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WHIM Syndrome is a rare immunodeficiency caused by gain-of-function CXCR4 mutations. Here we report a decrease in bone mineral density in 25% of WHIM patients and bone defects leading to osteoporosis in a WHIM mouse model. Imbalanced bone tissue is observed in mutant mice combining reduced osteoprogenitor cells and increased osteoclast numbers. Mechanistically, impaired CXCR4 desensitization disrupts cell cycle progression and osteogenic commitment of skeletal stromal/stem cells, while increasing their pro-osteoclastogenic capacities. Impaired osteogenic differentiation is evidenced in primary bone marrow stromal cells from WHIM patients. In mice, chronic treatment with the CXCR4 antagonist AMD3100 normalizes in vitro osteogenic fate of mutant skeletal stromal/stem cells and reverses in vivo the loss of skeletal cells, demonstrating that proper CXCR4 desensitization is required for the osteogenic specification of skeletal stromal/stem cells. Our study provides mechanistic insights into how CXCR4 signaling regulates the osteogenic fate of skeletal cells and the balance between bone formation and resorption.

International audience; Osteoporosis carries a high medical, economic, and societal burden principally because of the risk of severe fractures. The objective of this cost-of-illness study was to describe health resource utilization and associated costs in all patients aged ≥50 years hospitalized for a severe osteoporotic fracture over a 6-year period (2009 to 2014) in France. Data were extracted from the French national healthcare database (SNDS) on all health care resource utilization between the index date (date of hospitalization for first fracture during the enrollment period) and study end (December 31, 2016) or until the patient died. Costing was restricted to direct costs and determined from the payer perspective. Variables related to costs were identified through multivariate logistic regression analysis. A total of 356,895 patients were included (median follow-up 39.1 months). In the year after the index fracture, 36,622 patients (10.5%) were rehospitalized for a fracture-related reason. Only 18,474 (5.3%) underwent bone densitometry and 58,220 (16.7%) received a specific treatment. The total annual per capita osteoporosis-related cost in the year after the index severe osteoporotic fracture was €18,040 (from €8598 for multiple ribs to €21,085 for hip fracture) of which €17,905 was incurred by fracture-related costs. The cost incurred by management of osteoporosis was €135. Over years 2 to 5, the mean annual per capita costs of fracture treatment (€806, mostly attributable to the treatment of refractures) continued to dominate those of osteoporosis management (€99). Total annual cost of care was €1260 million (year 2014). Variables associated with higher cost were older age, male sex, site of fracture, a history of prior osteoporotic fracture, and the number of refracture events. The 5-year cost of severe osteoporotic fractures to the French health care system is high and mostly attributable to the treatment of refractures. Improved fracture prevention measures in patients with osteoporosis is crucial to reduce the economic burden of the disease. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Background: Transient osteoporosis of the hip (TOH) is a poorly understood and forgotten clinical entity. The diagnosis is often delayed, and inappropriate treatment is provided, due to the lack of its awareness among the clinicians. Materials and Methods: Twelve patients (11 male and one female) within the age group of 35–50 years, were identified retrospectively from the hospital records between July 2011 and June 2015 who had evidence of TOH on clinical and radiological parameters. Results: All the patients were treated conservatively by nonweight bearing mobilization, anti-inflammatory drugs, bisphosphonates, calcium, and Vitamin D supplements. None of our patients had any symptoms after 6 months of conservative management. The disease did not progress, and there was no evidence of hip joint involvement in any of the cases. Plain radiographs were not diagnostic in the early detection of TOH. Magnetic resonance imaging was found to be highly specific and sensitive in diagnosing TOH. The clinical condition of TOH is characterized by its acute onset of hip pain in middle-aged people, and its symptoms are out of proportion to the radiological findings. Conclusion: The TOH is a nondestructive and self-limiting condition of the hip, which responds well to the conservative treatment. We believe that TOH could be a subset of complex regional pain syndrome type 1, as it has many similarities in clinical presentation and management. Awareness of this entity is important to the clinicians for an early diagnosis and to avoid unnecessary treatment for other mimicking conditions.

There are no recommendations for management secondary osteoporosis (SO) in the paediatric population. Biphosphonates (BP) represent the only available treatments but are not registered for this use in children. Our objectives were to survey the French paediatric rheumatologists on their practice in managing SO complicating systemic inflammatory diseases and to review the literature. Methods: we reviewed the literature using MEDLINE and COCHRANE databases. Were selected studies with : a paediatric population suffering from SO due to juvenile systemic lupus, juvenile arthritis, Still’s disease, dermatomyositis, connective tissue disease, and vasculitis, treated by BP, and in which the effect of the treatment (bone mineral density (BMD) and vertebral fracture (VF) ) were analysed. We also emailed a questionnaire to the mailing list of the SOFREMIP (French society of paediatric rheumatology), to survey paediatric specialists on their use of BP. Results: forty-eight physicians answered the questionnaire (28%). 83 % of them did not investigate SO at the initial diagnosis of the rheumatic disease, and 45.8% did during the follow-up only if there were symptoms of VF. Paediatricians began a treatment with BP in most cases when a fracture occurred. No severe secondary effects were notified. Forty on forty-eight physicians declared being in favour to use BP (grade >5/10). The fears raised by BP were the lack of guidelines, the possible consequences on growth and futures pregnancies. Ten studies were selected from the literature review. They showed that BP had a positive effect on BMD. Conclusion: BP are effective increasing BMD Z-score and relieving VF-related pain. Their efficacy preventing new fractures is unclear. Paediatrician are still looking for guidelines.; Il n’existe pas de recommandation encadrant le dépistage et la prise en charge de la fragilité osseuse (FO) secondaire chez l’enfant. Les seuls traitements utilisés sont les biphosphonates (BP) qui n’ont pas l’AMM en pédiatrie. L’objectif de notre travail est d’analyser les données de la littérature sur les BP dans la prise en charge de la FO secondaire aux maladies rhumatologiques et inflammatoires systémiques en pédiatrie. Cette revue de la littérature est enrichie d’une analyse des pratiques des rhumato-pédiatres, via un questionnaire. Matériel et méthodes : nous avons réalisé une revue systématique de la littérature sur MEDLINE et la COCHRANE. Ont été sélectionné les études ayant : population< 18 ans, atteinte de lupus juvénile, arthrite juvénile idiopathique, maladie de Still, dermatomyosite, connectivite ou vascularite, et ayant reçu des BP et disposant de résultats de densité minérale osseuse (Z-Score) et/ou taux d’incidence de fractures vertébrales (FV). Nous avons diffusé un questionnaire interrogeant les pratiques et le point de vue des rhumato-pédiatres sur les BP. Résultats : quarante-huit médecins ont répondu (28%). La plupart ne réalisent pas de dépistage systématique de la FO au diagnostic initial (83,3%). 45,8% dépistent ensuite seulement si l’enfant est symptomatique. Les médecins initient un traitement par BP en cas d’ostéoporose fracturaire. Aucun effet secondaire grave n’a été rapporté. 40/48 médecins se disent favorables aux BP (note>5/10). Les craintes liées aux BP sont : l’absence de recommandation, l’effet à long terme sur la croissance, et les grossesses futures. 10 études ont été sélectionnées et montrent un effet des BP sur la densité osseuse. Conclusion : les BP ont pour conséquence d’augmenter le Z-score et de soulager les douleurs liées aux FV. Leur effet sur la diminution de l’incidence des FV n’est pas démontré en raison d’un trop petit nombre d’études. Les praticiens sont en demande de recommandations sur le sujet.

Comment on : - Primary Osteoporosis Is Not Reflected by Disease-Specific DNA Methylation or Accelerated Epigenetic Age in Blood. [J Bone Miner Res. 2018] - Epigenetic Aging in Osteoporosis. [J Bone Miner Res. 2018]; International audience

Background: the study of the relationship between morphological features of back muscles and osteoporotic vertebral fracture risk seems promising, as biomechanics appears to play an important role in the occurrence of such fractures. Material and methods: this retrospective study included 89 patients originating from the STIC 1 and STIC 2 randomized controlled trials. Total cross-sectional area (CSA), fatty infiltration and pure muscle CSA of the para-spinal muscles, and total CSA of the psoas muscles were assessed on the CT-scan which had been performed upon inclusion. The number of new fractures (worsening prevalent fracture or incident fracture) occurring during follow-up was retrieved. The implication of muscle features in vertebral fracture risk within one year following treatment was assessed with univariate and multivariate logistic regressions (taking gender, age, BMI and number of prevalent fractures into account). Results: lower para-spinal muscle CSA at T6 level and psoas muscle CSA at L3 level, higher fatty infiltration of para-spinal muscles at L3 level, and lower pure muscle CSA of para-spinal muscles at L3 level predicted the risk of new fracture within a year following a symptomatic vertebral fracture (95,5% treated by vertebral augmentation) in multivariate analyses (p

Osteoporosis and overweight/obesity constitute major worldwide public health burdens. Aging is associated with a decrease in hormonal secretion, lean mass and bone mass, and an increase in fat accumulation. It is established that both obesity and osteoporosis are affected by genetic and environmental factors, bone remodeling and adiposity are both regulated through the hypothalamus and sympathetic nervous system. Oxytocin (OT), belongs to the pituitary hormone family and regulates the function of peripheral target organs, its circulating levels decreased with age. Nowadays, it is well established that OT plays an important role in the control of bone and fat mass and their metabolism. Of note, OT and oxytocin receptor knock out mice develop bone defects and late-onset obesity. Thus OT emerges as a promising molecule in the treatment of osteoporosis and obesity as well as associated metabolic disorders such as type 2 diabetes and cardiovascular diseases. In this review, we will discuss findings regarding the OT effects on bone and fat mass.

International audience; Gallium (Ga) is a semi-metallic element that displays antitumor, antiresorptive, anti-inflammatory and immunosuppressive properties. Among all these properties, antitumor properties were the most extensively applied and have shown efficacy in treatment of Paget's disease, myeloma and hypercalcemia in cases of malignancy. By contrast, no clinical trials have been conducted in prevention and/or treatment of osteoporosis. In this article I focus on Ga effects on bone tissue and cells, as well as on molecular mechanisms governing Ga internalization into cells. Eventually, the potential of Ga as an antiosteoporotic agent is discussed.

International audience; Background/aim: Cirrhosis is considered as a risk factor for osteoporosis whose prevalence is poorly known. The aim was to assess prospectively bone mineral density (BMD) in patients with alcoholic or viral compensated cirrhosis. Methods: From 2006 to 2008, patients with viral or alcoholic compensated cirrhosis had BMD assessment by dual-energy X-ray absorptiometry. The prevalence of osteopenia (-2.5 SD < T-score < -1 SD) and osteoporosis (T-score

Background Only a few studies have used in/opposed phase method for a quantitative evaluation of fat fraction in the spine. Purpose To compare multivoxel proton MR spectroscopy and chemical-shift gradient-echo MR imaging for bone marrow fat quantification in vertebral compression fractures (VCF). Material and Methods Vertebral marrow fat quantification in fifteen patients was measured at 3.0-T. Multi-voxel proton spectroscopy (MRS) and in/opposed-phase MR imaging using a fat map build with a triple-echo gradient-echo sequence was used. All the patients had benign vertebral collapse. Bone marrow fat content was evaluated by both techniques in compressed (acute or chronic) and in non-compressed vertebrae. Results The percentage of fat fraction measured by the triple-echo sequence was well correlated with those calculated by MRS ( r2 = 0.85; P < 10−4). There was a significant decrease of fat fraction in acute VCF versus both chronic VCF ( P < 10−9) and non-fractured vertebrae ( P < 10−7). There was no significant difference in fat fraction evaluated by both techniques between non-fractured vertebrae and chronic VCF. Conclusion We have validated the in/opposed phase method compared with MRS for vertebral bone marrow fat quantification. The fat mapping using a triple-echo gradient-echo sequence allows distinguishing acute and chronic benign VCF.

Genetic hemochromatosis is a cause of osteoporosis; mechanisms leading to iron-related bone loss are not fully characterized. We assessed the bone phenotype of HFE −/− male mice, a mouse model of hemochromatosis. They had a phenotype of osteoporosis with low bone mass and alteration of the bone microarchitecture. Genetic hemochromatosis is a cause of osteoporosis. However, the mechanisms leading to iron-related bone loss are not fully characterized. Recent human data have not supported the hypothesis of hypogonadism involvement. The direct role of iron on bone metabolism has been suggested. Our aim was to assess the bone phenotype of HFE −/− male mice, a mouse model of human hemochromatosis, by using microcomputed tomography and histomorphometry. HFE −/− animals were sacrificed at 6 and 12 months and compared to controls. There was a significant increase in hepatic iron concentration and bone iron content in HFE −/− mice. No detectable Perls’ staining was found in the controls’ trabeculae. Trabecular bone volume (BV/TV) was significantly lower in HFE −/− mice at 6 and 12 months compared to the corresponding wild-type mice: 9.88 ± 0.82% vs 12.82 ± 0.61% (p = 0.009) and 7.18 ± 0.68% vs 10.4 ± 0.86% (p = 0.015), respectively. In addition, there was an impairment of the bone microarchitecture in HFE −/− mice. Finally, we found a significant increase in the osteoclast number in HFE −/− mice: 382.5 ± 36.75 vs 273.4 ± 20.95 ¢/mm2 (p = 0.004) at 6 months and 363.6 ± 22.35 vs 230.8 ± 18.7 ¢/mm2 (p = 0.001) at 12 months in HFE −/− mice vs controls. Our data show that HFE −/− male mice develop a phenotype of osteoporosis with low bone mass and alteration of the microarchitecture. They suggest that there is a relationship between bone iron overload and the increase of the osteoclast number in these mice. These findings are in accordance with clinical observations in humans exhibiting genetic hemochromatosis and support a role of excess iron in relation to genetic hemochromatosis in the development of osteoporosis in humans.

International audience; Excess dietary proteins and "acid ash" diets have been suspected to increase the risk of osteoporosis, but experimental and epidemiological evidence is mixed. We aimed to determine whether the association between protein intake and the overall acid-base equilibrium of the diet (as renal net acid excretion [RNAE] estimate) and fracture risk vary according to calcium intake. During an average of 8.37 +/- 1.73 yr of follow-up, 2408 women reported a fracture (excluding high-impact trauma) among 36,217 postmenopausal women from the E3N prospective study. We used Cox regression models to study the interaction between calcium and, respectively, proteins and RNAE, from the 1993 dietary questionnaire for fracture risk determination, adjusting for potential confounders. There was no overall association between fracture risk and total protein or RNAE. However, in the lowest quartile of calcium (

Objective. – To evaluate whether performing cognitive tasks while exercising influenced the effects of an exercise program designed to reduce the risk of falling in elderly women with osteoporosis. Methods. – We included 68 osteoporotic women older than 70 years of age (mean age, 73.5 years ± 1.6) who followed a program of 12 sessions of balance, coordination, and ambulation exercises designed to lessen the risk of falling. The patients were divided into two groups based on proximity to the study centers. The groups were randomly allocated to the exercise program alone (N = 31, single-task group) or to the same program combined with cognitive tasks performed while exercising (N = 37, dual-task group). Timed up-and-go tests and one-leg balance (OLB) tests were done at baseline, at the end of the exercise program, and 3 months after the end of the exercise program. Results. – In both groups, the exercise program produced significant improvements in up-and-go and OLB times. Additional improvements occurred over the first 3 months following the program. Adding cognitive exercises did not provide added efficacy. Conclusions. – Balance was improved after the exercise sessions. The improvements were clinically significant and increased over time. © 2006 Published by Elsevier SAS.

Item does not contain fulltext In humans, low peak bone mass is a significant risk factor for osteoporosis. We report that LRP5, encoding the low-density lipoprotein receptor-related protein 5, affects bone mass accrual during growth. Mutations in LRP5 cause the autosomal recessive disorder osteoporosis-pseudoglioma syndrome (OPPG). We find that OPPG carriers have reduced bone mass when compared to age- and gender-matched controls. We demonstrate LRP5 expression by osteoblasts in situ and show that LRP5 can transduce Wnt signaling in vitro via the canonical pathway. We further show that a mutant-secreted form of LRP5 can reduce bone thickness in mouse calvarial explant cultures. These data indicate that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass. Gong, Y

ObjectivesTo assess bone mineral density (BMD) at lumbar spine and hip in a large cohort of patients with early inflammatory back pain (IBP) suggestive of axial spondyloarthritis (SpA), and to assess systemic and bone inflammation (according to MRI) as risk factors of low BMD.Patients and Methods332 (52.4% male) patients with IBP suggestive of axial SpA defined by Calin or Berlin criteria were recruited; they had lumbar spine and hip BMD and body composition measurements. Low BMD was defined by Z≤−2 (at least one site). Clinical, biological (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and imaging (x-rays, spine and sacroiliac joint MRI) parameters were compared in patients with and without low BMD (Z≤−2). Significant parameters in univariate analysis were tested in multivariate models.ResultsPatients (mean age 33.8 years) had a short duration of axial symptoms (mean 1.6 years); 71.4% fulfilled the Assessment of Spondyloarthritis International Society criteria for axial SpA and HLA-B27 was present in 62.1%. 43 (13.0%) had low BMD (88% male). Multivariate logistic regression showed that parameters significantly associated with low BMD (any site) were the presence of bone marrow oedema (inflammatory lesions) on MRI (OR 4.63, p=0.001), either ESR or CRP (OR 2.60, p=0.037) and male gender (OR 9.60, p=0.0004).ConclusionsThis study conducted in a large cohort of young adults with early IBP suggestive of SpA shows that 13.0% of patients have a low BMD and that the main risk factor associated with low BMD was inflammation on MRI.

International audience; Genetic haemochromatosis is a hereditary disease characterised by tissue iron overload. In Caucasians it is most often due to homozygous C282Y HFE gene mutation, but other genes may be involved. Without treatment by venesections, patients can develop life-threatening visceral damage such as liver cirrhosis and carcinoma, diabetes or heart failure. This treatment has been remarkably successful in preventing these complications, but patients survive with other symptoms of the disease susceptible to impair, sometimes seriously, their quality of life. This is the case of arthropathy and osteoporosis complicating haemochromatosis. In this chapter, focus has been placed on the rheumatological complications of genetic haemochromatosis.

International audience; Prevalence of osteoporosis, a systemic disease characterized by an impairment of bone mass, will continue to increase due to an ageing population and result in greater risks of fractures with disastrous medical and socioeconomic consequences. A better understanding of the regulation pathway of bone remodeling has led to the identification of new therapeutic targets. Denosumab, a monoclonal antibody against Receptor Activator of Nuclear factor κB-ligand (key molecule in osteoclastogenesis) is a fast-working, reversible antiresorptive treatment. A subcutaneous injection is required twice a year, a significant advantage over bisphosphonates whose efficiency is limited by an inadequate long-term compliance. The only anabolic agent currently available, Teriparatide (parathyroid hormone residues 1-34), administered daily via subcutaneous injection, stimulates both sides of bone remodeling in favour of bone formation. Anti-sclerostin antibodies neutralize an inhibitor of Wnt pathway, the master switch for osteoblastic differentiation, and meet the challenge of pioneering an anabolic drug that does not increase bone resorption. If the tolerance of these promising treatments is good in clinical trials of short duration, their implication in signaling pathways affecting various tissues means that one has to keep a very close watch on their long-term potential risks. Finally, the endocrinologists must be aware that the local regulating factors of bone remodeling recently identified (sclerostin, osteoprotegerin) seem to be the key mediators of hormones with bone tropism.

International audience; Objectives: Spousal concordance has already been observed for several other diseases but it has not yet been studied for bone loss. Our aim was to determine whether or not bone changes were the same within spouses who have shared the same environment for many decades.Methods: We conducted a prospective study on an average of 5±3 years in a single center. We evaluated in the 104 spouses who came at least twice and had more than 1 year of follow-up the changes in bone mineral density (BMD) at femoral neck adjusted on weight and height, and on hormone replacement therapy use and duration for women. Lifestyle characteristics and biological parameters were evaluated at baseline.Results: The mean (±SD) baseline age of wives was 63±5 years and that of their husbands was 66±5 years. They had been living together for 40±8 years. Most of the environmental baseline factors were correlated within partners: BMI (r=0.26, P

International audience

International audience; Both estrogen receptor (ER) and peroxisome proliferator-activated receptor gamma (PPARgamma) regulate bone metabolism, and because steroid receptor coactivator (SRC)-2 (TIF-2) enhances ER and PPARgamma activity, we examined the consequences of deletion of SRC-2 on bone using SRC-2 knock out (KO) mice. Loss of SRC-2 resulted in increased bone mass, with SRC-2 KO mice having 80% higher trabecular bone volume as compared with wild type mice. SRC-2 KO mice also had a marked decrease (by 50%) in bone marrow adipocytes. These data suggested that marrow precursor cells in the SRC-2 KO mice may be resistant to the inhibitory effects of endogenous PPARgamma ligands on bone formation. Consistent with this, compared with cultures from wild type mice, marrow stromal cultures from SRC-2 KO mice formed significantly more mineralized nodules (by 3-fold) in the presence of the PPARgamma agonist, rosiglitazone. Using chromatin immunoprecipitation analysis, we demonstrated that in bone marrow stromal cells, loss of SRC-2 leads to destabilization of the transcription complex at the peroxisome proliferator response elements of a number of PPARgamma target genes, resulting in an overall decrease in the expression of adipocyte-related genes and a marked decrease in adipocyte development. Using ovariectomy with or without estrogen replacement, we also demonstrated that SRC-2 KO mice were partially resistant to the skeletal actions of estrogen. Collectively, these findings indicate that loss of SRC-2 leads to partial skeletal resistance to the ER and PPARgamma, but resistance to PPARgamma is dominant, leading to increased bone mass. Modulating SRC-2 action may, thus, represent a novel therapeutic target for osteoporosis.

International audience; During the past decade, major advances have reported the importance of the vitamin D on the bone metabolism, and recent studies have suggested the potential non skeletal effects of the vitamin D. Adequate vitamin D contributes to reduce the risk of non vertebral fractures, improves the neuromuscular function and reduces the risk of falls when serum 25OHD level are greater than 30ng/mL (75nmol/L). A possible role of vitamin D has been implicated in the reduction of mortality, of the non-skin cancers, of the risk of infections, of inflammatory diseases, of cardiovascular diseases and maybe osteoarthritis. However the current level of evidence for associations is weaker than for skeletal effects. Serum 25OHD level is influenced by several factors (cutaneous vitamin D production, fat mass, dietary sources, UV-B exposure, latitude, season...), and the measurement of the serum 25OHD level is the only way to determine the vitamin D status. It is recommended to measure the serum 25OHD level in patients with osteoporosis or at risk of osteoporosis, and to correct the deficiency.

International audience; Microarchitecture of trabecular bone is a very important component of bone quality in osteoporosis and a determinant of vertebral fracture in men with low bone mineral density (BMD). In contrast to women, male osteoporosis is, in most cases, secondary. The relationships between microarchitecture and different risk factors have never been evaluated in men. About 152 men with low BMD at the lumbar spine or hip (BMD, T-score < -2.5) were included in this study. Risk factors were: age, BMI, alcohol intake, corticosteroid therapy, hypogonadism, and chronic diseases. Transiliac bone biopsies were obtained and histomorphometry was done on an image analyzer; the following parameters were measured: cortical thickness (Ct.Th), trabecular bone volume (BV/TV), trabecular thickness (Tb.Th), separation (Tb.Sp) and number (Tb.N), interconnectivity Index (ICI), star volume of the bone marrow, and strut analysis with node and free-end count. The 50 men with two risk factors had a lower BMD, lower Ct.Th and a significant higher star volume than those with one factor or idiopathic osteoporosis. The 26 men with at least three risk factors, had a lower BMD, a reduction of BV/TV and Ct.Th and a marked disorganization of the trabecular network (increased Tb.Sp, ICI, star volume, and free-end to free-end struts). The prevalence of vertebral fractures was higher in these patients. When the main risk factor was considered, a marked decrease in trabecular bone connectivity was observed in hypogonadic men. In osteoporotic men, higher the number of risk factors, lower the connectivity of trabecular network and higher the vertebral fracture risk.

International audience; BACKGROUND: International recommendations such as the CONSORT and International Conference on Harmonisation statements recognize patient adherence to prescribed treatment as an important aspect of a treatment's evaluation, but this issue is little assessed. OBJECTIVES: To evaluate how medication adherence was assessed and reported in recently published randomized controlled trials (RCTs). MATERIAL AND METHODS: All publications of RCTs assessing pharmacological treatments in 6 major chronic diseases published in high-impact-factor journals in 2003 and 2004 were selected from the Medline database. Two investigators analyzed how medication adherence was assessed and reported. RESULTS: A total of 192 publications were analyzed: 71 in HIV infection, 48 diabetes mellitus, 24 rheumatoid arthritis, 23 asthma, 15 hypertension, 7 osteoporosis, and 4 about 2 of these diseases. The assessment of medication adherence was documented in 69 (35.9%) publications, by counting pill intake in half of these. Results of adherence were reported in 64 (33.3%) publications. Adherence was reported as a quantitative measure: Proportion of the treatment prescribed in 27 articles and as a qualitative measure (adherent patient, yes/no) in 41 (in 4 reports both techniques were used). When reported, the median intake of prescribed medication was 93%, and the median proportion of "nonadherent" patients was 6.2%. CONCLUSIONS: There is important variability in the assessment and reporting of medication adherence in published RCTs of pharmacological treatments of selected chronic diseases, for a given disease and across diseases. Standardization is advisable to allow for comparisons among studies.

International audience; BACKGROUND: International recommendations such as the CONSORT and International Conference on Harmonisation statements recognize patient adherence to prescribed treatment as an important aspect of a treatment's evaluation, but this issue is little assessed. OBJECTIVES: To evaluate how medication adherence was assessed and reported in recently published randomized controlled trials (RCTs). MATERIAL AND METHODS: All publications of RCTs assessing pharmacological treatments in 6 major chronic diseases published in high-impact-factor journals in 2003 and 2004 were selected from the Medline database. Two investigators analyzed how medication adherence was assessed and reported. RESULTS: A total of 192 publications were analyzed: 71 in HIV infection, 48 diabetes mellitus, 24 rheumatoid arthritis, 23 asthma, 15 hypertension, 7 osteoporosis, and 4 about 2 of these diseases. The assessment of medication adherence was documented in 69 (35.9%) publications, by counting pill intake in half of these. Results of adherence were reported in 64 (33.3%) publications. Adherence was reported as a quantitative measure: Proportion of the treatment prescribed in 27 articles and as a qualitative measure (adherent patient, yes/no) in 41 (in 4 reports both techniques were used). When reported, the median intake of prescribed medication was 93%, and the median proportion of "nonadherent" patients was 6.2%. CONCLUSIONS: There is important variability in the assessment and reporting of medication adherence in published RCTs of pharmacological treatments of selected chronic diseases, for a given disease and across diseases. Standardization is advisable to allow for comparisons among studies.

International audience; Il n'y a pas de résumé disponible

International audience; OBJECTIVES: To determine the number of women in France at least 50 years of age with risk factors for osteoporosis likely to lead to bone mineral density measurement, an investigation reimbursed by the French national health insurance system in patients at risk for osteoporosis. The study was commissioned by the French health authorities. MATERIALS AND METHODS: Risk factors for osteoporosis were defined as recommended by the French Agency for Accreditation and Evaluation in Health (ANAES) in 2001. The study data were from nine cohort studies done in France and from the National Health Insurance Agency for the Rhone-Alpes region of France. Risk factor prevalences in France were standardized by extrapolation according to the age distribution in France. RESULTS: Overall, data were collected in 123,986 women aged 50 years or older. From these data, risk factor estimates were as follows: menopause before 40 years of age, 1.5 million women; body mass index (BMI) lower than 19 kg/m(2), nearly 700,000; history of fracture, more than 2 million; history of femoral neck fracture in the mother, more than 1 million; history of health problems potentially responsible for osteoporosis, 400,000; and history of long-term glucocorticoid therapy, 612,000. In all, 3,186,318 (30%) women were estimated to have at least one risk factor and 785,512 (7.5%) at least two risk factors. CONCLUSIONS: Although our study sample was not representative of the population residing in France, the large sample size and diversity of data sources support the validity of our estimate of the prevalence of risk factors for osteoporosis in postmenopausal women living in France.

Osteoporosis is a common complication in cystic fibrosis (CF) patients. In this study, we performed a histomorphometric analysis of the bones of a mouse genetic model of human CF in which both copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene are inactivated. We find that, even in the absence of obvious nutritional and therapeutic differences, the CFTR mutation is associated with severe osteopenia. Bone mineral density (BMD) of total body and of individual bones is significantly diminished. CFTR mutants display a striking significant (50%) reduction of cortical bone width and thinner trabeculae. Analysis of dynamic parameters indicates a significant reduction of bone formation and a concomitant strong increase in bone resorption. Active osteoclasts where found mostly associated with cortical bone. Our data support the concept that CF-associated osteoporosis is part of the syndromic symptoms associated with the CFTR mutation.

Between the 31st March and the 3rd April 2001 the EMBO workshop ‘Genetics of Osteoporosis: from Basic to Clinical Research’ was held in Sestri Levante, Italy. The complete programme of the meeting and all the abstracts can be found online (http://ermes.cba.unige.it/genospora/EMBO.htm). ![][1] Osteoporosis is a complex disease characterized by a reduction in bone mass with associated bone microarchitectural deterioration and a high risk of fractures. Although environmental factors like nutrition and mechanical load, as well as lifestyle, may influence the development of the disease, family and twin pair studies have suggested that there is also a strong genetic component in a predisposition to osteoporosis. Two separate approaches have guided the research of scientists interested in understanding the genetics of osteoporosis. On one side, basic molecular biologists are unravelling the regulatory cascades that control osteoblast and osteoclast differentiation and thereby bone mass. On the other, geneticists, epidemiologists and clinical researchers are looking for genetic mutations and factors that can predispose individuals to the development of the disease. The objective of this EMBO workshop on the genetics of osteoporosis (http://ermes.cba.unige.it/genospora/EMBO.htm) was to bring together clinicians and basic scientists and to stimulate mutual discussion and the transfer of ideas. The regulation of bone mass depends on the balance between the amount of bone formed by osteoblasts and the amount of bone resorbed by osteoclasts. Insight into the genetic factors predisposing to the disease depends on understanding the mechanisms that control the differentiation and the function of these cells. This knowledge is emerging from three major areas. First, many functional data on the transcriptional regulatory cascades that control differentiation of bone cells are accumulating. Some of the major highlights and new discoveries presented at this meeting were indeed reports of new bone‐specific trans and cis regulatory elements. Secondly, the signalling pathways involved in osteoclast … [1]: /embed/graphic-1.gif