Extensive Osteolysis Research Articles

Periprosthetic humeral fractures: Strategies and techniques for osteosynthesis

The prevalence of periprosthetic humeral fractures (PHF) is currently low and accounts for 0.6-2.4%. Due to an increase in the rate of primary implantations a quantitative increase of PHF is to be expected in the near future. The majority of PHF occur intraoperatively during implantation with an increased risk for cementless stems and when performing total arthroplasty. Additional risk factors are in particular female gender and the severity of comorbidities. In contrast, postoperative PHF mostly due to low-energy falls, have a prevalence between 0.6% and 0.9% and are significantly less common. The prognosis and functional outcome following revision by open reduction internal fixation (ORIF) essentially depend on a thorough assessment of the indications for revision surgery, the operative treatment and the pretraumatic functional condition of the affected shoulder. In the armamentarium of periprosthetic ORIF of the humerus cerclage systems and locking implants as well as a combination of both play a central role. In comminuted fractures with extensive defect zones, severely thinned cortex or extensive osteolysis a biological augmentation of the ORIF should be considered. In this context when the indications are correctly interpreted, especially in the case of a stable anchored stem, various groups have reported that a high bony union rate can be achieved. As the treatment of PHF is complex it should be performed in dedicated centers in order to adequately address potential comorbidities, especially in the elderly population.

Extensive osteolysis of the maxillofacial skeleton – a case report & review of literature

Extensive osteolysis of the maxillofacial skeleton – a case report & review of literature

IMAGING DIAGNOSIS: COMPUTED TOMOGRAPHIC FINDINGS IN A CASE OF ADENOSQUAMOUS CARCINOMA OF THE HEAD AND NECK IN A CAT

A 15-year-old female spayed domestic long-haired cat was referred for trismus, hypersalivation, and bilateral ocular discharge. On examination, the cat showed pain on palpation of the left zygomatic arch, palpable crepitus of the frontal region, and limited retropulsion of both globes. A contrast-enhanced sinonasal computed tomographic study was performed, showing facial distortion and extensive osteolysis of the skull, extending beyond the confines of the sinonasal and paranasal cavities. Additionally, soft tissue and fluid accumulation were observed in the nasal cavities and paranasal sinuses. Postmortem biopsy samples acquired from the calvarium yielded a histologic diagnosis of sinonasal adenosquamous carcinoma, a rare and particularly aggressive neoplasm previously only reported in the esophagus of one cat.

Characterization of a murine model of metastatic human non-small cell lung cancer and effect of CXCR4 inhibition on the growth of metastases.

Despite successful preclinical testing carried out through the use of subcutaneous xenografted tumors, many anti-cancer agents have gone on to fail in human trials. One potential factor accounting for this discrepancy may relate to the inadequacy of the commonly employed preclinical models to recapitulate the human disease, particularly when it comes to discovery of agents that are effective against advanced disease. Herein, we report the characterization of a NSCLC model and an exploration of the impact that a CXCR4 inhibitor, AMD3100, had on NCI-H1299-derived metastasis. These cells express a variety of metastasis-promoting factors, hence we selected them for a study of their metastatic colonization potential. To accomplish this, luciferase-expressing H1299 (H1299-luc2) cells were inoculated into athymic mice via the intracardiac route. This strategy produced adrenal, bone, ovarian, and pancreatic metastases, sites commonly involved in human metastatic NSCLC. Notably, micro-computed tomography and histological evaluation of the skeletal lesions revealed the presence of extensive osteolysis. To investigate the potential role of CXCR4 in mediating metastatic colonization of tissues, AMD3100 was administered to mice inoculated with H1299-luc2 cells. While this treatment did not appreciably alter the frequency of metastatic colonization, it was able to slow the growth of macrometastases. This model, recapitulating some of the events seen in late-stage human NSCLC, may prove useful in the evaluation of new therapies targeting metastatic disease.

Abstract 4858: A novel strategy for the selective and tissue specific inhibition of MMPs in active breast cancer to bone metastases

Abstract Bone metastasis is a common event during breast cancer progression: The delicate balance between bone matrix synthesizing osteoblasts and bone resorbing osteoclasts activities is typically subverted by the presence of tumor cells at the bone site. The resulting incurable lesions cause extensive osteolysis and severely impact the patient's quality of life. Understanding how active breast-to-bone metastases manipulate the bone microenvironment is critical for the development of new therapies to treat the disease. We have recently shown in preclinical animal models of breast to bone metastases that MMP-2 proteolytic activity is critical for the growth of the tumor and the associated osteolysis. We therefore hypothesized that the selective inhibition of MMP-2 at the tumor site would be a potent means through which to prevent the progression of the malignancy. Given that previous broad-spectrum MMP inhibitor (MMPI) trials were unsuccessful mainly because of consistent side effects, we took a novel chemical approach to generate a selective MMPI that would preferentially target the skeleton. To this end, we utilized a bisphosphonate backbone (tiludronate) to synthesize an MMPI (BMMPI) with high specificity for MMP-2 (IC50 0.14± 0.04μM). To test the efficacy of the BMMPI in vivo, we inoculated 6-week old immunocompromized female mice with a luciferase expressing osteolytic breast cancer cell line, PyMT-Luc (105 cells). Following tumor injection, mice (n=6/group) received saline, tiludronate (25mg/kg, to control for bisphosphonate effects) or BMMPI (25mg/kg) sub-cutaneously, twice weekly. Tumor growth was measured by quantitating luminescence over time. Our results show that application of the BMMPI significantly reduced the breast cancer growth over a two-week period (p<0.05). Furthermore, using Faxitron analysis to determine the extent of tumor induced bone destruction, we observed significantly less osteolysis in the tibia images of BMMPI treated mice compared to the control group. Our initial studies also suggest that BMMPIs perform better than clinically used bisphosphonates such as tiludronate. We are currently following up our in vivo/ex vivo analyses with histomorphometrical and histology approaches. In conclusion, our data thus far demonstrate that an MMP-2 specific BMMPI may be an effective means to prevent the progression of breast to bone metastases while at the same time eliminating some of the noted off-target effects of broad-spectrum MMP inhibitors. Since bisphosphonates are well tolerated in the clinical setting, we predict that BMMPIs could be rapidly translated to the patient. Citation Format: Marilena Tauro, Antonio Laghezza, Paolo Tortorella, Conor C. Lynch. A novel strategy for the selective and tissue specific inhibition of MMPs in active breast cancer to bone metastases. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4858. doi:10.1158/1538-7445.AM2014-4858

Abstract 1167: Osteolysis, splenic and hepatic extramedullary hematopoiesis, MDSCs, tumor growth, and metastases by orthotopic mammary tumors are increased by alcohol consumption and fatty diets

Abstract Fatty diets can induce low-grade inflammation that we report is increased by chronic alcohol consumption (CAC). CAC as 16.6% of total calories when administered in combination with the Lieber-DeCarli high-fat diet increases inflammation included hepatic and splenic extramedullary hematopoiesis (EMH) as assessed by flow cytometry, immunohistochemistry and a colony forming unit-granulocyte macrophage (CFU-GM) assay. Further, an increased number of hepatic myeloid derived suppressor cells (MDSCs) CD11b+Gr1+ cells that were predominantly Ly6cbr are observed. The increase in MDSCs is associated with an increased number of hepatic non-parenchymal cells including adipocytes (Oil Red O). Consistent with the increased number of hepatic MDSCs and EMH is a decrease in bone marrow cellularity and progenitor cells measured by flow cytometry (Lin-CD11b-Gr1-Sca-1+) and CFU-GM/femur. Unexpectedly, we observed demineralization and osteolytic lesions by micro computed tomography (micro CT) in all bones examined including femur, tibia, fibula and vertebral column that was associated with osteoclast activity (Trap+). Osteolysis was most notable in the fibula and vertebral spurs associated with osteoclast channels, and the demineralization appeared to be associated with areas of active myelopoiesis. The low grade, chronic inflammation associated with the Lieber-DeCarli fatty diet and CAC accelerated the induction of orthotopic 4T1 mammary tumors, resulting in extensive bone osteolysis, demineralization and increased metastases at aberrant sites including splenic, cardiac, hepatic, and extensive lymph node foci in addition to peritoneal and pleural effusions. The latter were haemorrhagic with a predominant nucleated cell infiltrate composed of bands, segs and myelocytes, supporting EMH. These results support the suggestion that a high-fat diet and CAC together increase tumor induction, metastasis and pathology in association with MDSC mobilization, expansion and EMH resulting in increased numbers of osteoclasts, associated bone demineralization and suppression of T-cell frequency and function. These results support the development of combination therapy strategies incorporating multiple molecular therapeutics that inhibit OCs, MDSCs and their associated mediators. Citation Format: Anand Dusad, Saraswoti Khadge, Geoffrey M. Thiele, Michael J. Duryee, Holly C. Britton, Lynell W. Klassen, Alicia J. Dafferner, Tracy Farrell, Timothy R. McGuire, Carlos D. Hunter, Karen C. Easterling, Karen J. O'Kane, John Graham Sharp, James E. Talmadge. Osteolysis, splenic and hepatic extramedullary hematopoiesis, MDSCs, tumor growth, and metastases by orthotopic mammary tumors are increased by alcohol consumption and fatty diets. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1167. doi:10.1158/1538-7445.AM2014-1167

Use of permanently placed metal expandable cages for vertebral body reconstruction in the surgical treatment of spondylodiscitis.

This is a retrospective study of 15 patients treated for spondylodiscitis with implanted metal cages. The purpose of this study is to investigate the outcomes of patients treated with permanently placed metal hardware in vertebral body reconstruction for spondylodiscitis. The use of metal implants in the face of infection has classically been discouraged in orthopedic literature because of the ability of bacteria to form biofilms on metal surfaces. Traditional treatment of spondylodiscitis has been aggressive debridement followed by reconstruction with bone grafts. Expandable metallic cages made reconstruction of these defects significantly easier. However, concern exists that metallic implants affect the resolution of infection. A search of the authors' patient database from 2005 to 2009 revealed 21 patients with spondylodiscitis treated with anterior debridement and reconstruction with an expandable metallic cage. Fourteen patients (15 cases) had sufficient documented clinical follow-up and were available for review. Resolution of infection was determined by evaluating symptoms, laboratory data, and final radiographic result. Of the 15 cases, all had clinical resolution of infection with an average follow-up time of 25 months. An average loss of 1.9° of correction was observed when comparing final follow-up radiographs with initial postoperative radiographs. Radiograph review revealed no extensive osteolysis around the hardware or progressive collapse. These results suggest that the use of expandable metal cages maintains alignment while not perpetuating infection. The spine appears to provide a unique environment that permits the use of metal implants in the setting of infection.

Management of Extensive Talar Osteolysis with Agility™ Total Ankle Replacement Systems Using Geometric Metal-reinforced Polymethylmethacrylate Cement Augmentation

The Agility™ Total Ankle Replacement System, almost exclusively without polymethylmethacrylate cement fixation, was the most commonly used implant in the United States from 1998 to 2007. Much attention has been given to the intraoperative complications and incision healing-related problems. However, it is the intermediate- and long-term complications, specifically, aseptic osteolysis, talar component loosening, subsidence, and progressive malalignment, that require careful consideration, because the revision options are limited. We describe a technique for management of extensive talar aseptic osteolysis for revision of Agility™ total ankle replacement systems with use of geometric metal-reinforced polymethylmethacrylate cement augmentation. This technique preserves the subtalar joint, provides immediate component stability and restoration of component alignment and height, and is a cost-effective alternative to other available options and still allows for additional revision should late failure occur.

Cytopathologic characteristics and differential diagnostic considerations of osteolytic myxopapillary ependymoma

Myxopapillary ependymoma (MPE) is a rare variant of conventional ependymoma found predominantly in the sacrococcygeal region in young adults and characterized by its distinct epithelial and stromal components (WHO grade I designation). MPE with extensive osteolysis is extremely uncommon and only up to 40 cases have been documented. A case is presented here in which imprint smears of a sacral tumor in an 18-year-old man revealed complex papillary structures, small loose clusters, or cord-like structures of bland tumor cells embedded in a myxoid or mucinous background. The tumor cells possessed uniformly round nuclei with a smooth nuclear outline, fine granular chromatin, and small nucleoli. Slender cytoplasmic fibrillary processes and occasional intracytoplasmic vacuoles were observed. A cytologic diagnosis of a MPE was suggested and histochemical and immunohistochemical studies were conducted on formalin-fixed, paraffin-embedded material. Immunohistochemically, the tumor cells showed diffuse and strong membranous and cytoplasmic staining for cytokeratin AE1/AE3, glial fibrillary protein, and S-100 protein, but negative for epithelial membrane antigen, pan-neuroendocrine markers (i.e., NSE, chromogranin A, synaptophysin), or brachyury. The proliferative index with MIB-1 was around 10%. The diagnosis of osteolytic MPE was confirmed based on cytopathologic, histopathological, immunohistochemical results, radiologic findings, and the location of the tumor. We demonstrated here the cytopathological features of osteolytic MPE with emphasis on differential diagnostic considerations.

Clinical and radiographic comparisons of two different radial head implant designs

There is little comparative data to guide implant choice for radial head replacements. The purpose of this study was to evaluate the clinical and radiographic results between patients who received a smooth-stemmed bipolar radial head implant and patients who received an in-growth monopolar prosthesis. Twenty-seven patients requiring a metallic radial head implant in the management of acute or chronic elbow trauma were evaluated. Fourteen patients received a smooth-stemmed bipolar prosthesis and 13 patients received a press-fit monopolar prosthesis. Patients returned for follow-up at an average of 33 months (range, 18-57). Outcome assessments included joint motion, elbow stability, grip strength, pain, the Mayo Elbow Performance Index, and the Disability of Arm, Shoulder and Hand questionnaire. Radiographs were reviewed for joint congruence, ectopic bone, periprosthetic osteolysis, degenerative arthritis, and capitellar wear, and selected patients were tested for inflammatory markers and metal ion levels. The differences between patient groups for elbow flexion and forearm pronation averaged 10° or less. There were no other pertinent differences between groups for standardized patient and examiner-determined outcomes. There was a trend for ectopic bone to develop more commonly around the smooth-stemmed implants, while periprosthetic osteolysis was more pronounced in cases with the press-fit design. Inflammatory markers were normal, and metal ion levels did not exceed values reported for a well-functioning hip arthroplasty. Outcomes at short- to mid-term follow-up were similar with either implant design. Loosening of a press-fit prosthesis may lead to extensive osteolysis, but of undetermined clinical consequence.

Abstract 1426: Functional analysis of membrane bound versus soluble RANKL: implications for cancer-induced osteolysis.

Abstract The primary site of prostate cancer metastasis is the skeleton with the resultant metastases containing areas of extensive osteogenesis and osteolysis. The latter is a process controlled by multinucleated osteoclasts and receptor activator of nuclear kappa B ligand (RANKL) is critical for osteoclastogenesis. RANKL is a type II transmembrane molecule that forms a trimer on the cell surface and mediates its effects via RANK. We have shown that matrix metalloproteinases-3 and -7 (MMP-3, MMP-7) can process RANKL to a soluble form, sRANKL. The objective of this study is to determine the functionality of membrane bound RANKL versus sRANKL in promoting osteoclastogenesis. Full-length murine RANKL cDNA was isolated and inserted into the pcDNA 3.1(+) expression construct. In vitro translation experiments demonstrated that RANKL was being generated and could be processed by MMP-3 and MMP-7. N-terminal amino acid sequencing revealed that the site of cleavage occurs in the juxtamembrane region of RANKL between amino acids 145 and 146. We hypothesized that cleavage in the juxtamembrane region could generate an active soluble form of sRANKL. Osteoclastogenesis and resorption assays with myeloid precursors demonstrated the functionality of sRANKL. To determine whether RANKL or sRANKL is the major mediator of osteoclastogenesis in vivo we have generated RANKL mutants that are resistant to cleavage by MMPs and other proteases. Using a site directed mutagenesis kit we have designed a number of mutants and found that Δ158, (deletion of amino acids 71-157) and, Δ148, deletion of amino acids 72-147), were resistant to proteolytic cleavage. We anticipate that the while Δ158 and Δ148 are resistant to cleavage, they will be functional. We will therefore test the functionality of these two deletion mutants in-vitro by co-culturing myeloid precursor cells with Cos-7/Cos-1 cells expressing wild type and mutant RANKL proteins. In conclusion, we have demonstrated that RANKL is proteolytically cleaved to generate a soluble active form. We have generated non-cleavable mutant forms of RANKL that will allow us to assess the role of membrane bound versus soluble RANKL in-vitro and in-vivo. The results of these experiments will further elucidate the roles of RANKL and sRANKL in prostate to bone metastases in addition to being informative for the engineering of future RANKL based therapies. Citation Format: Jeremy J. McGuire, Mitsuru Futakuchi, Conor Lynch. Functional analysis of membrane bound versus soluble RANKL: implications for cancer-induced osteolysis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1426. doi:10.1158/1538-7445.AM2013-1426

Osteonecrosis associated with dental implants in patients undergoing bisphosphonate treatment

Bisphosphonate-related jaw necrosis (BRONJ) associated with dental implants is a rare but continuously reported complication. To verify clinical and pathological characteristics of BRONJ around dental implants, the present study analyzed clinical, radiographic and histopathological findings of these lesions. Nineteen patients were diagnosed with osteonecrosis of the jaw associated with dental implants and treated at our institute from 2008 to 2011. The patients' medical history, demographic features, radiographic, and histopathological findings along with information on bisphosphonates (BP) administration were analyzed. The majority of BRONJ patients associated with dental implants used oral BP for osteoporosis. The patients were divided into two groups: BP initiation before (n = 16) and after (n = 3) implant surgery. Only three patients (15.8%) could be regarded as "implant surgery-triggered" BRONJ. Many patients (n = 9) showed successful osteointegration after fixture installation to an average of 35 months (11-82 months) until the development of osteonecrosis. The histological features of the lesion showed that the necrotic bone with empty lacunae was infiltrated by inflammatory cells and bacterial colonies. Viable osteocytes were also observed in some areas of the bony specimens. Three types of bone destruction pattern were observed: (i) complete necrosis of the bone around the implant (frozen type), (ii) extensive osteolysis around the implant with or without sequestra (osteolytic type), and (iii) sequestration of bone with an implant maintaining direct implant-bone contact (en block sequestration type). These findings could be existed at the same lesions depending on the degree of local bone destruction and the severity of the infection. These results and those of others suggested that already osseointegrated dental implants can also cause the osteonecrosis around the implant after BP administration. En block sequestration of bone with implant might be one of the characteristics of implant-related BRONJ, which is different from peri-implantitis-induced bone destruction. The possible role of microcracks in this type of bone destruction needs to be examined further.

A rare case of bilateral large osteolysis following cemented and cementless total knee arthroplasties

A 66-year old woman (BMI 36) presented for routine follow-up after undergoing total knee arthroplasty (TKA) in the right knee 12 years ago, and TKA in the left knee 4 years ago. The right TKA was a cementless cruciate-retaining prosthesis (Encore Medical Foundation Knee, femoral component porous coated CoCrMb alloy, tibial component Ti-alloy with 4 screws, PE insert 9 mm). The left TKA was a cemented cruciate-retaining prosthesis (Zimmer Natural Knee II, femoral component CoCrMb alloy, tibial baseplate component Ti-alloy, PE insert 9 mm). The patient reported only mild problems (knee score 88 points, function score 60 points). Radiographs and CT scans revealed extensive osteolysis at the proximal medial tibia of both knees (Figures 1 and ​and2).2). There was a mild varus malalignment (4°) of both legs. Rotational alignment measured on the CT scans showed a rotational mismatch between femoral and tibial components of 8° (femoral internal rotation) in the right knee and no mismatch (1° of femoral internal rotation) in the left knee. Figure 1. Anterioposterior and lateral radiograph and CT scans showing osteolysis of the distal right femur and the proximal tibia 12 years after implantation of a cemenless TKA. Figure 2. Anterioposterior and lateral radiograph and CT scans showing osteolysis of the distal left femur and the proximal tibia 4 years after implantation of a cemented TKA. Open biopsy was performed bilaterally to rule out a possible malignancy or infection. Microscopic histological examination revealed chronic inflammation and hisitocytic infiltrates in both knees. Polyethylene particles were observed within the cytoplasma of the histiocytes. There was no evidence of metal debris. All microbiological cultures were negative. During revision, both tibial baseplates were manually assessed as being well fixed to the lateral tibial bone stock, providing no evidence that baseplate loosening was the cause of the osteolysis. However, upon removal of the baseplates, the cortical bone at the proximal medial tibia was observed to be very thin and completely missing in some regions, as already revealed on the CT scans. Osteolytic defects were filled with autologous cancellous bone and augmented with bone cement, and both knees were implanted with a modular constrained TKA prosthesis.

Implant therapy on patients treated with oral bisphosphonates

Aim Bisphosphonates represent a group of drugs with a significant effect on bone structure preventing bone remodelling. They can be administered for the treatment of osteoporosis, Paget’s disease, osteogenesis imperfecta, osteopenia and bone metastases. The aim of this study was to discuss the necessary precautions for successful implant therapy on patients treated with per os bisphosphonates. Case reports Two female patients, both in the seventh decade of life, requested implant therapy. Their medical history was significant for osteoporosis, managed with per os bisphosphonates (Risedronate and Alendronate, respectively), without other risk factors for osteonecrosis. The duration of bisphosphonate administration was 4 years and 2 months respectively. After consultation with the treating physician, the patients stopped the bisphosphonates 3 months before and 3 months after the placement of the implants. The patients received antibiotic coverage for the surgical interventions. The treatment plan was completed uneventfully with placement of fixed prostheses without complications during a 2-year follow-up period. Conclusion The greatest dental treatment-related risk for patients on bisphosphonate therapy is bisphosphonate-associated osteonecrosis, which presents with exposure of avascular bone of the jaws and, according to the clinical stage, pain, inflammation, fractures and/or extensive osteolysis. Most of reported cases of bisphosphonate-associated osteonecrosis consist of patients on intravenous drug therapy who had undergone dentoalveolar surgery. Patients on per os bisphosphonates may undergo all types of dentoalveolar surgery, including implant placement, as long as the necessary precautions (bisphosphonate discontinuation, antibiotic coverage, meticulous oral hygiene) are taken.

Cementless Total Hip Arthroplasty Using a Modular Femoral Component in Patients with Femoral Head Osteonecrosis: Comparison of Metal-on-Metal and Ceramic-on-Ceramic Articulation

� Purpose: The purpose of this study was to evaluate the clinical and radiological outcomes after total hip arthroplasty using the S-ROM modular system for osteonecrosis of the femoral head, and to compare the results between the groups using metal-on-metal articulation and ceramic-on-ceramic articulation. Materials and Methods: Sixty-six patients (78 hips) with osteonecrosis of the femoral head were evaluated after primary total hip arthroplasty between January 2001 and December 2004, using an S-ROM proximal modular femoral stem. The average follow-up was 77 months (range, 60 to 122 months) and all patients were followed for more than five years. Results: The average Harris hip score improved from 53 points to 88.5 points at the final follow-up. At the latest radiologic evaluation, sixty-seven stems had bony ingrowth stability, and 10 stems had stable fibrous ingrowth. However, one stem had diffuse extensive osteolysis and loosening, which was revised at 9 years. Postoperative complications included 4 cases of heterotrophic ossificiation, 1 case of linear fracture after insertion of the femoral stem, 1 case of dislocation, 2 cases of infection, and 1 case of extensive osteolysis and loosening. There were 3 cases of revision and Kaplan-Meier survivorship analysis with revision estimated at a 95.7% chance of survival for the femoral component during 122 months. Conclusion: Our study showed that total hip arthroplasty using the S-ROM modular system with metal-on-metal articulation or ceramic-on-ceramic articulation had favorable clinical and radiological mid- to long-term results.

Severe lameness caused by metastatic renal adenocarcinoma of the third phalanx in a Warmblood mare

Malignant osseous neoplasia has been extremely rarely reported in the horse and, therefore, it is not commonly considered as a differential diagnosis for acute lameness. In the present report, a 19-year-old Warmblood mare in poor body condition and with a history of chronic haematuria, presumably attributable to renal neoplasia, was referred with acute, progressive, unilateral right forelimb lameness with marked unilateral digital pulsation and metacarpal oedema. No hoof abscess was found. Radiographic examination revealed a well defined osteolytic area in the dorsomedial half of the third phalanx. Dermal laminae at the dorsomedial aspect of the hoof showed a dark red appearance with poor vascularisation. Thoracic radiographs revealed pulmonary nodules. As osseous metastasis of the third phalanx was suspected, the mare was subjected to euthanasia. Post mortem histopathological examination confirmed the diagnosis of primary renal adenocarcinoma with metastasis to the lungs, myocardium, along the perirenal lymphatic tract and to the third phalanx, with extensive osteolysis in the latter location. Post mortem computed tomography of the hoof provided excellent visualisation of the osseous metastasis. The rare possibility of osseous metastatic neoplasia should be included in the differential diagnosis of severe lameness, especially in aged horses with a history of chronic renal disease.

Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

BackgroundPeriprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin) deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in Calca -/- mice.MethodsWe used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE) particles in 10 C57BL/6J wild-type (WT) mice and twenty Calca -/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1), WT with UHMWPE particles (Group 2), Calca -/- mice without UHMWPE particles (Group 3), Calca -/- mice with UHMWPE particles (Group 4), Calca -/- mice without UHMWPE particles and calcitonin substitution (Group 5), and Calca -/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6). Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP) + cells.ResultsBone resorption was significantly increased in Calca -/- mice compared with their corresponding WT. The eroded surface in Calca -/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in Calca -/- mice after particle implantation. Serum OPG (osteoprotegerin) increased significantly after CT substitution.ConclusionsAs anticipated, Calca -/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.

Cementless Total Hip Arthroplasty Using Titanium, Plasma-Sprayed Implants: A Study with 10 to 15 Years of Follow-up

To evaluate long-term outcomes of total hip arthroplasty (THA) using the Perfecta cementless system. 73 men and 76 women aged 65 to 88 (mean, 71) years underwent 168 THAs using the Perfecta cementless system and were followed up for a mean of 13 (10 to 15) years. 19 patients had bilateral THA. The diagnoses were idiopathic osteoarthritis (n=121), osteonecrosis of the femoral head (n=25), rheumatoid arthritis (n=14), and post-traumatic osteoarthritis (n=8). Patients were evaluated clinically and radiographically before and after THA. The mean Harris hip score improved from 40 to 84 (p<0.001); the score was excellent or good in 130 hips, fair in 17, and poor in 21. The mean Merle D'Aubigne score improved from 4 to 10 (p<0.001); the score was excellent or good in 138 hips, fair in 9, and poor in 21. Poor results were due to aseptic revision of the cup (n=16) or stem (n=3) or deep infection (n=2). Thigh pain that limited activities of daily living was noted in 3 hips. 142 patients could walk without a limp, 5 had a slight limp, and 3 had a moderate limp and used a cane. The mean Short Form-12 score for the physical function was 49 and for the mental health was 56; the mean Western Ontario and McMaster Universities Osteoarthritis Index was 39; the mean visual analogue scale score for satisfaction was 8. Two patients developed deep infection at postoperative months 8 and 50 and were treated with 2-staged revision. Five patients had hip dislocation within 2 months; 3 of whom endured recurrent dislocation and underwent revision surgery; they had acetabular malposition with excessive anteversion despite a correct acetabular angle. 13 other cups were revised because of loosening or extensive osteolysis (n=10) and polyethylene wear (n=3) after a mean interval of 6 (range, 4-10) years. Three stems were revised because of aseptic loosening after a mean interval of 7 (range, 6-9) years. The survivorship at 14 years was 99% for stems and 91% for cups. The long-term outcome of the Perfecta cementless stem was good; most major complications occurred in the cup.

Bone tumours affecting the spine in children and adolescents

Abstract Children and adolescents may present with non-specific back pain, commonly associated with developmental or psychosocial factors and with a benign and self-limiting course. The assessment of a child with back pain can be challenging and requires skill and expertise coupled with a high index of suspicion. Tumours affecting the vertebral column or the spinal cord should be always considered in the differential diagnosis of back pain in young patients. Bone tumours involving the spine are usually primary and benign, with a favourable outcome if appropriate treatment is applied at an early stage. Any delay in diagnosis can lead to prolonged morbidity, as well as the development of spinal deformity. This can be either a painful scoliosis, which starts as an antalgic deformity but gradually becomes structural, or a deformity affecting the coronal and sagittal planes due to extensive osteolysis as the result of the destructive course of a neoplasm. Primary malignant bony tumours are less common, but are associated with more severe morbidity and often respond poorly to treatment, despite recent advances in surgical techniques, chemo- and radiotherapy. This review summarizes current knowledge concerning bone tumours of the spine and provides a rational approach to the evaluation and management of this group of patients.

Osteolysis Propensity Among Bilateral Total Hip Arthroplasty Patients

Because some patients with high wear rates demonstrate extensive osteolysis whereas other patients with similarly high wear rates show little or no evidence of osteolysis, we hypothesized that both polyethylene wear and a patient-specific propensity mediate the development of osteolysis. We evaluated wear and osteolysis using computed tomography and radiographs among 46 patients who had undergone bilateral total hip arthroplasties (THAs). A radiographic patient-specific propensity for osteolysis associated with each THA was quantified by dividing the amount of osteolysis by the volumetric wear. Using a multivariate regression analysis to simultaneously consider the influence of polyethylene wear and patient propensity, we found that both factors are associated with the amount of osteolysis around a THA and that they appear to be of similar importance.