-
Canadian Journal of Surgery. Journal... 2024Large-diameter head (LDH) total hip arthroplasty (THA) with a monobloc acetabular component improves hip stability. However, obtaining initial press-fit stability is...
Total hip arthroplasty with monobloc press-fit acetabular components and large-diameter bearings for atypical acetabula is safe: a consecutive case series of 125 hips with mean follow-up of 9 years.
BACKGROUND
Large-diameter head (LDH) total hip arthroplasty (THA) with a monobloc acetabular component improves hip stability. However, obtaining initial press-fit stability is quite challenging in atypical acetabula. The purpose of this study was to assess primary and secondary fixation of monobloc cups in atypical acetabula.
METHODS
In this consecutive case series, the local arthroplasty database was used to retrospectively identify patients with secondary osteoarthritis who underwent primary hip replacement with press-fit only LDH monobloc acetabular components between 2005 and 2018 and who had a minimum of 2 years of follow-up. Radiographic evaluation was performed at last follow-up, and patient-reported outcome measures (PROMs) were assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Forgotten Joint Score (FJS), and the Patient's Joint Perception (PJP) question.
RESULTS
One hundred and six LDH THAs and 19 hip resurfacings were included in the study. Preoperative diagnoses included hip dysplasia (36.8%), Legg-Calve-Perthes disease (32.0%), osteoarthritis with acetabular deficiency (17.6%), periacetabular osteotomy (8.0%), arthrodesis (4.0%), and osteopetrosis (1.6%). After a mean follow-up of 9.2 years, no aseptic loosening of the acetabular component was recorded nor observed on radiologic review. There were 13 (10.4%) revisions unrelated to the acetabular component fixation. The mean WOMAC and FJS scores were 9.2 and 80.9, respectively. In response to the PJP question, 49.4% of the patients perceived their hip as natural, 19.1% as an artificial joint with no restriction, 31.5% as an artificial joint with restriction, and none as a non-functional joint.
CONCLUSION
Primary press-fit fixation of monobloc acetabular components with LDH implanted in atypical acetabula led to secondary fixation in all cases with low revision and complication rates and great functional outcomes. With careful surgical technique and experience, systematic use of supplemental screw fixation is not essential in THA with atypical acetabula.
Topics: Humans; Arthroplasty, Replacement, Hip; Acetabulum; Follow-Up Studies; Retrospective Studies; Reoperation; Osteoarthritis; Hip Prosthesis; Treatment Outcome
PubMed: 38320777
DOI: 10.1503/cjs.014022 -
Bone Research Jun 2024DNAX-associated protein 12 kD size (DAP12) is a dominant immunoreceptor tyrosine-based activation motif (ITAM)-signaling adaptor that activates costimulatory signals...
DNAX-associated protein 12 kD size (DAP12) is a dominant immunoreceptor tyrosine-based activation motif (ITAM)-signaling adaptor that activates costimulatory signals essential for osteoclastogenesis. Although several DAP12-associated receptors (DARs) have been identified in osteoclasts, including triggering receptor expressed on myeloid cells 2 (TREM-2), C-type lectin member 5 A (CLEC5A), and sialic acid-binding Ig-like lectin (Siglec)-15, their precise role in the development of osteoclasts and bone remodeling remain poorly understood. In this study, mice deficient in Trem-2, Clec5a, Siglec-15 were generated. In addition, mice double deficient in these DAR genes and FcεRI gamma chain (FcR)γ, an alternative ITAM adaptor to DAP12, were generated. Bone mass analysis was conducted on all mice. Notably, Siglec-15 deficient mice and Siglec-15/FcRγ double deficient mice exhibited mild and severe osteopetrosis respectively. In contrast, other DAR deficient mice showed normal bone phenotype. Likewise, osteoclasts from Siglec-15 deficient mice failed to form an actin ring, suggesting that Siglec-15 promotes bone resorption principally by modulating the cytoskeletal organization of osteoclasts. Furthermore, biochemical analysis revealed that Sigelc-15 activates macrophage colony-stimulating factor (M-CSF)-induced Ras-associated protein-1 (RAP1)/Ras-related C3 botulinum toxin substrate 1 (Rac1) pathway through formation of a complex with p130CAS and CrkII, leading to cytoskeletal remodeling of osteoclasts. Our data provide genetic and biochemical evidence that Siglec-15 facilitates M-CSF-induced cytoskeletal remodeling of the osteoclasts.
Topics: Animals; Osteoclasts; Signal Transduction; Macrophage Colony-Stimulating Factor; rap1 GTP-Binding Proteins; Mice; Cytoskeleton; Mice, Knockout; Mice, Inbred C57BL; Membrane Proteins; rac GTP-Binding Proteins; Membrane Glycoproteins; Receptors, Immunologic; Immunoglobulins
PubMed: 38849345
DOI: 10.1038/s41413-024-00340-w -
Pediatric Transplantation May 2024Osteopetrosis is a group of geneticall heterogeneous disorders resulting from impaired osteoclast function and bone resorption. The identification of specific genetic...
BACKGROUND
Osteopetrosis is a group of geneticall heterogeneous disorders resulting from impaired osteoclast function and bone resorption. The identification of specific genetic mutations can yield important prognostic and therapeutic implications. Herein, we present the diagnosis and successful application of hematopoietic stem cell transplantation (HSCT) in a patient with osteopetrosis caused by carbonic anhydrase II deficiency (Intermediate osteopetrosis).
CASE PRESENTATION
Herein, we describe a 2.5-year-old male patient born to consanguineous parents who presented at 8-month-old with hydrocephaly, brain shunt, and developmental delay. Later at 9 months old, he was found to have eye disorder such as nystagmus, fracture of the elbow, abnormal skeletal survey, normal cell blood count (CBC), and severe hypocellularity in the bone marrow. Further evaluation showed renal tubular acidosis type 2. Whole-exome sequencing revealed a pathogenic homozygous variant in intron 2 of the carbonic anhydrase 2 gene (CA2) gene (c.232 + 1 G>T). The diagnosis of intermediate autosomal recessive osteopetrosis was established, and allogenic HSCT from his mother, a full-matched related donor (MRD), was planned. The conditioning regimen included Busulfan, Fludarabine, and Rabbit anti-thymocyte globulin. Cyclosporine and Mycophenolate Mofetil were used for graft-versus-host-disease prophylaxis. He Engrafted on day +13, and 95% chimerism was achieved. He is currently doing well without immunosuppressive therapy, now 12 months post HSCT, with normal calcium level and improving visual quality and FISH analysis revealed complete donor chimerism.
DISCUSSION
HSCT could be a promising curative treatment for intermediate osteopetrosis and can provide long-term survival. Ongoing challenges in various aspects of HSCT remain to be addressed.
Topics: Humans; Male; Osteopetrosis; Hematopoietic Stem Cell Transplantation; Child, Preschool; Iran; Carbonic Anhydrase II; Acidosis, Renal Tubular; Transplantation, Homologous; Carbonic Anhydrases; Urea Cycle Disorders, Inborn
PubMed: 38655726
DOI: 10.1111/petr.14689 -
Access Microbiology 2023() is a Gram-positive coccus of the family . It can be found in a variety of vegetables and dairy products. is an opportunistic pathogen with intrinsic resistance to...
() is a Gram-positive coccus of the family . It can be found in a variety of vegetables and dairy products. is an opportunistic pathogen with intrinsic resistance to vancomycin and teicoplanin. In this case report, we discuss a rare case of -associated bacteraemia in a patient with osteopetrosis. A 4-year-old girl was admitted to the paediatric emergency department with acute fever without other signs. Blood culture revealed an infection with . Using the streptococcus antibiogram, the isolate was resistant to vancomycin, teicoplanin, rifampicin and sulfamethoxazole-trimethoprim but sensitive to β-lactams, gentamicin, streptomycin, azithromycin, clarithromycin, lincomycin, clindamycin and erythromycin. The patient was treated with intravenous ceftriaxone and gentamicin, and subsequently with oral amoxicillin. After a favourable course, she was discharged from the hospital on the 10th day. The modes of transmission and physiopathology of remain unknown. Factors associated with this infection include compromised immunity, previous antibiotic therapy especially with vancomycin, and application of a central venous catheter. In our patient, the risk factors for infection were pancytopenia and multiple transfusions used to treat bone marrow failure. The source of the bacteraemia could have been the cutaneous route, but it could also have been digestive due to the reservoir of the bacteria. is known as an opportunistic bacterium. Further studies on its pathogenesis and other risk factors are needed to understand the true prevalence of this potentially fatal bacterium in compromised individuals, such as the case of our patient.
PubMed: 37970073
DOI: 10.1099/acmi.0.000439 -
JBMR Plus Aug 2023Osteosclerotic metaphyseal dysplasia (OSMD) is a very rare autosomal-recessive disease caused by mutations in the leucine-rich repeat kinase 1 (LRRK1) gene. It is a...
Osteosclerotic metaphyseal dysplasia (OSMD) is a very rare autosomal-recessive disease caused by mutations in the leucine-rich repeat kinase 1 (LRRK1) gene. It is a sclerosing skeletal dysplasia characterized by osteosclerosis of the long bones, predominantly at the metaphyses and vertebrae. Phenotypic features can be short stature, pathological fractures, delayed development, and hypotonia, but they are not uniformly present, and relatively few cases are known from the literature. A 40-year-old man was seen at our bone center because of nonspontaneous multiple peripheral low-energy trauma fractures since puberty. He had no other complaints and his family history was negative. Except for a relatively short stature (167 cm; -1.5 SD), there were no abnormalities on examination, including laboratory tests. Initially, a suspicion was raised of osteogenesis imperfecta, but bone mineral density was high and X-rays of the whole skeleton showed osteosclerosis of the metaphyses of long bones and vertebrae. Whole-exome sequencing showed a homozygous, likely pathogenic, variant (American College of Medical Genetics and Genomics criteria class 4) in the LRRK1 gene, fitting the diagnosis of OSMD. In conclusion, we described a 40-year-old patient with osteosclerotic metaphyseal dysplasia caused by a homozygous variant in the LRRK1 gene, resulting in multiple fractures of the long bones without other features of the disease, adding to the phenotypic variation of OSMD. © 2023 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PubMed: 37614307
DOI: 10.1002/jbm4.10755 -
Orthopedic Reviews 2024Osteopetrosis, a rare condition arising from osteoclast dysfunction, is characterised by increased bony density and obliteration of the intramedullary canal. While total...
Osteopetrosis, a rare condition arising from osteoclast dysfunction, is characterised by increased bony density and obliteration of the intramedullary canal. While total knee arthroplasty (TKA) is preferred for osteoarthritic patients with osteopetrosis, inherent disease characteristics pose surgical challenges. This article presents a patient with osteopetrosis treated with robotic arm-assisted TKA (RA-TKA). This approach provided precise bone resection, obviates the need for intramedullary guides, minimizes saw disposal, and reduces surgical duration, with satisfactory short-term outcomes. RA-TKA may be an effective treatment for osteoarthritis in patients with osteopetrosis.
PubMed: 38435436
DOI: 10.52965/001c.94238 -
Journal of Pediatric Endocrinology &... Jul 2023Osteopetrorickets is a rare complication of autosomal recessive ("malignant") osteopetrosis. Its prompt diagnosis is essential, because early suspicion of infantile...
Osteopetrorickets is a rare complication of autosomal recessive ("malignant") osteopetrosis. Its prompt diagnosis is essential, because early suspicion of infantile osteopetrosis enables treatment with human stem cell transplantation, depending on the gene involved. It is important to identify not only the characteristic radiological changes of rickets, but also the coexistence of increased bone density, so as not to miss this very rare entity. Herein, a brief case report is presented.
Topics: Humans; Osteopetrosis; Rickets; Hypophosphatemia; Radiography; Hematopoietic Stem Cell Transplantation
PubMed: 37141118
DOI: 10.1515/jpem-2023-0001 -
Journal of Leukocyte Biology Mar 2024Macrophage and osteoclast proliferation, differentiation and survival are regulated by colony-stimulating factor-1 receptor (CSF1R) signaling. Osteopetrosis associated...
Relative contributions of osteal macrophages and osteoclasts to postnatal bone development in CSF1R-deficient rats and phenotype rescue following wild-type bone marrow cell transfer.
Macrophage and osteoclast proliferation, differentiation and survival are regulated by colony-stimulating factor-1 receptor (CSF1R) signaling. Osteopetrosis associated with Csf1 and Csf1r mutations has been attributed to the loss of osteoclasts and deficiency in bone resorption. Here we demonstrate that homozygous Csf1r mutation in rat leads to delayed postnatal skeletal ossification associated with substantial loss of osteal macrophages (osteomacs) in addition to osteoclasts. Osteosclerosis and site-specific skeletal abnormalities were reversed by intraperitoneal transfer of wild-type bone marrow cells (BMT) at weaning. Following BMT, IBA1+ macrophages were detected before TRAP+ osteoclasts at sites of ossification restoration. These observations extend evidence that osteomacs independently contribute to bone anabolism and are required for normal postnatal bone growth and morphogenesis.
PubMed: 38526212
DOI: 10.1093/jleuko/qiae077 -
The Journal of Clinical Endocrinology... Jun 2024Autosomal dominant osteopetrosis (ADO) is a rare genetic disorder resulting from impaired osteoclastic bone resorption. Clinical manifestations frequently include...
CONTEXT
Autosomal dominant osteopetrosis (ADO) is a rare genetic disorder resulting from impaired osteoclastic bone resorption. Clinical manifestations frequently include fractures, osteonecrosis (particularly of the jaw or maxilla), osteomyelitis, blindness, and/or bone marrow failure. ADO usually results from heterozygous missense variants in the Chloride Channel 7 gene (CLCN7) that cause disease by a dominant negative mechanism. Variants in the T-cell immune regulator 1 gene (TCIRG1) are commonly identified in autosomal recessive osteopetrosis but have only been reported in 1 patient with ADO.
CASE DESCRIPTION
Here, we report 3 family members with a single heterozygous missense variant (p.Gly579Arg) in TCIRG1 who have a phenotype consistent with ADO. Three of 5 protein prediction programs suggest this variant likely inhibits the function of TCIRG1.
CONCLUSION
This is the first description of adult presentation of ADO caused by a TCIRG1 variant. Similar to families with ADO from CLCN7 mutations, this variant in TCIRG1 results in marked phenotype variability, with 2 subjects having severe disease and the third having very mild disease. This family report implicates TCIRG1 missense mutations as a cause of ADO and demonstrates that the marked phenotypic variability in ADO may extend to disease caused by TCIRG1 missense mutations.
Topics: Humans; Osteopetrosis; Mutation, Missense; Male; Female; Pedigree; Adult; Vacuolar Proton-Translocating ATPases; Phenotype; Middle Aged; Genes, Dominant
PubMed: 38261998
DOI: 10.1210/clinem/dgae040 -
Stem Cell Research Apr 2024Infantile Malignant Osteopetrosis (IMO) is a rare, severe autosomal recessive form of osteopetrosis. Here, the peripheral blood mononuclear cells (PBMCs) extracted from...
Infantile Malignant Osteopetrosis (IMO) is a rare, severe autosomal recessive form of osteopetrosis. Here, the peripheral blood mononuclear cells (PBMCs) extracted from a patient with IMO carrying a compound heterozygous mutation in T cell immune regulator 1, ATPase H + transporting V0 subunit a3 (TCIRG1) gene (c.242delC; c.1114C > T) were successfully reprogrammed using Sendai virus encoding the four Yamanaka factors. The generated hiPSCs, IMO-hiPSCs, displayed typical embryonic stem cell-like morphology and were verified by expression of pluripotency markers such as OCT4, SOX2, NANOG, TRA-1-60 and SSEA4, as well as in vivo and in vitro differentiation into derivatives of three germ layers.
Topics: Humans; Induced Pluripotent Stem Cells; Osteopetrosis; Leukocytes, Mononuclear; Mutation; Genes, Homeobox; Cell Differentiation; Vacuolar Proton-Translocating ATPases
PubMed: 38335662
DOI: 10.1016/j.scr.2024.103330