Osteoporosis and cement usage in total hip arthroplasty.

PURPOSE: Cement usage in total hip arthroplasty (THA) is increasingly common. However, osteoporosis-related fracture risk in cemented vs uncemented THA patients is poorly characterized. We aim to analyze the usage of metabolic bone care and osteoporosis fracture risk in cemented vs uncemented THA patients using FRAX and radiographic bone measurements. METHODS: Chart review on 250 THA patients was performed retrospectively. Demographics, FRAX scores, hip radiograph measurements, osteoporosis diagnosis, treatment and screening were compared between cemented and uncemented THA patients. Logistic regression model was used to analyze factors influencing cement usage. RESULTS: Cemented THA patients have significantly higher osteoporosis-related fracture risk as measured by FRAX major (20% vs 13%) and FRAX hip (8% vs 5%). There is no significant difference in osteoporosis treatment, vitamin D / calcium supplementation, or metabolic bone disease screening based on patients' cement status. Female sex and rheumatoid arthritis status significantly predict cement usage, but FRAX scores do not predict cement usage. Additionally, 50% (10/20) of patients with Dorr C classification were uncemented. CONCLUSION: Although some patients undergoing THA with high osteoporosis-related fracture risk were identified and cemented, some risk factors including poor proximal femur shape (by Dorr classification) and poor bone quality (as measured by FRAX score) were potentially overlooked. Cemented patients had an increased risk for fractures but did not receive appropriately increased osteoporosis screening or treatment. LEVEL OF EVIDENCE: III.

Long-Term Patient Outcomes for Treatment of Difficult Osteochondral Lesions of the Talus with Particulated Juvenile Allograft Cartilage Implantation ± Calcaneal Autograft: A Cohort Study.

BACKGROUND: Osteochondral lesions of the talus (OCLT) are common injuries that can be difficult to treat. To date, long-term patient reported outcome measures (PROMs) of patients with particulated juvenile allograft cartilage implantation with or without calcaneal autograft have not been compared. METHODS: Thirteen patients with difficult to treat OCLTs underwent arthroscopic-assisted implantation of particulated juvenile allograft cartilage (DeNovo NT®) with or without autogenous calcaneal bone grafting by a single surgeon. Calcaneal bone graft use was determined by lesion size > 150 mm2 and/or deeper than 5 mm. Patients were evaluated using physical examination, patient interviews, and PROMs. RESULTS: When comparing patients in regards to calcaneal bone graft implantation, no difference in age, BMI, pre-operative PROMs, or follow-up was noted, however, calcaneal bone graft patients did have a significantly larger lesion size (188.5 ± 50.9 vs. 118.7 ± 29.4 mm2 respectively; p value = 0.027). VAS and FAAM ADL scores during final follow-up improvement did not significantly differ between cohorts. The FAAM Sports score improved significantly more for the DeNovo alone group compared to the bone graft cohort (p value = 0.032). The AOFAS score improvement did not differ between cohorts (p value = 0.944), however, the SF-36 PCS improved significantly more for the DeNovo alone group compared to the bone graft cohort (p value = 0.038). No intraoperative/perioperative complications were observed with calcaneal bone grafting. CONCLUSION: While patients followed over the course of ~ 8 years after implantation of particulated juvenile allograft cartilage (DeNovo NT®) with/without autogenous calcaneal bone graft had positive post-operative PROMs, patients without calcaneal bone graft had significantly greater improvement in functional outcome scores. Whether these differences are due to graft incorporation or larger lesion size is unclear. LEVEL OF EVIDENCE: III, retrospective cohort study.

Early outcomes of the Exactech Vantage fixed-bearing total ankle replacement.

Aims: The Vantage Total Ankle System is a fourth-generation low-profile fixed-bearing implant that has been available since 2016. We aimed to describe our early experience with this implant. Methods: This is a single-centre retrospective review of patients who underwent primary total ankle arthroplasty (TAA) with a Vantage implant between November 2017 and February 2020, with a minimum of two years' follow-up. Four surgeons contributed patients. The primary outcome was reoperation and revision rate of the Vantage implant at two years. Secondary outcomes included radiological alignment, peri-implant complications, and pre- and postoperative patient-reported outcomes. Results: There were 168 patients (171 ankles) included with a mean follow-up of 2.81 years (2 to 4.6) and mean age of 63.0 years (SD 9.4). Of the ten ankles with implant failure (5.8%), six had loosening of the tibial component. In the remaining four failed implants, one was due to periprosthetic joint infection (PJI), one was due to loosening of the talar component, and two were due to loosening of both the tibial and talar components. Seven patients underwent reoperation: irrigation and debridement for superficial infection (n = 4); bone grafting for cysts (n = 2); and open reduction internal fixation (n = 1). Asymptomatic peri-implant lucency/subsidence occurred in 20.1% of ankles, with the majority involving the tibial component (n = 25). There were statistically significant improvements in PROMs in all domains. Conclusion: Short-term results of this implant demonstrate early survival comparable to the reported survivorship of similar low-profile, non-stemmed implants. Radiological lucency occurred more commonly at the tibial component, and revisions occurred primarily due to loosening of the tibial component. Further research is needed to evaluate longer-term survivorship.

Osteoid Osteomas of the Talus: A Case Report of Four Patients.

Osteoid osteomas are benign bone tumors that are commonly found in the cortical segments of long bone but can occasionally occur in the talus of the foot. They typically present in younger males and are characterized by lesions with a vascularized nidus surrounded by sclerotic bone. Plain radiographs can often miss the diagnosis, requiring further imaging with computed tomography (CT) or magnetic resonance imaging (MRI). Lesions often lead to a significant inflammatory response resulting in an impaired range of motion and nocturnal pain. Conservative management with non-steroidal anti-inflammatory medications and a walking boot is considered first-line therapy, with failure to respond being an indication for surgical intervention. Surgical treatment traditionally consisted of en bloc resection but has been replaced by CT-guided radio-frequency ablation (RFA) when conservative management has failed. Four cases of osteoid osteoma of the talus are presented which all went on to RFA after conservative management failed. The patients' non-specific symptomatology and unremarkable findings on plain radiographs led to further evaluation using MRI or CT, which aided in the diagnosis. Following imaging, RFA was performed which resulted in 100% relief of pain and symptoms in all four patients and a return to full activity without limitations. Osteoid osteomas of the talus present unique challenges due to the non-specific symptoms and complex surrounding anatomy that accompanies this condition. Management should include the use of CT for localization and RFA of the lesion, which we have shown leads to complete resolution of symptoms and return to normal daily activities.

Genetic therapy in a mitochondrial disease model suggests a critical role for liver dysfunction in mortality.

The clinical and largely unpredictable heterogeneity of phenotypes in patients with mitochondrial disorders demonstrates the ongoing challenges in the understanding of this semi-autonomous organelle in biology and disease. Previously, we used the gene-breaking transposon to create 1200 transgenic zebrafish strains tagging protein-coding genes (Ichino et al., 2020), including the lrpprc locus. Here, we present and characterize a new genetic revertible animal model that recapitulates components of Leigh Syndrome French Canadian Type (LSFC), a mitochondrial disorder that includes diagnostic liver dysfunction. LSFC is caused by allelic variations in the LRPPRC gene, involved in mitochondrial mRNA polyadenylation and translation. lrpprc zebrafish homozygous mutants displayed biochemical and mitochondrial phenotypes similar to clinical manifestations observed in patients, including dysfunction in lipid homeostasis. We were able to rescue these phenotypes in the disease model using a liver-specific genetic model therapy, functionally demonstrating a previously under-recognized critical role for the liver in the pathophysiology of this disease.

Rbbp4 loss disrupts neural progenitor cell cycle regulation independent of Rb and leads to Tp53 acetylation and apoptosis.

BACKGROUND: Retinoblastoma binding protein 4 (Rbbp4) is a component of transcription regulatory complexes that control cell cycle gene expression. Previous work indicated that Rbbp4 cooperates with the Rb tumor suppressor to block cell cycle entry. Here, we use genetic analysis to examine the interactions of Rbbp4, Rb, and Tp53 in zebrafish neural progenitor cell cycle regulation and survival. RESULTS: Rbbp4 is upregulated across the spectrum of human embryonal and glial brain cancers. Transgenic rescue of rbbp4 mutant embryos shows Rbbp4 is essential for zebrafish neurogenesis. Rbbp4 loss leads to apoptosis and γ-H2AX in the developing brain that is suppressed by tp53 knockdown or maternal zygotic deletion. Mutant retinal neural precursors accumulate in M phase and fail to initiate G0 gene expression. rbbp4; rb1 mutants show an additive effect on the number of M phase cells. In rbbp4 mutants, Tp53 acetylation is detected; however, Rbbp4 overexpression did not rescue DNA damage-induced apoptosis. CONCLUSION: Rbbp4 is necessary for neural progenitor cell cycle progression and initiation of G0 independent of Rb. Tp53-dependent apoptosis in the absence of Rbpb4 correlates with Tp53 acetylation. Together these results suggest that Rbbp4 is required for cell cycle exit and contributes to neural progenitor survival through the regulation of Tp53 acetylation.