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Biomedical subjects

R Eastell

Publications and source records attributed to R Eastell.

At least 145 records · Page 8Linked to original sources

Different responses of biochemical markers of bone resorption to bisphosphonate therapy in Paget disease.

We examined the response of different biochemical markers of bone resorption to bisphosphonate therapy (400 mg of etidronate daily for 6 months) in mild Paget disease (n = 14). Urinary markers included hydroxyproline (OHP), total (T) and free (F) pyridinolines (Pyds) determined by HPLC, immunoreactive FPyds, immunoreactive TPyds, and the N- and C-terminal telopeptides of type I collage (NTx, CL). Serum measurements included tartrate-resistant acid phosphatase (TRAcP) and the C-terminal telopeptide of type I collagen (ICTP). ICTP and TRAcP showed a minimal response to therapy (% change at 6 months, -13.1 +/- 6.8 and -6.7 +/- 3.4, respectively). The response was greatest for urinary telopeptides (NTx and CL; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectively). The response was somewhat greater for TPyds than for FPyds. We conclude that: (a) ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b) oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine show a somewhat greater response to therapy than do FPyds and may be more sensitive indicators of bone resorption; and (c) as yet no evidence suggests that these markers are substantially better predictors of the clinical response to therapy than serum total alkaline phosphatase or urinary OHP. There are several problems with the interpretation of these measurements in Paget disease, and the clinical utility of these measurements remains uncertain.

Acid Phosphatase↗

Bone mineral density of the hand in rheumatoid arthritis.

OBJECTIVE: To determine the reproducibility, accuracy, and linearity of hand bone mineral content (BMC) measurements, and to evaluate the influence of hand posture; to determine the relationship of hand bone mineral density (BMD) to generalized osteopenia in rheumatoid arthritis (RA); and to determine the relationship between hand BMD and disease severity in early RA. METHODS: Hand BMD was measured by dual-energy x-ray absorptiometry (DXA). We studied 70 postmenopausal women with steroid-treated RA (established RA), ages 49-79, and 20 age-matched healthy controls to determine the relationship to generalized osteoporosis; we also studied 20 patients aged 23-74 years with early RA to determine the relationship between disease severity and hand BMD. RESULTS: Reproducibility of hand BMD was to within 1%. In established RA, there was a greater decrease in juxtaarticular BMD (23% at the hand) than in generalized BMD (16% at the femoral neck, 11% at the lumbar spine, and 11% total body) compared with that in age-matched controls. Hand BMD correlated with skeletal size and BMD at other skeletal sites. In established RA, there was no effect of disease duration, disability, or steroid therapy. In early RA, hand BMD correlated with age and disease activity. CONCLUSION: Measurement of hand BMD by DXA is accurate and precise. Hand BMD reflects BMD at other skeletal sites in patients with RA, and is a marker of disease severity in patients with early disease. It may be a sensitive marker of disease progression and response to therapeutic intervention.

Aged↗

Diagnostic value of estimated volumetric bone mineral density of the lumbar spine in osteoporosis.

Bone mineral density (BMD) measurements by dual-energy x-ray absorptiometry (DXA) are planar measurements. By measuring planar BMD in anteroposterior (AP) and lateral projections, it is possible to estimate the volumetric BMD by assuming that the vertebral body is an ellipsoid cylinder. Correction for the third dimension could improve the diagnostic accuracy of spinal BMD measurement in osteoporosis. The aims of this study were (1) to determine the effect of aging on volumetric BMD compared to planar measurements; and (2) to evaluate the diagnostic accuracy of volumetric BMD in comparison to planar measurements. We studied 26 postmenopausal women with osteoporotic vertebral fractures and 114 age- and sex-matched controls without vertebral fractures from a population-based group. AP and lateral decubitus BMD of the lumbar spine were measured by DXA using a Lunar DPX (precision error for AP measurement, 0.8%; for lateral measurement of vertebra L3, 6.4%). Between the ages of 51 and 85 years the decreases in volumetric BMD of L3 (vol L3), lateral BMD of L3 (lat L3), AP BMD of L3 (AP L3), and AP BMD of L2-4 (AP L2-4) were 31, 28, 17, and 17%, respectively. The decrease in BMD compared to controls in the osteoporotics for vol L3, lat L3, AP L3, and AP L2-4 were 31, 34, 23, and 23%; expressed as Z scores, the decreases were -1.36, -1.33, -1.46, and -1.47 standard deviation units. The areas under ROC analysis curves for vol L3, lat L3, AP L3, and AP L2-4 were 85, 86, 87, and 87%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Diclofenac sodium inhibits bone resorption in postmenopausal women.

BACKGROUND: The results of experimental studies with animals indicated that prostaglandins stimulate bone resorption, that skeletal production of prostaglandin E2 is enhanced by ovariectomy and is diminished by 17 beta-estradiol, and that the nonsteroidal anti-inflammatory drug (NSAID) naproxyn prevents bone loss after ovariectomy. Studies were carried out to investigate the effects of the NSAID diclofenac sodium on bone and mineral metabolism in premenopausal women and to compare the effects of diclofenac sodium and conjugated estrogens on bone and mineral metabolism in postmenopausal women. PATIENTS AND METHODS: Ten healthy premenopausal women and 17 healthy postmenopausal women were studied while not being treated and again after 4 weeks of treatment with diclofenac sodium, 150 mg per day in divided doses (both groups), and conjugated estrogens, 0.625 mg per day (postmenopausal women). Cross-linked N-telopeptides of type I collagen were measured in the urine as an index of bone resorption. The postmenopausal women were separated into two groups, responders and nonresponders, based on their response to conjugated estrogens as assessed by linear discriminant analysis for groups. Conjugated estrogens lowered urinary N-telopeptides of type I collagen in responders, but not in nonresponders. RESULTS: Urinary cross-linked N-telopeptides were higher in the eight postmenopausal women responders than in the nine postmenopausal nonresponders or in the premenopausal women, and were not altered by diclofenac sodium in premenopausal women. In the eight postmenopausal women with higher rates of bone resorption, diclofenac sodium and conjugated estrogens significantly lowered both urinary calcium concentration and urinary cross-linked N-telopeptides. The effects of the two drugs were comparable. CONCLUSION: The preliminary results demonstrate that, at the dose used, diclofenac sodium is almost as effective as conjugated estrogens for decreasing bone loss in postmenopausal women. Further studies will be needed to determine whether diclofenac sodium can prevent postmenopausal bone loss.

Adult↗

Stable strontium absorption as a measure of intestinal calcium absorption: comparison with the double-radiotracer calcium absorption test.

1. Stable strontium (Sr) has been proposed as an alternative to calcium (Ca) isotopes for the measurement of intestinal Ca absorption. The aim of this study was to compare the time course and fractional absorption of Ca and Sr, when both are measured using dual-tracer techniques. 2. 45Ca and Sr absorption tests were carried out on consecutive days in patients with osteoporosis (n = 10) or chronic renal failure (n = 7). Both tests were repeated in four patients with chronic renal failure after treatment with calcitriol (1 microgram daily for 10 days). 3. The time course of Ca absorption was determined using the 85Sr (intravenous)/45Ca (oral) dual-tracer technique, and the time course of Sr absorption using 85Sr (intravenous)/stable Sr (oral). Oral tracers were administered on consecutive days with a test meal containing 5.3 mmol of Ca and 2.5 mmol of either stable Sr or Ca carrier. The fractional absorption of 45Ca and Sr at 6h (FA360) and the absorption rate as a function of time were calculated by deconvolution. 4. The mean FA360 for Sr (20.2%) was lower than the mean FA360 for 45Ca (37.8%, P < 0.001, paired t-test), but the time course of Sr absorption was similar to that of Ca. There was a significant correlation between the FA360 for 45Ca and Sr, although the relationship was improved by including a quadratic term (R2 = 0.89, P < 0.001, significance of quadratic term, P < 0.05). After 1,25-dihydroxyvitamin D treatment, the FA360 of stable Sr increased 4.29-fold, whereas the FA360 of 45Ca increased only 2.4-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Biochemical markers of bone turnover in girls during puberty.

OBJECTIVE: Bone turnover and the rate of bone growth increase dramatically during puberty. A number of new assays for the estimation of bone resorption and formation rates have been developed over recent years, and puberty acts as a convenient model for evaluation of these measurements. The aim of this study was to explore the interrelationships between pubertal development, biochemical markers of bone turnover, insulin-like growth factor I and oestradiol in healthy pubertal girls. SUBJECTS: Ninety-one healthy girls (ages 11.6-15.5 years) were studied. All subjects were apparently healthy, and were not taking medications known to influence calcium homeostasis. Breast examination was performed to assess pubertal stage according to Tanner. The adult reference range for biochemical markers of bone turnover was obtained from concurrent studies on 42 healthy premenopausal women ranging in age between 20 and 45 years. DESIGN AND MEASUREMENTS: Blood samples were obtained from subjects between 0800 and 1000 h. Urine samples were collected between 1330 and 1600 h. We measured total and bone specific alkaline phosphatase, osteocalcin, and type I procollagen carboxyterminal propeptide as markers of bone formation. Tartrate resistant acid phosphatase, carboxyterminal pyridinoline cross-linked telopeptide, creatinine corrected urinary deoxypyridinoline, immunoreactive urinary pyridinolines, and urinary galactosyl hydroxylysine were measured as markers of bone resorption. RESULTS: Bone turnover as reflected by each of the markers was maximal in mid puberty (breast Tanner stages II and III) and decreased towards adult levels in late puberty (P < 0.001). However, the magnitude of the mid-pubertal increase differed between markers. In particular, the pubertal increase in levels of bone specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline were higher than the increase shown by the other markers. All markers were significantly lower after the menarche. Circulating insulin-like growth factor I and insulin like growth factor binding protein-3 were not important determinants of pubertal changes in bone turnover. In contrast, there was a significant negative correlation between oestradiol and all markers of bone formation and resorption during puberty. CONCLUSIONS: The greater pubertal increase in levels of bone specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline suggests that these markers may be relatively more sensitive as indicators of skeletal health during puberty. The differences between markers may reflect differences in the bone specificity of the analytes, or differing mechanisms of production and clearance. The negative correlation between oestradiol and markers of bone resorption and formation suggests that this hormone may be responsible for the reduction in bone turnover in late puberty.

Acid Phosphatase↗

Excretion of pyridinium crosslinks correlates with disease activity and appendicular bone loss in early rheumatoid arthritis.

OBJECTIVE: To establish if urinary excretion rates of the collagen crosslinks pyridinoline and deoxypyridinoline, which are known to be elevated in established rheumatoid arthritis (RA), are useful markers of bone loss in this disease. METHODS: Eight hour urine collections on all patients and 52 controls were performed, and the rates of pyridinoline and deoxypyridinoline excretion were measured. Bone mineral density (BMD), by dual energy x-ray absorption, and full laboratory and clinical assessments were performed. RESULTS: The rates of excretion of pyridinoline and deoxypyridinoline were significantly increased in patients compared with controls (p < 0.001). Pyridinoline excretion was associated with increased disease activity (ESR/CRP) but not disability (HAQ score/Functional Grade), and correlated with BMD loss at the femoral neck (p < 0.01). CONCLUSION: The excretion of collagen crosslinks may be useful as markers of bone and cartilage turnover in patients with RA.

Acute Disease↗

The effect of calcium supplementation on the circadian rhythm of bone resorption.

Bone resorption shows a circadian rhythm in human subjects, but the physiological mechanisms underlying this rhythm are unknown. We compared the circadian rhythm of bone collagen degradation in 18 premenopausal women before and after oral calcium supplementation (1000 mg calcium for 14 days). Subjects were randomized to receive calcium at either 0800 h or 2300 h. Continuous 48-h urine collections and 1 day of 4-h urine collections were obtained before and after the 14-day supplementation period. We measured urinary deoxypyridinoline (Dpd) and the cross-linked N-telopeptide of type I collagen (NTx) as biochemical markers of bone resorption. There was a significant effect of time of day on excretion of Dpd and NTx (analysis of variance, P < 0.001) with peak excretion between 0300-0700 h and a nadir between 1500-1900 h. The mean amplitude (peak to trough) was similar for Dpd and NTx (70.3% and 63.3%, respectively). Evening calcium supplementation resulted in marked suppression of the nocturnal increase in Dpd and NTx and reversed the usual nocturnal increase in the level of parathyroid hormone. In contrast, morning calcium supplementation had no significant effect on the circadian rhythm of Dpd or NTx. Evening calcium supplementation suppressed overall daily excretion of Dpd by 20.1% (P = 0.03) and NTx by 18.1% (P = 0.03). Morning calcium supplementation had no significant effect on overall daily excretion of either Dpd or NTx. We conclude that evening calcium supplementation suppresses the circadian rhythm of bone resorption. The daily rhythm of PTH secretion or calcium intake is likely to be an important determinant of this rhythm. Experimental protocols designed to investigate the effect of calcium supplementation on bone mineral density should take the timing of supplementation into account.

Adult↗

Impact of anomalous vertebral segmentation on measurements of bone mineral density.

In anteroposterior (AP) bone mineral density (BMD) measurements of the lumbar spine (LS), the presence of ribs is used to identify vertebra T12. Similarly, in lateral LS-BMD measurements, the position of the iliac crest is used to identify the lumbar vertebrae. The aim of this study was to determine the impact of variations in spinal segmentation and iliac crest position on BMD measurements. In 375 women (ages 50-85 years) radiographs were taken of the thoracic and lumbar spine, as well as AP measurement of LS-BMD, by dual-energy x-ray absorptiometry (DXA). In 121 subjects lateral decubitus LS-BMD was also measured. Anomalous spinal segmentation was found in 16.5%, and L1 would have been incorrectly identified on the AP-DXA image in 13%. The change in BMC and BMD between adjacent vertebrae was greater in the upper than the lower lumbar spine. Misidentification of L1 for T12 resulted in underestimation of the bone mineral content in grams (BMC) of L1 by a mean of 11.5 +/- 14.4% (SD; range -33.5 to 33.5%). For the usual region of interest, L2-4, the BMC (g) was underestimated by 8.4 +/- 8.7% (range -1.5 to 29.2%), with the BMD (g/cm2) underestimated by 3.6 +/- 4.8% (range -5.4 to 11.6%). The position of the iliac crest on the lateral decubitus DXA scans would have led to misidentification of either L2 or L4 for L3 in 15 cases (12%). This resulted in the BMD of L3 being underestimated by 2.7 +/- 19.4% (range -242.4 to 34.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗