Risk Factor For Future Fracture Research Articles

994 CURRENT SECONDARY PREVENTION AFTER HIP FRACTURE IN ENGLAND AND WALES—RESULTS FROM THE NATIONAL HIP FRACTURE DATABASE (NHFD)

Abstract Introduction National clinical audit seeks to enhance the quality of care of the 75,000 people who break their hip in the UK each year. A key aim for the National Hip Fracture Database (NHFD) is to encourage secondary fracture prevention through bone health assessment and the appropriate provision of anti-osteoporosis medication (AOM). We set out to describe trends in anti-osteoporosis medication prescription, and to examine the types of oral and injectable AOM being prescribed both before and after a hip fracture. Method We used data freely available from the NHFD www.nhfd.co.uk to analyse trends in oral and injectable AOM prescription across a quarter of a million patients presenting between 2016 and 2020, and more detailed information on the individual type of AOM prescribed for 63,284 patients from 171 hospitals in England and Wales who presented in 2020. Results Most patients (88.2%) were not taking any AOM when they presented with hip fracture. Half of all patients (49.9%) were prescribed AOM treatment by the time of discharge, but the proportion deemed ‘inappropriate for AOM’ varied hugely (0.2–83.6%) in different hospitals. Nearly two thirds (64%) of those who were previously taking an oral bisphosphonate were simply discharged on the same type of medication. The total number of patients started on oral medication fell by 11.4% over 5 years. The number started on injectable AOM almost doubled to 14.4% over the same period, but remains hugely variable across the country, with rates ranging 0–67% across different units. Conclusion A recent hip fracture is a strong risk factor for future fractures. If teams are to learn from each other’s experience and patients are to be protected against further fragility fractures the huge variability in approaches, and in particular to the use of injectables, in different trauma units across England and Wales requires further investigation.

Fragility fracture patients with a history of prior fractures more likely to present with multiple risk factors: findings from a province-wide fracture liaison service.

Our primary objective was to examine whether fragility fracture patients presenting to a provincial fracture liaison service (FLS) having a history of prior fractures, versus those without, differ in demographic characteristics and risk factors for future fracture. A secondary objective was to understand if those who report two or more prior fractures differ from those reporting one prior fracture. This cohort study included fragility fracture patients aged 50 + enrolled in the Ontario FLS between July 2017 and September 2019. Patients with versus those without prior fractures were compared on age, sex, index fracture site, biological parents' history of hip fracture, current fracture due to a fall, history of feeling unsteady when walking, history of falls in the past year, smoking, oral steroid use, and comorbid chronic conditions. Pearson's chi-square, Fischer's exact, and analysis of variance tests were used to assess differences. Among 14,454 patients, 16.8% (n = 2428) reported a history of one or more prior fractures after the age of 40. They were significantly more likely to be older, female, with a higher number of comorbidities, with greater incidence of falls, and feel unsteady when walking. Compared to those with one prior fracture, patients with greater than one prior fracture were more likely to report falls in the past year and feel unsteady when walking. Findings suggest that FLS fragility fracture patients who had sustained prior fragility fracture are an important high-risk subgroup that warrants further attention within FLS priority pathways in order to disrupt their fragility fracture cycle.

Guideline adherence by physicians for management of glucocorticoid-induced osteoporosis in Japan: a nationwide health insurance claims database study.

Adherence of physicians to guidelines for glucocorticoid (GC)-induced osteoporosis (GIO) management is currently unclear. This study aimed to clarify the state of guideline adherence by physicians in Japan and identify factors associated with guideline adherence using a nationwide health insurance claims database (NDBJ). Patients aged ≥ 50years who were prescribed GC for ≥ 90days after 180days without a GC prescription and who were followed up for osteoporosis (OP) management for the subsequent 360days during the period spanning 2012-2018 were selected from the NDBJ. Guideline adherence was evaluated with the proportion of patients who received OP management as recommended by the Japanese guidelines. Information on previous vertebral and hip fractures, dementia, and polypharmacy was obtained. Factors associated with OP management were evaluated by logistic regression analysis. A total of 512,296 patients were considered to be at high risk of fracture according to the guidelines. Proportions of patients receiving OP management (BMD testing or anti-OP medications) have increased in recent years. In 2017, 33.7% of men and 55.3% of women received OP management in the initial 90days of GC therapy. Female sex, previous anti-OP medications, polypharmacy, and higher GC dose were significantly associated with receiving OP management, while dementia showed an inverse association. A prior history of hip fracture, a strong risk factor for future fracture, was not significantly associated with receiving OP management. Although guideline adherence by physicians has increased in recent years, it remains suboptimal. Further efforts to improve guideline adherence are necessary. The present study is not registered.

Risk of Subsequent Fractures in Postmenopausal Women After Nontraumatic vs Traumatic Fractures

The burden of fractures among postmenopausal women is high. Although nontraumatic fractures are strong risk factors for future fracture, current clinical guidelines do not address traumatic fractures. To determine how future fracture risk varies according to whether an initial fracture is traumatic or nontraumatic. We conducted a prospective observational study using data from the Women's Health Initiative Study (WHI) (enrollment, September 1994-December 1998; data analysis, September 2020 to March 2021), which enrolled postmenopausal women aged 50 to 79 years at baseline at 40 US clinical centers. The WHI Clinical Trials and WHI Bone Density Substudy, conducted at 3 of the clinical centers, asked participants to report the mechanism of incident fractures. Of 75 335 participants, information regarding incident fracture and covariates was available for 66 874 participants (88.8%), who comprised the analytic sample of this study. Mean (SD) follow-up was 8.1 (1.6) years. None. Incident clinical fractures were self-reported at least annually and confirmed using medical records. Participants reported the mechanism of incident fracture as traumatic or nontraumatic. Among the 66 874 participants in the analytic sample (mean [SD] age, 63.1 [7.0] years and 65.3 [7.2] years among women without and with clinical fracture, respectively), 7142 participants (10.7%) experienced incident fracture during the study follow-up period. The adjusted hazard ratio (aHR) of subsequent fracture after initial fracture was 1.49 (95% CI, 1.38-1.61). Among women whose initial fracture was traumatic, the association between initial fracture and subsequent fracture was significantly increased (aHR, 1.25; 95% CI, 1.06-1.48). Among women whose initial fracture was nontraumatic, the association between initial fracture and subsequent fracture was also increased (aHR, 1.52; 95% CI, 1.37-1.68). Confidence intervals for associations between initial fracture and subsequent fracture were overlapping for traumatic and nontraumatic initial fracture strata. In this cohort study, among postmenopausal women older than 50 years, fracture was associated with a greater risk of subsequent fracture regardless of whether the fracture was traumatic or nontraumatic. These findings suggest that clinical osteoporosis assessment should include high-trauma as well as low-trauma fractures.

Premenopausal and early postmenopausal trabecular bone score (TBS) and fracture risk: Study of Women's Health Across the Nation (SWAN).

Evidence that trabecular bone score (TBS), an index of bone microstructure, is a risk factor for future fracture comes mainly from studies of late postmenopausal women. To discern whether premenopausal TBS or early postmenopausal TBS predict fracture. A 22-year, prospective analysis from the Study of Women's Health Across Nation. Community-based cohort. 272 Black, 174 Japanese, and 364 White women. Incident fractures: 292 in premenopausal sample and 141 in early postmenopausal sample. Separate Cox proportional hazard regressions modeled time to incident fracture as a function of TBS measured during premenopause or early postmenopause. Models were initially adjusted for age, race/ethnicity, SWAN clinical site, body mass index, use of calcium, vitamin D, bone beneficial or bone adverse medication. Next, we added lumbar spine (LS) or femoral neck (FN) bone mineral density (BMD) and, finally, history of prior fracture, to the models. For each standard deviation decrement in premenopausal TBS, fracture hazard was elevated by 17% (relative hazard [RH] 1.17 [95% CI, 1.02-1.35]); after adjusting for LS or FN BMD, the relation between premenopausal TBS and fracture was no longer statistically significant. There was a similar-magnitude, marginally statistically significant, association between early postmenopausal TBS and fracture, unadjusted for BMD (RH 1.15 [0.95-1.39]). Variation in premenopausal TBS is related to fracture risk, but this association is not independent of BMD.

The ten-year probability of fractures with the FRAX tool: which threshold for intervention to be used and how?

Objective: to analyze the clinical and organizational feasibility of using different intervention thresholds for the Russian population. Subjects and methods . The probability of fractures using the Russian FRAX model was calculated on a sample of 3,866 postmenopausal female residents from 6 cities of the Russian Federation. Different intervention thresholds, including fixed (20% for major fractures and 3% for hip fractures), age-dependent (European and Russian) ones, as well as alternative models, were analyzed. The proportion of women to be treated was estimated using different intervention thresholds. Results and discussion. The analysis of the effectiveness of the thresholds showed that the European threshold was the least appropriate one for the formed sample, since more than half (53.6%) of the women to be treated using the threshold, while the vast majority (90%) of the patients were in the younger age groups (50—54 years). There were very similar results of the effectiveness analysis of the fixed threshold (according to the USA National Osteoporosis Foundation — NOF) recommendations and that of the age-dependent threshold for Russia (in the context of the national clinical recommendations). Using the NOF approach in our sample could identify 47.8% of the postmenopausal women to be treated for osteoporosis. Their proportion rose from 29.6% of the patients aged 50—54 years to 80.6% of those aged 85 years and older. The alternative analyses of age-dependent thresholds showed great effectiveness when the fracture was considered not as a risk factor for future fractures, but as a clinical disease manifestation that was sufficient to recommend that the patient should be treated without FRAX counting. However, with their use, the proportion of older people to be treated remains not high enough. In this connection, there remains a need to search for the more adequate application of the existing intervention threshold or to develop a new, for example, hybrid variant of the age-dependent threshold.

Imminent risk of fracture after fracture.

A history of fracture is a strong risk factor for future fractures. The aim of the present study was to determine whether the predictive value of a past MOF for future MOF changed with time. The study was based on a population-based cohort of 18,872 men and women born between 1907 and 1935. Fractures were documented over 510,265 person-years. An extension of Poisson regression was used to investigate the relationship between the first MOF and the second. All associations were adjusted for age and time since baseline. Five thousand thirty-nine individuals sustained one or more MOFs, of whom 1919 experienced a second MOF. The risk of a second MOF after a first increased by 4% for each year of age (95% CI 1.02-1.06) and was 41% higher for women than men (95% CI 1.25-1.59). The risk of a second MOF was highest immediately after the first fracture and thereafter decreased with time though remained higher than the population risk throughout follow-up. For example, 1year after the first MOF, the risk of a second fracture was 2.7 (2.4-3.0) fold higher than the population risk. After 10years, this risk ratio was 1.4 (1.2-1.6). The effect was more marked with increasing age. The risk of MOF after a first MOF is increased over the whole follow-up, but the imminent risk is even higher. If the acute increment in risk in the few years following MOF is amenable to therapeutic intervention, then immediate short-term treatments may provide worthwhile clinical dividends in a very cost-effective manner, particularly in the elderly.

Assessment of bone mineral content and fracture risk: a UK prospective cohort study

BackgroundPoor early growth is associated with reduced adult bone mineral content (BMC), but not bone mineral density (BMD). Although low BMD is a well-established risk factor for future fracture, little is known about the performance characteristics of BMC in fracture prediction. We therefore investigated the predictive value of bone area, BMC, and BMD for incident fracture in a prospective cohort of UK women. MethodsWomen aged 20–80 years, recruited from four general practices in Southampton, underwent assessment by dual energy X-ray absorptiometry between 1991 and 1993. All women were then contacted in 1998–99 with a validated postal questionnaire to collect information on incident fractures and potential confounding factors including medication use. All fractures were confirmed by assessment of images and radiology reports by a research nurse. Cox proportional hazards models were used to explore the risk of incident fracture and results expressed as gradient of risk (GR) and 95% CI. Associations were adjusted for age, body-mass index, alcohol consumption, smoking, hormone replacement therapy, medications, and history of fracture. This study was approved by the Southampton Joint Ethics Committee. Findings674 women were recruited and 443 responded to the questionnaire. 55 women (12%) reported a fracture. In fully adjusted models, femoral neck BMC and BMD were similarly predictive of incident fracture (GR 1·64, 95% CI 1·19–2·26 [p=0·002] and 1·76, 1·19–2·60 [p=0·005], respectively). By contrast, femoral neck bone area was not associated with incident fracture (1·15, 0·88–1·50; p=0.32). Similar results were found with bone indices at the lumbar spine and whole body. InterpretationBMC and BMD seem to predict incident fracture with similar gradients of risk, even after adjustment for body size. These findings suggest that factors in early life that are associated with total skeletal mineralisation are likely to have implications for adult fracture risk. FundingMedical Research Council; British Heart Foundation; Arthritis Research UK; National Osteoporosis Society; International Osteoporosis Foundation; National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust; NIHR Musculoskeletal Biomedical Research Unit, University of Oxford.

Association between trabecular bone score and risk factors for fractures in Korean female patients with rheumatoid arthritis

Objective: To identify the association between trabecular bone score (TBS) and other known risk factors for fractures in rheumatoid arthritis (RA) patients.Methods: One hundred female RA patients aged ≥50 years were enrolled. The following risk factors for fracture were selected: prevalent vertebral fracture (VF), bone mineral density (BMD), TBS, and 10-year probability of major osteoporotic fracture by FRAX® (MOF-FRAX scores). The associations between risk factors were identified, and accuracy of TBS, BMD, and FRAX scores to detect the prevalent VF, the strongest risk factor for future fracture, were assessed.Results: Twenty-six patients were revealed to have moderate to severe VFs. There was a modest negative correlation between MOF-FRAX score and TBS (r = −0.367, p < 0.01), while there was no correlation between MOF-FRAX score and L-spine BMD (r = −0.050, p = 0.62). The areas under curves (AUCs) were 0.818, 0.683, and 0.518 for the MOF-FRAX score, TBS, and L-spine BMD, respectively. Among patients with glucocorticoids (GC) use (n = 57), AUCs were 0.762, 0.758, and 0.448 for their MOF-FRAX score, TBS, and L-spine BMD, respectively.Conclusions: TBS showed better correlation with MOF-FRAX score than BMD, and it was superior to BMD in identifying prevalent VFs in RA patients, especially who are in use of GCs.

Prior fracture as a risk factor for future fracture in an Australian cohort.

This study investigated the influence of prior fracture on the risk of subsequent fracture. There was a higher risk of subsequent fracture in both young and older adult age groups when Australian males or females had already sustained a prior fracture. Fracture prevention is important throughout life for both sexes. The purpose of this study was to determine the impact of prior fracture on the risk of subsequent fracture across the adult age range in Australian males and females. All-cause fractures were grouped into age categories for males and females enrolled in the Geelong Osteoporosis Study (Australia) using retrospective self-report data and prospective radiology-confirmed data. For all age categories, the relative risk (RR and 95% confidence interval (CI)) of subsequent fracture in a later age category was compared between those with prior fracture and those without. For both sexes, childhood fracture increased the risk of subsequent fracture in adolescence (males: RR 21.7; 95% CI 16.0, 27.4; females: RR 8.1; 3.5, 12.8). Males with adolescent fracture had increased risk of subsequent fracture in early adulthood (RR 11.5; 5.7, 17.3) and mid-adulthood (RR 13.0; 6.3, 19.7). Additionally, males with young adulthood or mid-adulthood fracture had increased risk of subsequent fracture in the following age group (RR 11.2; 4.4, 17.9, and RR 6.2; 0.8, 11.7, respectively). Mid-adult fractures increased the risk of subsequent fracture in older adulthood (RR 6.2; 0.8, 11.7). Females with childhood or adolescent fracture had an increased risk of fracture in young adulthood (RR 4.3; 0.7, 7.9, and RR 10.5; 4.4, 16.6), and prior fracture in older adult life increased the risk of subsequent fracture in old age (RR 14.9; 6.4. 23.3). Fracture prevention strategies may be more effective if attention is directed towards individuals with prior fracture at any age as they have a higher likelihood of sustaining a subsequent fracture later in life.

Mild morphometric vertebral fractures predict vertebral fractures but not non-vertebral fractures

In this meta-analysis of the control arms of four phase 3 trials, mild vertebral fractures were a significant risk factor for future vertebral fractures but not for non-vertebral fracture. A prior vertebral fracture is a risk factor for future fracture that is commonly used as an eligibility criterion for treatment and in the assessment of fracture probability. The aim of this study was to determine the prognostic significance of a morphometric fracture according to the severity of fracture. We examined the control (placebo) treated arms of four phase 3 trials. Vertebral fracture status was graded at baseline in 7,623 women, and fracture outcomes were documented over the subsequent 20,000 patient-years. Fracture outcomes were characterised as a further vertebral fracture, a non-vertebral fracture or a clinical fracture (non-vertebral plus clinical vertebral fracture). The relative risk of fracture was computed from the merged β coefficients of each trial weighted according to the variance. Mild vertebral fractures were a significant risk factor for vertebral fractures [risk ratio (RR) = 2.17; 95% CI = 1.70-2.76] but were not associated with an increased risk of non-vertebral fractures (RR = 1.08; 95% CI = 0.86-1.36). Moderate/severe vertebral fractures were associated with a high risk of vertebral fractures (RR = 4.23; 95% CI = 3.58-5.00) and a moderate though significant increase in non-vertebral fracture risk (RR = 1.64; 95% CI = 1.38-1.94). Prior moderate/severe morphometric vertebral fractures are a strong and significant risk factor for future fracture. The presence of a mild vertebral fracture is of no significant prognostic value for non-vertebral fractures. These findings should temper the use of morphometric fractures in the assessment of risk and the design of phase 3 studies.

SP0063 Osteoporosis implications for primary care

Recent decades have seen the emergence of a number of major pharmacological interventions to reduce the risk of osteoporotic fracture. The most commonly used agents in Europe are the bisphosphonates,...

Defining High Risk of Osteoporotic Fracture

: There is no universally accepted definition for patients at high risk of osteoporotic fracture. : This study aimed to survey Spanish rheumatologists; to obtain opinions about risk factors, and an acceptable definition for patients at high risk of osteoporotic fracture; and to compare daily practice patterns with current osteoporosis guidelines. : A total of 174 rheumatologists from throughout Spain completed an online survey about various risk factors for fragility fracture and about the management of patients with osteoporosis in clinical practice. Results were reviewed by a coordinating committee of osteoporosis experts and were compared with published national and international guideline recommendations. : Almost all rheumatologists who completed the survey (99%) consider that a group of patients exists with a high risk of osteoporotic fracture and that this group should be managed appropriately. Previous fracture is considered the most important risk factor, particularly in cases of multiple fracture, severe vertebral fracture, hip fracture, or fracture despite osteoporosis treatment. However, in osteoporosis guidelines, age, bone mineral density, and previous fragility fracture are the most important risk factors for new fracture. Furthermore, Spanish rheumatologists tend to treat patients at high risk of fracture with anabolic therapy (e.g., teriparatide), whereas guidelines make no such recommendation. : In osteoporosis, a large gap exists between implementation of guideline recommendations and actual clinical practice; this may be due, in part, to heterogeneity among existing guidelines. Thus, inclusion in guidelines of a practical definition of high risk of osteoporotic fracture may provide significant opportunities to improve patient care and prevent future fragility fractures. :

Biomechanics of Vertebral Fractures and the Vertebral Fracture Cascade

Vertebral fractures (VFxs) are the most common osteoporotic fracture, and are a strong risk factor for future fracture. The presence of a VFx greatly increases the risk of sustaining subsequent VFxs-a phenomenon often referred to as the "vertebral fracture cascade." VFxs do not occur uniformly along the spine, but occur more often at the mid-thoracic and thoracolumbar regions than elsewhere. It is likely that both the vertebral fracture cascade and the bimodal distribution of VFx along the spine are attributable to biomechanical factors. VFxs occur when the forces applied to the vertebral body exceed its strength. Loading on the spine is primarily determined by a person's height, weight, muscle forces, and the task or movement performed, but can also be affected by other factors, such as spinal curvature and invertebral disk deterioration. Vertebral strength is determined mainly by bone size, shape, and bone mineral density, and secondarily by bone microarchitecture, collagen characteristics, and microdamage. Better understanding of VFx etiology is hampered by the fact that most VFxs do not come to clinical attention; therefore, the factors and activities that cause VFxs remain ill defined, including possible differences in the etiology of acute fractures versus those of slow onset. Additional research is needed to elucidate the precise mechanical, morphologic, and biological mechanisms that underlie VFx to improve strategies for assessing VFx risk and preventing the vertebral fracture cascade.

Low rates of treatment in postmenopausal women with a history of low trauma fractures: results of audit in a Fracture Liaison Service

A past history of low trauma fracture is a strong risk factor for future fractures in postmenopausal women and national guidance recommends treatment in the majority of such women To establish the prevalence of bone protective therapy use in postmenopausal women with a history of low trauma fracture Design and Clinical audit of 1641 postmenopausal women presenting with a low trauma fracture to the Fracture Liaison Service at Addenbrooke's Hospital, Cambridge between January 2006 and December 2007. A total of 526 (31%) women presenting with a fracture had a past history of fracture, defined as a low trauma fracture after the age of 45 years. The wrist was the most common site of previous fracture, followed by hip, hand or foot, lower leg and humerus. Of these women, only 27.6% were receiving bone protective therapy with a bisphosphonate (89%) or other medication. Calcium and vitamin D supplements were received by 35.6%. The highest rates of treatment were seen for spine and hip fracture (61.9 and 49.3%, respectively). Only 45.1% of women aged 75 years and over with a previous history of fracture were receiving bone protective therapy. The results of our audit demonstrate low rates of treatment in postmenopausal women with a history of low trauma fracture. Better education of healthcare professionals, more consistent recording of fractures in primary care and the use of clearly defined care pathways that involve patients and their carers provide rational approaches to reducing this care gap.

Simply Ask Them About Their Balance--Future Fracture Risk in a Nationwide Cohort Study of Twins

The principal causal components of an osteoporotic fracture are a fall and weakened bone strength. While bone quality measures have been frequently studied, the ability of simple measures of impaired balance to predict fracture risk has received less attention. Computer-assisted telephone interviews were conducted between 1998 and 2000 among 24,598 Swedish twins aged 55 years or older. Impaired balance at the time of interview was reported by 2,890 (12%) of the twins. Twin pairs who were discordant with regard to impaired balance were selected for analysis and followed for fractures through 2005. In a pairwise analysis, the odds ratio for hip fracture was 3.13 (95% confidence interval (CI): 1.62, 6.05) among twins with impaired balance as compared with their co-twins with normal balance. When previously recognized clinical risk factors for osteoporotic fracture were considered in the model, the odds ratio for hip fracture with impaired balance was 3.88 (95% CI: 1.40, 10.72). Approximately 40% of all hip fractures were attributable to impaired balance. The odds ratios for any fracture and any osteoporotic fracture for twins with impaired balance were 2.00 (95% CI: 1.29, 3.11) and 2.39 (95% CI: 1.49, 3.82), respectively. These results imply that self-reported impaired balance is a novel and readily assessed risk factor for future fractures in the elderly.

The synergistic effect of bone mineral density and methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) on fractures

A functional polymorphism in methylenetetrahydrofolate reductase (MTHFR) has been identified at codon 677 (C677T). The T-allele variant (valine type) has lower enzyme activity than the wild type (C-allele or alanine type), resulting in a slightly elevated homocysteine level, which has been recently recognized as a risk factor for fracture. However, whether subjects bearing the T allele have higher susceptibility to fractures is still controversial. We have investigated the effects of MTHFR polymorphism on fracture susceptibility in Japanese postmenopausal women. A total of 502 postmenopausal ambulatory Japanese women were followed up for 5.1 +/- 3.4 (mean +/- SD) years, and a total of 155 patients with incident fractures (121 patients with vertebral fractures and 34 cases with fractures at other sites) were recorded. When compared with the patients without any fractures, the patients with incident fractures were older, had more prevalent fractures, had higher urinary levels of bone turnover markers as well as plasma homocysteine level, but were shorter in body height and had lower bone mineral density. The prevalence of the TT genotype of MTHFR was significantly higher in the patients with incident fractures compared to the other genotypes. The subjects with the TT genotype had a higher incidence rate of fracture and higher plasma level of homocysteine than the subjects bearing the non-TT genotype. This relationship was observed in both osteoporotic and nonosteoporotic groups. The hazard ratio for TT genotype without osteoporosis, non-TT genotype with osteoporosis, and TT genotype with osteoporosis was 1.49 (0.91-2.45), 3.64 (2.50-5.29), and 7.21 (4.34-11.97), respectively, compared to the non-TT genotype without osteoporosis. A higher hazard ratio for the TT genotype with osteoporosis was still apparent after adjustment for age, body size, and number of prevalent vertebral fractures. These results indicate that the TT genotype of MTHFR may be a risk factor for future fracture in addition to the traditional risk factors.

Daily practice using the guidelines for prevention and treatment of osteoporosis. How do we realize the bone quality in routine practice using Japanese guideline for osteoporosis prevention and treatment?

Bone quality is thought to encompass the structural and material properties of bone that are affected by turnover rate. The concept of bone quality is included in Japanese Guideline for Osteoporosis prevention and treatment. Evidence has accumulated that collagen cross-links play important roles in bone strength. We have demonstrated that the quantitative and qualitative deterioration of lysyl oxidase controlled and non-enzymatic cross-links (Advanced glycation end products, AGEs, Pentosidine) of collagen in patients with osteoporotic femoral neck fracture cases might be affected by hyperhomocysteinemia (Saito M, Calcif Tissue Int, 2006), oxidative stress, vitamin B status (Saito M, Osteoporos Int, 2006) . Recently, Shiraki et al. demonstrated that a functional polymorphism in methylenetetrahydrofolate reductase (MTHFR) polymorphism, T allele (C677T), may be a risk factor for future fracture in addition to the traditional risk factors (Shiraki M, Saito M, et al., J Bone Miner Metab, in press). In addition, we have reported that a higher urinary pentosidine was an independent risk factor, for vertebral fracture in a 5-year prospective study in Japanese women (Shiraki M, Saito M, et al., J Bone Miner Metab, 2008). If confirmed in large, prospective trials, measurement of serum homocysteine and serum or urinary excretion of pentosidine might be characterized as markers reflecting bone collagen deterioration.

The relationship of an Asian-specific screening tool for osteoporosis to vertebral deformity and osteoporosis

An Asian-specific screening tool for osteoporosis, the so-called OSTA index, was devised and is likely to be helpful in determining which postmenopausal women need bone mineral density (BMD) measurement. Besides BMD, prevalent vertebral fracture is a strong risk factor for future fractures. However, the relationship of the OSTA index to prevalent vertebral fractures is currently unknown. In this study, we evaluated the performance of the OSTA index in elderly Thai women and assessed the relationship of the index to prevalent vertebral deformities. Subjects consisted of 741 healthy Thai elderly women. BMD was measured by DEXA and T-score <or=2.5 SD is defined as osteoporosis. Prevalent vertebral deformities were determined by morphometric X-ray absorptiometry. OSTA index >-1 is classified as having low risk of osteoporosis, -1 to -4 as intermediate risk and, <-4 as high risk. Data were expressed as mean +/- SD. The mean age and body weight of subjects were 67 +/- 4.8 years and 57.8 +/- 8.7 kg, respectively. The area under the ROC curve for OSTA index to identify osteoporosis at femoral neck and lumbar spine was 0.80 and 0.72, respectively. Femoral neck osteoporosis was found in 40.4%, 6.3%, and 2.4% of subjects with high-risk, intermediate-risk, and low-risk OSTA indexes, respectively. With regard to vertebral deformities, the area under the ROC curve relating OSTA index to vertebral deformities was 0.70 (P < 0.001). The prevalence of vertebral deformities in according to the OSTA index was 19.2% in the high-risk, 7.9% in the intermediate-risk, and 2.8% in the low-risk group. We concluded that the OSTA index can be of assistance in the selection of postmenopausal women for BMD measurement. In addition, this index may be helpful in the identification of postmenopausal women with vertebral deformity and those who need antifracture treatments.

Hyperkyphotic posture and risk of future osteoporotic fractures: the Rancho Bernardo study.

It is unknown whether kyphosis of the thoracic spine is an independent risk factor for future osteoporotic fractures. In 596 community-dwelling women, we found that with increasing kyphosis, there was a significant trend of increasing fracture risk that was independent of previous history of fractures or BMD. It is unknown whether kyphosis of the thoracic spine is an independent risk factor for future osteoporotic fractures. We conducted a prospective cohort study of 596 community-dwelling women, 47-92 years of age. Between 1988 and 1991, BMD of the hip and spine and kyphosis were measured. Kyphosis was measured by counting the number of 1.7-cm blocks necessary to place under the occiput so participants could lie flat without neck hyperextension. New fractures were reported over an average follow-up of 4 years. Using a cut-off of at least one block, 18% of the participants had hyperkyphotic posture (range, one to nine blocks). There were 107 women who reported at least one new fracture (hip, spine, wrist, clavicle, shoulder, arm, hand, rib, pelvis, leg, or ankle). In logistic regression analyses, older women with hyperkyphotic posture (defined as at least one block) had a 1.7-fold increased risk of having a future fracture independent of age, prior fracture, and spine or hip BMD (95% CI: 1.00-2.97; p = 0.049). There was a significant trend of increasing fracture risk with increasing number of blocks, with ORs ranging from 1.5 to 2.6 as the number of blocks increased from one to at least three blocks compared with those with zero blocks (trend p = 0.03; models adjusted for age, baseline fracture, spine or hip BMD). Stratification by baseline fracture status and controlling for other possible confounders or past year falls did not change the results. Whereas hyperkyphosis may often result from vertebral fractures, our study findings suggest that hyperkyphotic posture itself may be an important risk factor for future fractures, independent of low BMD or fracture history.