B.E.C. Nordin

EFFECT OF AGE ON CALCIUM ABSORPTION

Abstract Calcium absorption was measured by plasma radioactivity after oral calcium isotopes in seventy-five men and one hundred and fifteen women aged 20-95 years. Absorption of calcium fell with age after about 60 years and everyone over 80 had significant malabsorption. This malabsorption of calcium in the elderly may well be due to vitamin-D deficiency, and could play a significant role in the pathogenesis of fractures in old people.

FREQUENCY OF OSTEOMALACIA AND OSTEOPOROSIS IN FRACTURES OF THE PROXIMAL FEMUR

Abstract A quantitative histological examination was made of iliac-crest biopsy specimens obtained from 125 cases of fracture of the proximal femur (102 women and 23 men). 35 women (34%) demonstrated a more severe degree of osteoporosis than would be expected for their age and 35 (including 10 of those with osteoporosis) had some evidence of osteomalacia. There was some evidence of osteomalacia in 11 (47%) men. 5 women and 2 men with osteomalacia had previously undergone partial gastrectomy. It is suggested that osteomalacia in the elderly makes an important contribution to the steep rise in femoral-neck fractures with advancing age in the U.K. and that this is attributable to an absolute or relative deficiency of vitamin D. It is also suggested that at least some of the osteoporotic component may also be attributable to a degree of vitamin-D deficiency sufficient to cause malabsorption of calcium but not sufficient to produce osteomalacia.

CALCIUM CRYSTALLURIA IN RECURRENT RENAL-STONE FORMERS

Abstract The volume of crystals excreted by controls and stone-forming patients was measured in fresh urine at body temperature. Six male patients with idiopathic recurrent renal-stone disease had a sustained crystalluria on a normal but constant dietary intake of calcium, phosphorus, oxalate, and fluid. Below pH 6.2 the crystals consisted only of calcium oxalate and above pH 6.2 mainly of calcium phosphate. Six healthy male controls investigated under the same conditions of diet and fluid intake excreted significantly less crystalline calcium oxalate than did the stone-formers. Separate oral doses of calcium citrate and sodium oxalate further enhanced the crystalluria of the stone-formers but had little effect in the controls. The difference between the two groups was due mainly to a difference in crystal size rather than crystal numbers. The calcium-oxalate crystalluria in the recurrent stone-formers was mainly of octahedral crystals of calcium oxalate dihydrate, often in aggregates up to 200 μ in diameter, whereas in the controls the calcium oxalate was in the form of very small particles with little or no aggregation. The increased crystalluria of the stone-formers was assor ciated with increased concentrations of calcium and oxalate in the urine.

The crush fracture syndrome in postmenopausal women

It is widely agreed that however osteoporosis may be defined and whatever the contribution of ageing or other causes may be, there is an unmistakable osteoporotic syndrome characterised by vertebral crush fractures with or without biconcavity which occurs predominantly in post-menopausal women. This syndrome, which was first clearly identified by Albright, Smith and Richardson in 1941, is generally easily recognised on lateral radiographs of the thoracic and lumbar spine, but its underlying cause and, therefore, the most effective form of treatment have yet to be defined. This chapter assembles the principal radiological, histological and metabolic data that we have collected over a period of years in a series of 58 postmenopausal women with vertebral crush fractures in whom none of the recognised causes of this condition, such as steroid therapy, hyperthyroidism, and realabsorption syndrome, were present. Although it has not been possible, even in the limited group, to identify a single pathogenic mechanism, we nonetheless believe that these cases have sufficient features in common to permit certain general conclusions on the causes and treatment of the condition.

ROLE OF KIDNEY IN REGULATION OF PLASMA-CALCIUM

Abstract It is suggested that it is the action of parathyroid hormone on renal tubular reabsorption of calcium which is mainly responsible for plasma-calcium homœostasis in man.

BONE FORMATION AND RESORPTION AS THE DETERMINANTS OF TRABECULAR BONE VOLUME IN POSTMENOPAUSAL OSTEOPOROSIS

Histomorphometry has been applied to trabecular bone samples obtained post-mortem from young and old women without known bone disease and to bone biopsy specimens from patients with postmenopausal osteoporosis. Bone volume was significantly lower in the old than young controls and significantly lower again in the osteoporotics. The loss of bone with age associated with a rise in surface resorption but no change in forming surface, and the further loss in osteoporotics was associated with a further rise in resorption and a small non-significant fall in forming surfaces. It is suggested that trabecular bone volume is determined by the relation between total forming surface on the one hand and percent surface resorption on the other, and this relationship is expressed in mathematical terms. Age-related bone loss (simple osteoporosis) in women is accounted for by increased resorption, and accelerated osteoporosis is mainly due to a further increase in resorption.

Effects of natural and artificial menopause on plasma and urinary calcium and phosphorus.

Abstract Plasma and urinary levels of calcium and phosphorus have been determined in 39 healthy premenopausal women, 28 post-menapausal women in whom the menopause had been natural, and 51 women who had undergone bilateral salpingo-oophorec- tomy. The levels were increased after the menopause, particularly where this bad been artificial. It is suggested that loss of œ strogenic activity at the menopause results in increased bone resorption. It is not clear, however, whether the resultant negative calcium balance is the cause of or the result of osteoporosis in post-menopausal women.

SEASONAL VARIATION OF HISTOLOGICAL OSTEOMALACIA IN FEMORAL-NECK FRACTURES

Abstract In a series of 134 iliac-crest biopsies from unselected cases of fracture of the proximal femur, the proportion with evidence of osteomalacia varied with the season. The highest frequency of abnormal calcification fronts (43%) was observed in February to April and the lowest (15%) in August to October. The highest frequency of abnormal osteoid-covered surfaces (47%) was observed in April to June and the lowest (13%) in October to December. The overall frequency of osteomalacia in femoral-neck-fracture cases in Leeds seems to be about 37%. It is concluded that variation in hours of sunshine is responsible for a seasonal variation in osteomalacia in these cases and, possibly, in the elderly population as a whole.

PARATHYROID ACTIVITY AND POSTMENOPAUSAL OSTEOPOROSIS

Abstract The mean cortical-area/total-area (C.A./ T.A.) ratios have been worked out from X-rays of the second metacarpal in three groups of women: idiopathic hypoparathyroidism, postoperative controls, and primary hyperparathyroidism. Each group contained premenopausal and postmenopausal women. The C.A./T.A. value for postmenopausal women with hyperparathyroidism (0.69) was significantly lower than that for both the postmenopausal hypoparathyroid and the premenopausal hyperparathyroid groups. It seems that parathyroid hormone is a mediator in age-related osteoporosis.

ACTION OF 1α-HYDROXY VITAMIN D3 ON CALCIUM ABSORPTION AND BONE RESORPTION IN MAN

Abstract Synthetic 1α-hydroxy-vitamin D 3 (1α-hydroxycholecalciferol, 1α-H.C.C.) was given orally in a dose of 25 μg. per day to groups of patients in whom calcium malabsorption is a recognised feature. Patients responded with an increase in plasma calcium and phosphate and in calcium absorption irrespective of their pre-treatment values. Net calcium resorption from bone was increased in all patients with normal renal function. In patients with renal failure, however, net bone resorption tended to decrease. The onset of action was rapid and could be seen within 24 hours. On stopping the vitamin the effects were not maintained and their disappearance depended on the duration of treatment. 1α-H.C.C. is very potent in man and will be useful in treatment of patients with calcium malabsorption. The malabsorption of calcium of elderly people is not due to failure of the absorptive mechanism in the small bowel since it responds to 1α-H.C.C. but the dose will need to be less than 25 μg. per day to avoid excessive bone resorption and hypercalcaemia.