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Biomedical subjects

A G Need

Publications and source records attributed to A G Need.

At least 19 recordsLinked to original sources
PubMed1997

Relations between calcium intake, calcitriol, polymorphisms of the vitamin D receptor gene, and calcium absorption in premenopausal women.

The relations between calcium absorption, dietary calcium intake, 1,25-dihydroxyvitamin D3 (calcitriol), and vitamin D receptor (VDR) gene polymorphisms were evaluated in 99 healthy women who were approaching menopause (mean age: 47 y, range: 43-53 y). Dietary calcium was assessed by food-frequency questionnaire and calcium absorption was measured by a single-isotope radiocalcium test. VDR alleles were classified according to the presence (b, t, a) or absence (B, T, A) of the BsmI, TaqI, and ApaI restriction enzyme cutting sites. Radiocalcium absorption was positively related to serum calcitriol (r = 0.23, P < 0.05) and inversely related to dietary calcium intake (r = -0.26, P < 0.01). There was, however, no significant relation (r = 0.10) between serum calcitriol concentrations and dietary calcium. Radiocalcium absorption was higher in the bbaaTT haplotype (P < 0.05) and the aa genotype (P < 0.05), polymorphisms said to be associated with a higher bone density. We conclude that serum calcitriol and dietary calcium are independent determinants of calcium absorption in premenopausal women and that VDR gene polymorphisms influence calcium absorption.

Adult↗
PubMed1996

Regional bone mineral density interrelationships in normal and osteoporotic postmenopausal women.

We describe a prospective study in which bone mineral density (BMD) was measured in total body and regions, proximal femur, lumbar spine, and forearm in 84 apparently normal postmenopausal women with normal spinal radiographs and in 47 women with 1-10 wedged or compressed vertebrae. There was a history of peripheral fracture in 35 of the 84 controls and 30 of the 47 osteoporotics (p < 0.02) but there was no association between vertebral fracture and wrist fracture. At all sites and regions, the differences in BMD between the "normal"and "osteoporotic" women was highly significant and all but "ribs" and "arms" remained significant after correction for menopausal age. In the whole set, and in both subgroups, the coefficients of correlation between sites and regions were all highly significant (p < 0.001). Nonetheless, some sites discriminated better between the two groups than others. Standardized odds ratios (OR) for vertebral fracture versus no-fracture were calculated by logistic regression and expressed as the rise in OR for each standard deviation (SD) fall in bone density. This ratio was greatest (3.4) in "pelvis" and weakest (1.7) in "ribs" but all were statistically significant. Geometric mean regression equations were calculated for all the 78 possible pairs of sites and regions in the 84 normal subjects and the deviations of the osteoporotic women from these normal slopes calculated. In most pairs of sites and regions, the vertebral fracture cases were scattered around the normal group's slope but fell lower down on both axes. The bone deficits in the osteoporotics compared with young normal women ranged from -14% in "head" to -40% in Ward's triangle and the T-scores ranged from -1.9 in "ribs" to -3.9 in the forearm. Sensitivity ranged from 17% in "ribs" to 36.2% in Ward's triangle. Specificity varied between 88 and 94% and the percent correctly classified ranged from 62.6% in "ribs" to 72.5% in Ward's triangle. We conclude that primary postmenopausal osteoporosis affects the entire skeleton but that some sites discriminate better between vertebral fracture and nonfracture cases regardless of whether they represent cortical or trabecular bone.

Absorptiometry, Photon↗
PubMed1996

Vitamin D receptor genotypes are related to bone size and bone density in men.

Three restriction fragment length polymorphisms in the vitamin D receptor gene have been associated with a low bone density in twin and female population studies, but no studies have been conducted exclusively in men. We studied 146 normal men aged 20-83 years. Bone density was measured in the spine, hip, whole body and forearm, and the Bsm polymorphism for the vitamin D receptor was detected by the polymerase chain reaction. Men with genotype BB tended to have a lower bone density at all but one site than the other genotypes. In the men < or = 50 years of age bone density in the forearm was 7% lower in the BB than the Bb and bb groups (P = 0.030) but bone mineral content did not differ between the groups. Bone area was greater in the BB genotype at all sites. This was statistically significant in the forearm (P = 0.026). We conclude that BB genotype is associated with lower bone density in men, which may be due to larger bone size rather than reduced bone mass.

Absorptiometry, Photon↗
PubMed1995

Effect of age on bone density and bone turnover in men.

OBJECTIVE: Little is known about the pattern of age-related bone loss in men, and although androgens are required for optimum bone mass it is not clear whether the fall in bone mass with age in men is related to falling androgens. DESIGN: Cross-sectional measurement of bone density, at five sites, and markers of bone resorption and formation in 147 normal volunteers aged 20-83 years. SUBJECTS: Healthy laboratory workers, hospital staff, their relatives, and husbands of women attending our osteoporosis clinic. MEASUREMENTS: Forearm density (fat corrected), spine L2-L4, femoral neck, Ward's triangle and trochanter density; serum procollagen I C-terminal extension peptide, osteocalcin, bone alkaline phosphatase and collagen I C-terminal telopeptide; fasting urine hydroxyproline/creatinine, pyridinoline/creatinine and deoxy-pyridinoline/creatinine; and free androgen index (FAI), measured as serum testosterone/sex hormone binding globulin. RESULTS: Bone loss accelerated at most sites after age 50. There was a significant fall in FAI from the third decade onwards. The levels of all bone markers fell with age. CONCLUSIONS: Bone loss in men appears to accelerate from age 50 and is associated with decreased bone formation which may be associated with falling levels of free androgen.

Adult↗
PubMed1995

Relationship between fractional calcium absorption and gastric emptying.

The relationship between calcium absorption and gastric emptying and the precision of measurement of fractional calcium absorption using a single isotope technique were evaluated in 14 normal postmenopausal women (age range 61-72 years). On two occasions separated by between 5 and 15 days, each subject was given 250 mL water containing 0.2 MBq of 45Ca in 20 mg of calcium carrier as the chloride, 20 mg kg-1 paracetamol and 9 MBq of 99mTc sulphur colloid. Venous blood samples were taken at -2, 15, 30, 45, 60, 90, 120, 150 and 180 min after consumption of the drink, and gastric emptying (GE) was monitored with a gamma camera. Fractional calcium absorption in the first hour (alpha 6) was calculated from the blood samples obtained at 15, 30, 45, 60, 90 and 120 min. An absorption rate was also derived from the 60 min sample using only a calibration curve (alpha 1). There were close correlations between radiocalcium absorption on the two study days (r = 0.89, P < 0.001 for both alpha 1 and alpha 6) and between alpha 1 and alpha 6 (r = 0.93, P < 0.001). Plasma paracetamol concentrations at 15 min were directly related to the early phase of GE (r = 0.42, P < 0.05). In contrast, calcium absorption was inversely related to GE (r = 0.45, P < 0.05). We conclude that radiocalcium absorption is not greatly influenced by gastric emptying rate and that the single blood sample procedure has similar precision to the six-blood sample test.

Acetaminophen↗
PubMed1995

The 5-year reproducibility of calcium-related biochemical variables in postmenopausal women.

A total of 19 measured and derived bone-related biochemical variables were determined in 307 postmenopausal volunteers on two occasions, 5 years apart. The plasma variables with the highest coefficients of determination (r2) were plasma globulins, alkaline phosphatase, creatinine and calculated ionized and ultrafiltrable calcium. In the urine, the highest r2 values were in respect of fasting urine calcium excretion corrected for urine sodium, hydroxyproline excretion, and the maximal renal tubular reabsorption of calcium and phosphate (TmCa/GFR and TmP/GFR). The components of variance of TmCa/GFR and TmP/GFR show marked individuality but their methods determination meet the criterion for acceptable analytical goals. We conclude that most of the measured and derived bone-related biochemical variables in fasting plasma and urine are sufficiently reproducible in postmenopausal women to be useful for ranking individuals for a period up to 5 years.

Biomarkers↗
PubMed1994

Biochemical effects of a calcium supplement in postmenopausal women with primary hyperparathyroidism.

Oral calcium loading is known to decrease parathyroid hormone levels in primary hyperparathyroidism. We have examined the effects of a calcium supplement on bone resorption in postmenopausal primary hyperparathyroidism. Fasting blood and urine samples were obtained in 12 postmenopausal women (median age 64 yr) with primary hyperparathyroidism associated with mild hypercalcemia (plasma calcium < 3.00 mmol/l). Further samples were obtained 12 hours after a 1 g calcium supplement given at 2100 h. After calcium administration there were rises in plasma ionized calcium (p < 0.02), plasma phosphate (p < 0.05) and the renal tubular maximum reabsorption capacity for phosphate (p < 0.01) and falls in parathyroid hormone (p < 0.05) and the renal tubular maximum reabsorption capacity for calcium (p < 0.05). The urinary calcium/creatinine increased (p < 0.01) and the urinary hydroxyproline/creatinine (p < 0.02) fell. These results indicate that calcium loading inhibits bone resorption in postmenopausal women with mild primary hyperparathyroidism.

Absorption↗
PubMed1994

Oral calcium suppresses biochemical markers of bone resorption in normal men.

Calcium supplementation decreases bone resorption and retards bone loss in women. There is little information about the effects of calcium supplementation in men. The effects of a 1-g oral calcium load at 0900 on bone-related biochemical variables were evaluated in 13 normal men (aged 51-70 y). Calcium administration was associated with increases in plasma ionized calcium (P < 0.001) and urinary calcium (P < 0.001), and a decrease in plasma parathyroid hormone (P < 0.001). There was a nonsignificant trend (r = -0.47, P = 0.11) for the decrease in plasma parathyroid hormone to be related to radiocalcium absorption. After the calcium load there were decreases in the urinary hydroxyproline-creatinine ratio from 11 +/- 1.1 to 7.9 +/- 0.6 (P < 0.01), the urinary deoxypyridinoline-creatinine ratio from 14.0 +/- 1.8 to 10.1 +/- 0.9 (P < 0.05), and the urinary pyridinoline-creatinine ratio from 52 +/- 5 to 40 +/- 3 (P < 0.01) between baseline and 6 h. There was no change in plasma osteocalcin. These observations indicate that a 1-g calcium load suppresses biochemical markers of bone resorption for > or = 6 h in normal men and support the concept that calcium supplementation may be useful in the prevention of bone loss in men.

Absorption↗
PubMed1994

Treatment of osteoporosis in the elderly.

Fracture risk is adversely related to bone density, wherever it is measured. Women should be screened by bone densitometry around the time of the menopause and treated with calcium or hormones if the density is low. Women with vertebral compression should be treated with calcitriol if calcium absorption is low, with hormones if urine calcium is high, and with calcitriol and hormones if both abnormalities are present. It is uncertain whether newer treatments offer any advantages over this regimen. Vitamin D is indicated in household individuals or others with low levels of 25 OHD to prevent loss from secondary hyperparathyroidism and perhaps also to improve muscle power.

Aged↗
PubMed1994

Primary hyperparathyroidism.

Primary hyperparathyroidism is not rare. It is particularly common after the age of 50 and may affect up to 3% of postmenopausal women. It is commonly found as a result of blood tests performed for other reasons and is therefore often asymptomatic. Surgical treatment is recommended for patients with renal stone disease, plasma calcium above 3 mmol/L and accelerated bone loss (e.g., bone density < 3 standard deviations below the young normal mean). There is considerable debate about whether mild asymptomatic disease should be treated, but if there is rapid bone loss, either surgical or medical therapy with hormones or bisphosphonates is indicated.

Aging↗
PubMed1993

A 5-year longitudinal study of forearm bone mass in 307 postmenopausal women.

We measured forearm bone mineral content at the beginning and end of a 5 year period in 307 untreated postmenopausal volunteers. We also measured height, weight, and a number of biochemical variables in plasma and urine after an overnight fast. The initial mean age of the subjects was 59.0 years (range 39-72), and the mean years since menopause was 10.0 (range 1-37). The mean forearm BMC fell from 1034 +/- 9.6 (SEM) to 982 +/- 9.3 mg/cm (P < 0.001). The coefficient of correlation between the first and second measurements was 0.96. The mean rate of change was -1.0% per annum (with a 99% range of -4 to 1% per annum), which agreed well with previous estimates from cross-sectional data. There was a significant negative correlation between rate of change in bone mass and initial value (r = -0.23; P < 0.001), which was eliminated by expressing change as a percentage of initial bone mass. Of the other variables measured, the one that was most significantly related to the percentage change in bone mass was the urinary hydroxyproline/creatinine ratio (r = -0.35; P < 0.001), which we regard as a marker only. By stepwise regression, the only significant determinants of the rate of change in bone mass were body weight (positive, P < 0.001), years since menopause (positive, P < 0.005), urine calcium (negative, P < 0.01), and serum estrone (positive, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effects of skin thickness, age, body fat, and sunlight on serum 25-hydroxyvitamin D.

We tested the hypothesis that the age-related decline in skin thickness may contribute to the age-related decline in serum 25-hydroxyvitamin D [25(OH)D]. We measured skinfold thickness on the back of the hand, serum 25(OH)D, height, and weight in 433 normal postmenopausal women. We also noted the average daily hours of sunlight in the month in which the observations were made and in the preceding 2 mo. Serum 25(OH)D was positively related to hours of sunlight (with a time lag of 2 mo) and to skin thickness, and negatively to body mass index (wt/ht2). Serum 25(OH)D fell significantly after age 69 y. Seasonal variation of serum 25(OH)D was greater in lean than in fat subjects, which we attributed to the larger fat mass and consequent larger pool size in the latter group. The results suggest that the tendency for serum 25(OH)D to fall with age is due in part to the age-related decline in skin thickness.

Adipose Tissue↗
PubMed1993

The nature and significance of the relationship between urinary sodium and urinary calcium in women.

Orally or parenterally administered sodium is known to increase urinary calcium in experimental animals and humans, and there is well-documented correlation between urinary sodium and calcium in 24-h urine collections from normal subjects and renal stone formers. The correlation between urinary sodium and calcium is generally sodium driven, i.e., it is the sodium load that influences urinary calcium rather than vice versa, but the converse may also occur, as after an oral calcium load or in hypercalcemia. When sodium is the determinant, 100 mmol of sodium takes out approximately 1 mmol of calcium in the urine. When calcium load is the determinant, each millimole of calcium appearing in the urine is associated with an extra 10-20 mmol of sodium. Sodium-dependent calcium loss may continue indefinitely, but calcium-dependent natriuresis is self-limiting. There is a significant correlation between calcium and sodium in fasting urine from both pre- and postmenopausal women, but there is more calcium relative to sodium in postmenopausal women than in premenopausal women. In postmenopausal but not premenopausal women, urinary hydroxyproline is also related to obligatory sodium and calcium output, and restriction of salt intake lowers not only urinary sodium but also calcium and hydroxyproline. There is not only an increase in obligatory calcium excretion at the menopause, but also an increase in the fasting urinary sodium, which in turn accounts for some of the increase in calcium output. This rise in fasting urinary sodium represents a delay in sodium excretion that may have a significant effect on calcium homeostasis.

Adult↗
PubMed1993

Effects of norethisterone on bone related biochemical variables and forearm bone mineral in post-menopausal osteoporosis.

OBJECTIVE: Progestogens may be a useful therapeutic alternative to oestrogen in the treatment of post-menopausal osteoporosis. The purpose of this study was to determine the effects of norethisterone on forearm bone mineral content and bone related biochemical variables in patients with post-menopausal osteoporosis. DESIGN/PATIENTS: The effects of treatment with norethisterone (5 mg/day) on bone related biochemical variables was determined in 44 women with post-menopausal osteoporosis. The effects of norethisterone on forearm bone mineral content (FMC) were evaluated by serial measurements in 39 of these women. MEASUREMENTS: We measured forearm mineral content, forearm mineral density, forearm fat content and fat-corrected forearm mineral density. Biochemical measurements included plasma calcium and plasma calcium fractions (ionized, protein bound, complexed and ultrafiltrable), alkaline phosphatase, bicarbonate, phosphate, albumin and globulins, serum parathyroid hormone, osteocalcin and 1,25-dihydroxyvitamin D, radiocalcium (45Ca) absorption and fasting urinary calcium/creatinine, sodium/creatinine, phosphate/creatinine and hydroxyproline/creatinine molar ratios. RESULTS: After 4 months of treatment norethisterone produced a fall in plasma calcium (mean +/- SEM from 2.40 +/- 0.14 to 2.32 +/- 0.13 mmol/l, P < 0.001), primarily in the non-ionized calcium, due to a decrease in plasma bicarbonate (from 29 +/- 0.28 to 27 +/- 0.28 mmol/l, P < 0.001). There were decreases in urinary calcium/creatinine (from 0.41 +/- 0.03 to 0.19 +/- 0.02, P < 0.01) and sodium/creatinine (from 15 +/- 1.1 to 10 +/- 0.93, P < 0.001) molar ratios and a rise in the renal tubular maximum for calcium reabsorption (TmCa) (from 2.36 +/- 0.041 to 2.55 +/- 0.059 mmol/l of glomerular filtrate, P < 0.001). Plasma phosphate, urinary phosphate/creatinine and tubular maximum for phosphate reabsorption (TMP) all fell (P < 0.01). Both the urinary hydroxyproline/creatinine (P < 0.001) and plasma alkaline phosphatase (P < 0.001) fell. Serum parathyroid hormone rose from 4.1 +/- 0.36 to 5.5 +/- 0.51 pmol/l (P < 0.02) and radiocalcium absorption increased from 0.67 +/- 0.08 to 0.81 +/- 0.10 fx/h (P < 0.01). There was no change in serum 1,25-dihydroxy vitamin D. After treatment with norethisterone for 4 months there was an increase in forearm bone mineral content (P < 0.05) and a decrease in forearm fat content (P < 0.02). After two years treatment with norethisterone fat-corrected forearm bone mineral content rose (mean change 17.0 +/- 5.5 mg/cm, P < 0.01). CONCLUSIONS: These results suggest that norethisterone prevents bone loss in post-menopausal osteoporosis by decreasing bone turnover, has a vitamin-D independent effect on intestinal calcium absorption, and increases serum parathyroid hormone levels.

Adult↗
PubMed1993

The effect of chlorothiazide on bone-related biochemical variables in normal post-menopausal women.

OBJECTIVE: To evaluate the effects of short-term administration of chlorothiazide on fasting urinary hydroxyproline, an index of bone resorption, and other bone-related biochemical parameters in normal post-menopausal women. DESIGN: Subjects served as their own control before and after chlorothiazide treatment. SETTING: Subjects were recruited by advertisement. PARTICIPANTS: Thirteen healthy post-menopausal women with a mean age of 65 years. INTERVENTION: Each subject was given chlorothiazide 500 mg bd po for 7 days. Fasting blood and urine samples were obtained immediately before the commencement of chlorothiazide (day 1) and 2 and 7 days after starting chlorothiazide. RESULTS: Chlorothiazide decreased the urinary calcium/creatinine (mean value day 1, 0.267; day 2, 0.143; day 7, 0.135; P < 0.001) and hydroxyproline/creatinine (day 1, 0.0192; day 2, 0.0145; day 7, 0.0139; P < 0.02) molar ratios. CONCLUSION: Chlorothiazide decreases fasting urinary hydroxyproline, a marker of bone resorption in post-menopausal women. This observation supports a potential role for thiazide diuretics in the prevention of osteoporosis. The observed fall in urinary hydroxyproline is of the same order as that seen after treatment with estrogen or calcium supplements.

Acid-Base Equilibrium↗