A longitudinal study of the effects of aging on bone width, bone mineral content/bone width and degree (pattern) of bone mineral distribution was made in 4 groups composed of 76 cases of healthy subjects and patients. Group of healthy men was composed of 15 subjects (mean ages of 60 years), healthy adult women; 23 subjects (36 years), healthy aged women; 24 subjects (75 years) and patients with rheumatoid arthritis; 15 female patients (63 years).
With Norland Digital Bone Densitometer Medel 278, bone mineral analysis was performed at the accurately same location of left radius before and after 15 months.
Bone width slightly, but not significantly decreased in every groups, and decreased more in the groups with advancing the bone atrophy during 15 months. Bone mineral content/bone width increased significantly in the groups of the healthy men and healthy adult women. The ratio slightly increased or kept the same level in the healthy condition, and rapidly decreased in the bed-ridden condition in every groups.
In conclusion, the bone atrophy in senile stage advanced by the bed-ridden condition and the accumulation of the immobilization caused the osteoporosis, although the bone in the physiological condition maintained the bone mineral instead of effects of aging.

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For the clinical evaluations of combined therapy of alfacalcidol and calcium in osteoporosis, 45 patients were divided into three groups. Each group was composed of 15 patients with osteoporosis in senile stage. In group I, patients were treated with alfacalcidol 1μg and calcium 0.92g per day for about one year. In group II, patients were treated with less amount of alfacalcidol with or without calcium. In group III, patients were treated with estriol and/or calcium.
In group I, significant increase of metacarpal index and decrease of serum alkaline phosphatase, inorganic phosphorus and magnesium levels were recognized. In complications, two patients with hypercalcemia were present in each group of I and II. Every complications disappeared following no irreversibly permanent changes within a few days by the interruption of combined therapy. The regular biochemical examinations and patients' knowledges about the complications will prevent the hypercalcemia.
It was concluded that the combined therapy was most effective to osteoporosis among three kinds of therapies.

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Of the incisor dentin of the rats administered nickel acetate, in the ground sections hypermineralized layers and in the decalcified sections deeply stained layers with hematoxylin appeared 12-24 hours after the injection. Decrease of the rate of dentin formation began soon after the injection and continued for 3 or 4 days. This peculiar response of the dentin by nickel salt was discussed.

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A scale to measure the mineral density of the hard tissue was made from bone ash and resin, and contact microradiographs (CMR) of ground sections of the rat incisor were taken with the scale. A scale to measure the absorbance of decalcified sections stained with hematoxylin was made from chondroitin sulfate and resin. Microphotographs of CMR and decalcified sections stained with hematoxylin were taken with their scales, the densities of them were measured by the use of a micro-densitometer, and the mineral densities of ground sections and the rates of variation of the absorbance in decalcified sections stained with hematoxylin were evaluated.
The result of the application to the hypermineralized layer induced in rat incisor dentin by nickel salt showed that the rate of increase of the mineral density in the ground sections and the absorbance in the decalcified sections stained with hematoxylin changed with the dose and they depended upon the distance from the apex of the cross section cut from the incisor but their dependence showed a reverse tendency, that is, the rate of increase of the mineral density increased with approaching to the incisal edge whereas it of the absorbance increased with approaching to the apex. The relationship between mineral density and staining ability with hematoxylin was discussed.

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Mineral density of three different parts along the dentinal tubul in each of cross sections cut according to their distance from the incisal apex was determined. The density of the dentin was almost independent of the time when the dentin was produced and dependent on the resion where the dentin was formed. The density of the dentin increased as the region approached from the edge to the apex of the incisor. This result suggests the difference in activity of odontoblasts to participate in formation of the dentin in their regions.

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To verify the proposal that the administration of phosphate stimulates the secretion of PTH, a bone activator, 5 patients with osteoporosis were treated with phosphate and calcitonin. PTH secretion increased markedly in response to the treatment with phosphate. Calcitonin was administered intermittently to depress bone absorption. After 6 months treatment, histological examinations in 2 patients showed significantly active changes, absorption and formation, in bone areas, although the bone area was increased in one patients and reduced in the other. The discrepancy of this finding may be due to the technique for bone biopsy. Thus the principle of the present treatment agrees with ADFR treatment proposed by Frost and contributes a beneficial effect in the therapy of osteoporosis.

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A 37-year-old man with long-term dialysis treatment was presented. He had been treated with hemodialysis two or three times a week and had received aluminium hydroxide (10g/day), 1α-OH-D₃ (0.25r/day) and calcitonin (80-120mrc/w) for the therapy of renal osteodystrophy. At about 5 years later of the start of hemodialysis, he complained of severe pain on both patella, tuberositas tibiae and right articulatio cubiti. At that time, his serum calcium concentration was 4.5 mEq/liter, serum phosphate, 5.7mg/dl, alkaline phosphatase, 45 K-A unit (normal; 3-12), and PTH, 0.74ng/ml (normal; less than 0.4). The findings of bone X-ray in tibiae showed advanced osteoporotic changes. At 3 years later of the appearance of these symptoms, Dihydrotachysterol (DHT) was medicated instead of 1α-OH-D₃. After the treatment of DHT for 5 weeks, his severe bone pains described above were dramatically ameliorated without any changes in laboratory data. The mechanism of the effect of DHT on his bone pains superior to 1α-OH-D₃is not clear.

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Serum Ca, Ca corrected by albumin, Na, creatinine, uric acid, total protein, albumin, cholesterol, GOT and GPT as well as age, sex and duration of hospitalization were used as factors to analyze influence on the outcome of disease of the elderly admitted to Katsuragi Hospital. Over a period of 3 years, 158 patients were discharged with improvement, but 432 died of various diseases of old age such as cerebrovascular disease, cancer and infection. Among these factors, the most important factor threatening the the survival of these patients was hypocalcemia, followed by high serum creatinine, in addition to advanced age and prolonged hospitalization, while other factors had relatively minor influence. Serum calcium thus appears to be quite important as the index to predict the outcome of the diseases of the elderly, probably reflecting the level of nutritional intake of calcium and vitamin D.

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Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) inhibits calcification and bone resorption, in both of tissue cultures and experimental animals, and these effects have been attributed to physicochemical interactions with calcium phosphate crystals. There have also been observations suggesting the involvement of this compound in factors related to cellular metabolism.
We examined the effects of EHDP on alkaline phosphatase and acid phosphatase activities in bone production and fracture repair of young rats and in skeletal development of mouse fetus, using enzyme-histochemical techniques.
EHDP did not inhibit the alkaline phosphatase activity. This may indicate that inhibition of calcification by EHDP does not occur through an impaired activity of alkaline phosphatase. On the other hand, acid phosphatase activity in the areas of metaphysis was slightly inhibited. Therefore the inhibition of bone resorption by EHDP may be in part due to the interference of EHDP in bone cell metabolism.

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Treatment with 1α, 24 dihydroxy vitamin D₃ (1, 24(OH)₂D₃) was evaluatedin a patient aged 7 years and 10 months old, who was an untreated girl with primary hypophosphatemic rickets.
After oral administration of 1, 24(OH)₂D₃, 1μg/day for 4 weeks, her radiographic findings was showed healing of rickets. Fasting serum P concentration was not increased, thereafter oral phosphate was started and 1, 24(OH)₂D₃ dosage was increased to 3μg/day. However fasting serum P concentrations showed no remarkable changes. After changing the 1, 24(OH)₂D₃ to the same dosage of 1α, 25 dihydroxy vitamin D₃ (1, 25(OH)₂D₃) the radiographic findings and fasting serum P concentration showed no remarkable changes. Serum alkaline phosphatase activity decreased slightly. During both treatment the serum Ca and the urinary Ca/creatinine ratio stayed within the normal range. The serum concentrations of 1, 25(OH)₂D₃ were low before and during the treatment with 1, 24(OH)₂D₃.
Growth acceleration was 123% of that expected for change in chronological age after treatment.
It is concluded that both 1, 24(OH)₂D₃ and are effective in the treatment of primary hypophosphatemic rickets.

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The association of pseudogout with hyperparathyroidism and gout have been reported by many researchers. According to Mc Carty, the incidence of the association between pseudogout and hyperparathyroidism is 7.2%, however, Resnick or Bjelle found no association between the two diseases.
Pseudogout has another association with gout, an incidence of from 8% to 0%. There have been no reports on the association between pseudogout and hyperparathyroidism or pseudogout and gout in Japan. However, we have experienced a case of pseudogout associated with hyperparathyroidism and gout.
The clinical features of the case were of great interest, and are discussed in the attached paper. The reason for this association remains obscure, however, though it suggests that some underlying predisposition to crystal deposition is common to these three diseases.

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Eight millimeter trephine defects in the adult rat skull, which do not spontaneously heal, were filled with a bovine bone morphogenetic protein (BMP). Under the influence of BMP, the defects healed both by bony ingrowth at the trephine rim and by new bone formation in dura mater zone in 4 weeks after BMP implantation. Especially primitive cells of the dura are highly responsive to the BMP. The new bone formation process occurs even across a cellulose acetate membrane that isolates the dura mater from bony margins of the skull but permits diffusion of BMP. The pericytes in the dura mater are the target cell of BMP. The repair of experimental skull defects in the rat with BMP is more rapid and greater than in the rat with bone matrix gelatin.

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Five wemen with postmenopausal osteoporosis were treated with 1α-OH-D₃ for the period eight to twelve months.
Before and after the treatment iliac bone biopsies were performed. Undecalified 5μm thick section of the biopsy specimens were histomorphometrically compared with the normal.
Serum calcium, phosphorus and alkaline phosphatase were also examined.
The results were as follows;
1. In a case with normal level of serum calcium and phosphoruse, but with slightly high level of serum alkaline phosphatase, pretreatment-biopsy specimen showed osteoporomalacia histomorphometrically.
2. Io two cases with normal level of serum calcium, phosphorus and alkaline phosphatase specimens revealed osteoporomalacia.
3. Aftertreatment-biopsy showed improvement of osteomalacic factors in these three cases.
4. Other two cases with low turnover in remodelling, but without osteomalacia before the treatment, showed increased turnover rate after the treatment. Although one of these two cases showed an increase in bone mass, but the other case showed further decrease.

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A method to measure cortical thickness of rat tibia with 10-fold image magnified by a projector from soft X-ray radiograph of legs proved to have a high precision. Reproducibility study based on X-ray pictures obtained by five times sequential radiographing in three rats revealed that the mean and standard deviations of percentage coefficients of variation were 0.20±0.04 in external diameter (D), 0.80±0.43 in internal diameter (d) and 0.83±0.21 in combined cortical thickness (D-d).
Bone index L(D²-d²) (L: bone length) showed a good correlation with fat-free dry bone weight (n=29, r=0.843). The most suitable index for normalizing skeletal size was (D²-d²)/D.

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A 8-year-old girl with typical pseudohypoparathyroidism and a 38-year-old mother with pseudopseudohypoparathyroidism are presented. The girl was treated with 1α-hydroxyvitamin D₃ which normalized her serum calcium levels within six days. However, the renal response observed by urinary excretion of phosphate and cyclic AMP to administration of parathyroid hormone could not be restored during the treatment.
Quantitative histological study of the iliac bone was achieved in these two patients. The iliac bone of this patient with pseudopseudohypoparathyroidism showed low turnover osteoporosis. Specimens of ectopic bone from her hand histologically indicated to have active bone formation and resorption.
The iliac bone of the case with pseudohypoparathyroidism revealed the increasing of active bone resorption and the widened osteoid seams. This data suggested that the bone of this patient seemed to have ability to respond to a high level of serum parathyroid hormone.

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Alkaline phosphatase from swine kidney cortex was purified by a series of procedures; butanol extraction, isoelectric and acetone precipitation, ammonium sulfate fractionation and also ion-exchange, concanavalin A (Con A) affinity chromatography and gel filtration. Elution profile of Con A affinity chromatography showed that the enzyme contains a carbohydrate moiety which reacts with Con A. The purified enzyme was found to be a homogeneous glycoprotein having a molecular weight of 160, 000 by polyacrylamide gel- and immunoelectrophoresis. The result that the molecular weight of the enzyme decreased to one half that of native molecule after heated in sodium dodecyl sulfate (SDS) solution indicates a dimer structure of the enzyme comprising two similar or identical subunits of 80, 000 daltons.
The rabbit antiserum against the swine kidney alkaline phosphatase cross-reacted to phosphatases of bovine enamel organ and human fibrous dysplasia bone.

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Osteoporosis was induced in adult rats by oophorectomy. The tibial cortical thickness was then measured radiologically following the treatment with active vitamin D, 1, 25(OH)₂D₃, for 12 weeks at the daily dose of 0.05 to 3.00μg/rat, 1.25(OH)₂D₃ increased the periosteal diameter and decreased the endosteal diameter. In the microradiographic evaluation, bone resorption was observed in the intracortical bone associated with periosteal new bone formation. Size-corrected fat-free dry bone weight (W/LD) was increased in dose-dependent.
It suggests that 1, 25(OH)₂D₃ is useful for the treatment of postmenopausal osteoporosis.

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