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Biomedical subjects

J E Aaron

Publications and source records attributed to J E Aaron.

52 records · Page 3Linked to original sources

Osteomalacia in Paget's disease treated with short term, high dose sodium etidronate.

Eleven patients with Paget's disease treated with sodium etidronate 20 mg/kg/day for two and four weeks showed significant reductions in plasma alkaline phosphatase activity and urinary hydroxyproline excretion, both of which are biochemical markers of bone turnover. After four weeks of treatment, however, histological examination of iliac crest biopsy samples showed that despite a rapid reduction in bone resorption there was an appreciable mineralisation defect; even after only two weeks' treatment the abnormalities in bone formation persisted for up to 10 weeks. The adverse effects of sodium etidronate on mineralisation cannot be dissociated from its beneficial effect on resorption even when it is given for short periods.

Aged↗

Osteoporosis in hypogonadal men: role of decreased plasma 1,25-dihydroxyvitamin D, calcium malabsorption, and low bone formation.

To investigate the pathogenesis of osteoporosis in male hypogonadism we have investigated a heterogeneous group of 13 men with hypogonadism: 7 men (median age 60, range 31-79) with two or more vertebral crush fractures and 6 men (median age 61.5, range 28-76) without vertebral fractures. The group with crush fractures had trabecular and cortical osteoporosis as assessed by Singh grade, iliac crest trabecular bone volume, and metacarpal cortical area/total area. This was accompanied by an altered trabecular architecture with a reduction in number of trabeculae but no change in trabecular width, which contrasts with age-related bone loss in men where there is no reduction in trabecular number but thinning of trabeculae. The fracture group had significantly lower plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations than the nonfracture group, and this was associated with malabsorption of calcium. Irrespective of the presence or absence of osteoporosis, treatment with testosterone led to a significant increase in total and free plasma 1,25(OH)2D and an improvement in calcium absorption measured with radiocalcium and by balance techniques. In addition, urine biochemistry, metabolic balance studies, and bone biopsy suggest that skeletal retention of calcium and bone formation are increased by testosterone treatment. We conclude that male hypogonadism causes both cortical and trabecular osteoporosis and altered trabecular architecture. A major risk factor for the development of osteoporosis is reduction in plasma 1,25(OH)2D, leading to malabsorption of calcium and reduced bone formation.

Adult↗

Staining of the calcification front in human bone using contrasting fluorochromes in vitro.

Histological studies on bone from the human iliac crest have suggested that if the customary techniques of labeling in vivo with certain fluorochromes such as tetracycline are replaced or augmented by simple whole tissue staining in vitro using the same reagents, differences in the pattern of extracellular fluorescence between normal and pathological states are retained. In particular, the association of the fluorescence with the calcification front in stained examples is closely comparable to similar examples that have been labeled (r = 0.988, p less than 0.001) and to other tinctorial methods (r = 0.891, p less than 0.001). While the stain alone lacks the time lapse of multiple labels, when administered some days after a single label at the time of biopsy, it provides an effective second marker and a measure of mineralization rate that does not differ significantly from that using double labels. Moreover, since the problems of toxicity are avoided by staining, a range of contrasting fluorochromes previously restricted to animal studies may now be used in man. In particular, the enhanced color differentiation brought about by the combination of tetracycline label followed by xylenol orange stain improves image resolution and greatly aids interpretation.

Bone Diseases↗

Dialysate aluminium concentration and renal bone disease.

We studied 40 patients maintained on regular hemodialysis, using radiology and quantitative bone histology to assess the relationship between renal bone disease and exposure to aluminium. Fractures were significantly more common in patients exposed to high dialysate aluminium concentrations. The histologic indices of osteomalacia were significantly related to the prevailing dialysate aluminium concentration, in such a way that higher aluminium levels were associated with more osteomalacia. Patients who had been exposed to higher concentrations of aluminium also tended to have a lower plasma phosphate concentration, and associated hypercalemia was seen in 6 patients with osteomalacia. These findings suggest that aluminium is a toxic agent associated with a mineralizing defect in the bone of renal failure patients. This may explain the incomplete response of some patients with renal osteomalacia to administration of 1,25-dihydroxy vitamin D.

Adolescent↗

Effect of oophorectomy and calcium deprivation on bone mass in the rat.

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.

Animals↗

Vitamin D resistant hypophosphataemic osteomalacia: treatment with 1alpha-hydroxyvitamin D3.

Ten patients with vitamin D resistant hypophosphataemic osteomalacia are described. They had hypophosphataemia with a decreased tubular reabsorption of phosphate, malabsorption of calcium and phosphorus, proximal myopathy and extensive osteomalacic changes on iliac crest bone biopsy. The plasma alkaline phosphatase and urine hydroxyproline, however, were raised in only some of the patients. Treatment with 1alpha-hydroxyvitamin D3 in high doses rapidly cured the myopathy, increased calcium and phosphorus absorption and retention and healed the osteomalacia. Phosphorus supplements were not required.

Adolescent↗