Tohru Tsunenari

Quantitative computed tomography of lumbar vertebrae in Japanese patients with osteoporosis

Vertebral trabecular bone mineral density of both healthy Japanese subjects and Japanese patients with osteoporosis was measured by quantitative computed tomography (QCT) technique. The age-related reduction rate in vertebral trabecular bone mineral density of control females averaged 1.1% per year, from age 20 to 80, with an accelerated loss demonstrated after age 40. In the male controls, trabecular bone mineral density declined by an average of 0.9% per year. These values were found to be similar to the University of California at San Francisco (UCSF) QCT data (US Caucasians: 1.2% for female, 0.72% for male). Therefore, it appears that age-related rates of trabecular bone loss in the lumbar vertebrae may be similar for both Japanese and Caucasians. However, when compared to average values in UCSF QCT data of comparable age and sex, the mean values in Japanese appear to be approximately 10-20 mg/cm3 lower than Caucasian counterparts. All female patients with osteoporosis as evidenced by atraumatic vertebral fracture had QCT values below 50 mg/cm3. It is suggested that the Japanese may have lower trabecular bone mineral density than Caucasians but may also have a lower threshold for fracture of the vertebrae. Further studies are needed to establish the possible racial differences in vertebral trabecular bone mineral density, and to determine whether these possible disparities are related to genetic differences, or to differences in body size, dietary intake, physical activity or other lifestyle/environmental factors.

Bone histomorphometric analysis for the cause of osteopenia in vitamin C-deficient rat (ODS rat)

SummaryA particular strain of rat, the osteogenic disorder rat (ODS rat), was established in 1973. Phenotypic expression of od/od in ODS rat develops signs characteristic of a vitamin C-deficient animal, with bleeding tendencies and limb fractures. We investigated the bone histomorphometry to clarify the pathogenesis of osteopathy found in ODS rat. Bone histomorphometry revealed that static parameters reflecting bone formation were found to be remarkably decreased in od/od rats. These observations were more prominent in the metaphysis of distal femurs of od/od rats than those in the tail vertebrae. Parameters reflecting bone resorption in od/od rats were reduced in the distal femoral metaphysis, but were similar to those of controls in the tail vertebrae. These parameters were restored to control levels after ascorbic acid supplementation to pair-fed od/od rats. The mineral appositional rate in od/od rats was not significantly different from that in controls. Although body weight gain in pair-fed controls was significantly reduced compared to those fedad libitum, histomorphometric parameters, on the contrary, were unaltered between these groups. Our present study provides evidence that the cause of osteopenia found in od/od rat is attributable to an imbalance between the total amounts of resorption and formation, and the pathogenesis of osteopathy could be due to ascorbic acid deficiency itself rather than malnutrition.

MENOPAUSE-RELATED CHANGES IN BONE MINERAL DENSITY IN JAPANESE WOMEN : A LONGITUDINAL STUDY ON LUMBAR SPINE AND PROXIMAL FEMUR

We investigated 2-year longitudinal changes of bone mineral density (BMD) in lumbar spine and proximal femur in 64 Japanese women aged 38–67. Forty subjects were premenopausal (mean age 44.9) and 24 postmenopausal (mean age 54.6) at enrollment of the study. Six subjects experienced menopause during the 2-year study period and were defined as the perimenopausal group. Measurements of BMD were performed using dual-energy X-ray absorptiometry at L2–4, femoral neck, greater trochanter, and Wards triangle. Paired t test revealed no significant decrease in BMD at any site in the premenopausal group. Significant annual decrease in BMD was observed in the perimenopausal group at L2–4, femoral neck, and greater trochanter. A similar tendency was observed in Wards triangle, but did not reach statistical significance. In the postmenopausal group, significant decrease in BMD was found at the proximal femur, but not at L2–4. Significant inverse correlation between age and change rate of BMD was found at L2–4, but not at the proximal femur, in premenopausal women. In postmenopausal women, there was a significant association between body weight (BW) change and change rate in BMD at L2–4, femoral neck, or greater trochanter. This association was not found in the premenopausal group. These results suggest that effect of menopause on BMD may be different in individuals and sites of the skeleton. BW change may affect change in BMD in postmenopausal women. However, the limited variability in both BW and BMD changes among premenopausal women in this study may explain the poor association between change in BW and change in BMD in the premenopausal group. As individual differences in each group is considerably large, annual measurements of BMD may be necessary to find possible candidates for early intervention.

Quantitative computed tomography: Comparison of two calibration phantoms

Vertebral trabecular mineral density of healthy Japanese (91 females and 67 males) was measured using the quantitative computed tomography (QCT) technique in a cross-sectional study. We compared estimates of vertebral bone density using two calibration phantoms: the Genant K2HPO4 phantom developed by Genant and a solid CaCO3 phantom developed by Chugai Pharmaceutical. Using the CaCO3 phantom, the rate of decrease of spinal trabecular mineral with age in control females averaged 1.1% per year from age 20 to 80, with an accelerated loss demonstrated at menopause (1.8%). Trabecular bone mass in male controls declined an average 0.9% per year. There was a highly significant correlation between the results obtained with each phantom (r=0.980, p<0.001). This relation was linear over the range of bone mass (60 –172 mg K2HPO4/cm3), and was expressed by the equation y(CaCO3)=1.26×(K2HPO4)+12.3 There was, however, some dispersion of the data around the regression. The calibration phantom used for the measurement of the vertebral trabecular bone should need to be more consistent in longitudinal studies. Apart from this consideration, a solid Chugai phantom can be said to be useful having practical advantages in its flexibility.

Radial bone mineral content of normal Japanese infants and prepubertal children: influence of age, sex and body size

The present study was performed to measure appendicular bone mass of Japanese infants and children, and to assess the influence of age, sex and body size on bone mass during the period of bone growth. The bone mineral content (BMC) and bone width (BW) at the distal third of the radius were measured by single photon absorptiometry (SPA) in 229 healthy Japanese infants and children aged 0-12 years, and the BMC/BW ratio was calculated to give the bone mineral density (BMD). BMC and BW increased with age until 2 years, while BMD did not obviously change until 2 years. After 2 years of age, the overall effect of aging appeared more prominent in BMC and BMD than in BW. There were no significant differences in BMC, BW and BMD between males and females aged 0-12 years. Age, body height, and body weight were strongly correlated with three parameters of bone mass (BMC, BW, and BMD). Among the three parameters of bone mass, BMC showed the highest Pearson coefficient of correlation with age (r = 0.955), body height (r = 0.957) and body weight (r = 0.966), as compared with BW and BMD. The present cross-sectional study provides normative data of the appendicular bone mass in healthy Japanese children, which may serve as a standard for assessment of bone mineralization in Japanese infants and children with medical problems.

Altered parathyroid hormone- or calcitonin-stimulated adenosine 3′,5′-monophosphate release by isolated perfused bone from glucocorticoid-treated rats

SummaryThe present studies were designed to examinein vivo effects of glucocorticoid on PTH-or calcitonin (CT)-stimulated adenosine 3′,5′-monophosphate (cAMP) release from the isolated perfused bone of rat and to test whether the duration of glucocorticoid administration influenced such effects. We assessed the ability of acute (24 hour) or chronic (2 week) dexamethasone administration to modulate the cAMP response to 5 μg human PTH-(1–34) or 1 μg eel CT. Acute treatment with dexamethasone (1 mg/100 g body wt) increased the cAMP response to PTH, but decreased the response to CT. This enhanced effect on PTH-stimulated cAMP release was not apparent in the presence of phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX, ImM). In contrast, chronic dexamethasone treatment (0.2 mg daily for 2 weeks) led to a decrease in both PTH- and CT-stimulated cAMP release. Such impaired response of the dexamethasone-treated bones to PTH was also found in rats that underwent parathyroidectomy 24 hours before sacrifice. These data indicate that 1) the duration of glucocorticoid administration may influence the effect of PTH on bone and 2) glucocorticoid may decrease cAMP-mediated CT function, regardless of the duration of treatment.

Therapeutic Trial of Hematological Disorders with Intermittent Administration of High-Dose 1-Alpha-Hydroxyvitamin D3

Aplastic anemia and myelodysplastic syndrome were successfully treated with an intermittent administration of high-dose 1 alpha-hydroxy-vitamin D3, an active analogue of 1,25-dihydroxyvitamin D3. This effect was considered to be through the differentiation-inducing and immunomodulatory actions of 1,25-dihydroxyvitamin D3. The only adverse effect was hypercalciuria which was controllable by decreasing the dose.

Effect of ascorbic acid deficiency on calcium metabolism in bone of rat with hereditary defect in L-ascorbic acid biosynthesis

A strain of Wistar rat with a hereditary defect in L-ascorbic acid biosynthesis named osteogenesis disorder (OD) rat was used to explore the effect of ascorbic acid deficiency on bone metabolism. OD rats showed lower levels of serum phosphorus, alkaline phosphatase and urinary hydroxyproline than normal rats. Bone histological studies revealed that the essential feature of OD rats was the failure of bone formation. Very few osteoblasts were seen, but mineralization per se seemed to occur normally despite impaired formation of a new matrix. The cAMP response of the bone to parathyroid hormone (PTH) was examined, using isolated perfused femora. Cyclic AMP response to PTH was significantly lower in OD rats than in normal rats.OD rats showed a histological picture with severely reduced bone formation and impaired cAMP response to PTH, which suggests that ascorbic acid deficiency might induce osteoblastic insufficiency. OD rats provide us a useful animal model to study the effect of ascorbic acid deficiency on bone metabolism.

Can serum osteocalcin levels predict bone turnover in patients with osteoporosis

The assessment of bone metabolism by biochemical markers remains difficult problem. Serum osteocalcin, synthesized in bone cells, is now becoming a sensitive indicator of bone turnover in patients with metabolic bone diseases. We measured serum osteocalcin levels by radioimmunoassay in 18 patients with osteoporosis and examined whether they reflect bone formation, resorption or both. We found that serum osteocalcin levels in biopsy-identified osteoporotics were widely ranged (1.8 – 18.8 ng/ml). Tetracycline double labeling method exibited two types of labeling pattern in the iliac bone, that is double labeled or no double labeled (impaired labeled) pattern. Serum concentrations of osteocalcin in patients with double labeling were significantly higher than those with impaired labeling (11.2±4.0 vs 4.1 ±2.1 ng/ml, P<0.01). Furthermore, serum osteocalcin levels showed a significantly positive linear correlation with the parameters reflecting bone formation, but not with bone resorption. These data indicate that serum osteocalcin levels reflect bone formation in osteoporotics and thereby could be a useful indicator of osteoblastic function in osteoporosis.