Biomedical subjects
Publications and source records attributed to Hideki Masaki.
Strontium ranelate, which has dual effects of decreasing bone resorption and increasing bone formation, is a new orally active drug to treat osteoporosis. Although the clinical values are scientifically proved and the governments admit as one of the treatment for osteoporosis in many countries, the clinical trial is still undergoing in Japan.
The pathogenesis of steroid (glucocorticoid)-induced bone loss is still unclear. But, bone formation is known to be quickly decreased in early stage of steroid administration, followed by reduction of bone resorption. The reductions of bone resorption markers are small if low dose of steroid is administered, and the changes are accelerated dose dependently, probably due to secondary hyperparathyroidism. The short term intravenous administration of steroid induces transient suppression of bone turnover even in high dose administration. Therefore, it seems that the degree of changes in bone turnover markers induced by steroid is affected not only by the dosage but also by the period of steroid administration. The reduction of osteocalcin is more sensitive than bone alkaline phosphatase for the detection of the suppression of bone formation, although metabolism of osteocalcin induced by steroid may influence the change.
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In order to evaluate the efficacy and safety of intermittent subcutaneous administration of 1-34 N-terminal peptide of human parathyroid hormone (hPTH 1-34), 100 units of hPTH 1-34 was subcutaneously injected once a week for 1 year in ten patients with primary osteoporsis (one male and nine females) with no qualitative abnormality of the bone according to the results of iliac crest biopsy performed previously, followed by a second biopsy after the end of the 1-year administration. Written consent of the patients for participation in the study was obtained. The mean lumbar bone mineral density (LBMD) definitely increased, by 1.8%, 3.4%, and 4.6% after 12, 24, and 48 weeks of hPTH administration, in accordance with previous clinical studies. Histomorphometric analysis after double-tetracycline labeling was completed in six patients (one male and five females) after the exclusion of those who dropped out because of adverse events unrelated to the test drug, or refusal of continuation. Examination of thin hard-tissue sections revealed no qualitative abnormalities of bone tissue or bone marrow cavity, such as osteomalacia, woven bone, or osteitis fibrosa, precluding the contribution of qualitatively abnormal tissue elements to any changes of LBMD in response to hPTH 1-34 administration. Histomorphometric measurement in the second biopsy revealed a tendency for an increase of bone volume, a significant increase of osteoid surface, and a tendency for an increase in other parameters of bone formation, compared with values obtained in the preadministration biopsy. Indices of two-dimensional microstructure obtained by microfocus computed tomography (CT) and results of node-strut analysis indicated improvement of trabecular continuity. In five patients in whom three-dimensional reconstruction images were analyzed, there were significant increases of bone volume and trabecular thickness, and a significant decrease in the trabecular bone pattern factor, a parameter related to the continuity, suggesting an improvement of the three-dimensional trabcular microstructure. Intermittent weekly subcutaneous injections of hPTH (1-34) for 48 weeks increased trabecular bone volume and improved microstructure, without causing the appearance of abnormal bone elements in primary osteoporosis.
Twenty elderly osteoporotic women with vertebral fracture(s) were randomly allocated to two groups; women in the MK(4) group received calcium with menaquinone 4 (MK(4)) at a dose of 45 mg/day for 2 weeks, and women in the control group received calcium alone for the same period. Serum intact osteocalcin (OC) and undercarboxylated osteocalcin (uc-OC) levels were measured by immunoradiometric assay and enzyme immunoassay, respectively, at baseline and on the 7th and 14th days following the start of the treatment. There were no differences in the baseline data including age, weight, phylloquinone, menaquinone 4, menaquinone 7, OC, and uc-OC levels between the MK(4) group and the control group. Administration of MK(4) significantly raised the MK(4) level from 0.20 +/- 0.10 (mean +/- SE) pg/ml to 15.09 +/- 5.62 pg/ml ( P < 0.04), and reduced serum uc-OC levels from 2.80 +/- 0.93 ng/ml to 1.76 +/- 0.56 ng/ml ( P < 0.05) at the end of the study, respectively. No significant changes in these levels were observed in the control group. Serum OC levels were stable during the period in both groups. In this randomized prospective study, the MK(4) group shows a reduction in the serum uc-OC level within 2 weeks without any significant change in OC, suggesting that the uc-OC is changed to carboxylated OC. This early effect of MK(4) on bone metabolism may be estimated by the measurement of serum uc-OC in elderly osteoporotic women with vertebral fractures.