The pathogenesis of heterotopic ossification after traumatic brain injury. A review of current literature.

Neurogenic heterotopic ossification (NHO), mostly defined as a benign process of formation of bone outside the skeletal system, after traumatic brain injury (TBI) is a musculoskeletal disorder that causes pain and reduces the range of motion, often leading to marked impairment of quality of life. The pathogenic factors that link the brain and bone and cause the formation of heterotopic bone are largely unknown. This article will try to summarize the current literature on the pathogenesis of NHO and accelerated fracture healing after TBI. The heterotopic formation of bone after TBI seems to be inducted by a complex interplay between local and systemic factors. For all different forms of HO, the same three conditions are required for the formation of ectopic bone : The presence of osteoprogenitor cells, a permissive environment, and a stimulating factor. The osteoprogenitor cells are thought to be of mesenchymal origin, however recent research suggests a possible neural origin. The permissive environment is created mainly by reactions to hypoxia and both local and sensory nerve inflammation. Many possible inducing factors have been described ; the endogenic route is thought to be the most dominant in the stimulation of HO formation after TBI. The pathogenesis of NHO remains largely unknown, recent research, however, has discovered interesting topics for further research and new possible targets in the prevention of NHO.

Traumatic brain injury enhances the formation of heterotopic ossification around the hip: an animal model study.

INTRODUCTION: The incidence of heterotopic ossification (HO) is at its highest when trauma of the hip or pelvis concurs with traumatic brain injury (TBI). The pathogenic mechanisms underlying the neurogenic enhancement of the formation of HO remain, however, poorly understood. Hence, the goal of the present study was to develop a novel small animal model that combines hip and brain trauma that can prove the enhancement of HO around the hip after TBI. MATERIALS AND METHODS: Forty male Wistar rats were divided into four groups, to undergo hip surgery alone (group 1), hip surgery + moderate TBI (group 2), hip surgery + severe TBI (group 3) and only severe TBI (group 4). The femoral canal was reamed up to 2 mm and a muscle lesion was made to simulate hip surgery. An established controlled cortical impact model was used to create a TBI. Twelve weeks after surgery, the hip with the proximal half of the femur and the pelvic bone was removed and subjected to micro-computed tomography (µCT) analysis. A quantitative analysis using a modified Brooker score as well as a quantitative analysis using a bone-to-tissue ratio was used. RESULTS: No HO could be found in all the ten animals that did not undergo hip surgery (group 4). In the animals that did undergo surgery to the hip, no HO was found in only one animal (group 1). All the other animals developed HO. In this study, significantly more HO was found in animals that underwent an additional severe TBI. CONCLUSION: The newly developed rat model, with a combined hip and brain trauma, showed an enhancement of the HO formation around the hip after severe TBI.

Conventional versus direct magnetic resonance imaging in detecting labral lesions in femoroacetabular impingment - a retrospective multicenter study.

The purpose of this study was to assess the reliability of Direct Magnetic Resonance Arthography (MRA) and Conventional Magnetic Resonance Imaging (MRI) in diagnosing labral lesions in patients with symptoms of femoroacetabular impingement (FAI). Materials and methods: Imaging and surgical data (n=490) were retrospectively collected from 5 high-volume centres providing arthroscopic treatment of FAI patients. Preoperative magnetic resonance imaging findings were compared with the actual surgical findings regarding labral condition in order to assess the effectiveness of MRI and MRA in identifying the presence of labral tears in patients with FAI. The results of this study indicate that MRI and MRA may both be useful for the diagnosis of acetabular labral lesions. The accuracy is slightly higher for MRI (71,4 %) compared to MRA (68,2 %), although MRA has higher sensitivity (74.4%,) as compared to MRI (66,9%). Conclusions: In a clinically suspected labral tear MRA has higher sensitivity than MRI. Further studies on asymptomatic patients may be needed to determine the specificity of different MRI techniques.

Contamination risk of synovial biopsy cultures in total hip arthroplasty: a prospective review of 100 cases.

INTRODUCTION: Cultures of deep synovial biopsies remain an important tool in diagnosing periprosthetic joint infection, a devastating complication following total hip arthroplasty (THA). Recent reports of unexpected positive intraoperative cultures in aseptic revision arthroplasty, however, challenge the validity and interpretation of these cultures. The aim of this study was to evaluate the contamination risk of synovial biopsy cultures collected intraoperatively during primary THA of healthy subjects. METHODS: Synovial biopsies for culture were collected during primary total hip arthroplasty procedures from 100 consecutive cases. The synovial biopsies were taken within the first 15 minutes after skin incision. Biopsy specimen were cultured on 4 different media for 8 or 15 days. Positive cultures were identified using Maldi-Tof spectrometry. RESULTS: 16 cultures yielded a bacterium, suggesting a false positive result of 16%. The mean time for the cultures to become positive was 6.29 days (standard deviation [SD] 3.90) with a maximum of 15 days. Proprionibacterium acnes and Staphylococcus epidermidis were most commonly cultured with 6 positive results for both bacteria. CONCLUSIONS: Our study yielded a 16% false positive rate in cultures of synovial biopsy taken during primary total hip arthroplasty of healthy subjects, suggesting that contamination risk of these synovial biopsy cultures may be larger than assumed by clinicians.

Surface Functionalization of Orthopedic Titanium Implants with Bone Sialoprotein.

Orthopedic implant failure due to aseptic loosening and mechanical instability remains a major problem in total joint replacement. Improving osseointegration at the bone-implant interface may reduce micromotion and loosening. Bone sialoprotein (BSP) has been shown to enhance bone formation when coated onto titanium femoral implants and in rat calvarial defect models. However, the most appropriate method of BSP coating, the necessary level of BSP coating, and the effect of BSP coating on cell behavior remain largely unknown. In this study, BSP was covalently coupled to titanium surfaces via an aminosilane linker (APTES), and its properties were compared to BSP applied to titanium via physisorption and untreated titanium. Cell functions were examined using primary human osteoblasts (hOBs) and L929 mouse fibroblasts. Gene expression of specific bone turnover markers at the RNA level was detected at different intervals. Cell adhesion to titanium surfaces treated with BSP via physisorption was not significantly different from that of untreated titanium at any time point, whereas BSP application via covalent coupling caused reduced cell adhesion during the first few hours in culture. Cell migration was increased on titanium disks that were treated with higher concentrations of BSP solution, independent of the coating method. During the early phases of hOB proliferation, a suppressive effect of BSP was observed independent of its concentration, particularly when BSP was applied to the titanium surface via physisorption. Although alkaline phosphatase activity was reduced in the BSP-coated titanium groups after 4 days in culture, increased calcium deposition was observed after 21 days. In particular, the gene expression level of RUNX2 was upregulated by BSP. The increase in calcium deposition and the stimulation of cell differentiation induced by BSP highlight its potential as a surface modifier that could enhance the osseointegration of orthopedic implants. Both physisorption and covalent coupling of BSP are similarly effective, feasible methods, although a higher BSP concentration is recommended.

The role of muscular trauma in the development of heterotopic ossification after hip surgery: An animal-model study in rats.

BACKGROUND: Heterotopic ossification (HO), the formation of bone in soft tissues, is a frequent complication after surgery of the hip and the pelvis. Although the pathophysiological entities responsible for the formation of HO remain largely unclear, muscle trauma is alleged to play a central role in the pathogenic mechanisms underlying HO. However, for this observation, made by many surgeons for decades, no objective evidence has been provided yet. METHODS: Fifty male Wistar rats were subjected to surgery of the right hip. The femoral canal was reamed in three steps up to 2mm. Animals formed 2 groups: in group 1 (25 animals) every effort was taken not to injure the muscles. In contrast, in the rats of group 2 (25 animals), an additional muscle lesion was created. Twelve weeks after surgery, the amount of heterotopic bone was assessed using micro-computed tomography, and classified using a modified Brooker classification system. A chi-square test was used to assess the statistical hypothesis comparing both groups. RESULTS: A significant higher amount of heterotopic bone was observed in animals that underwent additional muscular trauma. CONCLUSION: According to our data, muscle trauma seems to play an important role in the development of HO after hip surgery. Hence, during surgery, particular care not to injure the surrounding muscular tissue should be taken.

A new small-animal model for the study of acquired heterotopic ossification after hip surgery.

OBJECTIVE: Heterotopic ossification (HO)--the formation of bone in soft tissues--is a frequent problem after surgery of the hip and pelvis, but little is known about its underlying pathogenic mechanisms. It is vital to study the underlying pathogenesis in animal models to develop and evaluate new prophylactic regimens directed against HO. However, previously developed small-animal models for the study of HO imitate neither surgery nor trauma-mechanisms that potentially cause HO. Hence, the goal of this study was to develop a novel small-animal model imitating hip surgery that can reliably produce HO. METHODS: Twenty male Wistar rats were subjected to surgery of the right hip during which the femoral canal was reamed in three steps up to 2 mm, and a muscle lesion was made. Twelve weeks after surgery, the amount of heterotopic bone was assessed using micro-computed tomography. RESULTS: Eighteen of 20 animals showed HO around the hip 12 weeks after surgery. The amount of heterotopic bone varied from very small particles up to near ankylosis. CONCLUSION: A rat model of hip/pelvic surgery that does not use exogenous osteogenic stimulus and can reliably produce HO was developed.

The diagnostic value of SE MRI and DWI of the spine in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma.

OBJECTIVES: To evaluate DWI of the bone marrow in the differentiation of monoclonal gammopathy of undetermined significance (MGUS), smouldering myeloma (SMM) and multiple myeloma (MM). METHODS: The retrospective study includes 64 patients with MGUS, 27 with SMM, 64 with new MM and 12 controls. Signal intensity (SI) of spinal SE-MRI and DWI (b0-1000) as well as apparent diffusion coefficients (ADC) were measured in the T10 and L3. Qualitative assessment of b-images was performed by one experienced radiologist. RESULTS: ADC600 and ADC1000 are the best ADC values in differentiating patient groups (p < 0.030). SIT2, SIb1000 and ADC1000 are higher and SIT1 lower in L3 compared to T10 (p < 0.050). All quantitative parameters of L3 can differentiate significantly between MGUS and MM (p < 0.050) and between patients with percentage plasma cells (PC%) between 0-10 % compared to >50 % (p = 0.001). Only SIT2 for L3 can differentiate MGUS from SMM (p = 0.044) and PC%0-10 from PC%10-25 (p = 0.033). Qualitative interpretation of b1000 images allows differentiating MM patients from those with MGUS or SMM (p < 0.001). CONCLUSIONS: Spinal SE-MRI can differentiate among MGUS, SMM, MM and control subjects. DWI based on the SI on b1000 images and ADC values is increased in MM compared to MGUS and SMM. Qualitative assessment of b-images can differentiate MM from MGUS or SMM. KEY POINTS: • ADC values are higher in patients with MM compared to MGUS • DWI parameters change late in disease evolution • DWI is sensitive but not specific in diagnosing patients with MM • Qualitative DWI assessment is good in detecting myeloma patients.

Bilateral pseudarthrosis of the femoral neck in a 25-year-old male with hereditary hypophosphatemic rickets.

Hereditary hypophosphatemic rickets (HHR) is a rare disorder of renal phosphate wasting and the most common form of heritable rickets. Here, we report a case of an active 25-year-old male with HHR showing atraumatic bilateral femoral neck pseudarthrosis after 4 years of consecutive knee pain. A conservative therapy was administered, taking into account both the risks of surgical treatment and the little impairment even in the sport activities which the patient experienced.

Animal models for acquired heterotopic ossification.

Heterotopic ossification (HO), the ectopic formation of bone in soft tissues, is a relevant musculoskeletal disorder that, by reduction of range of motion, may lead to significant impairment of quality of live. HO can either be acquired or hereditary. Acquired HO is seen most often after hip prosthetic surgery and pelvic trauma. In contrast, hereditary HO is commonly observed in the axial skeleton, but can affect every joint. Substantial effort has been directed towards understanding the pathophysiology and towards finding both, effective prophylactic and therapeutic treatments. Every improvement of the understanding of the pathophysiologic changes underlying HO as well as the rationale of prophylactic and therapeutic treatment regimens in the end, is based on the study of appropriate animal models. Although intriguing models of 'genetic' HO have been developed recently, their relevance to acquired HO remains questionable. As there is still neither proper treatment nor reliable prophylaxis, animal models will remain important in the study of HO. Currently, there are 6 different animal models regularly used for the study of acquired HO. Some of these models can reflect a merely particular part of the disease. Hence, selection of the appropriate animal model for the study of HO is exceedingly important. The present paper reviews the history and major features of the different animal models of acquired HO, and reveals some of the insights gained through the study of animal models; important biochemical and pathophysiological key features are highlighted. Clinical studies have proved indometacine, celecoxib and radiation therapy to be effective in reducing the occurrence of HO, but not always be able to prevent it.