Beneficial effects of strontium ranelate compared to alendronate on bone micro-structure - a 2-year study

Aims: In a head-to-head study, we compared the effects of strontium ranelate (SrRan) and alendronate (ALN), anti-osteoporotic agents with antifracture efficacy, on bone microstructure, a component of bone quality, hence of bone strength. Methods: In a randomised, double-dummy, double-blind controlled trial, 88 postmenopausal osteoporotic women were randomised to SrRan 2g/day or ALN 70mg/week for 2 years. Microstructure of the distal radius and distal tibia were assessed by HR-pQCT after 3,6,12,18 and 24 months of treatment. Primary endpoint was HR-pQCT variables relative changes from baseline. An ITT analysis was applied. Results: Baseline characteristics were similar in both groups (mean ±SD): age: 63.6±7.5 vs. 63.7±7.6 yrs; L1-L4T Score: -2.7±0.8 vs. -2.8±0.8g/cm², Cortical Thickness (CTh), trabecular bone fraction (BV/TV) and cortical density=721±242 vs. 753±263μm, 9.5±2.5 vs. 9.3±2.7%, and 750±87 vs. 745±78mg/cm3 respectively. Over 2 yrs, distal radius values changes were within 1 to 2% without significant differences except cortical density. In contrast distal tibia CTh, BV/TV, trabecular and cortical densities increased significantly more in the SrRan group than in the ALN group (Table). No significant between-group differences were observed for the remaining measured parameter (trabecular number, trabecular spacing, and trabecular thickness). After 2 years, L1- L4 and hip aBMD increases were similar to results from pivotal trials (L1-L4:+6.5% and +5.6%;total hip:+4.1% and +2.9%, in Sr- Ran and ALN groups, respectively). In the SrRan group, bALP increased by a median of 18% (p<0.001) and sCTX decreased by a median of -16% (p=0.005) while in the ALN group, bALP and CTX decreased by median of -31% (p<0.001) and -59% (p<0.001) respectively. Relative changes from baseline to last observation (%) SrRan ALN Estimated between group difference p value CTh (μm) 6.29±9.53 0.93±6.23 5.411±1.836 0.004 BV/TV (%) 2.48±5.13 0.84±3.81 1.783±0.852 0.040 Trabecular density (mgHA/cm3) 2.47±5.07 0.88±4.00 1.729±0.859 0.048 Cortical density (mgHA/cm3) 1.43±2.77 0.36±2.14 1.137±0.530 0.045 The two treatments were well tolerated. Conclusions: Within the constraints related to HRpQCT technology, it appears that strontium ranelate has greater effects than alendronate on distal tibia cortical thickness, trabecular and cortical bone densities in women with postmenopausal osteoporosis after two years of treatment. A concomitant significant increase in bone formation marker is observed in the SrRan group.

Alterations of bone microarchitecture in young patients with inflammatory bowel diseases are associated with fracture risk during growth

Aims: Inflammatory bowel diseases (IBD) appearing during childhood and adolescence compromise peak bone mass acquisition and increase fracture risk. The structural determinants of bone fragility in IBD however remain unknown. Methods: We investigated volumetric bone mineral density (vBMD), trabecular and cortical bone microstructure at distal radius and tibia by high-resolution pQCT (XtremeCT, Scanco, Switzerland), aBMD at distal radius, hip and spine and vertebral fracture assessment (VFA) by DXA in 107 young patients (mean age 22.8 yrs, range 12.2-33.7 yrs; 62 females and 45 males) with Crohn's disease (n=75), ulcerative colitis (n=25), undetermined colitis (n=2), and no definitive diagnosis (n=5), and in 389 healthy young individuals. Results: Mean disease duration was 6.1 yrs, 89/107 IBD patients received corticosteroids, 83 other immunomodulators, and 59 vitamin D. Clinical fractures were reported by 38 patients (mean age at 1st fracture, 12.6 yrs), the vast majority of the forearm, arm or hand; 5 had vertebral crush fractures (Grade 1 or 2) and 11 had multiple fractures. As compared to healthy controls (matched 2:1 for age, sex, height and fracture history), the 102 patients with established IBD had similar weight but significantly lower aBMD at all sites, lower trabecular (Tb) BV/TV and number, and greater Tb separation and inhomogeneous Tb distribution (1/SD TbN) at both distal radius and tibia, lower tibia cortical thickness (CTh), but no differences in cortical vBMD nor bone perimeter. Among IBD's, aBMD was not associated with fractures (by logistic regression adjusted for age, age square, sex, height, weight and protein intake). However, radius and tibia Tb BV/TV, thickness and SD 1/TbN, as well as radius Tb separation and perimeter, were significantly associated with fracture risk (fully adjusted as above), whereas cortical vBMD and CTh were not. After adjustment for aBMD at radius, respectively at femur neck, radius SD 1/TbN and tibia BV/TV, TbTh and perimeter remained independently associated with fracture risk. Conclusions: Young subjects with IBD have low bone mass and poor bone microarchitecture compared to healthy controls. Alterations of bone microarchitecture, particularly in the trabecular bone compartment, are specifically associated with increased fracture risk during growth.

Success of a general school-based physical activity intervention on bone mineral content depends on pubertal stage but not on gender

Aims: We performed a randomised controlled trial in children of both gender and different pubertal stages to determine whether a school-based physical activity (PA) program during a full schoolyear influences bone mineral content (BMC) and whether there are differences in response for boys and girls before and during puberty. Methods: Twenty-eight 1st and 5th grade classes were cluster randomised to an intervention (INT, 16 classes, n=297) and control (CON; 12 classes, n=205) group. The intervention consisted of a multi-component PA intervention including daily physical education during a full school year. Each lesson was predetermined, included about ten minutes of jumping or strength training exercises of various intensity and was the same for all children. Measurements included anthropometry (height and weight), tanner stages (by self-assessment), PA (by accelerometry) and BMC for total body, femoral neck, total hip and lumbar spine using dualenergy X-ray absorptiometry (DXA). Bone parameters were normalized for gender and tanner stage (pre- vs. puberty). Analyses were performed by a regression model adjusted for gender, baseline height, baseline weight, baseline PA, post-intervention tanner stage, baseline BMC, and cluster. Researchers were blinded to group allocation. Children in the control group did not know about the intervention arm. Results: 217 (57%) of 380 children who initially agreed to have DXA measurements had also post-intervention DXA and PA data. Mean age of prepubertal and pubertal children at baseline was 9.0±2.1 and 11.2±0.6 years, respectively. 47/114 girls and 68/103 boys were prepubertal at the end of the intervention. Compared to CON, children in INT showed statistically significant increases in BMC of total body (adjusted z-score differences: 0.123; 95%>CI 0.035 to 0.212), femoral neck (0.155; 95%>CI 0.007 to 0.302), and lumbar spine (0.127; 95%>CI 0.026 to 0.228). Importantly, there was no gender*group, but a tanner*group interaction consistently favoring prepubertal children. Conclusions: Our findings show that a general, but stringent school-based PA intervention can improve BMC in elementary school children. Pubertal stage, but not gender seems to determine bone sensitivity to physical activity loading.

The emergence of parental and paternity leaves in Switzerland : a challenge to gendered representations and practices of parenthood?

The thesis addresses the issue of parenthood and gender equality in Switzerland through the emergence of parental leave policies. This is an original and relevant research topic, as Switzerland is one of the few industrialized countries that have not yet implemented a parental or paternity leave. I first describe the emergence of parental leave policies in the last ten to fifteen years in the political, media, and labor-market spheres. Secondly, adopting a gender and discursive theoretical approach, I analyze whether and to what extent this emergence challenged gendered representations and practices of parenthood. The multilevel and mixed-methods research design implies analyzing various data sets such as parliamentary interventions (N=23J and newspaper articles (N=579) on parental leave policies. A case study of a public administration which implemented a one-month paid paternity leave draws on register data of leave recipients (N=95) and in-depth interviews with fathers and managers (n=30). Results show that parental leave policies, especially in recent years, have been increasingly problematized in the three social spheres considered, as a result of political and institutional events. While there is a struggle over the definition of the legitimate leave type to implement [parental or paternity leave) in the political sphere, paternity leave has precedence in the media and labor-market spheres. Overall, this emergence contributes to making fatherhood visible in the public sphere, challenging albeit in a limited way gendered representations and practices of parenthood. Along with representations of involved fatherhood and change in gender relations, different roles and responsibilities are attributed to mothers and fathers, the latter being often defined as secondary, temporary and optional parents. Finally, I identify a common trend, namely the increasing importance of the economic aspects of parental leave policies with the consequence of sidelining their gender-equality potential. The dissertation contributes to the literature which analyzes the interconnections between the macro-, the meso- and the micro-levels of society in the constitution of gender relations and parenthood. It also provides useful tools for the analysis of the politics of parental leave policies in Switzerland and their effects for gender equality. - Cette thèse traite de la parentalité et de l'égalité de genre en Suisse à travers l'émergence des congés parentaux. Ce sujet de recherche est original et pertinent puisque la Suisse est à ce jour un des seuls pays industrialisés à ne pas avoir adopté de droit au congé parental ou paternité. Cette recherche décrit l'émergence des congés parentaux au cours des 10 à 15 dernières années dans les sphères politique, médiatique et du marché de l'emploi en Suisse. En combinant perspective de genre et analyse de discours, elle examine dans quelle mesure cette émergence remet en question les représentations et pratiques genrées de parentalité. Des méthodes de recherche mixtes sont employées pour analyser des interventions parlementaires (N=23) et des articles de presse (N=579) sur les congés parentaux. L'étude de cas d une entreprise publique qui a adopté un congé paternité payé d'un mois s'appuie sur des données de registre (N=95) et des entretiens semi-structurés avec des pères et des cadres (n=30). Les résultats indiquent que dans les trois sphères considérées, les congés parentaux ont reçu une attention croissante au cours de ces dernières années, en lien avec des événements politiques et institutionnels. Alors que dans la sphère politique il n'y a pas de consensus quant au type de congé considéré comme légitime (congé parental ou paternité), dans les sphères médiatique et du marché de l'emploi le congé paternité semble l'emporter. Dans l'ensemble, l'émergence des congés parentaux contribue à rendre la paternité plus visible dans l'espace public, remettant en question-bien que d'une manière limitée-les représentations genrées de la parentalité. En effet, d'une part l'image de pères impliqués et de rapports de genre plus égalitaires au sein de la famille est diffusée. D'autre part, mères et pères continuent à être associés à des rôles différents, les pères étant définis comme des parents secondaires et temporaires. Finalement, l'analyse révèle une tendance générale, soit l'importance croissante accordée aux aspects économiques des congés parentaux, avec pour conséquence la mise à l'écart de leur potentiel pour l'égalité de genre. Cette thèse contribue à la recherche sur les liens entre les niveaux macro- meso- et microsociaux dans la constitution des rapports de genre et de la parentalité. Elle propose également des outils pour analyser les politiques de congés parentaux en Suisse et leurs implications pour l'égalité de genre.

Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice.

Trabecular bone score (TBS) is a recently-developed analytical tool that performs novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry (DXA) images, and thereby captures information relating to trabecular microarchitecture. In order for TBS to usefully add to bone mineral density (BMD) and clinical risk factors in osteoporosis risk stratification, it must be independently associated with fracture risk, readily obtainable, and ideally, present a risk which is amenable to osteoporosis treatment. This paper summarizes a review of the scientific literature performed by a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Low TBS is consistently associated with an increase in both prevalent and incident fractures that is partly independent of both clinical risk factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More recently, TBS has been shown to have predictive value for fracture independent of fracture probabilities using the FRAX® algorithm. Although TBS changes with osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and it is not clear how change in TBS relates to fracture risk reduction. TBS may also have a role in the assessment of fracture risk in some causes of secondary osteoporosis (e.g., diabetes, hyperparathyroidism and glucocorticoid-induced osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment in combination with both aBMD and FRAX.