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Biomedical subjects

A M Parfitt

Publications and source records attributed to A M Parfitt.

At least 109 records · Page 6Linked to original sources
PubMed1991

A randomized trial of sodium fluoride as a treatment for postmenopausal osteoporosis.

The anti-fracture efficacy of sodium fluoride (NaF) was evaluated in 84 postmenopausal white women with spinal osteoporosis. The dose of NaF used was 75 mg/day and all patients in this prospective, randomized, double-blind, placebo-controlled clinical trial received calcium supplements (carbonate salt) 1500 mg/day in addition to participating in a structured physical therapy program. For each of the outcome measures (change in stature, change in cortical bone mass in the forearm and development of new vertebral fractures determined by change in vertebral morphometry and by scintigraphy) there was no significant difference between the fluoride or placebo treated groups. Side effects, predominantly gastrointestinal symptoms and the development of the painful lower extremity syndrome, occurred significantly more frequently in the fluoride group (P less than 0.05). Peripheral fractures were not more frequent in the fluoride group. We conclude that, in the dose and manner used in this study, NaF is no more effective than placebo in retarding the progression of spinal osteoporosis. There is no role for NaF in the treatment of osteoporosis outside the confines of clinical research.

Aged↗
PubMed1991

Difference in label length between demethylchlortetracycline and oxytetracycline: implications for the interpretation of bone histomorphometric data.

We measured the individual lengths of fluorescent labels on the three subdivisions of the endosteal envelope in iliac bone biopsy specimens produced by the administration of both oxytetracycline and demethylchlortetracycline. Fifty-one healthy subjects and 53 patients with postmenopausal osteoporosis were labeled in the stated order, and 8 osteopenic patients were labeled in the reverse order. Whatever the order of administration, the demethylchlortetracycline label was longer than the oxytetracycline label. We conclude: (1) the difference in label lengths reflects a difference between the two compounds in some intrinsic property, whether physical, chemical, or pharmacokinetic. (2) If the calculation of extent of mineralizing surface is based on the mean length of the two labels, a suitable correction should be applied to the shorter label; alternatively, the length of the longer label alone should be used. (3) Unlabeled osteoid not due to label escape probably results from slow terminal mineralization after cessation of matrix synthesis during which too few tetracycline molecules are incorporated to exceed the threshold for visible fluorescence, rather than from the temporary interruption of mineralization followed by its resumption.

Adult↗
PubMed1991

Hypophosphatemic rickets with hypocalciuria following long-term treatment with aluminum-containing antacid.

We present what we believe is the first case of rickets following prolonged treatment with aluminum containing antacids that bind phosphate, in an 18-year-old mentally retarded boy with cerebral palsy and spastic quadriplegia. As expected, serum calcitriol was increased and urinary phosphate excretion was very low. However, in contrast to all published cases of antacid induced hypophosphatemic osteomalacia in adults, despite a substantial increase in bone resorption reflected by urinary total hydroxyproline excretion, urinary calcium excretion was low rather than high, and significant hypocalcemia occurred after antacids were ceased and a phosphate salt administered. We suggest that the skeleton was so under-mineralized because of growth during prolonged phosphate deficiency, possibly augmented by anticonvulsant administration and immobilization, that increased bone resorption did not release enough calcium to cause hypercalciuria, or to prevent hypocalcemia during resumption of normal mineralization.

Adolescent↗
PubMed1991

The ambiguity of interstitial bone thickness: a new approach to the mechanism of trabecular thinning.

The assumption that a change in interstitial bone thickness reflects a converse change in resorption depth was recently found to be incorrect. Accordingly, we re-examined previously published data concerning trabecular thickness and wall thickness in 15 patients with nonosteomalacic osteopenia following intestinal bypass surgery for obesity. The average number of remodeling cycles completed since the operation was calculated according to two assumptions: First, that the measured activation frequency had been present since the operation; second, that activation frequency had increased in the first two years after operation because of secondary hyperparathyroidism. In comparison with mean wall thickness in 40 normal subjects (38.6 microns), resorption depth calculated in accordance with the first assumption was significantly increased (54.1 microns; p less than 0.001), but calculated in accordance with the second assumption was unchanged (42.1 microns; NS). Reasons are given for believing that the second assumption is more likely to be correct than the first. Mean trabecular thickness and mean wall thickness were significantly correlated (r = 0.68; p less than 0.005). We conclude: 1) Mean resorption depth cannot be inferred from interstitial bone thickness, but can be calculated if the number of remodeling cycles corresponding to the observed structural changes is known. 2) Even though interstitial bone thickness is reduced, trabecular thinning following intestinal bypass surgery is mainly due to decreased wall thickness, as the result of defects in the recruitment and/or function of osteoblasts. The same probably applies to cancellous osteopenia in various other gastrointestinal and hepatobiliary disorders. 3) The study of intestinal bone disease may shed light on the pathogenesis of other, more common, forms of osteoporosis.

Bone Density↗
PubMed1991

Cell kinetics in parathyroid adenomas: evidence for decline in rates of cell birth and tumour growth, assuming clonal origin.

OBJECTIVE: We aimed to provide a cell kinetic explanation for the demonstrated lack of disease progression in most patients with mild, asymptomatic primary hyperparathyroidism. DESIGN: We compared cell birth rates, estimated at the time of adenoma excision, with the lowest birth rates needed to grow tumours of the observed size. PATIENTS: Sixty-three patients with primary hyperparathyroidism due to a single chief cell adenoma who had normal renal function were followed up for long enough to demonstrate cure after surgical excision. MEASUREMENTS: Fresh adenoma tissue was incubated with tritiated thymidine. The proportion of cells synthesizing DNA was determined directly by radioautography in 18 cases, and indirectly from the regression of label index on rate of DNA synthesis in 45 cases. The birth rate of new cells was calculated assuming the duration of S phase to be 12 hours. The number of cells in each adenoma was estimated both from parenchymal weight and from total DNA content, and the minimum birth rate needed to produce this number of cells from a single cell, beginning in utero, was calculated on an exponential model. RESULTS: The mean observed birth rate of new cells (mean (SD)) was 17.3 (11.1)%/year, and the minimum needed birth rate was 42.8 (21.6)%/year, significantly, (P less than 0.001) higher than the observed birth rate. CONCLUSIONS: The rate of mitosis had fallen substantially during the life span of most parathyroid adenomas. To account for this, we propose that the mutation implied by a clonal origin increases the secretory setpoint. Because proliferation, as well as hormone secretion, is influenced by calcium in parathyroid cells, the expected result would be rapid initial growth, slowing down as tumour size reached an asymptotic value corresponding to the total rate of hormone secretion needed to raise the plasma calcium to the new setpoint.

Adenoma↗
PubMed1990

Frequency distributions of tetracycline-based measurements: implications for the interpretation of bone formation indices in the absence of double-labeled surfaces.

The frequency distributions of mineral apposition rate (MAR) and mineralizing surface (MS), measured separately on the intracortical, endocortical, and cancellous surfaces in 46 normal subjects and 79 patients with postmenopausal osteoporosis, indicated that MAR has a finite lower limit of 0.3 mu/day (uncorrected for section obliquity) but that MS has no finite lower limit. We conclude that in the absence of labels MAR, and indices derived from it, must be treated as missing values, but that MS and indices with MS in the numerator should be allowed to take values of zero. To avoid infinite values for indices with MS in the denominator, we propose that osteoid mineralization rate (the reciprocal of mineralization lag time) and osteoblast vigor (the reciprocal of formation period) be used instead. For surfaces with genuine single labels (SL) but no double labels, we propose that MS is calculated as SL/2 and that for MAR either the lower limit of 0.3 or the mean measured value from other surfaces be used for calculating derived indices.

Adult↗
PubMed1990

Idiopathic acquired diffuse osteosclerosis in a young woman.

We describe a young woman who acquired a painful, diffuse osteosclerosis of the cervical, thoracic, and lumbar spine, pelvis, and long bones of the legs as an adult. Bone densitometry showed a large increase in apparent bone density. Skeletal radiographs demonstrated progressive endosteal and periosteal thickening of the cortices. A bone scan showed increased uptake of radiolabel. The serum total alkaline phosphatase and 1,25-(OH)2D3 levels were substantially elevated and the immunoreactive PTH was mildly elevated. Bone biopsy showed increased bone turnover, especially on endocortical and intracortical surfaces, but the structural indices were normal. By 4 years after presentation the bone pain had remitted and the serum alkaline phosphatase, 1,25-(OH)2D3, and PTH were normal. No cause for the occurrence of osteosclerosis in this patient could be found.

Absorptiometry, Photon↗
PubMed1989

The direct examination of three-dimensional bone architecture in vitro by computed tomography.

We describe a new method for the direct examination of three-dimensional bone structure in vitro based on high-resolution computed tomography (CT). Unlike clinical CT, a three-dimensional reconstruction array is created directly, rather than a series of two-dimensional slices. All structural indices commonly determined from two-dimensional histologic sections can be obtained nondestructively from a large number of slices in each of three orthogonal directions. This permits a comprehensive description of structural variation within a specimen and greatly facilitates the study of structural anisotropy. A measure of three-dimensional connectivity (Euler number/tissue volume) has been determined for the first time in human cancellous bone and shown to correlate with several two-dimensional histomorphometric indices. The method has the potential for overcoming many of the limitations of current approaches to the study of bone architecture at the microscopic level.

Bone and Bones↗
PubMed1989

The parathyroid glands in chronic renal failure: a study of their growth and other properties made on the basis of findings in patients with hypercalcemia.

We investigated the growth of hyperplastic parathyroid glands removed at operation from 16 patients with chronic renal failure complicated by hypercalcemia, by incubating fresh tissue with tritiated thymidine. In each gland the proportion of cells synthesizing DNA was determined directly by counting labeled nuclei after autoradiography and indirectly from incorporation of label into DNA, and the mean diameter of chief cell nuclei was measured. Both DNA synthesis and mean nuclear diameter were positively correlated with plasma calcium level. Assuming the mean duration of S phase to be 12 hours, the birthrate of new cells (mean +/- SD) was 18.5% +/- 23.6% per year, significantly (p less than 0.05) greater than the 11.5% +/- 7.4% per year found in 63 parathyroid adenomas previously studied. On the basis of estimated disease duration, the minimum birthrate needed to grow glands of the observed weight was 23.4% +/- 16.5% per year. The similarity between observed and needed birthrates indicates that the glands were growing almost as fast as when renal failure began, and that parathyroid growth was no longer regulated in accordance with normal plasma calcium homeostasis. To account for this, we propose that the disordered growth is a consequence of an increase in secretory set point, which in turn is a consequence of calcitriol deficiency. Because the effectiveness of parathyroid hormone is impaired in renal failure, a large increase in total hormone secretion is needed to raise the plasma calcium level to the new set point, and the necessary increase in gland size can be achieved only by a sustained increase in the rate of cell division.

DNA↗
PubMed1988

Mild asymptomatic primary hyperparathyroidism is not a risk factor for vertebral fractures.

STUDY OBJECTIVE: To determine the prevalence of vertebral fractures in patients with mild asymptomatic primary hyperparathyroidism and to ascertain whether this prevalence is increased in comparison with the rate in a retrospective control group previously studied at the same institution or with current estimates of the risk for vertebral fractures in subjects of similar age. DESIGN: Prospectively collected data were retrospectively analyzed and compared with data from a historical control group at the same institution and with published data. SETTING: The outpatient department of a bone and mineral metabolism clinic. PATIENTS: A consecutive series of patients with mild asymptomatic primary hyperparathyroidism diagnosed between 1 January 1976 and 31 December 1985. Criteria for inclusion in the study were the absence of symptoms due to hyperparathyroidism, no current kidney stone disease, no radiographic evidence of osteitis fibrosa, a serum calcium level of less than 3.00 mmol/L, a serum creatinine level of less than 133 mumol/L, and a forearm bone density value not more than 2.5 standard deviations below the age-, sex-, and race-adjusted normal value. INTERVENTIONS: A conservative nonintervention study. MEASUREMENTS AND MAIN RESULTS: The prevalence of vertebral fractures in 174 patients (mean age, 62 years) with mild asymptomatic primary hyperparathyroidism was 1.7%; in a subset of white women, the prevalence was 2.8%. These rates were not higher than those expected, by comparison with the rate in a retrospective control group or with the risk for vertebral fractures in subjects of similar age, and may even be lower. CONCLUSIONS: The risk for vertebral fractures is not increased in patients with mild asymptomatic primary hyperparathyroidism and is not a reason to recommend surgical intervention in asymptomatic patients. The increased rates of vertebral fractures that occurred in other series are probably due to the use of inappropriate controls and the influence of referral or selection bias, the inclusion of patients with severer disease, and the effect of geographic differences in vitamin D nutrition on the expression of disease. Possible differences between lateral spine and lateral chest radiographs for determining vertebral body shape need further study.

Aged↗
PubMed1988

Static and tetracycline-based bone histomorphometric data from 34 normal postmenopausal females.

Transilial bone biopsies were obtained from 34 healthy postmenopausal women following in vivo fluorochrome labeling. Stained and unstained undecalcified sections were evaluated using a Merz grid. Standard histomorphometric data from cancellous bone tissue were collected and the results were evaluated and presented as variables commonly used in bone histomorphometry. The normal ranges, medians, means, and standard deviations for the group of 34 are presented in tabular form for structural, surface, basic dynamic, and derived dynamic data. Similar data for individuals grouped by ages 45-54, 55-64, and 65-74 are also presented. Secular trends for the whole group are evaluated. The structural and surface data are not much different from previous reports of sudden-death accident victims, when methodologic differences are considered. The mineral apposition rate (MAR) was 0.53 +/- 0.08 micron/day, similar to previous reports in cancellous bone, but one-third less than in cortical bone. MAR showed a marked decline with age. In contrast, the extent of tetracycline-labeled surfaces varied widely without a secular trend. Double-label surface (dLS/BS) ranged from 0.5 to 8.0% and single-label surface (sLS/BS), from 0.5 to 10.5%. Mineralizing osteoid surface (MS/OS) varied from 2 to 64%. Using only double-label surface to represent mineralizing surface, volume-based bone formation rate (BFR/BV) ranged from 0.7 to 28%/yr, and the remodeling period (Rm.P) varied from 0.28 to 4.5 years. Calculations using other representations of mineralizing surface [double plus one-half single label (MS/BS"); all label (MS/BS')] are also presented. These bone histomorphometric data are important because: (1) they come from a cohort of living subjects that was recruited solely for the purpose of establishing normal bone histomorphometry; (2) they represent the age range of patients with postmenopausal osteoporosis; and (3) they markedly expand the bone histomorphometric database of healthy persons given in vivo fluorochrome labeling prior to transilial biopsy.

Aged↗