Symposium on metabolic bone disease.

of Short Papers INVESTIGATION OF BONE MINERALISATION USING TECHNIQUES FOR ELEMENTAL MICROANALYSIS AND IMAGE ANALYSIS WITH TIlE ELECfRON MICROSCOPE. D. W. Dempster, H. Y. Elder, V. A. Moss, W. A. P. Nicholson, D. A. Smith, Departments of Physiology, Natural Philosophy and Medicine (Western Infirmary), University ofGlasgow. Advances in solid state physics have permitted the combination of x-ray elemental analysis with the high special resolution of transmission electron microscopy. Ultra-rapid cooling techniques and anhydrous preparation routes can preserve fiffusible substances including electrolytes in their in vivo locations. Fully quantitative analyses can be obtained from ultrathin sections of mineralized tissue using the Hall continuum normalization method. We have shown that mineralization failure in the osteoid of osteomalacic rats is caused not by a failure to accumulate adequate Ca or P but probably by a failure of mineral release (1). Simple and rapid methods are now also available for preparation of relatively large areas of bone mineral surface for scanning electron microscopy and a number of forming and eroding mineral surface types have been characterised. Using image analysis, quantitative ·discrimination between normal and pathological mineral surfaces is possible (2) and automated computer texture recognition is now being developed. References 1 Dempster DW, Elder HY, Nicholson WAP, Smith DA. Microprobe analysis of calcium and phosphorus levels in rachitic rate osteoid. J PhysioI1980; 300:67. 2 Dempster DW, Elder HY, Smith DA. Scanning electron microscopy of rachitic rate bone. Scan Electron Microsc. 1979;2:513-520. CLINICAL EXPERIENCE OF OSTEOMALACIA IN GLASGOW. L. M. Matheson, J. Henderson, W. B. McIntosh, M. G. Dunnigan, Department of Medicine, Stobhill General Hospital, Glasgow. The present study had two parts: a) a review of eighteen Asian female patients admitted to Glasgow hospitals between 1973-83. b) a biochemical screening of 220 randomly selected Asian women aged 21 to 60 years. Twentv seven women had evidence of osteomalacia: nine ~ith biochemical evidence only were found on screening. Eight Hindu/Sikh women had severe disease with positive aetiology; seven were lactovegetarians. No severe bone disease was found in Moslems. An assessment of sunlight exposure showed no significant difference between religious groups and no correlation was made with the occurrence of osteomalacia. A seven day weighed dietary survey of 100 women showed a correlation between osteomalacia and lactovegetarianism; the chapatti content of the diets was uniform. Although osteomalacia has a multifactorial aetiology, our conclusion is that, in the adult Asian female population in Glasgow, severe disease is found in lactovegetarians i.e. Hindu/Sikh women. We hypothesise that there may be as yet undetected vitamin D in animal products exerting a protective effect against osteomalacia. STUDIES WITII BONE-SEEKING ISOTOPES. D. A. S. Smith and M. Forwell, University Department of Medicine, Gardiner Institute, Western Infirmary, Glasgow. The controversy as to whether decreased bone formation or increased bone resorption is the major cause of osteoporosis has been revived in recent studies by Meunier et al. (1981) and White et al. (1982).Using biopsy specimens and histological techniques they describe considerable heterogenicity in the rates of bone formation and destruction in their patients. Bone-seeking isotopes can be a useful non-invasive technique for measuring bone formation rate. It would also have the advantage of sample size. However, there have been the problems of whether isotopes go only to bone-forming sites, and if exchange of isotope for stable calcium distorts the measurements. We have carried out a series of animal experiments in order to demonstrate the distribution of bone-seeking isotopes. Our studies indicate that isotope uptake is a true measure of new bone formation. Using ·'Sr, we have measured the rate of bone formation in 65 postmenopausal women ranging in age from 45 to 86 years. There was a significant fall in the rate of bone formation of 1.12 per cent per year which paralleled the rate of loss of bone (1.10% per year), measured as the fall in metacarpal index in these patients. We would suggest that a fall in bone formation rate makes a major contribution to the development of osteoporosis. References 1 Meunier PJ, Sellami S, Briancow D. Edouard C. Histological heterogeneity of apparently idiopathic osteoporosis. In: DeLuca HF. Frost HM, Jee WSS, Johnston CC Jr , Parfitt AM. eds. Osteoporosis: Recent Advances in Pathogenesis and Treatment. Baltimore: University Park Press 1981;293-301. 2 Whyte MP, Bergefield BA. Murphy WA. Avioli LV. Teitelbaum SL. Am J Med 1982;72:192-202. LONG-TERM OSTROGEN THERAPY. D. McKay Hart, H. I. Abdalla, Department of Obstetrics and Gynaecology, Stobhill General Hospital, Glasgow. Mestranol (ethinyl oestradiol3-methyl ether) 40 IJog daily was prescribed for a carefully matched active and placebo group of patients who had undergone total hysterectomy and bilateral salpingo-oophorectomy, the study commencing in 1%8. The density of the right middle metacarpal was measured by photon absorptiometry in the Bone Metabolism Unit, Western Infirmary, Glasgow. The effects of metacarpal bone mineral content of age at operation, years from surgical menopause, body weight, smoking habit, parity and lactation history are presented comparing the placebo group with the actively treated group. The findings indicate that oestrogen protects against post-oophorectomy bone mineral loss. OSTEOPOROSIS IN THE ELDERLY. W. J. MacLennan, Department of Geriatric Medicine, Ninewells Hospital, Dundee. Osteoporosis presents in old people as vertebral collapse or a fractured hip. Dementia and ataxia are as important as osteoporosis in the latter. The metacarpal index is useful in epidemiological work, but in clinical work a chest X-ray and X-ray of dorsal vertebrae is more useful. A discriminant equation of serum calcium and phosphate levels is useful in excluding osteomalacia. Plasma 250HD levels are less useful. An ESR should be used to exclude multiple myeloma. Bone rarefaction occurs in association with ageing and, in women, is closely related to postmenopausal oestrogen deficiency. Renal function also declines in old age, but the effect of this on bones is unclear. The calcium intake of old people may be inadequate. This may exacerbate bone loss. Osteoporosis also may be caused by mild but prolonged vitamin D deficiency. Though exercise can effect exercise changes in physical activity have little effect on bone mass in old age. However, multiple pregnancies reduce the risk of osteoporosis. Disorders contributing to bone loss in old age include diabetes, thyrotoxicosis, rheumatoid arthritis and corticosteriod therapy. The simplest and safest way of preventing bone loss in old age is to give calcium supplements. Oestrogen therapy requires further evaluation. ACUTE CHANGES IN PLASMA IMMUNOREACI1VE PARATHYROID HORMONE AND CALCITONIN DURING MAINTENANCE HAEMODIALYSIS. G. H. Beastall, M. A. Bell, J. A. Fyffe", M. D. Gardner, I. S. Henderson", A. C. Kennedy" , Departments. of Clinical Biochemistry and Medicine", Royal Infirmary, Glasgow. Attempts to offset the hypocalcaemia of severe CRF usually include haemodialysis (HD) against a fluid containing supraphysiologicallevels of Ca2 +. We have examined he acute effects of this procedure on the hormones of calcium homeostasis-parathyroid hormone (PTH) and calcitonin (Cf). Sixteen subjects each showed a fall in PTH and a rise in Cf immediately following maintenance HD. A subsequent study in eight Symposiumon MetabolicBoneDisease subjects revealed that Cf increases lineraly with time of HD, whilst PTH appears to be removed by dialysis rather than suppressed by increased CA2+ may help to counter the secondary hyperparathyroidism of CRF. THE 24-HOUR WHOLE-BODY RETENTION OF Tc-99m DIPHOSPHONATE TECHNIQUE. I. Fogelman, R. G. Bessent, M. L. Smith, D. M. Hart, I. T. Boyle, University Department of Medicine, Royal Infirmary, Glasgow and Department of Obstetrics, Stobhill Hospital, Glasgow. While the Tc-99m diphosphonate bone scan may be of considerable value in the assessment of patients with metabolic bone disease it is unfortunately least likely to be of assistance in those patients providing the most difficulty in clinical practice, and for example patients with osteoporosis, mild primary hyperparathyroidism or sub-clinical osteomalacia often have normal bone scans. However, if increased bone turnover is present, there will be an absolute increase in skeletal uptake of any bone seeking radiopharmaceutical and clearly an accurate means of quantitating this would be of diagnostic value. To this end we developed a technique whereby the whole-body retention of Tc-99m labelled HRDP (WBR) was measured 24 hours after injection, using a standard shadow-shield whole-body monitor. At this time the non-skletal (soft tissue) diphosphonate has been largely excreted via the urinary tract and the remaining activity in the body primarily reflects skeletal uptake of tracer. With the WBR technique it has been shown that patients with osteomalacia, primary hyperparathyroidism, renal osteodystrophy and Paget's disease can be clearly differentiated from a control population. In addition, each individual patient's result in these groups lies outside the control range. In osteoporosis we find that the majority of results are normal and have shown that those subjects with elevated values also have histoligical evidence of increased bone turnover. Whole-body retention provides a sensitive means of assessing skeletal metabolism. This test is very simple to perform, is non-invasive and uses an extremely small amount of radioactivity. TWO CAUSES OF OSTEOMALACIA UNRELATED TO VITAMIN D DEFICIENCY. B. F. Boyce, University Department of Pathology, Glasgow Royal Infirmary. Patients recei