1168
criptine may be given subsequently to control the endocrinopathy if this is not relieved by surgery and radiation. In patients in whom the tumour is confined to the pituitary fossa a trial of bromocriptine is undertaken. In those in whom a full response, as previously defined, is obtained, external radiation is applied to the tumour and bromocriptine is continued, to be withdrawn annually to ascertain if the radiation has suppressed G.H. secretion. When a partial response is obtained with bromocriptine the decision to continue this alone or offer external radiation or more definitive local treatment (e.g., yttrium-90 implantation or trans-sphenoidal hypophysectomy) depends on many factors, particularly the extent of the response and the age and medical condition of the individual patient. If there is no response to bromocriptine, definitive local therapy remains the treatment of choice particularly in younger acromegalics with active disease. The dosage regimen is now 2.5mg twice daily with meals for one week to allow the patient to become accustomed to the drug, then 2’5 mg six-hourly for a week and 5 mg six-hourly subsequently. Clinical and biochemical effects can be assessed within a month, but this interval is too short for radiological changes to be apparent. We are grateful to Dr J. Anderson for evaluation of the Hindex ; to Mr A. L. Crombie for ophthalmic assessment; to Dr J. Marks and Mrs J. Alcock for S.E.R. estimation; to Dr A. Burridge for radiological assessment, to Sister G. M. Smith and Sister P. M. Fletcher for their help; to Mr W. M. Ross and Mr R. M. Kalbag for their cooperation; to Dr W. P. Maclay and the late Dr. E. R. Evans (Sandoz Ltd.) for the supply of bromocriptine ; to Dr W. R. Butt for the gift of antisera of L.H./F.S.H. and purified pituitary F.S.H.; and to Dr Anne Stockell-Hartree for pituitary L.H. used for labelling.
TREATMENT OF OSTEOPOROSIS OF AGEING WITH 1&agr;-HYDROXYCHOLECALCIFEROL
O. H. SØRENSEN Medical Department E, Frederiksberg Hospital; Department of Physical Medicine, City Hospital; Royal Dental College; and Department
Chiodini, P. G., Botalia, L., Cremascoli, G., Muller, E. E. Silverstrini, F. J. clin. Endocr. Metab. 1974, 38, 910. 5. Thorner, M. O., Chait, A., Aitken, M., Benker, G., Bloom, S. R., Mortimer, C. H., Sanders, P., Stuart-Mason, A., Besser, G. M. Br. med. J. 1975, i, 299. 6. Clark, F., Brown, H. J. ibid. 1970, i, 713. 7. Clark, F., Brown, H. J. ibid. 1970, ii, 543. 8. Ormston, B. J., Garry, R., Cryer, R. J., Besser, G. M., Hall, R. Lancet, 1971, ii, 10. 9. Hartog, M., Gaafar, M. A., Meisser, B., Fraser, T. R. Br. med. J. 1964, ii, 1229. 10. Hall, R., Amos, J., Ormston, B. J. ibid. 1971, i, 582. 11. Shaw, R. W., Butt, W. R., London, D. R., Marshall, J. C. J. Obstet. Gynœc. Br. Commonw. 1974, 81, 632. 12. Trinder, P. Ann. Clin. Biochem. 1969, 6, 24. 13. Mattingly, D.J. clin. Path. 1962, 15, 374. 14. Strauss, J. S., Pochi, P. E.J. invest. Derm. 1961, 36, 293. 15. Cunliffe, W. J., Shuster, S. Br. J. Derm. 1969, 81, 697. 16. Burton, J. L., Cunliffe, W. J., Shuster, S. ibid. 1970, 82, 497. 17. Fluckiger, E., Wagner, H. R. Experientia, 1968, 24, 1130. 18. Billewicz, W. Z., Anderson, J., Lind, T. Br. med. J. 1973, i, 573. 19. Lutterback, P. M., Pryor, J. S., Varga, L., Wenner, R. ibid. 1971, iii, 228. 20. Besser, G. M., Parke, L., Edwards, C. R. W., Forsyth, I. A., McNeilly, A. S. ibid. 1972, iii, 669. 21. del Pozo, E., Brundel, Re R., Varga, L., Friesen, H. J. clin. Endocr. Metab. 1972, 35, 768. 22.
Rolland, R., Schellekens, L. A., Liquin, R. M. Clin. Endocr. 1974, 3,
155. 23. del Pozo, E., Audibert, A. New Engl.J. Med. 1972, 287, 723. 24. Besser, G. M., Paxton, A. M., Johnson, S. A. N., Moody, E.
J., Mortimer, C. H., Hall, R., Gomez-Pan, A., Schally, A. V., Kastin, A. J., Coy, D. H. Lancet, 1975, i, 1166.
Seven
were
cal fitness. Increased bone formation and mineralisation were seen on iliac-crest bone biopsy, and this was sup-
ported by an increased osteoblastic activity demonstrated by histochemical measurement of alkaline-phosphatase activity. Bone histology furthermore showed a reduced bone resorption, which was supported by a reduced urinary excretion of total hydroxyproline. Photon absorptiometry of the forearm accorded with the histological findings, showing a significant increase in the bone mineral
content.
Serum-calcium
rose
in all
developing transitory hypercalcæurinary excretion of calcium and magnesium significantly. The serum concentrations of 25-hydroxycholecalciferol and parathyroid hormone were not significantly affected by the treatment. It is
patients,
one
a severe
mia. The increased
concluded that 1&agr;-H.C.C. is an effective tool in the treatment of senile osteoporosis. Introduction
1.
1972. 4. Liuzzi, A.,
of Orthopœdic Surgery, University Hospital, Copenhagen, Denmark
patients with osteoporosis of agetreated with synthetic 1&agr;-hying droxycholecalciferol (1&agr;-H.C.C.) for 3-4 months. The compound was given at a daily oral dose of 2 µg together with an oral supplement of 1 g of calcium. Clinically there was a striking improvement in the patients’ physi-
Summary
REFERENCES
Griffith, R., Fluckiger, E. CB-154 Pharmacological and Toxicological data. Sandoz, Basle, Switzerland. December, 1972. 2. Corrodi, H., Fuxe, K., Hokfelt, T., Lidbrink, P., Ungerstedt, U. J. Pharmac. Pharmacol. 1973, 25, 409. 3. Hokfelt, T., Fuxe, K. Brain-endocrine Interactions; p. 181. Basle,
L. HJORTH I. REIMANN R. B. ANDERSEN
B. LUND I. KJAER T. FRIIS
osteoporosis of ageing, bone resorption exceeds bone formation. Many compounds have been used to reduce resorption or to stimulate formation, but none with convincing effect. The pathogenesis of age-related bone loss is not clear, but one explanation is the progresIN
sive decline in intestinal calcium absorption.’ Peacock et awl. have demonstrated that this malabsorption is not due to a basic defect in the intestinal calcium-transport mechanism, since it can be corrected with the active vitamin-D analogue, la-hydroxycholecalciferot (l
criptine may be given subsequently to control the endocrinopathy if this is not relieved by surgery and radiation. In patients in whom the tumour is confined to the pituitary fossa a trial of bromocriptine is undertaken. In those in whom a full response, as previously defined, is obtained, external radiation is applied to the tumour and bromocriptine is continued, to be withdrawn annually to ascertain if the radiation has suppressed G.H. secretion. When a partial response is obtained with bromocriptine the decision to continue this alone or offer external radiation or more definitive local treatment (e.g., yttrium-90 implantation or trans-sphenoidal hypophysectomy) depends on many factors, particularly the extent of the response and the age and medical condition of the individual patient. If there is no response to bromocriptine, definitive local therapy remains the treatment of choice particularly in younger acromegalics with active disease. The dosage regimen is now 2.5mg twice daily with meals for one week to allow the patient to become accustomed to the drug, then 2’5 mg six-hourly for a week and 5 mg six-hourly subsequently. Clinical and biochemical effects can be assessed within a month, but this interval is too short for radiological changes to be apparent. We are grateful to Dr J. Anderson for evaluation of the Hindex ; to Mr A. L. Crombie for ophthalmic assessment; to Dr J. Marks and Mrs J. Alcock for S.E.R. estimation; to Dr A. Burridge for radiological assessment, to Sister G. M. Smith and Sister P. M. Fletcher for their help; to Mr W. M. Ross and Mr R. M. Kalbag for their cooperation; to Dr W. P. Maclay and the late Dr. E. R. Evans (Sandoz Ltd.) for the supply of bromocriptine ; to Dr W. R. Butt for the gift of antisera of L.H./F.S.H. and purified pituitary F.S.H.; and to Dr Anne Stockell-Hartree for pituitary L.H. used for labelling.
TREATMENT OF OSTEOPOROSIS OF AGEING WITH 1&agr;-HYDROXYCHOLECALCIFEROL
O. H. SØRENSEN Medical Department E, Frederiksberg Hospital; Department of Physical Medicine, City Hospital; Royal Dental College; and Department
Chiodini, P. G., Botalia, L., Cremascoli, G., Muller, E. E. Silverstrini, F. J. clin. Endocr. Metab. 1974, 38, 910. 5. Thorner, M. O., Chait, A., Aitken, M., Benker, G., Bloom, S. R., Mortimer, C. H., Sanders, P., Stuart-Mason, A., Besser, G. M. Br. med. J. 1975, i, 299. 6. Clark, F., Brown, H. J. ibid. 1970, i, 713. 7. Clark, F., Brown, H. J. ibid. 1970, ii, 543. 8. Ormston, B. J., Garry, R., Cryer, R. J., Besser, G. M., Hall, R. Lancet, 1971, ii, 10. 9. Hartog, M., Gaafar, M. A., Meisser, B., Fraser, T. R. Br. med. J. 1964, ii, 1229. 10. Hall, R., Amos, J., Ormston, B. J. ibid. 1971, i, 582. 11. Shaw, R. W., Butt, W. R., London, D. R., Marshall, J. C. J. Obstet. Gynœc. Br. Commonw. 1974, 81, 632. 12. Trinder, P. Ann. Clin. Biochem. 1969, 6, 24. 13. Mattingly, D.J. clin. Path. 1962, 15, 374. 14. Strauss, J. S., Pochi, P. E.J. invest. Derm. 1961, 36, 293. 15. Cunliffe, W. J., Shuster, S. Br. J. Derm. 1969, 81, 697. 16. Burton, J. L., Cunliffe, W. J., Shuster, S. ibid. 1970, 82, 497. 17. Fluckiger, E., Wagner, H. R. Experientia, 1968, 24, 1130. 18. Billewicz, W. Z., Anderson, J., Lind, T. Br. med. J. 1973, i, 573. 19. Lutterback, P. M., Pryor, J. S., Varga, L., Wenner, R. ibid. 1971, iii, 228. 20. Besser, G. M., Parke, L., Edwards, C. R. W., Forsyth, I. A., McNeilly, A. S. ibid. 1972, iii, 669. 21. del Pozo, E., Brundel, Re R., Varga, L., Friesen, H. J. clin. Endocr. Metab. 1972, 35, 768. 22.
Rolland, R., Schellekens, L. A., Liquin, R. M. Clin. Endocr. 1974, 3,
155. 23. del Pozo, E., Audibert, A. New Engl.J. Med. 1972, 287, 723. 24. Besser, G. M., Paxton, A. M., Johnson, S. A. N., Moody, E.
J., Mortimer, C. H., Hall, R., Gomez-Pan, A., Schally, A. V., Kastin, A. J., Coy, D. H. Lancet, 1975, i, 1166.
Seven
were
cal fitness. Increased bone formation and mineralisation were seen on iliac-crest bone biopsy, and this was sup-
ported by an increased osteoblastic activity demonstrated by histochemical measurement of alkaline-phosphatase activity. Bone histology furthermore showed a reduced bone resorption, which was supported by a reduced urinary excretion of total hydroxyproline. Photon absorptiometry of the forearm accorded with the histological findings, showing a significant increase in the bone mineral
content.
Serum-calcium
rose
in all
developing transitory hypercalcæurinary excretion of calcium and magnesium significantly. The serum concentrations of 25-hydroxycholecalciferol and parathyroid hormone were not significantly affected by the treatment. It is
patients,
one
a severe
mia. The increased
concluded that 1&agr;-H.C.C. is an effective tool in the treatment of senile osteoporosis. Introduction
1.
1972. 4. Liuzzi, A.,
of Orthopœdic Surgery, University Hospital, Copenhagen, Denmark
patients with osteoporosis of agetreated with synthetic 1&agr;-hying droxycholecalciferol (1&agr;-H.C.C.) for 3-4 months. The compound was given at a daily oral dose of 2 µg together with an oral supplement of 1 g of calcium. Clinically there was a striking improvement in the patients’ physi-
Summary
REFERENCES
Griffith, R., Fluckiger, E. CB-154 Pharmacological and Toxicological data. Sandoz, Basle, Switzerland. December, 1972. 2. Corrodi, H., Fuxe, K., Hokfelt, T., Lidbrink, P., Ungerstedt, U. J. Pharmac. Pharmacol. 1973, 25, 409. 3. Hokfelt, T., Fuxe, K. Brain-endocrine Interactions; p. 181. Basle,
L. HJORTH I. REIMANN R. B. ANDERSEN
B. LUND I. KJAER T. FRIIS
osteoporosis of ageing, bone resorption exceeds bone formation. Many compounds have been used to reduce resorption or to stimulate formation, but none with convincing effect. The pathogenesis of age-related bone loss is not clear, but one explanation is the progresIN
sive decline in intestinal calcium absorption.’ Peacock et awl. have demonstrated that this malabsorption is not due to a basic defect in the intestinal calcium-transport mechanism, since it can be corrected with the active vitamin-D analogue, la-hydroxycholecalciferot (l
