Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease.

BACKGROUND: The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI. METHODS: We analysed serum DKK1 levels and their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S). RESULTS: Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = - 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = - 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased ß-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001). CONCLUSIONS: Our study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice.

Effects of Adding Extracorporeal Shockwave Therapy (ESWT) to Platelet-Rich Plasma (PRP) among Patients with Rotator Cuff Partial Tear: A Prospective Randomized Comparative Study.

A rotator cuff tear is a prevalent ailment affecting the shoulder joint. The clinical efficacy of combined therapy remains uncertain for partial rotator cuff tears. In this study, we integrated extracorporeal shockwave therapy (ESWT) with platelet-rich plasma (PRP) injection, juxtaposed with PRP in isolation. Both cohorts exhibited significant improvements in visual analogue scale (VAS), Constant-Murley score (CMS), degrees of forward flexion, abduction, internal rotation, and external rotation, and the sum of range of motion (SROM) over the six-month assessment period. The application of ESWT in conjunction with PRP exhibited notable additional enhancements in both forward flexion (p = 0.033) and abduction (p = 0.015) after one month. Furthermore, a substantial augmentation in the range of shoulder motion (SROM) (p < 0.001) was observed after six months. We employed isobaric tag for relative and absolute quantitation (iTRAQ) to analyze the differential plasma protein expression in serum samples procured from the two groups after one month. The concentrations of S100A8 (p = 0.042) and S100A9 (p = 0.034), known to modulate local inflammation, were both lower in the ESWT + PRP cohort. These findings not only underscore the advantages of combined therapy but also illuminate the associated molecular changes.

Does preoperative dipyridamole-thallium scanning reduce 90-day cardiac complications and 1-year mortality in patients with femoral neck fractures undergoing hemiarthroplasty?

BACKGROUND: This study aimed to evaluate the effect of dipyridamole-thallium scanning (DTS) on the rates of 90-day cardiac complications and 1-year mortality in patients with a femoral neck fracture treated with hemiarthroplasty. METHODS: Between 2008 and 2015, 844 consecutive patients who underwent cemented or cementless hemiarthroplasty were identified from the database of a single level-one medical center. One-hundred and thirteen patients (13%) underwent DTS prior to surgery, and 731 patients (87%) did not. Patient characteristics, comorbidities, surgical variables, and length of the delay until surgery were recorded. A propensity score-matched cohort was utilized to reduce recruitment bias in a 1:3 ratio of DTS group to control group, and multivariate logistic regression was performed to control confounding variables. RESULTS: The incidence of 90-day cardiac complications was 19.5% in the DTS group and 15.6% in the control group (p = 0.343) among 452 patients after propensity score-matching. The 1-year mortality rate (10.6% vs 13.3%, p = 0.462) was similar in the two groups. In the propensity score-matched patients, utilization of DTS was not associated with a reduction in the rate of 90-day cardiac complications (matched cohort, adjusted odds ratio [aOR] = 1.32; 95% confidence interval [CI] 0.75-2.33, p = 0.332) or the 1-year mortality rate (aOR = 0.62; 95% CI 0.27-1.42, p = 0.259). Risk factors for cardiac complications included an American Society of Anesthesiologists grade ≥ 3 (OR 3.19, 95% CI 1.44-7.08, p = 0.004) and pre-existing cardiac comorbidities (OR 5.56, 95% CI 3.35-9.25, p < 0.001). Risk factors for 1-year mortality were a long time to surgery (aOR 1.15, 95% CI 1.06-1.25, p = 0.001), a greater age (aOR 1.05, 95% CI 1.00 to 1.10, p = 0.040), a low body mass index (BMI; aOR 0.89, 95% CI 0.81-0.98, p = 0.015), and the presence of renal disease (aOR 4.43, 95% CI 1.71-11.46, p = 0.002). DISCUSSION: Preoperative DTS was not associated with reductions in the rates of 90-day cardiac complications or 1-year mortality in patients with a femoral neck fracture undergoing hemiarthroplasty. The necessity for DTS should be re-evaluated in elderly patients with femoral neck fractures, given that this increases the length of the delay until surgery. LEVEL OF EVIDENCE: Prognostic level III.