Morii H (ed): CalcIUm-Regulating Hormones. I. Role 111 Disease and Aging. Contrib Nephrol. BaseL Karger, 1991, vol 90, pp 223 - 227
Decreased Bone Mineral Density in Diabetic Patients on Hemodialysis Hiroshi Nishitani", Takami Miki", Hirotoshi Morii a , Yoshiki Nishizawa a , Eiji Ishimura", Satoru Hagiwaraa, Kiyoshi Nakatsuka ", Makoto Yamakawa b "Second Department of Internal Medicine, Osaka City UniverSity Medical School, Osaka, Japan; bKldney Center, Shirasagi Hospital, Osaka, Japan
Metabolic bone disease leading to bone mineral loss and clinical symptoms is a well-recognized problem in patients with chronic renal failure [1]. Osteopenia and low levels of bone formation have been observed in diabetic patients with and without chronic renal failure [2,3], Renal osteodystrophy in diabetic patients on hemodialysis (OM-HO) might be somewhat different from that in nondiabetic patients on hemodialysis (non-OM,HO). In this study, bone mineral density (BMO) was measured in patients with and without diabetes mellitus on hemodialysis, and factors that contribute to differences in calcium metabolism were identified.
Two studies were done. One was a comparison of BMD in non-DM,HD patients and DM-HD patients. The seco nd was a companson of possible factors affecting calcium metabolism In the higher and lower BMD groups in the DM-HD patients. In the first study, 60 patients on hemodialysIs, 30 with and 30 wIthout diabetes mellitus, were studied. AI! patients were men. In the second study, a total of 41 DM-HD patients, 26 men and 15 women , were studied. BM D was measured by dual-energy X-ray absorptlOmetry (DEXA; Hologlc QDR I,OOO jW) in the third lumbar vertebra (L,), head , pelvis, and whole body. Before the measurements of BMD, blood samples were drawn , and serum values (reference values in parentheses) of total calcium (4.2 - 5.1 mEqfl) and phosphate (2.5 - 4.5 mg/dl) were measured on an auto-analyzer (Hitachi 726). Serum Immunoreactive parathyroid hormone (c-PTH) was measured by a c-termlnal radioimmunoassay (lmmuno Nuclear Corp., Minn.). The serum aluminum level was meas ured by flameless atomic absorption spectrophotometry. Student's t test was used for statistical analysis.
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Methods
Nlshltam et al.
224
Tahle I ComparI so n of BMD between the non-DM ,HD and the DM-HD groups
n Age. years Time SInce first dialysIs. months L, BMD. g/cm 1 Head BMD. g/cm 1 PelvIc BMD. g/cm 2 Whole-body BMD, g/cm" Serum Ca. mEq /i P, mg/dl cPTH. ng/ml Dose of D,. Jig
non-DM ,HD
DM-HD
30 587±7.4 71.9±36.6 0.954±0.176 1.787 ± 0 .233 0.771 ± 0.037 0.967 ± 0.093
30 58.3 ± 27.7 ± 0.947 ± 1.626 ± 0.760 ± 0.874 ±
7.8 23 .4*** 0.152 0.316* 0.152 0 113 .
4.7 1 ± 6.07 ± 3.39 ± 0.20 ±
0.38 1.65 3.73** 0.21"*
4.90 ± 6.17 ± 7.75 ± 0.38 ±
0.34 1.16 7.32 0.30
*p < 0.05; **p < 0.01; ***p < 0.005.
Clinical and biochemical results and BMD in the first study are given in table I. The patients were 58.7 ± 7.4 (mean ±SD) years old in the non-DM.HD group and 58.3 i. 7.8 years old in the DM-HD group. The difference was not significant. The time since the first dialysis was 7\.9 ± 36.6 months in the non-DM,HD group and 24.7 ± 23.4 months in the DM-HD group; this difference was significant (p < 0.005). The L) BMD of the non-DM,HD group was 0.954 ± 0 .176 g/cm 2 a nd that of the DM-HD group was 0.947 ± 0 .152 g/cm 2 . The BMD of the head for the non-DM ,HD group was 1.787 ± 0.233 g/cm 2 and 1.626 ± 0 .316 in the DM-HD group. The pelvic BMD was 0.771 ± 0.037 g/cm 2 in the nonDM,HD group and 0.760 ± 0 .152 g/cm 2 in the DM-HD group. The wholebody BMD of the non-DM,HD group was 0.967 ± 0.093 g/cm 2 and that of the DM-HD group was 0.874 ± 0.113 g/cm 2 . The BMDs of the DM-HD group were lower in these areas and whole-body than those in the non-DM ,HD group; the differences in the L) and in the pelvic BMD were slight, but a significant difference was found in the head (p < 0.05). The whole-body BMD of the DM-HD group was about 90% that of the non-DM,HD group, but the difference was not significant. In both groups, the serum total calcium level was being controlled well at a mean of 4.90 ± 0 .34 mEg/I in the non-DM,HD group and 4.71 ± 0.38 mEq/1 in the DM-HD group. The serum phosphate level was
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Results
Decreased BMD in DIabetic Patients on HemodialysIs
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6.17 ± 1.16 mgjdl in the non-DM,HD group and 6.07 ± 1.65 mgjdl in the DM-HD group. There were no significant differences in the serum total calcium and phosphate values between the two groups. The serum c-PTH level of the non-DM,HD group was 7.75 ± 7.32 ng/ ml and that of the DM-HD group was 3.39 ± 3.73 ngjmi. The serum c-PTH level of the non-DM,HD group was significantly higher (p < 0.01). The dose of la-hydroxy-vitamin D3 (la-OH-D3) given to the patients for maintenance of the serum calcium level and suppression of secondary hyperparathyroidism was 0.38 ± 0.30 pgjday in the non-DM,HD group and 0.20 ± 0.21 pg/day in the DM-HD group. The daily dose of la-OH-D 3 taken by the non-DM,HD group was larger. In the second study, factors which may contribute to the differences in BMD were compared in the DM-HD patients divided into higher and lower BMD of the head. The group with higher head BMD had a value 110% of the mean value or more; there were 20 such patients, II men and 9 women. The group with lower BMD of the head contained 21 subjects, 15 men and 6 women. The mean ages of the group with higher and the group with lower values were 63.2 ± 8.3 and 57.0 ± 9.9 years. Respectively, the time since the first dialysis was 27.8 ± 24.0 months in the group with higher values and 34.7 ± 34.6 months in that with lower values. The mean body weight of the group with higher BMD was 59.0 ± 12.1 kg and that in the group with lower BMD 52.9 ± 8.8 kg. The degree of obesity of the patients in the group with higher BMD was 112.1 ± 12. I % and that in the group with lower BMD 97.0 ± 14.3%; this difference was significant (p < 0.005). The mean height of the patients was not different in the two groups, at 158.2 ± 8.1 cm in the group with higher BMD and 160.8 ± 7.3 cm in the group with lower BMD. Biochemical test results of the group with higher BMD and that with lower BMD were: serum total calcium, 4.88 ± 0.4 and 4.67 ± 0.35 mEg/I; serum phosphate, 6.35 ± 1.63 and 5.67 ± 1.63 mg/dl; serum aluminum, 2.20 ± 1.05 and 1.97 ± 1.36 gjdl; serum c-PTH level, 3.43 ± 2.92 and 4.50 ± 5.85 ng/ml. There were no significant differences in the biochemical test results, respectively, between the two groups. The dose of la-OH-D 3 in the group with higher values was 0.23 ± 0.22 pg/day and that in the group with lower values was 0.17 ± 0.10 pg/day. The difference was not significant (table 2).
Important causes of bone mineral loss in patients on hemodialysis are secondary hyperparathyroidism, low plasma levels of 1.25(OHhD3, and
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Discussion
226
Nlshltam et al. Table 2. Companson of factors head BMD
In
calcIUm metabolism of DM-HD patients with high and low
> 110% n (M/ F) Age, years Time since first dialYSIS. months Body weight, kg Obesity. % Body height. cm Serum Ca. mEgjl P, mEg/l AI. pg/dl cPTH, mEg/l Dose of D J , pg =
20 (11 /9) 63.2 ± 8.3 27.8 ± 24.0 59.0 ± 12. I 112.1 ± 12.1 158.2 ± 8.1 4.88 6.35 2.20 3.43 0.23
± ± ± ± ±
0.40 1.63 1.05 2.92 0.22
21 (15/6) 57.0 ± 9.9 34.7 ± 34.6 52.9 ± 8.8 97.0 ± 14.3160.8 ± 7.3* 4.67 ± 0.35 5.67 ± 1.63 197 ± 1.36 4.50 ± 5.85 0.17±0.10
Mean BMD. *p < 0.005.
osteoporosis in women [I]. The BMD of men did not decrease with age, unlike the changes observed in women [4]. In diabetic patients, osteopenia has been reported [2]. In uremic diabetic patients, a decreased incidence of secondary hyperparathyroidism has been found compared with uremic nondiabetic patients [5]. Recently, the number of diabetic uremic patients on hemodialysis is rapidly increasing. More needs to be known about metabolic bone disease in diabetic uremic patients on hemodialysis. In this study, significant differences were found in the head BMD, time since first dialysis, serum c-PTH level, and dose of IIX-OH-D3 between the non-OM ,HO group a nd the OM-HO group. The head BMO was lower, the time since first dialysis was shorter, the serum c-PTH level was lower, and the dose of IIX-OH-D) was less in the DM-HO group. In a study reported elsewhere, we have found that whole-body BMD is negatively correlated with the serum c-PTH level and it is not correlated with the time since first dialysis. Differences in the time since first dialysis and in the serum c-PTH level seem not to be causes of the lower BMD in diabetic patients. Bone mineral loss was affected by vitamin D administration, and a lower dose of IIX -OH-D3 may be the reason for the lower BMO in our OM-HO group, but the difference was only 0.18 Jig/day . Thus, the reason is not clear. To study the factors that affect the BMD in diabetic uremic patients on hemodialysis, a second study was performed here. In that study,
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100%
Decreased Bone Mineral Density in Diabetic Patients on Hemodialysis Hiroshi Nishitani", Takami Miki", Hirotoshi Morii a , Yoshiki Nishizawa a , Eiji Ishimura", Satoru Hagiwaraa, Kiyoshi Nakatsuka ", Makoto Yamakawa b "Second Department of Internal Medicine, Osaka City UniverSity Medical School, Osaka, Japan; bKldney Center, Shirasagi Hospital, Osaka, Japan
Metabolic bone disease leading to bone mineral loss and clinical symptoms is a well-recognized problem in patients with chronic renal failure [1]. Osteopenia and low levels of bone formation have been observed in diabetic patients with and without chronic renal failure [2,3], Renal osteodystrophy in diabetic patients on hemodialysis (OM-HO) might be somewhat different from that in nondiabetic patients on hemodialysis (non-OM,HO). In this study, bone mineral density (BMO) was measured in patients with and without diabetes mellitus on hemodialysis, and factors that contribute to differences in calcium metabolism were identified.
Two studies were done. One was a comparison of BMD in non-DM,HD patients and DM-HD patients. The seco nd was a companson of possible factors affecting calcium metabolism In the higher and lower BMD groups in the DM-HD patients. In the first study, 60 patients on hemodialysIs, 30 with and 30 wIthout diabetes mellitus, were studied. AI! patients were men. In the second study, a total of 41 DM-HD patients, 26 men and 15 women , were studied. BM D was measured by dual-energy X-ray absorptlOmetry (DEXA; Hologlc QDR I,OOO jW) in the third lumbar vertebra (L,), head , pelvis, and whole body. Before the measurements of BMD, blood samples were drawn , and serum values (reference values in parentheses) of total calcium (4.2 - 5.1 mEqfl) and phosphate (2.5 - 4.5 mg/dl) were measured on an auto-analyzer (Hitachi 726). Serum Immunoreactive parathyroid hormone (c-PTH) was measured by a c-termlnal radioimmunoassay (lmmuno Nuclear Corp., Minn.). The serum aluminum level was meas ured by flameless atomic absorption spectrophotometry. Student's t test was used for statistical analysis.
Downloaded by: Université de Paris 193.51.85.197 - 2/9/2020 5:13:27 PM
Methods
Nlshltam et al.
224
Tahle I ComparI so n of BMD between the non-DM ,HD and the DM-HD groups
n Age. years Time SInce first dialysIs. months L, BMD. g/cm 1 Head BMD. g/cm 1 PelvIc BMD. g/cm 2 Whole-body BMD, g/cm" Serum Ca. mEq /i P, mg/dl cPTH. ng/ml Dose of D,. Jig
non-DM ,HD
DM-HD
30 587±7.4 71.9±36.6 0.954±0.176 1.787 ± 0 .233 0.771 ± 0.037 0.967 ± 0.093
30 58.3 ± 27.7 ± 0.947 ± 1.626 ± 0.760 ± 0.874 ±
7.8 23 .4*** 0.152 0.316* 0.152 0 113 .
4.7 1 ± 6.07 ± 3.39 ± 0.20 ±
0.38 1.65 3.73** 0.21"*
4.90 ± 6.17 ± 7.75 ± 0.38 ±
0.34 1.16 7.32 0.30
*p < 0.05; **p < 0.01; ***p < 0.005.
Clinical and biochemical results and BMD in the first study are given in table I. The patients were 58.7 ± 7.4 (mean ±SD) years old in the non-DM.HD group and 58.3 i. 7.8 years old in the DM-HD group. The difference was not significant. The time since the first dialysis was 7\.9 ± 36.6 months in the non-DM,HD group and 24.7 ± 23.4 months in the DM-HD group; this difference was significant (p < 0.005). The L) BMD of the non-DM,HD group was 0.954 ± 0 .176 g/cm 2 a nd that of the DM-HD group was 0.947 ± 0 .152 g/cm 2 . The BMD of the head for the non-DM ,HD group was 1.787 ± 0.233 g/cm 2 and 1.626 ± 0 .316 in the DM-HD group. The pelvic BMD was 0.771 ± 0.037 g/cm 2 in the nonDM,HD group and 0.760 ± 0 .152 g/cm 2 in the DM-HD group. The wholebody BMD of the non-DM,HD group was 0.967 ± 0.093 g/cm 2 and that of the DM-HD group was 0.874 ± 0.113 g/cm 2 . The BMDs of the DM-HD group were lower in these areas and whole-body than those in the non-DM ,HD group; the differences in the L) and in the pelvic BMD were slight, but a significant difference was found in the head (p < 0.05). The whole-body BMD of the DM-HD group was about 90% that of the non-DM,HD group, but the difference was not significant. In both groups, the serum total calcium level was being controlled well at a mean of 4.90 ± 0 .34 mEg/I in the non-DM,HD group and 4.71 ± 0.38 mEq/1 in the DM-HD group. The serum phosphate level was
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Results
Decreased BMD in DIabetic Patients on HemodialysIs
225
6.17 ± 1.16 mgjdl in the non-DM,HD group and 6.07 ± 1.65 mgjdl in the DM-HD group. There were no significant differences in the serum total calcium and phosphate values between the two groups. The serum c-PTH level of the non-DM,HD group was 7.75 ± 7.32 ng/ ml and that of the DM-HD group was 3.39 ± 3.73 ngjmi. The serum c-PTH level of the non-DM,HD group was significantly higher (p < 0.01). The dose of la-hydroxy-vitamin D3 (la-OH-D3) given to the patients for maintenance of the serum calcium level and suppression of secondary hyperparathyroidism was 0.38 ± 0.30 pgjday in the non-DM,HD group and 0.20 ± 0.21 pg/day in the DM-HD group. The daily dose of la-OH-D 3 taken by the non-DM,HD group was larger. In the second study, factors which may contribute to the differences in BMD were compared in the DM-HD patients divided into higher and lower BMD of the head. The group with higher head BMD had a value 110% of the mean value or more; there were 20 such patients, II men and 9 women. The group with lower BMD of the head contained 21 subjects, 15 men and 6 women. The mean ages of the group with higher and the group with lower values were 63.2 ± 8.3 and 57.0 ± 9.9 years. Respectively, the time since the first dialysis was 27.8 ± 24.0 months in the group with higher values and 34.7 ± 34.6 months in that with lower values. The mean body weight of the group with higher BMD was 59.0 ± 12.1 kg and that in the group with lower BMD 52.9 ± 8.8 kg. The degree of obesity of the patients in the group with higher BMD was 112.1 ± 12. I % and that in the group with lower BMD 97.0 ± 14.3%; this difference was significant (p < 0.005). The mean height of the patients was not different in the two groups, at 158.2 ± 8.1 cm in the group with higher BMD and 160.8 ± 7.3 cm in the group with lower BMD. Biochemical test results of the group with higher BMD and that with lower BMD were: serum total calcium, 4.88 ± 0.4 and 4.67 ± 0.35 mEg/I; serum phosphate, 6.35 ± 1.63 and 5.67 ± 1.63 mg/dl; serum aluminum, 2.20 ± 1.05 and 1.97 ± 1.36 gjdl; serum c-PTH level, 3.43 ± 2.92 and 4.50 ± 5.85 ng/ml. There were no significant differences in the biochemical test results, respectively, between the two groups. The dose of la-OH-D 3 in the group with higher values was 0.23 ± 0.22 pg/day and that in the group with lower values was 0.17 ± 0.10 pg/day. The difference was not significant (table 2).
Important causes of bone mineral loss in patients on hemodialysis are secondary hyperparathyroidism, low plasma levels of 1.25(OHhD3, and
Downloaded by: Université de Paris 193.51.85.197 - 2/9/2020 5:13:27 PM
Discussion
226
Nlshltam et al. Table 2. Companson of factors head BMD
In
calcIUm metabolism of DM-HD patients with high and low
> 110% n (M/ F) Age, years Time since first dialYSIS. months Body weight, kg Obesity. % Body height. cm Serum Ca. mEgjl P, mEg/l AI. pg/dl cPTH, mEg/l Dose of D J , pg =
20 (11 /9) 63.2 ± 8.3 27.8 ± 24.0 59.0 ± 12. I 112.1 ± 12.1 158.2 ± 8.1 4.88 6.35 2.20 3.43 0.23
± ± ± ± ±
0.40 1.63 1.05 2.92 0.22
21 (15/6) 57.0 ± 9.9 34.7 ± 34.6 52.9 ± 8.8 97.0 ± 14.3160.8 ± 7.3* 4.67 ± 0.35 5.67 ± 1.63 197 ± 1.36 4.50 ± 5.85 0.17±0.10
Mean BMD. *p < 0.005.
osteoporosis in women [I]. The BMD of men did not decrease with age, unlike the changes observed in women [4]. In diabetic patients, osteopenia has been reported [2]. In uremic diabetic patients, a decreased incidence of secondary hyperparathyroidism has been found compared with uremic nondiabetic patients [5]. Recently, the number of diabetic uremic patients on hemodialysis is rapidly increasing. More needs to be known about metabolic bone disease in diabetic uremic patients on hemodialysis. In this study, significant differences were found in the head BMD, time since first dialysis, serum c-PTH level, and dose of IIX-OH-D3 between the non-OM ,HO group a nd the OM-HO group. The head BMO was lower, the time since first dialysis was shorter, the serum c-PTH level was lower, and the dose of IIX-OH-D) was less in the DM-HO group. In a study reported elsewhere, we have found that whole-body BMD is negatively correlated with the serum c-PTH level and it is not correlated with the time since first dialysis. Differences in the time since first dialysis and in the serum c-PTH level seem not to be causes of the lower BMD in diabetic patients. Bone mineral loss was affected by vitamin D administration, and a lower dose of IIX -OH-D3 may be the reason for the lower BMO in our OM-HO group, but the difference was only 0.18 Jig/day . Thus, the reason is not clear. To study the factors that affect the BMD in diabetic uremic patients on hemodialysis, a second study was performed here. In that study,
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