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Diabetic osteopenia
Diabetes Research and Clinical Practice, 1 (1989) 161-162 Elsevier
161
DIABET 00298
Letter to the Editor
Tygerberg, Re: Diabetic osteopenia Dear Sir, The recent case report published in your journal (Cockram, C.S. (1988) 5,77-80) on fractures due to generalised osteoporosis in a patient with diabetes mellitus again posed the question as to whether the skeleton should be regarded as a ‘target organ’ in subjects with diabetes. Although relatively little is known about the effects of this disease on the metabolism of minerals and the integrity of bone, sufficient evidence has accumulated to suggest that involvement of the skeletal system should be regarded as yet another complication of diabetes, both in man and in animals with experimentally induced insulin-deficiency syndromes. The earliest effect of the diabetic environment on bone is seen in the increased prevalence of skeletal malformations in the fetuses of diabetic mothers. The second category of bone abnormalities known to occur in diabetes results from the continuing trauma following diabetic neuropathy. This so-called diabetic osteopathy is characterised by focal osteolysis, bone fragmentation, sclerosis, periosteal new bone formation and Charcot’s neurogenic arthropathy and is usually evident in the small bones of the foot and less frequently involves the knees, upper extremities or vertebrae. It is, however, the role of diabetes as the cause of a metabolic bone disease resulting in a generalised decrease in bone mass or osteopenia that has attracted attention recently. A reduced bone mass in patients with diabetes has been documented employing various techniques including conventional X-rays [l-5], 016%8277/89/$03.50
0 1989 Elsevier Science Publishers
10 January
1989
radiogrammetry of cortical width [ 6-121, photon absorption densitometry [ 13-161, resonant frequency analysis of the ulna [ 171 and total-body neutron activation analysis [ 181. The co-existence of juvenile insulin-dependent diabetes and osteopenia appears to be firmly established. Adultonset diabetic populations, more heterogeneous as regards the type of diabetes, the therapy and the presence of complications or co-existent disease, are characterised by sub-populations with either a decreased, a normal or an increased bone mass ; the latter appears to be more prevalent among obese elderly females [ 19,201. The clinical significance of these alterations of bone mass in diabetic patients remains controversial. While many studies [ 3,5,21,22] have clearly implicated diabetes as a common and important aetiological factor in the development of skeletal fractures, other [ 231 have failed to reveal an increased fracture rate among diabetic populations as a whole. This is not surprising if we acknowledge previous reports that a given adult diabetic population comprises a mixture of patients, some with decreased, but also many with an increased bone mass. Well-planned, prospective longitudinal studies of clearly defined diabetic sub-populations are the only way to resolve this important issue. Studies in human diabetic patients noting decreased quantities of osteoid and delayed osteon closure rates, as well as the histological and biochemical (decreased skeletal alkaline phosphatase, urinary hydroxyproline and serum osteocalcin levels) evaluation of the chronic (7-week) insulinopenic rat model, reveal that diabetic osteopenia represents a form of low-turnover osteoporosis without evidence of hyperparathy-
B.V. (Biomedical
Division)
162
roidism or osteomalacia [ 8-12,241. The genesis of diabetic bone disease appears to be multifactorial and involves not only a direct insulin effect on skeletal tissue, but may also relate to alterations in systemic (nutritional, acid-base, adrenocortical, mineral, PTH and vitamin D) and/or local (prostaglandins, insulin growth factors, interleukins) growth modulators [ 8- 121. Stephen F. Hough Endocrine Unit, Tygerberg Hospital, P.O. Box 63, Tygerberg 7505, South Aftica
References 1 Morrison, L. B. and Bogan, I. K. (1927) Bone development in diabetic children: a roentgen study. Am. J. Med. Sci. 174, 313-319. 2 Albright, F. and Reifenstein, E. C. (1948) Parathyroid Glands and Metabolic Bone Disease: Selected Studies. Williams and Wilkins, Baltimore, MD. 3 Berney, P. W. (1952) Osteoporosis and diabetes mellitus. J. Iowa State Med. Sot. 42, 10-12. 4 Fischer, E. and Hauser, D. (1970) Kompaktadicke von Ruppen und Schliisselbein: Einfluss demineralisierender Erkrankungen. Med. Klin. 65, 1212-1216. 5 Menczel, J., Makin, M., Robin, G., Jaye, I. and Naor, E. (1972) Prevalence of diabetes mellitus in Jerusalem: its association with presenile osteoporosis. Israel J. Med. Sci. 8, 918-919. 6 Santiago, J. V., MacAllister, W. H., Ratzan, S. K., Bussman, Y., Haymond, M. W., Shackelford, G. and Weldon, V. V. (1977) Decreased cortical thickness and osteopenia in children with diabetes mellitus. J. Clin. Endocrinol. Metab. 45, 845-848. I Frazer, T. E., White, N. H., Hough, F. S., Santiago, J. V.. McGee, B. R. and Avioli, L. V. (198 1) Alterations in circulating vitamin D metabolites in the young insulin dependent diabetic. J. Clin. Endocrinol. Metab. 53, 1154-l 159. 8 Hough, F. S., Avioli, L. V., Bergfeld, M. A., Fallon, M. D., Slatopolsky, E. and Teitelbaum, S. L. (1981) Correction of abnormal bone and mineral metabolism in chronic streptozotocin-induced diabetes mellitus in the rat by insulin therapy. Endocrinology 108, 2228-2233. 9 Hough, F. S., Russell, J. E., Teitelbaum, S. L. and Avioli, L. V. (1982) Calcium homeostasis in chronic streptozotocin-induced diabetes mellitus in the rat. Am. J. Physiol. 242, E451-E456. 10 Hough, F. S., Fausto, A., Sonn, Y., Dong Jo, 0. K., Birge,
S. J. and Avioli, L. V. (1983) Vitamin D metabolism in the chronic streptozotocin-induced diabetic rat. Endocrinology 113, 790-796. 11 Hough, F. S. (1987) Alterations of bone and mineral metabolism in diabetes mellitus. Part I. An overview. S. Afr. Med. J. 72, 116-119. 12 Hough, F. S. (1987) Alterations of bone and mineral metabolism in diabetes mellitus. Part II. Clinical studies in 206 patients with type I diabetes mellitus. S. Afr. Med. J. 72, 120-126. 13 Levin, M. E., Boisseau, V. C. and Avioli, L. V. (1976) Effects of diabetes mellitus on bone mass in juvenile and adult onset diabetes. N. Engl. J. Med. 294, 241-245. 14 Ringe, J. D., Kuhlencordt, F. and Kruse, H. P. (1976) Bone mineral determinations on longterm diabetics. Am. J. Radiol. 126, 1300-1301. 15 Rosenbloom, A. L., Lezotte, D. C., Weber, F. T., Gudat, J., Heller, D. R., Weber, M. L., Klein, S. and Kennedy, B. B. (1977) Diminution of bone mass in childhood diabetes. Diabetes 26, 1052-1055. 16 McNair, P., Madsbad, S., Christensen, M. S., Faber, 0. K., Binder, C. and Transbol, I. (1979) Bone mineral loss in insulin-treated diabetes mellitus: studies on pathogenesis. Acta. Endocrinol. 90,463-469. 17 Jurist, J. M. (1970) In vivo determination of the elastic response of bone: II. Ulnar resonant frequency in osteoporotic, diabetic and normal subjects. Phys. Med. Biol. 15,427-434. 18 Cohn, S. H., Shukla, K. K. and Ellis, K. H. (1974) A multivariate predictor for total body calcium in man based on activation analysis. Int. J. Nucl. -Med. Biol. 1, 131-134. 19 Meema, H. E. and Meema, S. (1967) The relationship of diabetes mellitus and body weight to osteoporosis in elderly females. Can. Med. Ass. J. 96, 132-139. 20 De Leeuw, I. and Abs, R. (1977) Bone mass and bone density in maturity-type diabetes measured by the lz51 photon absorption technique. Diabetes 26, 1130-l 135. 21 Al&m, P. A. (1964) An epidemiologic study of cervical and trochanteric fractures of the femur in an urban population: analysis of 1664 cases with special reference to etiologic factors. Acta Orthop. Stand. 65, 75-77. 22 Von Neumann, H. W., Arnold, W. D. and Hein, W. (1972) Das Vorkommen eines Diabetes mellitus bei 201 Patienten mit Schenkelhalsfrakturen und Wirbelkorperkompressionsfrakture. Zentralbl. Chir. 97, 831-836. 23 Heath, H., Lambert, P. W., Service, F. J. and Amaud, S. B. (1979) Calcium homeostasis in diabetes mellitus. J. Clin. Endocrinol. Metab. 49, 462-466. 24 Ishida, H., Seino, Y., Taminato, T., Usami, M., Takeshita, N., Seino, Y., Tsutsumi, C., Moriuchi, S., Akiyama, Y., Hara, K. and Imura, H. (1988) Circulating levels and bone contents ofbone y-carboxyglutamic acid-containing protein are decreased in streptozotocin-induced diabetes. Possible marker for diabetic osteopenia. Diabetes 37, 702-706.
161
DIABET 00298
Letter to the Editor
Tygerberg, Re: Diabetic osteopenia Dear Sir, The recent case report published in your journal (Cockram, C.S. (1988) 5,77-80) on fractures due to generalised osteoporosis in a patient with diabetes mellitus again posed the question as to whether the skeleton should be regarded as a ‘target organ’ in subjects with diabetes. Although relatively little is known about the effects of this disease on the metabolism of minerals and the integrity of bone, sufficient evidence has accumulated to suggest that involvement of the skeletal system should be regarded as yet another complication of diabetes, both in man and in animals with experimentally induced insulin-deficiency syndromes. The earliest effect of the diabetic environment on bone is seen in the increased prevalence of skeletal malformations in the fetuses of diabetic mothers. The second category of bone abnormalities known to occur in diabetes results from the continuing trauma following diabetic neuropathy. This so-called diabetic osteopathy is characterised by focal osteolysis, bone fragmentation, sclerosis, periosteal new bone formation and Charcot’s neurogenic arthropathy and is usually evident in the small bones of the foot and less frequently involves the knees, upper extremities or vertebrae. It is, however, the role of diabetes as the cause of a metabolic bone disease resulting in a generalised decrease in bone mass or osteopenia that has attracted attention recently. A reduced bone mass in patients with diabetes has been documented employing various techniques including conventional X-rays [l-5], 016%8277/89/$03.50
0 1989 Elsevier Science Publishers
10 January
1989
radiogrammetry of cortical width [ 6-121, photon absorption densitometry [ 13-161, resonant frequency analysis of the ulna [ 171 and total-body neutron activation analysis [ 181. The co-existence of juvenile insulin-dependent diabetes and osteopenia appears to be firmly established. Adultonset diabetic populations, more heterogeneous as regards the type of diabetes, the therapy and the presence of complications or co-existent disease, are characterised by sub-populations with either a decreased, a normal or an increased bone mass ; the latter appears to be more prevalent among obese elderly females [ 19,201. The clinical significance of these alterations of bone mass in diabetic patients remains controversial. While many studies [ 3,5,21,22] have clearly implicated diabetes as a common and important aetiological factor in the development of skeletal fractures, other [ 231 have failed to reveal an increased fracture rate among diabetic populations as a whole. This is not surprising if we acknowledge previous reports that a given adult diabetic population comprises a mixture of patients, some with decreased, but also many with an increased bone mass. Well-planned, prospective longitudinal studies of clearly defined diabetic sub-populations are the only way to resolve this important issue. Studies in human diabetic patients noting decreased quantities of osteoid and delayed osteon closure rates, as well as the histological and biochemical (decreased skeletal alkaline phosphatase, urinary hydroxyproline and serum osteocalcin levels) evaluation of the chronic (7-week) insulinopenic rat model, reveal that diabetic osteopenia represents a form of low-turnover osteoporosis without evidence of hyperparathy-
B.V. (Biomedical
Division)
162
roidism or osteomalacia [ 8-12,241. The genesis of diabetic bone disease appears to be multifactorial and involves not only a direct insulin effect on skeletal tissue, but may also relate to alterations in systemic (nutritional, acid-base, adrenocortical, mineral, PTH and vitamin D) and/or local (prostaglandins, insulin growth factors, interleukins) growth modulators [ 8- 121. Stephen F. Hough Endocrine Unit, Tygerberg Hospital, P.O. Box 63, Tygerberg 7505, South Aftica
References 1 Morrison, L. B. and Bogan, I. K. (1927) Bone development in diabetic children: a roentgen study. Am. J. Med. Sci. 174, 313-319. 2 Albright, F. and Reifenstein, E. C. (1948) Parathyroid Glands and Metabolic Bone Disease: Selected Studies. Williams and Wilkins, Baltimore, MD. 3 Berney, P. W. (1952) Osteoporosis and diabetes mellitus. J. Iowa State Med. Sot. 42, 10-12. 4 Fischer, E. and Hauser, D. (1970) Kompaktadicke von Ruppen und Schliisselbein: Einfluss demineralisierender Erkrankungen. Med. Klin. 65, 1212-1216. 5 Menczel, J., Makin, M., Robin, G., Jaye, I. and Naor, E. (1972) Prevalence of diabetes mellitus in Jerusalem: its association with presenile osteoporosis. Israel J. Med. Sci. 8, 918-919. 6 Santiago, J. V., MacAllister, W. H., Ratzan, S. K., Bussman, Y., Haymond, M. W., Shackelford, G. and Weldon, V. V. (1977) Decreased cortical thickness and osteopenia in children with diabetes mellitus. J. Clin. Endocrinol. Metab. 45, 845-848. I Frazer, T. E., White, N. H., Hough, F. S., Santiago, J. V.. McGee, B. R. and Avioli, L. V. (198 1) Alterations in circulating vitamin D metabolites in the young insulin dependent diabetic. J. Clin. Endocrinol. Metab. 53, 1154-l 159. 8 Hough, F. S., Avioli, L. V., Bergfeld, M. A., Fallon, M. D., Slatopolsky, E. and Teitelbaum, S. L. (1981) Correction of abnormal bone and mineral metabolism in chronic streptozotocin-induced diabetes mellitus in the rat by insulin therapy. Endocrinology 108, 2228-2233. 9 Hough, F. S., Russell, J. E., Teitelbaum, S. L. and Avioli, L. V. (1982) Calcium homeostasis in chronic streptozotocin-induced diabetes mellitus in the rat. Am. J. Physiol. 242, E451-E456. 10 Hough, F. S., Fausto, A., Sonn, Y., Dong Jo, 0. K., Birge,
S. J. and Avioli, L. V. (1983) Vitamin D metabolism in the chronic streptozotocin-induced diabetic rat. Endocrinology 113, 790-796. 11 Hough, F. S. (1987) Alterations of bone and mineral metabolism in diabetes mellitus. Part I. An overview. S. Afr. Med. J. 72, 116-119. 12 Hough, F. S. (1987) Alterations of bone and mineral metabolism in diabetes mellitus. Part II. Clinical studies in 206 patients with type I diabetes mellitus. S. Afr. Med. J. 72, 120-126. 13 Levin, M. E., Boisseau, V. C. and Avioli, L. V. (1976) Effects of diabetes mellitus on bone mass in juvenile and adult onset diabetes. N. Engl. J. Med. 294, 241-245. 14 Ringe, J. D., Kuhlencordt, F. and Kruse, H. P. (1976) Bone mineral determinations on longterm diabetics. Am. J. Radiol. 126, 1300-1301. 15 Rosenbloom, A. L., Lezotte, D. C., Weber, F. T., Gudat, J., Heller, D. R., Weber, M. L., Klein, S. and Kennedy, B. B. (1977) Diminution of bone mass in childhood diabetes. Diabetes 26, 1052-1055. 16 McNair, P., Madsbad, S., Christensen, M. S., Faber, 0. K., Binder, C. and Transbol, I. (1979) Bone mineral loss in insulin-treated diabetes mellitus: studies on pathogenesis. Acta. Endocrinol. 90,463-469. 17 Jurist, J. M. (1970) In vivo determination of the elastic response of bone: II. Ulnar resonant frequency in osteoporotic, diabetic and normal subjects. Phys. Med. Biol. 15,427-434. 18 Cohn, S. H., Shukla, K. K. and Ellis, K. H. (1974) A multivariate predictor for total body calcium in man based on activation analysis. Int. J. Nucl. -Med. Biol. 1, 131-134. 19 Meema, H. E. and Meema, S. (1967) The relationship of diabetes mellitus and body weight to osteoporosis in elderly females. Can. Med. Ass. J. 96, 132-139. 20 De Leeuw, I. and Abs, R. (1977) Bone mass and bone density in maturity-type diabetes measured by the lz51 photon absorption technique. Diabetes 26, 1130-l 135. 21 Al&m, P. A. (1964) An epidemiologic study of cervical and trochanteric fractures of the femur in an urban population: analysis of 1664 cases with special reference to etiologic factors. Acta Orthop. Stand. 65, 75-77. 22 Von Neumann, H. W., Arnold, W. D. and Hein, W. (1972) Das Vorkommen eines Diabetes mellitus bei 201 Patienten mit Schenkelhalsfrakturen und Wirbelkorperkompressionsfrakture. Zentralbl. Chir. 97, 831-836. 23 Heath, H., Lambert, P. W., Service, F. J. and Amaud, S. B. (1979) Calcium homeostasis in diabetes mellitus. J. Clin. Endocrinol. Metab. 49, 462-466. 24 Ishida, H., Seino, Y., Taminato, T., Usami, M., Takeshita, N., Seino, Y., Tsutsumi, C., Moriuchi, S., Akiyama, Y., Hara, K. and Imura, H. (1988) Circulating levels and bone contents ofbone y-carboxyglutamic acid-containing protein are decreased in streptozotocin-induced diabetes. Possible marker for diabetic osteopenia. Diabetes 37, 702-706.