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Proton pump inhibitors (PPIs) are widely used for acid-related gastrointestinal disorders; however, concerns have arisen about their prolonged and inappropriate use. Although generally considered safe, recent evidence has linked PPI use with an increased risk of kidney disease, stomach cancer, pneumonia, dementia, cardiovascular events and potential bone health problems. This systematic review examines the effects of PPIs on bone health, including osteoporosis and changes in phosphocalcic and magnesium metabolism, through a comprehensive analysis of the recent literature. The relationship between PPIs, bone mineral density and fracture risk, especially in populations with comorbidities, is complex and we propose a focus based on recent data. Studies of the effect of PPI use on bone mineral density have shown mixed results and require further investigation. Observational studies have indicated an increased risk of fractures, particularly vertebral fractures, associated with PPI use. Recent meta-analyses have confirmed an association between PPI use and hip fractures with a dose-dependent effect. More recently, PPIs have been associated with serious disturbances in phosphocalcic and magnesium metabolism that require careful management and discontinuation. Proton pump inhibitor-induced hypomagnesemia (PPIH) is a well-established phenomenon. In addition, hypocalcemia secondary to severe hypomagnesemia has been described. Despite growing evidence of PPI-related risks, further research is essential to better understand the complex mechanisms, as most data are from observational studies and do not establish a causal relationship. This review emphasizes the need for judicious prescription practices, particularly in long-term use scenarios and rheumatological contexts., (Copyright © 2024 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Bone forming agents, also known as anabolic therapies, are essential in managing osteoporosis, particularly for patients at very high-risk of fractures. Identifying candidates who will benefit the most from these treatments is crucial. For example, this group might include individuals with severe osteoporosis, multiple vertebral fractures, a recent fragility fracture or those unresponsive to antiresorptive treatments. Definitions of patients with a very high fracture risk vary across nations, are often based on fracture history, bone mineral density (BMD), and/or fracture risk calculated by FRAX® or other algorithms. However, for very high-risk patients, anabolic agents such as teriparatide, abaloparatide, or romosozumab are commonly recommended as first-line therapies due to their ability to stimulate new bone formation and improve bone microarchitecture, offering significant benefits in rapid fracture reduction over antiresorptive therapies. The cost-effectiveness of these agents is a critical consideration for decision-makers. Despite their higher costs, their effectiveness in significantly reducing fracture risk and improving quality of life can justify the investment, especially when long-term savings from reduced fracture rates and associated healthcare costs are considered. Additionally, after completing a course of anabolic therapy, transitioning to antiresorptive agents like bisphosphonates or denosumab is crucial to maintain the gains in bone density and minimize subsequent fracture risks. This sequential treatment approach ensures sustained protection and optimal resource utilization. In summary, the effective use of bone forming agents in osteoporosis requires a comprehensive strategy that includes accurate patient identification, consideration of cost-effectiveness, and implementation of appropriate sequential treatments, ultimately maximizing patient outcomes and healthcare efficiency., (© 2024. The Author(s).)

The purpose of this multicentric study was to evaluate the prevalence and causes of Elevated Bone Mass (EBM) in patients who underwent DXA scanning over a 10-year period. The prevalence of EBM was 1 in 100. The main causes of EBM were degenerative spine disorders and renal osteodystrophy., Introduction: Reports of elevated bone mass (EBM) on routine dual energy X-Ray absorptiometry (DXA) scanning are not infrequent. However, epidemiological studies of EBM are few and definition thresholds are variable. The purpose of this French multicentric study was to evaluate the prevalence and causes of EBM in adult patients who underwent DXA scanning over a 10-year period., Methods: This multicentric, retrospective study was conducted in six French regional bone centres. DXA databases were initially searched for individuals with a bone mineral density (BMD) Z-score ≥ +4 at any site in the lumbar spine or hip from April 1st, 2008 to April 30st, 2018., Results: In all, 72,225 patients with at least one DXA scan were identified. Of these, 909 (322 men and 587 women) had a Z-score ≥ + 4, i.e. a prevalence of 1.26% [1.18-1.34%]. The DXA scan reports and imagery and medical records of the 909 EBM patients were reviewed and 936 causes were found. In 42 patients (4%), no cause could be determined due to unavailability of data. Artefactual causes of EBM were found in 752 patients (80%), in whom the predominant cause was degenerative disease of the spine (613 patients, 65%). Acquired causes of focal EBM-including Paget's disease (n = 7)-were found in 12 patients (1%), and acquired causes of generalized EBM-including renal osteodystrophy (n = 32), haematological disorders (n = 20) and hypoparathyroidism (n = 15)-in 84 patients (9%). Other causes were rare hereditary diseases and unknown EBM in 19 (2%) and 27 (3%) cases respectively., Conclusions: The prevalence of EBM was approximately 1 in 100. These findings suggest that degenerative disease of the spine is the main cause of EBM, but that acquired or hereditary diseases are also causal factors., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Background: Radiofrequency Echographic Multi Spectrometry (REMS) is a non-ionizing technology for the densitometric assessment of osteoporosis. It has already been validated in Italian women with respect to the current clinical reference technology, Dual-energy X-ray Absorptiometry (DXA)., Purpose: Aim of the current study was to assess the diagnostic accuracy of REMS technology with respect to DXA in a wider European clinical context., Methods: A total of 4307 female Caucasian patients aged between 30 and 90 years underwent DXA and REMS scans at femoral neck and/or lumbar spine (the site depending on the medical prescription). The acquired data underwent a rigorous quality check in order to exclude the erroneous DXA and REMS reports. The diagnostic agreement between the two technologies was assessed, also stratifying for patients' age groups. The ability to recognise previously fractured patients was also investigated., Results: Overall, 4245 lumbar spine scans and 4271 femoral neck scans were performed. The ability to discriminate patients with and without osteoporosis by femoral neck investigation resulted in sensitivity and specificity of 90.4% and 95.5%, respectively. For lumbar spine scans, a sensitivity of 90.9% and a specificity of 95.1% were obtained. The areas under the curve (AUCs) of the Receiver Operating Characteristic (ROC) curve evaluating the ability to discriminate groups of patients with previous osteoporotic fracture using DXA and REMS T-score values were 0.631 and 0.683 (p < 0.0001), respectively, for femoral neck scans, whereas 0.603 and 0.640 (p = 0.0002), respectively, for lumbar spine scans., Conclusion: The diagnostic effectiveness of REMS technology at reference anatomical sites for the assessment of osteoporosis has been confirmed in a large series of female patients, spanning from younger and pre-menopausal to elderly women up to 90 years, in a multicenter European clinical context., (Copyright © 2020. Published by Elsevier Inc.)

Background: Dual X-ray absorptiometry body composition measurements are widely used for clinical and research settings. It is well known that measurements vary across instruments, needing caution for longitudinal monitoring or multicentric studies. This study was to quantify intra- and inter-center variability of bone mineral content, bone mineral density, fat and lean body composition measurements between Hologic Discovery models in order to calculate the corrective factors to be applied for multicenter research projects., Materials and Methods: A whole body phantom composed of materials representing the thickness and percentage of bone, lean and fat mass in the human physiological range was analyzed ten times in three different centers using dual energy X-ray absorptiometry scanners (Two Hologic Discovery QDR A and one QDR W). In addition, we used a morphometric vertebral phantom to monitor stability and a three steps block phantom to check accuracy., Results: We found a good long-term stability and accuracy for the three devices. Intra-center coefficients of variation were within the range of the manufacturer acceptable values (bone mineral density: 1.40%, bone mineral content: 1%, area: 1.50%, fat mass: 0.89%, lean mass: 0.76%, total mass: 0.12%). Whereas the inter-center coefficient of variation exceeded 8% (bone mineral density: 8.18%, bone mineral content: 3.03%, area: 8.63%: fat mass: 3,92%, lean mass: 7.89%, total mass: 2.85%)., Conclusion: Our study showed that the discrepancies across centers remain a major concern, particularly with regard to body composition results. Our study highlight the need of cross calibration between densitometers and proposes corrective factors evaluated from a whole body phantom to lead multicentric studies adjustment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Reports of elevated bone mass (EBM) on routine DXA scanning are not infrequent. However, epidemiological studies of EBM are few in number and definition thresholds variable. The purpose of this study was to assess the prevalence and causes of EBM in the general population referred to a single university hospital - catering for a population of 4 million inhabitants - for DXA scanning., Material and Methods: DXA databases were initially searched for individuals with a bone mineral density (BMD) Z-score ≥+4 at any site in the lumbar spine or hip from April 1st, 2008 to April 30st, 2018. Two Hologic scanners were available at the Lille University Hospital (France). Prevalence of EBM was evaluated, as were causes associated with EBM., Results: At the lumbar spine, 18,229 bone density tests were performed in women and 10,209 in men. At the hip, 17,390 tests were performed in women and 9857 in men. The total number of patients who had at least one bone density test was 14,745, of which 64.2% were female. Of these 14,745 patients, 211 had a Z-score ≥+4 at any site, i.e. a prevalence of 1.43% [1.25%-1.64%]. The DXA scans and medical records of 92 men and 119 women with elevated BMD were reviewed to assess causes. An artefactual cause was found in 164 patients (75%) with EBM (mostly degenerative disease of the spine), and an acquired cause of focal EBM was found in only 2 patients, both of whom had sclerotic bone metastases from prostate cancer. An acquired cause of generalized EBM was found in 32 patients (15%), the vast majority of whom had renal osteodystrophy (n = 11), followed by hematological disorders (n = 9; e.g. myeloproliferative syndromes and mastocytosis) and diffuse bone metastases from solid cancer (n = 5). Of the remaining causes, rare hereditary diseases (e.g. osteopetrosis…) and unexplained EBM were found in 10 and 6 cases respectively., Conclusion: The prevalence of EBM (Z-score ≥+4 at any site) was 1.43% [1.25%-1.64%]. In nearly all instances (97.1%) the explanation for EBM could be found in the medical record and through conventional investigations. This study suggests that the main cause of EBM is degenerative disease of the spine. Further studies are needed to differentiate artefactual EBM from hereditary or acquired EBM, and to investigate unexplained EBM. Genetic testing may prove useful in elucidating rare unknown causes., Competing Interests: Declaration of competing interest Aurore Nottez, Sami Kolta, Georges Lion, Camille Ternynck, Isabelle Legroux-Gérot, Marie-Christine Vantyghem, Bernard Cortet and Julien Paccou declare that they have no conflict of interest regarding this study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Decreased mineral density is one of the major complications of anorexia nervosa. The phenomenon is even more pronounced when the disease occurs during adolescence and when the duration of amenorrhoea is long. The mechanisms underlying bone loss in anorexia are complex. Oestrogen deficiency has long been considered as the main factor, but cannot explain the phenomenon on its own. The essential role of nutrition-related factors-especially leptin and adiponectin-has been reported in recent studies. Therapeutic strategies to mitigate bone involvement in anorexia are still a matter for debate. Although resumption of menses and weight recovery appear to be essential, they are not always accompanied by a total reversal of bone loss. There are no studies in the literature demonstrating that oestrogen treatment is effective, and the best results seem to have been obtained with agents that induce bone formation-such as IGF-1-especially when associated with oestrogen. As such, bone management in anorexia remains difficult, hence, the importance of early detection and multidisciplinary follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Increased biochemical bone turnover markers (BTMs) measured in serum are associated with bone loss, increased fracture risk and poor treatment adherence, but their role in clinical practice is presently unclear. The aim of this consensus group report is to provide guidance to clinicians on how to use BTMs in patient evaluation in postmenopausal osteoporosis, in fracture risk prediction and in the monitoring of treatment efficacy and adherence to osteoporosis medication., Methods: A working group with clinical scientists and osteoporosis specialists was invited by the Scientific Advisory Board of European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)., Results: Serum bone formation marker PINP and resorption marker βCTX-I are the preferred markers for evaluating bone turnover in the clinical setting due to their specificity to bone, performance in clinical studies, wide use and relatively low analytical variability. BTMs cannot be used to diagnose osteoporosis because of low sensitivity and specificity, but can be of value in patient evaluation where high values may indicate the need to investigate some causes of secondary osteoporosis. Assessing serum levels of βCTX-I and PINP can improve fracture prediction slightly, with a gradient of risk of about 1.2 per SD increase in the bone marker in addition to clinical risk factors and bone mineral density. For an individual patient, BTMs are not useful in projecting bone loss or treatment efficacy, but it is recommended that serum PINP and βCTX-I be used to monitor adherence to oral bisphosphonate treatment. Suppression of the BTMs greater than the least significant change or to levels in the lower half of the reference interval in young and healthy premenopausal women is closely related to treatment adherence., Conclusion: In conclusion, the currently available evidence indicates that the principal clinical utility of BTMs is for monitoring oral bisphosphonate therapy.

A finding of high bone mineral density (BMD) from routine dual-energy X-ray absorptiometry (DXA) screening is not uncommon. No consensus exists about the definition of high BMD, and T-score and/or Z-score cutoffs of ≥+2.5 or ≥+4 have been suggested. The many disorders that can result in high BMD are usually classified based on whether the BMD changes are focal vs. generalized or acquired vs. constitutional. In over half the cases, careful interpretation of the DXA report and images identifies the cause as an artefact (e.g., degenerative spinal disease, vascular calcifications, or syndesmophytes) or focal lesion (e.g., sclerotic bone metastasis or Paget's disease). Generalized acquired high BMD may be secondary to a diverse range of disorders such as fluorosis, diffuse bone sclerosis related to renal osteodystrophy, hematological diseases, and hepatitis C. Identification of the cause may require additional investigations such as imaging studies, serum tryptase assay, or serological tests for the hepatitis C virus. Finally, high BMD is a feature of many genetic diseases, most notably osteopetrosis and the disorders caused by mutations in the sclerostin gene SOST (sclerosing bone dysplasia and van Buchem disease) or in the LRP5 gene encoding the low-density lipoprotein receptor-related protein 5 (which is the Wnt co-receptor)., (Copyright © 2018 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: In renal transplant patients, bone loss may be related to the drugs patients are taking but also to their past history of chronic kidney disease. The purpose of this study was to assess changes in BMD 2 years after an initial assessment (performed 9 months post transplantation) and the factors associated with these changes., Methods: This longitudinal study included patients who had undergone a renal transplantation between 2005 and 2011, and who were followed up at the Lille Regional University Hospital. Patients were included if they had a first bone evaluation (including bone densitometry, spine X-rays and biological assessment) and at least another BMD assessment. The first assessment was performed on average 9 months post transplantation. A second assessment was performed at 2 years., Results: Two hundred fifty-nine out of 366 patients satisfied the inclusion criteria. The population included 96 women. Mean age at transplantation was 49.7 ± 12.1 years. Mean duration of dialysis was 3.2 ± 3.3 years. For 75 patients (29.0%), corticosteroid treatment was discontinued 7 days after transplantation without subsequent resumption during follow-up. Vertebral fractures assessed by X-rays at baseline were found in 28 patients (10.8%). According to the WHO classification, 106 patients (40.9%) patients had osteoporosis and 111 patients (42.8%) had osteopenia at the first assessment. Oral bisphosphonates were prescribed for 95 patients. The decision to prescribe bisphosphonates was taken jointly by rheumatologists and nephrologists based on BMD assessment, past history of fracture and corticosteroid management. In all patients, BMD gains at the second evaluation (2.2 ± 0.79 years) compared with baseline were significant (3.9 ± 6.6, 2.6% ± 7.6, 3.0 ± 7.2% at the lumbar spine, femoral neck and total hip respectively; p < 0.0001). The difference in gain between bisphosphonate-treated and untreated patients was significant (+ 5.0 ± 0.8% (p < 0.0001), + 2.5 ± 1.0% (p = 0.01) and + 2.7 ± 0.9% (p < 0.01) at the lumbar spine, femoral neck and total hip respectively. The patients who benefited early corticosteroid discontinuation had higher gains in BMD at the lumbar spine (+ 2.1 ± 0.9%; p = 0.02) and total hip (+ 2.0 ± 1.0%; p = 0.04) compared to those for whom corticosteroid therapy was maintained. Stepwise regression analysis (patients without bisphosphonates) showed associations between change in BMD (femoral neck) and duration of corticosteroid therapy, bone alkaline phosphatase level at baseline, and absence of vertebral fracture. No correlation was found between change in BMD and duration of dialysis or renal function., Conclusion: Kidney transplant recipients have an increased risk of bone fragility in the year following transplantation. Bisphosphonates and early corticosteroid discontinuation can improve BMD.

In clinical practice, areal bone mineral density (aBMD) is usually measured using dual-energy X-ray absorptiometry (DXA) to assess bone status in patients with or without osteoporotic fracture. As BMD has a Gaussian distribution, it is difficult to define a cutoff for osteoporosis diagnosis. Based on epidemiological considerations, WHO defined a DXA-based osteoporosis diagnosis with a T-score <-2.5. However, the majority of individuals who have low-trauma fractures do not have osteoporosis with DXA (i.e., T-score <-2.5), and some of them have no decreased BMD at all. Some medical conditions (spondyloarthropathies, chronic kidney disease and mineral bone disorder, diabetes, obesity) or drugs (glucocorticoids, aromatase inhibitors) are more prone to cause fractures with subnormal BMD. In the situation of fragility fractures with subnormal or normal BMD, clinicians face a difficulty as almost all the pharmacologic treatments have proved their efficacy in patients with low BMD. However, some data are available in post hoc analyses in patients with T score >-2. Overall, in patients with a previous fragility fracture (especially vertebra or hip), treatments appear to be effective. Thus, the authors recommend treating some patients with a major fragility fracture even if areal BMD T score is above -2.5.

Context: There is growing interest in the relationship between bone marrow fat (BMF), bone mineral density (BMD), and fractures. Moreover, BMF might be influenced by metabolic diseases associated with bone loss and fractures, such as type 2 diabetes mellitus (T2DM), anorexia nervosa (AN), and obesity., Methods: The primary-source literature for this review was acquired using a PubMed search for articles published between January 2000 and April 2015. Search terms included BMF, BMD, fractures, T2DM, AN, and obesity. The titles and abstracts of all articles were reviewed for relevant subjects., Results: Magnetic resonance imaging, with or without spectroscopy, was used to noninvasively quantify BMF in humans. A negative relationship was found between BMD and BMF in both healthy and osteopenic/osteoporotic populations. Data are lacking on the relationship between BMF and fractures. Studies in populations of individuals with metabolic diseases such as T2DM, AN, and obesity have shown BMF abnormalities., Conclusions: We conclude that most human data demonstrate an inverse relationship between BMF and BMD, but data on the relationship with fractures are inconsistent and need further study. In daily practice, the usefulness for clinicians of assessing BMF using magnetic resonance imaging is still limited. However, the perspectives are exciting, particularly in terms of improving the diagnosis and management of osteoporosis.

The Trabecular Bone Score is a rather new index obtained at the lumbar spine at the same time as a real bone mineral density. It was developed to reflect bone microarchitecture. It was proposed to be easily used in everyday practice as a surrogate of bone strength. Our aim was to review 1. technical points such as correlations between Trabecular Bone Score and bone microarchitectural parameters, Trabecular Bone Score and bone strength, the effects of dual-energy X-ray absorptiometry image spatial resolution, age, macroarchitecture, body mass index, and osteoarthritis, on Trabecular Bone Score, and 2. evidences to use Trabecular Bone Score for separating individuals with fragility fractures from controls, predicting fragility fractures, and for longitudinally monitoring changes related to treatments. Correlations between Trabecular Bone Score and bone microarchitectural parameters vary widely across bone sites, microarchitectural parameters, and study designs. In vivo, the Trabecular Bone Score explains little of the variance in trabecular microarchitectural parameters. We emphasize that it is a texture parameter. The Trabecular Bone Score is reduced in patients with fragility fracture. Several retrospective and prospective studies have shown its discriminative ability regarding the fracture risk. When combining the areal Bone mineral Density and Trabecular Bone Score, the Trabecular Bone Score remains a predictor of fracture but not the areal Bone Mineral Density. However in prospective studies, the best predictor of fracture remains hip areal bone mineral density. Due to the lack of evidence, we recommend not to use Trabecular Bone Score for following patients treated by anti-osteoporotic drugs., (Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

The objective of this systematic literature review is to discuss the latest French recommendation issued in 2012 that a fall within the past year should lead to bone mineral density (BMD) measurement using dual-energy X-ray absorptiometry (DXA). This recommendation rests on four facts. First, osteoporosis and fall risk are the two leading risk factors for nonvertebral fractures in postmenopausal women. Second, BMD measurement using DXA supplies significant information on the fracture risk independently from the fall risk. Thus, when a fall occurs, the fracture risk increases as BMD decreases. Third, osteoporosis drugs have been proven effective in preventing fractures only in populations with osteoporosis defined based on BMD criteria. Finally, the prevalence of osteoporosis is high in patients who fall and increases in the presence of markers for frailty (e.g., recurrent falls, sarcopenia [low muscle mass and strength], limited mobility, and weight loss), which are risk factors for both osteoporosis and falls. Nevertheless, life expectancy should be taken into account when assessing the appropriateness of DXA in fallers, as osteoporosis treatments require at least 12months to decrease the fracture risk. Another relevant factor is the availability of DXA, which may be limited due to geographic factors, patient dependency, or severe cognitive impairments, for instance. Studies are needed to better determine how the fall risk and frailty should be incorporated into the fracture risk evaluation based on BMD and the FRAX® tool., (Copyright © 2014. Published by Elsevier SAS.)

Purpose of Review: This review highlights recently published data on the pathophysiology, guidelines and treatment of cystic fibrosis (CF)-related bone disease., Recent Findings: The exact role of the cystic fibrosis transmembrane conductance regulator (CFTR), specifically the ΔF508 allele, has been investigated in F508del-CFTR homozygous mice and the F508del-CFTR mutation may contribute to CF-related bone disease by slowing new bone formation. The European Cystic Fibrosis Society has issued guidelines for bone mineral density assessment, management of low-trauma fractures and bisphosphonate therapy. A systematic review based on meta-analyses reports that oral and intravenous bisphosphonates both improve bone mineral density in CF patients, but no data are available concerning the reduction of low-trauma fractures., Summary: European Cystic Fibrosis Society guidelines may help physicians to improve the management of CF-related bone disease.

Context: Adipokines (leptin, adiponectin, resistin, visfatin) and ghrelin may be implicated in bone metabolism., Objective: The aim was to perform an overview of the influence of blood levels of adipokines or ghrelin on bone mineral density (BMD), osteoporotic status, and fracture risk in healthy men and women., Data Sources: We reviewed Medline, Embase, and Cochrane databases up to March 2010 and abstracts of international meetings from 2008 to 2009., Study Selection: Fifty-nine studies meeting the inclusion criteria (healthy men or women evaluated for both BMD or fracture risk and at least one adipokine and/or ghrelin levels) were analyzed in the systematic review of the 931 references found in the electronic databases., Data Extraction: We used a predefined extraction sheet., Data Synthesis: We performed meta-analyses using the method of the inverse of the variance estimated pooled correlations between adipokines/ghrelin and BMD. Inverse correlations between adiponectin levels and BMD were highlighted (pooled r from -0.14 to -0.4). Leptin is positively associated to BMD, especially in postmenopausal women (pooled r from 0.18 to 0.33). High levels of leptin were reported to be predictive of low risk of fractures, whereas high levels of adiponectin may be predictive of high risk of vertebral fractures in men only. No discriminative capacity of osteoporotic status was reported. We found no convincing data to support an association between resistin, visfatin, or ghrelin and BMD., Conclusion: Adiponectin is the most relevant adipokine negatively associated with BMD, independent of gender and menopausal status. Inconsistent associations between adipokines and BMD are probably confounded by body composition, in particular fat mass parameters.

Given its increasing incidence and serious complications, osteoporosis requires safe and effective long-term treatment. Strontium ranelate (SR), a new anti-osteoporotic treatment with a unique mode of action, has been investigated in the SOTI (Spinal Osteoporosis Therapeutic Intervention) and the TROPOS (Treatment of Peripheral Osteoporosis) trials, two major 3-year multinational placebo-controlled phase 3 randomized clinical trials. Unlike antiresorptive agents, SR produced steady and significant bone mineral density increases that correlated directly with decreases in vertebral and hip fracture risk. The safety profile of SR was almost similar to placebo in both trials. A slight but significant increased risk of thromboembolism events was noted from the pooled phase 3 studies data. However, this increased was not found in a large retrospective observational study. Thus, SR demonstrates broad spectrum safety and efficacy in reducing the risks of both vertebral and nonvertebral (including hip) fractures in a wide variety of patients, and should be considered as a first-line option to treat women at risk of osteoporotic fractures, whatever their age, the severity of the disease, and their risk factors.

The purpose of this longitudinal study was to evaluate factors affecting changes in bone mineral density (BMD) in patients with anorexia nervosa (AN) and osteoporosis and, more particularly, to assess the benefits of hormone replacement therapy (HRT) on BMD in these patients. Our study involved 45 AN patients, 12 of whom had been treated by HRT for 2 years following a diagnosis of osteoporosis by densitometry (WHO criteria). Patients' mean age was 25.3 +/- 6.7 years. Mean duration of illness was 5.7 +/- 5.3 years. Serum calcium and phosphate were measured at baseline, as were bone remodeling markers. Osteodensitometry by dual-energy X-ray absorptiometry was performed at inclusion and after 2 years. After 2 years, no significant differences were observed between spine, femoral neck, and total hip BMDs either in the HRT group (P = 0.3, P = 0.59, P = 0.58) or in the nontreatment group (P = 0.17, P = 0.68, P = 0.98). Moreover, there were no significant differences between the two groups when changes in spine, femoral neck, and total hip BMDs at 2 years were compared (P = 0.72, P = 0.95, P = 0.58). In both groups, change in weight at 1 year correlated with change in spine BMD at 2 years (r = 0.35, P = 0.04) and change in total-hip BMD at 2 years (r = 0.35, P = 0.04) but not with change in femoral neck BMD at 2 years. Patients with a body mass index (BMI) > or = 17 kg/m(2) at 2 years showed a significant increase in total-hip BMD when compared with patients with a BMI < 17 kg/m(2) (+4.4% +/- 6.7 vs. -0.5% +/- 6.01, P = 0.03). No significant differences were observed for spine and femoral neck BMD. In patients who had recovered their menstrual cycle, significant increases were observed in spine BMD (+4% +/- 6.3 vs. -1.9% +/- 5.6, P = 0.008), femoral neck BMD (+3% +/- 6.2 vs. -2.4% +/- 8, P = 0.05), and total-hip BMD (+3% +/- 7.1 vs. -3.7% +/- 10, P = 0.04). Prevention of bone loss at 2 years in AN patients treated by HRT was not confirmed in this study. We did confirm that increase in weight at 1 year was the most predictive factor for the improvement of spine and hip BMD at 2 years.

The purpose of this cross-sectional study was to assess the extent of and mechanisms involved in bone loss in anorexia nervosa patients. We compared 113 anorexia nervosa patients (mean age 25 +/- 8 years, mean duration of disease 5.7 +/- 6.1 years) with 21 age-matched controls. Mean duration of amenorrhea was 3.2 +/- 4.7 years. We measured serum calcium and phosphate; bone remodeling markers (osteocalcin, bone-specific alkaline phosphatase [BSAP], serum crosslaps [CTX], and carboxyl-terminal telopeptide of type I collagen [ICTP]); follicle-stimulating hormone and luteinizing hormone levels; and estradiol (ultrasensitive assay), cortisol, urinary free cortisol, thyroid function, prolactin, and nutritional factors (insulin-like growth factor I [IGF-I], IGF binding protein 3 [IGFBP3]). In controls, only bone remodeling markers and nutritional factors were measured. Osteodensitometry was also performed on both patients and controls. Weight and body mass index (BMI) were significantly lower in anorexia nervosa patients than in controls (P < 0.0001). No significant differences were observed in biological indicators except for IGF-I, which was lower in anorexia nervosa patients (0.9 +/- 0.4 UI/mL) than in controls (1.5 +/- 0.4 UI/mL) (P < 0.0001). Densitometric measurements at three sites were significantly lower in anorexia nervosa patients and correlated with duration of disease and amenorrhea and with IGF-I at the hip only (P < 0.01). In the study population, osteoporosis was observed in 24 patients (21%) and osteopenia in 54 patients (48%). Patients with osteoporosis were significantly older and had longer disease and amenorrhea durations; lower weight and BMI; higher alkaline phosphatase, BSAP, and osteocalcin; and lower serum ICTP, IGF-I, and IGFBP3. All of these differences were significant and remained so even after multiple adjustments were made, except for IGF-I (P = 0.21). When multivariate analysis was performed, we found that age at onset of amenorrhea, weight, alkaline phosphatase, urinary free cortisol, and serum estradiol concentration accounted for 54% of the variance in spinal bone mineral density (BMD). Duration of amenorrhea, alkaline phosphatase, and weight explained 46.6% of the variance in femoral neck BMD. Duration of amenorrhea, IGF-I, and ICTP levels accounted for 38.6% of the variance observed in total hip BMD. The etiology of bone loss in patients with anorexia nervosa is multifactorial. Hypoestrogenia alone cannot account for this loss, and nutritional factors, IGF-I concentrations in particular, seem to play an important role.

Unlabelled: A few studies suggest that thiazide diuretic agents may have modest beneficial effects on bone. Few data are available on the effects of these medications in patients with osteoporosis and hypercalciuria., Objective: To evaluate the effects of thiazide diuretic therapy on bone mass and urinary calcium excretion in hypercalciuretic osteoporotic male patients., Patients and Methods: Osteoporosis was defined as a greater than 2.5 standard deviation (S.D.) decrease in bone mineral density (BMD) at the lumbar spine or hip (T-score). We used an open-label prospective design to compare 14 patients with hypercalciuretic osteoporosis treated with a thiazide diuretic for 18 months and 13 patients with primary osteoporosis treated with calcium and vitamin D supplementation. Mean age was 53.5 +/- 9.6 years in the thiazide group and 48.7 +/- 8.4 years in the calcium-vitamin D supplementation group. The following serum parameters were assayed at baseline: 25OH-D3, 1,25OH-D3, parathyroid hormone (PTH), and bone turnover markers. Urinary calcium excretion and BMD by dual-energy X-ray absorptiometry at the spine and hip were determined at baseline and after 18 months of treatment., Results: Annual BMD increases were similar in the two groups during the 18-month treatment period: lumbar spine, 0.6 +/- 2.5% (P = 0.47) in the thiazide group and 0.004 +/- 3% (P = 0.78) in the supplementation group; femoral neck, 0.47 +/- 2.6% (P = 0.89) and 1.1 +/- 3.2% (P = 0.22); total hip, 0.65 +/- 2.5% (P = 0.37) and 0.12 +/- 2.1% (P = 0.51). Urinary calcium excretion fell by 45.9% in the thiazide group from baseline to study completion (P = 0.0015)., Conclusion: We found no evidence that thiazide therapy increased bone mass in patients with hypercalciuria and osteoporosis as compared to calcium-vitamin D supplementation in patients with osteoporosis but no hypercalciuria. In contrast, our results establish the efficacy of thiazide diuretics in reducing urinary calcium excretion, an effect that may decrease the risk of urinary lithiasis. Studies in larger patient cohorts treated for longer periods are needed to confirm or refute our findings.

Relationships among quantitative ultrasound of bone (QUS), bone mineral density (BMD) and bone microarchitecture have been poorly investigated in human calcaneus.Twenty-four specimens, from 12 men and 12 women (mean age 78 +/- 10 years; range 53-93), removed from cadavers were studied. The feet were axially sectioned above the ankle. Two variables were measured for QUS (Achilles, Lunar): broadband ultrasound attenuation (BUA) and speed of sound (SOS). A third variable, the stiffness index (SI), which is a combination of both BUA and SOS, was also calculated. BMD (a lateral view) was measured on a QDR 2000 densitometer (Hologic). Bone microarchitecture was assessed by computed tomography (CT) using a conventional CT-system. Fifteen sagittal sections (1 mm in width and 2 mm apart) were selected for CT. Methods used for characterizing bone microarchitecture consisted in structural (trabecular network characterization) and a fractal analyses. The relationships between QUS and bone microarchitecture were assessed by simple linear regression analysis with and without adjustment for BMD (partial correlation) and by backward stepwise regression analysis. Strong relationships were found between BMD and QUS. Adjusted r(2) values were 0.545 for SOS and 0.717 for SI. Two microarchitectural variables were also significantly correlated with both SOS and SI: apparent trabecular separation (App Tr Sp) and trabecular bone pattern factor (App TBPF). After adjustment for BMD few correlations between QUS and microarchitectural variables were always significant. Adjusted squared semipartial coefficients of correlation (rsp2) values between SOS and bone microarchitecture were 6%, 6.8%, 13.2% and 4.6% for App BV/TV, App Tr Sp, App TBPF and fractal dimension (FD), respectively. For SI, corresponding figures were 3.7%, 4.1%, 5.2% and 3.2%. Backward stepwise regression analysis using BMD and microarchitecture showed a slight increase of r(2) values that varied from 8.4% for SI to 17.8% for SOS, compared with BMD alone. The current study suggests that although BMD is a major determinant of acoustic properties of human calcaneus, significant density independent relationships with bone microarchitecture should also be taken into account.

Quantitative ultrasound (QUS) measurement, a different approach to bone fragility assessment, has already been attempted in women with osteoporosis but rarely in men. In order to test its value and ability to identify osteoporotic men, a case-control prospective study was conducted using the Lunar Achilles, a device that measures attenuation and velocity parameters. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI), a composite parameter, were assessed through the heel of 66 osteoporotic patients, and compared with the results in 35 controls. Patients had sustained a low-trauma fracture and/or had a lumbar and/or femoral bone mineral density (BMD) more than 2.5 SD below the young male reference value. As expected, all QUS parameters were statistically lower in patients, as were the dual-energy X-ray absorptiometry (DXA) measurements at the hip and lumbar spine. The two methods were compared for their ability to predict the risk of osteoporotic fractures. The odds ratios (ORs), with their 95% confidence limits, for fractures per 1 SD decrease were significant, especially for SOS and SI (OR = 2.3 [1.4-3.6] and 2.1 [1.3-3.3] respectively) and to a lesser extent for BUA (1.6 [1.0-2.4]). Our study suggests that QUS is associated with a history of low-trauma fracture in men; sensitivity is, however, less than when results are compared with BMD measurements (OR = 2.8 [1.6-5.0] and 3.4 [1.6-7.0] for lumbar spine and hip, respectively). Prospective studies are required before QUS can be recommended for clinical use in male osteoporosis.

This study aimed to investigate the usefulness of computed tomography (CT) image analysis of the distal radius for comparing two groups of postmenopausal women matched for age and bone mineral density at both the lumbar spine and femoral neck. The first one consisted of 16 women with at least one vertebral fracture and the second consisted also of 16 women without disease affecting bone mass or bone metabolism. Eight slices were selected in each patient: four consecutive coronal slices and four consecutive axial slices. Bone texture analysis was performed using structural methods leading to the measurement of 24 features. Most of the structural variables derived from histomorphometric parameters and were measured after segmentation from a binary or a skeletonized image. Nine variables were significantly different between the two groups on axial slices: valley number, valley surface area, apparent bone volume/tissue volume (BV/TV), apparent trabecular separation, apparent trabecular number, trabecular bone pattern factor, trabecular skeletal length, node count, and node-to-node strut count. Also four variables were significantly different between osteoporotic women and controls on coronal slices: apparent BV/TV, trabecular partition, node-to-node strut count, and terminus-to-terminus strut count. In conclusion this study suggests that bone texture analysis could yield additional data on bone mass for explaining bone strength and therefore could be used for improving the prediction of fracture risk.

In a prospective case-control cross-sectional study, we investigated the usefulness of both computed tomography (CT) and magnetic resonance (MR) image analysis of the distal radius for distinguishing a small sample of fractured osteoporotic women from control women regardless of bone mineral density. The study population included 12 subjects who were divided into two groups according to their bone status. The first group consisted of six women with at least one vertebral fracture occurring in the absence of high-energy trauma, and the second group consisted of six women without disease affecting bone mass or bone metabolism. Cross-sectional and coronal slices were obtained from both CT and MR systems. For CT images, the slice thickness was 1000 jim and the plane resolution was approx 200 jim x 200 jim. MR images were obtained from a 1.5-T imager with a two-dimensional spin-echo Ti-weighted sequence leading to a slice thickness of 2000 jim and a plane resolution of 195 jim x 195 jim. Bone texture analysis was performed using fractal and structural methods leading to the measurement of 23 features. Most of the structural variables derived from histomorphometric parameters and were measured after segmentation from a binary or a skeletonized image. Bone densitometry was measured by dual-energy X-ray absorptiometry both at the lumbar spine and the nondominant femoral neck. On cross-sectional slices, 12 variables, mainly obtained from structural analysis, were significantly different between the two groups for CT images (p < 0.05) against two variables only for MR images (p < 0.05). The number of variables statistically different between the two groups was significantly higher for CT images compared with MR images (p = 0.003). In the same way, odds ratios for fracture per 1 control group standard deviation decrease were significant for 10 variables on CT images, whereas, in contrast, none of the variables measured on MRI images led to significant odds ratios. The results obtained for the two methods on coronal slices were poorer without a difference between either CT or MR images in terms of discrimination between fracture and nonfracture subjects. In conclusion, this study suggests that bone texture analysis obtained from CT compared with MRI offers a best discrimination between controls and osteoporotic patients, probably the result to the spatial resolution. which is better for CT than for MR images.

Quantitative ultrasound (QUS) of bone and new markers of bone remodeling have been poorly investigated in mild primary hyperparathyroidism (PHPT). In this study 26 patients (20 females and 6 males) were evaluated. BUA and SOS were measured by QUS at the heel. Markers of bone remodeling assessed were bone alkaline phosphatase (BAP), osteocalcin (OC), procollagen type I N- and C-terminal propeptides (PINP et PICP), and procollagen type I C-terminal telopeptide in blood and urine (ICTP and CTX). Bone mineral density (BMD) was measured at the lumbar spine (LS), femoral neck (FN), and Ward's triangle (WT). The control group comprised 35 sex- and age-matched subjects. The statistically significant variables between the two groups were (P < 0.05) BUA, BMD(LS), BMD(FN), BMD(WT), BAP, and OC. Corresponding z-scores were -0.55 +/- 0.75, -0.66 +/- 0.77, -0.66 +/- 0.71, -0.67 +/- 0.52, 1.87 +/- 3.87, and 1.93 +/- 3.53, respectively. Although PICP and PINP levels were higher in PHPT patients as compared with controls, the difference was not significant. Several markers of bone turnover were moderately correlated with both QUS (r = -0.39 to -0.55) and BMD (r = -0.48 to 0.63). In conclusion QUS seems to be a relevant tool in the assessment of bone status for patients with mild PHPT.

Quantitative ultrasound (US) measurements have been shown to be a new technique assessing bone status. This study aimed to assess a new US instrument, the DBM Sonic 1200(R) (IGEA) which permits the measurement of the speed of sound in the proximal phalanges (SOSp) of the hand. The results obtained were compared with DXA (SOPHOS) and US measurements at the calcaneus (Achilles(R) LUNAR). The in vivo precision expressed by coefficient of variation was 0.91%. Ultrasound measurements of phalanges were significantly correlated with BMD in the entire group of 90 subjects: osteoporotic patients (n = 47) and controls (n = 43) (r = 0.44, femoral neck and 0.45, lumbar spine, P < 0.01). A significant correlation was also found in the control group (r = 0.33, lumbar spine and 0.38, femoral neck, P < 0.05) but not in the osteoporotic group (r = 0.3, lumbar spine and 0.17, femoral neck, P > 0.05). Mean values for 31 postmenopausal, osteoporotic women and age-matched controls showed a significant decrease in US measurements at the phalanges (P < 0.05) and the calcaneus (P < 0.01) as well as bone mineral density (BMD) at the spine and femoral neck (P < 0.01) in the osteoporotic group. A decision threshold for a sensitivity of 80% for osteoporotic fractures resulted in a specificity value of only 37% for SOSp, between 53 to 65% for calcaneus US measurements and 45 to 56% for BMD. The Z score, the odds ratio, the ROC curves, and areas under the curves plotted for the subgroup of 31 fractures and their healthy controls showed poorer values for SOSp than BMD and calcaneus US measurements. In conclusion, US measurements of phalanges seem to be less efficient than calcaneus US and BMD measurements to distinguish osteoporotic from healthy women. Other studies and also prospective studies are required to assess the interest in fracture risk assessment.

Objective: To study the relationship between bone turnover markers and bone mineral density in patients with rheumatoid arthritis., Methods: We studied 54 patients, 24 of whom were receiving low dose steroids, and compared them to 54 age and sex matched controls., Results: An 8.2% decrease of femoral neck bone mineral density (BMD) was found in patients not taking steroids compared with controls (confidence interval 1.2-15.3%). Serum markers of bone turnover -- namely, procollagen type I C-terminal propeptide (PICP) and procollagen type I N-terminal propeptide (PINP), which reflect bone formation, and procollagen type I C-terminal telopeptide, which reflects bone resorption -- were significantly increased compared with controls (p < 0.05, p < 0.01, p < 0.01, respectively). Both PINP levels and PICP levels were correlated with the femoral neck BMD as well as osteocalcin levels: R = -0.32 (p < 0.05), R = -0.29 (p < 0.05), and R = -0.42 (p < 0.01), respectively. The best independent predictors of bone mass (stepwise multiple regression analysis) at the femoral neck were steroid use, osteocalcin levels, age, height, the presence of rheumatoid factor, and the Health Assessment Questionnaire score, which explained 61.6% of the variance in femoral neck BMD., Conclusion: Elderly patients with RA using steroids with severe disease and high levels of osteocalcin have marked osteoporosis at the hip.

Objectives: To study bone mass and the factors that influence bone mass in rheumatoid arthritis patients versus controls., Patients and Methods: 85 patients (73 women) with a mean age of 57 +/- 11 years and a mean disease duration of 13 +/- 9 years were compared to 85 age- and sex-matched controls. Among the patients, 62 (76%) had positive rheumatoid factor tests and 51 (60%) were receiving steroid therapy, with a mean daily dose of 10 +/- 4 mg and a mean duration of 7 +/- 6 years. The following parameters were determined: morning stiffness duration, painful and swollen joint counts, Lee's and Ritchie's indices, Health Assessment Questionnaire score, erythrocyte sedimentation rate, and C-reactive protein. Bone mineral density was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry (Sophos L-XRA)., Results: In the nonsteroid-treated patients, bone mineral density was similar to that in controls at the lumbar spine but was decreased by 8% (95% confidence interval [CI], 1.8-14.2%) at the femoral neck (0.76 +/- 0.14 g/cm2 versus 0.83 +/- 0.15 g/cm2; P = 0.03). Decreases of 11.5% (95% CI, 8.1-14.9%) at the lumbar spine and 10.4% (95% CI, 6.4-14.4%) at the femoral neck were found in the steroid-treated patients versus the nonsteroid-treated patients. In the patient group, femoral neck bone mineral density was significantly negatively correlated with age (r = -0.5), the Heath Assessment Questionnaire score (r = -0.27), and the erythrocyte sedimentation rate (r = -0.25), whereas only the first two variables were significantly correlated with lumbar bone mineral density. A multiple linear regression model including age, glucocorticoid use, rheumatoid factor, the Health Assessment Questionnaire score, and the erythrocyte sedimentation rate was constructed and adjusted for the number of variables. This model explained 44.7% of the variance of femoral neck bone mineral density., Conclusion: Rheumatoid arthritis is associated with a decrease in bone mass that is most marked in patients with active and/or severe disease and in those who take glucocorticoids.

We evaluated ultrasound propagation through the calcaneus using the Achilles Lunar unit in patients with postmenopausal or glucocorticoid-induced osteoporosis. Speed of sound, broadband ultrasound attenuation and a combination of these two parameters called stiffness were determined. Reproducibility was 0.23%, 2.6%, and 2.6% for these three parameters, respectively. Bone mineral density measured at the spine and femoral neck by absorptiometry was significantly correlated with all three ultrasound parameters in the women with postmenopausal osteoporosis (n = 47) and in the controls (n = 42). In the patients with glucocorticoid-induced osteoporosis (n = 35), only speed of sound was significantly correlated with the bone mineral density measurements. Mean values in the subjects with postmenopausal osteoporosis and in their age-matched controls were 1473 +/- 27.2 m/sec versus 1500.6 +/- 29.6 m/sec for speed of sound, 95.3 +/- 9.6 dB/Mhz versus 105.7 +/- 10.1 dB/Mhz for broadband ultrasound attenuation, and 56.1 +/- 13.2 versus 70.9 +/- 14.1 for stiffness, indicating a significant difference (P < 0.01). Z scores were -0.91, -1.1, -0.93, -0.97, and -1.05 for bone mineral density at the spine, bone mineral density at the femoral neck, speed of sound, broadband ultrasound attenuation and stiffness, respectively. Receiver Operating Characteristic curves showed that there were no statistically significant differences between the ultrasound parameters at the calcaneus and the absorptiometry measurements at the spine and femoral neck. Mean values in glucocorticoid-treated patients and age-matched controls were 1480 +/- 26.9 m/sec versus 1505.1 +/- 30.3 m/sec for speed of sound, 99.2/-11.4 dB/Mhz versus 105.9 +/- -10.2 dB/Mhz for broadband ultrasound attenuation, and 60.7 +/- 14 versus 72.1/14.5 for stiffness, again indicating a significant difference (P < or = 0.01). Z scores were -0.55, -0.65, -0.8, -0.67, and -0.78 for bone mineral density at the spine, bone mineral density at the femoral neck, speed of sound, broadband ultrasound attenuation and stiffness, respectively. Our data suggest that ultrasound parameters measured at the calcaneus are useful for evaluating postmenopausal and glucocorticoid-induced osteoporosis.

Rheumatoid arthritis is associated with locoregional decalcification, which can be clearly demonstrated at the distal radius using single-photon absorptiometry. Bone loss at this site is probably due to the predominant involvement of the hands and wrists during rheumatoid arthritis. Estimates of the frequency of generalized bone loss have varied with the measurement technique used and the study design. Studies using dual-photon absorptiometry with a radioactive source have yielded conflicting data. The most recent studies of bone mineral density used dual energy X-ray absorptiometry, which is currently the best method in terms of reproducibility and precision; results suggested bone loss in the proximal femur, whereas lumbar spine measurements were usually normal or very slightly decreased. Findings from the few longitudinal studies are discordant; this may be ascribable to differences in bone mass measurement techniques, study population characteristics, and follow-up duration. Whereas bone loss was not demonstrated in the earliest longitudinal studies, recent investigations suggested that bone mineral density was decreased in rheumatoid arthritis patients as compared with controls. Corticosteroid therapy, even in daily dosages of less than 10 mg/d prednisone-equivalent, was associated with an approximately 10% decrease in bone mass after six months, in both cross-sectional and longitudinal studies. Rheumatoid arthritis patients had a two-fold increase in fracture risk, independently from their bone mass. Factors associated with higher fracture risks were corticosteroid therapy, physical inactivity, and female gender.

Summary: The purpose of this study was to assess the performance of our Fracture Liaison Service (FLS) over a period of 2 years. Osteoporosis medication was prescribed for 243 patients, and zoledronic acid was the main drug prescribed (60.2%). Introduction: A Fracture Liaison Service (FLS) was implemented at Lille University Hospital in 2016. The main purpose of this study was to assess the performance of the FLS using criteria proposed by the International Osteoporosis Foundation (IOF). Methods: The criteria used were patient identification, patient evaluation, post-fracture assessment timing, vertebral-fracture identification, blood and bone mineral density (BMD) testing, falls prevention, multifaceted health and lifestyle risk-factor assessment, and medication initiation and review. Results: Between January 2016 and January 2018, 736 patients (≥ 50 years old) with a recent history of fragility fracture (≤ 12 months) were identified. The identification rate for hip fractures was 74.2%. However, patient evaluation for all type of fractures was quite low (30.3%) since many patients failed to attend the FLS unit. The reasons for non-attendance were refusal, agreed but subsequently failed to attend, and still waiting to be seen. In all, 256 patients (76.6% female, mean (SD) age 74.3 (11.0) years) were seen at the FLS. Mean (SD) post-fracture assessment timing was 13.3 (9.3) weeks. Of the 139 patients seen for a non-vertebral fracture, 103 were assessed for vertebral fractures, and at least one new vertebral fracture was found in 45 of them (43.7%). Osteoporosis medication was prescribed for 243 (94.9%) patients. The main osteoporosis drug prescribed was zoledronic acid (60.2%). Conclusions: Secondary prevention of osteoporotic fractures has improved since the implementation of the FLS. However, patient identification, patient evaluation, and post-fracture assessment timing still need to be improved. [ABSTRACT FROM AUTHOR]

Summary: We performed a study to identify potential causes and risk factors of vertebral fracture cascade. Vertebral fracture cascade is a severe clinical event in patients with bone fragility. Only half of patients have an identified cause of secondary osteoporosis.Introduction: Vertebral fracture (VF) is the most common osteoporotic fracture, and a strong risk factor of subsequent VFs leading to VF cascade (VFC). We prompted a study to identify potential causes and risk factors of VFC.Methods: VFC observations were collected retrospectively between January 2016 and April 2017. VFC was defined as an occurrence of at least three VFs within 1 year.Results: We included in 10 centers a total of 113 patients with VFC (79.6% of women, median age 73, median number of VFs in the cascade, 5). We observed 40.5% and 30.9% of patients with previous major fractures and a previous VF, respectively, and 68.6% with densitometric osteoporosis; 18.9% of patients were currently receiving oral glucocorticoids and 37.1% in the past.VFC was attributed by the physician to postmenopausal osteoporosis in 54% of patients. A secondary osteoporosis associated with the VFC was diagnosed in 52 patients: glucocorticoid-induced osteoporosis (25.7%), non-malignant hemopathies (6.2%), alcoholism (4.4%), use of aromatase inhibitors (3.6%), primary hyperparathyroidism (2.7%), hypercorticism (2.7%), anorexia nervosa (2.7%), and pregnancy and lactation-associated osteoporosis (1.8%). A total of 11.8% of cases were reported following a vertebroplasty procedure. A total of 31.5% patients previously received an anti-osteoporotic treatment. In six patients, VFC occurred early after discontinuation of an anti-osteoporotic treatment, in the year after the last dose effect was depleted: five after denosumab and one after odanacatib.Conclusion: The results of this retrospective study showed that only half of VFC occurred in patients with a secondary cause of osteoporosis. Prospective studies are needed to further explore the determinants of this severe complication of osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: Using case vignette methodology, this study shows that only 4% of patients are maintained on oral bisphosphonates over 5 years, and prescribers switch or stop the treatment in 20-30% of cases at each visit. There are few determinants of these changes. More information on appropriate follow-up could help in patients' management. Introduction: Persistence to oral bisphosphonates, the most commonly prescribed anti-osteoporotic treatments, is low. The aim of this study was to evaluate the role of rheumatologists on the treatment patterns, and to assess the determinants of treatment changes. Methods: We used the methodology of case vignettes with the participation of 142 rheumatologists. Three baseline clinical vignettes were presented: (1) the physician was asked to indicate the most appropriate period to schedule the next visit over 5 years, (2) the physician was tested about parameters for follow-up (including traps), and (3) various results (both clinical, biological, densitometric, and radiological) were given by random and analyzed as determinants of treatment changes. Results: The study allowed assessment of 426 virtual clinical cases. Clinical examinations, patient's height, inquiries about falls, and adherence to treatment were deemed necessary in > 90% of cases. Bone mineral density was measured in 22, 40, and 71% of cases at 2, 3, and 5 years, respectively. Dental follow-up was recommended in less than 25% of cases. Only 4.2% of patients were maintained on the same treatment at 5 years, and a change of treatment (stop or switch) occurs in 20-30% of cases at each visit. Significant determinants were adherence to treatment, serum C-terminal crosslinking telopeptide of type 1 collagen (CTX) value, change in patient's height, and the occurrence of an incident vertebral fracture. Conclusion: Our study shows that maintenance of oral bisphosphonate in postmenopausal women managed by rheumatologists is low; there are few determinants of these changes and more information on appropriate follow-up could help in patients' management. [ABSTRACT FROM AUTHOR]

Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society (EUGMS), in collaboration with the International Association of Gerontology and Geriatrics for the European Region (IAGG-ER), the European Union of Medical Specialists (EUMS), the International Osteoporosis Foundation - European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people. [ABSTRACT FROM AUTHOR]

Summary: Bone mineral density (BMD; measured by DXA) changes were observed at all sites at 1 year in 146 patients with anorexia nervosa. Four independent factors accounted for the variation in BMD at the spine: duration of anorexia, bone-specific alkaline phosphatase (BAP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and triiodothyronine (T3). No change in BMD was observed from 1 to 2 years during follow-up. Introduction: The purpose of this study was to assess changes in BMD at 1 and 2 years in anorexia nervosa patients, and to explore the relationships between change in BMD and various clinical and biological parameters measured at the first visit. Methods: BMD was measured in anorexia nervosa patients at inclusion, at 1-year follow-up ( n = 146) and at 2-year follow-up ( n = 89). Results: Bone loss was observed at all sites at 1 year. When multivariate analyses were performed, four independent factors accounted for the variation in BMD at the spine: duration of anorexia nervosa, BAP, ICTP, and T3. At the total hip site, leptin level was the main factor accounting for the variation in BMD. Strong correlations were also observed between weight at 1 year and change in BMD at 2 years. At the 2-year follow-up, no significant change in BMD was observed at the spine or femoral neck. In patients who were no longer amenorrheic at 1 year, a significant improvement in BMD at 2 years was observed at the total hip (+1.2%, p = 0.02) and femoral neck (+3.7%, p = 0.02). Similarly, in patients with a body mass index >17 kg/m at 1 year, an improvement in BMD at the total hip at 2 years was observed (+3%, p = 0.02) Conclusion: Bone loss in anorexia nervosa patients occurs at an early stage, and the factors influencing such are different at the spine and hip. [ABSTRACT FROM AUTHOR]

The diagnosis of osteoporosis rests on areal bone mineral density (BMD) measurement using DXA. Cancellous bone microarchitecture is a key determinant of bone strength but cannot be measured using DXA. To meet the need for a clinical tool capable of assessing bone microarchitecture, the TBS was developed. The TBS is a texture parameter that evaluates pixel gray-level variations in DXA images of the lumbar spine. The TBS variations may reflect bone microarchitecture. We explain the general principles used to compute the TBS, and we report the correlations between TBS and microarchitectural parameters. Several limitations of the TBS as it is used now are pointed out. We discuss data from currently available clinical studies on the ability of the TBS to identify patients with fractures and to evaluate the fracture risk. We conclude that this new index emphasizes the failure of the BMD T-score to fully capture the fragility fracture risk. However, although microarchitecture may influence the TBS, today, to the best of our understanding, there is no sufficient evidence that a TBS measurement provides reliable information on the status of the bone microarchitecture for a given patient. The TBS depends on gray-level variations and in a projectional image obtained in vivo, these variations can have many causes. Nevertheless, as clinical studies suggest that the TBS predicts the risk of fracture even after adjustment for BMD, we are encouraged to learn more about this score. Additional studies will have to be performed to assess the advantages and limitations of the TBS, in order to ensure that it is used appropriately in clinical practice. [ABSTRACT FROM AUTHOR]

Summary: Methods: Leptin levels were measured in 103 consecutive women with anorexia nervosa. Results: Spine BMD and Z-score values were found to be significantly lower in the low tertile compared with the highest tertile. Duration of amenorrhea and leptin level accounted for 27% of the variance in lumbar spine BMD. Introduction: The purpose of this study was to assess leptin levels and other biological variables in a population of anorexia nervosa patients. Methods: Leptin levels were measured consecutively in 103 women with anorexia nervosa (AN) with a mean age of 24.9 ± 7.4 years. Osteodensitometry was also performed by dual energy X-ray absorptiometry (DXA). Results: Spine bone mineral density (BMD) and Z-score values were found to be significantly lower in the low tertile compared with the highest tertile. Duration of amenorrhea and leptin level accounted for 27% of the variance in lumbar spine BMD. The mean leptin level was 3.9 ± 4.6 ng/mL (normal values, 3.5-11 ng/mL). The distribution of leptin values was not a Gaussian distribution, and a log-transformed was therefore performed. A significant correlation was found between leptin level and spinal BMD ( r = 0.3; p = 0.002); significant correlations were observed for both femoral neck and total hip BMDs. When leptin level values were divided into tertiles, spine BMD and Z-score values were found to be significantly lower in the lower tertile ( p = 0.04 and p = 0.02) compared with the highest tertile. For femoral neck BMDs, the T-score was slightly lower between low and high tertile, but the difference was not statistically significant ( p = 0.07). When multivariate analyses were performed, two independent factors which could possibly account for the variance in spinal BMDs were found. Duration of amenorrhea and leptin level accounted for 27% of the variance ( p < 0.0001). Conclusion: The mechanisms underlying bone loss in AN patients remain unclear and complex, involving hypoestrogenia as well as nutritional factors such as insulin-like growth factor and leptin. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: An anti-angiogenic effect of bisphosphonates has been reported in different experimental models. Zoledronic acid is currently administered in osteoporotic patients as a single 5 mg injection once a year and its vascular effect in bone has not been yet evaluated. Materials and methods: The vascular dose effect of a single injection of zoledronic acid was evaluated on healing vascularization developed under a bone chamber implanted on the calvaria of 30 rats. After 3 weeks of healing, the rats were randomized into 3 groups receiving an injection of either physiologic saline solution (PSS) or zoledronic acid tested at  120 μg/kg, the equivalent of a 5 mg dose of zoledronic acid in humans (Z120), and  400 μg/kg, a supra-pharmacologic dose (Z400). A longitudinal follow-up of the healing vascular network was carried out at days (D) 1, 3, 6, 9, 12, 15 and 28 after injection by intravital imaging. Variations in vascular density, total length of the vascular network and mean diameter of vascular network branches were determined by image analysis (Aphelion® software). Results: A decrease was observed in both vascular density and total length of the network in control and treated groups (time effect). No difference in variation in vascular density was observed between the PSS group and the Z120 group at any time point (p =NS). A trend to a higher decrease in vascular density was noted between D12 and D15 in the Z400 group. A significant decrease in total length was noted at D15 in the Z400 group (p =0.03) compared to the PSS group, whereas no change was noted in rats treated with  120 μg/kg compared to PSS rats on any of the follow-up days (p =0.2). No variation in mean diameter of vascular network branches was noted in any of the three groups at any of the follow-up days (p =0.53). Conclusion: A single injection of clinically relevant dosing regimens of zoledronic acid may not have a notable impact on vascularization in bone sites. The anti-angiogenic effect of bisphosphonates seems to express itself, in our model, at higher doses than those used in patients treated for osteoporosis. [Copyright &y& Elsevier]

Highlights • As HIV is now considered a chronic disease, there is a need to better measure the prevalence of low BMD and identify associated risk factors in untreated HIV-infected young men before long-term exposure to ART. The prevalence of low bone mineral density (Z-scores ≤ −2 at any of the three sites) in antiretroviral therapy-naive HIV-infected young men was 24.5% [95% CI, 13.3–38.9]. Risk factors associated with low Z-scores were those usually observed in HIV-infected individuals (low body mass index, current smoking and CD4+ cell count) or linked to endocrine hormone levels (estradiol, IGF-1). Abstract Objective We aimed to investigate the prevalence of low bone mineral density (BMD) and associated factors in antiretroviral therapy (ART)-naive HIV-infected young men. Methods In this cross-sectional study, dual-energy X-ray absorptiometry (DXA) was used to measure BMD. BMD at the lumbar spine, total hip and femoral neck sites was expressed as a Z-score (number of standard deviations away from the mean in an age, race and sex-matched reference population). Low BMD was defined as Z-scores ≤ −2 at any of the three sites. The prevalence of low BMD was evaluated at the lumbar spine, total hip and femoral neck sites, as were risk factors associated with Z-scores. Results The study cohort comprised 49 men, of whom 87.8% were white. Mean age was 31.6 (± 7.7) years and mean BMI was 22.7 (± 4.0) kg/m2. Half of patients (51.0%) were current smokers. The prevalence of low BMD was 24.5% [95% CI, 13.3–38.9]. Low estradiol levels and low BMI were associated with low Z-scores at each skeletal site, whereas current smoking and high IGF1 levels were associated with low Z-scores at the lumbar spine site. Among the HIV-related factors, low CD4+ cell count was associated with low Z-scores at the lumbar spine site. Conclusions We observed a high prevalence of low BMD in our ART-naive cohort of young men. Risk factors associated with low Z-scores were those usually observed in HIV-infected individuals (low BMI, current smoking and CD4+ cell count) or linked to endocrine hormone levels (estradiol, IGF-1). [ABSTRACT FROM AUTHOR]