Hypercalcemia and cancer: Differential diagnosis and treatment.

Incidentally detected hypercalcemia usually presents in an indolent manner and is most likely caused by primary hyperparathyroidism. In contrast, hypercalcemia in the patient with a history of cancer presents in a wide range of clinical settings and may be severe enough to warrant hospitalization. This form of hypercalcemia is usually secondary to hypercalcemia of malignancy and can be fatal. Hypercalcemia of malignancy is most commonly mediated by tumoral production of parathyroid hormone-related protein or by cytokines activating osteoclast degradation of bone. The initial workup, differential diagnoses, confirmatory laboratory testing, imaging, and medical and surgical management of hypercalcemia are described in the patient with cancer.

Bacterial infections exacerbate myeloma bone disease.

Multiple myeloma is characterized by osteolytic lesions caused by reduced bone formation and activated bone resorption. An important feature of myeloma is a failure of bone healing after successful treatment. In this work, clinical studies indicated a highly positive correlation between bone marrow bacteria abundance and bone lesion numbers of myeloma patients in complete remission. Coculture experiments demonstrated that marrow Escherichia coli (E. coli) promotes osteoclast differentiation and inhibits osteoblast differentiation. Mechanism studies showed that E. coli lipopolysaccharides (LPS) activated NF-κB p65 signaling and reduced phosphorylated smad1/5/9 binding ability with RUNX2 promoter, leading to decreased RUNX2 expression in osteoblast progenitors. Additionally, LPS enhanced phosphorylated NF-κB p65 binding ability with NFATc1 promoter, leading to increased NFATc1 expression in osteoclast progenitors. In vivo studies revealed E. coli contributes to osteolytic bone lesion, and elimination of E. coli infection assists healing of bone lesion in mouse model of myeloma in complete remission. These findings establish a heretofore unrecognized effect for E. coli in the genesis of myeloma bone disease and suggest a new treatment strategy.

Gorham Stout disease: 3 additional cases with 2 very rare polyostotic diseases.

Gorham Stout disease is a very rare monostotic or polyostotic osteolysis and physiopathology of the osteolysis is not yet fully understood. Three new cases are reported with their evolution and treatment. Among these 3 cases, two are very rare cases of polyostotic involvement. One patient finally deceased from respiratory complications despite limb amputation. The two others are alive. Both needed final reconstruction with massive bone allograft for one and with a prosthesis for the other. Monostotic osteolysis is the most frequent presentation of Gorham Stout disease and extensive polyostotic osteolysis is very rare. Treatment methods vary from one clinic to another, from drug treatment to surgical treatment with or without radiotherapy. Sometimes, as a last solution, an amputation of the affected limb is performed. The prognosis depends on the affected region and the reponse to various treatments. Chylothorax seems to be a factor of poor prognosis.

Mechanical loading attenuates breast cancer-associated bone metastasis in obese mice by regulating the bone marrow microenvironment.

Breast cancer, a common malignancy for women, preferentially metastasizes to bone and obesity elevates the chance of its progression. While mechanical loading can suppress obesity and tumor-driven osteolysis, its effect on bone-metastasized obese mice has not been investigated. Here, we hypothesized that mechanical loading can lessen obesity-associated bone degradation in tumor-invaded bone by regulating the fate of bone marrow-derived cells. In this study, the effects of mechanical loading in obese mice were evaluated through X-ray imaging, histology, cytology, and molecular analyses. Tumor inoculation to the tibia elevated body fat composition, osteolytic lesions, and tibia destruction, and these pathologic changes were stimulated by the high-fat diet (HFD). However, mechanical loading markedly reduced these changes. It suppressed osteoclastogenesis by downregulating receptor activator of nuclear factor Kappa-B ligand and cathepsin K and promoted osteogenesis, which was associated with the upregulation of OPG and downregulation of C/enhancer-binding protein alpha and proliferator-activated receptor gamma for adipogenic differentiation. Furthermore, it decreased the levels of tumorigenic genes such as Rac1, MMP9, and interleukin 1ß. In summary, this study demonstrates that although a HFD aggravates bone metastases associated with breast cancer, mechanical loading significantly protected tumor-invaded bone by regulating the fate of bone marrow-derived cells. The current study suggests that mechanical loading can provide a noninvasive, palliative option for alleviating breast cancer-associated bone metastasis, in particular for obese patients.

Controversies in the use of new bone-modifying therapies in multiple myeloma.

Bone-modifying therapies are essential in the treatment of patients with multiple myeloma. Zoledronic acid is preferred over other bisphosphonates due to its superiority in reducing the incidence of skeletal-related events and improving survival. The anti-receptor activator of nuclear factor-κΒ ligand (RANKL)-targeted agent denosumab has shown its non-inferiority compared to bisphosphonates in preventing skeletal-related events among newly diagnosed patients with myeloma bone disease. Denosumab may confer a survival benefit in patients eligible for autologous transplantation. Denosumab may present a safer profile for patients with renal impairment. Discontinuation of bone-directed therapies can be considered for patients with deep responses and after an adequate time period on treatment; however, a rebound effect may become evident especially in the case of denosumab. Three-monthly infusions of zoledronic acid or at-home denosumab administration should be considered during the coronavirus disease 2019 (COVID-19) pandemic. Measures to prevent hypocalcaemia, renal toxicity and osteonecrosis of the jaw are important for all bone-modifying agents.

Hypercalcemia and Disseminated Osteolytic Lesions With Normal Blood Counts and Absence of Circulating Blasts: A Rare Presentation of Childhood B-Lymphoblastic Leukemia.

Hypercalcemia and disseminated osteolytic bone lesions are a rare presentation of pediatric acute lymphoblastic leukemia (ALL). The authors report a 3-year-old boy who presented with hypercalcemia and diffuse osteolytic lesions involving axial and appendicular bones. He had normal complete blood count and the absence of blasts in peripheral smear; however, bone marrow aspirate and trephine were consistent with B-cell ALL. A review of the literature highlights the variable clinical outcome of this rare presentation depending on the presence of hypercalcemia and osteolytic lesions with or without chromosomal translocation t(17;19) and coagulation abnormalities. The patient had no coagulopathy and normal karyotype, and showed excellent response to initial treatment in terms of complete remission and negative minimal residual disease after standard-risk induction chemotherapy. Hypercalcemia with diffuse osteolytic lesions warrants bone marrow examination to rule out leukemia even in the absence of any abnormality in complete blood count. The case was reported for awareness of this rare presentation of ALL so that delays can be avoided for this potentially curable but life-threatening disease.

No differences between conservative and surgical management of acromioclavicular joint osteoarthritis: a scoping review.

PURPOSE: To conduct a scoping review to clarify the management of acromioclavicular joint osteoarthritis, as well as to identify any existing gaps in the current knowledge. METHODS: Studies were identified by electronic databases (Ovid, Pubmed) from their inception up to April 2nd, 2020. All studies reporting functional outcomes after conservative or surgical treatment of acromioclavicular joint osteoarthritis, either primary or secondary to trauma or distal clavicle osteolysis, were included. Following data were extracted: authors, year of publication, study design (prospective or retrospective), LOE, number of shoulders treated conservatively or surgically, patients' age, OA classification, type of conservative treatment, surgical approach, surgical technique, functional outcomes, complications, revisions, and length of follow-up. Descriptive statistics was used. Quality appraisal was assessed through the Cochrane risk of bias tool for LOE I/II studies, while the MINORS checklist was used for LOE III/IV studies. RESULTS: Nineteen studies were included for a total of 861 shoulders. Mean age of participants was 48.5 ± 7.4 years. Mean follow-up was 43.8 ± 29.9 months. Four studies reported functional results after conservative treatment, whereas 15 studies were focused on surgical management. No studies directly compared conservative and surgical treatment. Seven studies reported a surgical approach after failure of previous conservative treatment. All studies reported functional improvement and pain relief. Complication rate was low. Overall methodological quality of included studies was very low. CONCLUSION: Conservative and surgical treatments are both effective in acromioclavicular joint osteoarthritis management. However, available data did not allow to establish the superiority of one technique over another. LEVEL OF EVIDENCE: Level IV.

Management of Myeloma Bone Lesions.

Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal plasma-cell proliferation. The survival and prognosis of this condition have been significantly improved by treatment with active anti-MM drugs such as bortezomib or lenalidomide. Further, the discovery of novel agents has recently paved the way for new areas of investigation. However, MM, including myeloma-related bone diseases, remains fatal. Bone disease or bone destruction in MM is a consequence of skeletal involvement with bone pain, spinal cord compression, and bone fracture resulting from osteolytic lesions. These consequences affect disease outcomes, including patients' quality of life and survival. Several studies have sought to better understand MM bone disease (MBD) through the classification of its molecular mechanisms, including osteoclast activation and osteoblast inhibition. Bisphosphonates and the receptor activator of the nuclear factor-kappa B (NF-κB) ligand (RANKL) inhibitor, denosumab, prevent skeletal-related events in MM. In addition, several other bone-targeting agents, including bone-anabolic drugs, are currently used in preclinical and early clinical evaluations. This review summarizes the current knowledge of the pathogenesis of MBD and discusses novel agents that appear very promising and will soon enter clinical development.

Puerarin inhibits titanium particle-induced osteolysis and RANKL-induced osteoclastogenesis via suppression of the NF-κB signaling pathway.

Osteolysis around the prosthesis and subsequent aseptic loosening are the main causes of prosthesis failure. Inflammation due to wear particles and osteoclast activation are the key factors in osteolysis and are also potential targets for the treatment of osteolysis. However, it is not clear whether puerarin can inhibit chronic inflammation and alleviate osteolysis. In this study, we investigated the effect of puerarin on Ti particle-induced inflammatory osteolysis in vivo in rat femoral models and in vitro in receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast activation models. Our in vivo results showed that puerarin significantly inhibited Ti particle-induced osteolysis and the expression of matrix metallopeptidase 9 (MMP-9), nuclear factor of activated T cells 1 (NFATc1), tumour necrosis factor (TNF)-α and interleukin (IL)-6. In vitro, puerarin prevented RANKL-induced osteoclast differentiation, bone resorption and F-actin ring formation in a concentration-dependent manner. Furthermore, puerarin decreased the phosphorylation of p65 and prevented p65 moving from the cytoplasm to the nucleus. Puerarin also reduced the expression of osteoclast-specific factors and inhibited the inflammatory response. In conclusion, our study proves that puerarin can block the NF-κB signalling pathway to inhibit osteoclast activation and inflammatory processes, which provides a new direction for the treatment of osteolysis-related diseases.

Curcumin has immunomodulatory effects on RANKL-stimulated osteoclastogenesis in vitro and titanium nanoparticle-induced bone loss in vivo.

Wear particle-stimulated inflammatory bone destruction and the consequent aseptic loosening remain the primary causes of artificial prosthesis failure and revision. Previous studies have demonstrated that curcumin has a protective effect on bone disorders and inflammatory diseases and can ameliorate polymethylmethacrylate-induced osteolysis in vivo. However, the effect on immunomodulation and the definitive mechanism by which curcumin reduces the receptor activators of nuclear factor-kappa B ligand (RANKL)-stimulated osteoclast formation and prevents the activation of osteoclastic signalling pathways are unclear. In this work, the immunomodulation effect and anti-osteoclastogenesis capacities exerted by curcumin on titanium nanoparticle-stimulated macrophage polarization and on RANKL-mediated osteoclast activation and differentiation in osteoclastic precursor cells in vitro were investigated. As expected, curcumin inhibited RANKL-stimulated osteoclast maturation and formation and had an immunomodulatory effect on macrophage polarization in vitro. Furthermore, studies aimed to identify the potential molecular and cellular mechanisms revealed that this protective effect of curcumin on osteoclastogenesis occurred through the amelioration of the activation of Akt/NF-κB/NFATc1 pathways. Additionally, an in vivo mouse calvarial bone destruction model further confirmed that curcumin ameliorated the severity of titanium nanoparticle-stimulated bone loss and destruction. Our results conclusively indicated that curcumin, a major biologic component of Curcuma longa with anti-inflammatory and immunomodulatory properties, may serve as a potential therapeutic agent for osteoclastic diseases.

[Low-grade-infections after spondylodeses-A chameleon? : Current findings and therapeutic strategies]. / Low-Grade-Infektionen in der Wirbelsäulenchirurgie ­ Ein Chamäleon? : Neuste Erkenntnisse und Behandlungsstrategien.

BACKGROUND: Low-grade infections are caused by low-virulence pathogens. The course of these infections is often mild, which is why they are often delayed or not recognized at all. Chronic infections can lead to osteolysis and implant loosening. The rate of complications requiring revision, such as implant loosening or material failure, is known from the literature. However, the rate of low-grade infections in patients requiring spinal revision surgery remains unclear. PURPOSE: The aim of this review is to present the latest treatment strategies for low-grade infections. The diagnostic and therapeutic options are summarized in the form of algorithms. The aim of this work is to raise an awareness of the possibility of a low-grade infection in patients undergoing spinal revision surgery. MATERIALS AND METHODS: Review of the literature RESULTS: The detection of low-grade infections is difficult from both a clinical and a radiological point of view. In the event of unexplained implant loosening or failure despite the lack of local inflammatory signs and often normal laboratory parameters, a low-grade infection must be considered. Multiple microbiological sampling must be requested as part of the revision surgery. A histological examination is recommended for all revision surgery, especially if a low-grade infection is suspected. The diagnosis should ideally be completed by sonicating the implants with subsequent microbiological incubation of the preserved samples. If a low-grade infection is suspected, the biofilm-covered implant should be removed or replaced if instability/no fusion is present. The use of topical antibiotics could be useful, but its effectiveness in treating low-grade infections has not yet been sufficiently demonstrated. DISCUSSION: An algorithm for clinical decision-making in terms of diagnostic and therapeutic options is suggested.

LY411575, a potent γ-secretase inhibitor, suppresses osteoclastogenesis in vitro and LPS-induced calvarial osteolysis in vivo.

A series of osteolytic bone diseases are usually related to excessive bone resorption and osteoclast formation. Thus, agents or drugs which can target osteoclast development and attenuate bone loss are potentially considerable in preventing and treating of bone lytic diseases. In recent years, many studies have reported that Notch signaling has substantial impacts on the process of osteoclast differentiation, maturation, and bone destruction. In the present study, we showed that LY411575, a γ-secretase inhibitor, could potently suppress osteoclast differentiation, osteoclast-specific gene expression, and bone resorption via suppressing Notch/HES1/MAPK (ERK and p38)/Akt-mediated NFATc1 induction in vitro. Consistent with in vitro results, LY411575 exhibited protective effects in lipopolysaccharides-induced calvarial bone destruction in vivo. Collectively, these results indicate that LY411575 may have therapeutic potential in the treatment of osteoclast-mediated osteolytic bone diseases.

Three cases of multicentric carpotarsal osteolysis syndrome: a case series.

BACKGROUND: Multicentric carpotarsal osteolysis syndrome (MCTO) is characterized by progressive destruction and disappearance of the carpal and tarsal bones associated with nephropathy. MCTO is caused by loss-of-function mutations in the MAF bZIP transcription factor B (MAFB) gene. CASE PRESENTATION: This report describes three unrelated patients with MAFB mutations, including two male and one female patient. Osteolytic lesions in the carpal and tarsal bones were detected at 2 years, 12 years, and 14 months of age, respectively. Associated proteinuria was noted at 4 years, 12 years, and 3 months of age, respectively. Kidney biopsy was performed in two of them and revealed focal segmental glomerulosclerosis (FSGS). One patient showed progression to end-stage renal disease, that is by 1 year after the detection of proteinuria. The second patient had persistent proteinuria but maintained normal renal function. In the third patient, who did not undergo a kidney biopsy, the proteinuria disappeared spontaneously. The bony lesions worsened progressively in all three patients. Mutational study of MAFB revealed three different mutations, two novel mutations [c.183C > A (p.Ser61Arg) and c.211C > G (p.Pro71Ala)] and one known mutation [c.212C > T (p.Pro71Leu)]. CONCLUSION: We report three cases with MCTO and two novel MAFB mutations. The renal phenotypes were different among the three patients, whereas progressive worsening of the bony lesions was common in all patients. We also confirmed FSGS to be an early renal pathologic finding in two cases. A diagnosis of MCTO should be considered in patients with progressive bone loss concentrated primarily in the carpal and tarsal bones and kidney involvement, such as proteinuria.

Arthroscopic double bone block augmentation is a salvage procedure for anterior and posterior shoulder instability secondary to glenoid bone loss.

PURPOSE: The aim of this study was to describe a one-step arthroscopic anterior and posterior bone block augmentation technique for bidirectional shoulder instability and to present preliminary results. METHODS: Seven consecutive patients who underwent a concomitant anterior and posterior bone block procedure between 2007 and 2015 were retrospectively reviewed. Clinical scores, return to sport rate, and complications were assessed. Radiological outcome, with CT scan at 6 months and plain radiographs at final follow-up were reviewed. Patient reported functional outcomes were also assessed via phone or email interview. RESULTS: Seven consecutive patients were included in the study with a median age at surgery of 27 years. Median clinical and radiological follow-up was 7 months (4-72 months). Walch-Duplay score and Rowe scores were improved. Four patients were able to return to sport. One patient experienced recurrent dislocation, and one subjective instability/subluxation without confirmed recurrence. CT scan showed union in all cases, with one case of anterior bone block osteolysis and one case of partial posterior bone block osteolysis. Radiographs showed no detectable progression of osteoarthritis using the Samilson and Prieto classification. At final follow-up the median WOSI score was 187 (100-1140). CONCLUSIONS: An all-arthroscopic technique for the treatment of combined anterior and posterior glenoid bone loss as a cause of shoulder instability can provide fair to good clinical outcomes, with a low incidence of intra-operative complications. The rate of failure in our series remains higher than that seen in primary stabilization procedures. As such we consider this largely as a salvage procedure for cases in which alternative treatments have failed or are unlikely to succeed. LEVEL OF EVIDENCE: IV.

Rapidly Progressive Osteolysis and a Large Cystic Lesion that Destroyed the Inner Table of the Iliac Bone Following Cementless Total Hip Arthroplasty: A Case Report.

We report a case of rapidly progressive osteolysis and a very large cystic lesion that destroyed the inner table of the iliac bone following cementless total hip arthroplasty (THA). A 59-year-old female patient developed left hip pain at 11 years after THA. Osteolysis surrounding the acetabular cup was pointed out. She was brought to our hospital by ambulance due to severe left hip pain at 12 years after THA. Computed tomography (CT) showed that a cystic lesion in the pelvic cavity had destroyed the inner table of the iliac bone. Magnetic resonance imaging (MRI) showed a high signal intensity area of the hemorrhagic cystic lesion in the iliac bone in both T1-weighted and T2-weighted images. She underwent a liner and femoral head exchange, and required bone grafting and revision of the cup. The cystic lesion was removed and block-like allograft bone grafts were stuffed into the bone defects. If osteolysis and cystic lesions occur at the same time, not only the bone area around the implant but also a distant area like the inner table of the iliac bone may be destroyed. Additional tests such as CT or MRI may be useful to detect the presence of distant or cystic lesions. Early diagnosis and treatment are important because severe complications may occur in cases where osteolysis and cystic lesions coexist after THA.

DGKζ Downregulation Enhances Osteoclast Differentiation and Bone Resorption Activity Under Inflammatory Conditions.

Bone homeostasis is maintained by a balance between resorption of the bone matrix and its replacement by new bone. Osteoclasts play a crucially important role in bone metabolism. They are responsible for bone resorption under pathophysiological conditions. Differentiation of these cells, which are derived from bone marrow cells, depends on receptor activator of NF-κB ligand (RANKL). RANKL-induced osteoclastogenesis is regulated by the phosphoinositide (PI) signaling pathway, in which diacylglycerol (DG) serves as a second messenger in signal transduction. In this study, we examined the functional implications of DG kinase (DGK), an enzyme family responsible for DG metabolism, for osteoclast differentiation and activity. Of DGKs, DGKζ is most abundantly expressed in osteoclast precursors such as bone marrow-derived monocytes/macrophages. During osteoclast differentiation from precursor cells, DGKζ is downregulated at the protein level. In this regard, we found that DGKζ deletion enhances osteoclast differentiation and bone resorption activity under inflammatory conditions in an animal model of osteolysis. Furthermore, DGKζ deficiency upregulates RANKL expression in response to TNFα stimulation. Collectively, results suggest that DGKζ is silent under normal conditions, but it serves as a negative regulator in osteoclast function under inflammatory conditions. Downregulation of DGKζ might be one factor predisposing a person to osteolytic bone destruction in pathological conditions. J. Cell. Physiol. 232: 617-624, 2017. © 2016 Wiley Periodicals, Inc.

Identical Presentation of Scapular Osteolysis in Two Patients with Thoracic Kaposiform Hemangioendothelioma.

Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor that does not metastasize. We report two unique cases of KHE involving the right hemithorax and the upper ipsilateral extremity. Kasabach-Merrit phenomenon and osteolytic lesions in the scapula were observed in both cases.

Osteoclasts in Periprosthetic Osteolysis: The Charnley Arthroplasty Revisited.

BACKGROUND: Periprosthetic osteolysis by polyethylene wear debris-triggered osteoclasts is viewed as the main pathophysiological pathway in aseptic loosening in total hip arthroplasty. The present aim was to study osteoclast occurrence in osteolytic lesions in early and late revisions of the Charnley low-friction torque arthroplasty (CLFA). METHODS: Biopsies of the soft interface membrane and the adjacent bone were taken from osteolytic lesions during revision of 16 loose CLFA, early (2-6 years) or late (>10 years) after primary surgery. By light microscopy (LM), cell-dense regions with signs of osteoclast-mediated bone resorption were selected for transmission electron microscopy. Three additional patients were studied in LM for osteoclast markers (tartrate-resistant acid phosphatase and Cathepsin K). RESULTS: LM disclosed a low-grade chronic inflammation and birefringent particles in most sections. Multiple conglomerates of tartrate-resistant acid phosphatase positive and Cathepsin K positive mononuclear and multinucleated cells were found deep in the fibrous interface membrane. Transmission electron microscopy showed traces of polyethylene-like particles in 67%-100% of the cells. Osteoclast-like cells exhibiting resorptive activity were few (mean, 0.7%; standard deviation, 0.2%), and multinucleated cells, possibly osteoclast precursor cells, located immediately on the bone were also scarce (mean, 2.7%; standard deviation, 5.3%). Multinucleated (odds ratio, 3.0; 95% confidence interval, 1.7-5.5) and macrophage-like cells (odds ratio, 3.6; 95% confidence interval, 2.2-5.6) were typically located deeper in the inflammatory interface membrane with a pathologic appearance with distension and abundance of phagocytic vacuoles. There were no systematic differences in cell populations between early or late revisions. CONCLUSION: Despite probable ongoing osteoclastogenesis in the osteolytic lesions, there were few sites of osteoclast-mediated bone resorption. These findings attach a contributing biological explanation to the longevity of the CLFA.

The risk assessment of pathological fracture in the proximal femur using a CT-based finite element method.

BACKGROUND: Patients who have lytic bone lesions in their proximal femurs are at risk for pathological fracture. Lesions with high fracture risk are surgically treated using prophylactic osteosynthesis, whereas low-risk lesions are treated conservatively. However, it is difficult to discriminate between high- and low-risk lesions based on clinical and radiographic findings. The computed tomography (CT)-based finite element (FE) models are useful for predicting the fracture load on proximal femoral lytic lesions. MATERIALS AND METHODS: FE models were constructed from the quantitative CT scans of the femurs using software that created individual bone shapes and density distributions. Three independent observers measured the lesion size, Mirels' score, and thickness of the proximal femur along the horizontal plane. The predictive risk values of the proximal femur measured using the CT-based FE analysis were statistically compared. RESULTS: The patients were divided into two groups (high and low risk). The mean fracture load was significantly higher in the high-risk group than in the low-risk group (5395 ± 525 N, 2622 ± 364 N, respectively, p = 0.0003). No significant differences in age, body weight, lesion size or Mirels' score were observed between groups. However, the thickness of the medial cortex in the high-risk group according to the FE analysis was significantly thinner than that in the low-risk group. Furthermore, the medial cortex thickness was positively correlated with the predicted fracture load. An optimal cut-off value of 3.67 mm for the thickness of the inner cortex resulted in 100% sensitivity and 75.1% specificity values for classifying the patients based on their fracture risk. CONCLUSIONS: Our findings indicate that the FE method is useful for the prediction of the pathological fracture. This method shows a versatile potential for the prediction of pathological fracture and might aid in judging the optimal treatment to prevent fracture.

Wear products of total hip arthroplasty: The case of polyethylene.

Among the bearing surfaces involved in a total hip arthroplasty, ultra-high molecular weight polyethylene (UHMWPE) is the weak link. It is submitted to the friction of a harder bearing, producing wear particles, which, in turn, initiate an inflammatory reaction ultimately leading to osteolysis. This kind of bone deterioration sometimes turns out to an aggressive granuloma and may provoke implant loosening. Wear resistance of UHMWPE depends on its molecular weight and crystallinity. Some steps of the manufacturing process were improved to optimize its tribological properties and to slow down degradation resulting from mechanical (abrasion) and chemical (oxidation) phenomena. Its preparation and conservation must be performed in an inert atmosphere, i.e. without ambient oxygen. Its resistance to abrasion depends on its cross-linking degree. Its cross-linking rate was observed to increase proportionally to the irradiation doses, improving its wear resistance. However, its mechanical properties are impaired and moreover, it becomes oxidation sensitive. It is therefore necessary to submit it to a thermal treatment to eliminate free radicals that were produced during irradiation. More recently impregnation by vitamin E, a powerful anti-oxidant product, was proposed to preserve the polymer from in vivo oxidation while maintaining its mechanical properties. We raised the hypothesis that last-generation UHMWPE could offer the same wear resistance as the most performing bearings (ceramic-on-ceramic). Recent clinical results confirm the tribological performance of highly crosslinked UHMWPE in vivo. However, it remains to be seen whether this excellent wear resistance would persist under eccentric load such as edge loading, and if, in the long run, this kind of bearing proves capable of reducing the risk of osteolysis in young and active patients.