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Biomedical subjects

K Kushida

Publications and source records attributed to K Kushida.

At least 73 records · Page 4Linked to original sources

Urinary collagen crosslinks reflect further bone loss of femoral neck in osteoporotic patients undergoing vitamin D therapy.

Bone mineral density (BMD) of the lumbar (L2-LA) spine and femoral neck was measured annually for 2 years (3 times beginning at the beginning of year 1 and after each subsequent year) in 39 female patients with osteoporosis undergoing 0.5 or 1.0 microg daily doses of vitamin D therapy. At the time of the first BMD measurement, biochemical markers including serum alkaline phosphatase (ALP), urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr) and hydroxyproline (Hyp) were also measured. Urinary Pyr and Dpyr correlated with the percent changes of femoral neck BMD measurements taken the year following the sampling (Pyr: r=-0.622, p<0.001, Dpyr: r=-0.385, p<0.05). Only urinary Pyr correlated with the percent changes of femoral neck BMD measurements taken the following 2 years (r=-0.532, p<0.05). Neither serum ALP nor urinary Hyp correlated with the percent changes of spine or femoral neck BMD measurements taken the year or 2 years after the sera and urine sampling. In summary, we believe urinary Pyr and Dpyr can reflect subsequent bone loss of the femoral neck BMD having been measured only once during the course of a year.

Alkaline Phosphatase↗

The effects of menopausal status and disease activity on biochemical markers of bone metabolism in female patients with rheumatoid arthritis.

The effects of menopause and disease activity on bone metabolism in rheumatoid arthritis (RA) were studied by using biochemical markers of bone metabolism. We measured osteocalcin, bone-specific alkaline phosphatase, urinary total pyridinoline and deoxypyridinoline, and urinary free deoxypyridinoline in 78 female patients with RA (39 pre-menopause, Pre-RA; 39 post-menopause, Post-RA) and 54 female normal controls (28 pre-menopause, Pre-NC; 26 post-menopause, Post-NC). In Pre-RA, although bone formation was equal to Pre-NC, bone resorption increased. In Post-RA, however, bone formation was lower while bone resorption was higher than in Post-NC. The high disease activity RA group showed higher bone turnover than the low disease activity RA group. We conclude that menopause affects the bone turnover in RA as well as in normal controls. In Pre-RA, osteopenia is caused by the increase in bone resorption. In Post-RA, osteopenia is caused by the increase in uncoupling between bone formation and bone resorption. Furthermore, the high disease activity of RA induces high bone turnover.

Adult↗

Effects of low phosphate intake on bone and mineral metabolism in rats: evaluation by biochemical markers and pyridinium cross-link formation in bone.

We have investigated the changes in biochemical markers and in pyridinium cross-links in bone in hypophosphatemic rats. Six-week-old female Wistar rats were divided into two groups (normal diet and a phosphate-deficient diet) and fed for 8 weeks. A low phosphate intake caused a significant difference in the concentrations of osteocalcin and alkaline phosphatase with advancing rachitis as well as an increase in bone resorption marker concentrations in urine. Femur biochemical analysis revealed a significant (p < 0.005) increase in deoxypyridinoline per mole collagen in the phosphate-deficient group which suggested that urinary excretions of pyridinium cross-links might reflect not only bone resorption but also increased pyridinium cross-links in bone matrix collagen. Our results demonstrate that a low phosphate intake causes an increase of pyridinium cross-link formation as well as a discrepancy between the circulation levels of alkaline phosphatase and osteocalcin with advancing rachitis. These alterations induced by low phosphate intake should be considered when interpreting the values of biochemical markers.

Alkaline Phosphatase↗

The relationship between pentosidine and hemodialysis-related connective tissue disorders.

Dialysis-related amyloidosis (DRA), such as destructive spondyloarthropathy (DSA) and carpal tunnel syndrome (CTS), occurs in the connective tissues of patients on long-term hemodialysis (HD). Recently, it was suggested that advanced glycation end products (AGEs) and beta2-microglobulin (beta2m) modified with AGEs are related to DRA. The aim of this study is to elucidate whether serum levels of pentosidine, which is an AGE, relate to the occurrence of DRA in patients with long-term HD. 127 end-stage renal failure patients, with DSA or CTS and undergoing HD, were examined. Serum pentosidine was measured by the HPLC method with column switching. Beta2m and intact parathyroid hormone (i-PTH) were measured. Pentosidine levels were significantly elevated in the DSA, CTS, and DRA groups (patients in the DRA group had either DSA and/or CTS). There were no significant differences in the beta2m and i-PTH levels between any group. The duration of HD did not correlate with either pentosidine or beta2m levels, but did with i-PTH. Receiver-operating characteristic (ROC) analysis was performed to examine the discriminatory ability of pentosidine, beta2m, and i-PTH for DRA. The area under the ROC curve was the greatest for pentosidine. Serum beta2m levels were not related with the occurrence of DRA. The fact that serum pentosidine was higher in DRA than in non-DRA indicates that it has potential as an indicator of the occurrence of DRA in long-term HD patients.

Adult↗

The advanced glycation endproduct, pentosidine, in the carpal ligament in patients with carpal tunnel syndrome undergoing hemodialysis: comparison with idiopathic carpal tunnel syndrome.

BACKGROUND/AIMS: Carpal tunnel syndrome (CTS) is a major complication that occurs in the musculoskeletal system in patients on long-term hemodialysis (HD). Pentosidine is an advanced glycation endproduct (AGE) and there is evidence that shows AGEs contribute to the pathogenesis of the complications in patients undergoing HD. The aim of this study is to investigate whether pentosidine accumulates in the carpal ligament in patients undergoing HD with CTS in comparison with idiopathic CTS. METHODS: Carpal ligaments and skin were obtained during surgery from 28 patients with CTS undergoing HD and 13 patients with idiopathic CTS (ID CTS). Pentosidine was measured by HPLC after hydrolysis of the samples, and amyloid deposits in the samples of HD CTS were examined histologically. RESULTS: Pentosidine levels in ligament and skin were significantly higher in HD CTS than ID CTS. On the other hand, there was no difference in pyridinoline which is a physical cross-link between HD and ID CTS. Amyloid deposits were observed in 14 ligament samples, whereas there was none in 14 other samples. There was no significant difference in pentosidine and pyridinoline in ligament, pentosidine in skin, duration of HD and serum beta2-microglobulin between the amyloid+ group and the amyloid- group. CONCLUSION: A greater concentration of pentosidine in the carpal ligament in HD patients compared with idiopathic patients suggests that an accumulation of AGEs contributes to one of the pathologies of occurrence of CTS in patients undergoing HD.

Aged↗

The preventive and interventional effects of raloxifene analog (LY117018 HCL) on osteopenia in ovariectomized rats.

The effects of LY117018 HCL (LY) treatment on bone metabolism, spine bone mineral density (BMD), bone mineral content (BMC), and serum cholesterol were studied in ovariectomized (OVX) rats. Experiment 1 was designed to observe the preventive effects of LY on bone loss due to ovariectomy (OVX; prevention study). The rats were divided into three groups: sham group, OVX + vehicle, and OVX + LY. LY was administrated at the same time of OVX. Experiment 2 was designed to investigate the interventional effects of LY on OVX rats with osteopenia (intervention study). The rats were divided into the sham and OVX groups, first. The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post-OVX, the OVX rats were divided into two groups: OVX + vehicle and OVX + LY. The longitudinal effects of LY on bone were studied by dual-energy X-ray absorptiometry and biochemical markers including urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr), and serum osteocalcin. Urinary Pyr and Dpyr increased maximally at 6 weeks post-OVX, decreased at 12 and 18 weeks post-OVX, although the OVX rats had significantly higher levels of Pyr and Dpyr than the sham group during the experiment. LY was a very potent inhibitor of Pyr and Dpyr excretion while at the same time only partially reducing the bone loss in the high turnover phase at 6 weeks postovariectomy. However, at the later time points at 12 and 18 weeks, no further bone loss occurred in rats treated with LY, while the vehicle-treated group lost another 10% in spine BMD and BMC. LY also completely blocked further bone loss when used in an intervention protocol. LY significantly reduced serum cholesterol levels in OVX rats. The results suggest that LY is not fully protective during the early rapid bone loss phase, but the compound is fully protective during the later slow phase of bone loss in both the protocols.

Absorptiometry, Photon↗

A placebo-controlled, single-blind study to determine the appropriate alendronate dosage in postmenopausal Japanese patients with osteoporosis. The Alendronate Research Group.

Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate) is a potent inhibitor of bone resorption. The efficacy and safety of 36 weeks of treatment with alendronate were evaluated in Japanese women with osteoporosis, osteoporotic osteopenia or artificial menopause. The bone mineral density (BMD) of the lumbar vertebrae, markers of bone and calcium metabolism and clinical symptoms were monitored. A total of 113 randomly selected patients with osteoporosis or osteopenia were enrolled in the study, of whom 12 were excluded from the analyses because of lack of data. As a result, 101 patients were evaluated for the safety of the drug. Since eight patients were excluded from the efficacy analysis, 93 were evaluated. The incidence of adverse effects in the placebo (P), alendronate 2.5 mg/day (L) and alendronate 10 mg/day (H) groups increased with increasing dose of alendronate, being 6.1, 14.3 and 18.2%, respectively. The most common adverse effects were gastrointestinal symptoms, none of which was serious. Lumbar BMD increased after 36 weeks of drug administration to 5.21%, 5.64% and -0.90% in the L, H and P groups, respectively (P < 0.001, L vs. P and H vs. P). Serum alkaline phosphatase activity, serum osteocalcin and urinary deoxypyridinoline excretion were significantly decreased in a dose-related manner. Serum calcium and phosphorus were also significantly decreased after alendronate administration. Serum intact PTH was transiently increased. The present results indicate that alendronate effectively decreases bone turnover in a dose-related manner and increases lumbar BMD at a dosage of 2.5 mg/day, the lowest dose used in this study, in Japanese patients with osteoporosis.

Adult↗

Characteristics of biochemical markers in patients with metabolic bone disorders.

Biochemical markers of bone turnover are expected to have some different characteristics among bone metabolic disorders. We compared bone formation markers: serum total alkaline phosphatase (s-Alp), serum osteocalcin (s-OC) and serum carboxy-terminal propeptide of type I collagen (s-PICP); and bone resorption markers: serum carboxy-terminal telopeptide of type I collagen (s-ICTP), urinary pyridinoline (u-Pyr) and urinary deoxypyridinoline (u-Dpyr) to examine which marker is the most suitable and reliable to evaluate bone turnover in patients with osteoporosis (n = 29), osteomalacia (n = 10), primary hyperparathyroidism (n = 6) and renal osteodystrophy (n = 21). The value of s-Alp in the osteomalacia group was significantly higher than those in the normal control group and the osteoporosis group (p < 0.001), and T-score of s-Alp was significantly higher than those of s-OC and s-PICP in the osteomalacia group. The values of u-Pyr and u-Dpyr in the primary hyperparathyroidism group were significantly higher than those in the other groups (p < 0.001). S-PICP, which are not dependent upon renal function, was much higher in the renal osteodystrophy group than in all other groups. In the osteoporosis group, T-score of s-ICTP was significantly higher than those of s-OC. Thus, s-Alp was a good marker in osteomalacia, u-Pyr and u-Dpyr in primary hyperparathyroidism, s-PICP in renal osteodystrophy, and s-ICTP in osteoporosis.

Adult↗

[Photodensitometry].

Photodensitometry was developed by several investigators. This technique makes possible bone mass measurements from radiographs of the peripheral skeleton, most commonly the metacarpal and phalangeal bones. More recently, with the advent of computerized image processing, photodensitometry has become more precise and gained new respect for use in the diagnosis of osteoporosis. In addition, recent studies in which radiographic absorptiometry was used have demonstrated that the detection of accelerated bone loss in the early menopause with this technique is comparable to other densitometry techniques. Being cost effective, easy to perform, and universally available, all makes photodensitometry an increasing attractive option for non invasive bone assessment in both research and clinical practice.

Absorptiometry, Photon↗

Pentosidine in synovial fluid in osteoarthritis and rheumatoid arthritis: relationship with disease activity in rheumatoid arthritis.

OBJECTIVE: Pentosidine is an advanced glycation endproduct formed by glycosylation and oxidation. Our aim was to develop a means to measure pentosidine in synovial fluid (SF), and to compare its concentration in SF in patients with osteoarthritis (OA) and rheumatoid arthritis (RA), and to investigate the relationship between its concentration in SF and the disease activity of RA. METHODS: SF was collected from knee joints in 31 patients with RA and 40 with OA, who had hydrarthrosis. One patient with RA and 7 with OA who had the complication of diabetes mellitus or chronic renal failure made up the DM/CRF group, and the remaining patients made up the RA group (n = 30) and the OA group (n = 33). Pentosidine was measured by the direct HPLC method with column switching after hydrolysis of SF. RESULTS: Pentosidine was detected in all SF and was greater in RA (83.9 +/- 46.0 nmol/l, mean +/- SD) than in OA (40.1 +/- 19.6 nmol/l). Three DM/CRF patients undergoing hemodialysis had markedly high pentosidine levels (482.5 +/- 280.8 nmol/l). There was a significant correlation between pentosidine and C-reactive protein (CRP), erythrocyte sedimentation rate, and Lansbury Index (p < 0.01). Patients with RA were divided into high and low activity groups according to the CRP and Lansbury Index. Pentosidine was significantly higher in the high activity group (CRP > or = 2.0 mg/dl and Lansbury Index > or = 50%) than in the low activity group (CRP < 2.0 and/or Lansbury Index < 50) (100.9 +/- 42.8 vs 58.5 +/- 39.6 nmol/; p = 0.0013). CONCLUSION: Pentosidine in synovial fluid was higher in RA than in OA. Pentosidine levels in SF were related to the disease activity in RA.

Adult↗

[The current situation surrounding pharmacies and pharmacists].

As Japan's society continues to age, the Medical Insurance System has been substantially reviewed. As a result, 1. The medical care system has been separated from the custodial care system with the allocation of medical and custodial care insurance benefits. 2. The basis has been laid in terms of the legal provisions and the medical remuneration requirements for the establishment of a home care system. Amidst the major transformation of Japan's social order in the wake of these moves, the pharmacy and pharmacist are called upon to play a positive role in:1. Fostering the correct use of drugs through the sale of drugs and by filling prescriptions. 2. Assisting patients in self-medication. 3. Being involved in, and supporting, custodial medical care for the elderly and home care. While some 9,000 pharmacists join the profession each year, the situation regarding the training of pharmacists is marked by a serious dilemma between the demand for pharmacists as a medical resource and the practical conditions for obtaining the qualifications of a pharmacist. The system for training pharmacists is about to enter a new era with the review of the university and graduate school courses and the introduction of clinical training in the course. These changes are expected to produce very positive results.

Drug Therapy↗

Volumetric bone mineral density using peripheral quantitative computed tomography in Japanese women.

The present study evaluated a commercial device for peripheral quantitative computed tomography (pQCT) and examined the age-related changes in normal Japanese women. The volumetric bone mineral density (vBMD) of the distal radius [integral bone mineral density (BMDI), trabecular bone mineral density (BMDT) and cortical with subcortical bone mineral density (BMDSC)] was measured using pQCT (Norland-Stratec XCT960) in 617 healthy women aged 20-79 years and 75 subjects with osteoporosis aged 60-89 years who exhibited at least one vertebral fracture. The short-term precision errors in vivo (CV, %) were 1.1% for BMDI, 1.1% for BMDT and 1.2% for BMDSC. The correlations between pQCT and dual-energy X-ray absorptiometry measurements (Lunar DPX) of the lumbar spine were r approximately 0.8 (BMDI, BMDT and BMDSC). The maximal mean vBMD values were observed between 20 and 49 years; BMDI, BMDT and BMDSC all showed a linear postmenopausal decline averaging 1.1% per year. The overall decreases in vBMD from the peak values in those 70-79 years were 34%, 32% and 33% in BMDI, BMDT and BMDSC, respectively. The diagnostic sensitivity of osteoporosis was expressed as a T-score. T-scores using pQCT were -3.0 (BMDI), -2.4 (BMDT) and -2.9 (BMDSC). Bone mineral measurement of the distal radius may be useful in the evaluation of age-related bone loss and for the diagnosis of osteoporosis.

Adult↗

Evaluation of bone turnover in postmenopause, vertebral fracture, and hip fracture using biochemical markers for bone formation and resorption.

The purpose of this study is to evaluate bone turnover in postmenopausal status and established osteoporosis with vertebral fracture and hip fracture by assessing bone biochemical markers. Subjects were 50 healthy premenopausal subjects, 44 healthy postmenopausal subjects, 30 osteoporotic patients with vertebral fracture, and 31 osteoporotic patients with hip fracture. Alkaline phosphatase, osteocalcin, PICP, ICTP, NTx, free deoxypyridinoline, total pyridinoline and deoxypyridinoline were measured. In postmenopause, both Z-scores of bone formation markers and resorption markers were around 1-2. In osteoporosis, although Z-scores of bone formation markers were 0.4-2.8, resorption markers were 2.3-9.5. Moreover, Z-scores of resorption markers were higher in hip fracture than in vertebral fracture. These results indicate that bone formation and resorption increased and balanced in postmenopausal status. However, bone resorption increased more than bone formation and did not balance at all in osteoporosis. This imbalance is greater in hip fractures than in vertebral fractures.

Adult↗

Ultrasound bone densitometry of os calcis in elderly Japanese women with hip fracture.

We evaluated 138 elderly patients (mean age 79 years) within 2 weeks after hip fracture (67 cervical and 71 trochanteric) using an Achilles ultrasound bone densitometer (Lunar Corporation, Madison, WI). The ultrasound variables of speed of sound (SOS in m/second), broadband ultrasound attenuation (BUA in dB/MHz), and stiffness (%) index were measured on the os calcis. Ultrasound densitometry also was done on 563 normal postmenopausal women to assess normal age changes. An elderly subgroup (n = 138) served as age-matched controls for the hip fracture group. Further subgroups of 33 patients and 33 controls were compared for lumbar spine and femoral neck BMD. There were no statistically significant differences between the hip fracture group and age-matched controls in height and weight, but each ultrasound variable was significantly lower for the hip fracture group (P < 0.0001). For the hip fracture group, SOS was 1470 +/- 19 m/second, BUA was 84.3 +/- 8.4 dB/MHz, and the stiffness index was 47.8 +/- 9.2%, whereas for the age-matched controls, SOS was 1486 +/- 27 m/second, BUA was 94.0 +/- 11.4 dB/MHz, and the stiffness index was 59.1 +/- 12.5%. There were no significant differences between cervical and trochanteric hip fracture groups. Logistic regression analysis showed that a change of the ultrasound values by 1 standard deviation (SD) changed the odds ratio for SOS, BUA, and stiffness index by 2.51, 3.24, and 3.60, respectively. Ultrasound variables, particularly stiffness, were good indicators of hip fracture risk.

Aged↗

Bone density and body composition in Japanese women.

Total body bone mineral content (BMCTB in g) and density (BMDTB in g/cm2) and body composition were measured in 1006 healthy Japanese women aged 20-79 years using dual X-ray absorptiometry. Peak BMDTB was 1.11 +/- 0.05 g/cm2 in women 20-49 years, and mean BMDTB was 1. 019 g/cm2 in the 6th decade, 0.956 g/cm2 in the 7th decade, and 0. 900 g/cm2 in the 8th decade. BMDTB declined by 0.007 g/cm2/year in women after age 50. This age-related decline in BMD showed a similar pattern to that seen for the lumbar spine and femoral neck, but the actual rate of loss was lower for BMDTB than for these other measurement sites. There was no significant difference between a eumenorrheic premenopausal group and a group with irregular menses. BMCTB and BMDTB were associated with body build, lean tissue mass, and fat mass (r = 0.29 approximately 0.65 and 0.26 approximately 0.41, respectively). Bone mass and density decreased significantly in older women of all body builds. Premenopausal Japanese women had a 5% lower BMDTB than U.S. and European whites, but the difference was several times greater in postmenopausal than in premenopausal women.

Adult↗