責任者
伊東 伸朗（Nobuaki Ito）
メンバー
MD, Ph.D: 伊東 伸朗（Nobuaki Ito)（難治性骨疾患治療開発講座）
MD, Ph.D: 加藤創生（Hajime Kato） （留学中： Yale School of Medicine）
大学院生:日髙尚子（Naoko Hidaka）
大学院生:星野良朋（Yoshitomo Hoshino）
大学院生:木村聡一郎（Soichiro Kimura）
大学院生:洲之内尭（Takashi Sunouchi）
大学院生:入江航生（Koki Irie）
大学院生:渡部創（So Watanabe）（老年病科）
実験助手:尾崎 知子（Tomoko Ozaki)
研究室のより詳細な紹介は下記HPをご参照ください
研究内容
当研究室は臨床では内分泌疾患全般を診療していますが、特に骨粗鬆症や副甲状腺疾患、くる病・骨軟化症、悪性腫瘍に伴う高カルシウム血症や先天性骨代謝疾患などの骨ミネラル代謝疾患を専門的に診療しています。
① 骨粗鬆症
骨粗鬆症に関しては、骨折のリスクや骨折後に寝たきりとなるなどといった事後の影響を考えると、心筋梗塞や脳梗塞などの発症リスクとなる生活習慣病(高血圧や脂質異常症、糖尿病など)と同様に予防医学の観点で重要な疾患であると認知されてきています。骨粗鬆症は従来治療法が限られていましたが、近年様々な機序の製剤が開発されています。今後も新規の治療薬が保険適応となる予定であり、より患者さんの病態に応じたテーラーメード医療が可能な分野となってきています。
② 続発性骨粗鬆症と骨粗鬆症類縁疾患
内分泌内科では原発性副甲状腺機能亢進症やクッシング症候群といった続発性に骨粗鬆症を起こす様々な疾患や、くる病・骨軟化症、多発性骨髄腫などの骨粗鬆症類縁疾患の鑑 別診断を徹底することで、骨粗鬆症の原因となる重要な疾患を見逃さないようにしています。また骨粗鬆症のプライマリケアを担当することの多い整形外科医や一般内科医、および骨粗鬆症患者さんを対象として、比較的頻度の高い原発性副甲状腺機能亢進症、ビタミンD欠乏症性骨軟化症や、以下に記載しているFGF23関連低リン血症性くる病・骨軟化症や低ホスファターゼ症をといった続発性骨粗鬆症、骨粗鬆症類縁疾患が見逃されてしまう症例が減るように全国的な疾患啓発活動に注力しています。
③ FGF23 関連低リン血症性くる病・骨軟化症
臨床研究、基礎研究では、カルシウム感知受容体(CaSR)の遺伝子異常による新たな病態の解明を行ってきました。近年では腫瘍性骨軟化症(TIO)、X染色体連鎖性低リン血症性くる病(XLH)といった低リン血症性くる病・骨軟化症の原因となる血中のリン濃度調節ホルモン:FGF23をクローニングすると共に、その測定法を開発いたしました。またFGF23の測定が、骨ミネラル代謝異常症の診断に有用であることを示しました。またFGF23関連低リン血症性くる病・骨軟化症に対する抗FGF23抗体医薬が国内でも承認され、本症の治療法を画期的に飛躍させることが出来ました。
低リン血症性くる病・骨軟化症の鑑別診断においては、現在FGF23測定が保険適用となっていますが診断目的に原則1回のみの測定に限られています。医療機関等からの要請に応じて研究目的でのFGF23測定や遺伝性低リン血症性くる病・骨軟化症の遺伝子診断（FGF23、PHEX、DMP1、ENPP1、FAM20C、PTHR1、FGFR1-4、NF1、SLC34A1、SLC34A3遺伝子、SLC9A3R1、CLCN5、OCRL、CYP2R1、HNRNPC、CYP3A4など）を行っています(下記グループのHPをご参照ください)。
FGF23産生腫瘍が原因となる腫瘍性骨軟化症では、腫瘍の切除が根治治療となりますが、原因腫瘍のサイズが小さく局在診断が困難である事が多いため、当グループでは既に保険適応となっているソマトスタチン受容体シンチグラフィとともに、機能的局在診断の補助となる全身でのFGF23静脈サンプリングを特定臨床研究として施行しています。該当するご症例がおられましたら是非ご紹介ください。
上記臨床研究から得られる知見をもとに、基礎研究として2019年にはそれまでに明らかとされていなかった生体内での血中リン濃度感知機構（PiSR）において、FGFRが中心的な役割を担うことを徳島大学との共同研究で明らかとしました。今後はこのFGFRを介した生体のリン感知メカニズムのより詳細なメカニズムの解明や、FGFRのシグナル異常が関与する病態などについて更に検討を進めていきたいと考えています。
④ 低ホスファターゼ症
低リン血性くる病・骨軟化症と類似した疾患で、アルカリホスファターゼという酵素の異常により骨の局所でのリン濃度の低下が起こることでくる病・骨軟化症と同様の病態を呈する低ホスファターゼ症(HPP)という疾患があります。新生児や乳児期に発症する症例は非常に重篤で、肋骨の形成不全などから出生後に呼吸困難となり生命の危機に瀕する病型です。一方で、小児期や成人期まで明らかな症状を呈さずに、それ以降、偽骨折(強い運動負荷を伴わずに生じるヒビのような骨折)や通常の骨折を繰り返す比較的症状が軽度なHPPも存在しています。そのほとんどの症例が骨粗鬆症として、HPPの場合にはむしろ骨折リスクを増加させてしまうビスホスフォネートなどの骨吸収抑制薬での加療が行われていると考えられます。2015年に本症に対する酵素補充療法が保険適用となったこともあり、骨折を頻回に繰り返す成人例などから本症を、低ALP血症を手掛かりとして正しく診断することの重要性を啓発しております。HPPに関してもALPL遺伝子変異の遺伝子診断を承っておりますので、疑わしい症例がおられましたらご紹介頂けますと幸いです。
⑤ その他の骨代謝疾患
このほかにも骨形成不全症や軟骨無形成症、大理石骨病といった様々な遺伝性の骨代謝疾患の小児科からの移行や骨パジェット病、後縦靭帯骨化症などの病態解明のためのご紹介を受け入れております。また先天性もしくは後天性で原因が明らかでない骨代謝疾患などの原因を次世代シークエンサーなどの機器を利用して解明する検討も行っておりますので、診断に難渋する症例がございましたらご連絡頂けますと幸いです。
お知らせ
● 東京大学医学部附属病院で腫瘍性骨軟化症の原因腫瘍切除術を施行された患者さん、ならびに東京大学医学部附属病院整形外科・脊椎外科で研究にご参加されている患者さんへ
● 悪性腫瘍の骨転移に対するランマーク投与の安全性についての検討
連絡先
当研究室に興味のある方、FGF23 関連の臨床情報についてのお問い合わせ、FGF23 測定 依頼、研究の御相談、また低リン血症性くる病・骨軟化症患者さんからのお問い合わせ、 御相談を受け付けています。お気軽にご連絡ください。
ともに Ito N, et al. Clin Rev Bone Miner Metab 2014(業績 6)より
業績
Tanaka Y, Soen S, Hirata S, Okada Y, Fujiwara S, Tanaka I, Kitajima Y, Kubota T, Ebina K, Takashi Y, Inoue R, Yamauchi M, Okubo N, Ueno M, Ohata Y, Ito N, Ozono K, Nakayama H, Terauchi M, Tanaka S, Fukumoto S. The 2023 Guidelines for the management and treatment of glucocorticoid-induced osteoporosis. J Bone Miner Metab. 2024 Mar 28. doi: 10.1007/s00774-024-01502-w. Epub ahead of print. PMID: 38538869.
Tanaka H, Tamura M, Muto M, Kinoshita Y, Ito N, Oka A, Kitanaka S. A novel pathogenic variant in fibroblast growth factor 23 outside the furin-recognizing RXXR motif in an autosomal dominant hypophosphatemic rickets patient. Horm Res Paediatr. 2024 Mar 15. doi: 10.1159/000538388. Epub ahead of print. PMID: 38493780.
Ito N, Hidaka N, Kato H. Acquired Forms of Fibroblast Growth Factor 23-Related Hypophosphatemic Osteomalacia. Endocrinol Metab (Seoul). 2024 Mar 11. doi: 10.3803/EnM.2023.1908. Epub ahead of print. PMID: 38467164.
Hidaka N, Inoue K, Kato H, Hoshino Y, Koga M, Kinoshita Y, Takashi Y, Makita N, Fukumoto S, Nangaku M, Ito N. FGF-23, Left Ventricular Hypertrophy, and Mortality in Patients With CKD: A Revisit With Mediation Analysis. JACC Adv. 2024 Jan, 3 (1) .https://doi.org/10.1016/j.jacadv.2023.100747
Okajima K, Kobayashi H, Ito N, Kato H, Ishibashi Y, Zhang L, Tsuda Y, Tanaka S. Extended curettage for tumour-induced osteomalacia in the bone. Jpn J Clin Oncol. 2024 Jan 23:hyad180. doi: 10.1093/jjco/hyad180. Epub ahead of print. PMID: 38266040.
Tsuda Y, Yasunaga Y, Abe M, Hoshi K, Ito N, Kondo K, Okajima K, Zhang L, Kato H, Hidaka N, Tanaka S, Kobayashi H. Surgical and biochemical outcomes of phosphaturic mesenchymal tumors causing tumor-induced osteomalacia in the head and neck region. Oral and Maxillofacial Surgery Cases. 2023; 9 (4):100335. doi.org/10.1016/j.omsc.2023.100335.
Hidaka N, Murata H, Tachikawa K, Osaki K, Sekiyama T, Kinoshita Y, Kato H, Hoshino Y, Kimura S, Sunouchi T, Watanabe S, Nangaku M, Makita N, Michigami T, Ito N. The Effect of Asfotase Alfa on Plasma and Urine Pyrophosphate Levels and Pseudofractures in a Patient With Adult-Onset Hypophosphatasia. JBMR Plus. 2023 Nov 20;7(12):e10842. doi: 10.1002/jbm4.10842. PMID: 38130758; PMCID: PMC10731098.
Ito N, Hidaka N, Kato H. The pathophysiology of hypophosphatemia. Best Pract Res Clin Endocrinol Metab. 2023 Nov 30:101851. doi: 10.1016/j.beem.2023.101851. Epub ahead of print. PMID: 38087658.
Qian C, Ito N, Tsuji K, Sato S, Kikuchi K, Yoshii T, Miyata T, Asou Y. A PAI-1 antagonist ameliorates hypophosphatemia in the Hyp vitamin D-resistant rickets model mouse. FEBS Open Bio. 2023 Dec 5. doi: 10.1002/2211-5463.13745. Epub ahead of print. PMID: 38050660.
Arima T, Sugimoto K, Taniwaki T, Maeda K, Shibata Y, Tateyama M, Karasugi T, Tokunaga T, Sueyoshi T, Hisanaga S, Masuda T, Uehara Y, Yugami M, Matsushita K, Yonemitsu R, Kawakami J, Yoshimura N, Tanimura S, Kato H, Ito N, Inoue K, Bando K, Nakamura T, Miyamoto T. Cartilage tissues regulate systemic aging via ectonucleotide pyrophosphatase/phosphodiesterase 1 in mice. J Biol Chem. 2023 Nov 30:105512. doi: 10.1016/j.jbc.2023.105512. Epub ahead of print. PMID: 38042486.
Arai M, Ochi H, Sunamura S, Ito N, Nangaku M, Takeda S, Sato S. A Novel Long Noncoding RNA in Osteocytes Regulates Bone Formation through the Wnt/β-Catenin Signaling Pathway. Int J Mol Sci. 2023 Sep 4;24(17):13633. doi: 10.3390/ijms241713633. PMID: 37686441.
Kato H, Braddock DT, Ito N. Genetics of Diffuse Idiopathic Skeletal Hyperostosis and Ossification of the Spinal Ligaments. Curr Osteoporos Rep. 2023 Aug 2. doi: 10.1007/s11914-023-00814-6. Epub ahead of print. PMID: 37530996.
Kato H, Kimura S, Taguchi M, Sunouchi T, Hoshino Y, Hidaka N, Edvige Foligno N, Koga M, Manaka K, Tamiya H, Kawakami M, Kage H, Yasunaga Y, Nangaku M, Makita N, Ito N. FGF23-related hypophosphatemia in a patient with small cell lung cancer: a case report and literature review. Endocr J. 2023 Jul 20. doi: 10.1507/endocrj.EJ23-0086. Epub ahead of print. PMID: 37468265.
Hoshino Y, Manaka K, Sato J, Asatsuma Y, Horikoshi H, Takeuchi M, Ito N, Fujita M, Yasunaga M, Matsuda K, Honda A, Maki H, Masamoto Y, Kurokawa M, Nangaku M, Makita N. Recurrent bilateral adrenal infarction with myelodysplastic/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U): a case report. BMC Endocr Disord. 2023 Jun 5;23(1):128. doi: 10.1186/s12902-023-01384-5. PMID: 37277771.
Kobayashi H, Ito N, Nakai Y, Katoh H, Okajima K, Zhang L, Tsuda Y, Tanaka S. Patterns of symptoms and insufficiency fractures in patients with tumour-induced osteomalacia. Bone Joint J. 2023 May 1;105-B(5):568-574. doi: 10.1302/0301-620X.105B5.BJJ-2022-1206.R2. PMID: 37121579.
Kato H, Miyazaki H, Kimura T, Hoshino Y, Hidaka N, Koga M, Nangaku M, Makita N, Ito N. Clinical performance of a new intact FGF23 immunoassay in healthy individuals and patients with chronic hypophosphatemia. Bone Rep. 2023 Feb 2;18:101659. doi: 10.1016/j.bonr.2023.101659. PMID: 36817167; PMCID: PMC9932357.
Ramos P, Larson B, Ashrafzadeh-Kian S, Ito N, Kato H, Bornhorst JA, Algeciras-Schimnich A. Intact Fibroblast Growth Factor 23 (iFGF23) Concentrations in Hypophosphatemic Disorders. Endocr Pract. 2023 Jan 7:S1530-891X(23)00002-2. doi: 10.1016/j.eprac.2023.01.003. Epub ahead of print. PMID: 36627024.
Kato H, Koga M, Kinoshita Y, Hidaka N, Hoshino Y, Takashi Y, Arai M, Kobayashi H, Katsura M, Nakamoto Y, Makise N, Ushiku T, Hoshi K, Nangaku M, Makita N, Fukumoto S, Ito N. Utility of Multimodality Approach Including Systemic FGF23 Venous Sampling in Localizing Phosphaturic Mesenchymal Tumors. J Endocr Soc. 2022 Nov 24;7(2):bvac181. doi: 10.1210/jendso/bvac181. PMID: 36540156; PMCID: PMC9757682.
Kato H, Okawa R, Ogasawara T, Hoshino Y, Hidaka N, Koga M, Kinoshita Y, Kobayashi H, Taniguchi Y, Fukumoto S, Nangaku M, Makita N, Hoshi K, Nakano K, Ito N. Effect of conventional treatment on dental complications and ectopic ossifications among 30 adults with XLH. J Clin Endocrinol Metab. 2022 Dec 16:dgac732. doi: 10.1210/clinem/dgac732. Epub ahead of print. PMID: 36524341.
Hoshino Y, Hidaka N, Kato H, Koga M, Taniguchi Y, Kobayashi H, Nangaku M, Makita N, Ito N. Incidence of ossification of the spinal ligaments in acromegaly patients. Bone Rep. 2022 Oct 17;17:101628. doi: 10.1016/j.bonr.2022.101628. PMID: 36299702; PMCID: PMC9589022.
Ashrafzadeh-Kian SL, Ito N, Srivastava T, Garg U, Kato H, Algeciras-Schimnich A, Bornhorst JA. The Effect of Burosumab on Intact and C-terminal FGF23 Measurements. Clin Endocrinol (Oxf). 2022 Oct 20. doi: 10.1111/cen.14832. Epub ahead of print. PMID: 36263608.
Kato H, Hoshino Y, Hidaka N, Ito N, Makita N, Nangaku M, Inoue K. Machine Learning-Based Prediction of Elevated PTH Levels Among the US General Population. J Clin Endocrinol Metab. 2022 Sep 19:dgac544. doi: 10.1210/clinem/dgac544. Epub ahead of print. PMID: 36125184.
Brandi ML, Jan de Beur S, Briot K, Carpenter T, Cheong HI, Cohen-Solal M, Crowley RK, Eastell R, Imanishi Y, Imel EA, Ing SW, Insogna K, Ito N, Javaid K, Kamenicky P, Keen R, Kubota T, Lachmann RH, Perwad F, Pitukcheewanont P, Portale A, Ralston SH, Tanaka H, Weber TJ, Yoo HW, Sun W, Williams A, Nixon A, Takeuchi Y. Efficacy of Burosumab in Adults with X-linked Hypophosphatemia (XLH): A Post Hoc Subgroup Analysis of a Randomized Double-Blind Placebo-Controlled Phase 3 Study. Calcif Tissue Int. 2022 Aug 4. doi: 10.1007/s00223-022-01006-7. Epub ahead of print. PMID: 35927518.
Hidaka N, Koga M, Kimura S, Hoshino Y, Kato H, Kinoshita Y, Makita N, Nangaku M, Horiguchi K, Furukawa Y, Ohnaka K, Inagaki K, Nakagawa A, Suzuki A, Takeuchi Y, Fukumoto S, Nakatani F, Ito N. Clinical Challenges in Diagnosis, Tumor Localization and Treatment of Tumor-Induced Osteomalacia: Outcome of a Retrospective Surveillance. J Bone Miner Res. 2022 Jun 11. doi: 10.1002/jbmr.4620. Epub ahead of print. PMID: 35690913.
Hofstaetter JG, Atkins GJ, Kato H, Kogawa M, Blouin S, Misof BM, Roschger P, Evdokiou A, Yang D, Solomon LB, Findlay DM, Ito N. A Mild Case of Autosomal Recessive Osteopetrosis Masquerading as the Dominant Form Involving Homozygous Deep Intronic Variations in the CLCN7 Gene. Calcif Tissue Int. 2022 May 26. doi: 10.1007/s00223-022-00988-8. Epub ahead of print. PMID: 35618777.
Kato H, Ansh AJ, Lester ER, Kinoshita Y, Hidaka N, Hoshino Y, Koga M, Taniguchi Y, Uchida T, Yamaguchi H, Niida Y, Nakazato M, Nangaku M, Makita N, Takamura T, Saito T, Braddock DT, Ito N. Identification of ENPP1 haploinsufficiency in patients with diffuse idiopathic skeletal hyperostosis and early-onset osteoporosis. J Bone Miner Res. 2022 Mar 26. doi: 10.1002/jbmr.4550. Epub ahead of print. PMID: 35340077.
Kato H, Hidaka N, Koga M, Kinoshita Y, Makita N, Nangaku M, Ito N. Radiological evaluation of pseudofracture after the administration of asfotase alfa in an adult with benign prenatal hypophosphatasia: A case report. Bone Rep. 2021 Dec 29;16:101163. doi: 10.1016/j.bonr.2021.101163. PMID: 35024386; PMCID: PMC8728307.
Hidaka N, Kato H, Koga M, Katsura M, Oyama Y, Kinoshita Y, Fukumoto S, Makita N, Nangaku M, Ito N. Induction of FGF23-related hypophosphatemic osteomalacia by alcohol consumption. Bone Rep. 2021 Dec 15:101144 doi: 10.1016/j.bonr.2021.101144
Kato H, Hidaka N, Koga M, Kinoshita Y, Nangaku M, Makita N, Ito N. Altered Thyroid Function Tests Observed in Hypophosphatasia Patients Treated with Asfotase Alfa. Int J Endocrinol. 2021 Oct 28;2021:5492267. doi: 10.1155/2021/5492267. PMID: 34745256; PMCID: PMC8568557.
Ito N, Kang HG, Nishida Y, Evins A, Skrinar A, Cheong HI. Burden of disease of X-linked hypophosphatemia in Japanese and Korean patients: a cross-sectional survey. Endocr J. 2021 Nov 2. doi: 10.1507/endocrj.EJ21-0386. Epub ahead of print. PMID: 34732603.
Kato H, Ito N, Makita N, Nangaku M, Leung AM, Inoue K. Association of Serum Parathyroid Hormone Levels with All-cause and Cause-specific Mortality Among US Adults. Endocr Pract. 2021 Sep 23:S1530-891X(21)01233-7. doi: 10.1016/j.eprac.2021.09.005. Online ahead of print.PMID: 34563702
Briot K, Portale AA, Brandi ML, Carpenter TO, Cheong HI, Cohen-Solal M, Crowley RK, Eastell R, Imanishi Y, Ing S, Insogna K, Ito N, Jan de Beur S, Javaid MK, Kamenicky P, Keen R, Kubota T, Lachmann RH, Perwad F, Pitukcheewanont P, Ralston SH, Takeuchi Y, Tanaka H, Weber TJ, Yoo HW, Nixon A, Nixon M, Sun W, Williams A, Imel EA. Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension. RMD Open. 2021 Sep;7(3):e001714. doi: 10.1136/rmdopen-2021-001714.PMID: 34548383
Koga M, Kinoshita Y, Kato H, Kobayashi H, Shinoda Y, Nangaku M, Makita N, Dahir KM, Ito N. Massive calcification around large joints in a patient subsequently diagnosed with adult-onset hypophosphatasia. Osteoporos Int. 2021 Sep 8. doi: 10.1007/s00198-021-06145-5. Online ahead of print.PMID: 34494146
Kato H, Hidaka N, Koga M, Ogawa N, Takahashi S, Miyazaki H, Nangaku M, Makita N, Ito N. Performance evaluation of the new chemiluminescent intact FGF23 assay relative to the existing assay system. J Bone Miner Metab. 2021 Aug 5. doi: 10.1007/s00774-021-01258-7. Online ahead of print.PMID: 34351500
Ito N, Kubota T, Kitanaka S, Fujiwara I, Adachi M, Takeuchi Y, Yamagami H, Kimura T, Shinoda T, Minagawa M, Okazaki R, Ozono K, Seino Y, Fukumoto S. Clinical performance of a novel chemiluminescent enzyme immunoassay for FGF23. J Bone Miner Metab. 2021 Jul 13. doi: 10.1007/s00774-021-01250-1. Online ahead of print.PMID: 34255195
Kinoshita Y, Mohamed FF, Amadeu de Oliveira F, Narisawa S, Miyake K, Foster BL, Millán JL. Gene Therapy Using Adeno-Associated Virus Serotype 8 Encoding TNAP-D10 Improves the Skeletal and Dentoalveolar Phenotypes in Alpl-/- Mice. J Bone Miner Res. 2021 Jun 2. doi: 10.1002/jbmr.4382. Online ahead of print.PMID: 34076297
Kato H, Koga M, Kinoshita Y, Taniguchi Y, Kobayashi H, Fukumoto S, Nangaku M, Makita N, Ito N. Incidence of complications in 25 adult patients with X-linked hypophosphatemia. J Clin Endocrinol Metab. 2021 Apr 29:dgab282. doi: 10.1210/clinem/dgab282. Online ahead of print.PMID: 33912912
Ito N, Prideaux M, Wijenayaka AR, Yang D, Ormsby RT, Bonewald LF, Atkins GJ. Sclerostin Directly Stimulates Osteocyte Synthesis of Fibroblast Growth Factor-23. Calcif Tissue Int. 2021 Feb 22. doi: 10.1007/s00223-021-00823-6. Online ahead of print. PMID: 33616712
Kato H, Koga M, Kobayashi H, Maki H, Ikemura M, Kurokawa M, Nangaku M, Makita N, Ito N. Primary bone adult T cell lymphoma with multiple skeletal lesions and debilitating painful osteolysis: a case report. Osteoporos Int. 2021 May;32(5):1013-1017. doi: 10.1007/s00198-020-05720-6. Epub 2020 Oct 31.PMID: 33128574
Imanishi Y, Ito N, Rhee Y, Takeuchi Y, Shin CS, Takahashi Y, Onuma H, Kojima M, Kanematsu M, Kanda H, Seino Y, Fukumoto S. Interim Analysis of a Phase 2 Open-Label Trial Assessing Burosumab Efficacy and Safety in Patients With Tumor-Induced Osteomalacia. J Bone Miner Res. 2021 Feb;36(2):262-270. doi: 10.1002/jbmr.4184. Epub 2020 Nov 4.PMID: 32967046
Kobayashi H, Makise N, Ito N, Koga M, Zhang L, Ishibashi Y, Ikegami M, Shinoda Y, Akiyama T, Ushiku T, Tanaka S. Surgical margin for phosphaturic mesenchymal tumors in soft tissues: An analysis of the radiological histopathological correlation. J Orthop Sci. 2020 Aug 11:S0949-2658(20)30195-0. doi: 10.1016/j.jos.2020.07.006. Online ahead of print.J Orthop Sci. 2020. PMID: 32798110
Kubota T, Fukumoto S, Cheong HI, Michigami T, Namba N, Ito N, Tokunaga S, Gibbs Y, Ozono K. Long-term outcomes for Asian patients with X-linked hypophosphataemia: rationale and design of the SUNFLOWER longitudinal, observational cohort study. BMJ Open. 2020 Jun 29;10(6):e036367. doi: 10.1136/bmjopen-2019-036367. PMID: 32601114
Ito N, Fukumoto S. Congenital Hyperphosphatemic Conditions Caused by the Deficient Activity of FGF23. Calcif Tissue Int. 2021 Jan;108(1):104-115. doi: 10.1007/s00223-020-00659-6. Epub 2020 Jan 22.PMID: 31965220 Review.
Kobayashi H, Hirai T, Makise N, Ushiku T, Ito N, Koga M, Ikegami M, Shinoda Y, Akiyama T, Tanaka S. Reconstruction Using Frozen Autograft for Disseminated Phosphaturic Mesenchymal Tumor of the Humerus after a Pathological Fracture.Case Rep Orthop. 2019 Sep 4;2019:3015675. doi: 10.1155/2019/3015675. eCollection 2019.PMID:31565455
Sahoo SK, Kushwaha P, Bharti N, Khedgikar V, Trivedi R, Agrawal V, Ahmad N, Zaidi G, Paul L, Ito N, Bhatia E. Elevated FGF23 in a patient with hypophosphatemic osteomalacia associated with neurofibromatosis type 1. Bone. 2019 Dec;129:115055. doi: 10.1016/j.bone.2019.115055. Epub 2019 Aug 30. PMID:31476437
Insogna KL, Rauch F, Kamenický P, Ito N, Kubota T, Nakamura A, Zhang L, Mealiffe M, San Martin J, Portale AA. Burosumab Improved Histomorphometric Measures of Osteomalacia in Adults with X-Linked Hypophosphatemia: A Phase 3, Single-Arm, International Trial.J Bone Miner Res. 2019 Dec;34(12):2183-2191. doi: 10.1002/jbmr.3843. Epub 2019 Oct 1. PMID:31369697
Portale AA, Carpenter TO, Brandi ML, Briot K, Cheong HI, Cohen-Solal M, Crowley R, Jan De Beur S, Eastell R, Imanishi Y, Imel EA, Ing S, Ito N, Javaid M, Kamenicky P, Keen R, Kubota T, Lachmann R, Perwad F, Pitukcheewanont P, Ralston SH, Takeuchi Y, Tanaka H, Weber TJ, Yoo HW, Zhang L, Theodore-Oklota C, Mealiffe M, San Martin J, Insogna K. Continued Beneficial Effects of Burosumab in Adults with X-Linked Hypophosphatemia: Results from a 24-Week Treatment Continuation Period After a 24-Week Double-Blind Placebo-Controlled Period. Calcif Tissue Int. 2019 Sep;105(3):271-284. doi: 10.1007/s00223-019-00568-3. 2019 Jun 4. PMID:31165191
Takashi Y, Kosako H, Sawatsubashi S, Kinoshita Y, Ito N, Tsoumpra MK, Nangaku M, Abe M, Matsuhisa M, Kato S, Matsumoto T, Fukumoto S. Activation of unliganded FGF receptor by extracellular phosphate potentiates proteolytic protection of FGF23 by its O-glycosylation. Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11418-11427. PMID:31097591
Manaka K, Sato J, Kinoshita Y, Ito N, Fujita M, Iiri T, Nangaku M, Makita N. Effectiveness and safety of cinacalcet for primary hyperparathyroidism: a single center experience. Endocr J. 2019 Aug 29;66(8):683-689. doi: 10.1507/endocrj.EJ19-0034. Epub 2019 May 16. PMID:31092749
Kobayashi H, Makise N, Ushiku T, Ito N, Koga M, Shinoda Y, Tanaka S. Infiltrative nature of tumor-induced osteomalacia lesions in bone: Correlation between radiological and histopathological features. J Orthop Sci. 2019 Sep;24(5):900-905. doi: 10.1016/j.jos.2019.02.005. Epub 2019 Feb 21. PMID:30797665
Kinoshita Y, Takashi Y, Ito N, Ikegawa S, Mano H, Ushiku T, Fukayama M, Nangaku M, Fukumoto S. Ectopic expression of Klotho in fibroblast growth factor 23 (FGF23)-producing tumors that cause tumor-induced rickets/osteomalacia (TIO). Bone Rep. 2018; 31;10:100192. PMID:30627598
Insogna KL, Briot K, Imel EA, Kamenický P, Ruppe MD, Portale AA, Weber T, Pitukcheewanont P, Cheong HI, Jan de Beur S, Imanishi Y, Ito N, Lachmann RH, Tanaka H, Perwad F, Zhang L, Chen CY, Theodore-Oklota C, Mealiffe M, San Martin J, Carpenter TO; AXLES 1 Investigators. A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis J Bone Miner Res. 2018; 33: 1383-1393. PMID:29947083
Kinoshita Y, Fukumoto S. X-linked hypophosphatemia and FGF23-related hypophosphatemic diseases -Prospect for new treatment. Endocr Rev. 2018; 39 :274-291. PMID:29381780
Kobayashi H, Ito N, Akiyama T, Okuma T, Kinoshita Y, Ikegami M, Shinoda Y, Fukumoto S, Tanaka S, Kawano H. Prevalence and clinical outcomes of hip fractures and subchondral insufficiency fractures of the femoral head in patients with tumour-induced osteomalacia. Int Orthop. 2017; 41: 2597-2603. PMID:28836028
Kinoshita Y, Ito N, Makita N, Nangaku M, Fukumoto S. Changes in bone metabolic parameters following oral calcium supplementation in an adult patient with vitamin D-dependent rickets type 2A. Endocr J. 2017; 64: 589-596. PMID:28367941
Takashi Y, Kinoshita Y, Ito N, Taguchi M, Takahashi M, Egami N, Tajima S, Nangaku M, Fukumoto S. Tumor-induced Osteomalacia Caused by a Parotid Tumor. Intern Med. 2017; 56: 535-539.
Kobayashi H, Akiyama T, Okuma T, Shinoda Y, Oka H, Ito N, Fukumoto S, Tanaka S, Kawano H. Three-dimensional fluoroscopic navigation-assisted surgery for tumors in patients with tumor-induced osteomalacia in the bones. Comput Assist Surg (Abingdon). 2017; 12: 1-14.
Takashi Y, Kinoshita Y, Hori M, Ito N, Taguchi M, Fukumoto S. Patients with FGF23-related hypophosphatemic rickets/osteomalacia do not present with left ventricular hypertrophy. Endocr Res. 2017; 42: 132-137.
Kinoshita Y, Arai M, Ito N, Takashi Y, Makita N, Nangaku M, Shinoda Y, Fukumoto S. High serum ALP level is associated with increased risk of denosumab-related hypocalcemia in patients with bone metastases from solid tumors. Endocr J. 2016; 63: 479-484.
Hori M, Kinoshita Y, Taguchi M, Fukumoto S. Phosphate enhances Fgf23 expression through reactive oxygen species in UMR-106 cells. J Bone Miner Metab. 2016; 34: 132-139.
Tajima S, Takashi Y, Ito N, Fukumoto S, Fukuyama M. ERG and FLI1 are useful immunohistochemical markers in phosphaturic mesenchymal tumors. Med Mol Morphol. 2016; 49: 203-209.
Wijenayaka AR, Yang D, Prideaux M, Ito N, Kogawa M, Anderson PH, Morris HA, Solomon LB, Loots GG, Findlay DM, Atkins GJ. 1α,25-dihydroxyvitamin D3 stimulates human SOST gene expression and sclerostin secretion. Mol Cell Endocrinol 2015; 413: 157-167.
Takashi Y, Kinoshita Y, Makita N, Taguchi M, Takahashi K, Nangaku M, Fukumoto S. Rapid Recovery of Hypothalamic-Pituitary Axis after Successful Resection of an ACTH-secreting Neuroendocrine Tumor. Intern Med 2015; 54: 2201-2205.
Ito N, Wijenayaka AR, Prideaux M, Kogawa M, Ormsby RT, Evdokiou A, Bonewald LF, Findlay DM, Atkins GJ. Regulation of FGF23 expression in IDG-SW3 osteocytes and human bone by pro-inflammatory stimuli. Mol Cell Endocrinol. 2015; 399: 208-218.
Nakamura T, Aizawa T, Hoshikawa T, Ozawa H, Ito N, Fukumoto S, Itoi E, Kokubun S. Tumor-induced osteomalacia caused by phosphaturic mesenchymal tumor of the cervical spine. J Orthop Sci. 2015; 20: 765-771. PMID: 24504987
Kinoshita Y, Hori M, Taguchi M, Fukumoto S. Functional analysis of mutant FAM20C in Raine syndrome with FGF23-related hypophosphatemia. Bone. 2014; 67: 145-151.
Ito N, Peña AS, Perano S, Atkins GJ, Findlay DM, Couper JJ. First Australian report of vitamin D-dependent rickets type I. Med J Aust. 2014; 201: 420-421.
Kinoshita Y, Hori M, Taguchi M, Watanabe S, Fukumoto S. Functional activities of mutant calcium-sensing receptors determine clinical presentations in patients with autosomal dominant hypocalcemia. J Clin Endocrinol Metab. 2014; 99: E363-368.
Ito N, Findlay DM, Atkins GJ. Osteocyte Communication with the Kidney Via the Production of FGF23: Remote Control of Phosphate Homeostasis. Clin Rev Bone Miner Metab. 2014; 12: 44-58.
Ito N, Findlay DM, Anderson PH, Bonewald LF, Atkins GJ. Extracellular phosphate modulates the effect of 1α,25-dihydroxy vitamin D(3) (1,25D) on osteocyte like cells. J Steroid Biochem Mol Biol. 2013; 136: 183-186.
Kinoshita Y, Saito T, Shimizu Y, Hori M, Taguchi M, Igarashi T, Fukumoto S, Fujita T. Mutational analysis of patients with FGF23-related hypophosphatemic rickets. Eur J Endocrinol. 2012; 167: 165-172.
Kinoshita Y, Fujii H, Takeshita A, Taguchi M, Miyakawa M, Oyama K, Yamada S, Takeuchi Y. Impaired glucose metabolism in Japanese patients with acromegaly is restored after successful pituitary surgery if pancreatic {beta}-cell function is preserved. Eur J Endocrinol. 2011; 164: 467-473.
Ito N, Shimizu Y, Suzuki H, Saito T, Okamoto T, Hori M, Akahane M, Fukumoto S, Fujita T. Clinical utility of systemic venous sampling of FGF23 for identifying tumours responsible for tumour-induced osteomalacia. J Intern Med. 2010; 268: 390-394.
Sakurai-Chin C, Ito N, Taguchi M, Miyakawa M, Takeshita A, Takeuchi Y. Hypoglycemic coma in a patient with anorexia nervosa coincident with acute exacerbation of liver injury induced by oral intake of nutrients. Intern Med. 2010; 49: 1553-1556
Saito T, Fukumoto S, Ito N, Suzuki H, Igarashi T, Fujita T. A novel mutation in the GATA3 gene of a Japanese patient with PTH-deficient hypoparathyroidism. J Bone Miner Metab. 2009; 27: 386-389.
Saito T, Nishii Y, Yasuda T, Ito N, Suzuki H, Igarashi T, Fukumoto S, Fujita T. Familial hypophosphatemic rickets caused by a large deletion in PHEX gene. Eur J Endocrinol. 2009; 161: 647-651.
Shimizu Y, Tada Y, Yamauchi M, Okamoto T, Suzuki H, Ito N, Fukumoto S, Sugimoto T, Fujita T. Hypophosphatemia induced by intravenous administration of saccharated ferric oxide: another form of FGF23-related hypophosphatemia. Bone. 2009; 45: 814-816.
Kinoshita Y, Masuoka K, Miyakoshi S, Taniguchi S, Takeuchi Y. Vitamin D insufficiency underlies unexpected hypocalcemia following high dose glucocorticoid therapy. Bone. 2008; 42: 226-268.
Nasu T, Kurisu S, Matsuno S, Tatsumi K, Kakimoto T, Kobayashi M, Nakano Y, Wakasaki H, Furuta H, Nishi M, Sasaki H, Suzuki H, Ito N, Fukumoto S, Nanjo K. Tumor-induced hypophosphatemic osteomalacia diagnosed by the combinatory procedures of magnetic resonance imaging and venous sampling for FGF23. Intern Med. 2008; 47: 957-961.
Ito N, Fukumoto S, Takeuchi Y, Takeda S, Suzuki H, Yamashita T, Fujita T. Effect of acute changes of serum phosphate on fibroblast growth factor (FGF)23 levels in humans. J Bone Miner Metab. 2007; 25: 419-422.
Kawarazaki H, Shibagaki Y, Shimizu H, Kawarazaki W, Ito N, Ishikawa A, Fukumoto S, Fujita T. Persistent high level of fibroblast growth factor 23 as a cause of post-renal transplant hypophosphatemia. Clin Exp Nephrol. 2007; 11: 255-257.
Ito N, Fukumoto S, Taguchi M, Takeshita A, Takeuchi Y, Yamada S, Fujita T. Fibroblast growth factor (FGF)23 in patients with acromegaly. Endocr J. 2007; 54: 481-484.
Frishberg Y, Ito N, Rinat C, Yamazaki Y, Feinstein S, Urakawa I, Navon-Elkan P, Becker-Cohen R, Yamashita T, Araya K, Igarashi T, Fujita T, Fukumoto S. Hyperostosis-hyperphosphatemia syndrome: a congenital disorder of O-glycosylation associated with augmented processing of fibroblast growth factor 23. J Bone Miner Res. 2007; 22: 235-242.
Ito N, Fukumoto S, Takeuchi Y, Yasuda T, Hasegawa Y, Takemoto F, Tajima T, Dobashi K, Yamazaki Y, Yamashita T, Fujita T. Comparison of two assays for fibroblast growth factor (FGF)-23. J Bone Miner Metab. 2005; 23: 435-440.
Kinoshita Y, Taguchi M, Takeshita A, Miura D, Tomikawa S, Takeuchi Y. 1,25-dihydroxyvitamin D suppresses circulating levels of parathyroid hormone in a patient with primary hyperparathyroidism and coexistent sarcoidosis. J Clin Endocrinol Metab. 2005; 90:6727-6731.
Araya K, Fukumoto S, Backenroth R, Takeuchi Y, Nakayama K, Ito N, Yoshii N, Yamazaki Y, Yamashita T, Silver J, Igarashi T, Fujita T. A novel mutation in fibroblast growth factor 23 gene as a cause of tumoral calcinosis. J Clin Endocrinol Metab. 2005; 90: 5523-5527.
受賞歴
伊東 伸朗（Nobuaki Ito）
- 2006年 第24回 日本骨代謝学会 IOF-ANZBMS Travel Award
- 2007年 第20回 内科学会奨励賞
- 2009年 住友生命社会福祉事業団 海外医学研究助成金
- 2010年 上原記念生命科学財団 ポストドクトラルフェローシップ
- 2021年 INTERNATIONAL AWARD for publishing Excellence in CALCIFIED TISSUE INTERNATIONAL & MUSCULOSKELETAL RESEARCH
- 2023年 日本骨代謝学会フロンティア研究者助成
加藤 創生（Hajime Kato）
- 2021年 日本骨代謝学会優秀演題賞
- 2021年 日本骨代謝学会 ECTS Travel Award
- 2021年 日本骨代謝学会 ANZBMS Travel Award
- 2022年 第24回 日本骨粗鬆症学会 優秀ポスター賞
- 2022年 国際医学研究振興財団 海外留学助成(辞退)
- 2022年 内藤記念科学振興財団 海外留学助成金(辞退)
- 2022年 中富健康科学振興財団 留学助成金(辞退)
- 2023年 日本学術振興会 海外特別研究員
- 2023年 ECTS EAST-MEETS-WEST Award
- 2023年 ASBMR 2023 Young Investigator Travel Grant
日髙 尚子（Naoko Hidaka）
- 2015年 第112回日本内科学会総会医学生・研修医部門優秀演題賞
- 2022年 第39回 日本骨代謝学会優秀演題賞
星野 良朋（Yoshitomo Hoshino）
- 2021年 第672回 日本内科学会関東地方会指導医賞
- 2021年 東大病院優秀指導医賞
- 2023年 第96回日本内分泌学会学術総会「愛・内分泌」賞（優秀演題賞）
木村 聡一郎（Soichiro Kimura）
- 2023年 日本骨代謝学会 ANZBMS Travel Award
渡部 創（So Watanabe）（老年病科）
- 2023年 第96回日本内分泌学会学術総会「愛・内分泌」賞（優秀演題賞）