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Biomedical subjects

C R Dunstan

Publications and source records attributed to C R Dunstan.

80 records · Page 5Linked to original sources
PubMed1982

The effect of long-term low-dose diphosphonate treatment on rat bone.

Weaning, male rats were given ethane-1-hydroxy 1,1-diphosphonate (EHDP) or dichloromethylene diphosphonate (Cl2MDP) 0.5 mgP/kg/day for 140 days. Samples prepared after sacrifice were: (1) thin ground (30 micrometers) transverse tibial sections, (2) methacrylate-embedded 5 micrometers sections of the proximal tibial metaphysis, and (3) ultrathin calcified metaphyseal sections for electron microscopy. Cl2MDP reduced the diaphyseal medullary cavity, and EHDP increased the osteoid width. Both drugs increased endosteal bone apposition (possible secondarily to the impaired resorption) and, perhaps as a result, periosteal apposition was increased. Consequently, diaphyseal bone area was unchanged. Metaphyseal bone area was increased and osteoclast numbers reduced, in contrast to the increased osteoclast numbers reported previously in animal experiments with diphosphonates. Acid phosphatase activity within osteoclasts was markedly reduced with EDHP and unchanged with Cl2MDP. The ultrastructural changes in osteoclasts, i.e., a deficiency of ruffled borders, reduced numbers of cytoplasmic vacuoles and the presence of crystals between bone and the osteoclastic plasmalemma, were more marked with EHDP than Cl2MDP.

Animals↗
PubMed1982

Long-term experience with a calcium-thiazide treatment for Paget's disease of bone.

75 patients with Paget's disease of bone were treated with a drug combination intended to increase the production of endogenous calcitonin and decrease that of parathyroid hormone. The first regimen of oral calcium, thiazide diuretic, aluminum hydroxide and low-phosphorus diet was given to 41 patients for a mean of 800 days. A simpler regimen of oral calcium and thiazide diuretic was given to 34 patients for a mean of 750 days. There was a similar fall in mean plasma alkaline phosphatase to 71 +/- 24 (SD)% of initial with the first regimen and 72 +/- 17% with the second at 150 days, with a gradual rise after 500 days. Urinary hydroxyproline fell from 165 +/- 111 to 112 +/- 93 mg/day. Plasma calcium rose slightly with both regimens and plasma inorganic phosphorus fell with the first. Serum parathyroid hormone and calcitonin levels were unchanged. Urinary calcium was not changed by the first regimen and rose by 40 +/- 54 mg/24 h with the second. Clinical improvement approximately paralleled biochemical improvement. It is suggested that, in view of its low cost and convenience, this treatment has a place in the management of Paget's disease of bone.

Adult↗
PubMed1982

Bone metabolism in chronic renal failure.

Quantitative bone histology was carried out on 37 haemodialysis patients. Hyperparathyroid bone disease (HPT) was diagnosed by an elevated osteoclast count, and high counts were associated with classic osteitis fibrosa. Osteomalacia (OM) was found in two distinct though frequently overlapping forms, both with increased osteoid surface. In classic OM (type 1), present in 19% of patients the osteoid seams were wide and the mineral apposition rate low, with the tetracycline bands wide and merging together. In the more common form of OM (type 2), present in 81%, the mineralising surface, as shown by tetracycline uptake, was reduced, but the mineral apposition rate was normal. Tetracycline surface was highly correlated with osteoblast surface, suggesting that osteoblasts play a role in mineralisation, and that type 2 OM is caused by a reduction in osteoblast surface. The osteoblast surface also correlated with serum parathyroid hormone, and so secondary hyperparathyroidism may obscure the diagnosis of type 2 OM, which may be almost universally present in haemodialysis patients. Type 1 OM is not obscured by secondary hyperparathyroidism. Of the 37 patients 5 had HPT, 9 OM and 22 HPT + OM. Only one had normal bone. Biochemical parameters had limited predictive value. The study also did not support the suggestion that endogenous calcitonin protects against HPT disease.

Adult↗
PubMed1981

Lack of metabolic bone disease in patients with fracture of the femoral neck.

To examine the widely held belief that osteoporosis and osteomalacia are pathogenetic factors in femoral neck fracture, we compared such patients with vertebral fracture patients and controls. Cortical bone was measured in hand X-rays and cancellous bone in iliac crest biopsies, which were also used to assess osteoid, tetracycline and resorbing surface. The vertebral fracture patients were found to have a reduction of 53% and 41% in cancellous and cortical bone respectively compared to the controls, while in the much older femoral fracture patients the reductions were 19% and 16%. Three femoral fracture patients had mild osteomalacia from identifiable causes; a further one had fluorosis of bone and one had metastatic carcinoma; with the exception of these the osteoid covered surface of bone was less than in vertebral fracture patients and controls. We conclude that pathologic osteoporosis and osteomalacia are not major factors in the pathogenesis of femoral neck fractures, though the normal age related reduction in bone mass may contribute. There may be another age related factor weakening the femoral neck. It was also noted that when assessed by a sensitive histochemical technique for osteoclast identification, bone resorption was not increased in either of the fracture groups.

Adolescent↗
PubMed1980

Quantitative bone histology: a new method.

A method is described for quantitative histology of undecalcified bone using an embedding medium suitable for histochemistry. Six normal subjects were given tetracycline markers 24 and 3 d prior to the biopsy which was taken from the posterior iliac spine using an 8 gauge Jamshidi needle. The tissue was embedded in a mixture of equal parts methylmethacrylate and hydroxyethylmethacrylate. Three consecutive sections were cut and (1) stained histochemically for acid phosphatase activity to identify osteoclast cytoplasm, (2) stained with pyronin to identify osteoblast cytoplasm, (3) mounted unstained for tetracycline fluorescence. Tracings of the 3 sections were superimposed using a camera lucida attachment to the microscope, and the tracings quantitated with an electronic digitizer. The major parameters were bone area (17.1 +/- 4.4%) (mean +/- SD), osteoblast or forming surface (5.9 +/- 2.7%) and osteoclast or resorbing surface (1.0 +/- 0.3%). Bone apposition rate was 1.0 +/- 0.2 micrometers/day and resorption velocity (calculated by assuming bone formation and resorption to be equal) 8.4 +/- 4.1 micrometers/day. Mineralization was assessed by osteoid area (3.8 +/- 2.5%), osteoid surface (13.9 +/- 6.6%), tetracycline uptake at the mineralizing front (62.3 +/- 13.5%), and mineralization lag time (18.1 +/- 2.5 days).

Acid Phosphatase↗
PubMed1980

Quantitative bone histology in end-stage renal failure.

Bone biopsies from 37 haemodialysis patients were embedded in a methyl methacrylate:hydroxyethylmethacrylate mixture and consecutive sections taken for: (1) acid phosphatase activity (osteoclasts), (2) pyronin stain for RNA (osteoblasts), and (3) fluorescence for tetracycline. Images of the three sections were traced using a camera lucida and the tracing quantitated with a digitiser. Osteomalacia (OM) was diagnosed by increased osteoid with decreased tetracycline and hyperparathyroidism (HPT) by an increased osteoclast count. OM was present in 8 patients, HPT in 11, OM + HPT in 16, and no disease in 2. Biochemistry could not predict the histology. Histologically, though HPT could be satisfactorily diagnosed, problems still remain in the definition of OM, particularly when combined with HPT.

Bone Diseases↗
PubMedDate not supplied

Adult osteosclerosis.

Quantitative bone histology was carried out in five osteosclerotic adults. The bone was extremely hard in all patients, and open biopsy was usually required. One patient, aged 18 years, presented with hypoplastic anemia, and the most probable explanation for the osteosclerosis is a marrow stem cell defect leading to defective osteoclasts. Another had the dominant form of osteopetrosis. Her bone contained cartilage remnants, and there were many large, morphologically abnormal osteoclasts, which lacked normal cytoplasmic acid phosphatase activity. The third patient had chronic renal failure and osteomalacia; here the increased bone mass might have resulted from an inability of normal osteoclasts to resorb bone, due to the surface coating of osteoid, though an earlier increase of bone formation cannot be excluded. The fourth patient, who suffered from systemic mastocytosis, had high turnover bone, with greatly increased bone formation. The fifth patient, with fluorosis of bone, also had increased bone formation and resorption, the process being much more pronounced in the head of her pathologically fractured femur than it was in the iliac crest. In this patient some osteoclasts had reduced acid phosphatase activity and long cytoplasmic extensions, both changes similar to those observed in diphosphonate-treated animals. Very diverse processes can result in the increased cancellous bone mass producing the radiographic appearance of diffuse osteosclerosis.

Adolescent↗