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Biomedical subjects

A G Need

Publications and source records attributed to A G Need.

At least 37 records · Page 2Linked to original sources
PubMed1998

Intestinal calcium absorption in men with spinal osteoporosis.

OBJECTIVE: To investigate the role of serum 1,25-dihydroxyvitamin D (1,25D) in the decreased calcium absorption found in men with osteoporosis. DESIGN: Prospective study of patients referred to a university teaching hospital clinic for investigation of possible osteoporosis. PATIENTS: Male patients referred for investigation for osteoporosis, from 1981 to 1995, because of specific risk factors or radiological suspicion of osteoporosis. Men with vertebral compression fractures were compared with those without. MEASUREMENTS: Height and weight, radiocalcium absorption, serum 1,25D and fasting urinary calcium and hydroxyproline excretion. RESULTS: The men with vertebral fractures had higher fasting urinary hydroxyproline excretion (P = 0.003) and lower calcium absorption (P = 0.002) than the men without. Calcium absorption was positively related to 1,25D in both groups but the estimated calcium absorption at zero 1,25D was lower in the osteoporotic than the normal group. 1,25D was lower in the osteoporotic group than in the normal group. However this difference could only explain about half of the difference in calcium absorption between the groups. CONCLUSIONS: Calcium absorption is low in men with osteoporosis. About half of the deficit is due to low serum 1,25-dihydroxy vitamin D levels but there appears, in addition, to be some intestinal resistance to its effect on calcium absorption.

Adult↗
PubMed1998

Variation in the short-term changes in bone cell activity in three regions of the distal femur immediately following ovariectomy.

The effect of ovariectomy (OVX) on cancellous bone in the rat is not uniform at all sites of the skeleton. We report variation in the short-term effects of adult OVX in three regions of the distal femur: the diaphysis (DIA), the metaphysis (META), and the epiphysis (EPI). Cancellous bone parameters were estimated in the three separate zones of the femora and compared with changes in bone cell activity, as estimated by osteoclast surface (Oc.S) and bone formation rate (BFR). Changes were studied for 30 days in a series of rats either sham-operated (Sham) or ovariectomized (OVX) at 7 months of age. Oc.S and BFR were elevated following OVX in all regions. The time course for the OVX-induced changes differed between regions: DIA, both Oc.S and BFR were elevated at day 9; META, Oc.S was also elevated at day 9, while the rise in BFR was delayed until day 21; EPI, Oc.S remained stable but increased relative to ovary-intact rats by day 18 due to reduced levels in the latter, but BFR did not rise until day 28. These changes in bone cell activity following OVX produced a 71% reduction of cancellous bone in the DIA and a 35% reduction in the META. In contrast, no OVX-induced bone loss was observed in the EPI. This study shows that bone cell activity increases in each region of the distal femur within the first 30 days following OVX, independent of bone loss. However, the time course of increased bone cell activity is not uniform. These data highlight the role of local factors in the response to ovarian hormone deficiency.

Animals↗
PubMed1998

Modification and validation of a single-isotope radiocalcium absorption test.

UNLABELLED: This study was done to establish and allow for the influence of body weight on plasma radioactivity after administering radiocalcium to measure calcium absorption. METHODS: We administered 5 microCi 45Ca in 20 mg of calcium carrier in 250 ml distilled water to 103 premenopausal volunteers over the age of 40 yr, after an overnight fast. Venous blood was withdrawn when the dose was given (to serve as a blank) and exactly 60 min later, and the counts were determined in a liquid scintillation counter. After the exclusion of three outliers, the fraction of the administered dose per liter of plasma at 60 min was a curvilinear inverse function of body weight and a positive linear function of the reciprocal of body weight, with an r value of 0.45 (p < 0.001). This latter relationship then was used to correct the plasma radioactivity to a standard body weight of 65 kg, in which the volume of distribution of the dose was assumed to be 10 liters. This yielded the estimated fraction of the dose circulating at 1 hr, which then was converted into a fractional absorption rate from our previously published equation. RESULTS: In the 100 volunteers, the mean value of the radiocalcium absorption rate (termed alpha2, to distinguish it from our original calculation) was 0.75/hr, with 98 of the 100 values falling between 0.30 and 1.20. The value alpha2 was significantly related to serum calcitriol in these 100 volunteers (r = 0.29; p = 0.003) and in 89 normal postmenopausal women (r = 0.46; p < 0.001). It also was significantly related to the 24-hr urine calcium in the same 89 women (r = 0.48; p < 0.001) and to net calcium absorption corrected for intake in balance studies on another 103 postmenopausal women (r = 0.44; p < 0.001). In most respects, alpha2 was marginally superior to alpha1 but, unlike alpha1, was independent of body weight. CONCLUSION: The modified low-carrier radiocalcium absorption test is a valid indicator of calcium absorption status over a wide range of calcium intakes and is independent of body weight.

Body Weight↗
PubMed1997

The response to calcitriol therapy in postmenopausal osteoporotic women is a function of initial calcium absorptive status.

Calcitriol is used in the treatment of osteoporosis but the indications for its use have not been clearly defined. Because it stimulates calcium absorption, we have tended to select osteoporotic patients with low calcium absorption for this therapy and now report the results. We measured the hourly fractional rate of calcium absorption (alpha) with 45Ca and fasting urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (OHPr/Cr) in 103 postmenopausal women aged 68 (0.67SE) years with vertebral compression fractures (77) or forearm or vertebral bone density below the young normal range (26). They were given 0.25 microg daily of calcitriol (Rocaltrol, Roche, Basle, Switzerland) with a 1 g calcium supplement daily for 6-12 weeks, when the biochemical tests were repeated. Initial OHPr/Cr was inversely related to initial alpha (P = 0.001) and positively to initial Ca/Cr (P < 0.001). alpha rose on therapy from 0.47 (0.018) to 0.59 (0.018) per hour (P < 0. 001) and OHPr/Cr fell in the whole group from 19.1 (0.83) to 13.8 (0. 58) (P < 0.001). The change in alpha on therapy (corrected for the "regression to the mean effect") was inversely related to initial alpha (P < 0.001) as was the change in OHPr/Cr (P = 0.001). There was no relationship, however, between initial Ca/Cr and either the rise in alpha or the fall in OHPr/Cr on therapy. The data support the concept that low calcium absorption is a cause of negative calcium balance in postmenopausal osteoporosis and that the effectiveness of calcitriol therapy is inversely related to the initial rate of calcium absorption.

Adult↗
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↗