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LACTASE DEFICIENCY IN OSTEOPOROSIS
86
optic neuritis, the host response depending upon the genetic susceptibility of the individual to each of the two agents (or factors). An unsusceptible (BT 101-negative) individual is unlikely to get M.S. irrespective of the form of the infection or the season of onset. A susceptible (BT 101-positive) person is more likely to have "benign" optic neuritis if his infection is acquired in the summer months, but to progress to M.S. if his infection (which initially produces optic neuritis) arises in the winter. These findings reinforce the growing body of evidence that people in certain histocompatibility groups carry a substantially increased risk of contracting M.s. The seasonal trends must now be re-examined with larger groups. Comparison of optic-neuritis patients whose symptoms appeared in the winter months with genetically matched controls presumably exposed at the same time to similar environmental agents, might provide a clue to the much sought infectious aetiology of M.S.
LACTASE DEFICIENCY IN OSTEOPOROSIS OSTEOPOROSIS is a common disease of high morbidity and obscure pathogenesis. In postmenopausal osteoporosis oestrogen deficiency plays an important role; 12 other possible setiological factors include calcium deficiency,3 reduced circulating levels of 1,25-dihydroxyvitamin D3.hyperparathyroidism secondary to mild renal insufficiency, low total skeletal mass at maturity,6 and a high-protein diet. The role of calcium deficiency in human osteoporosis is controversial. Severe calcium deficiency can cause osteoporosis in animals,89 and small negative calcium balances have been recorded in postmenopausal osteoporosis.10 Dietary calcium intake may be lower in osteoporotic patients than in age and sex matched controls," although not everyone finds a relation between calcium intake and osteoporosis. 12 Fasting hypercalciuria3 and impaired intestinal calcium absorption 10 have been detected in some patients with postmenopausal osteoporosis, and in senile osteoporosis malabsorption of calcium13 and vitamin D14 could contribute to calcium deficiency. However, although calcium supplements may improve calcium balance in osteoporosis over short periods,15 the long-term results of calcium therapy are disappointing. 16 17 1. 2. 3. 4. 5
6. 7. 8.
P. H., Richardson, A. M. J. Am. med. Ass. 1941, 116, 2465. Meema, H. E., Meema, S. Can. med Ass. J. 1968, 99, 248 Nordin, B. E. C. Br. med. J. 1971, i, 571 Gallagher, J. C., Riggs, B. L., Eisman, J., Arnaud, S B., DeLuca, H. F. Clin. Res. 1976, 24, 580A Berlyne, G. M., Ben-Ari, J , Kushelevsky, A., Idelman, A., Galinsky, D., Hirsch, M., Shainkin, R., Yagil, R., Zlotnik, M Q. Jl. Med. 1975, 175, 505. Trotter, M., Broman, G E., Peterson, R. R. J. Bone Jt Surg. 1960, 42A, 50 Thompson, D. L., Frame, B. Ann intern Med. 1976, 85, 789 Crawford, J. D., Gribetz, D., Diner, W. C , Hurst, P., Castleman, B. Endoc-
Albright, F., Smith,
rinology, 1957, 61, 59. 9 Greaves, J. P., Scott, M. G, Scott, P. P. J. Physiol, Lond. 1959, 146, 36P. 10. Gallagher, J. C., Aaron, J., Horsman, A., Marshall, D. H., Wilkinson, R., Nordin, B. E. C. Clins. Endocr. Metab. 1973, 2, 293 11. Nordin, B. E. C. Lancet, 1961, i, 1011 12. Smith, R. W., Frame, B. New Engl. J. Med. 1965, 273, 73 13. Bullamore, J. R., Gallagher, J. C., Wilkinson, R., Nordin, B. E. C, Marshall, D. H. Lancet, 1970, ii, 535. 14. Barragry, J. M., France, M. W., Corless, D., Gupta, S. P. Switala, S., Boucher, B. J., Cohen, R. D. Clin. Sci. mol. Med. 1978, 55, 213 15. Whedon, G. D. Fedn Proc. 1959, 18, 1112. 16. Garn, S. M. Am. J. clin. Nutr. 1970, 23, 1149. 17. Horsman, A., Gallagher, J. C., Simpson, M., Nordin, B E C Br. med J.
1977, ii, 789.
The possible contribution of calcium deficiency to osteoporosis is relevant to reports of an increased prevalence of lactase deficiency in osteoporotic patients, since both dietary calcium intake and intestinal calcium absorption may be related to intestinal lactase activity. In 1967 Birge et al.18 reported reduced lactose absorption in 9 of 19 osteoporotic patients, and now Newcomer et
aI.l9 report lactose intolerance in 27% of female
osteoporotics (compared with only 3% of age, sex, and race matched controls). Support for Birge et al. comes also from a study of patients after partial gastrectomy:20 the clavicular cortical thickness declined more rapidly in hypolactasic subjects. Consumption of milk, a major source of dietary calcium, varies widely in people with lactase deficiency.21 Some have gastrointestinal symptoms after only very small amounts,22 while others can drink nutritionally adequate quantities;23but both Birge et al. and Newcomer et al. found a lower dietary calcium intake in their hypolactasic subjects. Investigations into the effect of lactose on intestinal calcium absorption have produced conflicting results both in animals and in man. Most animal work indicates that lactose enhances calcium absorption ’24-27 particularly in the ileum,2g but the relation of this effect to intestinal lactase activity is disputed .25 26 In man, some workers maintain that lactose normally increases intestinal calcium absorption and that in lactase-deficiency the opposite happens.29 30 But Pansu and Chapuy31 report that lactose stimulates calcium absorption in hypolactasic subjects. Thus, although the bulk of evidence in animals and man indicates that lactose can stimulate intestinal calcium absorption, the dependence of this effect on intestinal lactase activity is unclear. Since American Blacks, in whom lactase deficiency is higher total skeletal mass6 and a lower incidence of osteoporosis than Whites, most of whom are normolactasic, lactose intolerance alone cannot be a major factor in the pathogenesis of osteoporosis, although it may point to other, possibly genetically determined, mechanisms. If lactose does stimulate intestinal calcium absorption in hypolactasic man, the greater clinical lactose tolerance of American Blacks32 might protect them against osteoporosis; but the high incidence of osteoporosis in normolactasic populations remains unexplained. A reduced dietary calcium intake in hypolactasia may sometimes contribute to osteoporosis, but other factors must be more important. common, have a
18. 19. 20 21 22
23 24
Birge, S. J, Keutmann, H. T., Cuatrecasas, P., Whedon, G D. New Engl. J. Med 1967, 276, 445. Newcomer, A. D., Hodgson, S F , McGill, D. B., Thomas, P. J. Ann intern Med. 1978, 89, 218. Kocián, J., Vulterinovà, M., Bejblová , O., Skála, I. Digestion, 1973, 8, 324 Lisker, R., Aguilar, L., Zavala, C. Am.J. clin. Nutr. 1978, 31, 1499 Bayless, T. M., Rothfeld, B., Massa, C, Wise, L, Paige, D , Bedine, M S New Engl J. Med 1975, 292, 1156 Stephenson, L. S., Latham, M. C. Am. J clin. Nutr 1974, 296, 203 Lengemann, F. W., Wassermann, R. H, Comar, C L. J Nutr. 1959, 68,
443 25. Chang, Y-O., Hegsted, D M. ibid. 1964, 82, 297. 26. Fournier, P., Dupuis, Y., Fournier, A. Israel. J. med. Sci.
1971, 7, 389.
27. Armbrecht, H. J., Wasserman, R. H J. Nutr. 1976, 106, 1265. 28 Vaughan, O. W , Filer, L. J ibid. 1960, 71, 10. 29 Condon, J. R , Nassim, J. R., Millard, F. J. C., Hilbe, A , Stainthorpe. E M Lancet, 1970, i, 1027 30. Kocián, J , Skála, I., Bakos, K. Digestion, 1973, 9, 317. 31 Pansu, D , Chapuy, M C , Calc Tiss Res 1970, 4, 155 (suppl). 32. Cuatrecasas, P , Lockwood, D H , Caldwell, J R. Lancet, 1965, i, 14
optic neuritis, the host response depending upon the genetic susceptibility of the individual to each of the two agents (or factors). An unsusceptible (BT 101-negative) individual is unlikely to get M.S. irrespective of the form of the infection or the season of onset. A susceptible (BT 101-positive) person is more likely to have "benign" optic neuritis if his infection is acquired in the summer months, but to progress to M.S. if his infection (which initially produces optic neuritis) arises in the winter. These findings reinforce the growing body of evidence that people in certain histocompatibility groups carry a substantially increased risk of contracting M.s. The seasonal trends must now be re-examined with larger groups. Comparison of optic-neuritis patients whose symptoms appeared in the winter months with genetically matched controls presumably exposed at the same time to similar environmental agents, might provide a clue to the much sought infectious aetiology of M.S.
LACTASE DEFICIENCY IN OSTEOPOROSIS OSTEOPOROSIS is a common disease of high morbidity and obscure pathogenesis. In postmenopausal osteoporosis oestrogen deficiency plays an important role; 12 other possible setiological factors include calcium deficiency,3 reduced circulating levels of 1,25-dihydroxyvitamin D3.hyperparathyroidism secondary to mild renal insufficiency, low total skeletal mass at maturity,6 and a high-protein diet. The role of calcium deficiency in human osteoporosis is controversial. Severe calcium deficiency can cause osteoporosis in animals,89 and small negative calcium balances have been recorded in postmenopausal osteoporosis.10 Dietary calcium intake may be lower in osteoporotic patients than in age and sex matched controls," although not everyone finds a relation between calcium intake and osteoporosis. 12 Fasting hypercalciuria3 and impaired intestinal calcium absorption 10 have been detected in some patients with postmenopausal osteoporosis, and in senile osteoporosis malabsorption of calcium13 and vitamin D14 could contribute to calcium deficiency. However, although calcium supplements may improve calcium balance in osteoporosis over short periods,15 the long-term results of calcium therapy are disappointing. 16 17 1. 2. 3. 4. 5
6. 7. 8.
P. H., Richardson, A. M. J. Am. med. Ass. 1941, 116, 2465. Meema, H. E., Meema, S. Can. med Ass. J. 1968, 99, 248 Nordin, B. E. C. Br. med. J. 1971, i, 571 Gallagher, J. C., Riggs, B. L., Eisman, J., Arnaud, S B., DeLuca, H. F. Clin. Res. 1976, 24, 580A Berlyne, G. M., Ben-Ari, J , Kushelevsky, A., Idelman, A., Galinsky, D., Hirsch, M., Shainkin, R., Yagil, R., Zlotnik, M Q. Jl. Med. 1975, 175, 505. Trotter, M., Broman, G E., Peterson, R. R. J. Bone Jt Surg. 1960, 42A, 50 Thompson, D. L., Frame, B. Ann intern Med. 1976, 85, 789 Crawford, J. D., Gribetz, D., Diner, W. C , Hurst, P., Castleman, B. Endoc-
Albright, F., Smith,
rinology, 1957, 61, 59. 9 Greaves, J. P., Scott, M. G, Scott, P. P. J. Physiol, Lond. 1959, 146, 36P. 10. Gallagher, J. C., Aaron, J., Horsman, A., Marshall, D. H., Wilkinson, R., Nordin, B. E. C. Clins. Endocr. Metab. 1973, 2, 293 11. Nordin, B. E. C. Lancet, 1961, i, 1011 12. Smith, R. W., Frame, B. New Engl. J. Med. 1965, 273, 73 13. Bullamore, J. R., Gallagher, J. C., Wilkinson, R., Nordin, B. E. C, Marshall, D. H. Lancet, 1970, ii, 535. 14. Barragry, J. M., France, M. W., Corless, D., Gupta, S. P. Switala, S., Boucher, B. J., Cohen, R. D. Clin. Sci. mol. Med. 1978, 55, 213 15. Whedon, G. D. Fedn Proc. 1959, 18, 1112. 16. Garn, S. M. Am. J. clin. Nutr. 1970, 23, 1149. 17. Horsman, A., Gallagher, J. C., Simpson, M., Nordin, B E C Br. med J.
1977, ii, 789.
The possible contribution of calcium deficiency to osteoporosis is relevant to reports of an increased prevalence of lactase deficiency in osteoporotic patients, since both dietary calcium intake and intestinal calcium absorption may be related to intestinal lactase activity. In 1967 Birge et al.18 reported reduced lactose absorption in 9 of 19 osteoporotic patients, and now Newcomer et
aI.l9 report lactose intolerance in 27% of female
osteoporotics (compared with only 3% of age, sex, and race matched controls). Support for Birge et al. comes also from a study of patients after partial gastrectomy:20 the clavicular cortical thickness declined more rapidly in hypolactasic subjects. Consumption of milk, a major source of dietary calcium, varies widely in people with lactase deficiency.21 Some have gastrointestinal symptoms after only very small amounts,22 while others can drink nutritionally adequate quantities;23but both Birge et al. and Newcomer et al. found a lower dietary calcium intake in their hypolactasic subjects. Investigations into the effect of lactose on intestinal calcium absorption have produced conflicting results both in animals and in man. Most animal work indicates that lactose enhances calcium absorption ’24-27 particularly in the ileum,2g but the relation of this effect to intestinal lactase activity is disputed .25 26 In man, some workers maintain that lactose normally increases intestinal calcium absorption and that in lactase-deficiency the opposite happens.29 30 But Pansu and Chapuy31 report that lactose stimulates calcium absorption in hypolactasic subjects. Thus, although the bulk of evidence in animals and man indicates that lactose can stimulate intestinal calcium absorption, the dependence of this effect on intestinal lactase activity is unclear. Since American Blacks, in whom lactase deficiency is higher total skeletal mass6 and a lower incidence of osteoporosis than Whites, most of whom are normolactasic, lactose intolerance alone cannot be a major factor in the pathogenesis of osteoporosis, although it may point to other, possibly genetically determined, mechanisms. If lactose does stimulate intestinal calcium absorption in hypolactasic man, the greater clinical lactose tolerance of American Blacks32 might protect them against osteoporosis; but the high incidence of osteoporosis in normolactasic populations remains unexplained. A reduced dietary calcium intake in hypolactasia may sometimes contribute to osteoporosis, but other factors must be more important. common, have a
18. 19. 20 21 22
23 24
Birge, S. J, Keutmann, H. T., Cuatrecasas, P., Whedon, G D. New Engl. J. Med 1967, 276, 445. Newcomer, A. D., Hodgson, S F , McGill, D. B., Thomas, P. J. Ann intern Med. 1978, 89, 218. Kocián, J., Vulterinovà, M., Bejblová , O., Skála, I. Digestion, 1973, 8, 324 Lisker, R., Aguilar, L., Zavala, C. Am.J. clin. Nutr. 1978, 31, 1499 Bayless, T. M., Rothfeld, B., Massa, C, Wise, L, Paige, D , Bedine, M S New Engl J. Med 1975, 292, 1156 Stephenson, L. S., Latham, M. C. Am. J clin. Nutr 1974, 296, 203 Lengemann, F. W., Wassermann, R. H, Comar, C L. J Nutr. 1959, 68,
443 25. Chang, Y-O., Hegsted, D M. ibid. 1964, 82, 297. 26. Fournier, P., Dupuis, Y., Fournier, A. Israel. J. med. Sci.
1971, 7, 389.
27. Armbrecht, H. J., Wasserman, R. H J. Nutr. 1976, 106, 1265. 28 Vaughan, O. W , Filer, L. J ibid. 1960, 71, 10. 29 Condon, J. R , Nassim, J. R., Millard, F. J. C., Hilbe, A , Stainthorpe. E M Lancet, 1970, i, 1027 30. Kocián, J , Skála, I., Bakos, K. Digestion, 1973, 9, 317. 31 Pansu, D , Chapuy, M C , Calc Tiss Res 1970, 4, 155 (suppl). 32. Cuatrecasas, P , Lockwood, D H , Caldwell, J R. Lancet, 1965, i, 14