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Biomedical subjects

J Reeve

Publications and source records attributed to J Reeve.

At least 145 records · Page 8Linked to original sources

Dietary calcium as a statistical determinant of spinal trabecular bone density in amenorrhoeic and oestrogen-replete athletes.

A study investigating the relationship between spinal trabecular bone density (measured by QCT), dietary calcium (measured by questionnaire) and menstrual status in 67 elite female athletes was undertaken. Twenty-five athletes were amenorrhoeic, 27 eumenorrhoeic and 15 were taking an oral contraceptive. The mean bone density was significantly lower (P less than 0.0001) in the amenorrhoeics (168 mg/cm3; 95% confidence interval 154-182) than in the eumenorrhoeics (211 mg/cm3; 197-224) and oral contraceptive takers (215 mg/cm3; 197-233). There was also a significant positive linear correlation between trabecular bone density. However, factors with which calcium intake may be linked, such as energy intake and expenditure, were not measured and therefore it is possible that this relationship is indirect. Further studies on the relationship between dietary calcium and bone mineral density in young women are needed.

Adolescent↗

Whole-body and site-specific bone remodelling in patients with previous femoral fractures: relationships between reduced physical activity, reduced bone mass and increased bone resorption.

1. A new tracer method is described for the non-invasive measurement of bone formation in the proximal femur. The method is based on our previously described whole-body method using 85Sr as the tracer (Reeve, J., Hesp, R. & Wootton, R. Calcif. Tissue Res. 1976; 22, 191-206). It allows correction to be made for long-term exchange processes within the skeleton. 2. The method has been applied in a study of regional and whole-body bone formation in 12 rehabilitated patients who had previously suffered a fracture of the proximal femur. Twelve healthy control subjects were studied, who were selected for their good health and continued physical activity. The aim was to explore the relationship between bone formation and physical activity. 3. Bone formation was similar in the two groups, both regionally and in the whole body. Based on analyses of four cadaver specimens, bone formation in the proximal femur was about one and two-thirds times that in the whole skeleton when related to mass of calcium in the region of interest. 4. Whole-body bone resorption, estimated from five measurements per subject of hydroxyproline excretion in relation to creatinine excretion, was significantly higher in the fracture patients (P < 0.01, Wilcoxon's test). 5. Estimates of current physical activity (and immediate pre-fracture physical activity) were made with a newly devised questionnaire. Historical levels of physical activity (at ages 15-45 years) were determined with Astrom's questionnaire. No bone formation index correlated with any index of physical activity. Urinary hydroxyproline excretion correlated inversely both with current physical activity and historical physical activity (for both regression coefficients P < 0.01). 6. The results are discussed in the light of our current understanding of the control of bone remodelling by the discrete basic multicellular units of bone. The opportunity to study regional bone resorption by the additional use of serial dual X-ray absorptiometry of the same region will in future allow the direct monitoring of the effects of therapeutic interventions which have been designed to prevent contralateral hip fracture.

Aged↗

Future prospects for hormone replacement therapy.

To avoid the complication of osteoporosis, hormone replacement therapy (HRT) is now standard therapy in women with premature ovarian failure. The indications for HRT after the age of 50 are more controversial. There are strong indications from case-control studies that in N. America and Europe HRT protects against osteoporotic fracture, myocardial infarction and stroke; yet the evidence from case control studies is insufficiently precise to quantitate accurately the potential benefits that would accrue from its more widespread use. Clear guidelines also need to be established on the potential usefulness of selective prescribing of HRT using one or more screening procedures. The only effective way of achieving this and of quantitating the potential benefits of HRT with sufficient accuracy is by means of one or more randomized controlled trials. Future research will also address concerns such as the possible increase in the risk of breast cancer after 10 or more years of therapy. Critical to the more widespread acceptance of HRT may be the development of safe regimes which do not promote uterine bleeding as well as minimizing other unwanted side-effects.

Breast Neoplasms↗

Treatment of osteoporosis with parathyroid peptide (hPTH 1-34) and oestrogen: increase in volumetric density of iliac cancellous bone may depend on reduced trabecular spacing as well as increased thickness of packets of newly formed bone.

OBJECTIVE: We wished to determine whether treatment of vertebral osteoporosis with human parathyroid peptide 1-34 (hPTH 1-34), given as a daily injection with supplementary treatment with hormone replacement therapy (HRT), increases cancellous bone area in the ilium by increasing the size of packets of new bone. DESIGN AND MEASUREMENTS: The width of packets of cancellous bone (wall width) was measured at random intercepts and mean values calculated. Cancellous bone area and perimeter were also measured. Indices of trabecular separation and the complementary quantity trabecular number were derived according to Parfitt's method, as well as trabecular width. Patients were used as their own controls and changes in these indices calculated. Correlations were calculated for data obtained from independent measurements. PATIENTS: We studied eleven women with post-menopausal osteoporosis, diagnosed by fractures after exclusion of causes of secondary osteoporosis. RESULTS: One woman did not comply with her HRT therapy. In the others, treatment with hPTH 1-34 + HRT restored the characteristically depressed pre-treatment values of wall width to normal. Trabecular width increased approximately four times more than wall width. Changes in wall width correlated with changes in cancellous bone area; however, bone area increased considerably more than could be accounted for statistically by changes in wall width. A decrease in trabecular separation was found to account for the additional increase in bone area (P = 0.056). CONCLUSION: hPTH 1-34 + oestrogen and progestagen therapy increases the width of packets of new cancellous bone with consequent increases in the width of trabecular plates.

Aged↗

Coxarthrosis and femoral neck fracture.

A retrospective cross-sectional study of the roentgenograms of 300 hip fracture patients and 300 age- and gender-matched controls was performed to determine the relationship between fracture type, femoral neck trabecular bone integrity (as measured by the Singh index), osteoarthrosis, and age. Coxarthrosis was associated with a low incidence of intracapsular fracture but unchanged rates of extracapsular fracture. Singh grade declined with age in all groups of patients, although the rate of decline was reduced in control female patients with coxarthrosis compared with other diagnostic groups. When the coxarthrosis patients were included, the mean Singh grade for the female fracture patients was significantly reduced in patients compared with controls with or without age adjustment (3.88 versus 4.17). When patients with coxarthrosis were excluded from the analysis, this effect disappeared. It is suggested that the differences in Singh grades observed previously between femoral fracture patients and controls may have resulted from an undetected negative association between coxarthrosis and retention of trabecular integrity with aging.

Aged↗

Iliac trabecular bone formation predicts radial trabecular bone density changes in type 1 osteoporosis.

In 28 patients with idiopathic or postmenopausal type 1 (spinal crush fracture) osteoporosis, resorption indices and dynamic measurements of trabecular bone formation based on in vivo tetracycline labeling in 7.5 mm transiliac biopsies have been compared with trends in radial cortical and trabecular bone density measured with computed tomography. Positive correlations were observed between trabecular bone density trends in the radius and indices of bone formation in the ilium. These were improved when one of the two resorption indices was included with a formation index in bivariate regressions. Marked interindividual variations in radial bone density trends were also seen in cortical bone. These correlated poorly with trends in trabecular bone. Weak negative relationships between cortical bone trends and indices relating to bone formation and resorption were observed, but a positive association was seen with single-labeled surfaces on iliac trabeculae. If, as has been suggested, there are periodic variations in bone formation, the results suggest that axial and peripheral trabecular bone density trends are synchronized in osteoporosis, perhaps in response to systemic factors, such as circulating hormones.

Aged↗

hPTH 1-34 treatment of osteoporosis with added hormone replacement therapy: biochemical, kinetic and histological responses.

Twelve patients with vertebral fracture osteoporosis were recruited into a trial of treatment with hPTH 1-34 by daily injection for 1 year combined (from the 5th month) with an anti-resorptive agent (oestrogen, n = 9; nandrolone, n = 3). Treatment outcomes were monitored by biochemical and radiotracer measurements together with histomorphometry of transiliac biopsies before and at the end of treatment following double in vivo pre-labelling with demethylchlortetracycline. Indices of whole body bone formation, obtained from the analysis of 85Sr data, showed substantial increases (P less than 0.005) for all three indices measured) while biochemical (hydroxyproline) and kinetic measurements of bone resorption showed modest and equivocal changes only. As a result calcium balance improved. Gastrointestinal calcium absorption showed a tendency to improve, while urine calcium decreased; but these changes were statistically not significant except for radiocalcium absorption in the oestrogen treated subgroup. Histomorphometry revealed substantial increases in cancellous bone volume as reported previously with hPTH 1-34 given alone. However, iliac (as distinct from whole body) indices related to bone formation and resorption appeared to have returned towards pre-treatment values by the time of the second biopsy under the influence of the anti-resorptive agent given with the hPTH 1-34. It is confirmed that hPTH 1-34 therapy can increase iliac cancellous bone mass (as well as spinal cancellous bone mass as reported earlier) without a long-term increment in whole body bone resorption, providing the hPTH is combined with an anti-resorptive agent.

Aged↗

The relationship between serum vitamin D concentrations and in vivo tetracycline labeling of osteoid in crush fracture osteoporosis.

Twenty of 22 consecutive British patients with crush fracture osteoporosis had transiliac bone biopsies following double in vivo tetracycline labeling synchronized with the collection of serum for the measurement of vitamin D metabolites. A significant but direct (rather than inverse) relationship was found between 25-hydroxyvitamin D (calcidiol) levels and the fraction of cancellous surfaces covered with osteoid not taking either tetracycline label (r = 0.53, P less than 0.02). There was no correlation with 1,25-dihydroxyvitamin D levels. No patient had frankly thickened osteoid seams although 3 had reduced but measurable calcidiol levels. These results make it unlikely that the majority of patients with osteoporosis who have osteoid of normal thickness but reduced uptake of tetracycline have a mineralization defect secondary to vitamin D deficiency. The pathophysiological significance of unlabeled osteoid in osteoporosis requires further investigation.

Aged↗

A case of resolving idiopathic hypoparathyroidism.

A 72 year old man developed idiopathic hypoparathyroidism. The condition spontaneously resolved which, to our knowledge, has not been previously described. Causes of fluctuating hypocalcaemia are outlined and their possible relevance to our patient discussed.

Aged↗

Randomized, double-blind trial of deflazacort versus prednisone in juvenile chronic (or rheumatoid) arthritis: a relatively bone-sparing effect of deflazacort.

Thirty-four children with juvenile chronic (rheumatoid) arthritis were recruited to a randomized, double-blind study of deflazacort (an oxazolone derivative of prednisone) vs prednisone. All had been receiving glucocorticoid therapy for at least 1 year and required at least 5 mg/d of prednisolone (usually as 10 mg every 2 days). Thirty-one children completed the study. Bone density trends were measured in the spine by dual photon absorptiometry and in the forearm by single photon quantitative computed tomography at 3-monthly intervals. Trends (velocities) in bone and soft tissue growth were calculated. In the spine, bone growth correlated well with indices of soft tissue growth, but covariance analysis showed a significant advantage (P less than .007) of deflazacort when spinal bone mineral growth was compared to body surface area and weight. In part this was due to a temporary interruption in weight by children receiving deflazacort, whose gain in height was comparable with that of the prednisone group. Some children in both groups improved clinically and showed catch-up growth; in these children relative spinal bone mineral growth velocities were about twice those observed for height and weight. It is concluded that during the first year of deflazacort, their spinal bone mineral content at a level that was appropriate for their height and weight. Further observations are required to establish whether this advantage can be maintained subsequently. The anti-inflammatory effects of the two glucocorticoids appeared similar.

Adolescent↗

Treatment of type 1 Gaucher's disease affecting bone with aminohydroxypropylidene bisphosphonate (pamidronate).

Two patients with Type 1 (adult) Gaucher's disease and major skeletal involvement with multiple fractures have been treated with the second generation bisphosphonate pamidronate for extensive periods. There was evidence of an immediate reduction in bone resorption, with increased calcium absorption (delayed in Patient 1), improved calcium balance and maintained or improved bone density indices in the axial and peripheral skeleton. There was no evidence of immediate relapse on treatment cessation. No toxic effects of pamidronate treatment were identified and subjective skeletal pain diminished in both patients. Histomorphometry of transiliac bone biopsies obtained before the start of treatment, after double in vivo tetracycline labelling, represents one of the earliest reports of the quantitative findings in iliac bone invaded by Gaucher cells.

Adult↗

Menstrual state and exercise as determinants of spinal trabecular bone density in female athletes.

OBJECTIVE: To study the effects of amenorrhoea and intensive back exercise on the bone mineral density of the lumbar spine in female athletes. DESIGN: Cross sectional study comparing amenorrhoeic with eumenorrhoeic athletes and rowers with non-rowers. SETTING: The British Olympic Medical Centre, Northwick Park Hospital. PATIENTS: 46 Elite female athletes comprising 19 rowers, 18 runners, and nine dancers, of whom 25 were amenorrhoeic and 21 eumenorrhoeic. MAIN OUTCOME MEASURE: Trabecular bone mineral density of the lumbar spine measured by computed tomography. RESULTS: Mean trabecular bone mineral density was 42 mg/cm3 (95% confidence interval 22 to 62 mg/cm3) lower in the amenorrhoeic than the eumenorrhoeic athletes; this difference was highly significant (p = 0.0002). Mean trabecular bone mineral density was 21 mg/cm3 (1 to 41 mg/cm3) lower in the non-rowers than the rowers; this was also significant (p = 0.05). There was no interaction between these two effects (p = 0.28). CONCLUSION: The effect of intensive exercise on the lumbar spine partially compensates for the adverse effect of amenorrhoea on spinal trabecular bone density.

Adult↗

Treatment of osteoporosis with human parathyroid peptide and observations on effect of sodium fluoride.

OBJECTIVE: To evaluate the need for a randomised study of treatment of spinal osteoporosis with human parathyroid peptide in the secondary prevention of crush fractures; to study the effect of human parathyroid hormone peptide 1-34 plus sex hormones on vertebral body cancellous bone; and, separately, to determine the effect of relatively low doses of sodium fluoride plus calcium on spinal bone mineral density. DESIGN: Open study of patients with primary or postmenopausal osteoporosis. All patients had serial bone densitometry of the spine by quantitative computed tomography and dual photon absorptiometry as well as serial densitometry of the radial midshaft (cortical) and radial distal (trabecular) bone by quantitative computed tomography. Changes in the spinal bone not forming the spongiosa of the vertebral bodies ("cortical" bone) were determined from the difference between the two axial measurements, after correction to the same units of measurement. SETTING: Northwick Park Hospital and Medical Research Council Clinical Research Centre. PATIENTS: 24 Patients who fulfilled the conventional criteria for type 1 (vertebral) osteoporosis not secondary to recognised causes other than sex hormone deficiency and with at least one crush or wedge vertebral fracture and a spinal bone density (quantitative computed tomography) less than 80 mg/cm3 or two or more fractures. Twelve patients received human parathyroid peptide and 12 sodium fluoride; they were not randomised. MAIN OUTCOME MEASURES: Trends in axial and peripheral bone mass values determined by linear, time dependent regression analyses. RESULTS: The patients receiving the peptide showed a substantial increase in vertebral spongiosa (mean 25.6 mg/cm2 two years after the start of treatment). No significant changes were seen in spinal cortical or radial bone density. The patients receiving sodium fluoride showed roughly equal increases in cancellous and cortical bone over the same period (mean increase in vertebral spongiosa 16.1 mg/cm3). No significant changes were seen in radial bone. CONCLUSIONS: Treatment of postmenopausal women with human parathyroid peptide selectively increases spinal cancellous bone density by amounts that may prove useful in secondary prevention. Peptide treatment should now be tested in a randomised study in which the important end point is prevention of fractures as the usefulness of sodium fluoride in this context is doubtful.

Bone Density↗

Rapid periarticular bone loss in rheumatoid arthritis. Possible promotion by normal circulating concentrations of parathyroid hormone or calcitriol (1,25-dihydroxyvitamin D3).

For approximately 2 years, bone loss was measured in women with early stages of rheumatoid arthritis (RA) and in control subjects, using serial computed tomography and dual photon absorptiometry. Rapid trabecular bone loss from the distal radius was observed in the RA patients but not the controls. The bone loss correlated with initial plasma levels of parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol) concentrations. It has been suggested that these humoral factors may interact with cytokines or other mediators produced in the adjacent wrist joint. Losses of the cortical bone of the radial midshaft and the lumbar spine were modest and were comparable in the 2 groups. Indices relating to both bone formation and bone resorption predicted bone loss at these 2 sites, but changes in the parathyroid hormone and calcitriol concentrations did not.

Absorptiometry, Photon↗

Kinetics of intestinal calcium absorption in humans measured using stable isotopes and high-precision thermal ionization mass spectrometry.

Oral (44Ca: 0.13-0.20 mmol) and intravenous (42Ca: 0.02-0.037 mmol) isotopically enriched stable calcium (Ca) tracers were given together with an oral dose of 2.5 mmol of natural Ca to normal subjects. Blood and urine samples were collected up to 24 h after the tracer doses and atom fractions (AFs) of these tracers (relative to natural Ca) were measured by high-precision thermal ionization mass spectrometry (TIMS). The time-dependent fractional rate of oral dose absorbed and true fractional intestinal Ca absorption (alpha) were derived from the Afs by mathematical deconvolution. After 6 h, the ratio AF oral tracer/AF intravenous tracer in blood equalled that in urine and did not change thereafter. Reproducibility of the combination of chemical precipitation of Ca (from a urine standard) and subsequent TIMS measurements, in nine runs over 13 months, was 1.2% (coefficient of variation). This was in accord with the within-run reproducibility. An estimate of alpha derived from a single blood or urine measurement was 6-10% higher than the reference value obtained by deconvolution. This discrepancy could be explained by a correction factor depending, in part, on the elapsed time for peak Ca intestinal absorption rate. Instrumentally induced mass fractionation, as well as contributions from radiogenic Ca, had a significant effect on the accuracy and reproducibility of the ratio of AFs of tracers in blood and urine.

Administration, Oral↗

High indices of remodelling in iliac trabecular bone predict reduced forearm cortical bone mass indices in patients with proximal femoral fractures.

To investigate whether high bone turnover could be a predictor of cortical bone loss and a candidate risk factor for fractures of the proximal femur, 33 7.5-mm transiliac biopsies taken at fracture fixation from 48 patients who participated in a study of potential risk factors have been quantitated. Twenty-four of the 33 patients made good recoveries and about 6 weeks postoperatively consented to bone densitometry of the forearm midshaft. Forearm bone density correlated negatively (r = 0.77, P = 0.001) with the surface of trabecular bone covered with osteoid, which in osteoporotic patients with crush fractures of the vertebrae was previously shown to relate both to rates of bone formation and resorption. An important minority of these femoral fracture patients appeared to be suffering from high rates of iliac trabecular bone resorption. Thus, high bone remodelling activity could lead to excessive cortical thinning. This has pathogenetic implications which may be clinically important.

Aged↗