Biomedical subjects
Publications and source records attributed to A Horsman.
1. Plasma alkaline phosphatase activity and urine hydroxyproline excretion were measured in age-matched premenopausal and postmenopausal women. 2. Both measurements were found to be significantly higher in postmenopausal women. 3. It is proposed that the rise in the plasma alkaline phosphatase, like that in the hydroxyproline excretion, may reflect the onset of bone loss that occurs after the menopause.
1. We have examined the relation between the rate of cortical bone loss and other measured variables in 108 women, untreated and on various therapies, observed for nearly 300 patient years. The majority of the subjects were postmenopausal women with various degrees of simple osteoporosis, but a few cases of hyperparathyroidism and other calcium disorders were included. 2. Calcium balance, bone resorption rats, urinary hydroxyproline and plasma alkaline phosphatase were shown to be related to the rate of bone loss; patients with the more negative balance or the higher values of the other variables had significantly higher rates of loss. The rate of bone loss was independent of the rate of bone formation.
Explore the source record for details and available documents.
About 11% of post-menopausal women with wrist fractures have spinal osteoporosis with compressed vertebrae, and about 25% of postmenopausal osteoporosis patients have had a wrist fracture. The estimated prevalence of post-menopausal spinal osteoporosis is 4% of the female population at age 60 and about 8% at age 80. Osteoporotic patients have lower plasma oestrone and androstenedione levels, lower calcium absorption and higher urinary hydroxyproline than matched controls. Of six treatments tested in three different ways, the least successful were vitamin D2 and 1 alpha-OHD3 and the most successful were hormones with or without 1 alpha-(OH)2D3 and calcium supplements. Calcium and vitamin D given in combination occupied an intermediate position.
The mean calcium requirement of normal adults has been estimated from 212 calcium balances on 84 normal subjects and found to be 578 mg. The calcium allowance required to ensure that 95% of normal adults are in calcium balance is about 900 mg. Calcium requirement is relatively higher than that of phosphorus or magnesium because plasma calcium--and therefore urine calcium--is maintained at the expense of the skeleton in the presence of calcium deficiency, whereas plasma phosphate and magnesium--and therefore urine phosphate and magnesium--fall on phosphorus and magnesium deficient diets. Calcium requirement appears to rise at the menopause, and postmenopausal bone loss can be reduced by calcium supplements. In postmenopausal osteoporosis, the severe negative calcium balance can be corrected by giving calcium or calcium and vitamin D, but vitamin D alone is not beneficial. Similarly, bone loss, height loss and further vertebral compression can be reduced by calcium or calcium and vitamin D but not by vitamin D alone.
An experiment is described which shows that small rotations of metacarpals about their long axes produce small systemmatic changes in the cortical dimensions as measured by radiographic morphometry. The effect is of no significance in cross-sectional studies but is an important source of error in sequential studies.
The relative importance of genetic factors in the pathogenesis of age related bone loss has been investigated in a study involving 17 monozygotic (MZ) and 8 dizygotic (DZ) pairs of twins aged 64 to 75 years. Radiographic morphometry was performed at the midpoints of the 2nd, 3rd and 4th metacarpals of both hands and the mean total and cortical widths were evaluated. The heritability, h2, was calculated as the difference between the intrapair variances in same sexed DZ and MZ pairs divided by the intrapair variance in DZ pairs. The mean intrapair variance of both total and cortical width was found to be four to five times higher in DZ than in MZ pairs. The differences are highly significant with an h2 value between 0.7 and 0.8, indicating a predominant genetic influence. It is stressed that this result applies only to the population from which the twin sample was drawn.
1. The effects of a low calcium diet and of oophorectomy, separately and together, on cortical and trabecular bone mass, have been examined in mature female rats. 2. Calcium deprivation caused a significant decrease of weight, cortical cross-sectional area and ratio of cortical to total area in the femur, it significantly reduced the volume of trabecular bone and increased the percentage of osteoid surface in the tail vertebrae, and in addition increased the urinary excretion of phosphate and, initially, of hydroxyproline. 3. Oophorectomy caused similar though smaller changes in trabecular bone and urine, whereas the effects of oophorectomy on cortical bone were greater on a low calcium intake than on a normal intake. 4. The ash weight of the femora, expressed as a percentage of the total dry weight, was unaffected by calcium deprivation or oophorectomy alone but was significantly reduced when the two occurred together. 5. The percentage of resorption surfaces in the vertebrae tended to increase on the low calcium diet and after oophorectomy on the normal diet but decreased after oophorectomy on a low calcium diet. 6. It is concluded that oophorectomy and calcium deficiency each reduce bone mass in the adult rat but the greatest effect is seen when they are combined.
In a prospective trial in 72 postmenopausal women to compare the effects on bone loss of no treatment, treatment with oestrogen, and treatment with calcium the women were followed up for at least two years and examined densitometrically and morphometrically. Women in the untreated control group continued to lose bone during the two years, whereas the oestrogen-treated group lost none. Loss in the calcium-treated group was intermediate. Oestrogen appeared to inhibit endosteal bone resorption and may have stimulated subperiosteal bone apposition.
Explore the source record for details and available documents.
The application of a xenon-filled multiwire proportional counter to photon absorptiometry of bone mass is described. Performance characteristics obtained from a prototype system are discussed and future developments indicated.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Ten humeri and ten femora were radiographed in nine positions of longitudinal rotation. In each position total, medullary and cortical widths of the diaphyses (TW, MW, CW) were measured to assess the effect of rotation on these dimensions. The results were expressed as differences from the values in the neutral position (delta TW, delta MW, delta CW). In the humerus, medial rotation produced greater changes than lateral rotation. Though rotation in either direction increased CW, the systematic error due to medial rotation to only 5 degrees (approximately +0.0058 cm per degree) was more than double that due to lateral rotation. In the femur, lateral rotation had the greater effect, producing a marked decrease in CW (approximately -0.0072 cm per degree). Medial rotation produced only a slight increase in CW. The ratios CW/TW ("cortical index") and CA/TA ("area ratio") were calculated and expressed as differences from the values in the neutral position (delta CW/TW, delta CA/TA). Rotation affected these variables much less than the linear dimensions. Furthermore, through the variance of delta TW, delta MW and delta CA/TA increased only slightly or not at all. These results suggest that if radiographic morphometry is to be applied to the humerus and femur, these ratios rather than transverse dimensions should be used. Sequential changes in CW may be totally obscured by small rotational errors.
Sequential bone loss in 37 women with bilateral oophorectomy was monitored by radiographic morphometry. The changes in mean width of the cortices of the 2nd, 3rd and 4th metacarpals of both hands were determined using a semiautomated computer-controlled morphometer. It was found that a significantly greater rate of decrease of mean cortical width occurred in those women first observed within three years of the artificial menopause than in the other members of the group.
In 6 groups of peri- and post-menopausal women, there was an inverse relation between the urinary sediment smear maturation value and the fasting urinary hydroxyproline/creatinine ratio. Administration of ethinyloestradiol and Progynova both reduced urinary hydroxyproline into the pre-menopausal range, the fall being proportional to the starting value. Oestrogen therapy also produced a significant fall in plasma ionised calcium. In a prospective trial, oestrogen therapy prevented post-menopausal bone loss but calcium therapy was less effective. It is suggested that a high fasting urinary hydroxyproline/creatinine ratio might be taken as an indication for oestrogen therapy in post-menopausal women. In established post-menopausal osteoporosis, pre-disposing risk factors appear to be low calcium intake, malabsorption of calcium and low oestrogen status. These patients appear to represent the fast bone-losers in the post-menopausal population. The accelerated bone loss can be wholly or partially corrected by hormone replacement therapy and by calcium supplements given to those with normal absorption only. These therapies also prevent loss of height due to further crush fractures. The malabsorption of calcium is very resistant to vitamin D therapy but responds to 1alpha-OHD3. Balance data suggest that the most effective therapy may be a combination of 1alpha-OHD3 with oestrogen.
Plasma biochemistry, bone radiology and morphometry were studied in a group of 20 patients receiving maintenance hemodialysis. The aim was to determine if increasing the dialysate calcium concentration would decrease plasma parathyroid hormone and improve the radiologic appearances of bone in patients without producing serious side effects. Dialysate calcium concentration was increased stepwise from 4.5 to 6.0 and then to 7.0 mg/100 ml. Mean predialysis plasma calcium concentration increased from 9.4 to 9.7 and then to 10.0 mg/100 ml and mean predialysis phosphate concentration increased from 5.3 to 5.6 mg/100 ml. Parathyroid hormone concentration was elevated in all patients but the mean concentration did not change significantly although in seven patients a decrease occurred. Six patients had radiologic signs of renal bone disease, two patients showed improvement and three patients developed bone disease during the study. The patients with radiologic bone disease had the highest parathyroid hormone concentrations and the majority were female. Morphometric bone measurements showed that bone loss during the study occurred mainly in the male patients. Soft tissue calcification continued to appear during the study. Although the response to some patients to an increased dialysate calcium concentration was favorable, it was impossible to predict which types of patient would benefit from the use of a dialysate calcium concentration of 7.0 mg/100 ml.
The relationships between the rate of change of metacarpal cortical width, urinary hydroxyproline/creatinine ratio, net absorption of calcium and maturation value of vaginal smear have been examined in normal post-menopausal women and crush fracture cases. Rapid bone loss, high bone resorption and low calcium absorption are shown to be associated with poor oestrogen status, with crush fracture cases presenting an exaggerated view of the normal post-menopausal situation.