24-25-dihydroxyvitamin-d-3 and ipriflavone

We previously found that 3,9-bis(N,N-dimethylcarbamoyloxy)-5H- benzofuro[3,2-c]quinoline-6-one (KCA-098) inhibited bone resorption in organ culture. In this study, to determine if KCA-098 is therapeutically applicable for the treatment of osteoporosis, we compared the effect of KCA-098 on bone tissues with that of ipriflavone, a drug that is clinically used for the treatment of osteoporosis. Both KCA-098 and ipriflavone inhibited parathyroid hormone-, prostaglandin E2-, 1 alpha,25-dihydroxyvitamin D3- and interleukin 1 beta-induced bone resorption of fetal rat bones, but the inhibitory activity of KCA-098 was more potent than that of ipriflavone. In fact, the effective concentrations of KCA-098 were 10 to 100 times lower than those of ipriflavone. Oral administration of KCA-098 (1 and 3 mg/kg) or ipriflavone (100 mg/kg) to ovariectomized rats on a low-calcium diet increased the breaking force and bone density of the femora, indicating that KCA-098 is an effective on the whole animal as ipriflavone. Furthermore, KCA-098 increased the length and calcium content of 9-day chick embryonic femora cultured in vitro, whereas ipriflavone did not, suggesting that KCA-098 had a direct stimulatory effect on bone mineralization. Therefore, KCA-098 seems to be more potent than ipriflavone in stimulating bone tissue formation and may thus be expected to become a useful agent for the treatment of osteoporosis.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Bone and Bones; Bone Density; Bone Resorption; Calcification, Physiologic; Calcium; Calcium, Dietary; Chick Embryo; Coumestrol; Dinoprostone; Female; Femur; Interleukin-1; Isoflavones; Osteoporosis; Ovariectomy; Parathyroid Hormone; Rats; Rats, Wistar

We compared the effect of conservative treatment with that of surgical treatment after applying them on secondary hyperparathyroidism patients (2nd HPT) in order to study the application of surgery on 2nd HPT patients. We selected the test subject of 39 maintenance dialysis patients with complications of 2nd HPT. The conservative treatments were; elcitonine administration (40 u x 3/W) (group 1), ipriflavon administration (200 mg x 3/day) (group 2), and pulse treatment (1.25 (OH)2D3 6 micrograms/W) (group 3). For surgical treatment, we adopted total parathyroidectomy with auto-transplantation into the arm (PTX). The transition of serum parathyroid hormone (PTH-C), alkali-phosphatase (ALP), bone scintigraphy of every 6 months, and change of bone mineral content (BMC) were compared to judge the effects of treatments. We measured 1/3, 1/6 radial region with single photon absorptiometry (SPA) and L3 region with dual photon absorptiometry (DPA) to obtain BMC. We were forced to transfer the patients in groups 1 and 2 (conservative treatment) to pulse treatment or PTX as 12 months later they showed increase in serum PTH-C, ALP and significant drop (P less than 0.05) in BMC average change rate (1/3). In group 3 of pulse treatment, though significant decrease in serum ALP (P less than 0.01) was detected for 10 cases out of 12, serum PTH-C was either unchanged or increased for 4 cases with the value of more than 30 ng/ml. Furthermore the average change rate of BMC stayed at the same level.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Arm; Bone and Bones; Bone Density; Calcitonin; Chi-Square Distribution; Female; Humans; Hyperparathyroidism, Secondary; Isoflavones; Male; Middle Aged; Parathyroid Glands; Parathyroidectomy; Radionuclide Imaging; Transplantation, Autologous; Transplantation, Heterotopic