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Biomedical subjects

A M Parfitt

Publications and source records attributed to A M Parfitt.

At least 91 records · Page 5Linked to original sources
PubMed1993

Skin color and body size as risk factors for osteoporosis.

We compared skin color, body size and bone mineral density (BMD) among three groups of postmenopausal women: 104 healthy black women, 45 healthy white women, and 52 osteoporotic white women with vertebral fractures. Skin color was measured by reflectometry, stature with a Harpenden stadiometer, weight with digital scales, and radial BMD by single photon absorptiometry. There were no significant differences in mean skin color (age-adjusted) between the healthy and osteoporotic white women, although both white groups differed from the black group. There was no significant correlation between skin color and BMD (age- and weight/height-adjusted) in any of the groups. All three groups differed significantly in age-adjusted BMD, although there was less difference between the healthy blacks and whites when covariates (body size, age) were taken into account. We further investigated body size differences by estimating stature at age 55 in all three groups based on our observations that osteoporotic women with vertebral fractures lose height at a rate that is 2.6 times faster than that of healthy aging women. Our analyses indicate that the osteoporotics were not shorter than the normals before the onset of their disease (based on estimated height), and do not have a significantly smaller body mass (weight/height and weight/height 2) than the normal white women. Additionally, the osteoporotics are above the ideal body mass index recommended by the National Institutes of Health. We conclude that fair skin is not a risk factor for osteoporosis and that large body size is not protective against the development of osteoporosis, although it may have a salutary effect on BMD in both blacks and whites.

Aged↗
PubMed1993

Bone age, mineral density, and fatigue damage.

The most plausible purpose for bone remodeling is to prevent excessive aging of bone, which can cause osteocyte death and increase susceptibility to fatigue microdamage. The age of any particular volume of bone depends on two factors: the probability of remodeling beginning on the nearest bone surface, which is given by the local activation frequency; and the probability of a particular remodeling event penetrating to a specified distance from the surface. These two probabilities can be combined in a mathematical model. According to the model, within about 40 microns from the surface, the rate of surface remodeling is the main determinant of bone age, but beyond 40 microns, the distance from the surface becomes progressively more important. Beyond 75 microns, the bone is essentially isolated from surface remodeling. Application of the model to subjects with and without vertebral fracture indicated that the proportion of iliac cancellous bone with a mean age greater than 20 years was less than 20% in all the control subjects without fracture, but was more than 20% in about one-third of the patients with fracture. Bone age is a major determinant of the degree of mineralization, so that osteoporotic patients with prolonged bone age should have bone of higher true mineral density. Accordingly, mineral density distribution was determined by scanning electron microscopy with backscattered electron imaging, calibrated in terms of atomic number.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Radiation-associated hyperparathyroidism: comparison of adenoma growth rates, inferred from weight and duration of latency, with prevalence of mitosis.

In sporadic parathyroid adenomas, the birth rate of new cells, based on the proportion of S-phase cells at the time of surgical excision, is much too low to account for growth of the tumor from a single cell, as is required by monoclonal origin, even if the mutation occurred in utero, indicating that the rate of cell proliferation has slowed down during the course of the disease. In radiation-associated hyperparathyroidism, the age at irradiation provides a more accurate upper limit to the age of the tumor. The purpose of this study was to relate this age to the prevalence of mitosis as an alternative index of current cell proliferation. In 56 such patients, the geometric mean for the minimum cell birth rate needed for growth from a single cell to the observed size in the time available was 54.4%. In 44 patients, including 31 of the previous 56 and an additional 13, sampling an average of 220,000 cell profiles, 15 mitoses were found, an overall prevalence of 0.15/10(5), which corresponds to a cell birth rate of 2.7%/yr, assuming the duration of mitosis to be 0.5 h. If cases with no mitosis were assigned a value of half the detection limit, the geometric mean mitotic index was 0.360/10(5), and the corresponding cell birth rate was 6.4%/yr. This is more than 8 times smaller than the minimum birth rate required and 20 times smaller than the cell birth rate in meningiomas, suggesting that such extreme reduction of cell birth rate is a unique feature of parathyroid adenomas, rather than a general feature of all benign tumors. The data support the set-point hypothesis, which reconciles the earlier concept of focal hyperplasia with monoclonal origin and provides an alternative nonneoplastic mechanism of etiology for the usual nonprogressive form of the disease.

Adenoma↗
PubMed1993

Producing frozen sections of calcified bone.

We describe a procedure for the rapid production and maintenance of fresh frozen bone biopsies which can be used for a variety of immunohistochemical techniques. Within 5 min of excision, tissue is placed in cold 5% polyvinyl alcohol, surrounded with 3% carboxymethylcellulose in a hand made aluminum foil embedding mold and frozen by immersion in an absolute ethanol/dry ice slurry at -70 C. The tissue block is attached to the specimen stub with cryocompound and installed in a -32 C cryostat whose tungsten carbide D profile knife is maintained at -70 C. Automatic controls are set at a slow cutting speed and the "sectioning window" is adjusted to fit the biopsy size. Knife angle, thickness gauge and antiroll bar are changed to produce a complete section. The block face is smoothly "papered" with a polyvinylpyrrolidone (PVP) impregnated Ross lens paper strip. A single section is cut and positioned on a sequentially numbered, acid cleaned, double dipped chrome-alum gelatin coated slide; adhesion is aided by "press-blotting" with bibulous paper. Sections are stored at -20 C or in a desiccator at room temperature. A brief fixation followed by removal of the water soluble PVP and lens paper generates fresh frozen bone sections suitable for further analysis.

Bone and Bones↗
PubMed1992

Composite index of skeletal mass: principal components analysis of regional bone mineral densities.

Principal components analysis is a statistical method that is used to reduce and explore data to facilitate further analyses. This method was applied to bone mineral densities measured at seven sites in 109 black and 44 white women, ages 22-80, at an internal medicine clinic in urban Detroit. We excluded subjects with a history of diseases or drugs known to affect bone metabolism. Principal components analysis was used to summarize the interrelationship of the densities and yielded two major results. First, the seven site measurements were reduced to a single, composite index (PC1) of skeletal mass that accounted for 73% of the variation in density among subjects. PC1 had roughly equal weights among the sites. A second combination of the seven sites indicated that the contrast between axial and appendicular regional densities accounted for another 10% of the variation among subjects. In investigating the relationship of density to age, body mass index, and ethnic group, we found that the principal components composite index had a stronger correlation with age (r = -0.58) and with body mass index (r = 0.34) than almost all of the regional densities. Black-white differences were larger for the composite index than for any single site density. A multiple regression of the composite index on ethnicity, body mass index, and age yielded a larger R2 (0.46) than any of the individual site densities. The second principal component, although of theoretical interest, showed a minimal ability to discriminate among subjects using the three independent variables of this study.

Absorptiometry, Photon↗
PubMed1992

Bone resorption and formation on the periosteal envelope of the ilium: a histomorphometric study in healthy women.

Continuation of net periosteal bone gain after cessation of longitudinal growth has been inferred from sequential radiographic morphometry. Accordingly, we performed histomorphometry of the periosteal surfaces of transilial bone biopsies from 57 healthy women aged 24-74 years, 29 premenopausal and 28 postmenopausal. Compared to the endocortical surface, the extents of eroded and osteoid surfaces were very similar, but the extents of osteoclast- and osteoblast-covered surfaces were 80-90% smaller, and both wall thickness and osteoid thickness were about 30% lower. Double tetracycline labels were present in only 11 cases. The second (demethylchlortetracycline) label was almost four times as long as the first (oxytetracycline) label, a much greater difference than on the endocortical surface, so that the extent of mineralizing surface was based only on the second label. Even so, adjusted apposition rates and bone formation rates were only about 20% of the endocortical values, and unlike the endocortical surface, formation rates were not higher in the postmenopausal than in the premenopausal women. Resorption, reversal, and formation periods were each much longer than on the endocortical surface. There was no correlation between periosteal and endocortical values for any variable. At least 54% of total cement line length was scalloped, implying reversal of remodeling direction from resorption to formation, and at least 18% of total cement line length was smooth, implying temporary arrest of bone formation. Convincing evidence of modeling, related to growth or mechanical stimulation, was not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Implications of architecture for the pathogenesis and prevention of vertebral fracture.

Rapid loss of cancellous bone after menopause occurs by a mechanism that removes some structural elements completely, leaving those that remain more widely separated and less well connected. Slow loss of cancellous bone continues by a mechanism that reduces the thickness of the structural elements that survive the initial phase of rapid loss. Both processes have advanced further in patients with vertebral compression fracture due to osteoporosis, than in healthy subjects of similar age; whether this is because they began sooner, proceeded more rapidly or continued for longer is unknown. This overall concept, first developed about ten years ago, has now been confirmed by a variety of different methods including node-strut analysis, star volume and the change in curvature with profile dilation. Because part of the architectural contribution to compressive strength is captured by non-invasive densitometric methods, and the contribution of cortical bone to compressive strength is significant, it has been difficult to demonstrate an independent architectural component of bone fragility by in vitro comparison of structural measurements with biomechanical testing. Nevertheless, three independent clinical studies, comparing subjects with and without vertebral fracture, have each strongly suggested an independent architectural contribution to fracture risk. Complete removal of structural elements is initiated by focal perforation of trabecular plates, but the mechanism of perforation remains controversial.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

Parathyroid stimulation after bleeding in man.

A role for the PTH-calcium axis in the normal bone-marrow response to bleeding or erythropoietin administration has been demonstrated in rats. We studied 20 autologous blood donors, each donating two units of blood, who served as a human bleeding model. Fifteen patients completed the study. Blood donations were followed by a significant increase in serum intact PTH (2.15 +/- 0.67 to 2.81 +/- 0.84 pmol/l; p = 0.0003) and protein-corrected total calcium (2.43 +/- 0.09 to 2.49 +/- 0.08 mmol/l; p = 0.2). All the individual values remained within the normal range. PTH weakly correlated with the reticulocyte count, but not with the corrected serum calcium. We conclude that moderate bleeding in humans is followed by a physiological increase in serum PTH and calcium.

Adolescent↗
PubMed1991

Principal components analysis of regional bone density in black and white women: relationship to body size and composition.

Black and white women in the United States differ with respect to bone mass and the risk of developing osteoporosis. It has been suggested that greater body size among U.S. blacks may contribute to greater bone density in this group. It is not known whether the fat or lean component contributes more to this relationship. Bone density was measured at seven sites in 161 normal black and white women using single and dual photon absorptiometry. The first principal component accounted for 73% of the variance in the sample and constitutes an index of skeletal mass. The second principal component added another 10% and contrasts the axial and appendicular sites. Both the regional bone densities and the first principal component showed significantly greater bone densities for blacks; adjustment for body size reduced bone mass differences by approximately 50%. Body composition analysis done on a subset of these women indicated that the fat component of body mass may be the more important factor in its effect on bone mass.

Absorptiometry, Photon↗
PubMed1991

Structural and geometric changes in iliac bone: relationship to normal aging and osteoporosis.

We measured indices of bone volume (cancellous and cortical) and bone surface (cancellous, endocortical, and intracortical) in intact, full-thickness transiliac bone biopsies obtained from 47 healthy white women (23 premenopausal and 24 postmenopausal) and 82 patients with postmenopausal osteoporosis. In the normal subjects there was the expected loss of cancellous bone with age, best shown by a reduction in bone surface/tissue volume, but no fall in cortical thickness with age despite a significant reduction in forearm bone density measured by single-photon absorptiometry. Bone surface/bone volume was about four times higher in cancellous than in cortical bone, and cancellous bone contributed about one-third of the total bone volume and about two-thirds of the bone surface when related to the core volume referent. In the osteoporotic patients, core width, an index of iliac bone thickness at the biopsy site, was reduced by 10%, but we could not determine whether this was the result of compaction of the core or of bone slenderness. All indices of bone volume, cortical as well as cancellous, were significantly smaller, as were the values for forearm bone densitometry; the relative deficits at different sites depended on whether they were expressed as percentages or as zeta scores. Bone surface/bone volume was increased in both cancellous and cortical bone, but bone surface/tissue volume was reduced in cancellous bone and increased in cortical bone. The proportions of total bone volume and surface contributed by cancellous and cortical bone were almost the same as in normal postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A new method for measuring cancellous bone erosion depth: application to the cellular mechanisms of bone loss in postmenopausal osteoporosis.

We have devised a new method for measurement of final depth of erosion in cancellous bone with an intra-individual precision of 4.3% and applied it to determine the mechanism of continuing reduction in trabecular thickness after menopause. Mean erosion depth (SD) was 40.8 (2.0) microns in 10 healthy postmenopausal women and 41.4 (2.1) microns in 10 age-matched patients with postmenopausal osteoporosis; the difference was not statistically significant. In contrast, wall thickness, using a method based on density differences between new and old bone, was 39.5 (2.0) microns in the normal subjects and 35.3 (2.0) microns in the patients with osteoporosis (p less than 0.0001). The balance per remodeling cycle (delta BMU) was -1.34 (2.49) microns in the normal subjects and -6.11 (1.95) microns in the patients with osteoporosis. This difference was also highly significant (p less than 0.001). Indirect estimations of erosion depth and delta BMU, based on the fall in trabecular thickness from an assumed premenopausal value of 147 microns and the number of remodeling cycles accumulated since menopause, agreed closely with the measured values. Erosion depth measured by the Eriksen method also showed no significant difference between the two groups, but because the values were substantially higher delta BMU was improbably high in both groups, did not differ significantly between groups, and was inconsistent with the observed difference in trabecular thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Asymptomatic primary hyperparathyroidism discovered by multichannel biochemical screening: clinical course and considerations bearing on the need for surgical intervention.

The sustained effects of biochemical screening to increase both apparent incidence and age at diagnosis indicate that, without screening, most patients with primary hyperparathyroidism would would never be diagnosed. This suggests that asymptomatic patients discovered as a result of screening have a nonprogressive form of the disease, with adverse health effects that are few or nontraditional, for which treatment policies validated only in symptomatic patients may be inappropriate. Accordingly, in 1975 we formulated criteria for withholding surgical treatment from such patients. Of 174 who were eligible for study over a 10 year period, clinical, biochemical, and densitometric assessment was repeated after at least 1 year (mean 52 months) in 106 patients who did not differ in any initial characteristic from 68 patients in whom follow-up was inadequate. There was no change in symptoms, no disease complications, and no change in any index of hormone secretion or disease severity. In 30 patients, individual regression slopes against time were not significant for any serum measurement. In these patients the disease appeared to have stopped progressing by the time the diagnosis was made, most likely because of cessation of tumor growth. There was a significant deficit in appendicular cortical bone at the time of diagnosis but no further acceleration of bone loss thereafter. In an earlier study, surgical cure was followed by a modest increase in forearm bone density for the first 6 months, but even after 3 years only about 20% of the deficit was corrected. The deficit in bone density is smaller in the spine than in the forearm and is not accompanied by any increase in vertebral fracture risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗