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Biomedical subjects

D J Baylink

Publications and source records attributed to D J Baylink.

At least 289 records · Page 16Linked to original sources
PubMed1984

Long-term calcitonin therapy in postmenopausal osteoporosis.

Results are presented from a 2-year controlled study evaluating the efficacy of 100 units synthetic salmon calcitonin/d in the treatment of postmenopausal osteoporosis. All patients received 400 units D2 po qd and 1200 mg CaCO3 po qd. The 21 control and 24 treated patients (mean age 65) were not statistically different at baseline. Although mean total body calcium (TBCa) was not significantly different between treated and control patients throughout the study, mean differences in the change in TBCa from baseline (treated minus control) were significant at 12, 18, and 26 months. The mean slope of TBCa for treated patients, but not for controls, was significantly positive through 18 months. Iliac crest bone biopsies showed (1) a significantly greater percent total bone area in treated compared to control patients at 2 years, and (2) a significantly decreased percent resorbing surface in treated patients when evaluated by paired difference from baseline. At 4 months, serum calcium values were significantly lower in treated patients than in controls (mean difference, treated minus controls), but were not statistically different from controls at study completion. Urine calcium increased significantly for the first 4 months in treated subjects and then declined to baseline levels. Since urinary calcium increased, the increase in TBCa was probably associated with an increase in net intestinal calcium absorption.

Age Factors↗
PubMed1984

Osteoporosis associated with pregnancy and lactation: bone biopsy and skeletal features in three patients.

Case reports of three young patients who developed vertebral fractures and skeletal complications during pregnancy and/or lactation are presented. Radiologic features are described. All three had severe disease with three to nine vertebral fractures at presentation postpartum. In two patients, follow-up for 5-7.8 yr (including further pregnancy in each) revealed no further fractures. In general, serum and urine features were normal, the exceptions being a low serum 25-hydroxyvitamin D level (plus intermittent elevation of serum parathyroid hormone) in one, a tendency to low plasma alkaline phosphatase in another, and in the third (the most severely affected patient) a transient rise in urinary hydroxyproline and plasma alkaline phosphatase during a phase of bone loss following her second and third pregnancies. Bone biopsies performed 1 to 6-1/2 yr after parturition showed quantitative bone histologic features and bone formation rates that, as a group, were not significantly different from either normal or postmenopausal osteoporotic subjects. These patients did not have osteomalacia and did not show high turnover osteoporotic features. It is possible that this type of osteoporosis may be somewhat self-limiting, although this hypothesis is subject to great influence by any adaptive lifestyle changes introduced by the patient. The severe fracture history of these patients emphasizes the gravity of their bone disease and stresses the need for further study on the etiology and treatment of this form of osteoporosis.

Adolescent↗
PubMed1984

Regulation of bone repletion in rats subjected to varying low-calcium stress.

Weanling Sprague-Dawley rats subjected to varying degrees of low-Ca dietary stress (depletion) showed graded increases in the rate of endosteal bone formation when normal dietary Ca was restored (repletion). There was a strong positive correlation between the rate of bone resorption in depletion and the rate of bone formation attained after 1 wk of repletion. However, bone formation declined rapidly within the first 4 wk of repletion, despite the persistence of a substantial endosteal bone volume deficit. Furthermore the medullary area (indicative of bone volume) did not by itself determine the bone formation rate. Bone volume in test groups was restored to control levels after 6 mo of repletion, and this result could be predicted by a kinetic analysis. Thus, although very high rates of formation in early repletion decline rapidly, smaller increments relative to controls must be sustained for long periods. Our data indicate that increased formation rats at all stages of repletion are a consequence of elevations in both osteoblast number and osteoblast activity.

Animals↗
PubMed1984

Characterization of cells isolated and cultured from human bone.

Cells isolated from samples of human iliac crest and human femoral heads by collagenase digestion have been successfully cultured in Fitton-Jackson modified BGJb culture medium supplemented with penicillin (100 units/ml), streptomycin (100 micrograms/ml), and fetal calf serum (10%). Although only a low proportion of the cells survived the initial plating (less than 1%), cells established in culture were readily passaged. Examination of cells obtained at intervals during the collagenase digestion showed that the percentage of cells that attached increased with time of digestion. Rapid sample preparation of rat bone did not substantially increase the number of cells attaching. Thus, it seems unlikely that the low survival was due to loss of viability during sample transportation and preparation. Of several media tested BGJb supplemented with 10% fetal calf serum supported the best growth. Population doubling time averaged 104 hr. Cultured human bone cells were assayed for alkaline phosphatase activity using the azo dye method with naphthol ASTR phosphate as the substrate. A portion of the cells (19%) demonstrated high activity in all cultures examined regardless of the passage number of the culture. Autoradiography of cells exposed to [3H]thymidine showed incorporation of the label into both alkaline phosphate-positive and -negative cells. The stimulation of cell proliferation by growth factors was studied by determining the incorporation of [3H]thymidine into DNA. The specific skeletal growth factor from human bone stimulated cell proliferation several-fold with a half-maximal effect at 5 micrograms/ml. Insulin, epidermal growth factor, and a crude preparation of somatomedin C also stimulated cell proliferation.

Alkaline Phosphatase↗
PubMed1984

Skeletal scintigraphic changes in osteoporosis treated with sodium fluoride: concise communication.

An appendicular skeletal response to sodium fluoride (NaF) was detected by total skeletal scintigrams. Twelve postmenopausal osteoporotic women were treated with NaF (88 mg/day) and calcium (1500 mg/day). Total skeletal scintigrams were obtained before and during treatment. Within 4 to 21 mo (mean: 8.3), all 12 patients showed new areas of increased uptake corresponding to metaphyseal regions and short bones of the appendicular skeleton. The number of peripheral bones involved in each subject ranged from four to 12. The most frequently involved sites (11 of 12 patients) were the right distal femur and proximal tibia. Nine patients showed an increase in serum alkaline phosphatase activity, which was attributed to an increase in the skeletal isoenzyme. Seven of 12 patients developed bone pain in one or more of the regions of increased uptake. This study establishes that the skeletal scintigram is a sensitive index of the peripheral skeletal response to NaF.

Aged↗
PubMed1983

Fluoride directly stimulates proliferation and alkaline phosphatase activity of bone-forming cells.

Fluoride is one of the most potent but least well understood stimulators of bone formation in vivo. Bone formation was shown to arise from direct effects on bone cells. Treatment with sodium fluoride increased proliferation and alkaline phosphatase activity of bone cells in vitro and increased bone formation in embryonic calvaria at concentrations that stimulate bone formation in vivo.

Alkaline Phosphatase↗
PubMed1983

Calvarial cells synthesize 1 alpha,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3.

A metabolite of vitamin D has been isolated in pure form from incubation of 25-hydroxyvitamin D3 with embryonic chick calvarial cells that had been grown on Cytodex 1 microcarrier beads. The isolation involved dichloromethane extraction of the cells and incubation medium, followed by Sephadex LH-20 column chromatography and high-performance liquid chromatography of the extract. The metabolite was identified as 1 alpha,25-dihydroxyvitamin D3 by means of ultraviolet absorption spectroscopy, mass spectrometry, and sensitivity to oxidation by periodate. This metabolite was not produced by cell-free medium or by cells from embryonic chick liver, skin, or heart. In conclusion, (1) kidney cells are not unique in having 25-hydroxyvitamin D3:1 alpha-hydroxylase activity as previously believed and (2) vitamin D target tissues such as the skeleton may play a direct role in mediating the metabolism of 25-hydroxyvitamin D3 to 1 alpha,25-dihydroxyvitamin D3, a vitamin D metabolite active at those sites.

Animals↗
PubMed1983

Stanozolol in postmenopausal osteoporosis: therapeutic efficacy and possible mechanisms of action.

To assess the efficacy of the anabolic steroid stanozolol in the treatment of osteoporosis, a 29-month double-blind study was performed with 23 treated and 23 control postmenopausal osteoporotic women. Drug efficacy was assessed by serial determinations of total body calcium (TBC--total bone mass) by neutron activation analysis, regional bone mass (RBM) by single-photon absorptiometry, and by spinal roentgenograms. Total body calcium increased 4.4% from baseline values (P less than 0.01) in the treated group and remained unchanged in the control group; the difference in the change in TBC between the treated and control groups was significant (P less than 0.03). The effect of the drug on TBC persisted throughout the 29-month period. In contrast to TBC, measurements of RBM indicated no significant differences between the treated and placebo groups, suggesting a possible differential response to therapy at various skeletal sites. No new spinal compression fractures were noted in the treated group (compared with three new fractures in the control group). Assessment of serum and urine values indicated a decrease in the level of urinary calcium and an increase in the level of total urinary cyclic AMP in the treated group. These changes were observed even though the level of serum iPTH was significantly decreased during the study. An analysis of changes in bone biopsy specimens revealed no significant differences between the treated and control groups. Seventy-six percent of the treated subjects developed SGOT elevations or other side effects from the stanozolol therapy; at no time were these effects sufficiently severe to cause termination of medication. The data suggest that long-term use of stanozolol increases the net total bone mass above pretreatment levels.

Aged↗
PubMed1983

Cells isolated from embryonic intestine synthesize 1,25-dihydroxyvitamin-D3 and 24,25-dihydroxyvitamin-D3 in culture.

Cells isolated from embryonic chick intestine in culture convert 25-hydroxyvitamin-D3 to a number of more polar metabolites. Two of these metabolites have been identified with chemical and chromatographic methods as 24,25-dihydroxyvitamin-D3 (24,25(OH)2D3) and 1,25-dihydroxyvitamin-D3 (1,25(OH)2D3). The enzymes conform to substrate saturation kinetics. The apparent Km for substrate for the synthesis of 1,25(OH)2D3 and 24,25(OH)2D3 is 70 nM and 29 nM, respectively.

24,25-Dihydroxyvitamin D 3↗
PubMed1983

Hypercalcemia, excessive bone resorption, and neutrophilia in mice bearing a mammary carcinoma.

In an attempt to gain insight into the relationship between bone marrow and bone tissue, studies of bone metabolism and quantitative analysis of bone structure were carried out in mice following a transplantation of a granulocytosis-inducing mammary carcinoma. With the progression of the tumor growth and development of granulocytosis, there was a sharp increase in plasma calcium and urine calcium, both reaching over 200% of control values. Hypercalcemia was associated with a significant increase in urinary hydroxyproline (P less than 0.005), an increase in marrow medullary area (P less than 0.05), and an increase in number of endosteal osteoclasts (P less than 0.005), together indicating that the cause of hypercalcemia was an increase in bone resorption. In parallel with hypercalcemia and hypercalcuria, there was an increase in urinary cyclic AMP excretion. The removal of the tumor normalized both blood neutrophil counts and plasma calcium levels, suggesting that a humoral agent from the tumor tissue, rather than tumor metastasis to bones, may be responsible for the phenomena. These studies documented the association of excessive bone resorption in this animal model of tumor-induced neutrophilia; the model may prove useful for studies of tumor-associated hypercalcemia as well as studies of marrow and bone interactions.

Animals↗
PubMed1983

Effects of spaceflight on structural and material strength of growing bone.

Rats in space for 18.5 days did not exhibit the normal gain in femoral bone strength of terrestrial controls. The strength deficit may have been caused by multiple factors including a diminished bone formation and an inhibition of the gain in tissue material strength. Centrifugation at 1g in space substantially enhanced bone strength, possibly by promoting more normal tissue maturation. Full recovery of bone strength was achieved 25 days after reentry.

Animals↗
PubMed1983

Effect of dichloromethylene diphosphonate on bone metabolism in calcium and phosphorus-depleted rats.

In this paper we examine the effects of dichloromethylene diphosphonic acid (Cl2MDP) (1.0 mg P/kg) in rats which have high levels of bone resorption due to the consumption of low-calcium (0.2%) or low-phosphorus (0.2%) diets. Cl2MDP increased the number of osteoclasts as shown by an increased length of resorbing surface but decreased osteoclast activity as measured by the linear rate of bone resorption. These effects appeared to be greater in the low-calcium and low-phosphorus rats, where resorption rates were higher than normal. However, these interactions between dietary and Cl2MDP effects were not statistically significant by analysis of variance. Endosteal bone formation was decreased by Cl2MDP, and the magnitude of this was significantly less in rats receiving low-calcium or low-phosphorus diets where endosteal bone formation was already low. Small but statistically significant decreases were also evident in periosteal bone formation and mineralization parameters in Cl2MDP-treated rats whether on normal or low-calcium or low-phosphorus diets.

Animals↗
PubMed1982

Purification of a skeletal growth factor from human bone.

A skeletal growth factor was isolated and purified from demineralized human bone matrix. A dose of 6 micrograms/mL of the purified factor significantly increased the proliferation rate of embryonic chick bone cells in serum-free culture (292% of controls, p less than 0.0001) but had no effect on embryonic chick skin cells plated at the same initial density. The factor is sensitive to inactivation by trypsin and urea, but not by collagenase, 20% butanol, or 1% mercaptoethanol. It is also resistant to inactivation by heat (stable for 15 min at 75 degrees C) and extremes of pH (stable for 30 min at 4 degrees C from pH 2.5 to 10.0). Purification of the active factor by selective heat and acid precipitations, molecular sieve column chromatography, and preparative polyacrylamide gel electrophoresis provided a material that was homogeneous by the criteria of high-pressure liquid chromatography, polyacrylamide gel electrophoresis, and isoelectric focusing. The apparent molecular weight is 83 000. The purified factor increases bone cell proliferation at doses comparable to other mitogens: 0.3 microgram/mL (3.6 nM) significantly increases DNA synthesis to 231% of controls (p less than 0.001). The purified factor was also active on cultured embryonic chick bones, enhancing the growth rate of tibiae and femurs, as measured by increased dry weight (185% of controls, p less than 0.025) and [3H]proline incorporation (164% of control, p less than 0.001), respectively.

Animals↗