Search PubMed⌕ Search

Biomedical subjects

M W Davie

Publications and source records attributed to M W Davie.

At least 19 recordsLinked to original sources
PubMed1996

Inhibition of prostaglandin synthesis leads to a change in adherence of mouse osteoclasts from bone to periosteum.

When mouse parietal bones were incubated for 1 day in medium containing indomethacin (Ind), the number of tartrate-resistant acid phosphatase-positive osteoclasts (TRAP+OC) counted on the bone surface was drastically reduced. This reduction did not occur with calcitonin or if the endocranial membrane (periosteum) was removed prior to incubation with Ind. The aim of this work was to determine the mechanism involved. TRAP+OC were found to be increased on the endocranial membrane adjacent to the resorbing surface after Ind treatment, compared with cultures supplemented with parathyroid hormone (PTH) or prostaglandin E2 (PGE2). However, this increase accounted for only half of those lost from the bone surface. TRAP negative osteoclasts were also seen on the membrane and, to a lesser extent, on the bone. Increased TRAP specific activity could be extracted from the endocranial membranes of bones incubated with Ind compared with PGE2 controls. When bones that had been exposed to Ind were then cultured for 1 day in PGE2, an increase in TRAP+OC occurred. This increase was blocked by the removal of the endocranial membrane prior to incubation with PGE2. We conclude that when prostaglandin production ceases, TRAP+OC become less adherent to bone and more adherent to the endocranial membrane. Stimulators of bone resorption appear to reverse this process.

Acid Phosphatase↗
PubMed1996

Osteoclasts are not the major source of interleukin-6 in mouse parietal bones.

Interleukin-6 (IL-6) is produced by bone cells and has been shown to stimulate the proliferation of osteoclast progenitors. Which cells in bone produce IL-6 is controversial. This article tests the hypothesis that tartrate-resistant acid phosphatase-positive osteoclasts (TRAP + OC) in neonatal mouse parietal bones are the major source of IL-6. Bones were preincubated with indomethacin to decrease the number of TRAP + OC and the amount of IL-6 produced. Incubation with parathyroid hormone or prostaglandin E2 increased the number of TRAP + OC and the amount of IL-6 produced. Calcitonin and 17 beta-estradiol inhibited this increase in TRAP + OC but had no effect on IL-6 production. 1,25-dihydroxy-vitamin D3 also stimulated an increase in TRAP + OC number but did not cause increased IL-6 production. Both the endocranial and ectocranial membranes of these bones produced large amounts of IL-6. TRAP activity in extracts of endocranial membranes was 14-fold that of the ectocranial membrane and, histochemically, some TRAP + cells could be detected here. However, the ectocranial membranes produced more IL-6 than the endocranial membranes. We conclude that TRAP + OC are not a major source of IL-6 in this system.

Acid Phosphatase↗
PubMed1996

The relative contribution of disc and vertebral morphometry to the angle of kyphosis in asymptomatic subjects.

In order to investigate the relative contributions of vertebra and inter-vertebral disk to kyphosis, a series of 100 asymptomatic healthy women (age range 39-91 years) were studied to evaluate lateral dorsal appearances and possible related parameters of bone loss. Subjects underwent lateral dorsal spine radiography and single photon absorptiometry of the radius. There was a significant decrease in physical height in relation to age (P < 0.001) and this was directly related to an increasing thoracic kyphosis (P < 0.005). The angle of kyphosis was better related to the average anterior disc height (P < 0.001) than to average anterior vertebral height. The vertebral body ratio, however (anterior/posterior height), was more strongly related to angle of kyphosis than was disk ratio. The results also showed a fall in the proximal and distal radial bone mineral content with age (P < 0.001). These findings suggest that dorsal kyphosis as part of the ageing process may be as closely related to the physical integrity of the disc as to the vertebral body. Hence, therapy for age related bone mineral loss may have limited effect on a kyphotic deformity of the dorsal spine in otherwise asymptomatic patients.

Absorptiometry, Photon↗
PubMed1996

Etiology of rickets in Nigerian children.

We studied 26 Nigerian children with active rickets (13 boys, 13 girls), aged 1 to 5 years, and compared results of biochemical studies with those of healthy control subjects. The plasma 1,25-dihydroxyvitamin D level was elevated (568 +/- 317 pmol/L) and the 25-hydroxyvitamin D level was (36 +/- 28 mol/L) in the children with rickets compared with the control subjects (369 +/- 134 nmol/L and 69 +/- 22 nmol/L, respectively). The results suggest that rickets in Nigeria is largely the result of calcium deficiency and that vitamin D deficiency and possibly end organ resistance may be contributory factors.

Calcium↗
PubMed1995

The number of tartrate-resistant acid phosphatase-positive osteoclasts on neonatal mouse parietal bones is decreased when prostaglandin synthesis is inhibited and increased in response to prostaglandin E2, parathyroid hormone, and 1,25 dihydroxyvitamin D3.

The culture of parietal bones from 4-day old mice in indomethacin (Ind) for 1 day caused a large reduction in the number of tartrate-resistant acid phosphatase positive osteoclasts (TRAP + OC) relative to both control bones and to freshly isolated bones. This reduction did not occur if prostaglandin E2 (PGE2) was present. When 5-bromo-2'-deoxyuridine (BDU) was injected into 4-day old mice, newly formed TRAP + OC nuclei became labeled 1 day later; these bones were then cultured with Ind for 1 day. TRAP + OC and newly labeled TRAP+OC nuclei were commensurately decreased in number. This suggests an active down-regulation rather than merely the inhibition of new TRAP+OC formation. Incubation of bones with Ind and either PGE2, parathyroid hormone, or 1,25 dihydroxyvitamin D3 for 6 hours following a 1-day preincubation in Ind, resulted in an increase in TRAP + OC compared with Ind alone. Using BDU labeling in vitro and in vivo, we show that this increase in number of TRAP+OC is not the result of cell proliferation, but rather differentiation of postmitotic precursors.

Acid Phosphatase↗
PubMed1994

Interleukin-6 does not mediate the stimulation by prostaglandin E2, parathyroid hormone, or 1,25 dihydroxyvitamin D3 of osteoclast differentiation and bone resorption in neonatal mouse parietal bones.

The cytokine interleukin-6 (IL-6) was produced by neonatal mouse parietal bones during a 6- or 48-hour culture period in response to prostaglandin E2 (PGE2) and bovine parathyroid hormone (PTH) 1-34 fragment but not 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. At the same time there was an increase in tartrate-resistant, acid phosphatase-positive osteoclasts (TRAP+OC) with all three osteotropic effectors over 6 hours, and an increase in 45Ca release over 48 hours. TRAP+OC numbers on PGE2-stimulated bones were positively correlated with IL-6 concentration. Our aim was to determine if IL-6 mediated this response. Recombinant human IL-6 (rhIL-6) was added to parietal bones in culture at concentrations within the range that PGE2 or PTH would produce during incubation. However, over 6 or 48 hours, rhIL-6 did not stimulate TRAP+OC to increase in number nor did it cause an increase in calcium release over 48 hours. Adding an antibody against mouse IL-6 to bone cultures stimulated with PTH or PGE2 neutralized the resulting IL-6 bioactivity by up to 92% but did not inhibit TRAP+OC formation. We conclude that although IL-6 is produced in response to two important stimulators of bone resorption, it does not mediate osteoclast differentiation or bone resorption in this model.

Acid Phosphatase↗
PubMed1994

Prostaglandin E2 stimulates the production of interleukin-6 by neonatal mouse parietal bones.

The pleiotropic cytokine interleukin-6 (IL-6) is thought to be involved in bone homeostasis. A number of bone resorbing agents have been shown to induce the release of IL-6 from bone. We wished to determine whether prostaglandin E2 (PGE2), which is a mediator of bone resorption, can elicit the production of IL-6. IL-6 was measured by the proliferative response of B9 hybridoma cells and could be completely neutralised by an anti-IL-6 antibody. Parietal bones from neonatal mice were maintained in culture in the presence of indomethacin (10(-6) M) with or without PGE2. The time course and dose-response to PGE2 of IL-6 production were determined. After 6 h in culture, 10(-8) M PGE2 produced significantly more IL-6 than the controls (P < 0.005). PGE2 (10(-6) M) stimulated the production of a mean of 12.8 ng/ml IL-6 over 6 h. Preincubating bones with indomethacin for 20 h prior to a 6 h culture with indomethacin led to a lowering of the production of IL-6 (mean 1.8 ng/ml) compared to bones cultured without the preincubation period (5.8 ng/ml). When the indomethacin preincubation period was used, a significant increase in IL-6 production was found with 10(-9) M PGE2 (P < 0.005), and 10(-6) M PGE2 caused the production of 39.9 ng/ml IL-6 over 6 h. Stripping endocranial and ectocranial membranes from bones demonstrated the membranes to be the major site of IL-6 production. However, intact bones were required for maximal stimulated IL-6 production.

Animals↗
PubMed1994

Bone mineral content and density in healthy subjects and in osteogenesis imperfecta.

Lumbar spine bone mineral density in a cross sectional study of healthy subjects increased by 0.012 and 0.016 g/cm2/year in boys and girls respectively between 5 and 11 years of age. These rates increased five-fold in girls and threefold in boys between the ages of 11 and 13 years as a result of the bone mineral content increasing more rapidly than the coronal area at this age. By the age of 11 years the girls had 66% of the coronal area, 61% of the bone mineral density, and 41% of the bone mineral content of subjects aged 18-23 years. The ratio (lumbar spine bone mineral content/body weight) was constant in boys aged 6-13 years, but there were significant variations in girls. Femoral neck bone mineral density in both sexes changed little between 6 and 11 years and at 11 years was 69% of the adult values. Subjects with osteogenesis imperfecta had a low bone mineral density and bone mineral content for their age and weight. The z score of bone mineral density at the femoral neck was significantly lower than at the lumbar spine. In patients with recurrent fractures a low bone mineral density may help in identifying those with osteogenesis imperfecta and assist in their subsequent management.

Absorptiometry, Photon↗
PubMed1993

Osteoclast recruitment in mice is stimulated by (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate.

Though some evidence suggests that bisphosphonates (BPs) act directly on osteoclasts to inhibit bone resorption, other evidence suggests that they inhibit the development of the osteoclast. We found an increase in osteoclast recruitment in 2-day-old mice given (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD). A threefold increase in 5-bromo-2'-deoxyuridine (BrdU)-labeled osteoclast nuclei was observed on mouse parietal bones 3 days after APD injection. This suggests that inhibition of osteoclast development is not an action of APD in mice of this age. The mechanism of the increased recruitment was investigated. As osteoclast progenitors were not detected on parietal bones in vitro, we looked for an increase in circulating monocytes to account for the recruitment. No such increase was found, but when 51Cr-labeled bone marrow was injected intraperitoneally into mice given APD there was an increase in accumulation of 51Cr in calvaria and in femur and tibia over controls. This increase did not occur when 51Cr-labeled erythrocytes or free 51Cr was injected. We conclude that APD causes increased recruitment of osteoclast precursors by increasing the avidity of bone for hematopoietically derived cells.

Animals↗
PubMed1993

Vertebral deformity, bone mineral density, back pain and height loss in unscreened women over 50 years.

Bone mineral density (BMD) was measured in the lumbar spine using dual-energy X-ray absorptiometry in 222 unscreened women (aged 50-82 years), and information on back pain and historic loss of standing height was obtained at interview. Vertebral morphometry was performed on lateral spinal radiographs. The shape of the vertebral body was quantified using appropriate vertebral shape indices (VSIs), and vertebral deformities were identified using thresholds defined in terms of the means (M) and standard deviations (SD) of these VSIs for the whole group. Severity of deformity was defined as either grade 1 (M+2SD < VSI < M+3SD), grade 2 (M+3SD < VSI < M+4SD or grade 3 (VSI > M+4SD). Subjects with grade 1 vertebral deformities were older than subjects without such deformities, but did not have a reduced age-related Z-score of BMD. Grade 2 wedge and concave deformities were associated with a reduced age-related Z-score of BMD, suggesting that the aetiology of such deformities is closest to conventional concepts of 'osteoporotic fracture'. Grade 3 deformities were associated with neither increased age nor decreased BMD. Stature decreased in these subjects with age. Subjects reporting historic height loss had a higher mean number of wedge deformities. Subjects with back pain did not have a higher incidence of vertebral deformity than subjects without, confirming that many deformities were asymptomatic. Neither back pain nor historic loss of height were found to be associated with low spinal BMD.

Absorptiometry, Photon↗
PubMed1993

Vertebral morphometry in women aged 50-81 years.

Vertebral dimensions and vertebral shape indices (VSI) were investigated in T4-L4 in 926 females aged 50-81 years. The most consistent finding was the increase of inferior antero-posterior dimension with age. Wedging and concavity also increased with age but the changes were not significant at all vertebral levels. The value of VSIs also varied with level. Thus a particular degree of VSI, considered normal at one level or at one age, would be outside the reference range at a different level or age group. The number of subjects identified as osteoporotic by skewness (5.4%) or in excess of three standard deviations from the mean (6.5%) was much lower than in recent reports from North America. The number of subjects contributing to a skewed distribution increased with age from 0.5% at 55-59 years to 10.0% at 75-79 years. Change with age in the antero-posterior dimension could increase load-bearing area in older subjects, but the decline in bone density will be increased as a declining bone mineral content occupies a larger volume.

Aged↗
PubMed1993

A computerized technique for vertebral morphometry.

A new technique for morphometric measurement of vertebral bodies has been described, in which a computerized image analysis system was used to digitize and measure standardized lateral radiographs of the thoracic and lumbar spine. The sources of error in the radiographic system and the image analysis system were assessed using vertebral phantoms and test images. Oblique projection in the radiographic image of a vertebra did not produce a significant error in the measured area. The radiographic magnification was approximately 35%. Optical non-uniformity was detected in the image analysis system, and was ascribed to the lens optics. The maximum intra-observer and inter-observer variations in vertebral area were 3.1% and 5.3% respectively for experienced observers. The technique is applicable to clinical studies of large populations, and has value in investigating vertebral deformity in the management of metabolic bone disease.

Female↗
PubMed1993

Plasma aluminium in a reference population: the effects of antacid consumption and its influence on biochemical indices of bone formation.

Aluminium is involved in the etiology of several complications of chronic renal failure and has been firmly established as having toxic effects on bone tissue. We have measured plasma aluminium together with serum osteocalcin, procollagen I C-terminal peptide and total alkaline phosphatase activity in healthy subjects and in a group of subjects who consumed aluminium-containing and non-aluminium containing antacid preparations, with normal renal function. Age-related healthy reference ranges for plasma aluminium are presented and the effects of chronic antacid consumption on plasma aluminium and biochemical markers of bone formation investigated. In 172 healthy subjects the mean plasma aluminium concentration was 4.4 +/- 2.9 micrograms L-1, men having a significantly greater circulating aluminium load than women (5.4 +/- 2.8 micrograms L-1 vs. 4.0 +/- 2.8 micrograms L-1 respectively (P = 0.0039)). Older men were found to have significantly higher plasma aluminium levels than younger men. Increased plasma aluminium was seen in subjects taking antacids although this was not associated with significant changes in most indices of bone formation.

Adult↗