In elderly people with marginal exposure to the sunlight, males showed higher serum 25-hydroxycalciferol than females, whereas in those with ample or poor sunlight exposure, serum 25-hydroXycalciferol was higher or very low, respectively, exhibiting no sex difference in the vitamin D metabolite levels. The male predominance in serum25-hydroxycalciferol levels seen among some aged population would be explained, at least in part, by the result of animal experiment suggesting the stimulatory effect of testosterone on vitamin D biosynthesis induced by ultaviolet irradiation. Testosterone was, furthermore, shown to have hypocalcemic action, probably through suppression of bone resortopton in vitamin D depleted but not in replete rats. Clinical implication of these two-fold effects of testosterone observed in rats was discussed in relevance to male predominance in serum25-hydroxycalciferol level and bone mineral content in the aged population.

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Measurement of bone mineral content (BMC), intestinal ⁴⁷Ca absorption, and calcium regulating hormones and sex steroids in serum were performed on 32 healthy aged subjects and 26 control young subjects. In BMC, there was a progressive fall after age 40, with the rate of decrease being greater in women than in men. A significant correlation was observed between BMC and testosterone in the men and between estrogens and BMC in the women, suggesting the possible importance of testosterone in men and estrogens in women in maintaining bone mass. Plasma PTH showed no change with age. However, the reserve capacity of the parathyroid was significantly reduced in the aged women. Serum levels of ionized calcium were low in aged subjects, indicating a possible alteration with age in the feedback control between ionized calcium levels and parathyroid hormone secretion. C-cell funtion was also decreased with age. Plasma 1, 25-(OH) ₂D and ⁴⁷Ca absorption tended to decrease with age. Age-related bone loss could be a reflection of the interaction of these hormonal imbalance occurring with age.

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Serum 1, 25-dihydroxyvitamin D [1, 25 (OH) ₂D], parathyroid hormone (PTH), calcitonin (CT), calcium, inorganic phosphorus and alkaline phosphatase (Al-P'ase) levels were determined in 24 patients with senile or postmenopausal osteoporosis, which was diagnosed by lateral X-ray film of lumbar vertebrae and divided into 3 stages, porosis score I, II and III according to its severity. Serum calcium in osteoporotic group with porosis score II or III was within normal limits but significantly increased compared to that of the age-matched normal group. There was no significant difference in serum inorganic phosphorus and serum Al-P'ase levels between osteoporotic groups and age-matched normal group. Serum 1, 25 (OH) ₂D level determined by radioreceptor assay was significantly decreased in the osteoporotic group with porosis score III compared to that of normal group. Serum PTH was supernomal or higher than normal level in all of osteoporotic groups, while serum CT was within normal limits in those osteoporotic groups. There was no significant correlation among serum 1, 25 (OH) ₂D, PTH and CT or between any of these calcium-regulating hormones and serum calcium, inorganic phosphorus and Al-P'ase, either in osteoporotic groups or in normal group. From these results, it is presumable that a decrease in serum 1, 25 (OH) ₂D is not the only factor for the pathogenesis of senile osteoporosis, and some abnormality in the receptors of the target organs to 1, 25 (OH) ₂D₃ or some other factor than 1, 25 (OH) ₂D₃ might be playing a role for an increase of serum PTH level leading to an increase of bone resorption.

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Postmenopausal osteoporosis and senile osteoporosis are heterogeneous disorders that appear to be caused by several nonhormonal and hormonal factors. Of nonhormonal factors, age-related bone loss, the degree of bone density achieved in young adult life, and dietary intake and absorption of calcium appear to be important. Hormones that may be important in pathogenesis are parathyroid hormone (PTH), estrogen, 1, 25 (OH) ₂D, and possibly calcitonin. Postmenopausal estrogen deficiency accelerates bone loss by increasing responsiveness of bone to endogenous PTH. The resultant increase in release of calcium from bone is associated with normal or low values for serum immunoreactive PTH (iPTH)(except for a subset of 15% of the total which have high values and appear to represent a separate population). Some evidence suggests that subnormal calcium absorption, which is a common finding in postmenopausal osteoporosis and which may contribute to negative calcium balance, is caused by decreased conversion of 25-OH-D to1, 25 (OH) ₂D. Treatment of osteoporosis with either sex steroids (by antagonizing the effect of PTH on bone resorption) or orally administered calcium with or without vitamin D (by decreasing PTH secretion) decreases bone resorption. Long-term therapy with these agents, however, decreases bone formation thus, bone loss is only arrested or slowed. Although combined therapy with fluoride and calcium stimulates bone formation and appears to be capable of increasing bone mass, its long-term safety and efficacy in decreasing the the occurrence of fractures remain to be demonstrated.

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1. The current status of treatment for osteoporosis at the osteoporosis clinic of the Department of Orthopaedic Surgery, Kobe University School of Medicine is reported. A study was made in these osteoporotic patients to investigate the relationships between pain and x-rays and also between pain and the clinical laboratory findings in this particular disease.
2. When pains in osteoporosis were classified into4grades, severity I through severity IV, the more severe pain was found to be associated more frequently with elevated blood levels of alkaline phosphatase. Many of the patients with severe pain tended to show indistinct trabeculation and sclerosis of the upper and lower margins of vertebral bodies on x-rays while some demonstrated Looser's zones notably in the ribs.
3. A considerable portion of those patients who were receiving treatment under the diagnosis of osteoporosis were found to have evidence of osteomalacia, a finding pointing to the likelihood of coexistence of osteoporosis and osteomalacia. This possibility should therefore always be kept in mind when dealing with osteoporotic patients.

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The biological activity of 1 (OH) vitamin D₃ was evaluated in 2 cases of vitamin D dependency.
For the improvement of serum chemistry and increment of urinary excretion of calcium 1 (OH) vitamin D₃ was 500-1000 times more active than vitamin D₂.
The administration of 0.05 microg/kg/day and 0.1 microg/kg/day of 1 (OH) vitamin D₃ were equally effective to keep the serum chemistry within normal limits. However, urinary excretion of calcium increased to an abnormal height on 0.1 microg/kg/day of 1 (OH) vitamin D₃. On the other hand, administration of0.05microg/kg/day of 1 (OH) vitamin D₃ kept both serum level and urinary excretion of calcium normal.
It is suggested that0.05microg/kg/day is close to the optimum requirement of 1 (OH) vitamin D₃ in vitamin D dependency and this should correspond to the essential requirement of 1 (OH) vitamin D₃ in man.

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Muscles from two cases of osteomalacia were studied histochemically and electron-microscopically.
Histopathological finding were common in these two cases. There are (1) myopathic changes such as scattered muscle fiber atrophy, necrosis, and internal uuclei, (2) derangement of intermyofibrillar network. and (3) type II fiber atrophy. Electronmicroscopical finding corresponded well with light microscopical findings. These are distinct pathological features and deserves to be called osteomalacic myopathy. As the pathogenetic mechanism of this myopathy, phosphate depletion in the muscle cells resulting in disturbed glycolysis, and decreased vitamin D effects on muscle cells resulting in diminished calcium uptake by sarcoplasmic reticulum, are considered to be the most important two factors.

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A model of experimental renal osteodystrophy was established in the rats with chronic renal failure induced by partial nephrectomy and therapeutic effects of 1α-hydroxyvitamin D₃ (1α-OH-D₃) were studied. Male Wistar rats weighing 180g were 5/6 nephrectomized and fed a normal diet (Ca and P: 1%) for 6 months. After the surgery, serum creatinine levels increased 60% and thereafter continued to rise gradually with their growth for 4 to 5 months, followed by rapid increase. The serum phosphorus levels were also elevated concomitantly and the serum calcium concentrations were normal. Marked bone resorption accompanied with hypertrophy of parathyroid glands was observed by histological examinations (Tetrachrome-Fuchsin stain, contact microradiography and H-E stain). The bone resorption seemed to be due to secondary hyperparathyroidism.
Treatment with 0.25μg/kg/day p.o. of 1α-OH-D₃ for 10 days in the uremic state resulted in remarkable new bone formation which was confirmed by histological examinations. These results clearly demonstrated that the reduction of nephron mass play a critical clue of renal osteodystrophy and 1α-OH-D₃ appears to have a good potential for clinical use in patients with renal failure and metabolic bone diseasses

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Bone changes in138patients under hemodialysis were evaluated by radiological methods. Bone mass as was assessed by clavicular score was reduced in patients with chronic renal failure compared with control subjects, especially in male patients, and showed the gradual decrease with aging in both sexes. The incidence of disappearance of lamina dura and that of vascular calcification increased with aging in chronic renal failure. Although serum PTH did not show much difference among various age groups, serum CT and calcium were significantly elevated in 20-24 years of age group compared with other age groups. The etiology of decrease of bone mass in male subjects was discussed from the standpoint of decreased gonadal activity.

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During the hemodialysis treatment of 543 uremic patients for 10 years, significant complications concerning metabolic calcium disturbances, subperiosteal resorption, calcification of soft tissue or peripheral vessels, and fractures were noted. Significant elevation of alkaline phosphatase was induced for 5 years under hemodialysis using 5.0-6.0mg/dl dialysate calcium, but not under 7.5mg/dl dialysate calcium.
Plasma immunoreactive parathyroid hormone (iPTH) values were abnormally high with a few exceptions, without relationship to serum calcium levels. Among the patients with chronic renal failure on dietary control, osteomalacic changes were predominant, but their iPTH values were not always elevated. When the patients were treated for a long time with hemodialysis, the mixed type of osteomalacia and osteites fibrosa appeared. Administration of dihydrotachysterol and 1α-hydroxy-cholecalciferol to the patients on hemodialysis changed the mixed type of osteomalacia and osteitis fibrosa to the osteomalacic type with the marked reduction of osteoid seam thickness.

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The studies on two representatives of rickets in childhood are described in this report.
First, plasma levels of 25-hydroxyvitamin D (25-OH-D), serum calcium (Ca), and serum phosphorus (P) were measured in infantile rickets. Mean plasma level of 25-OH-D in rickets group was 13.1±5.7 (S. D.) ng/ml (n=36) which was not significantly lower than that in controls. In rickets group, serum Ca and P were within normal limits, though serum alkaline phosphatase increased significantly. In conclusion, rickets in low birth weight infants is not absolutely due to vitamin D deficiency. Our study suggests that the increase of requirement for vitamin D in low birth weight infants results in relative vitamin D deficiency. Second, clinical effects of massive doses of 1α-hydroxyvitamin D₃ (1α-OH-D₃) in patients with hypophosphatemic vitamin D resistant rickets (HVDRR) are shown in the latter half of this report.
Plasma level of 1, 25-(OH) ₂-D in patient T. H. increased from 22.5pg/ml to 80.4 pg/ml 2months after administration of 5μg/day of 1α-OH-D3. Plasma level of 1, 25-(OH) ₂-D in patient N. K. was 96pg/m_l 3 months after therapy with 1α-OH-D₃ at the dose level of 24μg/day.
Plasma level of 1, 25-(OH) ₂-D in patient M. Y. was 60pg/ml2 months after therapy at dose level of 16μg/day. Our data demonstrated that plasma levels of 1, 25-(OH) ₂D were relatively low in these patients even after administration of massive doses of 1α-OH-D₃. The present study suggests that the metabolism of 1, 25-(OH) ₂-D is accelerated in patients with HVDRR (Seino, in press). In two patients there was a rise in fasting serum phosphate associated with an increase in tubular reabsorption of phosphate.

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