Bariatric Surgery and Osteoporosis.

It has been increasingly acknowledged that bariatric surgery adversely affects skeletal health. After bariatric surgery, the extent of high-turnover bone loss is much greater than what would be expected in the absence of a severe skeletal insult. Patients also experience a significant deterioration in bone microarchitecture and strength. There is now a growing body of evidence that suggests an association between bariatric surgery and higher fracture risk. Although the mechanisms underlying the high-turnover bone loss and increase in fracture risk after bariatric surgery are not fully understood, many factors seem to be involved. The usual suspects are nutritional factors and mechanical unloading, and the roles of gut hormones, adipokines, and bone marrow adiposity should be investigated further. Roux-en-Y gastric bypass (RYGB) was once the most commonly performed bariatric procedure worldwide, but sleeve gastrectomy (SG) has now become the predominant bariatric procedure. Accumulating evidence suggests that RYGB is associated with a greater reduction in BMD, a greater increase in markers of bone turnover, and a higher risk of fracture than SG. These findings should be taken into consideration in determining the most appropriate bariatric procedure for patients, especially those at higher fracture risk. Before and after all bariatric procedures, sufficient calcium, vitamin D and protein intake, and adequate physical activity, are needed to counteract negative impacts on bone. There are no studies to date that have evaluated the effect of osteoporosis treatment on high-turnover bone loss after bariatric surgery. However, in patients with a diagnosis of osteoporosis, anti-resorptive agents may be considered.

Real-life golimumab persitence in patients with axial spondyloarthritis: post-hoc results of the prospective observational cohort study, GO-PRACTICE.

OBJECTIVES: To evaluate in clinical practice the persistence and safety of golimumab, together with the evolution of disease activity and patient reported outcomes, in adult patients with rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis (axSpA). This article focuses on the outcomes of golimumab treatment in axSpA patients. METHODS: Golimumab persistence 24 months after initial prescription (primary outcome) was assessed using Kaplan-Meier estimates. Secondary outcomes included evaluations of disease activity evolution (ASDAS and BASDAI), patient-reported outcomes (EQ-5D, SF-12 and HAQ), and golimumab's safety profile. RESULTS: Of 478 axSpA patients, 60.9% were biologic-naïve. Mean age and proportion of females were higher in biologics-pretreated patients (46.8 vs. 40.2 years, p<0.001 and 62.0% vs. 49.8%, p=0.009, respectively). Golimumab persistence at 24 months was 52.6% [95% CI 47.9-57.1%] in the axSpA cohort. It was 59.2% [95% CI 53.1-64.8%] and 42.7% [95% CI 35.3-49.8%] respectively, for biologics-naïve and biologics-pretreated patients (p<0.01), and 65.9% [95% CI 58.9-72.0%] and 41.5% [95% CI 35.2-47.6%], respectively for males and females (p<0.01). Reasons for golimumab discontinuation were primary non-response (37.4%), secondary non-response (24.8%) and intolerance (21.5%). Disease activity and patient reported outcomes improved significantly for those who persisted at 24 months and were higher for biologics-naïve patients. CONCLUSIONS: Golimumab persistence at 2 years in axSpA patients was 52.6%. Previous treatment with another biologic and female gender were associated with earlier discontinuation. Golimumab was a well-tolerated therapy for axSpA, with no new safety signals observed.

Proton Pump Inhibitors and Bone Health: An Update Narrative Review.

Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+ ATPase which controls acid production. Introduced to the market in 1989, their use has increased rapidly worldwide and they are now among the top 10 most prescribed drugs in the United States. As of 2015, the FDA has already approved six drugs of this class (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole and rabeprazole). Recently, the risks and benefits of long-term PPI use were questioned and many studies indicated that their use should be carefully considered, especially in young patients, whose treatment with these drugs could last many years. Even greater concerns have been raised about a potential positive association between PPIs and osteoporotic fracture risk including the hip, spine and wrist. Although based on observational studies, there is substantial evidence associating the long-term use of PPIs and fracture. This relationship is only partially admitted due to the lack of consistent effects of PPIs on bone mineral density loss. Therefore, this narrative review aimed to discuss the recent findings pertaining to the risk of osteoporotic fracture associated with PPIs, in particular prolonged use, and to call for further research to elucidate the mechanisms associated with this bone fragility.

Gene Expression and Chondrogenic Potential of Cartilage Cells: Osteoarthritis Grade Differences.

Recent data suggest that cells isolated from osteoarthritic (OA) cartilage express mesenchymal progenitor cell (MPC) markers that have the capacity to form hyaline-like cartilage tissue. Whether or not these cells are influenced by the severity of OA remains unexplored. Therefore, we analyzed MPC marker expression and chondrogenetic potential of cells from mild, moderate and severe OA tissue. Human osteoarthritic tibial plateaus were obtained from 25 patients undergoing total knee replacement. Each sample was classified as mild, moderate or severe OA according to OARSI scoring. mRNA expression levels of MPC markers-CD105, CD166, Notch 1, Sox9; mature chondrocyte markers-Aggrecan (Acan), Col II A1, hypertrophic chondrocyte and osteoarthritis-related markers-Col I A1, MMP-13 and ALPL were measured at the tissue level (day 0), after 2 weeks of in vitro expansion (day 14) and following chondrogenic in vitro re-differentiation (day 35). Pellet matrix composition after in vitro chondrogenesis of different OA-derived cells was tested for proteoglycans, collagen II and I by safranin O and immunofluorescence staining. Multiple MPC markers were found in OA cartilage resident tissue within a single OA joint with no significant difference between grades except for Notch1, which was higher in severe OA tissues. Expression levels of CD105 and Notch 1 were comparable between OA cartilage-derived cells of different disease grades and bone marrow mesenchymal stem cell (BM-MSC) line (healthy control). However, the MPC marker Sox 9 was conserved after in vitro expansion and significantly higher in OA cartilage-derived cells compared to its levels in the BM-MSC. The in vitro expansion of cartilage-derived cells resulted in enrichment while re-differentiation in reduction of MPC markers for all three analyzed grades. However, only moderate OA-derived cells after the in vitro chondrogenesis resulted in the formation of hyaline cartilage-like tissue. The latter tissue samples were also highly positive for collagen II and proteoglycans with no expression of osteoarthritis-related markers (collagen I, ALPL and MMP13). MPC marker expression did not differ between OA grades at the tissue level. Interestingly after in vitro re-differentiation, only moderate OA-derived cells showed the capacity to form hyaline cartilage-like tissue. These findings may have implications for clinical practice to understand the intrinsic repair capacity of articular cartilage in OA tissues and raises the possibility of these progenitor cells as a candidate for articular cartilage repair.

Real-life persistence of golimumab in patients with chronic inflammatory rheumatic diseases: results of the 2-year observational GO-PRACTICE study.

OBJECTIVES: GO-PRACTICE aimed to evaluate the persistence, clinical response and safety of golimumab in adult patients with chronic inflammatory rheumatic disease. METHODS: Prospective observational study with 24 months of follow-up, involving 134 rheumatologists from public or private health establishments in France. The primary outcome was the persistence of golimumab 24 months after initial prescription. Cumulative persistence probabilities were determined from Kaplan-Meier estimates. Secondary outcomes included an evaluation of disease activity and golimumab safety profile. RESULTS: Of 754 consecutively recruited patients, 170 had rheumatoid arthritis (RA) (54.3 years, 74.1% female, 64.7% biologics-naïve), 106 had psoriatic arthritis (PsA) (48.1 years, 70% female, 66.0% biologics-naïve) and 478 had axial spondyloarthritis (axSpA) (42.8 years, 54.6% female, 60.9% biologics-naïve). Golimumab persistence at 2 years was 56.5%, 45.1% and 52.6%, respectively, in RA, PsA and axSpA groups. Persistence was higher in biologics-naïve (58.3%) than in biologics pre-treated patients (42.7%, p<0.01). For 362 patients continuing golimumab at 2 years, disease activity improved significantly from baseline to 2 years: mean 28-joint disease activity score for RA and PsA was lowered by 2.06 and 1.89 points, and mean ankylosing spondylitis disease activity score was lowered by 3.11 points (p<0.0001) for axSpA. Patient appreciation of disease activity also improved; 8.9% of discontinuations were due to intolerance. CONCLUSIONS: Golimumab persistence was satisfactory at 2 years and accompanied by improvements in clinical effectiveness in 362 patients continuing golimumab at 2 years. Golimumab was well tolerated and its safety profile was consistent with those reported in previous studies.

Does the Severity of Obesity Influence Bone Mineral Density Values in Premenopausal Women?

The aim of this study was to compare bone mineral content (BMC), bone mineral density (BMD), and geometric indices of hip bone strength among 3 groups of adult obese premenopausal women (severely obese, morbidly obese, and super morbidly obese). This study included 65 young adult premenopausal women whose body mass index (BMI) > 35 kg/m2. They were divided into 3 groups using international cut-offs for BMI. Body composition and bone variables were measured by DXA. DXA measurements were completed for the whole body (WB), lumbar spine, total hip (TH), and femoral neck (FN). Geometric indices of FN strength (cross-sectional area, cross-sectional moment of inertia [CSMI], section modulus [Z], strength index [SI], and buckling ratio) were calculated by DXA. Results showed that age and height were not significantly different among the 3 groups. WB BMC values were higher in super morbidly obese women compared to severely and morbidly obese women. WB BMD, L1-L4 BMD, total hip BMD, FN BMD, cross-sectional area, CSMI, Z, and buckling ratio values were not significantly different among the 3 groups. SI values were lower in super morbidly obese compared to morbidly and severely obese women. In the whole population (n = 65), body weight, BMI, lean mass, fat mass, and trunk fat mass were positively correlated to WB BMC and negatively correlated to SI. Weight and lean mass were positively correlated to WB BMD and CSMI. Our findings suggest that the severity of obesity does not influence BMD values in premenopausal women.

Limb Muscular Strength and Bone Mineral Density in Elderly Subjects with Low Skeletal Muscle Mass Index.

The aim of the current study was to investigate the relationships between limb muscular strength and bone mineral density (BMD) in a group of elderly subjects with low skeletal muscle mass index (SMI).55 elderly Lebanese subjects (35 women and 20 men) participated in the current study. Handgrip, one-repetition maximum (1-RM) dumbbell curl (1-RM biceps), 1-RM lying one arm triceps (1-RM triceps), 1-RM calf raise, 1-RM leg extension and 1-RM leg curl were evaluated using validated methods.In both genders, 1-RM biceps, 1-RM triceps, 1-RM leg extension and 1-RM leg curl were positively correlated to total hip BMD. The current study shows that limb muscular strength is positively correlated to hip BMD in elderly subjects with low SMI. This may have clinical implications in the field of osteoporosis prevention in elderly subjects with low SMI.

Animal Model for Glucocorticoid Induced Osteoporosis: A Systematic Review from 2011 to 2021.

Clinical and experimental data have shown that prolonged exposure to GCs leads to bone loss and increases fracture risk. Special attention has been given to existing emerging drugs that can prevent and treat glucocorticoid-induced osteoporosis GIOP. However, there is no consensus about the most relevant animal model treatments on GIOP. In this systematic review, we aimed to examine animal models of GIOP centering on study design, drug dose, timing and size of the experimental groups, allocation concealment, and outcome measures. The present review was written according to the PRISMA 2020 statement. Literature searches were performed in the PubMed electronic database via Mesh with the publication date set between April, 2011, and February 2021. A total of 284 full-text articles were screened and 53 were analyzed. The most common animal species used to model GIOP were rats (66%) and mice (32%). In mice studies, males (58%) were preferred and genetically modified animals accounted for 28%. Our work calls for a standardization of the establishment of the GIOP animal model with better precision for model selection. A described reporting design, conduction, and selection of outcome measures are recommended.

Cumulative Effects of Strontium Ranelate and Impact Exercise on Bone Mass in Ovariectomized Rats.

OBJECTIVE: To explore the effect of physical exercise (EXE), strontium ranelate (SR), or their combination on bone status in ovariectomized (OVX) rats. DESIGN: Sixty female Wistar rats were randomized to one of five groups: sham (Sh), OVX (O), OVX+EXE (OE), OVX+SR (OSR), and OVX+EXE+SR (OESR). Animals in EXE groups were subjected to 10 drops per day (45 cm in height); rats in SR groups received 625 mg/kg/day of SR, 5 days/week for 8 weeks. Bone mineral density (BMD) and bone mineral content (BMC, dual-energy X-ray absorptiometry (DXA)), mechanical strength of the left femur (three-point bending test), and femur microarchitecture of (micro-computed tomography imaging, microCT) analyses were performed to characterize biomechanical and trabecular/cortical structure. Bone remodeling, osteocyte apoptosis, and lipid content were evaluated by ELISA and immunofluorescence tests. RESULTS: In OVX rats, whole-body BMD, trabecular parameters, and osteocalcin (OCN) levels decreased, while weight, lean/fat mass, osteocyte apoptosis, and lipid content all increased. EXE after ovariectomy improved BMD and BMC, trabecular parameters, cross-sectional area (CSA), moment of inertia, and OCN levels while decreasing osteocyte apoptosis and lipid content. SR treatment increased BMD and BMC, trabecular parameters, CSA, stiffness, OCN, and alkaline phosphatase (ALP) levels. Furthermore, fat mass, N-telopeptide (NTX) level, osteocyte apoptosis, and lipid content significantly decreased. The combination of both EXE and SR improved bone parameters compared with EXE or SR alone. CONCLUSION: EXE and SR had positive and synergistic effects on bone formation and resorption.

Sarcopenia negatively affects hip structure analysis variables in a group of Lebanese postmenopausal women.

BACKGROUND: The current study's purpose is to compare hip structural analysis variables in a group of postmenopausal women with sarcopenia and another group of postmenopausal women with normal skeletal muscle mass index. To do so, the current study included 8 postmenopausal women (whose ages ranged between 65 and 84 years) with sarcopenia and 60 age-matched controls (with normal skeletal muscle mass index (SMI)). Body composition and bone parameters were evaluated by dual-energy X-ray absorptiometry (DXA). RESULTS: Weight, lean mass, body mass index, femoral neck cross-sectional area (FN CSA), FN section modulus (Z), FN cross sectional moment of inertia (CSMI), intertrochanteric (IT) CSA, IT Z, IT CSMI, IT cortical thickness (CT), femoral shaft (FS) CSA, FS Z and FS CSMI were significantly greater (p < 0.05) in women with normal SMI compared to women with sarcopenia. In the whole population, SMI was positively associated with IT CSA, IT Z, IT CSMI, IT CT, FS CSA, FS Z, FS CSMI, FS CT but negatively correlated to IT buckling ratio (BR) and FS BR. CONCLUSION: The current study suggests that sarcopenia has a negative effect on hip bone strength indices in postmenopausal women.

Ixekizumab treatment of biologic-naïve patients with active psoriatic arthritis: 3-year results from a phase III clinical trial (SPIRIT-P1).

OBJECTIVE: The aim was to assess the safety and efficacy of up to 156 weeks of ixekizumab (an IL-17A antagonist) treatment in PsA patients. METHODS: In a phase III study, patients naïve to biologic treatment were randomized to placebo, adalimumab 40 mg every 2 weeks (ADA; active reference) or ixekizumab 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) after an initial dose of 160 mg. At week 24 (week 16 for inadequate responders), ADA (after 8-week washout) and placebo patients were re-randomized to IXEQ2W or IXEQ4W. Outcomes were evaluated using a modified non-responder imputation [linear extrapolation for radiographic progression (modified total Sharp score = 0)] during extended treatment until week 156. RESULTS: Of 417 patients, 381 entered the extension, and 243 of 381 (63.8%) completed the 156-week study. Incidence rates of treatment-emergent and serious adverse events, respectively, were 38.0 and 5.2 with IXEQ2W (n = 189) and 38.1 and 8.0 with IXEQ4W (n = 197). One death occurred (IXEQ4W). With IXEQ2W and IXEQ4W, respectively, the response rates persisted to week 156 as measured by the ACR response ≥20% (62.5 and 69.8%), ≥50% (56.1 and 51.8%) and ≥70% (43.8 and 33.4%), psoriasis area and severity index (PASI) 75 (69.1 and 63.5%), PASI 90 (64.5 and 51.2%) and PASI 100 (60.5 and 43.6%). Inhibition of radiographic progression also persisted to week 156 in 61% of IXEQ2W and 71% of IXEQ4W patients. CONCLUSION: In this 156-week study of ixekizumab, the safety profile remained consistent with previous reports, and improvements in signs and symptoms of PsA were observed, including persistent low rates of radiographic progression. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01695239, EudraCT 2011-002326-49.

Influence of sarcopenia on bone health parameters in a group of eumenorrheic obese premenopausal women.

INTRODUCTION: The aim of this study was to compare bone mineral density (BMD) and geometric indices of hip bone strength in a group of obese sarcopenic premenopausal women (n = 27) and a group of obese premenopausal women with normal appendicular lean mass (ALM)/body mass index ratio (BMI) (n = 26). MATERIALS AND METHODS: The ALM/BMI criterion of The Foundation for the National Institute of Health was used; women with an ALM/BMI ratio < 0.512 m2 were considered obese sarcopenic. Body composition and bone variables were measured by DXA. DXA measurements were completed for the whole body (WB), lumbar spine (L1-L4), total hip (TH) and femoral neck (FN). Hip geometry parameters including cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), strength index (SI) and buckling ratio (BR) were derived by DXA. RESULTS: Age, weight and BMI were not significantly different between the two groups. Height, lean mass, skeletal muscle mass index, ALM and the ratio ALM/BMI were significantly higher in obese women with normal ALM/BMI ratio compared to obese sarcopenic women. Fat mass percentage was significantly higher in obese sarcopenic women compared to obese women with normal ALM/BMI ratio. WB BMC, TH BMD, FN BMD, CSA, CSMI and Z were significantly higher in obese women with normal ALM/BMI ratio compared to obese sarcopenic women. In the whole population (n = 53), ALM and the ratio ALM/BMI were positively correlated to WB BMC, CSA, CSMI and Z. CONCLUSION: The present study suggests that sarcopenia negatively influences bone mineral density and hip geometry parameters before menopause in eumenorrheic obese women.

Gonadal hormones may predict structural bone fragility in elite female soccer player.

Purpose: This study determined the impact of menstrual status on bone tissue in elite post-pubertal female soccer players over an entire season.Methods: Fifty-one elite female soccer players participated. At baseline, forty-one were assigned to the low hormonal androgenic profile (low-HAPL) and 10 to the high hormonal androgenic profile (high-HAPL).Results: An 8-month training program led to increased bone mineral density content (p<0.05). The low-HAPL athletes improved the Narrow neck average cortical thickness (ACT) by 1.4% and reduced the corresponding Buckling ratio (BR) by 2.6%, thus decreasing the fracture risk (p<0.05). The high-HAPL athletes decreased the Narrow neck ACT by 5.4% and increased the BR by 2.6%, increasing fracture risk (p<0.05). Differences were assigned as being "very likely beneficial" for the low-HAPL athletes, supported by very large (d=3.41) and large (d=1.58) effect sizes for the Narrow neck ACT and BR, respectively.Conclusion: A season of soccer training has induced bone geometry improvements in adolescent females. Bone health parameters improved in the two clusters. However, high-HAPL athletes decreased its resistance to loading compare to low-HAPL athletes. Even if female players do not present clinical symptoms related to their hormonal status, sport medicine physicians should pay attention to their structural bone fragility.

Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial.

BACKGROUND: No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome. We compared the anti-fracture efficacy of teriparatide with risedronate in patients with severe osteoporosis. METHODS: In this double-blind, double-dummy trial, we enrolled post-menopausal women with at least two moderate or one severe vertebral fracture and a bone mineral density T score of less than or equal to -1·50. Participants were randomly assigned to receive 20 µg of teriparatide once daily plus oral weekly placebo or 35 mg of oral risedronate once weekly plus daily injections of placebo for 24 months. The primary outcome was new radiographic vertebral fractures. Secondary, gated outcomes included new and worsened radiographic vertebral fractures, clinical fractures (a composite of non-vertebral and symptomatic vertebral), and non-vertebral fractures. This study is registered with ClinicalTrials.gov (NCT01709110) and EudraCT (2012-000123-41). FINDINGS: We enrolled 680 patients in each group. At 24 months, new vertebral fractures occurred in 28 (5·4%) of 680 patients in the teriparatide group and 64 (12·0%) of 680 patients in the risedronate group (risk ratio 0·44, 95% CI 0·29-0·68; p<0·0001). Clinical fractures occurred in 30 (4·8%) of 680 patients in the teriparatide group compared with 61 (9·8%) of 680 in the risedronate group (hazard ratio 0·48, 95% CI 0·32-0·74; p=0·0009). Non-vertebral fragility fractures occurred in 25 (4·0%) patients in the teriparatide group and 38 (6·1%) in the risedronate group (hazard ratio 0·66; 95% CI 0·39-1·10; p=0·10). INTERPRETATION: Among post-menopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures is significantly lower in patients receiving teriparatide than in those receiving risedronate. FUNDING: Lilly.

Understanding Patients' Perspectives and Educational Needs by Type of Osteoporosis in Men and Women and People with Glucocorticosteroid-Induced Osteoporosis: A Qualitative Study to Improve Disease Management.

The aim of the study was to investigate similarities and differences in health beliefs, experiences and educational needs by type of osteoporosis (OP), particularly in people with glucocorticoid-induced OP (GIOP) and men. A qualitative study was conducted via focus groups involving post-menopausal women with or without osteoporotic fractures, osteoporotic men and people with GIOP. Fifty-three participants were included in eight groups. A wide range of health beliefs was found for all types of OP. Osteoporosis was considered a natural consequence of ageing except in men or conversely a serious disease associated with risk of new fractures and disability. GIOP patients had heterogeneous knowledge of OP and reported fewer prevention behaviours, and their quality of life was affected by the causal illness. Men had difficulties coping with the loss of their functional abilities and felt that OP was a "women's" disease. Beliefs about treatments ranged from confidence to fear of adverse effects or doubt about efficacy in all types of OP. Participants were interested in physical activity, fall prevention and diet, and preferred group sessions. GIOP patients and men had an interest in face-to-face education. Men were also interested in brief information including via the Internet. Patients' beliefs about OP differed by type of OP. Specific populations such as men or people with GIOP need particular care owing to experiences and needs. Offering group sessions in educational interventions is of interest to allow for sharing experiences and also face-to-face education for men and GIOP patients or the Internet for men.

Osteoarthritis biomarker responses and cartilage adaptation to exercise: A review of animal and human models.

Regular physical activity has been suggested as having both preventive and therapeutic benefits for individuals with osteoarthritis (OA). However, evidence of whether exercise and which type of exercise constitutes a benefit or a risk in the development and progression of OA remains debatable. This may be due to the evaluation of the effect of physical activity or new disease-modifying OA drugs which is currently based on radiographic criteria (eg, joint space width) and the lack of correlation with clinical signs and symptoms (eg, pain and loss of function). Moreover, OA typically manifests itself as changes within the joint space and subchondral bone as well as the whole joint structure, including progressive degradation of cartilage, menisci, ligaments, and synovial inflammation. Biomarkers are being developed to quantify joint remodeling and disease progression notably involving the articular cartilage and synovial fluid. The primary purpose of this review was to evaluate the current literature and to provide further insight based on OA biomarkers and the role physical activity plays in the management of OA. Osteoarthritis biomarkers together with radiographic imaging evidence will ideally guide healthcare providers to incorporate exercise recommendations into clinical management and offer patients evidence-based and individually tailored exercise prescriptions.

Implication of IL-17 in Bone Loss and Structural Damage in Inflammatory Rheumatic Diseases.

Proinflammatory cytokines play an important role in the systemic and focal bone loss associated with chronic inflammatory diseases. Targeting these cytokines with biologics and small molecules has led to a major improvement of the bone health of patients with inflammatory arthritis. Cytokines from the IL-17 family have been shown to be involved in the pathogenesis of several diseases such as spondyloarthritis, psoriatic arthritis, or psoriasis. IL-17A has been the first described and the most studied. The recent development of targeted therapies against IL-17A or its receptor and their efficacy has confirmed the importance of this cytokine in the development of inflammatory diseases. The aim of this review was to describe the effects of the IL-17 family and more particularly of IL-17A on bone and cartilage tissues. At the cellular level, IL-17A is proosteoclastogenic whereas its effects on osteoblasts depend on the stage of differentiation of these cells. In vivo, IL-17A is not required for normal bone homeostasis but plays an important role in bone loss notably in an ovariectomized mouse model of osteoporosis. Preliminary data from clinical trials showed a stabilisation of bone density in patients treated with anti-IL-17A antibodies. IL-17A plays a central role in the cartilage damage through the induction of collagenases and by decreasing the expression of their inhibitors in synergy with the other proinflammatory cytokines. The prevention of structural damage by anti-IL-17A therapies has been demonstrated in several pivotal clinical trials. Overall, blocking the IL-17A pathway seems to have a positive effect on the bone and cartilage damage observed in inflammatory arthritis. Differences and specificity of these effects compared to those already described with other biologics such as anti-TNF therapies remain to be explored.

Effects of Teriparatide in Patients with Osteoporosis in Clinical Practice: 42-Month Results During and After Discontinuation of Treatment from the European Extended Forsteo® Observational Study (ExFOS).

This study aimed to describe clinical outcomes in patients prescribed teriparatide and followed up for 18 months after stopping the drug in real-life conditions. The Extended Forsteo® Observational Study analysed incident clinical fractures in 6-month intervals using logistic regression with repeated measures. Changes in back pain (visual analogue scale) and health-related quality of life (HRQoL; EQ-5D questionnaire) were analysed using mixed models for repeated measures. Patients were analysed if they had a post-baseline visit, regardless of whether and for how long they took teriparatide. Of 1531 patients analysed (90.7% female, mean age: 70.3 years), 76 (5.0%) never took teriparatide. Median treatment duration was 23.6 months. The adjusted odds of clinical fracture decreased by 47% in the > 12- to 18-month treatment period (p = 0.013) compared with the first 6-month period, with no statistically significant reduction in the > 18- to 24-month interval. The clinical fracture rate remained stable during the 18 months' post-teriparatide, when approximately 98% of patients took osteoporosis medication (51% bisphosphonates). Clinical vertebral fractures were reduced at every time period compared with the first 6 months. Adjusted mean back pain scores decreased and EQ-5D scores increased significantly at each post-baseline observation. In a real-life clinical setting, the risk of clinical fractures declined during 24 months of teriparatide treatment. This reduction was maintained 18 months after stopping teriparatide. In parallel, patients reported significant improvements in back pain and HRQoL. The results should be interpreted in the context of the non-controlled design of this observational study.

Physical Performance Variables and Bone Mineral Density in a Group of Young Overweight and Obese Men.

The aim of this study was to explore the relationships between performances obtained in different physical tests and bone parameters (bone mineral density [BMD], bone mineral content, hip geometry indices, and trabecular bone score [TBS]) in a group of young Lebanese overweight and obese adult men. Fifty-two overweight and/or obese (body mass index > 25 kg/m2) young men whose ages range from 18 to 35 yr participated in this study. Weight and height were measured, and body mass index was calculated. Body composition, BMD, cross-sectional area and section modulus (Z) of the femoral neck (FN), and TBS were measured by dual-energy X-ray absorptiometry. Maximum oxygen consumption (VO2 max, in liter per minute) was determined by direct measurement while exercising on a medical treadmill. One-repetition-maximum half-squat and maximum power (P max) of the lower limbs were measured using validated exercises. Lean mass was a positive determinant of whole-body bone mineral content (r = 0.71, p < 0.001), FN cross-sectional area (r = 0.51, p < 0.001), and FN Z (r = 0.58, p < 0.001). VO2 max (in liter per minute) was a positive determinant of whole-body BMD (r = 0.47, p < 0.001), total hip BMD (r = 0.43, p < 0.01), and FN BMD (r = 0.42, p < 0.01). VO2 max (in milliliter per minute per kilogram) was a positive determinant of TBS (r = 0.30, p < 0.05). One repetition maximum was a positive determinant of L1-L4 BMD (r = 0.33, p < 0.05). This study suggests that VO2 max (in liter per minute) is a positive determinant of BMD, and VO2 max (in milliliter per minute per kilogram) is a positive determinant of TBS in overweight and obese men.

TGF-beta-induced early gene-1 overexpression promotes oxidative stress protection and actin cytoskeleton rearrangement in human skin fibroblasts.

BACKGROUND: Transforming growth factor beta inducible early gene-1 (TIEG-1), a member of the Krüppel-like factor, was identified as a primary response gene for TGF-ß. The role of TIEG-1 in skin repair has been mainly addressed in vivo on TIEG-1 null mice model and the mechanism remains unexplored. METHODS: We investigated the modulation of TIEG-1 expression in normal human skin fibroblasts by either down-expressing or overexpressing the gene. We evaluated reactive oxygen species production and the cell viability of treated cells. The effect of TIEG-1 overexpression was monitored by wound healing assay and immunofluorescence staining of actin fibers organization and alpha-smooth muscle actin (α-SMA). Western blots were carried out to identify the level of expression or phosphorylation of key proteins such as cofilin, Rho GTPases, and p38 mitogen-activated protein kinase (p38 MAPK). RESULTS: TIEG-1 down-regulation had a deleterious effect on the cell viability. It was significantly reduced (65±5%) and exposure to ultraviolet further increased this effect (47±3%). By contrast, cells overexpressing TIEG-1 had a reduced reactive oxygen species production (75%) compared to control and mock-transfected cells. This overexpression also resulted in formation of actin stress fibers and increased α-SMA expression and an enhanced wound healing feature. RhoB GTPase was upregulated and phosphorylation of cofilin and p38 MAPK was observed. CONCLUSION: TIEG-1 overexpression in normal human skin fibroblasts results in improved resistance to oxidative stress, myofibroblast-like conversion that involved RhoB signaling pathway with cofilin and p38 MAPK proteins activation. GENERAL SIGNIFICANCE: This study enlightens the role of TIEG-1 role in skin biology.