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Biomedical subjects

R Eastell

Publications and source records attributed to R Eastell.

At least 109 records · Page 6Linked to original sources
PubMed1998

A longitudinal study of bone gain in pubertal girls: anthropometric and biochemical correlates.

The aim of this longitudinal study was to investigate the factors associated with bone mineral acquisition in pubertal girls. Subjects were 37 healthy, Caucasian girls aged 12.1 years (SD 0.3). Measurements were made at 6-month intervals over a period of 18 months and included total body bone mineral content (TBBMC), total body bone mineral density (TBBMD), lean mass, and fat mass by dual-energy X-ray absorptiometry, anthropometry, lifestyle factors, four biochemical markers of bone turnover, hormonal status, and fractional calcium absorption. In multiple regression analysis, correlates of relative gain in TBBMC were gain in lean mass (p < 0.001) and estradiol (p = 0.008). For TBBMD, correlates were gain in lean (p < 0.001) and fat mass (p = 0.003), estradiol (p < 0.001), dietary energy intake (p = 0.003), and parathyroid hormone (p = 0.023). Statural growth and gain in bone mass were unrelated; both height velocity and bone turnover peaked approximately 20 months prior to menarche, whereas gain in bone mass peaked at menarche. Bone turnover markers correlated with height velocity (0.40 < r < 0.62), but not with bone gain. Estradiol was independently and negatively associated with all markers of bone turnover (-0.67 < r < -0.80). We conclude that estradiol is an important determinant of bone mineral gain in pubertal girls and is probably responsible for the reduction in bone turnover in late puberty; lean mass was the body composition parameter most closely associated with bone gain; height gain and bone gain are dissociated during the period of rapid growth at puberty; and bone turnover markers are modestly related to height gain, but are not predictive of bone gain.

Anthropometry↗
PubMed1998

Response of biochemical markers of bone turnover to hormone replacement therapy: impact of biological variability.

Biochemical markers of bone turnover may be useful to monitor patients taking hormone replacement therapy (HRT). The aim of this study was to assess the utility of markers in monitoring HRT by comparing the response of a large panel of markers to HRT with their within subject variability. We measured the response of markers to transdermal estradiol in 11 postmenopausal women over 24 weeks. We measured the within subject variability of markers in 11 untreated healthy postmenopausal women over the same period. The mean decrease in markers of bone formation after 24 weeks treatment ranged from 19% for procollagen type I C-terminal propeptide (PICP) to 40% for procollagen type I N-terminal propeptide (PINP). The mean decrease in markers of bone resorption ranged from 10% for tartrate-resistant acid phosphatase (TRAP) to 67% for C-terminal cross-linked telopeptide The least significant change (LSC at p < 0.05), calculated from the within subject variability in the untreated group, was used to define response. LSC for osteocalcin was 21%, bone alkaline phosphatase 28%, PICP 24%, PINP 21%, type I collagen telopeptide 28%, TRAP 17%, urinary calcium 90%, hydroxyproline 75%, total deoxypyridinoline 47%, free pyridinoline 36%, free deoxypyridinoline 26%, N-terminal cross-linked telopeptide 70%, and C-terminal cross-linked telopeptide 132%. The greatest number of responders after 24 weeks of treatment were found using PINP and osteocalcin (9 each), and free deoxypyridinoline (8 each) and total deoxypyridinoline (8 each) and total deoxypyridinoline (7 each). Lumbar spine bone mineral density defined four patients as responders. The ability to detect a response differs between markers and is not dependent on the magnitude of response to therapy.

Absorptiometry, Photon↗
PubMed1998

Bone mass and muscle strength in female college athletes (runners and swimmers).

OBJECTIVE: To determine whether female college athletes had increased muscle strength and bone mass in comparison with age-matched nonathletic female subjects and, if so, whether participation in weight-bearing versus non-weight-bearing exercise made a difference. MATERIAL AND METHODS: We performed a comparative statistical analysis of the bone mineral density (BMD) of the total body, lumbar spine, and femoral neck, maximal oxygen uptake (VO2max), muscle strength, and level of physical activity in 21 runners, 22 swimmers, and 20 control subjects. The study participants were female college students, 18 to 24 years old, who had had more than 8 normal menstrual cycles during the past year. RESULTS: Statistical analyses showed significantly higher VO2max in the two athletic study groups than in the control subjects (P < 0.0001). No significant difference in BMD was noted among the three groups. Total body BMD (r = 0.30; P = 0.02) and femoral neck BMD (r = 0.39; P = 0.002) were positively correlated with weight-bearing activity but not with non-weight-bearing activity. VO2Max (an index of physical fitness) was positively correlated with femoral neck BMD (r = 0.33; P = 0.009) and trochanteric BMD (r = 0.29; P = 0.021). Shoulder muscle strength (determined by isokinetic dynamometry) was positively correlated with total body BMD (r = 0.34; P = 0.007) and lumbar spine BMD (r = 0.28; P = 0.028). Swimmers had higher muscle strength in the back and upper extremities than did runners and control subjects. Hip girdle muscle strength was not significantly different among the three groups. Total body BMD had a positive correlation with percentage of body fat and height. Lumbar spine BMD was higher in subjects who had previously used oral contraceptives. The athletes had a lower percentage of body fat, were less likely to have used oral contraceptives, and had fewer years of normal menses than did the control subjects. CONCLUSION: Our study shows that (1) total body BMD and femoral neck BMD were significantly higher in the study group that performed weight-bearing exercises than in control subjects, (2) swimming exercise had no effect on BMD, and (3) although swimming is not a bone-building exercise, it can significantly improve shoulder, back, and grip muscle strength.

Adult↗
PubMed1997

Milk intake and bone mineral acquisition in adolescent girls: randomised, controlled intervention trial.

OBJECTIVES: To investigate the effect of milk supplementation on total body bone mineral acquisition in adolescent girls. DESIGN: 18 month, open randomised intervention trial. SUBJECTS: 82 white girls aged 12.2 (SD 0.3) years, recruited from four secondary schools in Sheffield. INTERVENTION: 568 ml (one pint) of whole or reduced fat milk per day for 18 months. MAIN OUTCOME MEASURES: Total body bone mineral content and bone mineral density measured by dual energy x ray absorptiometry. Outcome measures to evaluate mechanism included biochemical markers of bone turnover (osteocalcin, bone alkaline phosphatase, deoxypyridinoline, N-telopeptide of type I collagen), and hormones important to skeletal growth (parathyroid hormone, oestradiol, insulin-like growth factor I). RESULTS: 80 subjects completed the trial. Daily milk intake at baseline averaged 150 ml in both groups. The intervention group consumed, on average, an additional 300 ml a day throughout the trial. Compared with the control group, the intervention group had greater increases of bone mineral density (9.6% v 8.5%, P = 0.017; repeated measures analysis of variance) and bone mineral content (27.0% v 24.1%, P = 0.009). No significant differences in increments in height, weight, lean body mass, and fat mass were observed between the groups. Bone turnover was not affected by milk supplementation. Serum concentrations of insulin-like growth factor I increased in the milk group compared with the control group (35% v 25%, P = 0.02). CONCLUSION: Increased milk consumption significantly enhances bone mineral acquisition in adolescent girls and could favourably modify attainment of peak bone mass.

Adolescent↗
PubMed1997

Relationships between biochemical and symptomatic response in a double-blind randomised trial of pamidronate for metastatic bone disease.

PURPOSE: The aim of this study was to evaluate pamidronate for bone pain in a randomised double-blind trial and to evaluate the contribution of new markers of bone resorption in patients with bone metastases. PATIENTS AND METHODS: Fifty-two patients with painful bone metastases were randomised to receive a two-hour infusion of pamidronate 120 mg or an identical infusion of saline. Four weeks later, all patients received pamidronate 120 mg. Bone resorption markers measured included urinary calcium (uCa), hydroxyproline (Hyp), and the collagen breakdown products: NTx, Crosslaps and Free Dpd. RESULTS: Symptomatic response during the first four weeks was seen after pamidronate, but not with placebo (P < 0.05). Quality of life was maintained with pamidronate and deteriorated after placebo (P < 0.05). Resorption markers did not decrease after placebo, but NTx and Crosslaps both decreased by 70% after pamidronate (P = 0.001). A second infusion of pamidronate did not decrease resorption further, but maintained the suppression of resorption at similar levels for a further four weeks. Symptomatic response to pamidronate correlated closely with the rate of bone resorption; it was more frequent in those patients with an initial NTx value of < 2 times the upper limit of normal (17 of 27, 62%) and in those where the level of Ntx returned to normal (19 of 32, 59%), than in the patients with either high baseline values of NTx (> 2 times the upper limit of normal) or Ntx levels which failed to normalise for whom the response frequencies were 2 of 16 (13%) and 0 of 11 (0%), respectively. CONCLUSIONS: Subjective benefit after intravenous pamidronate is confirmed in this placebo-controlled study. The new bone resorption markers of collagen breakdown were able to predict clinical response to pamidronate.

Adult↗
PubMed1997

The effect of dietary sodium on calcium metabolism in premenopausal and postmenopausal women.

OBJECTIVE: To investigate the effects of high and low sodium diets on urinary calcium, bone turnover and calcium absorption in pre and postmenopausal women. DESIGN: Experimental, prospective and longitudinal study. SETTING: Samples were taken at the hospital and the diets were followed at home. SUBJECTS: Volunteers were recruited from the hospital and were either hospital staff or post-graduate students. No volunteers failed to complete the study but one was omitted from analysis due to lack of compliance. INTERVENTIONS: Eleven healthy premenopausal women aged 22-47 y and 11 healthy postmenopausal women ages 45-70 y followed a high (300 mmol/d) and a low (50 mmol/d) sodium diet for one week each. On the 7th day of each diet, blood and urine samples were taken. RESULTS: On the high sodium diet 24 h urinary sodium and calcium values relative to creatinine were significantly higher for all subjects (P < 0.05). Postmenopausal women on the high sodium diet had biochemical evidence of increased bone resorption in relation to the low sodium diet. However in premenopausal women there was no such change. Calcium absorption did not change significantly in either group. CONCLUSIONS: It appears that postmenopausal, but not premenopausal, women respond to a high sodium diet by an increase in bone resorption which may lead to reduced bone density. SPONSORSHIP: Arthritis and Rheumatism Council Project Grant R44.

Absorption↗
PubMed1997

Longitudinal changes of bone mineral density and bone turnover in postmenopausal women on thyroxine.

OBJECTIVE: The skeletal risks of subclinical hyperthyroidism in postmenopausal women on replacement thyroxine remain controversial. The aims of this study were to determine (1) the relationship between bone turnover and TSH levels and (2) whether reduction of thyroxine (T4) dose in postmenopausal women who have suppressed TSH levels is beneficial to bone mineral density (BMD) and bone turnover. DESIGN: A prospective study over 2 years of post-menopausal women treated with T4 with an age- and sex-matched healthy control group. PATIENTS AND MEASUREMENTS: Sixty-four post-menopausal women, ages 47 to 74 (61 +/- 9, mean +/- SD), on T4 for between 2 and 14 years. Patients were divided into three groups: group 1 (n = 23) with normal serum TSH levels, group 2 (n = 18) with suppressed serum TSH levels and group 3 (n = 23) with a history of thyroidectomy and suppressed TSH levels (patients with thyroid cancer). Thirty-six age-matched healthy postmenopausal women were recruited as a control group. Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and bone turnover, were evaluated at baseline and over 2 years in the four groups. Serum TSH levels were measured every 6 to 12 months. In group 2, the dose of T4 was reduced after the baseline measurement and serum TSH levels were remeasured 1 to 4 months later. Serum TSH levels returned to the reference range after the reduction of T4 dose in group 2. RESULTS: The serum TSH level, after log transformation, was negatively correlated with serum levels of osteocalcin (BGP), bone alkaline phosphatase (BAP) and urinary cross-linked N-telopeptides pyridinoline of type I collagen (NTx) (linear correlation, r = -0.41 P < 0.001, r = -0.29 P = 0.01 and r = -0.26 P = 0.033), respectively. There was no significant difference in BMD and bone turnover between the four groups at either baseline or follow-up (ANOVA, P > 0.05). The levels of serum BGP, BAP and urinary NTx decreased whereas lumbar spine and femoral neck BMD increased significantly in group 2 over 2 years (one sample t-test, P = 0.0021, 0.034, 0.0017, 0.011 and < 0.001, respectively). In group 2, the rates of change of lumbar spine and femoral BMD were increased significantly and the rates of change of serum BGP and urinary NTx were decreased significantly compared with other groups (Scheffe test, P < 0.05). CONCLUSIONS: In postmenopausal women on T4, bone turnover is related to the serum TSH level and a reduction of T4 dose in those with suppressed serum TSH levels can result in a decrease in bone turnover and an increase in bone mineral density.

Aged↗
PubMed1997

Glucocorticoid replacement therapy: are patients over treated and does it matter?

BACKGROUND AND OBJECTIVES: Adequate assessment of patients on glucocorticoid replacement therapy is of great importance to avoid the consequences of under or over treatment, but no simple test is available for this. The aims of this study were (1) to assess adequacy of glucocorticoid replacement in hypoadrenal patients, (2) to correlate serum cortisol levels (cortisol day curve) with 24-hour urine free cortisol excretion and (3) to assess the impact of glucocorticoid dose optimization on markers of bone formation and bone resorption. DESIGN: Cross-sectional study of current replacement therapy and a prospective study of the effect of dose alteration on bone turnover markers. PATIENTS: Thirty-two consecutive patients on replacement glucocorticoid therapy (12 Addison's disease, 20 hypopituitarism) from a University teaching hospital out-patient department. MEASUREMENTS: Serum and urinary cortisol, osteocalcin, N-telopeptide of type I collagen (NTX) and bone mineral density. RESULTS: 28/32 (88%) patients required a change of therapy; 24/32 (75%) a total reduction in dose, 18/32 (56%) a change in replacement therapy regimen or drug and 14/32 (44%) both changes. The mean daily dose of hydrocortisone was reduced from 29.5 +/- 1.2 to 20.8 +/- 1.0 mg. A significant correlation was found between peak cortisol and 24-hour urine free cortisol/ creatinine (Spearman correlation r = 0.60, P < 0.0001; n = 51). Following hydrocortisone dose reduction, median osteocalcin increased from 16.7 micrograms/l (range 8.2-65.7) to 19.9 micrograms/l (8.2-56.3); P < 0.01, with no change in the NTX/creatinine ratio. CONCLUSIONS: A high proportion of patients on conventional corticosteroid replacement therapy are over treated or on inappropriate replacement regimens. To reduce the long term risk of osteoporosis, corticosteroid replacement therapy should be individually assessed and over replacement avoided.

Addison Disease↗
PubMed1997

Growth in infancy and bone mass in later life.

OBJECTIVE: To examine the association between weight in infancy and bone mass during the seventh decade of life in a population based cohort for which detailed birth and childhood records were preserved. METHODS: 189 women and 224 men who were aged 63-73 years and were born in East Hertfordshire underwent bone densitometry by dual energy x ray absorptiometry. Measurements were also made of serum osteocalcin and urinary excretion of type 1 collagen cross linked N-telopeptide. RESULTS: There were statistically significant associations between weight at 1 year and bone mineral content (but not bone mineral density) at the spine (P < 0.02) and femoral neck (P < 0.01) among women, and spine (P < 0.03) among men. Although serum osteocalcin was negatively correlated with bone mineral density at both sites among men and women, infant weight was not significantly associated with either biochemical marker of bone turnover. CONCLUSIONS: These data confirm our previous observations that growth in infancy is associated with skeletal size in adulthood, and suggest that skeletal growth may be programmed during intrauterine or early postnatal life.

Aged↗
PubMed1997

Evaluation of new bone resorption markers in a randomized comparison of pamidronate or clodronate for hypercalcemia of malignancy.

PURPOSE: To compare the effects of two bisphosphonates on markers of bone resorption in a randomized double-blind trial for the treatment of hypercalcemia of malignancy. PATIENTS AND METHODS: Thirty-two patients with a serum calcium (sCa) level > or = 2.7 mmol/L that persisted after 48 hours of saline rehydration were randomized to receive pamidronate 90 mg or clodronate 1,500 mg. Bone resorption markers measured included urinary calcium (uCa), hydroxyproline (Hyp), deoxypyridinoline (Dpd), pyridinoline (Pyd), the cross-linking molecule at either the N-telopeptide (NTx) or the C-telopeptide (Crosslaps) regions of type I collagen, and free Dpd. RESULTS: Both bisphosphonates restored normocalcemia, but the duration of action was longer after pamidronate (P < .01). There was a mean pretreatment sevenfold increase in NTx, fivefold increase in Dpd and Crosslaps, and 2.5-fold increase in free Dpd. The changes in uCa were confounded by an increase in parathyroid hormone (PTH) (P < .05), which, through effects on the kidney, inhibits calcium excretion. Most resorption markers showed a larger decrease after pamidronate than clodronate (P < .01). NTx and Crosslaps showed the greatest decrease, being significantly different from any other marker in both arms (P < .01). There was a significant correlation between Dpd, NTx, and Crosslaps (P < .002), but not with uCa. CONCLUSION: The superiority of pamidronate in controlling hypercalcemia is mirrored by the changes observed in these markers. uCa is not an accurate bone resorption marker, which reflects the renal handling of calcium by PTH. NTx and Crosslaps showed the largest increase at baseline and the greatest change after treatment, which suggests these new markers may be more sensitive indicators of bone resorption.

Adult↗
PubMed1997

Treatment of isolated hypogonadotropic hypogonadism effect on bone mineral density and bone turnover.

Isolated hypogonadotropic hypogonadism (IHH) presents with delayed puberty in the late teens or early twenties, with a period of testosterone deficiency during active growth. The aims of the study were to determine 1) whether long term treatment of IHH results in normalization of bone density (BMD) and bone turnover, and 2) whether BMD and bone turnover respond to increasing doses of hCG. We studied 10 men, aged 26-46 yr, with IHH who were treated with hCG or testosterone esters (Sustanon) for 2-22 yr, with age at the start of treatment between 17-29 yr, and 10 age- and body weight-matched normal men as a control group. At baseline, lumbar spine, femoral neck, trochanter, and Ward's triangle BMD values were decreased, and serum bone Gla-protein, bone alkaline phosphatase, and urinary pyridinoline, deoxypyridinoline, and N-terminal telopeptide of type I collagen were increased compared with control values (by paired t test, P = 0.02, 0.03, 0.01, 0.05, 0.002, 0.02, 0.02, 0.007, and 0.006, respectively). The age at initial therapy was significantly correlated with total body BMD (r = -0.73; P = 0.017) and lumbar spine BMD (r = -0.756; P = 0.0097). Serum free testosterone was correlated with total body and trochanter BMD (r = 0.635; P = 0.048 and r = 0.629; P = 0.05), and serum free estradiol was correlated with total body and trochanter BMD (r = 0.641; P = 0.045 and r = 0.634; P = 0.048). Six of the 10 patients were recruited for a longitudinal study in which the dose of hCG was increased monthly from 2000 i.u. twice per week to 6000 i.u. twice per week. After increasing doses of hCG, levels of serum testosterone and estradiol and total body BMD increased significantly (by paired t test P = 0.001, 0.003, and 0.01, respectively). Serum bone Gla-protein levels increased by the first month and then decreased (paired t test, corrected by Bonferroni's method). Serum bone alkaline phosphatase and urinary N-terminal telopeptide of type I collagen/creatinine levels decreased significantly after increasing the dose of hCG. We conclude that patients with IHH who have serum testosterone within the laboratory reference range may require a higher dose of hCG to normalize BMD and bone turnover.

Adult↗
PubMed1997

Biochemical markers of bone resorption compared with estimates of bone resorption from radiotracer kinetic studies in osteoporosis.

The pyridinium cross-links of collagen pyridinoline (Pyd) and deoxypyridinoline (Dpd) are released during bone resorption and are neither metabolized nor absorbed from the diet. The aim of this study was to validate their use in osteoporosis. We studied 19 women with osteoporosis and estimated the bone resorption rate from a combined calcium balance/kinetics technique without (R) and with partial (R(H)) and "complete" (Res) correction for long-term exchange. The strongest correlation was observed between the bone-specific marker (Dpd) and with complete correction for long-term exchange (Res) (r = 0.71, p < 0.001). The intercept was not different from zero, suggesting that bone was the major source for Dpd. The crude ratio of Dpd to Res in the 19 women was 54.5; but the regression coefficient relating Dpd as the dependent variable to Res was 31.8 (95% CI 15.6-48.0), which was higher, but not significantly, than the ratio between Dpd and calcium (16.4) in 10 bone samples (cortical and trabecular bone). The weakest correlations between a biochemical marker and a kinetic index were those between hydroxyproline (a nonspecific marker of bone resorption) and R or R(H). Treatment with hormone replacement therapy (HRT) or HRT and parathyroid hormone peptide 1-38 in seven women over 1 year resulted in similar percent changes in the biochemical markers and estimates of bone resorption. We conclude that the measurement of Dpd provides a reasonably accurate assessment of bone resorption in osteoporosis, and in the context of several repeat 24-h collections of urine offers measurement precision that is similar to that obtainable with methods depending on the use of radioisotopic tracers and the assessment of metabolic calcium balance.

Aged↗
PubMed1997

The value of biochemical markers of bone turnover in osteoporosis.

A number of biochemical markers of bone turnover have been described and these reflect the activity of osteoblasts (bone formation) or osteoclasts (bone resorption). These markers have the following advantages for the measurement of bone turnover: (1) they are noninvasive; (2) inexpensive; (3) can be repeated on many occasions; (4) and reflect bone cell activity in the entire skeleton. They have disadvantages: (1) they do not provide information about the work of individual cells; (2) they do not reflect the process of mineralization; and (3) their levels may be affected by the rate of clearance. The markers have been used to study the pathogenesis of osteoporosis, identify postmenopausal women with accelerated bone loss, predict fracture independently of bone loss, predict response to therapy, and monitor response to therapy. They may also be useful in the setting of clinical trials for choosing minimal and maximal effective doses, understanding the mechanism of the changes in bone mineral density (BMD) and studying the effect and time course of changes in bone after cessation of therapy. Markers do not provide a surrogate for fracture risk or BMD. However, they do have uses in osteoporosis and can provide preliminary data in the short term that can be used in the design of longterm studies of BMD and fracture.

Alkaline Phosphatase↗
PubMed1996

The renal clearance of free and conjugated pyridinium cross-links of collagen.

We developed a sensitive reversed-phase high performance liquid chromatography (HPLC) assay to measure free and total Pyridinoline (Pyr) and Deoxypyridinoline (Dpyr) in serum. The method was used to measure total serum levels in seven premenopausal women (ages 52.2 +/- 2.4 years) and to investigate the renal clearance of free and conjugated Pyr and Dpyr in two groups of children (group 1: 13 girls, ages 11-13 years; group 2: 18 older children [2 male, 16 female], ages 13-18 years). Blood and 24-h urine samples were collected from the younger group to measure the renal clearance, and blood and 2-h morning urine samples from the older group were collected to investigate the fractional clearance. Total Pyr and Dpyr in the premenopausal women was 4.08 +/- 0.91 and 1.18 +/- 0.39 nmol/l, respectively. Free and total Pyr and Dpyr in serum and urine was elevated in both groups of children. The free serum levels were 16 and 18% in young and older children, respectively, compared with 40 and 46% in the urine. The percentage of free Dpyr in serum decreased with total urinary Pyr excretion (r = -0.56, p < 0.005, n = 31). The renal clearance of the free cross-link fraction in both groups was 4-fold higher than the conjugated fraction. The fractional clearance of the free fraction was greater than 1 (p < 0.001) and the conjugated fraction less than 1 (p < 0.001). The fractional excretion of free Dpyr increased with total urinary Pyr excretion (r = 0.66, p < 0.005, n = 13). We conclude that HPLC can be used to measure free and total Pyr and Dpyr in serum and that some free Pyr and Dpyr excreted in urine is produced by the kidney.

Adolescent↗