Positive correlation between the proximal femur Hounsfield units from routine CT and DXA results.

To determinate the correlation between the proximal femur Hounsfield unit (HU) value and dual-energy X-ray absorptiometry (DXA) results, and to identify its feasibility for opportunistic screening osteoporosis. A total of 680 patients underwent computed tomography (CT) containing proximal femur and DXA test within 6 months between 2010 and 2020 in our hospital. The CT HU value of four axial slices of the proximal femur were measured. The measurements were compared with the DXA results by Pearson correlation coefficient. Receiver operator characteristic curve were generated to identify the best cutoff for diagnosing osteoporosis. These 680 consecutive patients included 165 male and 515 female; the average age was 63.66 ± 11.36 years old, the mean interval time between two examinations was 45.43 days. The most representative CT HU value measurement was the 5-mm slice measurement. The average CT HU value was 59.3 ± 36.5 HU, and the differences among the three DXA defined bone mineral density (BMD) categories were significant (all p < 0.001). The Pearson correlation analysis showed that the proximal femur CT values had strong positive correlation with femoral neck T-score, femoral neck BMD and total hip BMD (r = 0.777, r = 0.748, r = 0.746, respectively; all p < 0.001). The area under the curve for CT value for diagnosing osteoporosis was 0.893 (p < 0.001), the best cutoff was 67 HU with 84% sensitivity, 80% specificity, 92% positive predictive value and 65% negative predictive value. Proximal femur CT values had good positive correlation with DXA results, which could be used to opportunistic screening for potential osteoporosis patient.

Reduction effect of oral pravastatin on the acute phase response to intravenous zoledronic acid: protocol for a real-world prospective, placebo-controlled trial.

INTRODUCTION: Zoledronic acid (ZA) has been used as a first-line treatment in patients with osteoporosis (OP) who receive an annual injection of 5 mg. However, side effects of bone pain and fever, known as the acute phase response (APR), have often been observed after clinical usage. A meta-analysis reported that the incidence of APR was 49.4% among patients with OP who received ZA for the first time and that 30% of patients with these adverse effects refused treatment in the following year. As a clinically used hypolipidaemic drug, statins can inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase to block the pathway upstream of farnesyl pyrophosphate synthase. This process can decrease the accumulation of isopentenyl pyrophosphate to prevent γδT-cell activation and inflammatory factor production, blocking APR occurrence. The aim of this study is to determine the reduction effect of oral pravastatin on APR and investigate the possible mechanisms underlying the effect in vivo. METHODS AND ANALYSIS: This will be a single-centre, placebo-controlled trial. Female participants will be allocated at a 1:1 ratio to receive either oral pravastatin or a placebo at 1-hour predose and 24 and 48 hours post-administration of ZA. The primary outcome will be the incidence of APR within 72 hours after ZA infusion. The secondary outcomes will include the occurrence time and severity of APR and the frequency and amount of acetaminophen usage within 72 hours after ZA infusion. This study will determine the preventive effect of oral pravastatin on APR in Chinese patients with OP, supporting the clinical application of ZA to alleviate concerns regarding safety and increase patient compliance. ETHICS AND DISSEMINATION: This study protocol has been registered with ClinicalTrials.gov. This study protocol was reviewed and approved by the Peking University Third Hospital Medical Science Research Ethics Committee. The results will be published in scientific peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04719481.

A Low-Profile and High-isolated MIMO Antenna for 5G Mobile Terminal.

An eight-element multiple-input multiple-output (MIMO) frame antenna array in the 3.5 GHz band (3400-3600 MHz) for 5G mobile terminal systems was presented. By using the adjacent grounding and electromagnetic coupling feeding technology, the loop antenna element could generate two resonant frequencies, thus effectively expanding its bandwidth. By adopting double-sided parallel strip line (DSPSL) technology, the electromagnetic coupling inside the loop antenna could be adjusted, and the size of the loop antenna could be effectively reduced so that the MIMO antenna array could obtain a low-profile structure. The total size of the MIMO array was 150 mm × 75 mm × 5.3 mm. Without additional isolation measures, the measured -6 dB impedance bandwidth (BW) was 3400-3660 MHz, and the minimum isolation between antenna elements was better than -20 dB. The proposed antenna was expected to be applied to 5G mobile terminals based on its low-profile, high-isolated characteristics, and good MIMO performance.

Prevalence of Osteoporosis in Patients Undergoing Lumbar Fusion for Lumbar Degenerative Diseases: A Combination of DXA and Hounsfield Units.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: To investigate the prevalence of osteoporosis (OP) in patients undergoing lumbar fusion for lumbar degenerative diseases (LDD). SUMMARY OF BACKGROUND DATA: OP is related to many complications after lumbar fusion for patients with LDD. There are sparse data on the prevalence of OP among this specific population. Moreover, LDD can falsely elevate the bone mineral density measured by dual energy x-ray absorptiometry (DXA), leading to unreliable diagnostic results. Computed tomography (CT) Hounsfield unit (HU) values can help identify osteoporotic patients undetected by DXA. METHODS: A total of 479 patients aged≥50 years undergoing lumbar fusion for LDD were reviewed. The diagnosis of OP using DXA was based on World Health Organization criterion. The criterion for OP diagnosed on CT scan was the L1-HU value≤110. RESULTS: The prevalence of OP diagnosed on lumbar DXA, hip DXA, and both was 32.4%, 19.6%, 39.7%, respectively. The females had higher prevalence of OP diagnosed on DXA (spine and hip) than males (48.9% vs. 27.1%, P < 0.001). In females but not males, the prevalence of OP significantly increased with age (females, 50-59: 28.0%, 60-69: 58.1%, ≥70: 78.8%, P < 0.001). Patients having primary diagnosis of degenerative lumbar scoliosis had the higher prevalence of OP than the rest patients (56.5% vs. 36.8%, P = 0.002). Among the 324 patients diagnosed with non-OP by lumbar DXA, the prevalence of OP diagnosed on CT scan was 25.9%, it increased with age and was also highest in patients with degenerative lumbar scoliosis. CONCLUSION: OP was quite common among patients aged≥50 years undergoing lumbar fusion for LDD, especially for females aged≥60 years or patients having degenerative lumbar scoliosis. Older patients or patients having degenerative lumbar scoliosis are more likely to have unreliable lumbar T-scores. Measurements of HU values can help identify more osteoporotic patients in this population. LEVEL OF EVIDENCE: 3.

Use of Hounsfield units of S1 body to diagnose osteoporosis in patients with lumbar degenerative diseases.

OBJECTIVEThe aim of this study was to evaluate the use of Hounsfield unit (HU) values of the S1 body to diagnose osteoporosis in patients with lumbar degenerative diseases.METHODSThe records of 316 patients of ages ≥ 50 years and requiring surgery for lumbar degenerative diseases were reviewed. The bone mineral density (BMD) of the S1 body and L1 was measured in HU with preoperative lumbar CT. Circular regions of interest (ROIs) were placed on midaxial and midsagittal images of the S1 body. Dual-energy x-ray absorptiometry (DXA) and the criterion of L1 HU ≤ 110 HU were used to diagnose osteoporosis. The area under the receiver operating characteristic curve (AUC) was calculated to assess the use of HUs of the S1 body to diagnose osteoporosis.RESULTSThe interobserver and intraobserver reliability of measuring HU of the S1 body was excellent with intraclass correlation coefficients over 0.8 (p < 0.001). The correlation between HUs of the S1 body and average T-score of L1-4 was significant with Pearson correlation coefficients ≥ 0.60 (p < 0.001). The AUCs for using HUs of the S1 body to diagnose osteoporosis were 0.86 and 0.88 for axial HU and sagittal HU, respectively (p < 0.001). The HU thresholds with balanced sensitivity and specificity for diagnosing osteoporosis were 202 HU for axial HU (sensitivity: 76%; specificity: 76%) and 185 HU for sagittal HU (sensitivity: 80%; specificity: 80%).CONCLUSIONSBoth sagittal and axial HUs of the S1 body are useful tools for assessing BMD and diagnosing osteoporosis. Measuring HUs of the S1 body preoperatively from lumbar CT may help with surgical planning for patients with lumbar degenerative diseases.

A Compact Broadband Antenna with Dual-Resonance for Implantable Devices.

A compact broadband implantable patch antenna is designed for the field of biotelemetry and experimentally demonstrated using the Medical Device Radiocommunications Service (MedRadio) band (401⁻406 MHz). The proposed antenna can obtain a broad impedance bandwidth by exciting dual-resonant frequencies, and has a compact structure using bent metal radiating strips and a short strategy. The total volume of the proposed antenna, including substrate and superstrate, is about 479 mm³ (23 × 16.4 × 1.27 mm³). The measured bandwidth is 52 MHz (382⁻434 MHz) at a return loss of -10 dB. The resonance, radiation and specific absorption rate (SAR) performance of the antenna are examined and characterized.

The use of CT Hounsfield unit values to identify the undiagnosed spinal osteoporosis in patients with lumbar degenerative diseases.

PURPOSES: Our purpose was to use computed tomography (CT) Hounsfield unit (HU) values to identify the undiagnosed spinal osteoporosis in patients with lumbar degenerative diseases. METHODS: A total of 334 patients with lumbar degenerative diseases were retrospectively reviewed and divided into two groups according to the degree of lumbar degenerative changes in preoperative lumbar CT images. Patients who had at least three vertebrae with severe degeneration at L1-L4 were placed in the degenerative group, and others were placed in the control group. HU value of trabecular bone in middle axial CT image of vertebral body, T-score and bone mineral density (BMD) at L1-L4 and hips were measured. CT HU thresholds for osteoporosis were obtained from control group and then applied to identify undiagnosed spinal osteoporosis. RESULTS: There were 182 patients in the degenerative group and 152 patients in the control group. CT HU value had a positive correlation with T-score and BMD of lumbar spine in both groups (P < 0.001), while the correlation coefficients at L1-L4 were higher in the control group (> 0.7) than in the degenerative group (< 0.7). T-score and BMD of lumbar spine were higher in the degenerative group (P < 0.05), while CT HU value, T-score and BMD of hips had no significant difference between two groups. According to the linear regression equations of vertebral T-score and CT HU value in the control group, the thresholds matching T-score of - 2.5 were 110, 100, 85 and 80HU for L1, L2, L3 and L4, respectively. Defining CT osteoporosis as L1 ≤ 110HU or L2 ≤ 100HU or L3 ≤ 85HU or L4 ≤ 80HU was 88.5% (69/78) specific and 60.8% (45/74) sensitive for distinguishing DXA osteoporosis of lumbar spine in the control group. The rate of undiagnosed spinal osteoporosis was higher in the degenerative group than in the control group according to CT HU thresholds (38.7% vs. 11.5%, P < 0.05). CONCLUSIONS: Degenerative changes in the lumbar spine can increase BMD and T-score provided by lumbar DXA, leading to an underestimation of vertebral osteoporosis. Thresholds for osteoporosis based on CT HU values can be used as a complementary method to identify undiagnosed spinal osteoporosis in patients with lumbar degenerative diseases. These slides can be retrieved under Electronic Supplementary Material.

Stattic inhibits RANKL-mediated osteoclastogenesis by suppressing activation of STAT3 and NF-κB pathways.

Tofacitinib, a small molecule JAK inhibitor, has been widely used to reduce inflammation and inhibit progression of bone destruction in rheumatoid arthritis. STAT3, a downstream signaling molecule of JAK, plays a key role in the activation of signaling in response to inflammatory cytokines. Thus, targeting STAT3 may be an inspiring strategy for treating osteoclast-related diseases such as rheumatoid arthritis. In this study, we first investigated the effects of Stattic, a STAT3 inhibitor, on receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis. Stattic inhibited osteoclast differentiation and bone resorption in RANKL-induced RAW264.7 cells in a dose-dependent manner. Stattic also suppressed RANKL-induced upregulation of osteoclast-related genes tartrate-resistant acid phosphatase, matrix metalloproteinase 9, cathepsin K, RANK, tumor necrosis factor receptor-associated factor 6, and osteoclast-associated receptor in RAW264.7 cells. Moreover, Stattic exhibited an inhibitory effect on cell proliferation and cell cycle progression at higher dosages. At the molecular level, Stattic inhibited RANKL-induced activation of STAT3 and NF-κB pathways, without significantly affecting MAPK signaling. In addition, Stattic inhibited RANKL-induced expression of osteoclast-related transcription factors c-Fos and NFATc1. Importantly, Stattic also prevented bone loss caused by ovariectomy. Together, our data confirm that Stattic restricts osteoclastogenesis and bone loss by disturbing RANKL-induced STAT3 and NF-κB signaling. Thus, Stattic represents a novel type of osteoclast inhibitor that could be useful for conditions such as osteoporosis and rheumatoid arthritis.

Comparison of the effects of once-weekly and once-daily rhPTH (1-34) injections on promoting fracture healing in rodents.

To compare the efficacy of once-weekly and once-daily subcutaneous injections of teriparatide (recombinant human parathyroid hormone 1-34) on fracture healing, 50 adult male Sprague-Dawley rats were subjected to a unilateral tibia fracture and received internal fixation with a Kirschner needle. Based on the injection dose and frequency, the rats were randomly divided into five groups (n = 10 each): subcutaneous injections of saline or 10 µg/kg/w, 20 µg/kg/w, 10 µg/kg/d, and 20 µg/kg/d teriparatide. Four weeks later, the rats were euthanatized, and the fractured tibiae were assessed using X-rays, dual-energy X-ray absorptiometry, micro-computed tomography, the three-point bending biomechanics test, and histology. Compared to the saline control group, either daily or weekly subcutaneous injections of teriparatide significantly increased bone mass, improved the bone microarchitecture, and promoted fracture healing (p < 0.05). There were no significant differences in bone mineral density (BMD), bone microstructure or bone strength between the 20 µg/kg/w and 10 µg/kg/d groups (p > 0.05). Teriparatide 20 µg weekly injections promoted bone fracture healing to the same extent as teriparatide 10 µg daily injections, which can dramatically decrease the cumulative dosage of teriparatide injections. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1145-1152, 2018.

A Convenient In Vivo Model Using Small Interfering RNA Silencing to Rapidly Assess Skeletal Gene Function.

It is difficult to study bone in vitro because it contains various cell types that engage in cross-talk. Bone biologically links various organs, and it has thus become increasingly evident that skeletal physiology must be studied in an integrative manner in an intact animal. We developed a model using local intraosseous small interfering RNA (siRNA) injection to rapidly assess the effects of a target gene on the local skeletal environment. In this model, 160-g male Sprague-Dawley rats were treated for 1-2 weeks. The left tibia received intraosseous injection of a parathyroid hormone 1 receptor (Pth1r) or insulin-like growth factor 1 receptor (Igf-1r) siRNA transfection complex loaded in poloxamer 407 hydrogel, and the right tibia received the same volume of control siRNA. All the tibias received an intraosseous injection of recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) or insulin-like growth factor-1 (IGF-1). Calcein green and alizarin red were injected 6 and 2 days before euthanasia, respectively. IGF-1R and PTH1R expression levels were detected via RT-PCR assays and immunohistochemistry. Bone mineral density (BMD), microstructure, mineral apposition rates (MARs), and strength were determined by dual-energy X-ray absorptiometry, micro-CT, histology and biomechanical tests. The RT-PCR and immunohistochemistry results revealed that IGF-1R and PTH1R expression levels were dramatically diminished in the siRNA-treated left tibias compared to the right tibias (both p<0.05). Using poloxamer 407 hydrogel as a controlled-release system prolonged the silencing effect of a single dose of siRNA; the mRNA expression levels of IGF-1R were lower at two weeks than at one week (p<0.01). The BMD, bone microstructure parameters, MAR and bone strength were significantly decreased in the left tibias compared to the right tibias (all p<0.05). This simple and convenient local intraosseous siRNA injection model achieved gene silencing with very small quantities of siRNA over a short treatment period (≤7 days).