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Biomedical subjects

R L Prince

Publications and source records attributed to R L Prince.

At least 73 records · Page 4Linked to original sources
PubMed1994

Long-term elevation of 1,25-dihydroxyvitamin D after short-term intravenous administration of pamidronate (aminohydroxypropylidene bisphosphonate, APD) in Paget's disease of bone.

We report the prolonged biochemical changes that occurred in patients with Paget's disease when treated for 2-10 days with pamidronate disodium (3-amino-1-hydroxypropylidine-1,1-bisphosphonate, APD), by i.v. administration and observed for 6 months following therapy. In all 24 patients studied, bone resorption (measured by urinary hydroxyproline/creatinine ratio, OHP/Cr) fell sharply on treatment, from 0.12 +/- 0.02 (mean +/- SEM; above reference limits) to 0.04 +/- 0.008 (reference range 0.006-0.027 for females, 0.005-0.020 for males), remaining at this level for 6 months after therapy. A fall in serum ionized calcium (Ca2+) to just below the reference limits with treatment (1.11 +/- 0.02 mM; reference range 1.14-1.18 mM), followed by a rapid return to normal levels (1.14 +/- 0.02 mM, mean +/- SEM) within 8 days of treatment, was presumably due to the cessation of release of calcium from bone. This was followed by secondary hyperparathyroidism and a rise in serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. The hormonal responses, however, were profound. Serum immunoreactive PTH (iPTH) rose to twice pretreatment values (86 +/- 11 pM, mean +/- SEM; reference range for iPTH, > 50 years, < 50 pM; < 50 years, < 40 pM), returning to normal 4-8 weeks after therapy. Serum 1,25-(OH)2D levels rose to three times pretreatment values (300 +/- 20 pM, mean +/- SEM; reference range 50-150 pM), remaining above reference limits 4-8 weeks after therapy (188 +/- 15 pM, mean +/- SEM) and returning to normal values only after 12 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Parathyroid function in mild to moderate renal failure: evaluation by oral calcium suppression test.

Alterations of PTH secretion in patients with mild to moderate chronic renal failure were evaluated using an oral calcium suppression test. Ionized calcium and PTH were measured at 0, 30, 60, 120, and 180 min after ingestion of 2 g elemental calcium in 18 patients and 15 control subjects. The mean glomerular filtration rate was significantly lower in the patients compared to the controls (58 +/- 18 vs. 100 +/- 12 mL/min, P < 0.01) but the basal ionized calcium and PTH were not significantly different. After ingestion of calcium there was a similar rise in ionized calcium with time in both patients and controls. However the mean PTH concentration in the patients was significantly higher than the controls at all equivalent ionized calcium concentrations. Overall the patients showed significantly less percentage suppression of PTH compared to control subjects, 63 +/- 10% vs. 74 +/- 9%, P < 0.01. The minimum PTH value was also higher in the patients than the controls, 1.2 +/- 0.7 vs. 0.7 +/- 0.3 pmol/L, P < 0.01. Thus although the majority of patients had PTH levels within the conventional reference range they demonstrated abnormal suppression of PTH secretion. The data from this study would further support the view that treatment for secondary hyperparathyroidism should be started early on in the course of chronic renal failure.

Administration, Oral↗
PubMed1993

Rapid, divergent changes in spinal and forearm bone density following short-term intravenous treatment of Paget's disease with pamidronate disodium.

Intravenous disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate (pamidronate disodium) was used to treat 39 patients (22 males and 17 females, age range 48-85 years) with symptomatic Paget's disease. Patients were stratified into three groups based on the biochemical severity of the disease as assessed by fasting urinary hydroxyproline excretion (HypE, mumol/liter GF, glomerular filtrate): group I (n = 23), HypE < 5.0, treated with 120 mg total dose over 2 or 4 days; group II (n = 6), 5.0 < or = HypE < or = 10.0, 180 mg over 3 or 6 days; and group III (n = 10), HypE > 10.0, 240 mg over 4 or 8 days. Bone mineral density (BMD) was measured before and 3 and 6 months following treatment in the spine (L1-4) using dual-energy x-ray absorptiometry and in the forearm at an ultradistal and a shaft site using single-photon absorptiometry. When groups I-III were combined, nonpagetic and pagetic lumbar spinal BMD had both risen significantly at 3 months compared with the pretreatment values (p < 0.001). In each group, lumbar spinal BMD in pagetic vertebrae rose markedly by 3 months, with no further significant change at 6 months. The percentage rises in the three groups were not different from each other at 3 or 6 months. Nonpagetic lumbar spinal BMD followed a similar and significant trend but with a significantly smaller rise than for pagetic bone. (For the combined groups, nonpagetic BMD rose 5.1 +/- 1.1% SEM, above pretreatment at 6 months; pagetic BMD rose 17.8 +/- 1.6%: significance of comparison = p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1993

Correlates of intestinal calcium absorption in women 10 years past the menopause.

Because intestinal calcium absorption may be an important independent determinant of calcium balance and therefore bone mass, we have studied this factor and other potential predictors in 196 healthy postmenopausal women. Gut calcium absorption was measured in each subject by a stable strontium method and expressed as a fractional absorption. The fractional absorption was significantly negatively correlated with years since menopause (YSM) (r = -0.15 P < 0.05) and dietary calcium intake (r = -0.15 P < 0.05), and significantly positively correlated with 24-hour urine calcium excretion (r = 0.31 P < 0.001) and body mass index (r = 0.20 P < 0.01). Apart from YSM, these factors remained as correlates in multiple regression analysis; the standardized regression coefficient was largest for 24-hour urine calcium excretion (0.32). Fractional absorption of calcium was not correlated with vertebral bone density. Thus, intestinal calcium absorption, although falling with increasing menopausal age and increasing calcium intake, is best correlated with the urine calcium excretion. This indicates either that gut calcium absorption is regulated in response to the magnitude of the urine calcium excretion or that the kidney maintains calcium balance by excreting what is absorbed by the intestine. The mechanisms whereby gut and renal calcium handling are correlated are uncertain.

Absorptiometry, Photon↗
PubMed1993

Screening for osteoporosis by bone densitometry: a stratified intervention approach.

We have performed computer modelling of the relationship between bone mass, age and hip fracture in a conditional probability model using a national population of 100,000 postmenopausal women aged 50 who have their bone density measured once. The computer model very closely reproduced the actual number of fractures in a Western Australian population. Intervention to bone loss completely in subjects with the lowest bone density (below 1 SD below the mean) would prevent 0.42 of a hip fracture per patient treated if the whole population were treated. Halving the rate of bone loss in the whole population would reduce hip fracture by two-thirds. These data suggest that hormone replacement therapy, which is the most effective therapy for preventing bone loss but which has the most side effects, should be focused on subjects with bone mass below 1 SD below the mean. The remainder of the population could be targeted with a public health campaign based on the lifestyle factors of increased dietary calcium and exercise which have been shown to slow but not stop bone loss.

Bone Density↗
PubMed1993

Fluoride treatment of osteoporosis: cyclical non-blinded or continuous blinded studies?

The future of sodium fluoride (NaF), the most potent osteoblast stimulator known to man, is in the balance. Of three recent randomized trials of continuous NaF only one found a significant in vertebral fractures in the NaF group. When data from the first year were excluded, two of the studies (those with the largest numbers) showed a significantly reduced risk of vertebral fracture on NaF. The effect of NaF on cortical bone is poorly documented. Two studies have shown reduced forearm cortical bone density with continuous NaF. A further two (histomorphometric) studies have shown the development of increased cortical porosity on continuous NaF treatment. In one, this was selectively at the external cortex and was linearly correlated with cancellous volume increase. Our pilot study using NaF administered cyclically has shown an encouraging (though non-significant) reduction in vertebral fracture rates (excluding year 1) and no fall in forearm cortical density. Another (US) cyclical study has shown no increase in cortical porosity. A current W. Australian randomized study of 50 patients is described where NaF dosage is varied proportional to the osteoblast response, and duration is dependent on densitometric and radiographic response. The future of NaF should involve cyclical administration, in cautious initial dosage (50-60 mg/day) of enteric-coated NaF, in conjunction with a potent inhibitor of resorption such as hormone replacement, bisphosphonates or calcitonin.

Aged↗
PubMed1993

The regulation of calcitriol by parathyroid hormone and absorbed dietary phosphorus in subjects with moderate chronic renal failure.

The two best-recognized stimuli for calcitriol production are parathyroid hormone (PTH) and dietary phosphorus deprivation. We studied the relative importance of these two stimuli in subjects with moderate chronic renal failure (MCRF). We recruited 10 subjects with MCRF aged 49 +/- 13 years (mean +/- SD) and having a creatinine clearance rate of 31 +/- 24 mL/min. After an overnight fast, they received 400 IU human PTH 1-34 subcutaneously, and blood and urine samples were collected over the subsequent 24 hours. They then took aluminum hydroxide 30 mmol/d for 2 months to reduce gut phosphorus absorption, at the end of which the PTH stimulation test was repeated. Responses were compared with those obtained in 11 normal subjects aged 44 +/- 16 years and having a creatinine clearance rate of 102 +/- 37 mL/min who were only studied while on their normal diet. Following PTH stimulation in the normal subjects but not the MCRF subjects, there was a significant increase in plasma calcium and calcitriol levels, with a significant decrease in renal phosphorus threshold. In both groups there was a similar and significant increase in urine cyclic adenosine monophosphate (cAMP) levels. Following restriction of absorption of dietary phosphorus in MCRF subjects, plasma calcitriol levels increased compared with baseline values. This study shows that these MCRF subjects were unable to respond with an increase in calcitriol to a PTH stimulus that produced a similar urine cAMP response in normal subjects. However, they were capable of responding to a reduction in phosphorus absorption with an increase in calcitriol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Fracture prevalence in an Australian population.

There is little published information on the epidemiology of fracture in Australia. We have therefore carried out a population-based retrospective study of fracture in an Australian population covering 1,073 subjects, 60 per cent of the eligible population over the age of 65 resident in Busselton in the southwest of Western Australia. They completed a questionnaire on the number of fractures, the skeletal site and the degree of trauma that caused the fracture. In this population, 39 per cent had sustained a total of 620 fractures, and 22 per cent of women and 6 per cent of men had sustained osteoporotic fractures. Hip and spine fractures accounted for only 9 per cent of osteoporotic fractures in females whereas wrist fractures accounted for 27 per cent, other upper limb fractures for 19 per cent and other lower limb fractures for 11 per cent. These results suggest that emphasis on spinal and hip fractures as the only manifestations of osteoporosis is inappropriate.

Adult↗
PubMed1992

Determinants of intact parathyroid hormone and free 1,25-dihydroxyvitamin D levels in mild and moderate renal failure.

Parameters of calcium and phosphate metabolism were measured in 27 patients with mild renal failure [glomerular filtration rate (GFR) 40-90 ml/min], 12 patients with moderate renal failure (GFR 20-39 ml/min) and in 12 healthy subjects. GFR was determined by technetium-99m diethylenetriamine penta-acetic acid clearance. Intact parathyroid hormone (PTH) was measured by a sensitive immunochemiluminometric assay and somatomedin-C was determined by radioimmunoassay. Both 1,25-dihydroxyvitamin D [1,25(OH)2D] and vitamin-D-binding protein were measured allowing calculation of the free 1,25(OH)2D index. By linear regression and multivariate analysis, PTH was negatively and independently correlated with GFR, plasma bicarbonate and 25-hydroxyvitamin D [25(OH)D] while free 1,25(OH)2D was positively correlated with GFR. Increased PTH secretion and reductions in 1,25(OH)2D were present in mild renal failure patients before any changes in plasma calcium, phosphate and bicarbonate were noted. Plasma alkaline phosphatase was significantly higher in mild chronic renal failure patients compared to normal subjects, possibly indicating early effects of the secondary hyperparathyroidism on the skeleton. Somatomedin-C did not correlate with the free 1,25(OH)2D index or a measure of 1,25(OH)2D production. It is concluded that the secondary hyperparathyroidism which occurs very early in the onset of chronic renal failure may be due to a reduction in the circulating concentration of 1,25(OH)2D consequent upon the renal failure. Low plasma bicarbonate and 25(OH)D also appear to be determinants of a raised PTH concentration. The compensatory increase in PTH presumably maintains extracellular calcium and phosphate levels constant but with possible deleterious effects on the skeleton.

Adult↗
PubMed1991

Prevention of postmenopausal osteoporosis. A comparative study of exercise, calcium supplementation, and hormone-replacement therapy.

BACKGROUND: Osteoporosis among older women is a major public health problem. We studied the effects of three approaches to the prevention of osteoporosis in women with low bone density. METHODS: One hundred twenty postmenopausal women (mean [+/- SD] age, 56 +/- 4) who were selected because they had low forearm bone density were enrolled in a double-blind, placebo-controlled, randomized study comparing the effects of an exercise regimen (exercise group, n = 41), exercise plus dietary calcium supplementation (exercise-calcium group, n = 39), and exercise plus continuous replacement of estrogen and progesterone (exercise-estrogen group, n = 40). Periodically during the two-year study period, we measured the women's bone density at three forearm sites, measured indexes of calcium metabolism, and recorded symptom scores. A comparison group of 42 women (mean age, 55.5 +/- 3.1) with normal bone density was also followed for two years. RESULTS: Significant bone loss in the distal forearm occurred in the group with normal bone density (control group) and the exercise group (change, -2.7 percent and -2.6 percent of the base-line value per year, respectively). Bone loss at the distal forearm site was significantly lower in the exercise-calcium group (-0.5 percent of the base-line value per year), and bone density increased at this site in the exercise-estrogen group (+2.7 percent of the base-line value per year). Bone loss at the median forearm site was significantly lower in the exercise-calcium group (-1.3 percent of the base-line value per year) than in the exercise group (-2.4 percent), and bone density at this site increased significantly in the exercise-estrogen group (+0.8 percent of the base-line value per year). Breast tenderness occurred in 47 percent of the women in the exercise-estrogen group but in only 20 percent in the other two treatment groups. Vaginal bleeding occurred at some time in 52 percent of the women who had not had a hysterectomy in the exercise-estrogen group, as compared with 11 percent and 12.5 percent, respectively, in the exercise and exercise-calcium groups. CONCLUSIONS: In postmenopausal women with low bone density, bone loss can be slowed or prevented by exercise plus calcium supplementation or estrogen-progesterone replacement. Although the exercise-estrogen regimen was more effective than exercise and calcium supplementation in increasing bone mass, it also caused more side effects.

Bone Density↗
PubMed1991

Lack of evidence for estrogen receptors in human and bovine parathyroid tissue.

It has been hypothesized that estrogen may have a direct effect to reduce the set-point for PTH secretion which may be implicated in its hypocalcemic action. If this is so, estrogen receptors should be demonstrable within parathyroid tissue. Seven human parathyroid adenomas and five samples of normal bovine parathyroid tissue were examined using classical hormone-binding techniques. In no case was there evidence of displaceable estrogen binding of high affinity and low capacity. To exclude the presence of receptors within a small subset of the cells, five of the human adenomas were further studied by immunohistochemistry using a monoclonal antibody to the human estrogen receptor. In no case was there evidence of estrogen receptors. We conclude that the hypocalcemic action of estrogen replacement is unlikely to be mediated via a classical estrogen receptor within the parathyroid, although normal parathyroid tissue was not studied.

Adenoma↗
PubMed1991

Transdermal estrogen replacement does not increase calcitonin secretory reserve in postmenopausal women.

The effect of transdermal estrogen replacement on ionized calcium and calcitonin levels was examined in 15 postmenopausal women. Following baseline measurement of calcitonin and ionized calcium in the fasting state, the effect of calcium infusion on calcitonin levels was studied. Estrogen replacement resulted in a fall in baseline ionized calcium, however, the rate of rise of calcium was the same before and after estrogen administration. Thus the time at which a particular calcium concentration was attained was later after the commencement of the calcium infusion following estrogen replacement. Although there was no detectable difference in baseline calcitonin concentrations (pre-estrogen, 2.4 +/- 0.4; post-estrogen, 2.1 +/- 0.4 pmol/l), following estrogen replacement the time at which a particular calcitonin concentration was attained was later after the commencement of the calcium infusion, reflecting the slower attainment of a particular calcium concentration (p = 0.014 by ANOVA). Analysis of total calcitonin production by area under the curve, however, did not show a significant difference before and after estrogen replacement (643 +/- 184 and 407 +/- 115 pmol.l-1.100 min-1, respectively). When the calcitonin response to calcium infusion was compared at the same calcium concentration, estrogen status had no effect on the relationship. We conclude that transdermal estrogen replacement has no effect on calcitonin secretory reserve in postmenopausal women and does not alter the relationship between elevated calcium and calcitonin levels. We cannot exclude an effect of estrogen on baseline calcitonin levels as the calcium concentration was lower but the calcitonin levels not different.

Administration, Cutaneous↗
PubMed1990

Alterations in vitamin D metabolites during treatment of Paget's disease of bone with calcitonin or etidronate.

We report serum 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25-(OH)2D], and 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels in untreated Paget's disease and the effect of treatment with either calcitonin (CT) or etidronate (EHDP) on these levels. In untreated Paget's patients serum 25-OHD (73 +/- 29 nmol/liter, n = 36, mean +/- SD) and 24,25-(OH)2D (0.3-12.9 nmol/liter, median 2.2, n = 36) levels were significantly lower than in age-matched controls (94 +/- 30 nmol/liter, n = 32, p less than 0.005, and 1.3-16.4 nmol/liter, median 5.3; n = 32, p less than 0.001, respectively). Also, the 24,25-(OH)2D levels correlated with the 25-OHD levels in the untreated Paget's patients (r = 0.56, p less than 0.01) and in the controls (r = 0.39, p less than 0.05). The percentage molar ratio of 24,25-(OH)2D to 25-OHD in Paget's patients had a median value of 3.7% (range 0.4-14.3%), which was not significantly different from controls, who had a median value of 5.6% (range 2.2-18%). There was no difference between the 1,25-(OH)2D, and immunoreactive PTH (iPTH) levels of Paget's patients and control subjects. The percentage molar ratio of 1,25-(OH)2D to 25-OHD in untreated Paget's patients (0.157 +/- 0.09%) was not significantly different from controls (0.124 +/- 0.05%) despite lower 25-OHD levels in Paget's patients. There was a significant inverse correlation between the severity of Paget's disease as measured by plasma alkaline phosphatase (AP) levels and 25-OHD levels (r = 0.392, p less than 0.02); however, 24,25-(OH)2D and 1,25-(OH)2D levels were not correlated with AP.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗
PubMed1990

Spontaneous hip fractures in fluoride-treated patients: potential causative factors.

Spontaneous fractures were reported to be rare (less than 1%) in 1664 hospital admissions for hip fracture in the 1950s in Sweden. We report 11 fluoride-treated postmenopausal patients who developed spontaneous fractures of the femoral necks, all subcapital initially. In 7 patients who continued treatment there were later femoral neck or shaft fractures; in 6, these were bilateral (one followed a fall). In all there were 19 spontaneous fractures: 5 were asymptomatic, including 2 with deformity; 12 fractures required surgery. Five were incomplete (stress) fractures. All were treated with supplementary calcium 1 g daily; 10 had vitamin D supplementation. In all patients where the timing was known, the initial and subsequent fractures were preceded by, or associated with increased bone turnover as measured by plasma alkaline phosphatase (pAlP) (i.e., they were all "good responders"). Two had pretreatment hip fractures following falls. We compared these 11 (Group 1) and another identically treated group of 14 patients (Group 2), without spontaneous femoral fractures and not different in mean age, pretreatment vertebral fractures, years since menopause, fluoride dosage, and plasma creatinine. Group 1 had a lower (p less than 0.05) index of cortical bone in the femoral neck, as assessed by the ratio "calcar width/femoral neck minimum width." The 6 biopsied fluorotic patients from Group 1 had a higher (p less than 0.05) bone fluoride content than the 4 biopsied fluorotic patients from Group 2. Furthermore, histological cortical features of thinning, increased porosity, and advanced tunneling resorption characterized Group 1 posttreatment biopsies. There were no significant differences in peak pAlP responses in the two groups. Mild asymptomatic vitamin D excess may have been a contributing factor in three Group 1 patients. Two further treatment groups have been studied more recently by forearm single-photon absorptiometry (SPA) at two sites; a cyclic NaF group (Group 3) and a calcium +/- vitamin D group (Group 4). Neither showed significant changes in forearm cortical bone density on treatment for 2 and 1.5 years, respectively, but Group 3 showed a significant increase in density at an ultradistal (60% trabecular) site. The pAlP response in Group 3 was significantly less than in Group 1. Spontaneous femoral neck or shaft fractures did not occur in either Groups 3 or 4. Therefore, we recommend: (1) Avoidance of sodium fluoride (NaF) treatment if pretreatment femoral fracture or thin femoral neck cortices exist.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1990

Bioactivity of amino terminal fragments of parathyroid hormone and parathyroid hormone related peptide in rat kidney slices: no effect of dietary phosphate deprivation.

Humoral hypercalcemia of malignancy has been associated with the production of a recently cloned peptide human parathyroid hormone related protein (hPTHRP). One of the markers of this disease is an increased urinary excretion of cyclic AMP. The postreceptor mechanism of action and physiological role of hPTHRP remain obscure. To study the activity of hPTHRP 1-34 compared to rat and human parathyroid hormone (PTH) 1-34 we incubated these peptides with rat kidney slices and measured the cyclic AMP generated in the supernatant. hPTHRP 1-34 was equipotent with human PTH 1-34 but both were 5 times less active than rat PTH 1-34. Previous studies have suggested that a low dietary phosphate intake results in renal resistance to the phosphaturic action of PTH perhaps mediated by reduced adenylate cyclase activation by PTH. To determine whether, during dietary phosphate restriction, hPTHRP 1-34 has actions different from hPTH 1-34 we studied their effects following dietary phosphate deprivation. Dietary phosphate restriction had no significant effect on the cyclic AMP generating activity of any of the peptides. We conclude that hPTHRP 1-34 may be operating through similar mechanisms as human PTH 1-34 and that the previously observed effects of dietary phosphate deprivation on PTH mediated cyclic AMP generation in a broken cell preparation do not occur in intact cell preparations.

Adenylyl Cyclases↗