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Masataka Shiraki

Publications and source records attributed to Masataka Shiraki.

At least 19 recordsLinked to original sources

Q89R polymorphism in the LDL receptor-related protein 5 gene is associated with spinal osteoarthritis in postmenopausal Japanese women.

STUDY DESIGN: An association study investigating the genetic etiology for spinal osteoarthritis. OBJECTIVE: To determine the association of single-nucleotide polymorphism (SNP) causing an amino-acid change (Q89R) in the low-density lipoprotein receptor-related protein 5 (LRP5) coding region with spinal osteoarthritis. SUMMARY OF BACKGROUND DATA: Wnt/beta-catenin signaling pathway regulates bone density through a Wnt coreceptor LRP5. This pathway is also involved in cartilage development and homeostasis, suggesting that genetic variation in LRP5 gene may affect the pathogenesis of cartilage-related diseases, such as osteoarthritis. METHODS: We evaluated the presence of osteophytes, endplate sclerosis, and narrowing of disc spaces in 357 Japanese postmenopausal women. Missense coding SNP for Q89R of LRP5 gene was determined using TaqMan polymerase chain reaction (PCR) method. RESULTS: We found that subjects without the R allele (QQ; n = 321) had a significantly lower osteophyte formation score than did subjects bearing at least one R allele (QR + RR; n = 36) (7.80 vs. 10.89, P = 0.0019 by analysis of covariance). CONCLUSIONS: We suggest that a genetic variation at the LRP5 gene locus is associated with spinal osteoarthritis, in line with the involvement of the LRP5 gene in the bone and cartilage metabolism.

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Randomized trial comparing low-dose hormone replacement therapy and HRT plus 1alpha-OH-vitamin D3 (alfacalcidol) for treatment of postmenopausal bone loss.

We conducted a prospective, randomized, multicenter, open-label 2-year trial with 76 postmenopausal women aged > or =60 years with low (T-score less than -1) lumbar bone mineral density (BMD). The hormone replacement therapy (HRT) group received a low dose of conjugated estrogen (CEE) at a dose of 0.31 mg/day +/- medroxyprogesterone acetate (MPA) 2.5 mg/day. Group HRT/D received the same dose of HRT together with alfacalcidol in a daily dose of 1.0 microg/day. Changes in lumbar BMD measured by dual energy X-ray absorptiometry (DXA) were followed every 6 months for 2 years. The lumbar BMD of group HRT increased 3.37% [95% confidence interval (CI) 1.6%-5.2%], 4.00% (95%CI 1.6%-6.4%), and 2.32% (95%CI -0.7% to 5.3%) at 12, 18, and 24 months, respectively, when the baseline value was taken as 0%. Lumbar BMD of group HRT/D showed a significant increase beyond 6 months. The percent increases for this group at 6, 12, 18, and 24 months were 6.18 (95%CI 1.3%-6.6%), 6.18% (95%CI 3.9%-8.5%), 7.17% (95%CI 4.3%-10.0%), and 8.75% (95%CI 6.0%-11.5%), respectively. In addition, there was a significant difference in the changes of the lumbar BMD between the two groups at 24 months, suggesting that the combination of HRT and alfacalcidol is more effective than HRT alone in terms of the BMD effect. This study is the first prospective trial demonstrating an additive effect of alfacalcidol on lumbar BMD in postmenopausal women receiving low-dose HRT. It suggests that the combination therapy can be considered to be a promising mode of treatment for bone loss after menopause.

Absorptiometry, Photon↗

The sample size required for intervention studies on fracture prevention can be decreased by using a bone resorption marker in the inclusion criteria: prospective study of a subset of the Nagano Cohort, on behalf of the Adequate Treatment of Osteoporosis (A-TOP) Research Group.

In drug developments for osteoporosis, large-scale and longterm fracture prevention studies have been required. We investigated whether or not it was possible to reduce the sample size and observation period under new selection criteria for an osteoporotic fracture-prevention study. A Poisson regression model was used to identify independent risks for incident vertebral fracture in 515 postmenopausal women who had had no intervention for osteoporosis; this group was a subset of Nagano Cohort participants. The total observation period for this group was 2,577 person-years, and a total of 146 new vertebral fractures were observed. Risk assessment for incident vertebral fracture among numerical covariates revealed that the following items showed significant independent risks for incident fractures; namely, baseline age (hazard ratio [HR]; 1.84; 95% confidence interval (CI), 1.44-2.35; P < 0.001), number of preexisting vertebral fractures (HR, 1.28; 95% CI, 1.17-1.40; P < 0.001), baseline lumbar bone mineral density (LBMD) (HR, 0.79; 95% CI, 0.71-0.88; P < 0.001), and urinary excretion of deoxypyridinoline (DPD) (HR, 1.18; 95% CI, 1.03-1.35; P = 0.016). Because the initial urinary excretion of DPD was found to be a risk for incident vertebral fracture, in addition to the conventional risks, we assessed whether or not the sample size or observation period could be reduced by the incorporation of the urinary excretion of DPD into the selection criteria of a fracture-prevention study. The assessment of sample size was calculated, using the log rank test, at a two-tailed significance level of 5% and with a power of 80%. When osteoporotic patients with preexisting fracture were selected (conventional criteria), the 3-year probability of vertebral fracture was estimated as 14.3% in the present population. On the other hand, the new vertebral fracture rate during 3 years in the osteoporotic patients with preexisting fracture plus high urinary DPD (HR, above 1.0); (new selection criteria) was estimated as 23.2%. When the HR between test drug and placebo was changed from 0.4 to 0.8, the required sample size for any level of HR showed a 40% reduction for the new selection criteria compared to the conventional criteria. Therefore, the addition of urinary DPD level to the selection criteria is useful to reduce sample size in an osteoporosis fracture-prevention study.

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Efficacy and tolerability of once-weekly administration of 17.5 mg risedronate in Japanese patients with involutional osteoporosis: a comparison with 2.5-mg once-daily dosage regimen.

In this multicenter, randomized, double-blind controlled trial, the efficacy and safety of once-weekly dosing with 17.5 mg risedronate was compared with once-daily dosing with 2.5 mg risedronate in Japanese patients with involutional osteoporosis. A total of 496 patients were randomized to receive either once-weekly (n = 249) or once-daily (n = 247) treatment. All patients were supplemented with 200 mg/day calcium. Following 48 weeks of treatment, the mean (+/-SD) percent changes, from baseline, in the bone mineral density of the lumbar spine (L2-L4 BMD) in the once-weekly and once-daily treatment groups were 5.36 +/- 4.27% and 5.87 +/- 4.47%, respectively. The difference between the groups was -0.5% (95% confidence interval: -1.35% to 0.35%), demonstrating that the effect on BMD of once-weekly treatment was not inferior to that of once-daily treatment. The time-course reductions in biochemical markers of bone resorption (urinary N- and C-telopeptide of type I collagen) and bone formation (bone-specific alkaline phosphatase) were similar for the two dosing regimens. There were no differences in the incidence of new vertebral fractures or the worsening of existing fractures between the once-weekly (2.2%) and once-daily (2.7%) dosing regimens. No significant differences were observed between the two dosing regimens in the incidence or the type of adverse events. However, 10.1% of the patients in the once-daily group withdrew due to adverse events as compared to 5.2% in the once-weekly group. Moreover, drug-related adverse events, including upper gastrointestinal disorders and abnormal changes in laboratory parameters, tended to be less in the once-weekly dosing regimen than in the once-daily dosing regimen. In conclusion, once-weekly oral dosing with 17.5 mg risedronate was well tolerated in Japanese osteoporotic patients, and showed equivalent efficacy to once-daily oral dosing with 2.5 mg risedronate. This once-weekly regimen is expected to provide a more convenient therapeutic option as an alternative to daily dosing and to enhance patient compliance in long-term therapy for osteoporosis.

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Vitamin K status of healthy Japanese women: age-related vitamin K requirement for gamma-carboxylation of osteocalcin.

BACKGROUND: Vitamin K deficiency is associated with low bone mineral density and increased risk of bone fracture. Phylloquinone (K1) and menaquinone 4 (MK-4) and 7 (MK-7) are generally observed in human plasma; however, data are limited on their circulating concentrations and their associations with bone metabolism or with gamma-carboxylation of the osteocalcin molecule. OBJECTIVES: The objectives were to measure the circulating concentrations of K1, MK-4, and MK-7 in women and to ascertain whether each form of vitamin K is significantly associated with bone metabolism. DESIGN: Plasma concentrations of K1, MK-4, MK-7, undercarboxylated osteocalcin (ucOC; measured by using the new electrochemiluminescence immunoassay), intact osteocalcin (iOC), calcium, and phosphorus; bone-derived alkaline phosphatase activity; and concentrations of urinary creatinine, N-terminal telopeptide, and deoxypyridinoline were measured in healthy women (n = 396). RESULTS: On average, MK-7 and MK-4 were the highest and lowest, respectively, of the 3 vitamers in all age groups. K1 and MK-7 correlated inversely with ucOC, but associations between nutritional basal concentration of MK-4 and ucOC were not observed. Multiple regression analysis indicated that not only K1 and MK-7 concentrations but also age were independently correlated with ucOC concentration and the ratio of ucOC to iOC. The plasma K1 or MK-7 concentration required to minimize the ucOC concentration was highest in the group aged > or =70 y, and it decreased progressively for each of the younger age groups. CONCLUSIONS: The definite role of ucOC remains unclear. However, if submaximal gamma-carboxylation is related to the prevention of fracture or bone mineral loss, circulating vitamin K concentrations in elderly people should be kept higher than those in young people.

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[A head-to-head comparative study for evaluation of effectiveness among drugs for osteoporosis].

Recent progress in osteoporosis treatment has realized prevention of osteoporotic fractures. However, there is no guideline regarding which agent should be used in an individual patient. In this report, we investigated the effectiveness of several drugs for osteoporosis in a head-to-head comparative study. A total of 776 osteoporotic patients were treated with alendronate (ALN, n=197), etidronate (EHDP, n=199), alfacalcidol (VD3, n=221) and vitamin K2 (K2, n=159). The control group (No, n=266) was followed without treatment. We followed their lumbar bone mineral density (LBMD), bone turnover markers (DPD or NTX or BAP) and presence or absence of incident vertebral fractures for more than 3 years. The mean age was 70 years old. The increase in LBMD after the treatment was highest in ALN treated group (8%) followed by EHDP (6%). VD3 (1-0%) and K2 (-2%). For the change in bone turnover marker after the treatment, ALN and EHDP treated groups showed significant decrease in bone resorption markers but not the VD3 and K2 treated groups. ALN group exhibited more powerful inhibition of fracture rate (Odds ratio 0.305 versus the control, p < 0.01) than the other groups (Odds ratios 0.604-0.668 versus the control p < 0.05). ALN treatment has achieved a wide range effectiveness regardless of fracture risk. On the other hand, EHDP showed significant inhibition of fracture in low risk osteoporosis. VD3 or K2 treated groups did not inhibit new fracture occurrence in low risk osteoporosis but did so in high risk osteoporosis suggesting that those agents may improve bone quality. In conclusion, ALN is thought to be the first line drug in terms of fracture prevention in osteoporosis and the other drugs should be given to the patients who could not recieve ALN.

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[Very old patients with osteoporosis should be treated with alendronate].

Although alendronate treatment for the prevention of osteoporotic fracture has been considered to be first line treatment, there is little knowledge whether very old osteoporosis should be treated with alendronate or not. To elucidate this question, we investigated the effectiveness of osteoporotic drugs in terms of effects of treatment on bone mineral density (BMD), bone resorption markers and fracture prevention in osteoporosis aged over 75 years old or less. A total of 1,041 postmenopausal osteoporosis cases were classified into 4 categories, Young controls (n = 165) and Old controls (n = 95) (Control group), Young (n = 309) and Old osteoporosis (n = 110) treated with alendronate (ALN group), and Young (n = 238) and Old osteoporosis (n = 124) treated with vitamins D3 or K2 (VDK group). We followed their lumbar BMD, urinary excretion of NTX and incident vertebral fracture rate for three years. The effects of the ALN treatment on lumbar BMD and on urinary NTX were not different between the two age-categorized osteoporosis groups, namely, the lumbar BMD increased by around 6-7% after ALN treatment in both Old and Young groups. The urinary excretion of NTX was decreased by 50% from baseline in both Old and Young ALN treated groups. Those effects of ALN were significantly superior to those in the controls and VDK-treated groups of both age categories. Therefore, ALN biological effects on bone were not age-dependent and the effects of ALN were strongest than the other treatments. The effects on fracture prevention in the Old ALN-treated group showed a 66.7% risk reduction rate (RRR) (p< 0.05) when the fracture incidence rate in the control group (50%) was taken as 100%, while it was 18.8% RRR (ns) in VDK-treated Old group. The Young group treated with ALN showed a 35.6% RRR from the Young control group (25% as 100%) (p<0.05). The VDK treated group did not show a significant RRR of incident fracture (24.4%). Thus, alendronate was the only effective modality to prevent fractures in both young and old osteoporosis. These results clearly indicated that very old osteoporotics should be treated with alendronate at this moment.

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[Pathogenesis of fracture will be important in the research work of osteoporosis].

Osteoporosis is characterized by compromised bone strength, and the increased susceptibility to fractures that impair patient's quality of life and increase mortality constitutes a national burden in the aging society. The pathogenesis of osteoporosis has been recently astringent on estrogen deficiency that induces secondary metabolic changes such as calcium imbalance. Thus, the main research issue in osteoporosis has been turning to the mechanical basis of bone fractures. According to the definition of osteoporosis proposed by National Institutes of Health, bone strength reflects the integration of two components: the bone mass (bone mineral density) and bone quality. Of the two, bone mineral density (BMD) is known to be the major determinant of future fracture risk. In contrast, bone quality assessment has not been applied to clinical practice except for the measurement of bone turnover markers. The present paper reviewed the bone quality concepts and discussed the future potential research propositions.

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Distinct association of gene polymorphisms of estrogen receptor and vitamin D receptor with lumbar spondylosis in post-menopausal women.

Contribution of genetic backgrounds to the etiology of lumbar spondylosis has been suggested by epidemiological studies. This study was designed to determine the association of restriction fragment length polymorphisms (RFLPs) of estrogen receptor (ER), vitamin D receptor (VDR), parathyroid hormone (PTH) and interleukin-1beta (IL-1beta) genes with the radiological severity of lumbar spondylosis at the disk level from L1/2 to L5/S1 in Japanese post-menopausal women. ER and VDR RFLP haplotypes were associated with the severity of spondylosis in the upper levels (L1/2 and L2/3) more than in the lower levels. Association of ER genotype was more pronounced in the group younger than average than in the older group, while that of VDR genotype was more significant in the older group. Neither PTH nor IL1-beta RFLP was associated with the severity at any levels in either stratified group. We thus conclude that ER and VDR genes may contribute to lumbar spondylosis in a distinct manner: estrogen sensitivity influences the severity in the early phase after menopause while vitamin D plays an important role at older ages when the contribution of estrogen loss is weaker.

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A new active vitamin D, ED-71, increases bone mass in osteoporotic patients under vitamin D supplementation: a randomized, double-blind, placebo-controlled clinical trial.

CONTEXT: ED-71 has been shown to increase lumbar bone mineral density (BMD) in osteoporotic subjects. However, vitamin D insufficiency might have influenced the effect of ED-71 on BMD. OBJECTIVE: Our objective was to examine whether ED-71 can increase BMD in osteoporotic patients under vitamin D supplementation. DESIGN, SETTING, AND PATIENTS: We conducted a randomized, double-blind, placebo-controlled clinical trial of 219 osteoporotic patients (49-87 yr of age). INTERVENTIONS: Subjects were randomly assigned to receive placebo or 0.5, 0.75, or 1.0 microg/d ED-71 for 12 months. All the subjects received 200 or 400 IU/d vitamin D(3). MAIN OUTCOME MEASURES: We assessed changes in lumbar and hip BMD and bone turnover markers from baseline. RESULTS: Lumbar BMD increased with ED-71 treatment for 12 months (2.2, 2.6, and 3.1% from baseline and 2.9, 3.4, and 3.8% vs. placebo group in subjects receiving 0.5, 0.75, and 1.0 microg ED-71, respectively). Total hip BMD also increased with 0.75 and 1.0 microg ED-71 (-0.8, 0.6, and 0.9% from baseline and 0.1, 1.5, and 1.8% vs. placebo group in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively). Bone formation and resorption markers were suppressed by approximately 20% after 12 months of 0.75 and 1.0 microg ED-71 treatment. Transient hypercalcemia over 2.6 mmol/liter occurred in 7, 5, and 23% of subjects in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively, but none of them developed sustained hypercalcemia. CONCLUSIONS: These results demonstrate that ED-71 treatment at around 0.75 microg/d can effectively and safely increase lumbar and hip BMD in osteoporotic patients with vitamin D supplementation.

Absorptiometry, Photon↗

Association of single nucleotide polymorphisms in the promoter region of the pro-opiomelanocortin gene (POMC) with low bone mineral density in adult women.

Among multiple factors influencing osteoporosis, genetic variations involved in bone-mineral metabolism can affect risks predisposing to the disease onset. Here, we studied single-nucleotide polymorphisms (SNPs) in the pro-opiomelanocortin (POMC) gene for possible association with bone mineral density (BMD) among 384 adult Japanese women and observed significant correlation between adjusted BMD and three SNPs in the promoter region (r>0.14, p<0.01). The most significant correlation was observed for -2353G/A (r=-0.16, p=0.002); homozygous carriers of the major (G) allele had the highest BMD (0.405+/-0.054 g/cm2) while heterozygous carriers were intermediate (0.390+/-0.053 g/cm2) and homozygous A-allele carriers had the lowest BMDs (0.369+/-0.048 g/cm2). Although no association was detected between these SNPs and body weight or body mass index (BMI), significant association was detected between the -2313A/C genotype and plasma total cholesterol level (r=-0.12, p=0.019). We propose that POMC is among the likely susceptibility genes for osteoporosis and may also be involved in dyslipidemia.

Adult↗

Association of a single nucleotide polymorphism in the lipoxygenase ALOX15 5'-flanking region (-5229G/A) with bone mineral density.

The 12/15-lipoxygenase gene Alox15 has been identified as a susceptibility gene for bone mineral density (BMD) in mice through combined genetic and genomic analyses. Here we studied the association between bone mineral density and an ALOX15 gene single nucleotide polymorphism to assess the potential involvement of the human ALOX15 gene in postmenopausal osteoporosis. Specifically, we examined the association between a single nucleotide polymorphism at -5299G/A in the ALOX15 5'-flanking region with BMD in 319 postmenopausal Japanese women (66.7 +/- 8.9 years, mean +/- SD). We found that subjects bearing at least one variant A allele (GA + AA; n = 273) had significantly lower Z scores for lumbar spine and total body bone mineral density than did subjects with no A allele (GG; n = 46) (lumbar spine, -0.25 +/- 1.34 versus 0.48 +/- 1.70; P = 0.0014; total body, 0.25 +/- 1.01 vs 0.62 +/- 1.11; P = 0.048). These findings suggest that the ALOX15 gene is one of the genetic determinants of BMD in postmenopausal women. Accordingly, this polymorphism could be useful as a genetic marker for predicting the risk of osteoporosis.

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Therapeutic effects of alendronate 35 mg once weekly and 5 mg once daily in Japanese patients with osteoporosis: a double-blind, randomized study.

The efficacy and safety of treatment with oral alendronate (ALN) 35 mg once weekly for 52 weeks were compared with those of ALN 5 mg once daily in a double-blind, randomized, multicenter study of Japanese patients with involutional osteoporosis. The primary efficacy end point was the percent change from baseline in the lumbar spine (L1-L4) bone mineral density (BMD) after 52 weeks of treatment. In this study, 328 patients were randomized to ALN 5 mg once daily (160 patients) or ALN 35 mg once weekly (168 patients). The adjusted mean percent change from baseline in lumbar spine (L1-L4) BMD after 52 weeks of treatment was 5.8% and 6.4% in the once-daily group and the once-weekly group, respectively (both P < 0.001). The 95% confidence interval for the difference in spine BMD change between the two treatment groups was -0.31% to 1.48%, indicating that the two regimens were therapeutically equivalent, since the confidence interval fell entirely within the predefined equivalence criterion (+/-1.5%). The time course of the spine BMD increase was also similar for both regimens. Regarding total hip BMD, mean changes from baseline at 52 weeks were 2.8% and 3.0% in the once-daily group and the once-weekly group, respectively. In addition, the bone markers (urinary deoxypyridinoline, urinary type-I collagen N-telopeptides, and serum bone-specific alkaline phosphatase) were reduced to a similar level by either treatment throughout the treatment period. The tolerability and safety profiles were also similar between the treatment groups. Taken together, we conclude that the efficacy and safety of the ALN 35-mg once-weekly regimen are therapeutically equivalent to those of the ALN 5-mg once-daily regimen.

Adult↗

[Effects of concurrent therapy for patients with osteoporosis].

In the WHO technical report, vitamin D metabolites have been suggested to have a role as an adjunctive therapy when given with an antiresorptive agent. Beneficial effects on BMD have been reported following the addition of calcitriol to alendronate, etidronate, and HRT, but no data on fracture rates are available. Here we summarize our clinical study on the concurrent therapy and review reports on the concurrent treatments.

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Association of multiple nucleotide variations in the pituitary glutaminyl cyclase gene (QPCT) with low radial BMD in adult women.

UNLABELLED: Correlation between 13 genetic variations of the glutaminyl-peptide cyclotransferase gene and adjusted aBMD was tested among 384 adult women. Among 13 variations with strong linkage disequilibrium, R54W showed a prominent association (p = 0.0003), which was more striking when examined among 309 elder subjects (> or =50 years; p = 0.0001). Contribution for postmenopausal bone loss was suggested. INTRODUCTION: Alterations in homeostatic regulation of estrogen through the hypothalamus-pituitary-gonadal axis (HPG axis) importantly affect the pathogenesis of osteoporosis. Osteoporosis-susceptibility genes have been proposed in this hormonal axis, such as estrogen receptor genes and the gonadotropin-releasing hormone gene (GnRH). Here we report another example of genes: glutaminyl-peptide cyclotransferase gene (QPCT), an essential modifier of pituitary peptide hormones, including GnRH. MATERIALS AND METHODS: Analyses of association of 13 single nucleotide polymorphisms (SNPs) at the QPCT locus with adjusted areal BMD (adj-aBMD) were carried out among 384 adult women. Linkage disequilibrium (LD) was analyzed by haplotype estimation and calculation of D' and r2. Multiple regression analysis was applied for evaluating the combined effects of the variations. RESULTS AND CONCLUSIONS: LD analysis indicated strong linkage disequilibrium within the entire 30-kb region of the QPCT gene. Significant correlations were observed between the genotypes of the six SNPs and the radial adj-aBMD, among which R54W (nt + 160C>T) presented the most prominent association (p = 0.0003). Striking association was observed for these SNPs among the 309 subjects >50 years of age (R54W, p = 0.0001; -1095T>C, p = 0.0002; -1844C>T, p = 0.0002). Multiple regression analyses indicated that multiple SNPs in the gene might act in combination to determine the radial adj-aBMD. These results indicate that genetic variations in QPCT are the important factors affecting the BMD of adult women that contribute to susceptibility for osteoporosis. The data should provide new insight into the etiology of the disease and may suggest a new target to be considered during treatment.

Adult↗

Absolute height reduction and percent height ratio of the vertebral body in incident fracture in Japanese women.

Vertebral fractures are the most common complication associated with osteoporosis. The definition of prevalent or incident vertebral fractures is important in epidemiological evaluation and in clinical trials of osteoporosis treatment. There have been few reports regarding the morphometric cutoff criteria for incident fractures in Asians, and only a few reports of their occurrence in Caucasians. The aim of this study was to establish a definition for incident fractures in Japanese women. A total of 279 women, aged 64.8 +/- 9.9 (mean +/- SD) years, were recruited, and repeated thoracolumbar spinal radiographs were performed at a mean of 1.45 +/- 0.44 years after the baseline film. Vertebral fractures were graded from 0 to 3 in both baseline and follow-up films using a semiquantitative assessment by the consensus of three readers. Incident fractures were defined as an increase of grade, except grade 3, and a vertebral body height of less than 12 mm on the baseline film. As morphometric criteria, both absolute height reduction (AHr) and the percent height ratio (PHr) were calculated. Prevalent fractures were observed in 207 vertebrae (6.2%) and 85 cases (30.5%), and incident fractures in 42 vertebrae (1.3%) and 29 cases (10.4%). As morphometric criteria for incident fracture, both a PHr > or =15% and an AHr > or =3 mm or > or =4 mm indicated sensitivity of 49.17% and 50.83% and specificity of 99.92% and 99.90%, respectively. In conclusion, the morphometric criteria of incident fracture combined with a semiquantitative assessment will provide useful information in the study of clinical osteoporosis, especially for international comparisons.

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