京都大学 / 新制・論文博士 / 博士(医学) / 乙第13437号 / 論医博第2236号 / 新制||医||1054(附属図書館) / (主査)教授 松田 秀一, 教授 中山 健夫, 教授 森本 尚樹 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Aim: The overall aim is to (i) analyze the prognosis of dental implant treatment concerning marginal bone loss (MBL) in patients undergoing or have undergone treatment with bone antiresorptive or antiangiogenic medication for osteoporosis (ii) and additional purpose to assess the available scientific literature in the first aim concerning the risk of getting medication-related osteonecrosis of the jaw (MRONJ) associated with dental implant installation.  Material and methods: A systematic literature search was conducted in October 2021 in the following three databases; MEDLINE/PubMed, Cochrane Library and Web of Science. PRISMA 2009 Flow Diagram were used for the selection process, whereas the included studies were evaluated for quality assessment using Newcastle Ottawa Scale (NOS).  Results: The search resulted in four included studies considering the eligibility criteria. The studies evaluated MBL in osteoporotic patients undergoing or have undergone oral bisphosphonate (BP) treatment before and/or during implant placement. MRONJ was also assessed in all four articles.  Conclusions: The results of this present study do not indicate that patients undergoing or have undergone antiresorptive or antiangiogenic medication for osteoporosis are at an increased risk of MBL in dental implants during follow-up periods. The present data assessing the risk for developing MRONJ remains low for osteoporotic patients. Therefore, dental implant surgery is considered possible with success in osteoporotic patients receiving earlier mentioned medications. However additional studies are required to evaluate the effects on this patient group concerning osseointegration of dental implant regarding MBL. / Syfte: Syftet med denna studie är att analysera prognosen för implantatbehandling avseende marginell benförlust (MBL) hos patienter som genomgår eller har genomgått behandling med benantiresorptiv eller antiangiogen medicin för osteoporos. Ytterligare utförs en bedömning av tillgänglig vetenskaplig litteratur gällande risken för läkemedelsrelaterad käkbensnekros (MRONJ) associerat med implantatinstallation hos patienter som genomgår eller har genomgått behandling med benantiresorptiv eller antiangiogen medicin. Material och metod: En systematisk elektronisk litteratursökning genomfördes i oktober 2021 i följande tre databaser; MEDLINE/PubMed, Cochrane Library och Web of Science. PRISMA 2009 Flow Diagram användes för urvalsprocessen, varav de inkluderande studierna kvalitetsgranskades enligt Newcastle Ottawa Scale (NOS). Resultat: Sökningen resulterade i fyra studier, enligt inklusions- och exklusionskriterier. Studierna utvärderade MBL hos osteoporospatienter som går eller har gått behandling med orala bisfosfonater före eller under implantatinstallationen. MRONJ fastställdes i alla fyra artiklar. Slutsats: Resultatet av denna studie indikerar inte att patienter som genomgår eller har genomgått behandling med benantiresorptiv eller antiangiogen medicin för osteoporos löper en ökad risk för MBL av dentala implantat under uppföljningsperioder. Nuvarande data bedömer att risken för att utveckla MRONJ är fortfarande låg för osteoporos patienter. Därför antas implantatkirurgi kunna utföras på osteoporos patienter som står på denna medicinering. Dock krävs ytterligare studier för att utvärdera effekterna av denna patientgrupp gällande osseointegration av dentala implantat avseende MBL.

Despite the continued development of specialized immunosuppressive therapies in the form of monoclonal antibodies, glucocorticoids remain a mainstay in the treatment of rheumatological and auto-inflammatory disorders. Therapeutic glucocorticoids are unmatched in the breadth of their immunosuppressive properties and deliver their anti-inflammatory effects at unparalleled speed. However, long-term exposure to therapeutic doses of glucocorticoids decreases bone mass and increases the risk of fractures – particularly in the spine – thus limiting their clinical use. Due to the abundant expression of glucocorticoid receptors across all skeletal cell populations and their respective progenitors, therapeutic glucocorticoids affect skeletal quality through a plethora of cellular targets and molecular mechanisms. However, recent evidence from rodent studies, supported by clinical data, highlights the considerable role of cells of the osteoblast lineage in the pathogenesis of glucocorticoid-induced osteoporosis: it is now appreciated that cells of the osteoblast lineage are key targets of therapeutic glucocorticoids and have an outsized role in mediating their undesirable skeletal effects. As part of this article, we review the molecular mechanisms underpinning the detrimental effects of supraphysiological levels of glucocorticoids on cells of the osteoblast lineage including osteocytes and highlight the clinical implications of recent discoveries in the field.