Bone Infarct Associated Osteosarcoma: Epidemiologic and Survival Trends

Background Bone tumors are not a frequent occurrence and bone-infarct-associated sarcomas are even rarer. The prognosis of this disease is poor and its treatment remains a challenge. Nevertheless, hardly any analyses in literature report on secondary osteosarcoma (SO) on bone infarct and most of the data available do not provide sufficient details. We evaluated whether this condition could be further characterized and if prognosis could be influenced by the chemotherapy treatment. In particular, we sought to determine (1) the main features of this rare disease; (2) the overall survival (OS) rate; (3) the OS rate associated to chemotherapy treatment; (4) the correspondence between our results and published data in terms of survival. Methods We retrospectively reviewed patients admitted at Rizzoli Orthopedic Institute of Bologna between 1992 and 2018 (1465 total cases of osteosarcoma). We identified a list of 11 cases of SO on bone infarct (cohort 1). We conferred about the epidemiology, surgical and chemotherapy (ChT) treatment and surveillance of infarct-associated osteosarcoma showing the correlation to data present in literature, corresponding to 15 case reports published within 1962-2018 (cohort 2). Results (1) cohort 1 was made of 11 patients: six females and five males, median age was 55 years. Nine (81%) were grade 4, two (19%) grade 3. Tumor predominantly arise on distal femur (64%). Most of patients had localized osteosarcoma at the diagnosis (81%); resection surgery was the elective treatment (73%) followed by amputation (18%). Of 11 patients, seven received also ChT (64%). (2) Five-years OS was 62% (95% CI: 28-84). Median OS was 74 months (95% CI: 12-not reached). The cumulative incidence of cancer-related deaths (CICRD) was 37.7% (95% CI: 11.4-64.5) at 120 months. (3) In the group treated with only surgery OS was 50% at 5 years. For patients treated with any form of ChT, OS was 71% at 5 years (p=0.4773) and hazard ratio (HR) 0.56. The CICRD was 29% (at 2 years of follow-up. Instead, it was of 50% for patients treated only with surgery. (4) Median survival was 74 months and 19 months for cohort 1 and cohort 2 respectively (p=0.09). Data analysis showed a decreased HR for cohort 1 compared to cohort 2 (HR 0.378). Results confirmed also stratifying for age and ChT administration (HR 0.355). Conclusions Based on this work, our opinion is that the choice to undergo the patients to ChT combined to surgery could improve their prognosis.

Enhancing the radiological classification system from the distal femur to the proximal tibia

Introduction The inner diaphyseal diameter of the distal femur, at 20 cm from the lateral joint line, is the strongest risk factor for predicting aseptic loosening in total knee arthroplasty using rotating hinge prosthesis. In this context, the Citak classification has been introduced presenting three different types of the distal femur anatomy. The aim of the study is to develop a novel classification system for the proximal tibia. Materials and Methods Two-hundred patients with standard knee antero-posterior radiographs were included in this study. We measured the inner diameter of the tibia 16 cm distally from the tibial plateau and 3 cm distally from the tibial spine. The ratio between these two measurements was applied as the novel index ratio. Results According to the 25th and 75th percentiles, three groups can be clustered for each gender. A higher distribution of the type B pattern was found in female and male patients. However, type A with a narrow inner diaphyseal diameter was less common in female patients The median intra-observer reliability for rater 1 was 0.997. The inter-observer reliability was high (ICC 0.998). There was a moderate correlation between the AP diameter and height (r = 0,568); a low correlation between the AP diameter and weight (r = 0.376). The novel index shows no significant correlation between the index ratio and height (r = 0.082), weight (r = 0.014) or BMI (r= - 0.038). The novel index shows no statistically significant correlation between the index ratio and height (r = 0.082) or weight (r = 0.014) or BMI (r= - 0.038). Conclusion The novel classification presents three different types of tibia for each gender: type C has a wider inner diaphyseal diameter compared to type A with a narrow inner diaphyseal diameter. Type B has the widest distribution among the subjects.

Differences in pathways contributing to thyroid hormone effects on postnatal cartilage calcification versus secondary ossification center development

The proximal and distal femur epiphysis of mice are both weight bearing structures derived from chondrocytes but differ in development. Mineralization at the distal epiphysis occurs in an osteoblast rich secondary ossification center (SOC), while the chondrocytes of the proximal femur head (FH) in particular, are directly mineralized. Thyroid hormone (TH) plays important roles in distal knee SOC formation, but whether TH also affects proximal FH development remains unexplored. Here, we found that TH controls chondrocyte maturation and mineralization at the FH in vivo through studies in Thyroid stimulating hormone receptor (Tshr -/-) hypothyroid mice by X-ray, histology, transcriptional profiling, and immunofluorescence staining. Both in vivo, and in vitro studies conducted in ATDC5 chondrocyte progenitors concur that TH regulates expression of genes that modulate mineralization (Bsp, Ocn, Dmp1, Opn, and Alp). Our work also delineates differences in prominent transcription factor regulation of genes involved in the different mechanisms leading to proximal FH cartilage calcification and endochondral ossification at the distal femur. The information on the molecular pathways contributing to postnatal cartilage calcification can provide insights on therapeutic strategies to treat pathological calcification that occurs in soft tissues such as aorta, kidney, and articular cartilage.