Acquired osteomalacia.
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Acidosis, Renal Tubular↗
Biomedical subjects
N H Bell
Publications and source records attributed to N H Bell.
Prostaglandin E2 administered by subcutaneous pellets causes local inflammation and systemic bone loss: a model for inflammation-induced bone disease.
The effects of prostaglandin E2 (PGE2) given in controlled-release pellets or by daily sc injection for 21 days on mineral homeostasis and bone histomorphometry were compared in 7-week-old female rats. Sham operation and ovariectomy were performed at the beginning of the studies. In experiment 1, 7.5 mg PGE2 or drug-free, controlled-release pellets were implanted sc at the back of the neck on day 7. In experiment 2, 3 mg/kg body weight of PGE2 or vehicle was injected sc daily beginning on day 7. The animals were sacrificed on day 28 of the two experiments, and the tibiae were removed for histomorphometric analysis of the diaphysis and metaphysis. When administered by pellets in experiment 1, PGE2 lowered serum 1,25-dihydroxyvitamin D and did not influence weight gain, serum calcium, phosphorus, or magnesium, cross-sectional or medullary areas, periosteal bone formation and apposition rates, endosteal bone formation and apposition rates, or endosteal tetracycline-labeled perimeter. PGE2 lowered cancellous bone area and cancellous bone perimeter in both the sham-operated and ovariectomized rats. In contrast, when administered by sc injection in experiment 2, PGE2 reduced weight gain, increased serum magnesium, increased cortical area, and reduced medullary area without changing cross-sectional area, increased periosteal bone formation and apposition rates and endosteal bone and apposition rates, did not alter endosteal tetracycline-labeled perimeter, and increased cancellous bone area and cancellous bone perimeter in both sham-operated and ovariectomized animals. PGE2 produced local inflammation when given by pellets, and the serum concentration of 13,14-dihydro-15-ketoprostaglandin E2, the major metabolite of PGE2, increased when PGE2 was given by sc injection but not when administered by pellets. Thus, PGE2 given sc by controlled-release pellets (1) produces local inflammation and systemic bone loss without increasing PGE2 systemically and (2) provides a model for inflammation-induced loss of cancellous bone. The results also indicate that the pellet is not a valid means for the delivery of PGE2 to the general circulation.
Analysis of Variance↗
Demonstration of a difference in urinary calcium, not calcium absorption, in black and white adolescents.
Bone mineral density (BMD) of the forearm, lumbar spine, and femoral neck is greater in black than in white children. Studies were performed to determine whether differences in intestinal absorption of calcium or urinary calcium or both account for an assumed more positive calcium balance and greater bone mass in black children. Normal black and white boys and girls were admitted to a metabolic ward and given a constant daily diet containing 1000 mg calcium, 60% as calcium carbonate, for 2 1/2 days (study I) or 3 1/2 days (study II). Fasting blood and 24 h urine collections were obtained, and in study II, unidirectional fractional absorption of calcium (alpha) was determined with stable isotopes of calcium. It was found that (1) serum 25-hydroxyvitamin D (25-OHD) and urinary calcium were lower and serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] was higher in black than in white children, and (2) alpha was higher in boys than in girls with no racial difference, and (3) there were significant positive correlations between alpha and urinary calcium in the blacks and in the black and white children together. It is concluded that (1) alpha is higher in boys than in girls and (2) a lower urinary calcium, not increased intestinal absorption of calcium, is the means for a more positive calcium balance in blacks that accounts for the racial difference in BMD.
Absorption↗
Increased calcium intake does not suppress circulating 1,25-dihydroxyvitamin D in normocalcemic patients with sarcoidosis.
Ca absorption is regulated by 1,25(OH)2D, and serum values vary inversely with Ca intake. In sarcoidosis, 1,25(OH)2D is produced by alveolar macrophages in response to gamma-interferon, and patients may develop hypercalcemia after prolonged exposure to sunlight and increased dermal production of vitamin D3. To determine if increased Ca intake suppresses serum 1,25(OH)2D in normocalcemic patients and to identify those at risk, 17 normal subjects and 11 patients were studied on a metabolic ward for two and one-half days while receiving first 400 and then 1,000 mg/d of Ca. On the low Ca intake, serum angiotensin-converting enzyme (ACE), an index of disease activity, was higher in only three of the patients than in the controls, mean serum 1,25(OH)2D was higher in the patients, and mean serum total Ca, serum Ca++, and urinary Ca were not different in the two groups. On the higher Ca intake, mean urinary Ca increased in both groups, but mean serum 1,25(OH)2D was suppressed only in the normal subjects. Thus, 1,25(OH)2D production is abnormally regulated, indicating that (a) normocalcemic patients with sarcoidosis are at risk for developing abnormal Ca metabolism, and (b) a better index of disease activity is provided by the oral Ca suppression test than by serum ACE.
Adult↗
Evidence that estrogen binding sites are present in bone cells and mediate medullary bone formation in Japanese quail.
Studies were carried out in Japanese quail to characterize the binding of estrogen to bone cells and to determine whether induction of medullary bone by estrogen is mediated by estrogen receptors. First, attempts were made to identify specific, high affinity nuclear binding sites for estrogen with a nuclear exchange assay in oviduct and femora from laying female quail and in liver, kidney, and femora from adult male quail treated with estradiol valerate (2 mg per bird). High-affinity nuclear estrogen binding sites were detected in each of the tissues except femora. Second, estrogen binding sites in femora from male quail were localized by radioautography after treatment with 100 microCi of [3H]-17 beta-estradiol ([3H]-E). Estrogen binding sites were present at 1 and 3 h after administration of [3H]-E, and binding of the radiolabeled hormone was prevented by the simultaneous administration of an excess of radioinert estrogen. Third, estradiol valerate (.4 mg) was given as a bolus to adult male Japanese quail. Five days later, the quail had hypercalcemia due to accumulation of phosvitin in serum, had an extensive network of medullary bone at the femur midshaft, and had reduced cortical bone area. The nonsteroidal, anti-estrogen tamoxifen (2 mg/day) prevented estrogen-induced hypercalcemia, medullary bone formation, and reduction of cortical bone area. Fourth, the estrogen target cells in femora from adult male quail that were induced to differentiate to osteoblasts by estrogen treatment were located by [3H]-proline radioautography as early as 12 h following administration of the hormone. These results are interpreted as evidence that induction of medullary bone is a process mediated by estrogen receptor.
Animals↗
Ovariectomy selectively reduces the concentration of transforming growth factor beta in rat bone: implications for estrogen deficiency-associated bone loss.
Previous work showed that production of transforming growth factor beta (TGF-beta) by osteoblast-like rat UMR 106 cells was increased by 17 beta-estradiol at physiological concentrations. To determine whether ovariectomy alters the concentration of TGF-beta in rat long bones, female Sprague-Dawley rats were either sham-operated (n = 19) or ovariectomized (n = 19), pair-fed a semisynthetic diet for 6 weeks, and sacrificed. Tibial and femoral diaphyses were removed and extracted by demineralization. Ovariectomy lowered serum estrogen; did not alter body weight, serum magnesium, or serum 1,25-dihydroxyvitamin D; and produced only modest differences in serum calcium and phosphate concentrations. Hydroxyproline was higher and extractable protein was lower in bones from ovariectomized rats than in bones from sham-operated rats; calcium content did not differ between the two groups of animals. Ovariectomy lowered the concentration of TGF-beta in bone but did not change the concentration of insulin-like growth factors I or II compared with values in bone from control animals. The reduction of bone TGF-beta was evident 6 weeks after surgery but not at 3 weeks. Treatment of ovariectomized rats with estrogen eliminated the TGF-beta deficit. To determine whether 17 beta-estradiol increased TGF-beta production by normal bone cells, mouse osteoblasts were treated for 2 days with 17 beta-estradiol. The production of TGF-beta was increased almost 2-fold by 1 nM 17 beta-estradiol, and short-term treatment stimulated the intracellular accumulation of TGF-beta 1 mRNA. We conclude that ovariectomy reduces deposition of TGF-beta in rat bone and that diminished skeletal TGF-beta could play a role in the pathogenesis of bone loss, fractures, and microfractures that occur in estrogen-deficient states. Our results support the possibility that estrogen and bone TGF-beta may be necessary for normal maintenance of the skeleton in female rats.
Animals↗
Effects of gallium on bone in the rat.
Gallium nitrate lowers the serum calcium in patients with hypercalcemia caused by malignancy and is available for clinical use. The mechanism for the hypocalcemic action is unknown, however. The present studies were undertaken to determine the effects of gallium on bone metabolism. Normal male rats were implanted subcutaneously with mineralized allogeneic bone matrix. Histomorphometry of the implants and of tibiae was determined after three doses of tetracycline administered at intervals of 1 week. Gallium as nitrate was administered daily by intraperitoneal injection at doses of 0.9, 1.8, and 3.6 mg elemental gallium per kg body weight for 21 days in one study and at 3.5 mg/kg for 33 days in a second study. All the gallium-treated rats gained weight. Rats given gallium at doses of 3.5 mg/kg or more grew at a lower rate than untreated controls (-7 and -10% at doses of 3.5 and 3.6 mg/kg, respectively; p less than 0.05). At a dose of 0.9 mg/kg, gallium did not inhibit bone resorption or lower serum calcium but inhibited bone formation by 32% and bone apposition by 36% at the endosteal surface of the tibia. At a dose of 1.8 mg/kg, gallium produced modest hypocalcemia, prevented a rise in circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D], inhibited bone resorption in implants, and inhibited bone formation by 19% and bone apposition by 18%. At a dose of 3.5 mg/kg, gallium lowered the serum calcium and serum 1,25-(OH)2D, inhibited growth, and accentuated the antiresorptive and antiformative effects seen at the two lower doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Osteomalacia and rickets.
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Bone and Bones↗
Vitamin D deficiency causes a selective reduction in deposition of transforming growth factor beta in rat bone: possible mechanism for impaired osteoinduction.
We demonstrated previously that implants of bone matrix prepared from vitamin D-deficient (-D) rats were less osteoinductive and contained less extractable mitogenic activity compared with control implants prepared from vitamin D-replete (+D) rats and proposed that bone from -D rats is deficient in one or more specific growth factors. To test this hypothesis, bones from rats that were fed either +D or -D diets and kept in the dark for 8 wk were extracted and assayed for insulin-like growth factors I and II (IGF-I and IGF-II) and transforming growth factor beta (TGF-beta), the three most abundant growth factors in rat bone, and osteocalcin. Serum calcium, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] were determined at sacrifice. In -D rats, there were significant reductions in serum calcium, 25-hydroxyvitamin D3, and 1,25(OH)2D3 and skeletal TGF-beta but no differences in extractable skeletal protein, IGF-I, IGF-II, or osteocalcin compared with +D rats. To determine whether 1,25(OH)2D3 increased TGF-beta production by bone cells, we treated mouse calvaria for 6 days and mouse osteoblasts for 2 days with 10 nM 1,25(OH)2D3. Production of TGF-beta was increased almost 100% by 1,25(OH)2D3. We conclude that vitamin D deficiency reduces deposition of TGF-beta in rat bone and that diminished skeletal TGF-beta could contribute to the previously observed decrease in osteoinduction in implants from -D rat bone. The findings support the possibility that vitamin D and bone-derived TGF-beta are required for normal repair of the skeleton.
Animals↗
Demonstration that bone mass is greater in black than in white children.
Osteoporosis and hip fractures are less common and bone mass is greater in black than in white women. To determine if bone mass is greater in black than in white children, bone mineral density (BMD) of the midradius by single-photon absorptiometry and BMD of the lumbar spine (L1-L4), trochanter, and femoral neck by dual-photon absorptiometry were measured in 20 black boys, 18 black girls, 33 white boys, and 35 white girls between the ages of 7 and 12 years. Mean age (10.4 +/- 0.3 versus 10.2 +/- 0.2 years) and body weight (39 +/- 2 versus 38 +/- 2 kg) in the blacks and whites, respectively, were not different in the two groups, and the ages and weights of the boys and girls were not different from each other. BMD were significantly greater in black than in white children at each site, in the black than in white boys at the trochanter and femoral neck, and in the black than in white girls at each site. In both races, BMD varied directly with age and body weight. Multivariate analysis showed that BMD were greater at the midradius, lumbar spine, trochanter, and femoral neck in the black than in the white children, that BMD of the lumbar spine was greater in the girls than in the boys, and that BMD of the trochanter and femoral neck were greater in the boys than in the girls. There were significant partial correlations between race and BMD and between BMD and body weight at each site, between sex and BMD at the lumbar spine, trochanter, and femoral neck, and between age and BMD at the midradius, trochanter, and femoral neck. Race, sex, age, and body weight together accounted for 49-66% of the variation in bone mass. Thus, BMD of the midradius, spine, and hip are greater in black than in white children, body weight and age are important determinants of bone mass, and some sex differences in bone mass are present at this age.
Absorptiometry, Photon↗
Endocrine complications of sarcoidosis.
Sarcoidosis is a multisystem disorder of unknown etiology that frequently involves the lymph nodes, lungs, eyes, and skin. The disease can involve any organ system, and noncaseating granulomas are characteristically present. Synthesis of 1,25-dihydroxyvitamin D, the most biologically active form of vitamin D, occurs in granulomatous tissue and may give rise to increases in its concentration in the peripheral circulation and to hypercalcemia and hypercalciuria. Infiltration of endocrine organs also occurs. Involvement of the hypothalamus and pituitary can cause primary polydipsia and disordered regulation of thirst; diabetes insipidus, impaired secretion of anterior pituitary hormones (with clinically apparent hypothyroidism, hypogonadism, hypoadrenalism, or impaired growth), and increases in serum prolactin may also result. Galactorrhea, however, seldom occurs. Involvement of the thyroid and adrenal glands rarely leads to hypofunction. Involvement of the pancreas rarely occurs but does not produce diabetes mellitus. Involvement of the male reproductive system results in epididymitis and hypogonadism, and involvement of the uterus causes abnormalities in menstrual function.
Calcium↗
Alteration of vitamin D metabolism in Mexican-Americans.
Studies were performed to investigate vitamin D metabolism in Mexican-Americans. Groups of 15 whites and 16 Mexican-Americans ranging in age from 18 to 41 years were evaluated. All of them were within 25% of their ideal body weight. Each of them was admitted to the Clinical Research Center of the University of Texas Health Science Center and placed on a daily diet estimated to contain 400 mg calcium and 900 mg phosphate. It was found that whereas serum vitamin D (1.8 +/- 0.5 versus 7.6 +/- 1.3 ng/ml, P less than 0.001) and serum 25-hydroxyvitamin D (9 +/- 1 versus 17 +/- 2 ng/ml, P less than 0.01) were significantly lower and serum 1,25-dihydroxyvitamin D (37 +/- 2 versus 28 +/- 2 pg/ml, P less than 0.001) was significantly higher in the Mexican-Americans than in the whites, serum calcium (9.1 +/- 0.1 versus 9.2 +/- 0.1 mg/dl), magnesium (1.84 +/- 0.07 versus 1.80 +/- 0.07 mEq/liter), and Gla protein (19 +/- 3 versus 21 +/- 2 ng/ml) were not different in the two groups. Urinary calcium (144 +/- 14 versus 124 +/- 16 mg/day), phosphate (672 +/- 51 versus 683 +/- 44 mg/day), sodium (110 +/- 8 versus 99 +/- 9 mEq/day), potassium (43 +/- 4 versus 49 +/- 3 mEq/day), and magnesium (7.3 +/- 0.7 versus 7.7 +/- 0.5 mEq/day) and creatinine clearance (173 +/- 14 versus 154 +/- 7 liters/day) were not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Influence of age and body weight on spine and femur bone mineral density in U.S. white men.
Bone mineral density (BMD) was measured in normal white males using 153 Gd dual-photon absorptiometry. Measurements were made on the lumbar spine (n = 315) and on the proximal femur (n = 282) utilizing three regions of interest. There was a small but significant age-related decrease in spinal BMD (r = -0.11; -0.001 g/cm2 per year) and trochanteric BMD (r = 0.27; -0.002 g/cm2 per year). The BMD of the other femoral sites decreased more rapidly; the femoral neck (r = -0.58; -0.005 g/cm2 per year) and Ward's triangle (r = -0.69; -0.007 g/cm2 per year) declined by about 21 and 34%, respectively, from age 20 to age 70. These femoral BMD decreases were three to four times greater than those usually seen in the peripheral skeleton in males but less than the decreases of 25-30 and 40% in the femoral neck and Ward's triangle of white females. This pattern of aging bone loss may partially explain the paucity of spine fractures and the lower incidence of hip fractures in males versus females.
Adult↗
The effects of fluoride on bone and implant histomorphometry in growing rats.
The effects of fluoride at concentrations of 2.0 and 4.5 mM in drinking water on growth rate, vitamin D, water and mineral metabolism, bone histomorphometry, and osteoinduction of demineralized allogenic bone matrix (DABM) were compared in the rat. Whereas fluoride did not influence fluid intake or growth rate at the lower concentration, it increased fluid intake and inhibited growth rate at the higher concentration. Fluoride produced dose-related increases in serum fluoride and alkaline phosphatase but did not alter serum 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D. Serum calcium and phosphate were reduced by fluoride at concentrations of 2.0 mM but not 4.5 mM. Cancellous bone fractional area was increased by fluoride at 2.0 mM and was reduced by fluoride at 4.5 mM. Fluoride had no effect on cancellous bone surface length or the percentage surface lined by osteoblasts and osteoclasts. Fluoride increased medullary area and decreased the endosteal bone formation rate. Fluoride increased periosteal bone formation and apposition rates at concentrations of 2.0 mM but not 4.5 mM. Fluoride inhibited mineralization in DABM implants, and at the higher concentration, fluoride increased the formation of new bone matrix. These results indicate that in the rat, fluoride increases cortical and trabecular bone at therapeutic doses and reduces trabecular bone at toxic doses. The serum concentration of fluoride at therapeutic doses in the rat is similar to that in patients with osteoporosis who are on treatment with fluoride. In the rat, there is a narrow range between toxic and therapeutic doses.
Alkaline Phosphatase↗
Differential effects of gonadal function on bone histomorphometry in male and female rats.
The effects of castration on bone histomorphometry and mineral homeostasis were compared in male and female rats. Measurements were performed 4 weeks after sham operation or gonadectomy. Orchiectomy produced increases in serum calcium and decreases in serum testosterone and androstenedione, whereas ovariectomy produced decreases in serum estradiol and testosterone. Orchiectomy did not alter static bone histomorphometric measurements of the tibial diaphysis, whereas ovariectomy increased cross-sectional and medullary areas, lowered endosteal tetracycline-labeled surface length, and markedly increased endosteal nonlabeled surface length. Orchiectomy decreased mean periosteal bone formation rate and mean periosteal bone apposition rate, whereas ovariectomy increased both measurements. Orchiectomy and ovariectomy markedly diminished trabecular area and trabecular surface length at the tibial metaphysis. Orchiectomy did not alter the number of osteoclasts per mm trabecular surface or the percentage of trabecular surface covered by osteoclasts, whereas ovariectomy increased both measurements. These findings indicate that gonadal hormones produce separate and distinct effects on bone metabolism as determined by histomorphometry in male and female rats.
Animals↗
Influence of body habitus and race on bone mineral density of the midradius, hip, and spine in aging women.
Osteoporosis and fractures of the hip are less common in black women and in obese white women than in nonobese white women. To determine the effects of race, age, and body weight on bone mineral density (BMD), BMD of the lumbar spine, trochanter, and femoral neck were determined by dual-photon absorptiometry in 131 nonobese white women and 34 nonobese black women, all of whom were within 30% of their ideal body weight, and in 24 obese white women and 27 obese black women, all of whom weighed more than 30% of their ideal body weight and were in the same age range as the nonobese women. All of them were 51 years of age or older, and most of them were postmenopausal. BMD of the midradius was measured by single-photon absorptiometry. Whereas body weight was significantly higher in the black as compared to the white women, the ages of the two groups were not different from each other. BMD declined with age and increased with body weight in both the black and white women at each of the four sites measured. After adjusting for age and weight by covariate analyses, black women had greater BMDs than white women at the midradius, lumbar spine, and femoral neck (p less than 0.001), but not at the trochanter (p = 0.18). The increases in BMD observed in the obese and black women in the present study are consistent with the previous findings that osteoporosis and fractures of the hip are less common in black and in obese white women than in nonobese white women.
Aged↗
The effects of muscle-building exercise on bone mineral density of the radius, spine, and hip in young men.
We previously demonstrated that muscle-building exercise is associated with increases in serum Gla-protein, serum 1,25(OH)2D, and urinary cyclic AMP. These studies were interpreted to mean that this form of exercise increases bone formation and modifies the vitamin D-endocrine system to provide more calcium for bone. The present investigation was carried out in normal young adult white men to determine the effects of exercise on bone mineral density at weight-bearing and nonweight-bearing sites. Twelve men who had regularly engaged in muscle-building exercises (use of weights, exercise machines, or both) for at least 1 year and 50 age-matched controls (aged 19-40 years) were studied. The body weights of the two groups were not different from each other (78 +/- 2 vs. 74 +/- 1 kg, NS). Bone mineral density (BMD) of the lumbar spine, trochanter, and femoral neck was measured by dual-photon absorptiometry, and BMD of the midradius was measured by single photon absorptiometry. It was found that muscle-building exercise was associated with increased BMD at the lumbar spine (1.35 +/- 0.03 vs. 1.22 +/- 0.02 g/cm2, P less than 0.01), trochanter (0.99 +/- 0.04 vs. 0.86 +/- 0.02 g/cm2, P less than 0.01), and femoral neck (1.18 +/- 0.03 vs. 1.02 +/- 0.02 g/cm2, P less than 0.001) but not at the midradius (0.77 +/- 0.02 vs. 0.77 +/- 0.01 g/cm2, NS). These studies provide additional evidence that muscle-building exercise is associated with increases in BMD at weight-bearing sites but not at nonweight-bearing sites.
Adult↗
Granulomatous infiltration of the talus and abnormal vitamin D and calcium metabolism in a patient with sarcoidosis: successful treatment with hydroxychloroquine.
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Bone Diseases↗