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Human articular cartilages of various ages were digested with collagenase, and the fluorescence of the digests was measured as a function of age. At acidic pH, all collagenase-treated fractions were found to contain two main fluorophores with fluorescence maxima at 395 and 385 nm (excitation at 295 and 335 nm, respectively). Each fluorophore was isolated from the hydrolysate and its structure was deduced from spectral and chemical data. The 395/295 nm fluorophore was identified as pyridinoline, which is one of the non-reducible cross-linkages in collagen. The 385/335 nm fluorophore was identical to pentosidine, which was isolated from human dura mater and characterized by Sell and Monnier in 1989. Our results showed that the amount of pentosidine per collagen in human articular cartilage increases linearly with age (r = 0.929, p less than 0.005), while the amount of pyridinoline per collagen remained constant and was not correlated with age (r = 0.20). On the other hand, the amount of pentosidine per pyridinoline increased exponentially during life (r2 = 0.839, p less than 0.05).

To evaluate the efficacy and safety of alendronate, a double-masked, active (alfacalcidol) controlled comparative study for 48 weeks was carried out in a total of 210 Japanese patients with osteoporosis. The doses of alendronate and alfacalcidol were 5 mg/day and 1 microgram/day, respectively. The lumbar bone mineral density (LBMD) values observed at 12, 24, 36 and 48 weeks after the initiation of alendronate treatment were 3.53 +/- 0.53%, 5.37 +/- 0.62%, 5.87 +/- 0.74% and 6.21 +/- 0.59% (mean +/- SE), respectively, higher than the baseline value. Corresponding values in the alfacalcidol group were 1.50 +/- 0.43%, 0.69 +/- 0.63%, 1.12 +/- 0.60% and 1.36 +/- 0. 63%, respectively. There was a significant difference between the two groups at each time point (p<0.05 or p<0.001). The bone turnover markers were depressed during treatment in the alendronate group: -32.2% for alkaline phosphatase, -53.7% for N-terminal osteocalcin and -45.0% for urinary deoxypyridinoline compared with the corresponding baseline values. On the contrary, no notable changes in these parameters were observed in the alfacalcidol group. Treatment with alendronate caused a transient decrease in serum calcium concentrations associated with an increase in the serum level of intact parathyroid hormone. In contrast, treatment with alfacalcidol resulted in a tendency of these parameters to change in the opposite direction. No difference in fracture incidence between the two groups was observed. The overall safety of alendronate was comparable to that of alfacalcidol. In conclusion, although it was a relatively short-term study of 48 weeks, the results of the present study indicate that alendronate at the daily dose of 5 mg was effective in increasing LBMD and that no serious drug-related adverse events were observed in the alendronate-treated patients. Alendronate is more efficacious than alfacalcidol in increasing bone mineral density, although the mechanisms of the actions of the two drugs are apparently different.

Since the plasma level of MMP-3 in GOA was higher than that in KOA patients, it may be a superior indicator for whole-joint degeneration.

The metacarpal bone mineral density (BMD) and metacarpal index (MCI) of the second metacarpal bone were measured by computed X-ray densitometry (CXD) (Teijin Ltd., Tokyo), which we have established with the development of microdensitometry of radiographs. In this study, we evaluated the basic attributes of this CXD method and determined the age-related changes in both metacarpal measurements in normal Japanese women. The precision in vivo was measured in eight subjects. The precision errors [coefficient of variation (CV)] were 0.2-1.2% CV for metacarpal BMD and 0.4-2.0% CV for MCI, respectively. We have obtained low precision error and more rapid analysis, within 3 minutes respectively, compared with the previous methods. Age-related changes in the metacarpal measurements were evaluated in 1438 normal women. Both measurements showed the most significant decrease in the sixth decade of life. The rate of decrease in the sixth decade was 1.6%/year for metacarpal BMD and 1.5%/year for MCI. On comparison between metacarpal BMD by CXD and spine BMD using dual energy X-ray absorptiometry (DXA) in 248 normal women with and without menstruation, the two measurements were found to be similarly decreased in the subjects within 5 years after menopause. There was also no significant difference in the Z-score between metacarpal BMD and spine BMD within 5 years after menopause. These results indicate that early postmenopausal bone loss occurs not only in the spine but also in the metacarpal bone.(ABSTRACT TRUNCATED AT 250 WORDS)

The velocity (SOS), attenuation slope (BUA) and stiffness index in the os calcis were measured using the 'Achilles' ultrasound bone densitometer (Lunar, Madison, WI). We evaluated the basic attributes of this ultrasound bone densitometer, and showed the age-related changes in ultrasound values in normal Japanese women. The precision was measured in vivo on ten occasions over a 2-week period in 5 subjects. The short-term precision errors (CVs) in vivo were 0.6% for stiffness index, 0.3% for SOS and 1.0% for BUA. Spine, femur neck and total body BMD using dual X-ray absorptiometry (DXA) were highly correlated with stiffness index (r = 0.80, 0.77 and 0.78, respectively) in 194 subjects. Ultrasound values for patients with osteoporosis were significantly lower than those for the normal controls. The Z-score compared with young normals was significantly higher for spine bone mineral density (-4.4) than for stiffness index (-3.5); BUA and SOS gave significantly lower Z-scores -2.9 and -3.0, respectively). Ultrasound values were also lower compared with age-matched normal controls. The Z-score for stiffness index (-2.1) was significantly superior to that for either SOS or BUA (-1.5). Age-related change in ultrasound values was evaluated in 842 normal women. There was a decline in stiffness index of about 24% from the values in young adulthood to those of women in their seventies, about 75% of which occurred from age 44-49 years onward. These findings seem to indicate that the menopause affected the change in ultrasound values.(ABSTRACT TRUNCATED AT 250 WORDS)