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This paper reviews the possibilities offered by X-ray micro-CT in bone tissue engineering. This technique provides a fast, nondestructive, and 3D quantification of bone scaffolds, bone ingrowth, and microvascularization. Synchrotron radiation absorption and phase micro-CT offer additional advantages to image newly formed bone in bioceramic scaffolds and pre-bone matrix. [ABSTRACT FROM AUTHOR]

In this paper, some examples from the literature or from my own experience will be given to illustrate the influence of surface topography and surface chemistry at the nano- and micro-scale on the cell and tissue response. [ABSTRACT FROM AUTHOR]

Summary: This paper presents a prospective study on factors that could influence fracture risk after percutaneous vertebroplasty (PVP) in 115 osteoporotic patients. The mean follow-up was 39 months. The incidence of new fractures after PVP was 27.8%. Low body mass index (BMI), bone mineral density (BMD), and vitamin D are factors associated with increased risk of new fractures. Introduction: The purpose of this study was to evaluate factors that could increase the occurrence of new vertebral fractures (VFx) after PVP. Methods: In our prospective study, we included patients of both sexes with osteoporosis (OP) and at least one painful VFx. We performed a baseline biochemical evaluation (including vitamin D plasma levels) and collected demographic, BMD, and clinical data. One hundred fifteen patients were treated with PVP and assigned to oral bisphosphonates plus Ca and vitamin D. The patients returned to control visits after 1, 3, and 6 months and every 6 months thereafter. X-rays film of the dorsolumbar spine was repeated every 12 months, or in case of pain that would suggest VFx occurrence. Results: The mean follow-up was 39 ± 16 months (range, 15-79). Thirty-two patients (27.8%) had new fragility VFx, all symptomatic. All the fractured patients agreed to undergo a new PVP. We compared the patients who had new VFx to those who had not, and we found significantly lower BMI, total hip, and femoral neck T-scores in the group with new VFx. Furthermore, baseline plasma levels of 25(OH) vitamin D (25(OH)D) were significantly lower in this group. Upon analyzing plasma levels of 25(OH)D 12 months after PVP, we found that a significant difference still persisted: 22 ± 12 (group with new VFx) vs . 41 ± 22 ng/ml (group with no VFx; p < 0.01). Conclusion: We found that in patients with OP treated with PVP, the incidence of new VFx was 27.8% after 39 months; low BMI, BMD, and vitamin D are factors associated with increased risk of new VFx in patients treated with PVP. [ABSTRACT FROM AUTHOR]

Summary: This paper reviews the evidence for an association between atypical subtrochanteric fractures and long-term bisphosphonate use. Clinical case reports/reviews and case-control studies report this association, but retrospective phase III trial analyses show no increased risk. Bisphosphonate use may be associated with atypical subtrochanteric fractures, but the case is yet unproven. Introduction: A Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and the International Osteoporosis Foundation has reviewed the evidence for a causal association between subtrochanteric fractures and long-term treatment with bisphosphonates, with the aim of identifying areas for further research and providing recommendations for physicians. Methods: A PubMed search of literature from 1994 to May 2010 was performed using key search terms, and articles pertinent to subtrochanteric fractures following bisphosphonate use were analysed. Results: Several clinical case reports and case reviews report a possible association between atypical fractures at the subtrochanteric region of the femur in bisphosphonate-treated patients. Common features of these 'atypical' fractures include prodromal pain, occurrence with minimal/no trauma, a thickened diaphyseal cortex and transverse fracture pattern. Some small case-control studies report the same association, but a large register-based study and retrospective analyses of phase III trials of bisphosphonates do not show an increased risk of subtrochanteric fractures with bisphosphonate use. The number of atypical subtrochanteric fractures in association with bisphosphonates is an estimated one per 1,000 per year. It is recommended that physicians remain vigilant in assessing their patients treated with bisphosphonates for the treatment or prevention of osteoporosis and advise patients of the potential risks. Conclusions: Bisphosphonate use may be associated with atypical subtrochanteric fractures, but the case is unproven and requires further research. Were the case to be proven, the risk-benefit ratio still remains favourable for use of bisphosphonates to prevent fractures. [ABSTRACT FROM AUTHOR]

Summary: The study cohort comprised 196 females and 163 males. Lumbar spine bone mineral density (BMD) and magnetic resonance imaging (MRI) were acquired. Females had more severe disc degeneration than males. Lumbar spine lower BMD was associated with less severe disc degeneration. Lumbar disc spaces were more likely to be narrower when vertebral BMD was higher. Introduction: The purpose of this paper is to study the relationship between gender, BMD, and disc degeneration in the lumbar spine. Methods: The study cohort comprised 196 females and 163 males (age range 67-89 years) with no age difference between the two groups. Lumbar spine BMD was measured with dual X-ray densitometry, and MRI was acquired at 1.5 T. A subgroup of 48 males had additional lumbar vertebral quantitative computerized tomography densitometry. Lumbar disc degeneration was assessed using a MRI-based eight-level grading system. Results: Female subjects had more severe disc degeneration than male subjects. After removing age effect, a positive trend was observed between T-score and severity of lumbar disc degeneration. This was significant in female subjects while not significant in male subjects. Lumbar disc spaces were more likely to be narrowed when vertebral BMD was higher. These observations were more significant in the midlumbar region (L3/4 and L4/5) and less so at the thoracolumbar junction. Conclusion: Female subjects tended to have slightly more severe lumbar disc degeneration than male subjects. Lower lumbar spine BMD was associated with less severe disc degeneration. [ABSTRACT FROM AUTHOR]

Hand radiographs are obtained routinely to determine bone age of children. This paper presents a method that determines a Paediatric Bone Index automatically from such radiographs. The Paediatric Bone Index is designed to have minimal relative standard deviation (7.5%), and the precision is determined to be 1.42%. We present a computerised method to determine bone mass of children based on hand radiographs, including a reference database for normal Caucasian children. Normal Danish subjects (1,867), of ages 7–17, and 531 normal Dutch subjects of ages 5–19 were included. Historically, three different indices of bone mass have been used in radiogrammetry all based on $$ A = \pi {\text{ }}T{\text{ }}W\left( {{\text{1}} - T/W} \right) $$, where T is the cortical thickness and W the bone width. The indices are the metacarpal index A/ W2, DXR-BMD = A/ W, and Exton-Smith’s index A/( WL), where L is the length of the bone. These indices are compared with new indices of the form A/( W a L b), and it is argued that the preferred index has minimal SD relative to the mean value at each bone age and sex. Finally, longitudinal series of X-rays of 20 Japanese children are used to derive the precision of the measurements. The preferred index is A/( W1.33 L0.33), which is named the Paediatric Bone Index, PBI. It has mean relative SD 7.5% and precision 1.42%. As part of the BoneXpert method for automated bone age determination, our method facilitates retrospective research studies involving validation of the proposed index against fracture incidence and adult bone mineral density. [ABSTRACT FROM AUTHOR]

Our objective was to determine international estimates of the economic burden of falls in older people living in the community. Our systematic review emphasized the need for a consensus on methodology for cost of falls studies to enable more accurate comparisons and subgroup-specific estimates among different countries. The purpose of this study was to determine international estimates of the economic burden of falls in older people living in the community. This is a systematic review of peer-reviewed journal articles reporting estimates for the cost of falls in people aged ≥60 years living in the community. We searched for papers published between 1945 and December 2008 in MEDLINE, PUBMED, EMBASE, CINAHL, Cochrane Collaboration, and NHS EED databases that identified cost of falls in older adults. We extracted the cost of falls in the reported currency and converted them to US dollars at 2008 prices, cost items measured, perspective, time horizon, and sensitivity analysis. We assessed the quality of the studies using a selection of questions from Drummond’s checklist. Seventeen studies met our inclusion criteria. Studies varied with respect to viewpoint of the analysis, definition of falls, identification of important and relevant cost items, and time horizon. Only two studies reported a sensitivity analysis and only four studies identified the viewpoint of their economic analysis. In the USA, non-fatal and fatal falls cost US $23.3 billion (2008 prices) annually and US $1.6 billion in the UK. The economic cost of falls is likely greater than policy makers appreciate. The mean cost of falls was dependent on the denominator used and ranged from US $3,476 per faller to US $10,749 per injurious fall and US $26,483 per fall requiring hospitalization. A consensus on methodology for cost of falls studies would enable more accurate comparisons and subgroup-specific estimates among different countries. [ABSTRACT FROM AUTHOR]

This position paper of the International Osteoporosis Foundation makes recommendations for vitamin D nutrition in elderly men and women from an evidence-based perspective. [ABSTRACT FROM AUTHOR]

This paper reviews briefly the development and clinical use of FRAX® in the development of assessment guidelines for osteoporosis. Fractures are the clinical consequence of osteoporosis and are a major cause of morbidity and mortality worldwide. Several treatments are available that have been shown to decrease the risk of fracture, but problems arise in identifying individuals at high fracture risk so that treatments can be effectively targeted. Case finding can be enhanced by the consideration of clinical risk factors that provide information on fracture risk over and above that provided by bone mineral density measurements. The FRAX tool integrates information on fracture risk from clinical risk factors with or without the use of BMD and can be used to improve the targeting of individuals at high fracture risk. [ABSTRACT FROM AUTHOR]

This paper provides recommendations for fair and unbiased relationship between academic scientists and the pharmaceutical industry. Real or perceived problems in the relationship between academics and the industry have been the subject of much recent debate. It has been suggested that academic clinicians should sever all links with the industry—a view that is rarely challenged. Academic experts and members of the pharmaceutical industry were invited to an expert consensus meeting to debate this topic. This meeting was organized by the Group for the Respect of Ethics and Excellence in Science. Conflict of interest, competing interest, right and duties of academic scientist, authorship, and staff and student education were discussed. Guidelines for a transparent, ethical, strong, and successful partnership between the academic scientist and the pharmaceutical industry have been provided. The Group support interactions between the industry and clinicians provided that it is transparent and ethical. [ABSTRACT FROM AUTHOR]

While hip protectors are effective in some clinical trials, many, including all in community settings, have been unable to demonstrate effectiveness. This is due partly to differences in the design and analysis. The aim of this report is to develop recommendations for subsequent clinical research. In November of 2007, the International Hip Protector Research Group met to address barriers to the clinical effectiveness of hip protectors. This paper represents a consensus statement from the group on recommended methods for conducting future clinical trials of hip protectors. Consensus recommendations include the following: the use of a hip protector that has undergone adequate biomechanical testing, the use of sham hip protectors, the conduct of clinical trials in populations with annual hip fracture incidence of at least 3%, a run-in period with demonstration of adequate adherence, surveillance of falls and adherence, and the inclusion of economic analyses. Larger and more costly clinical trials are required to definitively investigate effectiveness of hip protectors. [ABSTRACT FROM AUTHOR]

Hip protectors represent a promising strategy for preventing fall-related hip fractures. However, clinical trials have yielded conflicting results due, in part, to lack of agreement on techniques for measuring and optimizing the biomechanical performance of hip protectors as a prerequisite to clinical trials. In November 2007, the International Hip Protector Research Group met in Copenhagen to address barriers to the clinical effectiveness of hip protectors. This paper represents an evidence-based consensus statement from the group on recommended methods for evaluating the biomechanical performance of hip protectors. The primary outcome of testing should be the percent reduction (compared with the unpadded condition) in peak value of the axial compressive force applied to the femoral neck during a simulated fall on the greater trochanter. To provide reasonable results, the test system should accurately simulate the pelvic anatomy, and the impact velocity (3.4 m/s), pelvic stiffness (acceptable range: 39-55 kN/m), and effective mass of the body (acceptable range: 22-33 kg) during impact. Given the current lack of clear evidence regarding the clinical efficacy of specific hip protectors, the primary value of biomechanical testing at present is to compare the protective value of different products, as opposed to rejecting or accepting specific devices for market use. [ABSTRACT FROM AUTHOR]

This study estimated the 10-year probability of osteoporotic fracture in Hong Kong Southern Chinese based on a simplified model of the recently developed WHO fracture risk prediction tool (FRAX®). Thus, the data provides further insights into potential development of a population-specific FRAX® model for Hong Kong in the future. The purpose of this paper was to estimate the 10-year probability of osteoporotic fracture in Hong Kong (HK) Southern Chinese according to age and bone mineral density (BMD) T-score at the femoral neck based on the methodology of the FRAX® risk assessment tool calibrated to the epidemiology of HK. Hip fracture data was obtained from the Clinical Data Analysis Reporting System (CDAS) of the Hospital Authority of HK and population size and death rates were taken from the HK Government Census and Statistics Department. Fracture probability was calculated using the cut-off values for T-scores derived from the NHANES III data for Caucasian women aged 20–29 years for BMD at the femoral neck. In this study, the 10-year probability of osteoporotic fracture in HK Southern Chinese increased markedly with increasing age and decreasing femoral neck BMD T-scores in both women and men. Interestingly, at low T-scores, the increase in 10-year probability of osteoporotic fracture in women with age was greater than in men. Fracture probabilities were substantially higher than those from mainland China. Based on this evidence, and until we have HK Southern Chinese population-specific information, we recommend the application of the Caucasian risk profile to calculate the absolute fracture risk for HK Southern Chinese subjects. [ABSTRACT FROM AUTHOR]

Using a Markov state-transition model, we estimated fractures averted with risedronate using two different types of clinical efficacy data. Summary data, as opposed to individual patient data (IPD), underestimated the number of fractures averted when applied in a specified high risk population. The choice of clinical efficacy data is an important consideration in health economic models evaluating osteoporosis therapies. This paper contrasts fracture reduction estimates for risedronate utilizing efficacy data from two approaches to meta-analysis: summary data versus individual patient data. We also examined differences in fracture reduction explained by varied cohort selection, especially the inclusion of low- versus high-risk populations. Using a Markov state-transition model, we compared fractures averted over 3 years in a hypothetical cohort by inputting fracture risk reduction estimates (risedronate versus placebo) from two data sources (summary data versus IPD). The cohort consisted of 100,000 Canadian women, age ≥65 years with osteoporosis (WHO criteria T-score ≤ -2.5) and prevalent morphometric vertebral fracture. Non-vertebral fractures averted with risedronate were: 3,571 and 6,584 per 100,000 women for summary data and IPD, respectively. For vertebral fractures, the numbers were 8,552 and 10,127. When IPD versus summary data was used, an additional 3,013 more non-vertebral fractures and 1,575 vertebral fractures were averted. Relative risk estimates from IPD analyses were the best choice for modelling fracture outcomes when applied in a specified high-risk population. In addition to superior statistical methodology, they utilized RCT cohorts that are more representative of higher risk patients requiring treatment (osteoporotic women ≥65 years with a prevalent vertebral fracture). [ABSTRACT FROM AUTHOR]

One year of once weekly alendronate, when given shortly after the surgical repair of a hip fracture, produces reductions in bone markers and increases proximal femoral bone density. The therapy was well tolerated. Hip fracture is the most devastating type of osteoporotic fracture and increases notably the risk of subsequent fractures. The aim of this paper was to evaluate the effects of 1 year therapy with a weekly dose of alendronate in the bone mineral density and bone markers in elderly patients after low trauma hip fracture repair. Two hundred thirty-nine patients (81 ± 7 years; 79.8% women) were randomized to be treated either with calcium (500 mg/daily) and vitamin D3 (400 IU/daily; Ca–Vit D group) or with alendronate (ALN, 70 mg/week) plus calcium and vitamin D3 (500 mg/daily and 400 IU/daily, respectively; ALN + Ca–Vit D group). One hundred forty-seven (61.5%) patients completed the trial. Alendronate increased proximal femoral bone mineral density (BMD) in the intention-to-treat analysis (mean difference (95% confidence interval); total hip 2.57% (0.67; 4.47); trochanteric 2.96% (0.71; 5.20), intertrochanteric 2.32% (0.36; 4.29)), but the differences were not significant in the BMD of the femoral neck (0.47%; (−2.03; 2.96) and the lumbar spine (0.69%; (−0.86; 2.23)). Bone turnover markers decreased during alendronate treatment. The present study demonstrates for the first time the anti-resorptive efficacy of alendronate given immediately after surgical repair in an elderly population with recent hip fracture. This effect should positively affect the rate of subsequent fractures. [ABSTRACT FROM AUTHOR]

We performed a meta-analysis of cross-sectional studies on serum 25(OH)D status globally. Serum 25(OH)D levels on average were 54 nmol/l, were higher in women than men, and higher in Caucasians than in non-Caucasians. There was no trend in serum 25(OH)D level with latitude. Vitamin D deficiency was widespread. We studied vitamin D status (expressed as serum 25-hydroxy-vitamin D [25(OH)D]) in native subjects worldwide. Meta-analysis and meta-regression of studies reporting on 25(OH)D in healthy subjects retrieved from Pubmed, Embase and Web of Science using the terms “serum”, “25-hydroxy-vitamin D”, “cholecalciferol”, and “human”. A total of 394 studies were included. The mean 25(OH)D level was 54 nmol/l (95% CI: 52–57 nmol/l). Women had borderline significantly higher 25(OH)D levels than men, and Caucasians had higher levels than non-Caucasians. 25(OH)D levels were higher in subjects aged >15 years than in younger subjects. Unadjusted there was no significant decrease in 25(OH)D with latitude (slope of curve −0.03 ± 0.12 nmol/l per degree latitude north or south of equator, p = 0.8). There was a significant decline with latitude for Caucasians (−0.69 ± 0.30 nmol/l per degree, p = 0.02), but not for non-Caucasians (0.03 ± 0.39 nmol/l per degree, p = 0.14). After adjustment for age, gender, and ethnicity, no overall correlation was present between 25(OH)D and latitude (−0.29 ± 0.24 nmol/l per degree, p = 0.23). There was no overall influence of latitude on 25(OH)D. However, in separate analyses 25(OH)D decreased with latitude in Caucasians but not in non-Caucasians. A widespread global vitamin D insufficiency was present compared with proposed threshold levels. [ABSTRACT FROM AUTHOR]

Introduction The aim was to analyse data on the use of biochemical bone turnover markers (BTM) in postmenopausal osteoporosis. Methods We carried out a comparative analysis of the most important papers concerning BTM in postmenopausal osteoporosis that have been published recently. Results The BTM levels are influenced by several factors. They are moderately correlated with BMD and subsequent bone loss. Increased levels of bone resorption markers are associated with a higher risk of fracture. Changes in the BTM during the anti-osteoporotic treatment (including combination therapy) reflect the mechanisms of action of the drugs and help to establish their effective doses. Changes in the BTM during the anti-resorptive treatment are correlated with their anti-fracture efficacy. Conclusion Biological samples should be obtained in a standardised way. BTM cannot be used for prediction of the accelerated bone loss at the level of the individual. BTM help to detect postmenopausal women who are at high risk of fracture; however, adequate practical guidelines are lacking. BTM measurements taken during the anti-resorptive therapy help to identify non-compliers. They may improve adherence to the anti-resorptive therapy and the fall in the BTM levels that exceeds the predefined threshold improves patients’ persistence with the treatment. There are no guidelines concerning the use of BTM in monitoring anti-osteoporotic therapy in postmenopausal women. [ABSTRACT FROM AUTHOR]

Clinical performance of osteoporosis risk assessment tools was studied in women aged 67 years and older. Weight was as accurate as two of the tools to detect low bone density. Discriminatory ability was slightly better for the OST risk tool, which is based only on age and weight. Screening performance of osteoporosis risk assessment tools has not been tested in a large, population-based US cohort. We conducted a diagnostic accuracy analysis of the Osteoporosis Self-assessment Tool (OST), Osteoporosis Risk Assessment Instrument (ORAI), Simple Calculated Osteoporosis Risk Estimation (SCORE), and individual risk factors (age, weight or prior fracture) to identify low central (hip and lumbar spine) bone mineral density (BMD) in 7779 US women aged 67 years and older participating in the Study of Osteoporotic Fractures. The OST had the greatest area under the receiver operating characteristic curve (AUC 0.76, 95% CI 0.74, 0.77). Weight had an AUC of 0.73 (95% CI 0.72, 0.75), which was ≥AUC values for the ORAI, SCORE, age or prior fracture. Using cut points from the development papers, the risk tools had sensitivities ≥85% and specificities ≤48%. When new cut points were set to achieve a likelihood ratio of negative 0.1–0.2, the tools ruled out fewer than 1/4 of women without low central BMD. Weight identified low central BMD as accurately as the ORAI and SCORE. The risk tools would be unlikely to show an advantage over simple weight cut points in an osteoporosis screening protocol for elderly women. [ABSTRACT FROM AUTHOR]

This 6-month randomized double-blind placebo-controlled trial shows that risedronate is well tolerated and effective in improving lumbar spine BMD and reducing loss of BMD at the hips in patients receiving high-dose prednisolone. Bisphosphonates have proven benefits in patients receiving chronic low-dose glucocorticoids. However, whether they are effective in preventing bone mineral density (BMD) loss during periods of high-dose glucocorticoid treatment is unclear. The objective of this paper is to study the efficacy of risedronate in preventing bone mineral density (BMD) loss in users of high-dose glucocorticoids. Adult patients with medical diseases treated with high-dose prednisolone (>0.5 mg/kg/day) were randomized to receive risedronate (5 mg/day) or placebo for 6 months in a double-blind manner, along with elemental calcium (1,000 mg/day). Changes in BMD were studied. One hundred and twenty patients were recruited (82 women, age 42.8 ± 14.3 years, 63% corticosteroid-naive, 30% women postmenopausal) and 103 completed the study. Baseline clinical characteristics and BMD were similar in the risedronate and placebo groups. At 6 months, a significant gain in spinal BMD was observed in the risedronate group (+0.7 ± 0.3%; p = 0.03) but a drop was detected in the placebo group (−0.7 ± 0.4%; p = 0.12). After adjustment for baseline BMD, age, gender, body mass index and cumulative prednisolone dosages, the inter-group difference in spinal BMD remained significant (1.4%; p = 0.006). Both groups had a significant drop in hip BMD, but the magnitude was greater in the placebo arm (−0.8 ± 0.4% in risedronate versus −1.3 ± 0.5% the in placebo). No new fractures developed. Subgroup analysis of corticosteroid-naive patients yielded similar results. Upper gastrointestinal adverse events were numerically more frequent in the risedronate group. Risedronate improves spinal BMD in users of high-dose glucocorticoids. [ABSTRACT FROM AUTHOR]

This article presents information related to the new service launched by "Osteoporosis International," (OI ). Online First is the immediate online publication of all accepted papers as soon as the authors have returned the corrected proofs. Whereas the fully electronic versions of OI used to appear at the same time as the print journal, from now on the electronic version of all articles will be available to subscribers via the Internet weeks before the printed version appears. This means an enormous reduction in publication time.

Osteoporosis in men is less studied than in women. Few data concern biochemical bone turnover markers (BTM) in men and their potential use. We evaluated papers concerning BTM in men cited on Medline. Selection of studies were based on the number of subjects, age range, group homogeneity, follow-up duration, number of BTM. BTM levels are high in young men, then decrease with age.In elderly men, bone resorption increases with age more than bone formation. Variability of individual values is high and their significance is unclear. In elderly men, BTM levels correlate negatively with bone mineral density suggesting that accelerated bone turnover underlies age-related bone loss. Data on the prediction of accelerated bone loss and fractures by BTM in men are scant. Testosterone treatment induces a decrease in bone resorption followed by a decrease in bone formation. Bisphosphonates and calcitonin decrease BTM levels in osteoporotic men. Parathyroid hormone 1–34 and growth hormone induce a rapid increase in bone turnover followed by a progressive slowdown. Few studies concern BTM in men. Currently available data are not sufficient to suggest guidelines for the practical use of BTM in the clinical management of the osteoporosis in elderly men. [ABSTRACT FROM AUTHOR]

Hip fractures are responsible for excessive mortality, decreasing the 5-year survival rate by about 20%. From an economic perspective, they represent a major source of expense, with direct costs in hospitalization, rehabilitation, and institutionalization. The incidence rate sharply increases after the age of 70, but it can be reduced in women aged 70–80 years by therapeutic interventions. Recent analyses suggest that the most efficient strategy is to implement such interventions in women at the age of 70 years. As several guidelines recommend bone mineral density (BMD) screening of postmenopausal women with clinical risk factors, our objective was to assess the cost-effectiveness of two screening strategies applied to elderly women aged 70 years and older. A cost-effectiveness analysis was performed using decision-tree analysis and a Markov model. Two alternative strategies, one measuring BMD of all women, and one measuring BMD only of those having at least one risk factor, were compared with the reference strategy “no screening”. Cost-effectiveness ratios were measured as cost per year gained without hip fracture. Most probabilities were based on data observed in EPIDOS, SEMOF and OFELY cohorts. In this model, which is mostly based on observed data, the strategy “screen all” was more cost effective than “screen women at risk.” For one woman screened at the age of 70 and followed for 10 years, the incremental (additional) cost-effectiveness ratio of these two strategies compared with the reference was 4,235 euros and 8,290 euros, respectively. The results of this model, under the assumptions described in the paper, suggest that in women aged 70–80 years, screening all women with dual-energy X-ray absorptiometry (DXA) would be more effective than no screening or screening only women with at least one risk factor. Cost-effectiveness studies based on decision-analysis trees maybe useful tools for helping decision makers, and further models based on different assumptions should be performed to improve the level of evidence on cost-effectiveness ratios of the usual screening strategies for osteoporosis. [ABSTRACT FROM AUTHOR]

The skeleton alters its geometry following trauma, the introduction of artificial defects and of fatigue-induced microcracks. The precise mechanism by which the skeleton adapts remains unclear. Microcracks might directly affect the cell by damaging the osteocyte cell network or causing apoptosis. Bone microstructure may play an important role in these processes by diverting and arresting propagating microcracks and so prevent fracture failure. This paper discusses the effects of microstructure on propagating cracks, how microdamage may act as a stimulus for bone adaptation and its potential effects on bone biochemistry. [ABSTRACT FROM AUTHOR]

Sacral insufficiency fractures (SIFs) are often overlooked in elderly patients presenting with low back and pelvic pain following no or minimal trauma. The aim of this review is to raise awareness and outline the clinical presentation, methods of diagnosis and treatment of SIFs. Insufficiency fractures represent a special category of stress fractures that occur in bones with reduced mineral content and elastic resistance. SIFs, a well-defined subgroup of the latter group, are not uncommon, but lack of clinical suspicion results in many being undiagnosed. SIFs are set to become an important clinical entity of both social and economic significance as the Western population ages. Subtle clinical presentations and signs coupled with radiographic findings that can mimic other unrelated or overlapping conditions, such as sacroiliac joint infection, spinal stenosis and metastatic bone disease, often make SIF diagnosis a challenge. The aim of this review is to increase awareness among clinicians, highlighting SIFs as an important differential diagnosis to be considered when patients present with low back and pelvic pain and subsequently allow prompt management. The paper provides an overview of epidemiology, anatomical considerations, relevant pathophysiology and risk factors, presenting symptoms and signs, investigations and imaging techniques, differential diagnoses and current treatment methods available for the management of SIFs. [ABSTRACT FROM AUTHOR]

The objective of this paper was to determine the persistence with teriparatide at 12 months in all patients in the UK who were prescribed the treatment since its launch. Virtually all patients prescribed teriparatide in the UK receive treatment through Healthcare at Home, Basingstoke, UK. Data was obtained to assess the start date, discontinuation date and reason for discontinuation in all patients receiving teriparatide since its launch. Persistence was defined as the number of patients continuing treatment. A total of 1,104 patients were included in the analysis. The median duration of use in all patients was 252 days. Of the 435 patients who were at least 12 months post-initiation of treatment, persistence was 87%. Forty-two patients (3.8%) had discontinued treatment due to adverse events. This study demonstrates that persistence with teriparatide at 12 months is very high and is probably greater than that of existing oral therapies for osteoporosis. The reasons for the high persistence rates seen with teriparatide are likely to be multi-factorial. The high persistence rates should help to optimise the effectiveness of therapy in this group of high-risk patients. [ABSTRACT FROM AUTHOR]

Racial disparities have been identified in a number of areas in clinical medicine. Patients diagnosed with osteoporosis should be treated similarly regardless of race. However, limited data are available on the relative frequency of treatment by race after diagnosis of osteoporosis. We analyzed all 739 dual-energy X-ray absorptiometry (DXA) results obtained of women 50 years old and older between 1998 and 2002 at our medical center. Our study sample was 82% Caucasian and 15% African American. Of 353 women who had low bone mineral density on first DXA, we abstracted the electronic and paper medical records to compare treatment rates by race. Of the women diagnosed with osteoporosis or osteopenia, 80.0% and 68.3%, respectively, were started on antiresorptive medications. Of the African American women, 61.9% diagnosed with osteoporosis were started on antiresorptive treatment compared with 83.3% of Caucasian women ( p<0.05). African American women with low bone mass were less likely than Caucasian women to be smokers ( p<0.05) and use alcohol ( p<0.01) but were more likely to be on corticosteroids ( p<0.05). No other significant differences were found among treated and nontreated groups that might explain the disparity in treatment. A smaller proportion of African American than Caucasian women with osteoporosis received antiresorptive medications after a DXA diagnosis. This significant disparity requires further study in a larger population. [ABSTRACT FROM AUTHOR]

Intervention thresholds (ITs), the 10-year hip fracture risk at which treatment can be considered to be cost-effective, have previously been estimated for Sweden and the UK. The aim of this study was to provide a Markov cohort model platform for a multinational estimation of thresholds at which intervention becomes cost-effective and to investigate and determine the main factors behind differences in these thresholds between countries. Intervention thresholds were estimated for Australia, Germany, Japan, Sweden, Spain, the UK and USA using a societal perspective. The model was populated with as much relevant country-specific data as possible. Intervention was assumed to be given for 5 years and to decrease the risk of all osteoporotic fractures by 35%. The societal willingness to pay (WTP) for a quality-adjusted life-year (QALY) gained was set to the gross domestic product (GDP) per capita multiplied by two. In the base case analysis, the 10-year hip fracture probability at which intervention became cost-effective varied across ages and countries. For women starting therapy at an age of 70 years, the IT varied from a hip fracture probability of 5.6% in Japan to 14.7% in Spain. The main factors explaining differences in the IT between countries were the WTP for a QALY gained, fracture-related costs and intervention costs. The ITs presented in this paper are appropriate for use in treatment guidelines that consider health economic aspects, and they can be used in combination with fracture risk prediction algorithms to improve the selection of patients who are suitable for osteoporotic intervention. [ABSTRACT FROM AUTHOR]

Introduction: Assessment of the predictive power of a newly introduced diagnostic technique with regard to fracture risk is frequently limited by the enormous costs and long time periods required for prospective studies. A preliminary estimate of predictive power usually relies on cross-sectional case-control studies in which bone measurements of normal and fractured subjects are compared. The measured discriminatory power is taken as an estimate of predictive power. Because of possible sample selection bias, study participants may have different bone mineral density (BMD) values, and fractured patients may have fractures of different severity levels. The same diagnostic techniques for the measured discriminatory power, expressed as odds ratios, will differ among studies with different patient and control populations. Methods: In this paper, we propose a weighted logistic regression approach to adjust the odds ratio in order to reduce the effect of sampling bias. The weight is derived from age, deformity severity, BMD, and the interactions of these, using the propensity score theory and reference population data. Results: Simulation examples using data from the Osteoporosis and Ultrasound Study (OPUS) demonstrate that such a procedure can effectively reduce the estimation bias of odds ratios introduced by sampling differences, such as for dual x-ray absorptiometry (DXA) scans of the spine and hip as well as various quantitative ultrasound techniques. The derived estimated odds ratios are substantially less biased, and the corresponding 95% confidence intervals contain the true odds ratios from the population data. Conclusions: We conclude that a statistical correction procedure based on propensity scores and weighted logistic regression can effectively reduce the effect of sampling bias on the odds ratios calculated from cross-sectional case-control studies. For a new diagnostic technique, hip BMD and deformity severity information are necessary and likely sufficient to derive the propensity scores required to adjust the measured standardized odds ratios. [ABSTRACT FROM AUTHOR]

Recent advances in the understanding of the epidemiology of osteoporosis suggest that certain parts of the current European guidelines for the registration of drugs in osteoporosis might be no longer substantiated. The object of this review is to provide the European regulatory authorities with an evidence-based working document providing suggestions for the revision of the “Note for guidance for the approval of drugs to be used in postmenopausal osteoporosis” (CPMP/EWP/552/95). Following an extensive review of the literature (1990–2004), the Group for the Respect of Ethics and Excellence in Science (GREES) organized a workshop including European regulators, academic scientists and representatives of the pharmaceutical industry. The outcomes of this meeting reflect the personal views of those who attended and should not, in any case, be seen as an official position paper of any regulatory agency. The group identified a certain number of points that deserve discussion. They mainly relate to the nature of the indication being granted to new chemical entities (treatment of osteoporosis in women at high risk of fracture instead of prevention and treatment of osteoporosis), the requirements of showing an anti-fracture efficacy on all or on major nonvertebral fractures (instead of the hip), the duration of pivotal trials (2 years instead of 3) and the possibility of considering bridging studies for new routes of administration, new doses or new regimens of previously approved drugs. The group also recommends that an indication could be granted for the treatment of osteoporosis in males on the basis of a placebo-controlled study, with bone mineral density changes after 1 year as the primary endpoint, for medications approved in the treatment of osteoporosis in women at high risk of fractures. [ABSTRACT FROM AUTHOR]

Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and an increased risk of fragility fractures. Bone mineral density (BMD) is the most important determinant of osteoporotic fracture risk, but the genes responsible for BMD regulation and fracture are incompletely defined. To enable multi-center studies to examine the genetic influences on BMD there is a requirement to standardize measurements across different manufacturers of bone densitometers, different versions of machines and different normative ranges. This paper describes a method developed to allow near-identical subjects with low age-adjusted BMD (based on Z-scores) to be recruited in 17 centers using 27 different densitometers. Cross-calibration was based on measurements using a European spine phantom circulated to all centers and measured ten times on each individual machine. From theses values an individual exponential curve, based on nominal versus observed BMD, was derived for each machine. As expected, there were large and significant variations in nominal BMD values, not only between scanners from different manufacturers but also between different versions of scanners from the same manufacturer. Hologic scanners tended to underestimate the nominal BMD, while Lunar scanners overestimated the value. Norland scanners gave mixed values over estimating BMD at the lower nominal value (0.5 g/cm2) while underestimating the value at the higher value (1.5 g/cm2). The validity of the exponential equations was tested using hip and spine measurements on 991 non-proband women from a familial osteoporosis study (FAMOS). After cross-calibration there was a considerable reduction in variation between machines. This observation, coupled with the absence of a similar reduction in variation attributable to a linear regression on age, demonstrated the validity of the cross-calibration approach. Use of the cross-calibration curves along with a standard normative range (in the case of this study, the Hologic normative range) allowed age-specific Z-scores to be used as an inclusion criterion in this genetic study, a method that will be useful for other trials where age-specific BMD inclusion criteria are required. [ABSTRACT FROM AUTHOR]

The BMD reference curve is the reference value used for diagnosing osteoporosis and assessing bone mass changes. Its accuracy would affect the correctness of T -score and Z -score values and thus the reliability of diagnostic results. In this paper, we report the use of a new method, a Cartesian coordinate numeration system, to establish BMD reference curves at different skeletal sites in women. In a reference population of 3,919 women ranging in age from 5–85 years, we used the dual X-ray absorptiometry (DXA) bone densitometer to measure BMD at the posteroanterior spine (PA; vertebrae L1–L4), followed by a paired PA/lateral spine scan of the vertebral bodies of L2–L4, expressed in g/cm2 and g/cm3, and of the hip and forearm. We chose the cubic regression model to best fit BMD curves that varied with age at different skeletal sites. We then referred the BMD of the fitting curves established by the method of the coordinate numeration system as reference curves, compared them to BMD reference curves derived from the fitting curve equation or age cross-section, and calculated the deflection degrees of the BMD reference curves acquired from the fitting curve equation. At the PA spine, lateral spine (expressed in g/cm3), femoral neck, Ward’s triangle and radius + ulna ultradistal, the reference curves calculated from the equation were significantly lower than those confirmed by the method of the coordinate numeration system; whereas, at the lateral spine (expressed in g/cm2), total hip, and radius + ulna 1/3 sites, the reference curves derived from the equation were markedly higher than those acquired from the coordinate numeration system. The differences in the two kinds of reference curves calculated by these two different methods gradually increased along with the increment in ages of the women. At the peak value of the reference curves, the BMD calculated from the equation deflected from 2.02% to −10.0% from the BMD acquired from the coordinate numeration system at different skeletal sites, and from 21.5% to −121.8% until the age of 85 years. The highest positive deflection of 65.2% existed at the lateral spine (expressed in g/cm2) and the lowest positive deflection of 21.5% at the total hip. The maximum negative deflection of −121.8% was at the radius + ulna ultradistal, and the minimum negative deflection of −32.6% at the PA spine. The BMD curve acquired from age cross-section was highly positive compared with the one derived from the coordinate numeration system ( r =0.955–0.985 p =0.000) with no significant difference between them. Various analysts used such a method to obtain the coefficient of variance (CV) in BMD precision on each curve that was from 0.05–0.19%. Our study shows that the Cartesian coordinate numeration system is an accurate, precise and reliable method and can serve to reveal the serious drawbacks of using the fitting curve equation to calculate BMD. The BMD reference curves established by this coordinate numeration system maintained the authenticity of the fitting curve, whereas, using the fitting curve equation to obtain BMD reference curves at different skeletal sites led to distortion, and resulted in false increases or decreases in T -score and Z -score values. [ABSTRACT FROM AUTHOR]

Vertebral collapse is one of the most common fractures associated with osteoporosis. The subsequent back pain is severe and often requires medications, bed rest and hospitalization to control pain and improve mobilization. The purpose of this systematic review was to assess the effects of calcitonin versus placebo for the treatment of acute pain in patients sustaining stable, recent, osteoporotic vertebral compression fractures. MEDLINE (1966–2003), EMBASE (1980–2003), Cochrane Controlled Trial Registry (2003, volume 3), other databases, and conference proceedings were searched for relevant research. Primary study authors and the pharmaceutical manufacturer were contacted, and bibliographies of relevant papers were hand-searched. Randomized, double-blind, placebo-controlled trials comparing calcitonin versus placebo for the acute pain of recent osteoporotic vertebral compression fractures were included. Two reviewers extracted data, performed numeric calculations and extrapolated graphical data independently. The combined results from five randomized controlled trials, involving 246 patients, determined that calcitonin significantly reduced the severity of pain using a visual analogue scale following diagnosis. Pain at rest was reduced as early as 1 week into treatment (weighted mean difference [WMD] =3.08; 95% confidence interval [CI]: 2.64, 3.52) and this effect continued weekly to 4 weeks (WMD =4.03; 95% CI: 3.70, 4.35). A similar pattern was seen for pain scores associated with sitting, standing, and walking. Side effects were gastrointestinal, minor and often self-limited. Calcitonin appears to be effective in the management of acute pain associated with acute osteoporotic vertebral compression fractures by shortening time to mobilization. [ABSTRACT FROM AUTHOR]

The intravertebral vacuum cleft sign (VCS) is an uncommon radiological sign, characterized by a radiolucent zone in the vertebral body. It is composed of 95% nitrogen and small amounts of oxygen and carbon dioxide. Post-traumatic ischemic necrosis could be its physiopathological mechanism, along with other pathologies like osteoporosis, corticosteroid therapy, diabetes, arteriosclerosis, alcoholism, multiple myeloma, bone metastasis and osteomyelitis. The broad diagnosis is made by antero-posterior X-ray, but computed tomography scan (CT scan) and magnetic resonance imaging (MRI) may help with the differential diagnosis. The aims of this paper are, on one hand, to communicate the clinical case of a 73-year-old osteoporotic woman with traumatic vertebral fractures who developed this sign in her radiological survey. On the other hand, its secondary aims are to review the medical literature about this sign and to show the clinical and radiological evolution after a percutaneous vertebroplasty. [ABSTRACT FROM AUTHOR]

Osteoporosis is a major public problem. More than 35 million Americans are at risk of developing osteoporosis. Nearly half of all women will have an osteoporotic fracture in their lifetime. Tubal ligation (tubal sterilization) is used more than any other single method of contraception in the USA and worldwide. In 1995, 34.6% (approximately 7 million) of ever-married US women between ages 35-44 years had undergone tubal ligation. Tubal sterilization may disturb ovarian function and be associated with more menstrual and menopausal symptoms and, thus, may be a risk factor for osteoporosis. The objective of this paper is to examine the possible association between tubal sterilization and osteoporotic fractures. Data are from a questionnaire mailed to a previously identified cohort of college/university alumnae who had graduated between 1926 and 1981. This study was performed during 1996 and 1997, 15 years after the initial study. The subjects were 3,940 women participants in the follow-up study. Their mean age was 53.7 years at time of reporting, ranging from 37 to over 80 years. Excluding deaths and non-deliverables the response rate was 85%. Of the 3,940 subjects, 491 (12.5%), and, of the ever-pregnant women, 15.5%, had undergone tubal sterilization (TS); 899 (22.8%) reported at least one fracture after age 20, and 70 (1.8%) at least one vertebral fracture after age 20, which had been confirmed by X-ray. TS was strongly associated with self-reports of vertebral fractures that had been confirmed by X-ray. The multivariable adjusted odds ratios and 95% confidence intervals for women 50 years and over and for women 55 years and over were, respectively, 2.7 (1.4, 5.0) and 3.3 (1.5, 7.0). Having had any fracture was not significantly associated with TS: odds ratio (OR) =1.1 for women 50 years and older and OR=1.3 for those 55 years and older. This epidemiological study in a cohort of highly educated, mostly Caucasian women shows an association between past tubal sterilization and self-reported X-ray-confirmed vertebral fractures. These results need to be confirmed in other cohorts-the pathophysiology of this association is worthy of further study. [ABSTRACT FROM AUTHOR]

During the last 10 years, we have witnessed an impressive increase in the number of studies examining knowledge about osteoporosis. The aim of the present paper is to examine the status of research on knowledge about osteoporosis by reviewing and analyzing the current literature as it pertains to assessment of knowledge about osteoporosis, factors associated with knowledge, and relationship between knowledge about osteoporosis and participation in health-related behaviors. Finally, future directions in the field are discussed. Many of the studies are still characterized by the lack of a theoretical framework, as well as by various methodological flaws. Serious deficits in knowledge are reported among healthy and diagnosed women and men, as well as among health professionals. Educational interventions are accompanied by an increase in knowledge, but no change in behavior. There is need to expand the research on knowledge about osteoporosis, especially in an effort to increase its impact on the prevention and early diagnosis of the disease. The deficits found in the knowledge of both the general population and among health care professionals, should be addressed by providing updated and reliable information through appropriate health promotion and professional venues. [ABSTRACT FROM AUTHOR]

Weight-bearing physical activity and calcium intake are two important behavioral influences for bone health. Physical-activity and calcium-intake intervention trials with youth have been implemented to evaluate their efficacy and effectiveness to decrease the risk for subsequent osteoporosis and fractures. Technical aspects of bone measurement have not been routinely reported in published trials of youth, even though they can have an impact on study findings and interpretation. This paper provides an overview of the outcome variables reported, and technical issues-such as software and bone detection, growth, and movement-that affect bone mass measurements among children and adolescents. It describes the implications of these issues for the interpretation of intervention effects observed in intervention trials, and provides recommendations for future research. [ABSTRACT FROM AUTHOR]

Measurement of bone mineral density (BMD) with central dual-energy X-ray absorptiometry (DXA) is the current “gold standard” for diagnosing osteoporosis and for monitoring patients. Errors in demographic information, improper patient positioning, incorrect scan analysis, and mistakes in interpretation can all lead to a wrong clinical decision or action. This paper reviews the fundamentals of positioning, scan analysis, and interpretation for central DXA and highlights some of the common pitfalls that may lead to erroneous results. [ABSTRACT FROM AUTHOR]

Over the last several years magnetic resonance (MR) imaging has emerged as a means of measuring in vivo 3D trabecular bone structure. In particular, MR based diagnosis could be used to complement standard bone mineral density (BMD) methods for assessing osteoporosis and evaluating longitudinal changes. The aim of this study was to demonstrate the feasibility of using the 3D-LSGA technique for the evaluation of trabecular bone structure of high-resolution MR images, particularly for assessing longitudinal changes, in vivo. First, the reproducibility of topological 3D-LSGA based measurements was evaluated in a set of seven volunteers, and coefficients of variations ranged from 3.5% to 6%. Second, high-resolution MR images of the radius in 30 postmenopausal women from a placebo controlled drug study (Idoxifene), divided into placebo (n=9) and treated (n=21) groups, were obtained at baseline (BL) and after 1 year of treatment (follow-up, FU). In addition, dual X-ray absorptiometry (DXA) measures of BMD were obtained in the distal radius. Standard morphological measurements based on the mean intercept length (MIL) technique as well as 3D-LSGA based measurements were applied to the 3D MR images. Significant changes from BL to FU were detected, in the treated group, using the topological 3D-LSGA based measurements, morphological measures of volume of connected trabeculae and App Tb.N from MIL analysis. The duration of the study was short, and the number of patients remaining in the study was small, hence these results cannot be interpreted with regard to a true therapeutic response. Furthermore, the site (wrist) and the drug (idoxifene) are not optimal for follow-up study. However, this paper demonstrated the feasibility of using 3D-LSGA based evaluation coupled with in vivo high-resolution MR imaging as a complementary approach for the monitoring of trabecular bone changes in individual subjects. [ABSTRACT FROM AUTHOR]

Vitamin D metabolites alphacalcidol and calcitriol (D-hormones) have been investigated for two decades, but few and conflicting results are available from high-quality randomized controlled trials. Our objectives were to provide an evidence-based update quantitatively summarizing their efficacy on bone mineral density (BMD) and fracture rate. We performed a systematic research of any randomized controlled trial containing relevant data, peer review, data extraction and quality scoring blinded for authors and data sources, and comprehensive meta-analyses of the relevant data. Inclusion criteria were: randomized controlled study, calcitriol or alphacalcidol, BMD or fractures in healthy/osteopenic/osteoporotic patients exposed or not to corticosteroids (CS). Analyses were performed in a conservative fashion using professional dedicated softwares and stratified by outcome, target patients, study quality, and control-group type. Results were expressed as effect size (ES) for bone loss or relative risk (RR) for fracture while allocated to D-hormones vs control. Publication bias and robustness were investigated. Of the trials that were retrieved and subsequently reviewed, 17 papers fitted the inclusion criteria and were assessed. Quality scores ranged from 20 to 100%, the mean (standard deviation) being 72 (22)%. Calcitriol and alphacalcidol were found to have the same efficacy on all outcomes at p>0.13. We globally assessed D-hormones effects in preventing bone loss in patients not exposed to CS, and found positive effect: ES=0.39 (p<0.001). For lumbar spine, this particular effect was 0.43 (p<0.001). D-hormones significantly reduced the overall fracture rates: RR=0.52 (0.46; 0.59) and both vertebral and non-vertebral fractures: RR=0.53 (0.47; 0.60) and RR=0.34 (0.16; 0.71), respectively. No statistical difference in response was observed between results from studies on healthy and osteoporotic patients or depending on the fact that controls were allowed to calcium supplementation. Treatment with D-hormones was evaluated for maintaining spinal bone mass in five trials of patients with CS-induced osteoporosis, and provided ES=0.43 at p<0.001. Only two studies specifically addressed the effects of calcitriol on spinal fracture rate. None of them provided significant results, and the global RR did not reach the significance level as well: RR=0.33 (0.07; 1.51). Our data demonstrated efficacy for DH on bone loss and fracture prevention in patients not exposed to CS and on bone loss in patients exposed to CS, in the light of the most reliable scientific evidence. Their efficacy in reducing the number of fractures in patients exposed to CS remains to be determined. [ABSTRACT FROM AUTHOR]

Definitions of adherence, also termed compliance, with use of hip protectors have varied in published studies, making interpretation of results difficult. This paper proposes standard definitions of adherence with the use of hip protectors. Adherence is the wearing of hip protectors in accordance with the recommendations of the study protocol, and is measured as the amount of time hip protectors are worn. When reporting use of hip protectors in clinical trials investigators should indicate the specific definition of adherence used, explicitly state the recommendation that was made for use of hip protectors during the study, and describe the methods of recording adherence. [ABSTRACT FROM AUTHOR]

Osteoporosis is currently defined on the basis of the T-score by dual-energy X-ray absorptiometry (DXA). Despite its limitations, this definition is applied worldwide. However, the normal values provided by manufacturers may not be fully representative of specific local populations. So far, there are no normative data in the Italian population using Hologic densitometers. The Densitometric Italian Normative Study (DINS) is an ongoing multi-center study that aims to establish reference values for bone densitometry with dual-energy X-ray absorptiometry (DXA) in the male and female Italian population. In this paper we report the results of the lumbar vertebrae (L2?L4) and proximal femur in 1,622 women aged 20?79 years. Bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry (DXA) on Hologic bone densitometers (Hologic, Waltham, Mass.). Most of the subjects were examined with a QDR 4500. The BMD of the lumbar vertebrae was virtually constant between 20 and 49 years (test for trend: P=0.66); the BMD values between 20?45 in premenopausal women (mean 1.036; SD 0.109 g/cm 2) were thus defined as the peak bone mass values, significantly lower compared to the Hologic reference curve (mean 1.079, SD 0.11 g/cm 2). The mean BMD values of the femoral neck were virtually identical to those of the NHANES study in the first 3 decades; after the age of 50 the BMD values were slightly greater than those of the NHANES subject. The subject classification according to the WHO criteria was similar using the DINS and NHANES reference values for the femur; for the spine, the Hologic reference values classified a larger proportion of women as osteoporotic (21 vs. 16%) or osteopenic (42 vs. 38%) compared to DINS. [ABSTRACT FROM AUTHOR]

Presents abstracts of papers discussed at the Fourth European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Treatment of osteoporosis; Comparison of the impact of vertebral fractures and hip fractures on the assessment of health utilities; Assessment of drug effectiveness in osteoarthritis; Clinical and economic impact of adherence to osteoporosis medication.

Recent interest has been shown in the potential beneficial effects of phytoestrogens on bone health. As the early years of menopause are a period of rapid bone loss, and the risk for osteoporosis increases substantially, the habitual intake of soy protein and isoflavones may play a role in the retardation of bone loss. This paper reports the results of the baseline cross-sectional analysis of the association between dietary soy protein intake and bone mineral density/content in a population-based study of Chinese women. The sample comprised 454 healthy Chinese women (mean age 55.1±3.57) within the first 12 years of postmenopause. We estimated the dietary intake of soy protein and isoflavones, and other key nutrients, including dietary protein and calcium, using the quantitative food frequency method. Bone mineral density (BMD) and content (BMC) at the spine, hip and total body were measured with a dual energy X-ray densitometer (Hologic 4500A). Soy protein consumption was categorized as quartiles of intake, and related to BMD values at the spine and hip, and BMC of total body. Stratified analyses were carried out among women within or at least 4 years postmenopausal. We observed few differences in BMD/BMC values among the intake quartiles in women within the first 4 years of menopause. However, among the later postmenopausal women, we noted a dose-response relationship with increasing higher BMD values at the trochanter, intertrochanter as well as the total hip and total body with increasing soy protein intake quartiles ( P<0.05 from tests for trend). The BMD values differed by about 4?8% between the first and fourth soy protein intake quartiles. Though women from the fourth intake quartile had a 2.9% higher BMD value compared with those from the first intake quartile, the difference was not statistically significant. Stepwise multiple linear regression analyses showed the association between soy intake quartiles and hip BMD as well as total body BMC values remained after adjusting for body weight, which was retained in the final model. Analyses based on soy isoflavones content yielded similar results. This study demonstrated that, among women after the initial few years postmenopausal, soy protein/isoflavones intake had a modest but significant association with hip BMD as well as total body BMC. The effects of soy protein and soy isoflavones on bone health should be further explored in populations with habitual dietary soy intake. [ABSTRACT FROM AUTHOR]

The aim of the present paper was to delineate in detail the dose-dependent effects of intermittent intravenous (IV) ibandronate treatment on the dynamics of markers of bone resorption and formation. The study included 73 healthy postmenopausal women between 50 and 70 years of age. Two groups received an IV injection of either 1 mg or 2 mg ibandronate on day 0 and 84 and one group, which received no treatment, served as control. Study duration was 168 days. Bone turnover was estimated by measuring the serum concentration of the C-terminal collagen I telopeptide (s-CTx, bone resorption) and osteocalcin (s-OC, bone formation) at 19 consecutive time-points. Serum CTx decreased rapidly reaching a nadir 7 days after drug administration. Maximal changes from baseline in the 1 and 2 mg ibandronate groups were -81% and -90%, respectively ( P<0.001). However, already 2 weeks after drug administration, s-CTx started to rise again in both treatment groups, reaching -16% and -20% by day 84, i.e. immediately before the second drug administration. In contrast, s-OC showed a slower but progressive decrease over time reaching a nadir at -35% inhibition after 5 months. On a group level, the suppression of bone resorption was greater or equal to the suppression of bone formation at all time points. However, the least significant change (LSC) analysis performed at the individual level highlighted individuals who at certain time points showed apparently greater suppression of formation than resorption, which could also contribute to the inefficacy of this dosing regime. Although the physiological relevance of this latter finding would require further analysis, the results draw attention to the need to optimize the intermittent IV dosing of ibandronate in order to approximate more closely the sustained and balanced anti-resorptive effect provided by daily oral treatment. [ABSTRACT FROM AUTHOR]

Abstract This paper aims to identify risk factors for hip fracture in Medicare skilled nursing facility (SNF) residents and to develop a predictive model based on routinely collected administrative data (the Minimum Data Set, MDS) to identify high-risk residents. Prospective cohort study of 28,807 North Carolina Medicare SNF residents aged >65 years with a complete MDS assessment in 1999. Demographic, historical, physical, cognitive, behavioral, activities of daily living, and medication variables were obtained from the MDS. Hip fracture occurring after the first MDS assessment identified by ICD-9 code was the outcome measure. Variables significantly associated with hip fracture by chi-square test in a randomly selected derivation sample were combined in a multivariable logistic model and in models stratified by gender. The models were validated in the remaining subjects. Variables significantly related to subsequent hip fracture in the full cohort include: female sex (odds ratio 1.3, 95% confidence interval 1.0-1.7), white race (2.3, 1.6-3.5), age (1.03 per year, 1.01-1.04), cognitive impairment (1.4, 1.8-1.8), incontinence (0.68, 0.5-0.9), prior fractures (1.6, 1.2-2.1), and prior falls (1.4, 1.2-1.8). In ambulatory non-Hispanic white women, anxiety (1.5, 1.0-2.1), anxiolytic use (1.4, 1.1-1.9), wandering (1.4, 1.0-2.2), and training in community skills (1.4, 1.1-1.8) were new significant variables. For ambulatory non-Hispanic white men, education level (2.0, 1.2-3.2), weight loss (0.5, 0.2-1.0), history of osteoporosis (3.0, 1.3-6.7), pathologic bone fracture (9.7, 2.2-42.6), COPD (2.1, 1.3-3.5), glaucoma (2.6, 1.0-6.2), and standing balance impairment (1.8, 1.0-3.3) were also significant. All models were highly correlated with subsequent hip fracture, but the discriminative ability was limited (c statistic 0.678). Risk factors explained more of hip fracture risk in non-Hispanic white men (c statistic 0.793) than non-Hispanic white women (0.658). Risk factors for hip fracture in Medicare SNF residents have similarities and differences from those previously identified in community-dwelling older adults. Osteoporosis screening and intervention should focus on the healthiest, most independent subset of residents who have the greatest fracture risk. [ABSTRACT FROM AUTHOR]

Presents abstracts of papers discussed at the Ninth Batch Conference on Osteoporosis. Fracture and risk prediction; Primary care program to reduce the incidence of osteoporotic fracture; Hormone replacement therapy; Osteoporosis in men; Determinants of bone size and the risk of fracture.

Osteoporosis treatment should not only prevent the loss of bone tissue, not interfere with apatite and avoid bone mineral changes at the crystal level, but should also increase the mechanical resistance of bone and thus protect the skeleton against new fractures. Mineral substance is crystallized as nonstoichiometric carbonated apatite ionic crystals of small size and extended specific surface. Consequently, they have a very large interface with extracellular fluids, and numerous interactions between ions from the extracellular fluid and ions constituting apatite crystals are thus possible. It is generally agreed that bone strength depends on the bone matrix volume and the microarchitectural distribution of this volume, while the degree of mineralization of bone tissue is almost never mentioned as a determinant of bone strength. We now have evidence that the degree of mineralization of bone tissue strongly influences not only the mechanical resistance of bones but also the bone mineral density. In adult bone, our model is based on the impact of changes in the bone remodeling rate on the degree of mineralization of bone tissue. The purpose of this paper is to report the main results concerning the interactions of strontium (Sr) with bone mineral in animals and in osteoporotic women treated with strontium ranelate (SR). These studies aimed to evaluate using X-ray microanalysis, X-ray diffraction and computerized quantitative contact microradiography: (1) the relative calcium and Sr bone content, (2) the distribution of Sr in compact and cancellous bone, (3) the dose dependence of the deposition of Sr in bone, (4) the interactions between Sr and mineral at the crystal level (in monkeys), (5) the influence of Sr on the mean degree of mineralization of bone tissue and on the distribution of the degree of mineralization of bone tissue, and (6) the bone clearance of Sr over short periods of time (6 and 10 weeks) after cessation of SR administration (monkeys treated for 13 and 52 weeks, respectively). In monkeys killed at the end of exposure (13 or 52 weeks), Sr was taken up in a dose-dependent manner into compact and cancellous bone, with a higher content in new bone than in old bone. The Sr content greatly decreased (about 2-fold) in animals killed 6 or 10 weeks after the end of treatment but this affected new bone almost exclusively. After SR treatment, there were no significant changes in crystal characteristics. Easily exchangeable in bone mineral, Sr was slightly linked to crystals by ionic substitution (generally 1 calcium ion substituted by 1 Sr ion in each unit cell). The degree of bone mineralization was not significantly different in the various groups of monkeys. Thus, at the end of long-term SR treatment and after a period of withdrawal, Sr was taken up in a dose-dependent manner into new bone without alteration of the degree of bone mineralization and with no major modification of bone mineral at the crystal level. In postmenopausal osteoporotic women treated with SR (0.5, 1 and 2 g/day) for 2 years, Sr was dose-dependently deposited into new bone without changes in the degree of mineralization of bone tissue. These findings could reflect dose-dependent stimulation of bone formation and are of potential value for the use of SR in the treatment of osteoporosis. In conclusion, the different studies performed on bone samples from monkeys and humans treated with various doses of SR showed that Sr was heterogeneously distributed between new and old bone but in a dose-dependent manner without alteration of the crystal characteristics and the degree of mineralization of bone tissue, even after long-term administration of often high doses of SR (the highest therapeutic dose used in humans is 4-fold lower than the lowest experimental dose administered to monkeys). This emphasizes the value, as antiosteoporotic treatment, of SR, which is safe at the bone mineral level. [ABSTRACT FROM AUTHOR]

Deleterious effect of oral corticosteroids on bone has been well documented, whereas this remains debated for inhaled ones (ICS). Our objectives were to analyze the effects of ICS on bone mineral density, fracture risk and bone markers. We performed an exhaustive systematic research of all controlled trials potentially containing pertinent data, peer-reviewed by a dedicated WHO expert group, and comprehensive meta-analyses of the data. Inclusion criteria were ICS, and BMD/markers/fractures in asthma/chronic obstructive pulmonary diseases (COPD) and healthy patients. Analyses were performed in a conservative fashion using professional dedicated softwares and stratified by outcome, study design and ICS type. Results were expressed as standardized mean difference/effect size (ES), relative risk (RR) or odds ratio (OR), depending on study design and outcome units. Publication bias was investigated. Twenty-three trials were reviewed; 11 papers fit the inclusion criteria and were assessed for the main analysis. Quality scores for the randomized controlled trials (RCTs) were 80%, 71% for the prospective cohort studies, and 78% for the retrospective cohort and cross-sectional studies. We globally assessed ICS effects on BMD and found deleterious effects: ES=0.61 (p=0.001) for healthy subjects, and ES=0.27 (p<0.001) for asthma/COPD patients. For these patients, this effect was 0.21 (p<0.01) at the lumbar spine, and 0.26 (p<0.001) at the hip or femoral neck. A single study evaluated the impact of ICS on hip fracture and reported an increased OR of 1.6 (1.24; 2.03). Lumbar fracture rate differences did not reach the level of statistical significance: 1.87 (0.5; 6.94). Osteocalcin and PICP were decreased and ICTP, pyridinoline and deoxypyridinoline levels were not significantly affected. Budesonide (BUD) appeared to be the ICS inducing the less deleterious effects on bone, followed by beclomethasone dipropionate (BDP) and triamcinolone (TRI). Publication bias investigation provided non-significant results. In our meta-analyses, BUD at a mean daily dose (SD) of 686 μg (158 μg), BDP at 703 μg (123 μg) and TRI at 1000 μg (282 μg) were found to affect bone mineral density and markers in patients suffering from the two major respiratory diseases. These findings could have practical implication in the long-term management of asthmatic and COPD patients. [ABSTRACT FROM AUTHOR]

Dual-energy X-ray absorptiometry (DXA) devices from the three main manufacturers provide different bone mineral density (BMD) values, due in part to technical differences in the algorithms for bone mineral content (BMC) and area measurements and in part to the use of different manufacturer-derived reference databases. As a result, significant differences exist between Hologic, Lunar and Norland systems in the reported young normal standard deviation scores or T-scores. In a number of European countries, including Belgium, a T-score below -2.5 is one of the key criteria for reimbursement of osteoporosis treatments. This paper addresses the first attempt to implement a nationwide, uniform expression of BMD in patients, in order to harmonize drug reimbursement. To this end, measures were taken to implement a uniform expression of BMD in Belgian patients, by converting each manufacturer's absolute BMD to standardized BMD (sBMD) values and by establishing a single national reference range. [ABSTRACT FROM AUTHOR]

: Much clinical research on osteoporosis is aimed at documenting a reduction in vertebral fracture rates, but there is considerable disagreement about defining normality. Most methods for measuring vertebral body dimensions use lateral radiographs. In the present paper, we investigate the reliability of magnetic resonance imaging (MRI) for normal reference determination. A validation study was performed on a cadaver by comparing vertebral body volume measured both with MRI (sagittal acquisition in T1 weighted sequence) and with immersion. MRI was then performed with the same protocol from T4 to L5 in a standard population of 80 women with no history of vertebral fractures. Then all vertebral measurements were standardized relative to each other, and means and standard deviations were calculated using a statistical fitting procedure derived from volume and medial area. The validation study confirmed the reproducibility and accuracy of MRI (intraclass correlation coefficient 0.95). There was a strong correlation between volume and medial area of vertebral bodies (Pearson correlation coefficient 0.95) and a constant relationship between the medial area of vertebral bodies for each subject (coefficient of variation 5.6%). The variations in vertebral body dimensions will allow comparison with pathologic vertebral fractures in further studies. This could be useful for monitoring osteoporosis treatments. [ABSTRACT FROM AUTHOR]