Intra-articular injection of hUC-MSCs expressing miR-140-5p induces cartilage self-repairing in the rat osteoarthritis Abstract Introduction Currently, osteoarthritis (OA) receives global increasing attention because it associates severe joint pain and serious disability. Stem cells intra-articular injection therapy showed a potential therapeutic superiority to reduce OA development and to improve treating outputs. However, the long-term effect of stem cells intra-articular injection on the cartilage regeneration remains unclear. Recently, miR-140-5p was confirmed as a critical positive regulator in chondrogenesis. We hypothesized that hUC-MSCs overexpressing miR-140-5p have better therapeutic effect on osteoarthritis. Materials and methods To enhance stem cell chondrogenic differentiation, we have transfected human umbilical cord mesenchymal stem cells (hUC-MSCs) with miR-140-5p mimics and miR-140-5p lentivirus to overexpress miR-140-5p in a short term or a long term accordingly. Thereafter, MSCs proliferation, chondrogenic genes expression and extracellular matrix were assessed. Destabilization of the medial meniscus (DMM) surgery was performed on the knee joints of SD rats as an OA model, and then intra-articular injection of hUC-MSCs or hUC-MSCs transfected with miR-140-5p lentivirus was carried to evaluate the cartilage healing effect with histological staining and OARSI scores. The localization of hUC-MSCs after intra-articular injection was further confirmed by immunohistochemical staining. Results Significant induction of chondrogenic differentiation in the miR-140-5p-hUC-MSCs (140-MSCs), while its proliferation was not influenced. Interestingly, intra-articular injection of 140-MSCs significantly enhanced articular cartilage self-repairing in comparison to normal hUC-MSCs. Moreover, we noticed that intra-articular injection of high 140-MSCs numbers reinforces cells assembling on the impaired cartilage surface and subsequently differentiated into chondrocytes. Conclusions In conclusion, these results indicate therapeutic superiority of hUC-MSCs overexpressing miR-140-5p to treat OA using intra-articular injection.

18 F-NaF-PET/CT in patients with primary hyperparathyroidism and brown tumors Abstract Introduction Brown tumors (BT) are non-neoplastic bone lesions infrequently occurring in patients with long-standing severe hyperparathyroidism (HPT). BT may be identified and characterized using 18-F-sodium fluoride-positron-emission-tomography/computed tomography (18F-NaF-PET/CT). We present a retrospective series of eight primary hyperparathyroidism (pHPT) patients with BT imaged with 18F-NaF-PET/CT. Materials and methods Imaging assessment included location, diameter, maximum standardized uptake value (SUVmax), metabolically active lesion volume (PETvol) of BT, total metabolically active bone volume (TMBvol) per patient and several computed tomography (CT) features of BT. Where appropriate, we analyzed the association between characteristic features of BT in 18F-NaF-PET/CT, histopathology, clinical symptomatology and laboratory parameters. Results In our cohort of 8 patients (median age, 49 years, range, 26–73), 72 BT were found. The mean PETvol of BT was 89.48 cm3 ± 122.81 cm3 and the mean SUVmax was 17.5 ± 7.8. The total PETvol of BT per patient correlated positively with serum calcium (r = 0.810, p = 0.015), and negatively with glomerular filtration rate (GFR) (r = − 0.762, p = 0.028). TMBvol correlated significantly with serum PTH (r = 0.810, p = 0.015), alkaline phosphatase (r = 0.762, p = 0.028), and duration of postoperative hospitalization (r = 0.826, p = 0.011, 24.3 days ± 19.8 days). Conclusion 18F-NaF-PET/CT is a valuable non-invasive whole-body imaging technique for the assessment of patients with pHPT and BT. TMBvol is associated with PTH and alkaline phosphatase, and the requirement for intense postoperative calcium substitution, which determines the duration of hospitalization.

Unaffected bone mineral density in Danish children and adolescents with type 1 diabetes Abstract Aims Adults with type 1 diabetes mellitus (T1D) have decreased bone mineral density (BMD). Our study aimed at determining BMD and the association to metabolic control in children and adolescents with T1D. Methods 244 patients (113 girls) with a median age of 14.3 years and T1D duration of 1–16 years were included. A dual-energy X-ray absorptiometry scan assessed BMD Z-scores excluding the head (total body less head, TBLH). TBLH-BMD were then investigated for associations to diabetes relevant variables such as HbA1c, insulin treatment, anthropometry and physical activity. Results In all participants the TBLH-BMD Z-score (0.22 ± 0.96) was significantly higher than the references. Separated by sex, TBLH-BMD Z-score in boys (0.11 ± 0.84) was no different from healthy peers whereas TBLH-BMD Z-score was significantly higher in girls (0.36 ± 1.09). The higher TBLH-BMD Z-score in girls were explained by higher BMI Z-scores. Participants with assumed final height (based on age) had an average TBLH-BMD Z-score of 0.78 ± 1.06, significantly higher than references independent of gender, HbA1c, height- and weight Z-scores. Multiple regression analyses showed that TBLH BMD Z-score associated negatively to HbA1c (P = 0.003), pump treatment (P = 0.019) and screen-time (P = 0.005) and positively to weight Z-score (P < 0.001). Physical activity, sex and puberty did not significantly associate to TBLH-BMD Z-score. Conclusion Unlike adults with T1D, BMD is not decreased in children and adolescents with T1D and even elevated after attained final height. As HbA1c negatively associates to BMD, decreased BMD may progress over time. Whether changes in microarchitecture or bone metabolism precede changes in BMD needs further investigation.

Correction to: The association of urinary pentosidine levels with the prevalence of osteoporotic fractures in postmenopausal women In the original publication of the article, the following sentence under the abstract section was published incorrectly as “A multivariable logistic regression analysis revealed that urinary pentosidine was significantly associated with the prevalence of fracture after adjustment for known risk factors for fracture (odds ratio 1.92, 95% CI 1.09–3.37, P = 0.023).”

Budget impact analysis of osteoporosis medications for primary prevention of fractures in Taiwan Abstract Introduction Taiwan's national health insurance currently only covers the use of osteoporosis drugs for the secondary prevention of fractures and does not provide coverage for primary prevention. The purpose of this study is to develop a model for analyzing the budgetary impact of the use of osteoporosis medications of primary prevention. Methods The budget impact model in this study is the “actual medication cost” minus the “medical expenses for all types of fractures that can be avoided by taking osteoporosis medications.” We developed six possible insurance payment plans for primary prevention based on the age of the patients and T-scores and performed eleven steps to estimate the budget impact of each payment plan. Results The results of this study indicated that there may be 71,220 (T-score ≤ − 3.0, 75 + y/o) to 157,515 (T-score ≤ − 2.5, 65 + y/o) people using the drugs, and the budget impact may be US$26.28–58.98 million in 2019. However, the payment plans may avoid 492–766 fracture events and save medical expenditures for fracture treatment by US$1.30–2.02 million. The average costs for primary prevention within a year will be US$53,386–77,006. Conclusion The budget impact of using osteoporosis medications to primary prevention of fractures is significant, but it can be compensated due to savings in fracture treatment costs.

Relationship between P1NP, a biochemical marker of bone turnover, and bone mineral density in patients transitioned from alendronate to romosozumab or teriparatide: a post hoc analysis of the STRUCTURE trial Abstract Introduction Procollagen type I N-terminal propeptide (P1NP), a bone formation marker, reportedly predicts bone mineral density (BMD) response to teriparatide treatment in treatment-naive patients with osteoporosis. Results from a randomized, phase 3, open-label, active-controlled trial— STRUCTURE—showed that in patients previously treated with bisphosphonates, romosozumab led to gains in hip BMD, which were not observed with teriparatide. This post hoc analysis investigated the comparative utility of early changes in P1NP in predicting BMD response in patients who participated in the STRUCTURE trial, which enrolled patients who switched treatment from bisphosphonates to romosozumab/teriparatide. Materials and methods Postmenopausal women (aged 55–90 years) with osteoporosis who had previously taken bisphosphonates were randomized to receive open-label subcutaneous romosozumab (210 mg once monthly; n = 218) or teriparatide (20 µg once daily; n = 218) for 12 months. BMD was assessed by dual-energy X-ray absorptiometry at the proximal femur and lumbar spine (LS) at baseline and months 6 and 12. To assess the utility of P1NP, the positive predictive value of increase from baseline in P1NP of > 10 µg/L at month 1 and achievement of various thresholds of percent change from baseline in BMD at month 12 were evaluated. Results Overall, 95% (191/202) of patients in the romosozumab group and 91% (183/201) in the teriparatide group demonstrated an increase in P1NP of > 10 µg/L from baseline at month 1. Among these patients, 18% and 3% of romosozumab-treated patients versus 60% and 12% of teriparatide-treated patients showed no increase from baseline (i.e., ≤ 0%) in total hip and LS BMD, respectively, at month 12. These data indicate that in patients switching from bisphosphonates to a bone-forming therapy, increases in P1NP do not help predict the hip BMD response. Although most patients treated with either teriparatide or romosozumab showed an increase in P1NP, the majority of patients on romosozumab showed an increase in hip BMD, while more than half of the patients on teriparatide did not. Teriparatide therapy did not increase total hip BMD in the majority of patients who transitioned from bisphosphonates to teriparatide. Conclusions Thus, increases in P1NP were not predictive of BMD response in the teriparatide group because in approximately 60% of the patients who were administered teriparatide, the hip BMD decreased independent of the change in P1NP levels.

Growth pattern of lumbar bone mineral content and trunk muscles in adolescent male soccer players Abstract Introduction Previous studies have reported that the peak in lean body mass (LBM) precedes the peak in bone mineral content (BMC). However, it is unknown whether the trunk region growth is similar. Materials and methods We investigated the difference between pubertal peak age in the increase of LBM in the trunk (trunk LBM) and pubertal peak age in the increase of BMC in the lumbar spine (lumbar BMC) in a longitudinal study of 201 Japanese male adolescent soccer players. The age of peak height velocity (PHV) and the developmental age were calculated. The participants were followed over a 2-year period, with height and dual-energy X-ray absorptiometry scans taken every 6 months. Results The trunk LBM (ρ = 0.732, p < 0.0001) and the lumbar BMC (ρ = 0.621, p < 0.0001) significantly correlated with the developmental age. The increase of trunk LBM and lumbar BMC was significantly different according to the developmental stages (Kruskal–Wallis test; p < 0.0001 and p < 0.001, respectively). We used a cubic spline to estimate the developmental age, when the increase reached its peak: the peak age of the increase in trunk LBM was estimated to be – 0.08 years (approximately – 1 month) prior to PHV age, whereas the peak age of the increase in lumbar BMC was estimated to be 0.42 years (approximately 5 months) after the PHV age. Conclusions The maximal increase in trunk LBM occurs just before PHV age and approximately 6 months before the maximal increase in lumbar BMC during the pubertal growth spurt in the Japanese adolescent male soccer players.

Journal of Bone and Mineral Metabolism Best Paper Award 2019

Retraction Note To: The relationship between subclinical thyroid dysfunction and the risk of fracture or low bone mineral density: a systematic review and meta-analysis of cohort studies The editors have retracted this article [1] because it shows significant overlap with a publication by Blum et al. [2] Limin Tian does not agree to this retraction. All the other authors have not responded to any correspondence from the editor about this retraction.

Correction to: Effectiveness of monthly intravenous ibandronate on the low responders to oral bisphosphonate: the MOVEMENT study In the original publication of the article, the Figures 2 and 3 were published incorrectly. The corrected figures are given below,