolutal tubule preparation in the present study and the mechanisms by which PTH affects phosphate transport in isolated perfused tubules and in vivo has not yet been ascertained.
Animals↗
Streptozotocin and bone resorption in vitro.
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Animals↗
Osteopetrosis, renal tubular acidosis and basal ganglia calcification in three sisters.
Three adult sisters with osteopetrosis in infancy had spontaneous resolution of bone modeling defects and osteosclerosis. During adolescence, basal ganglia calcification developed in two. Renal tubular acidosis (type I) was diagnosed in each during early adulthood. The disorder was transmitted apparently as a recessive trait--the same mode of inheritance as for the "malignant" form of osteopetrosis which is usually fatal during childhood. Electron microscopy of bone suggested that osteoclasts failed to form "ruffled membranes" characteristic of active bone resorbing cells. Chronic systemic acidosis may have ameliorated the skeletal manifestations of this new syndrome.
Acidosis, Renal Tubular↗
Effect of alcohol ingestion on bone and mineral metabolism in rats.
Chronic ethanol administration to growing rats for 56 days resulted in circulating levels of 140 mg/dl, approximating concentrations that characterize alcoholic intoxication in man. This degree of alcohol ingestion, although without gross or histological effect on the liver or testicles, was attended by decreased trabecular bone volume despite a normal rate of skeletal mineralization as measured by time-spaced tetracycline labeling. Concomitant serum levels of calcium, phosphate, magnesium, creatinine, glutamic oxalacetic transaminase, alkaline phosphatase, testosterone, and 25-hydroxyvitamin D were normal. Although alcohol treatment was associated with a significant decrease in urinary calcium excretion, it had no effect on phosphate excretion nor on its renal tubular reabsorption. The data reveal that circulating levels of alcohol that do not result in hepatic or testicular injury are toxic for bone.
Alcohol Drinking↗
Effects of semistarvation on skeletal homeostasis.
Rats were semistarved over a 7-week period, resulting in a loss of 28.2 +/- 1.6% (SEM) of their initial body weights, while ad libitum fed controls gained 15.1 +/- 1.8% (SEM). Bone loss occurred and skeletal turnover was markedly reduced in the semistarved rats, as evidenced by a paucity of osteoid and osteoclasts, failure of the bone to assume a tetracycline label, and reduced urinary hydroxyproline excretion. Despite these changes, there were no alterations of serum or bone alkaline phosphatase activity with semistarvation, and analysis of tibial mineral content revealed reductions only in magnesium and sodium. The malnourished animals, however, were hypercalciuric and hypophosphatemic. Semistarvation had no effect on circulating levels of immunoreactive parathyroid hormone or 25-hydroxyvitamin D, but did result in reduced serum levels of corticosterone, insulin, and 1,25-dihydroxyvitamin D. Therefore, it appears that the effects of semistarvation on the rat skeleton are osteoporotic rather than osteomalacic, and that the defect is the consequence of reduced bone turnover. The contribution which the abnormalities of bone-regulating hormones play in the genesis of this skeletal lesion remains to be determined.
Animals↗
Effect of the menstrual cycle on calcium-regulating hormones in the normal young woman.
To examine the effect of estrogens on circulating levels of calcium-regulating hormones, total serum calcium, ionized calcium, inorganic phosphate, immunoreactive parathyroid hormone, calcitonin, 1,25-dihydroxyvitamin D, and estradiol (E2) levels were assayed on menstrual cycle days 3 and 13 in 12 healthy young women. Despite a 3-fold increase in serum E2 levels by midcycle, no differences in the other factors were observed. Furthermore, iv infusion of calcium (3 mg/kg over a 10-min period) produced similar changes in the serum levels of immunoreactive parathyroid hormone and calcitonin on days 3 and 13 in 8 women. Our findings suggest that in normal menstruating women, endogenous increases in E2 neither directly nor indirectly stimulate 1,25-dihydroxyvitamin D production, nor do they affect circulating levels of the hormones known to influence calcium homeostasis in man.
Adult↗
Phosphate accumulation by the isolated renal tubule and the effects of parathyroid hormone and cyclic adenosine monophosphate.
The effects of metabolic and transport inhibitors and PTH, cAMP, db-cAMP, and theophylline on Pi uptake by an isolated rat renal tubular preparation has been investigated. Pi uptake by this preparation was a saturable process, was O2- and sodium-dependent, was inactivated by heat=treatment, and was inhibited by dinitrophenol. iodacetate, ouabain, and a decrease in temperature from 37 degrees to 4 degrees C. PTH and cAMP stimulated Pi uptake by energy-dependent and ouabain-inhibitable mechanisms.
Animals↗
Dog intestinal mucosa contains two vitamin D-stimulating calcium binding proteins.
Dog intestinal mucosa has been found to contain more than one vitamin D-responsive calcium-binding protein (CaBP). Duodenal and upper jejunal mucosa contains a protein that has a mol wt of 19,000 and a Kd of 1.2 microM, and that increases in activity over twofold after administration of 1,25 (OH)2 vitamin D3. This protein could not be demonstrated in ileal tissue. In ileal mucosa all the calcium binding activity resides in fractions that elute from Sephadex G200 with a mol wt of about 57,000. Calcium-binding activity was demonstrated in gel electrophoresis corresponding to a protein with an Rf of about 0.5, unlike the small CaBP, which has an Rf of 1.0. The calcium-binding activity from the ileum was demonstrated to coincide with a protein band on acrylamide gel electrophoresis, and to be destroyed by pronase. This large CaBP responded to 1,25 (OH02 vitamin D3 by increasing activity by about 50%, and was inhibited similarly to the small protein by Sr, Ba, and Mg. Neither fresh tissue homogenates, nor explants cultured up to 20 hr showed any evidence of the small CaBP on disc gel acrylamide electrophoresis. The small CaBP could be demonstrated on gel electrophoresis only in tissue that was partially autolyzed or was treated with a 10% (milligrams per milligram) solution of trypsin. The small CaBP was relatively resistant to trypsin. It is suggested that the small CaBP may be derived at least in part from the large protein.
Animals↗
Parathyroid hormone and the kidney in pseudohypoparathyroidism.
Although a relationship between parathyroid hormone, urinary cyclic AMP and phosphate excretion has been established, the exact molecular sequence which characterizes this cascade is still ambiguous. Consequently, the pathogenesis of inherited forms of hypocalcemia with defective renal responsivity to parathyroid hormone is still conjectural.
Adenylyl Cyclases↗