Inflammatory bowel diseases (IBDs) are associated with a decreased bone mineral density, but the impact on fractures is unknown. In our study, global risk of fracture is increased for patients with IBDs versus controls. This result will help to determine the appropriate assessment with early screening and management of osteoporosis. Inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), are associated with a decreased bone mineral density (BMD). However, the impact on fracture risk is unknown and data are contradictory across studies. In this systematic review and meta-analysis, we aimed to assess the risk of fracture and presence of low BMD in patients with IBDs compared to healthy controls. A systematic search of literature was conducted of MEDLINE, EMBASE, the Cochrane library and abstracts from appropriate scientific congresses. Studies were selected if they compared the incidence of fractures and/or BMD measurement by dual-energy X-ray absorptiometry in patients with IBDs and healthy sex- and age-matched controls. Data were extracted by two independent investigators. Meta-analysis was performed with the inverse variance approach to estimate pooled odds ratios (ORs) and risk ratios (RRs) with their 95% confidence intervals (CIs). Twenty-four studies met the inclusion criteria. On the basis of nine studies, global risk of fracture was increased for patients with IBDs versus controls (RR = 1.38, 95% CI 1.11-1.73; p = 0.005). Fracture risk with IBDs was significantly increased for vertebral fractures (OR = 2.26, 95% CI 1.04-4.90; p < 0.001), but not for any other site. The analysis of 16 studies evaluating BMD showed a significant decrease in mean BMD and Z-scores for IBD patients versus controls at all sites. In our meta-analysis, patients with IBDs have an increased risk of fractures, especially in the spine, and significant decreased BMD at all sites, which suggests the need for identifying high-risk individuals among this population.

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.

Ever since the introduction of highly active antiretroviral therapy (ART) in 1995, HIV infection has been linked to "metabolic" complications (insulin resistance, dyslipidemia, osteoporosis, and others). Studies suggested increased rates of myocardial infarction, renal insufficiency, neurocognitive dysfunction, and fractures in HIV-postitive patients. Even long-term suppression of HIV seemed to be accompanied by an excess of deleterious inflammation that could promote these complications. The aims of this viewpoint paper are to summarize recent data and to examine the possibility that the problem of aging-related morbidity in HIV might not be as dramatic as previously believed.

Due to the rising life expectancy, bone diseases (e.g. osteoporosis, osteoarthritis) and trauma (e.g. fracture) have become an important socio-economic burden. Accurate visualization and quantification of the bone microstructure in vivo is seen as an important step to enhance diagnosis and treatment. Micro-computed tomography (microCT) has become the gold standard in three-dimensional (3D) imaging of trabecular bone structure. Yet, usage is limited to ex vivo analyses, hence, it cannot be used to evaluate bone and bone adaptive responses in a patient. High-resolution peripheral computed tomography (HR-pQCT) is considered the best technique to measure the bone microarchitecture in vivo. By design HR-pQCT is limited to scanning extremities, such as the distal radius and distal tibia with a limited field of view and long scanning time (~2 à 3 min. for a stack of 0.9 cm). Cone-beam computed tomography (CBCT) is a promising alternative with a much larger field of view. Yet, CBCT is challenged by artefacts that reduce image contrast, such that it is currently being used for qualitative evaluation only. Therefore, the aims of this work were first to enhance image contrast and second to determine the accuracy of high-resolution CBCT for bone microarchitectural assessment. Trapezia of nineteen female arthritic patients were scanned twice ex vivo; once using CBCT (NewTom 5G, Cefla, Verona, Italy) at a nominal voxel size of 75 μm and once using microCT (SkyScan 1172, Bruker, Kontich, Belgium) at a voxel size of 19.84 μm. The CBCT-scans were reconstructed following 2 protocols: (1) using the commercial software delivered with the scanner and (2) using in-house developed software. After reconstruction and image processing, the images were segmented using adaptive thresholding. Bone morphometric parameters including bone volume (BV), total tissue volume (TV), bone volume fraction (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) and trabecular number (Tb.N) were calculated. Statistical evaluations were made at a significance level of 5%. Significant correlations were found between the CBCT-based bone parameters and the microCT-based parameters with R2 > 0.68 The in-house reconstructed software outperformed the commercial software. Better accuracy (overestimation of Tb.Th decreased from 114.24% to 59.96%) as well as higher correlations were observed for the in-house processed images. Still, a significant overestimation was observed for BV/TV and Tb. Th and an underestimation for Tb.N. We conclude that our CBCT image reconstruction improved image contrast which allowed for an accurate quantification of trabecular bone microarchitecture.

Pulsed electromagnetic fields (PEMFs) are effective in healing fractures and improving osteoporosis. However, their effect on mesenchymal cells remains largely unknown. In this study, the effects of PEMF on osteoblastogenesis and its underlying molecular signaling mechanisms were systematically investigated in C3H10T1/2 cells. C3H10T1/2 mesenchymal cells were exposed to 30-Hz PEMF bursts at various intensities for 3 consecutive days. The optimal PEMF exposure (30 Hz, 1 mT, 2 h/day) was applied in subsequent experiments. Our results suggest that intracellular [Ca2+]i in C3H10T1/2 cells can be upregulated upon exposure to PEMF and that PEMF-induced C3H10T1/2 cell differentiation was Ca2+-dependent. The pro-osteogenic effect of PEMF on Ca2+-dependent osteoblast differentiation was then verified by alkaline phosphatase (ALP) and von Kossa staining. Furthermore, PEMF promoted the gene expression and protein synthesis of the Wnt/β-catenin pathway. Increased [Ca2+]i in the nucleoplasm was followed by the mobilization and translocation of β-catenin into the nucleus in C3H10T1/2 cells. A model of Wnt/β-catenin signaling and the Wnt/Ca2+ signaling network is proposed. Taken together, these findings indicated for the first time that PEMF induces osteoblastogenesis through increased intracellular [Ca2+]i and the Wnt-Ca2+/Wnt-β-catenin signaling pathway in C3H10T1/2 mesenchymal cells.

Estrogen deficiency and inflammation are known to play important roles in bone metabolism and occurrence of osteoporosis. Monotropein as an iridoid glycoside is reported to decrease estrogen deficiency-induced bone loss and inhibit inflammatory response in LPS-induced RAW 264.7 macrophages. However, the effect of monotropein on bone loss in chronic inflammatory conditions remains unclear. It was found in the present study that monotropein significantly inhibited bone mass reduction and improved bone micro-architectures by enhancing bone formation and blocking increased secretion of inflammatory cytokines in osteoporotic mice induced by combined ovariectomy and LPS. Our in vitro experiment further demonstrated that monotropein was able to increase the proliferation and activity of alkaline phosphatase (ALP), bone matrix mineralization and the expression of bone matrix protein osteopontin (OPN) in osteoblastic MC3T3-E1 cells injured by LPS. In addition, monotropein significantly decreased the production of IL-6 and IL-1β, inhibited the nuclear translocation of p65 and NF-κB P50, and down-regulated the phosphorylation of NF-κB p65 and IKK, indicating that monotropein could attenuate inflammatory impairment to MC3T3-E1 cells by suppressing the activation of NF-κB pathway. All these results suggest that monotropein may prove to be a promising candidate for the prevention and treatment of inflammatory bone loss.