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Biomedical subjects

C R Dunstan

Publications and source records attributed to C R Dunstan.

At least 19 recordsLinked to original sources
PubMed1993

Measurement of osteoclasts and bone resorption by automated image analysis.

An automated image analysis method is described for measurement of osteoclasts and resorbing surface in calcified bone. Osteoclasts, osteoid, and mineralized bone were measured in a single section, reacted for acid phosphatase activity, and then stained with orange G and light green stain. Three images were acquired of each field with a monochromatic camera at illuminating wavelengths of 635, 540, and 480 nm (selected using a stage monochromator). These wavelengths were chosen according to the absorption spectra of the different image components to maximize absorption differences between osteoclasts (red), mineralized bone (blue/green), and osteoid (orange). These components were then discriminated according to operator-defined ranges of color density (mineralized bone) or color fraction (osteoid and osteoclasts). A gray level coded segmented image was produced, from which was determined the area, perimeter, and number of each component and the length of contact zones with the marrow and between these components. The method was evaluated by twice measuring 10 bone sections from patients with end-stage liver failure awaiting liver transplantation. The method was quite reproducible, with coefficients of variation varying between 4% for bone volume (% tissue volume) and 22% for osteoid surface (% bone surface). The sections were also measured using a previously established semiautomated method. Coefficients of variation between methods were higher varying between 4% for bone volume (% tissue volume) and 56% for osteoid volume (% bone volume). The automated method gave a substantial time saving compared to the semiautomated method. An interactive technique was used in adjacent sections to evaluate tetracycline labeling and osteoblast surfaces.

Adolescent↗
PubMed1992

Bone death in transient regional osteoporosis.

A 48-year-old man developed transient regional osteoporosis, with hip and later knee pain. He responded well to lumbar sympathectomy. The femur and tibia adjacent to the painful knee were osteoporotic, while the medial femoral condyle showed increased uptake in a bone scan. In the femoral condyle, bone histology showed areas of dead bone undergoing osteoclastic resorption, and increased bone formation. The tibial bone was histologically normal. The partial bone death in the distal femur suggests that the disorder may be related to both avascular necrosis of bone and reflex sympathetic dystrophy.

Bone Resorption↗
PubMed1992

Metabolic studies in kidney stone disease.

Patients with kidney stones (n = 59) and healthy controls (n = 31) collected a 24-hour urine sample and later underwent a 6-hour 'fast and load' test in which an oral calcium load was taken after 2 hours. In the 24-hour urine sample, mean calcium excretion was higher in patients than controls, while mean urate, oxalate and citrate levels were similar. The patients had higher levels of fasting plasma calcium, serum calcitriol and fasting urinary calcium, and lower levels of plasma phosphate than did the controls. Following the calcium load, plasma and urinary calcium increased similarly in both groups. Serum parathyroid hormone (PTH) levels were similar in both groups and decreased similarly following the calcium load. Multiple linear regression, relating the presence or absence of stone formation to all variables, found the only variables significantly related to stone formation to be plasma levels of calcium (p less than 0.001) and phosphate (p = 0.001) and fasting urinary urea (p less than 0.001), and 24-hour urinary calcium excretion (p less than 0.05). Urinary oxalate and citrate were not related to stone formation. The data do not support the hypothesis that primary stimulation by calcitriol produces a normal fasting plasma calcium level, with an exaggerated increase after an oral calcium load. The findings instead suggest an abnormality of parathyroid cell 'set point', such that PTH secretion continues until the plasma calcium level is a little higher and the phosphate a little lower than in controls.

Adult↗
PubMed1991

Treatment of Paget's disease of bone with a combination of intranasal salmon calcitonin and oral calcium and thiazide.

The purpose of this study was to establish the smallest dose of nasally administered salmon calcitonin (SCT) which, if given in conjunction with a previously published calcium/thiazide treatment, would be as effective as parenteral SCT in the treatment of Paget's disease of bone. Forty patients suffering from symptomatic Paget's disease were treated with 0.5 g calcium three times daily, 10 mg/day clopamide, and 400 IU nasally administered salmon calcitonin given once or twice weekly. This regimen was given for 5 months, after which all treatment was ceased for 4 months. Parenteral SCT (100 IU) was then given three times weekly for 5 months to 25 of the patients. With the oral/nasal treatment, the plasma alkaline phosphatase level (AP) decreased by 30 +/- 15 (SD)% when the SCT was given once weekly and by 39 +/- 11% (P less than 0.05) when the SCT was given twice weekly. There were similar decreases in the fasting urinary hydroxyproline:creatinine ratios. The parenteral SCT reduced the AP by 33 +/- 23%. Though reduction in bone pain was similar with both treatments, most patients preferred the oral/nasal treatment. It is concluded that the oral/nasal treatment, when the SCT is given twice weekly, has similar efficacy to parenteral SCT, and is a well tolerated, effective initial treatment for Paget's disease of bone.

Administration, Intranasal↗
PubMed1991

Bone loss after liver transplantation.

We studied 35 adult patients (mean age = 43 yr) referred for orthotopic liver transplantation. Spinal bone mineral density was measured by quantitative computed tomography scanning before transplantation (n = 35) and at 3 mo (n = 21) and 12 mo (n = 11) after orthotopic liver transplantation. The readings were corrected to age 50 yr, using the regression equations derived from normal control subjects. Quantitative bone histological studies were performed in 17 patients before orthotopic liver transplantation and 3 mo after orthotopic liver transplantation. Before orthotopic liver transplantation, the corrected spinal bone mineral density in men was 108 +/- 20 mg/cm3, less than in male control subjects (129 +/- 22 mg/cm3, p less than 0.005). In women patients the value was 117 +/- 27 mg/cm3, and in female control subjects 126 +/- 19 mg/cm3 (NS). However, women patients with primary biliary cirrhosis had lower spinal bone mineral density (106.5 +/- 14.8) than female control subjects (p less than 0.005). Histologically, the resorbing surface was near the normal mean, whereas the osteoblast surface, tetracycline surface and bone formation rate was lower in men (p less than 0.05) but not women. Spinal bone mineral density decreased by 24% in the first 3 mo after orthotopic liver transplantation with no further decrease at 12 mo. Five patients had vertebral fractures within 6 mo of orthotopic liver transplantation. One patient fractured a wrist and three had osteonecrosis of the hip or knee.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Bone death in hip fracture in the elderly.

We examined femoral head bone from 50 cadavers and from 21 patients who had suffered pathologic fracture of the femoral neck. We used a histochemical technique for lactate dehydrogenase (LDH) activity to demonstrate osteocyte viability. The femoral heads were removed within 36 hours of death or fracture, as LDH activity persists in the cytoplasm of viable cells for this time at 37 degrees after interruption of the blood supply. In the controls, there was an age-related reduction in mean osteocyte viability, from 88 +/- 7% (mean +/- SD) at age 10-29 years to 58 +/- 12% at age 70-89 years. In the hip fracture patients, mean osteocyte viability was 58 +/- 21% but there was much variability in both osteocyte viability and bone mass. In 5 fracture patients, there was extensive osteocyte death, suggesting that most of the femoral head bone was nonviable; these patients had little microfracture callus. Others had predominantly viable bone which was usually osteoporotic, and their bone frequently showed microfracture callus. Osteomalacia was not seen in any patient. It is suggested that bone death, in addition to osteoporosis, may sometimes contribute to hip fracture in the elderly.

Aged↗
PubMed1989

Measurement of bone in the os calcis: a clinical evaluation.

Bone mineral content (BMC) was measured in the os calcis of 232 normal subjects aged 17-82 years. The mean reproducibility (coefficient of variation) of the measurement was 1.8%. Substantial bone loss occurred between the ages of 20 and 50 years, and in females the menopause was associated with additional bone loss. There was no significant difference in the rate of bone loss in females and males, but the mean BMC was greater at all ages in males than in females. We also compared os calcis BMC with spinal bone mineral density (BMD), measured by quantitative computed tomographic (CT) scanning, in 85 subjects: 33 were normal controls, 19 had osteoporosis defined by the presence of one or more pathological fractures, and in the remainder the CT examination was performed at the patient's request. Os calcis BMC correlated with spinal BMD in both females (r = 0.69, p less than 0.001) and males (r = 0.84, p less than 0.001). However, the os calcis BMC did not reliably predict spine values around the CT "fracture threshold" of 90-100 mg/cm3 and did not correlate with osteoporotic fracture as well as did spinal BMD. It is concluded that measurement of the os calcis BMC is of limited clinical usefulness for the early diagnosis of osteoporosis.

Adolescent↗
PubMed1989

Bone histology in young adult osteoporosis.

Bone histology was quantitated in 10 osteoporotic patients aged between 17 and 51 years and in six healthy subjects aged between 23 and 43 years. The osteoporosis was of varying aetiology and was clinically stable. All patients were given tetracycline before biopsy and double tetracycline labelling was used in seven patients. Bone forming and resorbing surfaces were defined by the presence of osteoblasts and osteoclasts, respectively, which were identified by histochemical techniques. The associations between bone forming and resorbing surfaces were similar in patients and controls, though the range of values was wider in the patients than in the controls. Mineral apposition rate was normal in the osteoporotic patients, but there was a reduction in mineralising (tetracycline) surface, whether related to osteoid surface or to osteoblast surface. This did not indicate osteomalacia as the directly and indirectly measured mineralisation lag times were normal. The osteoid seams were thinner in osteoporotic patients than in controls. The data suggest that osteoclast and osteoblast numbers were normal in this group of osteoporotic patients but that the metabolic activity of osteoblasts was impaired.

Adolescent↗
PubMed1988

The effectiveness of a soluble calcium preparation as a gut phosphate binder.

We determined the phosphate binding capacity of a soluble commercial calcium preparation by carrying out metabolic balances on four normal subjects and by administering it for 4 weeks to six patients treated by maintenance hemodialysis. Each tablet of Sandocal 1000 (Sandoz, Australia) contained 1 g of elemental calcium as calcium lactate-gluconate 5.23 g and calcium carbonate 0.8 g. The metabolic balance study was performed over two consecutive nine-day periods. A constant, normal diet was consumed throughout, but in the second period one Sandocal 1000 tablet was added to each of the three major daily meals. Each period consisted of four days of equilibrium, then five days of collection of urine and feces. Polyethylene glycol 4,000 was used as a continuous fecal marker and carmine red was used to indicate gut transit time. Calcium supplementation increased fecal phosphate excretion by 11.2 +/- 2.3 mmol/d (SD), and decreased urinary phosphate by 8.4 +/- 2.6 mmol/d. Plasma calcium levels were unchanged, while plasma phosphate levels rose slightly. The increase in fecal phosphate was similar to that previously reported when calcium carbonate 8 g/d or aluminum hydroxide 6.4 g/d were administered. In the patients treated by maintenance hemodialysis, the reduction in plasma phosphate induced by Sandocal 1000, three tablets daily, was similar to that obtained with aluminum hydroxide 1.8 +/- 1.2 g/d. Hence, this calcium preparation appears to have a phosphate binding capacity similar to that of standard doses of aluminum hydroxide.

Adult↗
PubMed1987

Recovery from steroid-induced osteoporosis.

The reversibility of steroid-induced osteoporosis, a major complication of Cushing syndrome and long-term use of exogenous corticosteroids, is not well documented. We measured the bone mineral density of lumbar vertebras and the femoral neck by dual-photon absorptiometry and determined the biochemical variables of bone turnover in two patients successfully treated for Cushing syndrome who were followed for the next 24 months. Our data are the first to show marked increases in bone density (up to 20%) during the recovery period. The accompanying biochemical changes, particularly the marked increase in serum osteocalcin levels, confirm that enhanced bone formation occurred during the recovery phase. These findings suggest that steroid-induced osteoporosis can be reversed at least in young persons.

Adrenalectomy↗
PubMed1987

The pathogenesis of osteoarthritis of the hip. Evidence for primary osteocyte death.

Osteocyte viability was investigated in femoral head bone removed from 38 patients with chronic hip disease, with the use of a histochemical stain to demonstrate lactate dehydrogenase (LDH) activity in osteocytes. Where the osteocyte cytoplasm did not show LDH activity, the cell was considered dead; when several adjacent osteocytes were dead, the bone in that area was regarded as nonviable. The preoperative diagnoses were idiopathic osteoarthritis in 25, chondrocalcinosis in six, rheumatoid arthritis in two, Paget's disease in two, avascular necrosis in two, and congenital dislocation of the hip in one patient. In 16 of the patients with idiopathic osteoarthritis and the two with avascular necrosis, nonviable osteocytes were present in the central regions of many trabeculae, these areas usually being separated by cement lines from viable bone. The pattern suggested previous necrosis of part of the femoral head, with later new bone formation. The pattern was not observed in either control subjects, or patients with known articular disease, such as chondrocalcinosis. Bone collapse of variable severity was apparent radiographically in nine patients with histologic bone death, but not in other patients. Bone death is commonly present in idiopathic osteoarthritis and could be a cause rather than a result of the arthritis.

Adult↗
PubMed1986

Immobilization hypercalcaemia due to low bone formation and responding to intravenous sodium sulphate.

A young man developed acute renal failure and hypercalcaemia following severe burns. The hypercalcaemia was initially controlled by haemodialysis, but it persisted after return of renal function. Plasma PTH was inappropriately elevated, but the nephrogenous cyclic adenosine monophosphate level was low; thus the PTH was probably not biologically active, and may have been artefactually elevated by the moderate renal impairment. Bone histology, showed a normal resorbing surface, but a zero forming surface, implying that the bone dissolution leading to hypercalcaemia resulted from a failure of bone formation. Because of widespread infection and impaired renal function, the hypercalcaemia could not be treated by corticosteroid drugs, mithramycin or phosphate, and there was no response to salmon calcitonin. He was therefore treated with intravenous sodium sulphate, which increased urinary calcium excretion and reduced the plasma calcium. Sodium sulphate still has a role in the treatment of patients with hypercalcaemia.

Adult↗
PubMed1985

Treatment of childhood renal osteodystrophy with calcitriol or ergocalciferol.

Quantitative bone histology, biochemistry and height velocities were studied in 18 children suffering from chronic renal failure. Eight received calcitriol, 7 ergocalciferol and 3, though alloted to a treatment group, failed to comply with therapy. A histochemical stain for aluminum showed heavy deposition at the calcification front in 3 patients; 2, in the calcitriol group had severe osteomalacia which worsened during treatment, and 1 in the ergocalciferol group had osteomalacia which did not improve. One had never undergone hemodialysis. Bone histology improved markedly in the remaining 12 patients, whichever vitamin D preparation was used; it was unchanged in 3 non-compliant children. Plasma calcium levels rose while parathyroid hormone and alkaline phosphatase levels fell following both treatments, and were unchanged in non-compliant children. Hypercalcemia occurred more frequently following calcitriol therapy (11 episodes) than following ergocalciferol therapy (3 episodes). Height velocities, studied in 11 children, increased in 5 (3 on ergocalciferol and 2 on calcitriol) and were unchanged in 6 (1 on ergocalciferol, 5 on calcitriol). Improved bone histology did not correlate with increase in height velocity. As ergocalciferol and calcitriol had similar therapeutic effects and as side-effects were more common with calcitriol, it is concluded that calcitriol provides no advantage over ergocalciferol in the treatment of renal bone disease in children.

Alkaline Phosphatase↗
PubMed1985

Treatment of hemodialysis bone disease with 24,25-(OH)2D3 and 1,25-(OH)2D3 alone or in combination.

We studied the effects of vitamin D metabolites in 29 patients established on chronic hemodialysis. The patients were divided into four groups; one was treated with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] 0.5 microgram/day, one with 24R,25-dihydroxyvitamin D3 [24,25-(OH)2D3] 10 micrograms/day, and one with both metabolites. The control group was not given vitamin D. Plasma levels of both metabolites were low before treatment. 1,25-(OH)2D3 levels became normal, and 24,25-(OH)2D3 increased to supranormal levels after administration of the corresponding metabolite. Combined treatment produced still higher plasma levels of 24,25-(OH)2D3, suggesting an interaction between the two metabolites. Patients receiving 1,25-(OH)2D3 alone had a greater increase in plasma calcium than those receiving both metabolites. In control patients, hyperparathyroid bone disease worsened over the 10-month observation period. 1,25-(OH)2D3 improved hyperparathyroid bone disease in most patients, as reflected by a reduction in osteoclast and osteoblast numbers, but had no demonstrable effect on mild osteomalacia. 24,25-(OH)2D3 had no significant effect on plasma biochemistry or bone histology, and the effect of combined treatment on histology was similar to that of 1,25-(OH)2D3 alone. Stainable bone aluminum increased slightly in patients given 1,25-(OH)2D3, but aluminum did not affect the response to treatment. We conclude that 1,25-(OH)2D3 is a useful agent in the treatment of renal bone disease, but no therapeutic role is apparent for 24,25-(OH)2D3.

24,25-Dihydroxyvitamin D 3↗
PubMed1985

The effect of age on bone composition and viability in the femoral head.

We studied the effect of age on bone composition and osteocyte viability in femoral heads from fifty-one subjects. The assessment included determination of: bone volume, ash weight, calcium, and phosphorus content; osteocyte viability in fresh sections stained for lactate dehydrogenase activity; microfractures in fresh sections after removal of marrow elements; bone area, the presence of metabolic bone disease, and the histology of microfractures in embedded calcified sections; and the extent of trabecular microfractures. Bone area and numbers of microfractures were also assessed in eight elderly hip-fracture patients. Bone volume decreased with age, but there was considerable variation in each age group, and no significant difference between men and women. Ash weight and the bone content of calcium and phosphorus also decreased with age, but were constant if corrected for bone volume. Almost all osteocytes were viable in subjects who were younger than twenty-five years, and thereafter viability progressively decreased to a mean of 74 per cent in the eighth decade of life. There was a significant negative correlation between osteocyte viability and age. There was no evidence of metabolic bone disease in any patient. The numbers of microfractures increased with age and correlated negatively with bone viability (r = -0.31, p less than 0.05); in simple linear correlation a relationship between bone area and microfractures could not be demonstrated but in multiple linear correlation, after the inclusion of bone viability, there was an additional negative correlation between numbers of microfractures and bone area (p less than 0.005). Bone area and numbers of microfractures in hip-fracture patients were similar to those in age-matched controls.

Adolescent↗
PubMed1985

The pathogenesis of renal osteodystrophy: role of vitamin D, aluminium, parathyroid hormone, calcium and phosphorus.

Biochemical data and bone histology from 44 haemodialysis patients was compared using an histologic technique capable of evaluating separately the individual components of osteodystrophy. Hyperparathyroid bone disease was diagnosed by an elevated osteoclast count, and in advanced disease there was also fibrosis and woven bone. Osteomalacia, defined as an impairment in the rate of bone mineralisation, was present in two distinct forms: osteomalacia type I, characterised by wide osteoid seams, and osteomalacia type II, characterised by extensive thin, inactive osteoid. The histologic diagnoses were hyperparathyroid bone disease (15), osteomalacia type I (3), osteomalacia type II (6), hyperparathyroid bone disease and osteomalacia type I (12), hyperparathyroid bone disease and osteomalacia type II (6), normal (2). Aluminium was evident histochemically in 17 biopsies. Vitamin D metabolite levels were low in most patients and did not correlate with any biochemical or histological parameter. Parathyroid hormone levels were highly correlated with histological features of hyperparathyroid bone disease, and also correlated with plasma calcium, suggesting a degree of autonomy of parathyroid hormone secretion. Urea and creatinine were higher in the hyperparathyroid bone disease than the osteomalacia groups suggesting that poor dialysis contributes to the former. Statistical analysis showed that osteomalacia type I was associated with relatively low plasma calcium and phosphorus levels; osteomalacia type II was associated with increased bone aluminium and with the uraemic process itself, as reflected in the plasma creatinine level. This study shows relationships between renal osteodystrophy and plasma calcium and phosphorus levels, but no relationship with vitamin D metabolites. Aluminium appears to impair mineralisation even at relatively low levels of accumulation. However there are other unidentified factors associated with the uraemic process, contributing to all three components of renal osteodystrophy.

Adult↗