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H A Morris

Publications and source records attributed to H A Morris.

At least 19 recordsLinked to original sources
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↗
PubMed1997

Effects of dihydrotestosterone on bone biochemical markers in sham and oophorectomized rats.

Evidence exists to suggest that androgens stimulate bone formation in the estrogen-deficient state, however the mechanism of action is unclear. The following study investigates the effect of dihydrotestosterone (DHT) on biochemical markers of bone turnover and calcium homeostasis in sham and oophorectomized (oophx) rats when either vehicle, 40, 80, or 160 mg/kg body weight (bw) DHT were administered at the time of operation or at 15 weeks postoperation. Serum alkaline phosphatase (ALP) increased following DHT administration in sham and oophx rats in all groups (mean ALP +/- SEM [U/l] week 8; sham vehicle, 40 +/- 7; sham 160 mg DHT/kg bw, 72 +/- 5; oophx vehicle, 60 +/- 6; oophx 160 mg DHT/kg bw, 88 +/- 11) (p < 0.001). In contrast, serum osteocalcin was significantly suppressed in oophx rats administered DHT 15 weeks following operation (mean osteocalcin +/- SEM [micrograms/l] week 8; oophx vehicle, 17.6 +/- 3.5; oophx 160 mg DHT/kg bw, 10.5 +/- 1) (p < 0.01). Urine deoxypyridinoline was significantly decreased when DHT was administered 15 weeks postoophorectomy (p < 0.001); however, urine hydroxyproline was not affected by DHT treatment in any group. Urine calcium was decreased by DHT treatment (mean Ca/Cr +/- SEM week 8; sham vehicle, 0.87 +/- 0.13; sham 160 mg DHT/kg bw, 0.24 +/- 0.08; oophx vehicle, 0.68 +/- 0.16; oophx 160 mg DHT/kg bw; 0.45 +/- 0.1) (p < 0.005) which was associated with an increase in the renal tubular reabsorption of calcium (p < 0.05). This study demonstrates the direct effects of DHT on both bone cell activities and the renal handling of calcium.

Alkaline Phosphatase↗
PubMed1997

Increased urinary calcium excretion potentiates bone turnover in oophorectomized rats.

The differential effects of sodium-induced renal hypercalciuria on the biochemical markers of bone metabolism and calcium homeostasis were studied in oophorectomized (Oophx) and sham-operated rats. The rats consuming a normal (0.4%) calcium semisynthetic diet were randomly allocated to either 0, 0.4, 0.6, 0.9, or 1.25% NaCl in their drinking water for 7 days. At that time fasting blood and urine specimens were collected and analyzed for bone-related biochemical variables. The urinary calcium/creatinine ratio was increased with increasing urinary sodium (p < 0.01) in both sham and Oophx animals. The hydroxyproline/creatinine ratio was elevated as a result of Oophx (p < 0.001) and was raised with increasing urinary sodium in both sham (p = 0.012) and Oophx animals (p = 0.007). Serum osteocalcin and alkaline phosphatase were elevated in Oophx rats (p < 0.02). While serum osteocalcin was raised with increasing urinary sodium in Oophx rats (p = 0.035), there was no effect on osteocalcin levels in sham-operated rats. This study demonstrates that sodium-induced renal hypercalciuria potentiates bone turnover in Oophx rats as compared with ovary-intact rats and indicates important implications for the effect of dietary salt on bone turnover with ovarian hormone deficiency.

Animals↗
PubMed1996

Transcriptional synergism between vitamin D-responsive elements in the rat 25-hydroxyvitamin D3 24-hydroxylase (CYP24) promoter.

Transcription of the CYP24 gene is induced by 1,25-(OH)2D3 through a vitamin D receptor-dependent process. The functional activities of three possible vitamin D response elements (VDREs), located on the antisense strand of the rat CYP24 promoter, were investigated by transient expression of native and mutant promoter constructs in COS-1, JTC-12, and ROS 17/2.8 cells. A putative VDRE with a half-site spacing of 6 base pairs at -249/-232 (VDRE-3) did not contribute to 1,25-(OH)2D3 induced expression in the native promoter, although activity has been reported when the element was fused to the heterologous thymidine kinase promoter. Two VDREs with half-site spacings of 3 base pairs at -150/-136 and -258/-244 (VDRE-1 and VDRE-2, respectively), showed transcriptional synergism in COS-1 cells when treated with 1,25-(OH)2D3 (10(-7) to 10(-11) M). The contribution of both VDREs was hormone-concentration dependent from 10(-10) to 10(-12) M, with VDRE-1 demonstrating greatest sensitivity to 1,25-(OH)2D3. Transactivation by VDRE-1 was always greater than VDRE-2, but the converse was observed for the binding of vitamin D receptor-retinoid X receptor complex by each VDRE in gel mobility shift assays. The synergy observed between VDRE-1 and VDRE-2 may have important implications in cellular responses to different circulating levels of 1,25-(OH)2D3.

Animals↗
PubMed1996

Increased bone resorption precedes increased bone formation in the ovariectomized rat.

This study describes an increase in biochemical and histomorphometric markers of bone resorption prior to increased bone formation and trabecular bone loss in the ovariectomized rat. Six-month-old, female Sprague Dawley rats were either sham operated or ovariectomized (Ovx) and killed at 0, 6, 9, 15, 18, 21, and 42 days postoperation when femora were collected and trabecular bone volume (BV/TV) was determined from von Kossa silver-stained sections using the Quantimet 520 image analysis system in the distal region. A number of these sections were also examined unstained for fluorochrome labels, and stained for acid phosphatase to detect osteoclast-like cells (ACP surface). At 18 days postoperation, lumbar vertebrae were examined. Blood and urine specimens were analyzed for bone-related biochemical variables. ACP surface was significantly greater in Ovx rats compared with sham at 6 days postoperation (mean ACP surface (%TS) +/- SEM: sham 36.4 +/- 1.9; Ovx 40.3 +/- 1.2, P < 0.05) as was urinary hydroxyproline excretion. Serum osteocalcin and alkaline phosphatase activity were not elevated in Ovx rats compared with Sham until 9 days postoperation. Mineral apposition rate (MAR) was increased at 12 days after ovariectomy (mean MAR (microm/day) +/- SEM: sham 0.85 +/- 0.06; Ovx 1.23 +/- 0.06, P < 0.05). Trabecular bone volume (BV/TV) at a specific site in the metaphyseal-diaphyseal core area was significantly lower at 15 days postoperation (mean (%) +/- SEM: Sham 7.40 +/- 1.23, Ovx 4.25 0 0.65, P < 0.05). There was no difference in lumbar vertebral BV/TV between the two groups at 18 days postoperation, however, ACP surface was elevated in the Ovx rats (P < 0.05). A systemic increase in bone resorption at 6 days postovariectomy precedes increased formation whereas the length of time required for the dissolution of trabeculae postoperation is determined locally.

Animals↗
PubMed1996

Estradiol treatment transiently increases trabecular bone volume in ovariectomized rats.

The effect of short-term estradiol treatment, administered from the time of ovariectomy, on increased bone turnover and subsequent bone loss was studied in the rat. Adult female Sprague-Dawley rats were ovariectomized and administered daily subcutaneous (s.c.) injections of 17 beta-estradiol at 8 micrograms/ kg per day (Low) and 20 micrograms/kg per day (High) or vehicle alone (Veh). Femoral trabecular bone volume (BV/TV) and trabecular number (Tb.N) in the distal femur were transiently increased at 6 days postoperation in a dose-dependent manner following estradiol administration [mean +/- SEM: BV/TV (%), day 0, 6.6 +/- 0.2; day 6, Veh 7.8 +/- 0.4, Low 10.2 +/- 2.2, High 12.8 +/- 1.7 (p < 0.05); Tb.N (/mm), day 0, 2.30 +/- 0.24; day 6, Veh 2.89 +/- 0.33, Low 3.4 +/- 0.7, High 4.39 +/- 0.34 (p < 0.05)]. Estradiol prevented the ovariectomy-induced decrease in BV/TV and Tb.N between 9 and 15 days observed in Veh rats. Both serum alkaline phosphatase and urine hydroxyproline excretion were maintained at preoperative levels or lower from day 6 postoperation with high dose estradiol. Serum osteocalcin, however, rose above preoperative levels with estradiol at days 6 and 9, but returned to these values on days 15 and 21 postoperation. These results suggest that estradiol, administered from the time of ovariectomy, immediately suppressed markers associated with osteoblast proliferation/matrix synthesis and bone resorption. Mineralization does not appear to be so rapidly suppressed by estradiol with relatively high levels immediately following administration, resulting in a transient increase in trabecular bone volume and trabecular number.

Alkaline Phosphatase↗
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↗
PubMed1996

Selections from current literature: cholelithiasis, cholecystectomy and the risk of colorectal cancer.

The study by Ekbom et al. clearly demonstrates that, overall, there is no increased risk of colorectal cancer following cholecystectomy. However, it is noted that women have a slight increase in the risk of proximal colon cancer following cholecystectomy. The reasons for this finding remain unclear. However, since this finding has been consistent in several studies, it is probably not an artifact, but a true association that may warrant further investigation. It is possible that the association noted between cholecystectomy and colorectal cancer is due not to the cholecystectomy, but to the reason why cholecystectomies are performed, namely the presence of gallstones. The cholecystectomy itself may simply be a surrogate for cholelithiasis, which may be a true risk factor for colorectal cancer. Excess secondary bile acids may be carcinogenic or the factors which cause the formation of cholelithiasis may also increase the risk for developing colorectal cancer. An answer to the separate question of whether excessive laparoscopic cholecystectomies are being performed, or whether newer indications make the increased number of laparoscopic cholecystectomies appropriate, remain outstanding. This new procedure, despite being cheaper than the open cholecystectomy, has resulted in greater utilization of the world's dwindling health care resources. In conclusion, the decision to perform a cholecystectomy should be made only with consideration of the patient's current medical condition. There is no need to be concerned about any future increased risk of colorectal cancer following a cholecystectomy.

Aged↗
PubMed1995

The effect of oophorectomy on calcium homeostasis.

Postmenopausal bone loss is associated with a rise in the fasting urine calcium excretion which has been proposed to be a possible cause of increased bone resorption. The oophorectomized rat is widely used as a model of postmenopausal bone loss, but preliminary data suggest that urine calcium excretion is not increased following oophorectomy in this animal model. However the present detailed experimental protocol demonstrated that oophorectomy in adult rats increased the obligatory urine calcium excretion compared with ovary-intact rats (P < 0.001). Importantly urine hydroxyproline excretion was positively correlated with urine calcium only in the oophorectomized rats (P = 0.003). This urine calcium was positively correlated with urine phosphate excretion when dietary sodium was low (P < 0.001) and with urine sodium excretion when dietary sodium was elevated (P = 0.003). Calcium balance studies indicated a greater fall in calcium accretion in growing, oophorectomized rats (6 to 15 weeks of age) compared with ovary-intact animals and intestinal calcium secretion was the major component of the calcium balance to be affected. Losses of calcium in the urine were relatively minor in these growing rats.

Aging↗
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

Parathyroidectomy does not prevent bone loss in the oophorectomized rat.

The evidence for a role of parathyroid hormone in the bone loss after the menopause remains controversial. This study examines the effect of parathyroidectomy on femoral trabecular bone volume, thickness, and spacing and biochemical markers of bone turnover in the oophorectomized rat. Female Sprague-Dawley rats 3 months old were double sham operated (sham), oophorectomized (OPX), parathyroidectomized (PTX), or oophorectomized and parathyroidectomized (O/P) under halothane anesthesia. At 9 weeks postoperation, femoral trabecular bone volume (BV/TV) was lower in OPX and O/P rats compared with sham or PTX animals (BV/TV, %, mean +/- SEM): sham 25.9 +/- 0.5, OPX 15.1 +/- 0.9, PTX 24.1 +/- 0.9, O/P 17.3 +/- 0.5; p < 0.001). Urinary hydroxyproline excretion, serum osteocalcin, and alkaline phosphatase activity were higher in OPX and O/P rats compared with control animals at 3 weeks postoperation (OHPE microM GF, mean +/- SEM: sham 1.37 +/- 0.16, OPX 2.16 +/- 0.26, PTX 0.95 +/- 0.21, O/P 1.92 +/- 0.22, p < 0.005; osteocalcin, microgram/liter, sham 31.8 +/- 1.8, OPX 33.7 +/- 2.7, PTX 24.5 +/- 2.1, O/P 34.3 +/- 2.1, p < 0.025; alkaline phosphatase, U/liter, sham 90 +/- 3, OPX 125 +/- 9, PTX 87 +/- 9, O/P 116 +/- 11, p < 0.005). These data indicate postoophorectomy bone loss is not prevented by parathyroidectomy.

Alkaline Phosphatase↗
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

Oophorectomy in young rats impairs calcium balance by increasing intestinal calcium secretion.

Calcium balance and its major components (true calcium absorption, urinary calcium excretion and intestinal calcium secretion) were assessed by a 6-d balance technique in young (6-wk-old) rats fed a diet containing 7.2 g Ca/kg diet. Following either oophorectomy (oophx) or sham operation, the balance study was repeated at 9, 12 and 15 wk of age. Calcium balance decreased with age but remained positive in each group [mean (pooled SEM): sham, (6 wk) 0.86 to (15 wk) 0.27 (0.03) mmol/d (P < 0.0001); oophx, (6 wk) 0.91 to (15 wk) 0.22 (0.03) mmol/d (P < 0.0001)]. Analysis of variance of the change in calcium balance indicated that there was a significantly greater reduction in calcium balance in the oophx group compared with the sham-operated group. Intestinal calcium absorption decreased in each group with age [sham: (6 wk) 46.3% to (15 wk) 22.6% (1.5%) (P < 0.0001); oophx: (6 wk) 48.2% to (15 wk) 21.2% (1.5%) (P < 0.0001)]. There was a marked rise in intestinal calcium secretion in the oophx group compared with the sham-operated group at 6 wk post-operation (12 wk of age) [oophx: 0.33 (0.02) mmol/d; sham: 0.23 (0.02) mmol/d (P < 0.01)]. Urinary calcium excretion was not affected by either age or oophorectomy. We conclude that oophorectomy in young rats leads to a reduction in calcium accumulation, which is mainly the result of an increase in intestinal calcium secretion.

Aging↗