Studies of Osteoporosis
in Japan
Takuo Fujita Calcium deficiency appears to play a central role in the development of involutional osteoporosis, especially in Japan, where calcium intake hes been traditionally low, never reaching the current recommended daily allowance (RDA) of 800 mg/d. Compromised 1,25(OH), vitamin D synthesis in the aging kidney and age-bound changes of the intestine itself lead to calcium malabsorption; in addition, decreasing dietary intake of fat-soluble vitamins and reduced solar exposure associated with inadequate physical activity may contribute to calcium deficiency in old age. High salt intake and increasing
protein and phosphate intake tend to aggravate such a tendency. These factors appear to underlie, in part, the widespread use of vitamin D derivatives for the treatment of osteoporosis in Japan. In 1991, a large-scale, double-blind clinical trial established the superior effect of la(OH) vitamin D, in maintaining bone density over that of placebo. The effect of 0.5 pg/d 1.25~(OH),D, (calcitriol) in two divided doses compared favorably with that of 1 pg/d of la(OH) vitamin D, in a recently conducted multicenter, double-blind study on 595 patients with involutional osteoporosis. Spinal fracture rata was also reduced to one-half by administration of the vitamin D derivative for 1 year to 999 patients with osteoporosis. Q 1990 by W.B. Saunders Company.
0
STEOPOROSIS is a multifactorial disorder involving genetic, nutritional, endocrine, and physical factors, universally affecting elderly populations all over the world. When we assume that the same disease is prevalent everywhere, the profound differences in the therapeutic approach to this disease in different parts of the world are extremely difficult to explain. In the United States and Europe, the treatment of osteoporosis is based almost exclusively on the use of estrogen; in contrast, vitamin D derivatives are the most common medical therapies for osteoporosis in Japan, followed by calcitonin, and scarcely any estrogen is used (Fig 1). Whether this discrepancy is due to real differences in the pathogenesis or clinical manifestations of osteoporosis itself or, alternatively, to differences in the understanding of and approach to this disease in each country remains to be determined. CALCIUM,
VITAMIN
D, AND
70.1%
1 a(OH)D3
Calcitonins cr -
29.8%
OSTEOPOROSIS
The important role of vitamin D and its derivatives may be suggested by the following facts. First, intestinal calcium absorption declines with age, especially in osteoporotics, which may be explained by decreased dietary intake of vitamin D precursors, poor solar exposure, and decreasing renal 1,25(OH)D biosynthesis. Second, this decline in calcium absorption may lead to secondary hyperparathyroidism and increased bone resorption. Third, loss of the function of vitamin D as an immunoregulator may lead to abnormal lymphocyte subsets, a decrease of helper to suppressor cell ratio. This may be one of the factors for a decreased bone turnover leading to low turnover osteoporosis, which is reversed by la(OH)vitamin D,. Muscle weakness is a prominent feature of vitamin D deficiency and a small dose of vitamin D in osteomalcia is known to restore muscle strength promptly. Loss of muscle strength in vitamin D deficiency may lead to immobilization osteoporosis and vitamin D is expected to improve it.’ Japan is one of the representative calcium-deficient nations in the world. Even the recommended daily allowance (RDA) for calcium of 600 mg/d, which is lower than the 800 mg/d established in the United States, has never been reached by the Japanese population, although average calcium intake is gradually increasing in Japan from 300 mg/d Metabolism,Vol39,
c
No 4, Suppl 1 (April), 1990: pp 39-42
Calcium
1a25(OH)p3 lndomethasin
Osteoporotics
Fig 1.
Use frequency
of various therapies
for osteoporosis
in
From the Third Division, Department of Medicine, Kobe University School of Medicine. Kusunoki-cho, Kobe, Japan. Address reprint requests to Takuo Fujita. MD, Third Division, Department of Medicine, Kobe University School of Medicine, Kusunoki-cho. Kobe, Japan. B 1990 by W.B. Saunders Company. 0026-0495/90/3904-1005$3.00/O 39
TAKUO
FU JITA
..f _I1
25. OH-’ JiLD ng/rr II
Mean f
20
:-:;*,
1
S.E. PcO.01
L
10
Fig 2. Serum 26-(OHID, levels in relation to trsbeculsr patterns of the lumbar spine on lateral x-ray. Levels were significantly decreased in persons with advanced osteoporosis. Table 1. Renal Complications
of Treatment
Serum Creatinine increase (%)
With Vitamin D
Renal Calcification 1%)
Renal stone (%I
234 la(OH)D,
0
0
0
0.29
0
0
0.37
0
0.0001
432 l-25(OH)D, 8,093 1 a(OH)D,
%
I
p
in Japan
Takuo Fujita Calcium deficiency appears to play a central role in the development of involutional osteoporosis, especially in Japan, where calcium intake hes been traditionally low, never reaching the current recommended daily allowance (RDA) of 800 mg/d. Compromised 1,25(OH), vitamin D synthesis in the aging kidney and age-bound changes of the intestine itself lead to calcium malabsorption; in addition, decreasing dietary intake of fat-soluble vitamins and reduced solar exposure associated with inadequate physical activity may contribute to calcium deficiency in old age. High salt intake and increasing
protein and phosphate intake tend to aggravate such a tendency. These factors appear to underlie, in part, the widespread use of vitamin D derivatives for the treatment of osteoporosis in Japan. In 1991, a large-scale, double-blind clinical trial established the superior effect of la(OH) vitamin D, in maintaining bone density over that of placebo. The effect of 0.5 pg/d 1.25~(OH),D, (calcitriol) in two divided doses compared favorably with that of 1 pg/d of la(OH) vitamin D, in a recently conducted multicenter, double-blind study on 595 patients with involutional osteoporosis. Spinal fracture rata was also reduced to one-half by administration of the vitamin D derivative for 1 year to 999 patients with osteoporosis. Q 1990 by W.B. Saunders Company.
0
STEOPOROSIS is a multifactorial disorder involving genetic, nutritional, endocrine, and physical factors, universally affecting elderly populations all over the world. When we assume that the same disease is prevalent everywhere, the profound differences in the therapeutic approach to this disease in different parts of the world are extremely difficult to explain. In the United States and Europe, the treatment of osteoporosis is based almost exclusively on the use of estrogen; in contrast, vitamin D derivatives are the most common medical therapies for osteoporosis in Japan, followed by calcitonin, and scarcely any estrogen is used (Fig 1). Whether this discrepancy is due to real differences in the pathogenesis or clinical manifestations of osteoporosis itself or, alternatively, to differences in the understanding of and approach to this disease in each country remains to be determined. CALCIUM,
VITAMIN
D, AND
70.1%
1 a(OH)D3
Calcitonins cr -
29.8%
OSTEOPOROSIS
The important role of vitamin D and its derivatives may be suggested by the following facts. First, intestinal calcium absorption declines with age, especially in osteoporotics, which may be explained by decreased dietary intake of vitamin D precursors, poor solar exposure, and decreasing renal 1,25(OH)D biosynthesis. Second, this decline in calcium absorption may lead to secondary hyperparathyroidism and increased bone resorption. Third, loss of the function of vitamin D as an immunoregulator may lead to abnormal lymphocyte subsets, a decrease of helper to suppressor cell ratio. This may be one of the factors for a decreased bone turnover leading to low turnover osteoporosis, which is reversed by la(OH)vitamin D,. Muscle weakness is a prominent feature of vitamin D deficiency and a small dose of vitamin D in osteomalcia is known to restore muscle strength promptly. Loss of muscle strength in vitamin D deficiency may lead to immobilization osteoporosis and vitamin D is expected to improve it.’ Japan is one of the representative calcium-deficient nations in the world. Even the recommended daily allowance (RDA) for calcium of 600 mg/d, which is lower than the 800 mg/d established in the United States, has never been reached by the Japanese population, although average calcium intake is gradually increasing in Japan from 300 mg/d Metabolism,Vol39,
c
No 4, Suppl 1 (April), 1990: pp 39-42
Calcium
1a25(OH)p3 lndomethasin
Osteoporotics
Fig 1.
Use frequency
of various therapies
for osteoporosis
in
From the Third Division, Department of Medicine, Kobe University School of Medicine. Kusunoki-cho, Kobe, Japan. Address reprint requests to Takuo Fujita. MD, Third Division, Department of Medicine, Kobe University School of Medicine, Kusunoki-cho. Kobe, Japan. B 1990 by W.B. Saunders Company. 0026-0495/90/3904-1005$3.00/O 39
TAKUO
FU JITA
..f _I1
25. OH-’ JiLD ng/rr II
Mean f
20
:-:;*,
1
S.E. PcO.01
L
10
Fig 2. Serum 26-(OHID, levels in relation to trsbeculsr patterns of the lumbar spine on lateral x-ray. Levels were significantly decreased in persons with advanced osteoporosis. Table 1. Renal Complications
of Treatment
Serum Creatinine increase (%)
With Vitamin D
Renal Calcification 1%)
Renal stone (%I
234 la(OH)D,
0
0
0
0.29
0
0
0.37
0
0.0001
432 l-25(OH)D, 8,093 1 a(OH)D,
%
I
p
