Effect of physical activity on femoral bone density in men.
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Absorptiometry, Photon↗
Biomedical subjects
H A Morris
Publications and source records attributed to H A Morris.
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↗
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↗
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↗
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↗
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↗
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↗
Renal leak of calcium in post-menopausal osteoporosis.
BACKGROUND: Urine calcium after an overnight fast is higher in osteoporotic than in normal post-menopausal women. The question is whether this is the cause or effect of the bone-losing state. OBJECTIVE: To establish whether the elevated obligatory calcium loss in osteoporotic women is due to a raised filtered load of calcium or to reduced renal tubular reabsorption of calcium. DESIGN: Covariance analysis using total plasma calcium and its fractions as the covariates. PATIENTS: Eighty-two untreated post-menopausal women without vertebral compression and 137 untreated post-menopausal with vertebral compression all between the ages of 61 and 75 years. MEASUREMENTS: After an overnight fast, calcium, albumin, globulins, anion gap and bicarbonate were measured in the plasma, and calcium, sodium and creatinine in the urine. The calcium fractions in plasma and the calcium/creatinine and sodium/creatinine ratios in urine were calculated. Bone density was measured in the distal forearm. RESULTS: The ultrafiltrable and ionized calcium in the plasma and the calcium/creatinine ratio in the urine were significantly higher in the women with vertebral compression than in those without. On covariance analysis, neither total plasma calcium nor any of the plasma calcium fractions made a significant contribution to the difference in fasting urine calcium between normal and osteoporotic women, whether bone status was defined by vertebral compression or by bone density. CONCLUSIONS: The increased obligatory calcium loss in osteoporotic women is not due to an increase in the filtered load of calcium and must therefore reflect reduced renal tubular reabsorption. This implies that the calcium loss in the urine is not the result of increased bone resorption but is more likely to be causal.
Aged↗
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↗
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↗
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↗
The significance of transient left ventricular dilation during SPECT dipyridamole thallium-201 scintigraphy.
We assessed the significance of transient left ventricular dilation (TLVD) during single photon emission computed tomography (SPECT) dipyridamole thallium-201 scintigraphy (DTS) in 49 patients who underwent both DTS and diagnostic coronary arteriography. Quantitative analysis of DTS images and independent review by 3 experienced observers determined that 17 patients had TLVD and 32 patients had no TLVD. Patients with TLVD were similar to patients without TLVD with respect to age, history of myocardial infarction, coronary risk factors and occurrence of chest pain or electrocardiographic changes during DTS. The frequency of three-vessel coronary artery disease (3VD) was greater in patients with TLVD than in patients without TLVD (94% vs. 16%, p < 0.01). The sensitivity of TLVD was 76% and the specificity 96% for the detection of 3VD. Of the 16 patients with 3VD who manifested TLVD, standard SPECT DTS analysis demonstrated defect or perfusion abnormalities in 14 patients and no abnormalities in 2 patients. In conclusion, the finding of TLVD during SPECT DTS is a specific marker for severe coronary disease and can provide additive information to standard SPECT thallium-201 analysis.
Adult↗
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↗
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↗
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↗
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↗
Osteoporosis and vitamin D.
Bone "density" (bone mass/bone volume) declines with age from the menopause in women and from about age 55 in men. This fall in bone density (osteoporosis) weakens the bones and leads to a progressive rise in fracture rates, particularly in women. Many risk factors contribute to the bone-losing process, but one which attracts increasing attention is calcium absorption. The main physiological regulator of calcium absorption is vitamin D. This is manufactured in the skin under the influence of UV-light and then converted to more potent metabolites in the liver and kidney. Although the serum levels of the most potent metabolite 1,25(OH)2D3 (calcitriol) are generally normal in osteoporotic women, treatment with small doses of calcitriol (about 0.25 micrograms daily) has a remarkable effect on absorptive performance and slows down the rate of bone loss. Improved synthetic metabolites are under development. There is likely also to be greatly increased scope for the use of vitamin D itself in osteoporosis. With advancing age, there is a tendency for men and women to be exposed to less and less sunlight, which is the main natural source of vitamin D. Vitamin D levels, therefore, decline with age, particularly in those who are housebound, and are found to be low in most reported series of hip fractures. It is likely that this form of vitamin D "insufficiency" has an adverse effect on calcium absorption in the elderly which accelerates bone loss and increases the risk of hip fracture and can be treated with small doses of vitamin D or its 25-hydroxy derivative.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Effects of oophorectomy on biochemical and bone variables in the rat.
The metabolic effects of oophorectomy (Oophx) were studied in 6-month-old rats maintained on a normal chow diet. Nine weeks following operation, Oophx animals had a significantly lower femoral trabecular bone volume (BV/TV) than sham-operated animals; mean (SD) Oophx 8.5 (3.8)%; Sham 13.4 (2.5)%; P = 0.013). They also had a higher urine hydroxyproline (P less than 0.001), serum alkaline phosphatase activity (P less than 0.001), serum phosphate (P less than 0.001) and lower serum albumin (P less than 0.001) than the controls. Serum osteocalcin was inversely related to the BV/TV in the Oophx animals at 9 weeks post operation (r = -0.85, P = 0.007, n = 8). A fall in serum ionized calcium from 3 to 9 weeks post operation correlated with a fall in urinary hydroxyproline in the Oophx animals (r = 0.57, P = 0.002, n = 27). The data are consistent with a model of ovarian hormones acting directly to modulate bone cell activity as well as exerting an effect on the renal handling of phosphate.
Alkaline Phosphatase↗