To explore the relationship between action and metabolism of parathyroid hormone (PTH) in bone, we examined the effects of leupeptin, an inhibitor of cathepsin B (dieptidyl carboxypetidase), on the time course changes of PTH-stimulated cyclic AMP levels in cultured rat osteoenic sarcoma cells (UMR 106) and those of the imunoreactive PTH (iPTH) levels in the culture media. The PTH-mediated cyclic AMP production continued to increase throughout the 120-minute observation period, whereas carboxyl-terminal iPTH (c-iPTH) in the media decreased as time went on. Leupeptin significantly augmented the cyclic AMP production during the first 15 minutes of incubation with PTH compared to the control cultures without further increase in the subsequent 60-minute incubation. On the other hand, the levels of c-iPTH in the media of the 15-minute incubation were decreased by leupeptin compared to the leupeptinuntreated cultures with no further decrease of c-iPTH in the subsequent 60-minute cultures.
These findings suggest that there might be cathepsin B like activity in UMR 106, probably cleaving PTH, and such cleavage might be linked with the action of PTH on these bone-derived tumor cells.

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Localization of Ca-ATPase activity at pH 9.0 was examined using rat tail bones which had been treated with the perfusion decalcification technique. The lead citrate method after Ande et al. (1981) was used for demonstration of the enzyme activity. Ca-ATPase activity was localized on the plasma membrane and in the intracellular granules of osteoblasts.
The enzyme activity on the plasma membrane was mainly present on the lateral membrane. No significant activity was seen on the osteal surface and the vascular side of the plasma membrane. The reaction product was also observed in the intracellular granules which were spherical in shape and were filled with moderate electron dense materials.
No significant activity was present in osteoclasts or osteocytes in the present study.
Ca-ATPase in the bone seems to play an important role in Ca-transport between the bone fluid comparment and the extracellular fluid. However, it is still unknown how Ca-ATPase is associated with Ca-transport between the bone fluid compartment and the extracellular fluid.

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A multi-center double-blind study was carried out on the effect of TZ-CT, synthetic salmon calcitonin (S) on lumbago due to postmenopausal and senile osteoporosis using elcatonin (E) as the reference drug on 294 patients. Following results were obtained.
1. There was no significant difference in global improvement rating between S and E groups. Efficacy rate was 63.2% in S and 65.0% in E group.
2. There was no significant difference in overall safety between the groups. Safety rate was 95.7% in S and 95.6% in E group.
3. Smaller number of cases were judged useless according to the global utility rating in S than in E group. However, no significant difference in the global utility rating was noted between the groups. The global utility rate was 61.5% in S and 68.0% in group.
4. There was no significant difference in the incidence of side effects between the two groups, 4.4% in S and 4.7% in E group. Administration had to be discontinued due to side effects in a smaller number of cases in S than E group.
5. Serious abnormalities occurred in the labolatory data in neither of the two groups.
In conclusion, S was found to be favorably compared with E in the treatment for osteoporosis as to the efficacy and safety. Utility of S in the treatment of postmenopausal and senile osteoporosis was thus established.

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We found that osteomalacia and bone disease after gastrectomy were frequently seen in the patients, paticularly when they were intolerant to ingested milk, and when they recieved Billroth II procedure.
In order to clarify the mechanism of postastrectomy bone disorders, an experiment was performed using rats, and the following results were obtained.
1) When ⁴⁷Ca was given to the stomach with a 10% mono-or disaccharide solution, lactose most effectively transported ⁴⁷Ca from the intestine to the femur.
2) ⁴⁷Ca injected in the duodenum and upper jejunum was transported more effectively to the femur than that injected in the lower ileum.
3) The transport of ⁴⁷Ca from the intestine to the femur was greatly influenced by intestinal acidity.
On the basis of these results, it seems desirable to perform physiological anastomosis (Billroth I procedure) if possible and to take milk after operation.

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Morbidities of metacarpal bone atrophy were compared between patients with vibration disorder and control subjects, 77 male patients with vibration disorder and age-matched 28 male control patients (mean age, 54.0 and 55.7 years, respectively) were studied. The bone mineral density was assessed by Inoue's microdensitometry scanning method at a right second meatcarpal bone. As compared with two groups, the medular bone density and cortical bone density were significantly higher in patients with vibration disorder. The morbidities of metacarpal bone atrophy was significantly lower in patients with vibration disorder (2.7%) than control subjects (14.3%).

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We evaluated the role of prednisolone in calcium metabolic disturbance in nehrotic patients receiving long-term treatment with glucocorticoid, and the effects of 1α-hydroxyvitamin D₃ in these patients. Both serum 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D concentrations were below the normal range, the latter correlating inversely with the dose of prednisolone. The long-term treatment with prednisolone caused bone demineralization without hyperparathyroidism. The oral administration of 1α-hydroxyvitamin D₃ caused increases in urinary calcium excretion, as well as in serum 1, 25-dihydroxyvitamin D concentration, but a decrease in alkaline phospatase activity.
These data suggest that the reduced serum 1, 25-dihydroxyvitamin D concentration may be important in the pathogenesis of glucocorticoid-induced calcium metabolic disturbance, and that oral administration of 1α-hydroxyvitamin D₃ clinicaly useful for prevention of this metabolic disturbance.

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25-Hydroxyvitamin D and 1, 25-Dihydroxyvitamin D in Human Breast Milk in Japan. Kanji Yamaoka, Yoshiki Seino, Hyakuji Yabuuchi, Yoshiyuki Tanaka and Kazuhiko Nishimura. Department of Pediatrics, Osaka University School of Medicine, Osaka 553 Japan. We measured the vitamin D metabolites in ten samples of human breast milk collected during July, 1983, three to seven days after delivery of full term healthy infants. Breast milk was extracted by a modification of chloroform-methanol method. Thereafter the lipid extract was applied to a Seppak silica column followed by straight phase HPLC.
In breast milk from Japanese females, the concentration of 25-hydroxyvitamin D was 0.79±0.30ng/ml (mean±SD, n=10), which is higher than that in the North American women, and the concentration of 1, 25-dihydroxyvitamin D was 7.34±4.31pg/ml (n=9), which is slightly higher than that reported in North America. Although other vitamin D metabolites were not measured, the total vitamin D activity in Japanese human breast milk did not exceed 190 IU/l, which is lower than that recommended daily allowance of vitamin D.

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Twelve patients with senile osteoporosis were treated with 1, 25-dihydroxyvitamin D₃ [1, 25(OH)₂D₃] at the dose of 0.5μg/day per os for 9 months. Corrected serum calcium was significantly increased at 4 and 9 months of 1, 25(OH)₂D₃ administration compared to the pretreatment level, although they remained within normal limits. Serum alkaline phosphatase significantly decreased at 2 and 4 months of 1, 25(OH)₂D₃ administration compared to the pretreatment level. Serum parathyroid hormone level was normal and remained unchanged after 1, 25(OH)₂D₃ administration, while serum calcitonin significantly decreased at 2 months of 1, 25(OH)₂D₃ administration. Serum 1, 25(OH)₂D level was normal and tended to increase after 1, 25(OH)₂D₃ administration, while both serum 24, 25-dihydroxyvitamin D and serum 25-hydroxyvitamin D levels remained low even after the administration of 1, 25(OH)₂D₃. Lumbago was significantly decreased after 2 months of 1, 25(OH)₂D₃ administration. Bone mass of the second metacarpal determined by the micro ensito etry showed no significant changes after the administration of 1, 25(OH)₂D₃ to the osteoporotic patients for 9 months.

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