Hironobu Hoshino

Circadian Variation of Urinary Type I Collagen Crosslinked C-Telopeptide and Free and Peptide-Bound Forms of Pyridinium Crosslinks

This study was performed to investigate the circadian variation of urinary CrossLaps (CTx), which was the type I collagen peptide released during bone matrix degradation, and peptide-bound and free forms of urinary pyridinium crosslinks. Urine was obtained during the 24 h of the study in seven separate collections as follows: from 23:00 h to the first void (FV) followed by FV at 11:00, 11:00-14:00, 14:00-17:00, 17:00-20:00, 20:00-23:00, and 23:00 h to FV the next morning. Total, free, and peptide-bound pyridinoline (Pyr) and deoxypyridinoline (Dpyr) excretion measured by high-performance liquid chromatography (HPLC) and CTx measured by enzyme-linked immunosorbent assay in nine premenopausal women aged 22-40 years and nine osteoporotic women aged 65-83 years was analyzed. Among three parameters of Pyr measured by HPLC, a significant day and night difference was found only in total Pyr (21.9% higher at night than during the day in premenopausal women and 24.0% in osteoporotic women, whereas no significant day and night variation was found in free and peptide-bound Pyr in either group. In contrast, total and peptide-bound Dpyr were significantly (37.9% and 66.9%) higher at night than those during the day in premenopausal women (38.0%) and osteoporotic women (48.8%). For free Dpyr, there were no day and night differences in the two groups. The day and night variances were significantly greater in peptide-bound Dpyr than with total Dpyr in both groups. In urinary CTx, a significant circadian variation with a peak at night and a nadir at 17:00 h was found (p < 0.0001) (premenopausal was 54.0% higher at night than during the day; osteoporotic was 38.4%. In conclusion, urinary CTx represented remarkable circadian variation compared with urinary pyridinium crosslinks measured by HPLC. Furthermore, free pyridinium crosslinks did not undergo a circadian variation. Peptide-bound crosslinks might contribute mostly to the circadian variation of total excretion of pyridinium crosslinks.

Changes of biochemical markers during fracture healing.

The aim of this study was to evaluate the changes of biochemical markers during fracture healing in patients with osteoporosis. The study included 26 patients; 9 underwent hip hemiarthroplasty (mean age ± SD: 71.0 ± 10.2 years, group EN) for femoral neck fractures, 7 underwent osteosynthesis (75.3 ± 8.2 years, group OS) for trochanteric fractures, and 10 subjects had spinal compression fractures (68.2 ± 12.0 years, group CO). No operative procedures were performed in group CO. Urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr) by high performance liquid chromatography (HPLC), Crosslaps by both enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) (CTx-ELISA and CTx-RIA) and serum N-terminal mid-fragment osteocalcin (OCN-Mid) by ELISA were analyzed at the time of admission and at weeks 1, 2, 4, 8 and 24 after operation or, in the case of group CO, after admission. As a whole, bone resorption markers started to increase from week 1, with various peak values between weeks 4 and 8 depending upon the particular marker, but returned to the initial vales at week 24. OCN-Mid started to increase from week 8 and remained at elevated levels at week 24. In groups EN and OS, bone resorption markers changed in the same manner as they did as a whole group. OCN-Mid did not change in group EN, although it increased significantly from week 8 in group OS. No biochemical markers changed significantly in group CO. In conclusion, bone resorption was accelerated at an early stage due to acute osteonecrosis or bed rest, followed by bone formation due to callus or mechanical stress later on. As far as bone resorption markers are concerned, 24 weeks are enough to eliminate the effect of fracture.

Craniopelvic alignment in elderly asymptomatic individuals: analysis of 671 cranial centers of gravity.

Study Design. Prospective radiographical analysis using the cranial center of gravity (CCG) of sagittal vertical axis (SVA) in elderly asymptomatic individuals. Objective. To determine sex differences and age-related correlations of CCG and relationships between CCG and other spinopelvic parameters/health-related quality of life (HRQOL) measures. Summary of Background Data. Few studies have investigated CCG in a relatively large sample of elderly asymptomatic individuals. Methods. Six hundred seventy-one healthy participants older than 50 years (mean age, 72.9 yr; range, 50–92 yr) were enrolled. Whole-spine standing radiographs were obtained. The following radiographical measurements were obtained: (1) CCG–C7 SVA, (2) C7–SVA, (3) CCG–SVA, (4) C2–C7 lordosis angle, (5) thoracic kyphosis, (6) lumbar lordosis, (7) pelvic incidence, and (8) sacral slope. HRQOL measures included the EuroQol-5D and Oswestry Disability Index. Pearson product-moment correlation coefficients were calculated between pairs of radiographical measures and HRQOL. Results. Sex differences were observed in CCG–C7 SVA, CCG–SVA, C2–C7 Cobb angle, thoracic kyphosis, and pelvic incidence. Three SVA parameters (CCG–C7 SVA, C7–SVA, CCG–SVA) rapidly increased between seventh and ninth decades and were approximately 40, 80, and 120 mm, respectively, in the ninth decade. Age-related correlations were observed for all parameters without pelvic incidence, and the CCG measurement correlated the most with age. Furthermore, CCG–SVA correlated with other spinopelvic measurements and HRQOL. Conclusion. Age-related changes and sex difference in craniopelvic alignment were analyzed. Craniopelvic alignment became rapidly positive with age, particularly in the eighth decade. The CCG measurement correlated the most with age and may be a useful index marker of global spinal balance in decision making for surgical treatment of adult deformity involving cervical and thoracolumbar lesions. Level of Evidence: 4

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.

Changes in Levels of Biochemical Markers and Ultrasound Indices of Os Calcis Across the Menopausal Transition

Abstract: The aim of this longitudinal study was to investigate the changes in the levels of biochemical markers and ultrasound indices of os calcis across the menopausal transition. One hundred and ten healthy women (age 35–59 years at the 1992 baseline) participated in this 4-year population-based longitudinal study. Serum intact osteocalcin (IOC), urinary pyridinoline (Pyr), urinary deoxypyridinoline (Dpyr) and ultrasound indices were measured at baseline and after 4 years. The percentage changes in biochemical markers (%DIOC, %DPyr and %DDpyr) and the percentage decreases in the ultrasound indices (%DSOS, %DBUA and %DStiffness) were calculated. The values of %DIOC and %DDpyr in the perimenopausal subgroup (−4 to−3 years since menopause) and the values of %DSOS and %DStiffness in the perimenopausal subgroup (−2 to 0 years since menopause) were significantly higher than those in other groups. Pyr was significantly correlated with %DSOS (r=−0.467, p<0.01) and %DStiffness (r = −0.330, p<0.05) and Dpyr was significantly correlated with %DSOS (r=−0.390, p<0.05), %DBUA (r=−0.353, p<0.05) and %DStiffness (r = −0.454, p<0.05), while %DIOC was significantly correlated with %DSOS (r=−0.278, p<0.05), %DBUA (r=−0.369, p<0.01) and %DStiffness (r = −0.383, p<0.01) in the peri- and postmenopausal groups. These results indicate that the increase in bone turnover occurs 4 years before menopause. However, the correlations between biochemical markers and ultrasound indices were too low to allow prediction of bone change in the individual patient.

Bone turnover and cortical bone mineral density in the distal radius in patients with hyperthyroidism being treated with antithyroid drugs for various periods of time

Whether patients, who have lost bone mass, can be restored to age‐matched control levels by some means is still controversial. We investigated how the thyroid status after antithyroid drug therapy for various periods of time affects bone metabolism in patients with hyperthyroidism by assessing currently used biochemical markers of bone turnover and distal radius bone mineral density (BMD).

The Relationships Between the Degree of β-Isomerization of Type I Collagen Degradation Products in the Urine and Aging, Menopause and Osteoporosis with Fractures

Abstract: We have evaluated the effect of aging, menopause and osteoporosis on the measurements of both nonisomerized type I collagen C-telopeptide breakdown products (α-CTx) by radioimmunoassay (RIA) and β-isomerized type I collagen C-telopeptide breakdown products (β-CTx) by enzyme-linked immunosorbent assay (ELISA). In 86 premenopausal healthy women (PRE), 144 postmenopausal healthy women (POST), 74 patients with vertebral fractures (VX) and 61 patients with hip fractures (HX), urinary CTx excretion was measured by both ELISA and RIA assays. Samples were collected more than 6 months after fracture in the VX group and within 48 h after fracture in the HX group. In all subjects a highly significant correlation was found between α-CTx and β-CTx (r= 0.85). The values of β-CTx in the POST group greatly increased compared with those in the PRE group (% mean increase: 82%), while the values of α-CTx in the POST group moderately increased compared with those in the PRE group (% mean increase: 47%). The values of both α-CTx and β-CTx in the HX group were significantly higher than those in the other groups, but particularly the increase in mean α-CTx (211% for HX versus POST) was very high compared with the increase in mean β-CTx (68% for HX versus POST). Moreover, the α-CTx/β-CTx ratio in the HX group was significantly higher than in the other groups. These results suggest that both assays well reflect the increase in bone resorption associated with high bone turnover, especially, in osteoporotic patients with hip fracture. However, there was a difference between the urinary excretion of α-CTx and β-CTx in patients with hip fracture, so the α-CTx/β-CTx radio might be a good indicator reflecting the characteristics of bone metabolism for osteoporosis with hip fracture.

Quantitation of the crosslinks, pyridinoline, deoxypyridinoline and pentosidine, in human aorta with dystrophic calcification

Pyridinoline and, its minor analogue deoxypyridinoline, are trifunctional crosslinks of mature collagen in the connective tissues. Pentosidine, a new type of fluorescent crosslink, is possibly one of the senescent crosslinks but its function and metabolism are still unclear. In this study, we quantitated the crosslinks, pyridinoline, deoxypyridinoline and pentosidine, in human aorta which were obtained from 21 autopsy cases. In each case, the existence of dystrophic calcification in the aorta and complications (diabetes, chronic renal failure and hypertension) were examined. The determination of the content of the three crosslinks was carried out using high performance liquid chromatography (HPLC) analysis. In calcified lesions, the amount of deoxypyridinoline/collagen showed a decrease and the amount of deoxypyridinoline/pyridinoline showed a prominent decrease compared to those in non-calcified lesions (deoxypyridinoline/collagen, P < 0.005; deoxypyridinoline/pyridinoline, P < 0.0001). In non-calcified lesions without complications, the amount of pentosidine/pyridinoline and that of pentosidine/deoxypyridinoline significantly increased with age (pentosidine/pyridinoline, r = 0.704, P < 0.05; pentosidine/deoxypyridinoline, r = 0.624, P < 0.05). This result suggests a possible relationship between dystrophic calcification and crosslink formation of collagen in human aorta.

Comparison of serum and urinary C-terminal telopeptide of type I collagen in aging, menopause and osteoporosis.

BACKGROUND Urinary C-terminal telopeptide of type I collagen (u-CTx) has been reported to be a sensitive biochemical marker of bone turnover. There have been two assays for urinary CTx, which are alpha-CTx and beta-CTx. A newly developed immunoassay for serum CTx (s-CTx) is now available for assessment of bone resorption. We evaluated the effects of aging, menopause, and osteoporosis on the measurements of serum CTx and compared them to urinary CTx assays. METHODS In 79 premenopausal healthy women, 80 postmenopausal healthy women, 61 osteoporotic patients with vertebral fractures and 34 osteoporotic patients with hip fractures, s-CTx and urinary beta-CTx (u-betaCTx) were measured by ELISAs, and urinary alpha-CTx (u-alphaCTx) was measured by an RIA. RESULTS In all subjects, s-CTx significantly correlated with both u-alphaCTx (r=0.54) and u-betaCTx (r=0.51). There was no significant difference among s-CTx, u-alphaCTx and u-betaCTx in the T-scores of the postmenopausal group over the premenopausal group. These findings indicate that the value of s-CTx, as well as urinary CTxs, reflected the increase of bone resorption associated with menopause with a high degree of sensitivity. Patients with vertebral fractures had moderately increased concentrations of bone resorption markers compared to age-matched healthy postmenopausal women (T-score; s-CTx: 0.8, u-alphaCTx: 0.9, u-betaCTx: 0.7), whereas bone resorption markers in hip fracture patients were greatly increased compared to healthy postmenopausal women (T-score; s-CTx: 1.1, u-alphaCTx: 1.3 u-betaCTx: 1.3). The T-scores of u-CTxs against the postmenopausal group in vertebral fracture group and in hip fracture group were not significantly different from those of s-CTx. CONCLUSIONS s-CTx, as well as urinary CTxs, reflects the increase of bone resorption in patients with vertebral fractures and hip fractures.

CIRCULATING LEVELS OF VITAMIN K1, MENAQUINONE-4, AND MENAQUINONE-7 IN HEALTHY ELDERLY JAPANESE WOMEN AND PATIENTS WITH VERTEBRAL FRACTURES AND PATIENTS WITH HIP FRACTURES

Recently, vitamin K has become increasingly of interest in the bone metabol-ism field because of its role as a cofactor in the carboxylation of osteocalcin. Although the role of osteocalcin is not clear, noncarboxylated osteocalcin is one risk factor in hip fractures. It has been reported that the circulating levels of vitamin K1 in osteoporotic patients were significantly lower than those of age-matched control subjects. In this study, we measured circulating levels of vitamin K1, menaquinone-4 (MK-4) and menaquinone-7 (MK-7) in 23 normal healthy women aged 52–93 years (mean ± SD: 80.1 ± 3.5), 13 female patients with vertebral fractures aged 66–93 years (80.3 ± 7.8) and 38 female patients with hip fractures aged 76–87 years (79.8 ± 9.2), (all Japanese), in order to make sure whether these vitamin K levels were different in these three groups. Serum circulating levels of MK-4 was undetectable in most subjects (only one out of 74). Appreciable numbers from these three groups had undetectable levels of MK-7 (52% of the control group, 23% of the vertebral fracture group and 24% of the hip fracture group). Eight subjects from the normal control group (35%) and five patients from the vertebral group (38%) had undetectable levels of vitamin K1. We did not find a significant difference in the measurable levels of vitamin K1, MK-4 and MK-7 in patients with vertebral fractures or patients with hip fractures compared to age-matched normal controls. Undetectable levels of measured vitamin K1, MK-4 and MK-7 in most of subjects may significantly affect the results.