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Biomedical subjects

D J Baylink

Publications and source records attributed to D J Baylink.

At least 307 records · Page 17Linked to original sources
PubMed1982

Deficient calcitonin response to calcium stimulation in postmenopausal osteoporosis?

To test whether mobilisation of immunoreactive calcitonin in response to calcium challenge is reduced in postmenopausal osteoporosis, seventeen postmenopausal osteoporotic women with compression fractures and ten normal age-matched women were given intravenous infusions of 3 mg/kg elemental calcium over a 10 min period. Blood samples were obtained 5 min before and at 0, 10, 20, and 60 min after start of infusion for the measurement of serum calcium and plasma immunoreactive calcitonin. Serum calcium increased significantly from baseline in both normal and osteoporotic groups; immunoreactive calcitonin increased significantly in the controls 10 min and 20 min after the start of infusion, but in the women with osteoporosis calcitonin levels did not change significantly at any time. 20 min after the start of infusion the change in immunoreactive calcitonin from baseline was significantly less in osteoporotic women than in the controls. These data are consistent with a decreased immunoreactive calcitonin response to calcium infusion in postmenopausal osteoporotic women, and suggest that calcitonin deficiency may be involved in the development of postmenopausal osteoporosis.

Aged↗
PubMed1982

Extracts of bone contain a potent regulator of bone formation.

We prepared aqueous extracts of whole femorae and tibiae of embryonic chicks. An amount of extract containing 25 microgram of protein resulted in a 500% increase in DNA synthesis in calvarial cell culture, and significant effects were detected with 5 microgram (55%). The time course for stimulation of DNA synthesis showed a peak occurring 16-20 h after addition of the extract. This matrix factor is nondialyzable, and fractionation on a column of Sephadex G-100 indicated a molecular weight of 60-80,000. At the maximum dose used, [3H]proline incorporation into total protein of calvarial cells was increased by 55%, and thus far, all fractions active in promoting DNA synthesis have been found to increase collagen synthesis in cultured chick tibiae. These data are consistent with an effect on osteoblasts as well as bone precursor cells. Extracts prepared from tibiae of 2-day-old chicks, from which the marrow had been removed, also stimulated DNA synthesis (280% increase), thus ruling out the possibility that the factor is a relatively nonspecific nitrogen from the hematopoietic cell line. We conclude that bone matrix contains a substance which could regulate bone formation in vitro by control of mitosis in osteogenic precursors and/or stimulation of osteoblast activity.

Animals↗
PubMed1982

An improved technique for rapid autoradiography of cells and tissue sections.

We have demonstrated a method for autoradiography of cell and tissue preparations which is both rapid and safe. The method utilizes only the primary scintillator, PPO, placed under the final emulsion to facilitate activation of the silver grains in the emulsion. Exposure of the autoradiographs is complete under the conditions described within 4 h at ambient temperature. The method is sensitive to exposure time and to the concentration of added radioisotope. The exclusion of volatile, toxic chemicals from the preparations allows the experiments to be performed without any health hazard to the investigator.

Animals↗
PubMed1982

Bone matrix and mineral abnormalities in postmenopausal osteoporosis.

Iliac crest biopsies from 56 postmenopausal osteoporotic females with spontaneous compression fractures and decreased total body Ca were compared to similar tissue from 48 normal controls. Biopsies were analyzed for bone density, Na, Ca, Mg, P, Co3, and hydroxyproline (OH-P). From the results OH-P/matrix, % mineral, and the ion content of the mineral were calculated. osteoporotic subjects showed decreased bone density, % mineral in bone, and OH-P in the bone matrix. Within the mineral, CO3 and Ca/P were decreased, while Na and Mg were increased. Statistical analysis showed that matrix OH-P and % mineral varied independently, and therefore the patients were separated into 4 subgroups: Group Ia: decreased matrix OH-P with normal % mineral (n = 9), Group Ib: decreased matrix OH-P with decreased % mineral (n = 5), Group IIa: normal matrix OH-P with normal % mineral (n = 33), Group IIb: normal matrix OH-P with decreased % mineral (n = 9). Decreased % mineral was associated with decreased bone density and an increase in Na and Mg in the mineral, which suggests skeletal Ca deficiency. Decreased matrix OH-P was associated with decreased bone density and, in the low % mineral group, with decreased mineral CO3 and Ca/P, suggesting a mineral of decreased mean crystal size. When both abnormalities coexisted (Group Ib), the greatest reduction in total body Ca was seen. Patients with normal matrix and normal % mineral (Group IIa) still had decreased bone density. The results suggest that in a large, clinically homogeneous population of postmenopausal osteoporotic women, 4 subgroups can be identified by differences in chemical composition of iliac crest biopsies.

Adult↗
PubMed1982

Acute reduction in osteoclast number during bone repletion.

Growing rats were fed a calcium-deficient diet for 12 days to induce bone loss and were subsequently placed on a calcium-replacement diet for 1 to 3 days to evoke bone repletion. Control animals were fed the calcium-replacement diet continuously. Twelve days of calcium deprivation resulted in a 21-fold increase in the number of endosteal osteoclasts in the tibial diaphysis as compared with controls. These osteoclasts, however, rapidly disappeared from the endosteum after restoration of dietary calcium. Only 14% of these endosteal osteoclasts remained after 1 day, and no osteoclasts were present after 3 days of calcium replenishment. During this time, plump osteoblasts replaced osteoclasts on the endosteal surface. The number of osteoclasts in the marrow space also changed strikingly. An 11-fold increase in the number of osteoclasts in the marrow space occurred during the calcium-deprivation phase. However, the greatest increase (39-fold) was observed during the first day of calcium replenishment. Thereafter, the number of osteoclasts in the marrow space declined and, after 3 days of calcium replenishment, returned to the control level. During calcium replenishment, acid phosphatase-positive fragments in the marrow space appeared concomitantly with osteoclast disintegration and fragmentation. The kinetic changes and acid phosphatase staining of these fragments suggest that the fragments are the products of disintegrating osteoclasts, a finding consistent with the hypothesis that the fate of some osteoclasts in vivo is cell death. At the end of calcium deprivation, serum iPTH levels and the production of 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 were significantly increased compared to controls. After 3 days of calcium replenishment, serum iPTH had decreased to control levels, but the production of 1,25-dihydroxyvitamin D3 was still elevated. Changes in serum iPTH and the production of 1,25-dihydroxyvitamin D3 cannot, therefore, be totally responsible for the observed decrease in osteoclast number during bone repletion. Bone repair after calcium deprivation may be a locally controlled phenomenon.

Acid Phosphatase↗
PubMed1982

Effect of skeletal alkaline phosphatase inhibitors on bone cell proliferation in vitro.

Chicken skeletal alkaline phosphatase is subject to competitive inhibitions by vanadate (Ki = 0.38 mM in carbonate, Ki = 0.08 mM in Tris, both at pH 7.4) and phenylphosphonate (Ki = 15 mM in carbonate, Ki = 1.3 mM in Tris, both at pH 7.4), and uncompetitive inhibition by levamisole (Ki = 0.08 mM in carbonate, Ki = 0.10 mM in Tris, both at pH 7.4). The competitive inhibitors were more effective in Tris buffer because nonreactive ternary complexes were formed between alkaline phosphatase, the inhibitor and Tris. The effects of vanadate, phenylphosphonate and levamisole on the proliferation of embryonic chick calvarial cells in vitro were biphasic. Low doses of each agent stimulated 3H-thymidine incorporation into TCA-insoluble material; higher doses were inhibitory. Neither effect could be attributed to inhibition of alkaline phosphatase activity (e.g. 20 microM vanadate should inhibit alkaline phosphatase by 3% but stimulated cell proliferation by 187%; 50 microM vanadate should inhibit alkaline phosphatase by 7% but inhibited 3H-thymidine incorporation by 90%). None of the alkaline phosphatase inhibitors tested affected the cellular concentration of the enzyme during the 24-hour incubation. These studies indicate that alkaline phosphatase inhibitors can have nonspecific effects on bone cells in culture, and that for cells in the osteoblast cell line, an inhibition of alkaline phosphatase activity is not consistently related to a decrease in cell proliferation.

Alkaline Phosphatase↗
PubMed1982

Skeletal remodelling and bone related hormones in two adults with increased bone mass.

This study of two cases documents increased bone mass in a 30-yr old man and osteopetrosis in a 38-yr-old woman and examines the patients in terms of radiologic features, bone photon absorptiometry and bone biopsy analyses which include tetracycline kinetics. Both patients had elevated bone mass based on quantitative bone histology of iliac crest biopsies normal, or low PTH, and normal calcitonin values. However, they differed markedly from each other in other respects: One patient possessed significantly increased rates of bone formation and mineralization, had elevated serum alkaline phosphatase, increased total hydroxyproline over a 24 hour urine collection but displayed a normal amount of bone surface involved in resorption. The other subject had normal bone formation parameters, but had elevated serum acid phosphatase and a significantly elevated resorbing (crenated) surface. Although most theories ascribe and cause of osteopetrosis to decreased resorption, our study shows that increased bone formation, even when accompanied by normal resorption, can lead to the abnormal accumulation of bone mass. In this respect, the resorptive response of this patient was abnormal; the normal coupled relationship between bone formation and bone resorption, which ensures proper control of endosteal bone volume, had been lost.

Acid Phosphatase↗
PubMed1981

Human bone cells in culture metabolize 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3.

Bone cells respond to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) for mineral mobilization and contain receptors for 1,25(OH)2D3. We report here the expression of 25-hydroxyvitamin D3 (25 (OH)D3) metabolizing enzymes in primary cultures of human bone cells, as well as n a human osteosarcoma cell line. Human bone cells were obtained by enzyme digestion of the extracellular matrix of bone from iliac crest biopsies from 3 male patients without primary bone disease. These cells were plated (5 X 10(4)/min) in medium with 10% fetal calf serum and proliferated to confluence in 10-14 days. At confluence, the medium was replaced with serum-free medium. The cells were preincubated in this serum-free medium for 24 h prior to incubating them 2-4 h with [3H]25(OH)D3 (10-20 nM). The vitamin D metabolites synthesized during this incubation were extracted from the medium and cells with dichloromethane, then separated by chromatography on Sephadex LH-20, followed by high performance liquid chromatography. The cells synthesized 1,25(OH)2D3 and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) with the specific activities of the 1- and 24-hydroxylases similar in magnitude to those in kidney cells in vitro. The enzymes could be regulated by external perturbations, in that the activity of the 1-hydroxylase was inhibited by preincubation of the cells for 8 h with 1,25(OH)2D3 (10 nM), whereas the 24-hydroxylase was enhanced. Incubation of the cells in a low calcium medium (0.6 mM) depressed the 24-hydroxylase activity. We conclude: 1) normal human bone cells can produce 1,25(OH)2D3 and 24,25(OH)2D3 in vitro in amounts similar to kidney cells, suggesting a physiological significance and 2) this synthesis could account for the increase in osteoclast number in anephric patients with renal osteodystrophy.

24,25-Dihydroxyvitamin D 3↗
PubMed1981

Increased immunoreactive calcitonin in idiopathic hypercalciuria.

Serum immunoreactive calcitonin concentration (iCT) was determined in nine subjects with idiopathic hypercalciuria (IH), prior to and during oral phosphate supplementation (500 mg qid) to test the hypothesis that a renal phosphate leak was the primary defect resulting in IH in these patients. Prior to the oral phosphate supplementation, serum iCT was significantly elevated in the IH group, when compared to 26 normal individuals (75 +/- 7 vs 45 +/- 4 pg/ml, mean +/- SE, P less than .001). During oral phosphate treatment, however, serum iCT decreased to levels not significantly different from normals (39 +/- 3 and 50 +/- 5 pg/ml after 4 and 8 weeks, respectively). When data prior to and during phosphate supplementation were pooled, there was a significant correlation (r = .70, N = 26, P less than .001) between serum iCT and serum calcium. These observations suggest that the increased serum iCT in these subjects was a response to slight elevations in serum calcium, which are the result of normal physiological mechanisms to correct the renal phosphate leak.

Adult↗
PubMed1981

Parathyroid hormone stimulates bone formation and resorption in organ culture: evidence for a coupling mechanism.

We have developed an in vitro system, using embryonic chicken tibiae grown in a serum-free medium, which exhibits simultaneous bone formation and resorption. Tibiae from 8-day embryos increased in mean (+/- SD) length (4.0 +/- 0.4 to 11.0 +/- 0.3 mm) and dry weight (0.30 +/- 0.04 to 0.84 +/- 0.04 mg) during 12 days in vitro. There was increased incorporation of [3H]proline into hydroxyproline (120 +/- 20 to 340 +/- 20 cpm/mg of bone per 24 hr) as a measure of collagen synthesis, as well as a 62 +/- 5% increase in total calcium and 45Ca taken up as an indication of active mineralization. A physiologic concentration (1 pM) of parathyroid hormone was found to stimulate bone resorption over control levels in this system. Parathyroid hormone stimulated the release of [3H]hydroxyproline from the bone shafts but not from the cartilage ends, indicating the specificity of the response. With 1 pM parathyroid hormone we observed an acute inhibition of bone formation, followed (after 12-16 hr) by a chronic stimulation of bone formation during the 12-day incubation. Both mineral uptake and matrix formation were enhanced at approximately the same rate during the 12-day incubation. The chronic enhancement of formation required parathyroid hormone only for the initial 8-10 hr of incubation. These results could be explained by the production or release of a factor from bone to stimulate formation in response to the acute increase in resorption--a "coupling factor." Indeed, dialyzed culture medium conditioned by actively resorbing bones stimulated bone formation over controls when added to organ cultures at a 1:20 dilution. The factor is larger than 12,000 daltons as determined by dialysis. The factor is specific for the bone shaft and did not affect the cartilage ends.

Animals↗
PubMed1981

The diagnosis of osteoporosis.

A rational approach to the diagnosis of osteoporosis by the primary care physician is outline, with emphasis on the patient who presents with chronic back pain and a vertebral compression fracture. The basic information includes data from the patient's history and physical examination, laboratory, x-ray and bone biopsy studies, and determination of bone mineral content (BMC) by photon absorptiometry. Characteristic radiologic features associated with bone loss, BMC changes, and bone biopsy findings are illustrated. This diagnostic approach, summarized in a flow diagram, poses a series of questions; the answer to each question leads either ot a diagnostic conclusion or to further questions which must be answered. This permits decision as to whether a compression fracture is due to trauma, local osteoporosis, osteomalacia, secondary osteoporosis or primary osteoporosis. In te study population (150 subjects), 80 percent of patients presenting with vertebral compression fractures had primary osteoporosis.

Adult↗