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2.
J Bone Miner Metab ; 39(4): 700-711, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33821304

ABSTRACT

INTRODUCTION: Atypical femoral fractures (AFFs) have been correlated with long-term use of bisphosphonates (BPs), glucocorticoids (GCs), and femoral geometry. We investigated the incidence and characteristics of subtrochanteric (ST) and diaphyseal (DP) AFFs in all institutes in a super-aging prefectural area. MATERIALS AND METHODS: We performed a blinded analysis of radiographic data in 87 patients with 98 AFFs in all institutes in Yamagata prefectural area from 2009 to 2014. Among the 98 AFFs, 57 AFFs comprising 11 ST fractures in 9 patients and 46 DP fractures in 41 patients with adequate medical records and X-rays were surveyed for time to bone healing and geometry. RESULTS: Of the 87 patients, 67 received BPs/denosumab (77%) and 10 received GCs (11%). Surgery was performed in 94 AFFs. Among 4 AFFs with conservative therapy, 3 required additional surgery. In univariate regression analyses for ST group versus DP group, male-to-female ratio was 2/7 versus 1/40, mean age at fracture was 58.2 (37-75) versus 78 (60-89) years, rheumatic diseases affected 55.5% (5/9) versus 4.9% (2/41), femoral lateral bowing angle was 1.7 (0-6) versus 11.8 (0.8-24)°, GC usage was 67% (6/9) versus 4.9% (2/41), and bone healing time was 12.1 (6-20) versus 8.1 (3-38) months (p < 0.05). In multivariate analyses, higher male-to-female ratio, younger age, greater proportion affected by rheumatic diseases, and higher GC usage remained significant (p < 0.05). CONCLUSIONS: The incidence of AFFs in our prefectural area was 1.43 cases/100,000 persons/year. This study suggests that the onset of ST AFFs have greater correlation with the worse bone quality, vice versa, the onset of DP AFFs correlated with the bone geometry. The developmental mechanisms of AFFs may differ significantly between ST and DP fractures.


Subject(s)
Aging/pathology , Diaphyses/pathology , Femoral Fractures/epidemiology , Hip Fractures/epidemiology , Aged , Aged, 80 and over , Female , Femoral Fractures/diagnostic imaging , Hip Fractures/diagnostic imaging , Humans , Incidence , Japan/epidemiology , Male , Middle Aged , Multivariate Analysis , Regression Analysis , Risk Factors
3.
Clin Orthop Relat Res ; (430): 195-201, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15662324

ABSTRACT

In the current study, we investigated whether the systemic administration of alendronate, a third-generation bisphosphonate, suppressed the loosening of screws at the bone-screw interface. We systemically administered alendronate to rats fitted with external fixators. External fixators with two half pins were applied to the right femurs of rats, and alendronate was administrated once a week during a 5-week postoperative period. Radiographic, histologic, and immunohistochemical findings subsequently were analyzed. Treatment with alendronate reduced the width of the fibrous loosening membrane and the number of osteoclasts at the bone-screw interface. These findings indicate that systemic treatment with alendronate exerts an inhibitory effect on local bone resorption at the bone-screw interface.


Subject(s)
Alendronate/pharmacology , Bone Resorption/drug therapy , Bone Screws , External Fixators , Acid Phosphatase/drug effects , Acid Phosphatase/metabolism , Animals , Bone Resorption/metabolism , Cathepsin K , Cathepsins/drug effects , Cathepsins/metabolism , Disease Models, Animal , Femur , Isoenzymes/drug effects , Isoenzymes/metabolism , Male , Prosthesis Failure , Rats , Rats, Wistar , Tartrate-Resistant Acid Phosphatase
4.
J Bone Miner Metab ; 22(4): 346-51, 2004.
Article in English | MEDLINE | ID: mdl-15221493

ABSTRACT

Osteoclastogenesis is a key event of the cellular reaction in prosthetic loosening. Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) were used to study the localization and expression of receptor activator of nuclear factor kappa B ligand (RANKL), a potent factor for osteoclastogenesis in the membranous tissue formed around loosened prosthetic joint implants. RANKL was identified in a wide variety of cells appearing in this membranous tissue. At least three types of RANKL-positive cells were identified, including prolyl 4-hydroxylase (PH)-positive fibroblast lineage cells, CD68 cells, and tartrate-resistant acid phosphatase (TRAP)-positive mononuclear and multi-nucleated macrophage lineage cells. Tumor necrosis factor (TNF)-alpha-converting enzyme (TACE) was colocalized with RANKL in these cells, suggesting the in-situ release of this factor. RT-PCR confirmed the actual expression of the RANKL and TACE genes in the tissues around the loosened implant. These observational findings indicate the possible synthesis of RANKL by fibroblast and macrophage lineage cells, and suggest the in-situ involvement of RANKL in both osteoclastogenesis and osteoclastic bone resorptive events occurring in prosthetic joint loosening.


Subject(s)
Carrier Proteins/genetics , Carrier Proteins/metabolism , Joint Prosthesis/adverse effects , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Osteolysis/metabolism , ADAM Proteins , ADAM17 Protein , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Male , Metalloendopeptidases/genetics , Middle Aged , Osteolysis/pathology , RANK Ligand , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor Activator of Nuclear Factor-kappa B , Reverse Transcriptase Polymerase Chain Reaction
5.
Cancer Lett ; 199(2): 147-55, 2003 Sep 25.
Article in English | MEDLINE | ID: mdl-12969787

ABSTRACT

We investigated the effects of treatment with anti-parathyroid hormone-related protein (1-34) monoclonal murine antibody (anti-PTHrP MoAb) on apoptosis and the differentiation of chondrosarcoma HTB-94 cells. Treatment with anti-PTHrP MoAb accelerated apoptosis of HTB-94 cells in a dose-dependent manner, and anti-PTHrP MoAb also promoted the chondrogenic differentiation of HTB-94 cells. The induction of apoptosis by anti-PTHrP MoAb via imbalance of Bcl-2/Bax ratio and activation of caspase-3 may provide a mechanistic explanation for its potential antitumor effects. Our results suggest the possibility that anti-PTHrP MoAb may be beneficial as a new treatment for chondrosarcoma.


Subject(s)
Antibodies, Monoclonal/pharmacology , Apoptosis/drug effects , Bone Neoplasms/pathology , Cell Differentiation/drug effects , Chondrosarcoma/pathology , Parathyroid Hormone-Related Protein/immunology , Bone Neoplasms/immunology , Bone Neoplasms/metabolism , Caspase 3 , Caspases/metabolism , Cell Division/drug effects , Chondrosarcoma/immunology , Chondrosarcoma/metabolism , Collagen Type II/genetics , Collagen Type II/metabolism , Collagen Type X/genetics , Collagen Type X/metabolism , DNA Primers/chemistry , Humans , Immunoenzyme Techniques , Peptide Fragments/immunology , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , bcl-2-Associated X Protein
6.
J Bone Miner Res ; 17(5): 898-906, 2002 May.
Article in English | MEDLINE | ID: mdl-12009021

ABSTRACT

The bone morphogenetic protein (BMP) family consists of a large number of members and has diverse biological activities during development. Various tissues express pleural BMP family members, which seem to cooperatively regulate developmental events. Here, multiple BMP signals were inactivated in chondrocytes to clarify the function of BMPs during skeletogenesis. To obtain tissue-specific inactivation, Noggin gene (Nog) was overexpressed in cartilage under the control of a2(XI) collagen gene (Collla2) promoter/enhancer sequences. The resultant transgenic mice lacked most of their cartilaginous components, suggesting that cartilage does not develop without BMP signals. These effects seem to be mediated through down-regulation of Sox9 expression. Conversely, specific BMP signals were activated in the skeleton by targeted expression of Bmp4 in cartilage and the resultant phenotype was compared with that of transgenic mice expressing growth and differentiation factor-5 (GDF-5), another BMP family member. Overactivity of Bmp4 in the skeleton caused an increase of cartilage production and enhanced chondrocyte differentiation, as GDF5 expression did, but it did not disturb joint formation as GDF5 did. During skeletogenesis, unique roles of each BMP may reside in the regulation of joint development. Together with the common effect on the cartilage overproduction by Bmp4 and GDF5 overactivation, loss of cartilage by inactivation of multiple BMPs in Noggin transgenic mice indicates that signals for cartilage production are reinforced by multiple BMPs exclusively. These conclusions may account for the reason why multiple BMPs are coexpressed in cartilage.


Subject(s)
Bone Development/physiology , Bone Morphogenetic Proteins/physiology , Cartilage/growth & development , Joints/growth & development , Animals , Bone Morphogenetic Protein 4 , Bone Morphogenetic Proteins/genetics , Carrier Proteins , Cell Differentiation , Chondrocytes/cytology , Chondrocytes/physiology , Collagen Type XI/genetics , Collagen Type XI/physiology , Gene Expression , Growth Differentiation Factor 5 , In Situ Hybridization , Mice , Mice, Transgenic , Proteins/genetics , Proteins/physiology , Signal Transduction
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