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Decrease of bone mineral density in Japanese patients with non-metastatic prostate cancer treated with androgen deprivation therapy

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Title

Decrease of bone mineral density in Japanese patients with non-

metastatic prostate cancer treated with androgen deprivation

therapy( 内容と審査の要旨(Summary) )

Author(s)

加藤, 成一

Report No.(Doctoral

Degree)

博士(医学) 乙第1494号

Issue Date

2018-03-20

Type

博士論文

Version

none

URL

http://hdl.handle.net/20.500.12099/75267

※この資料の著作権は、各資料の著者・学協会・出版社等に帰属します。

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 Ặྡ㸦ᮏ⡠㸧  Ꮫ ఩ ࡢ ✀ 㢮  Ꮫ఩ᤵ୚␒ྕ  Ꮫ఩ᤵ୚᪥௜  Ꮫ఩ᤵ୚せ௳ Ꮫ఩ㄽᩥ㢟┠ ᑂ ᰝ ጤ ဨ ຍ ⸨ ᡂ ୍ 㸦ឡ▱┴㸧 ༤ ኈ㸦་Ꮫ㸧 எ➨  ྕ ᖹᡂ  ᖺ  ᭶  ᪥ Ꮫ఩つ๎➨㸲᮲➨㸰㡯ヱᙜ

Decrease of bone mineral density in Japanese patients with non-metastatic prostate cancer treated with androgen deprivation therapy 㸦୺ᰝ㸧ᩍᤵ ⛅ᒣ㻌 ἞ᙪ 㸦๪ᰝ㸧ᩍᤵ ఀ⸨㻌 ၿつ  ᩍᤵ ⸨⏣㻌 ᘅᚿ ㄽ ᩥ ෆ ᐜ ࡢ せ ᪨    ๓❧⭢⒴࡟ᑐࡍࡿ࢔ࣥࢻࣟࢤࣥ㝖ཤ⒪ἲ㸦DQGURJHQGHSULYDWLRQWKHUDS\$'7㸧ࡢ๪స⏝ࡢ ୍ࡘ࡟㦵ᐦᗘῶᑡࡀ࠶ࡿࠋ㸯ᖺ㛫ࡢ㦵ᐦᗘῶᑡࡣ⭜᳝࡛㸰㹼㸶㸣࡟ࡢࡰࡾ㸪ࡇࢀࡣ୍⯡㧗㱋⏨ᛶ ࡢ㸳㹼㸯㸮ಸ࡟࠶ࡓࡿࠋ$'7 ࡟క࠺㦵ᐦᗘῶᑡࡸ㦵ᢡࣜࢫࢡࡢቑຍ࡟㛵ࡍࡿሗ࿌ࡢ ከࡃࡣすὒㅖ ᅜ࠿ࡽࡢࡶࡢ࡛㸪࢔ࢪ࢔ே࡟㛵ࡍࡿሗ࿌ࡣᑡ࡞࠸ࠋࡑࡇ࡛㸪᪥ᮏ࡟࠾࠸࡚㠀㌿⛣ᛶ๓❧⭢⒴࡟ᑐ ࡍࡿ $'7 ࡀᝈ⪅ࡢ㦵ᐦᗘ࡟୚࠼ࡿᙳ㡪ࢆ᫂ࡽ࠿࡟ࡍࡿࡓࡵ࡟ᶓ᩿ㄪᰝࢆ⾜ࡗࡓࠋ   ࠙ᑐ㇟࡜᪉ἲࠚ 㠀㌿⛣ᛶ๓❧⭢⒴ࢆ᭷ࡍࡿ᪥ᮏேࡢ⏨ᛶ࡛㸪$'7 ࢆᣢ⥆ⓗ࡟ཷࡅ࡚࠸ࡿ  ே㸦㸣㸧㸪࠾ࡼࡧࡇ ࢀ࠿ࡽ $'7 ཷࡅࡿணᐃࡢ  ே㸦㸣㸧㸪࠶ࢃࡏ࡚  ேࢆᑐ㇟࡜ࡋࡓࠋᖹᆒᖺ㱋ࡣ s ṓ ࡛㸪๓❧⭢⒴ࡢ⑓ᮇࡣ 8,&& ศ㢮 6WDJHϨ㸩ϩࡀ  ౛㸦㸧㸪6WDJHϪࡀ  ౛㸦㸧࡛࠶ࡗࡓࠋ $'7 ᪋⾜ᝈ⪅ࡢᖹᆒ἞⒪ᮇ㛫ࡣ s ࣧ᭶࡛࠶ࡾ㸪㸰ᖺᮍ‶ࡀ  ே㸦㸧㸪㸲ᖺᮍ‶ࡀ  ே 㸦㸧㸪㸴ᖺᮍ‶ࡀ  ே㸦㸧㸪㸴ᖺ௨ୖࡀ  ே㸦㸧࡛࠶ࡗࡓࠋ

'XDOHQHUJ\ ;UD\ DEVRUSWLRPHWU\㸦௨ୗ '(;$ ἲ㸧ࢆ⏝࠸࡚ᑐ㇟ᝈ⪅ࡢ⭜᳝࡜኱⭣㦵㢁㒊ࡢ㦵ᐦ ᗘࢆ ᐃࡋࡓࠋࡲࡓ㸪㢕㸪⬚㸪⭜᳝ࡢ ; ⥺ṇ㠃࠾ࡼࡧഃ㠃ീࢆ᧜ᙳࡋ㸪᳝య㦵ᢡࡢ᭷↓ࢆㄪᰝࡋࡓࠋ ࡲࡓ㸪㦵௦ㅰ࣐࣮࣮࢝࡜ࡋ࡚ ERQHDONDOLQHSKRVSKDWDVH㸦௨ୗ %$3㸧࡜ XULQHW\SHϨFROODJHQFURVV OLQNHG1WHORSHSWLGH㸦௨ୗ XULQH17[㸧ࡲࡓࡣ WDUWUDWHUHVLVWDQWDFLGSKRVSKDWDVHE㸦௨ୗ 75$&3E ࢆ ᐃࡋ㸪㦵௦ㅰࡢ≧ែࢆㄪ࡭ࡓࠋࡉࡽ࡟㸪デ⒪㘓ࡸ㉁ၥ⣬ࢆ⏝࠸࡚ᖺ㱋㸪ERG\PDVVLQGH[ 㸦௨ୗ %0,㸧㸪$'7 ࡢෆᐜ㸪$'7 㛤ጞ᫬ࡢ SURVWDWHVSHFLILFDQWLJHQ 36$ 㸪⬨᳝ࡲࡓࡣ኱⭣㦵㦵 ᢡࡢ᪤ Ṕ࠾ࡼࡧᐙ᪘Ṕ㸪$'7 ୰ࡢ㦵ᢡ㸪ႚ↮㸪㐣ᗘࡢ㣧㓇㸪㧗⾑ᅽ㸪⢾ᒀ⑓㸪៏ᛶ⭈⮚⑓㸪㛵⠇ࣜ ࣐࢘ࢳ㸪ࢫࢸࣟ࢖ࢻ౑⏝ࡢ᭷↓ࢆㄪᰝࡋ㸪㦵ᐦᗘ࡟ᙳ㡪ࢆ୚࠼࠺ࡿせᅉࢆㄪᰝࡋࡓࠋ  ࠙⤖ᯝࠚ  $'7 ࡢ἞⒪ᮇ㛫ࡀ㛗ࡃ࡞ࡿ࡟ᚑ࠸㸪'(;$ ἲ࡟࠾ࡅࡿ⭜᳝࠾ࡼࡧ኱⭣㦵㢁㒊ࡢ㦵ᐦᗘࡣ᭷ព࡟పୗࡋ ࡓ㸦ࡑࢀࡒࢀ S  ࡜ S  ࠋ༢ኚ㔞ゎᯒ࡟࠾࠸࡚⭜᳝ࡢ㦵ᐦᗘ࡟ᙳ㡪ࢆ୚࠼ࡿ᭷ ព࡞ᅉᏊࡣ㸪$'7 ࡢ἞⒪ᮇ㛫㸪%0,㸪; ⥺⏬ീୖࡢ⬨᳝㦵ᢡ㸪%$3㸪XULQH17[ ࠾ࡼࡧ 75$&3E ࡛ ࠶ࡾ㸪኱⭣㦵㢕㒊ࡢ㦵ᐦᗘ࡟ᙳ㡪ࢆ୚࠼ࡿ᭷ព࡞ᅉᏊࡣ 㸪$'7 ࡢ἞⒪ᮇ㛫㸪%0,㸪ᖺ㱋㸪; ⥺⏬ീ ୖࡢ⬨᳝㦵ᢡ㸪%$3㸪XULQH 17[ ࠾ࡼࡧ 75$&3E ࡛࠶ࡗࡓࠋ୍᪉㸪$'7 ࡢ἞⒪ᮇ㛫࡜ %$3 ࠾ࡼࡧ 75$&3E ࡟ࡣᙅ࠸ṇࡢ┦㛵ࢆㄆࡵ㸪⬨᳝ࡲࡓࡣ኱⭣㦵㦵ᢡࡢ᪤ ࡢ࠶ࡿᝈ⪅ࡣ %$3 ࡀ㸪; ⥺⏬ീ ୖࡢ᳝య㦵ᢡࡀ࠶ࡿᝈ⪅ࡣ %$3 ࡜ 75$&3E ࡀ㸪㦵ᢡࡢ࡞࠸ᝈ⪅࡜ẚ࡭᭷ព࡟㧗࠿ࡗࡓࠋḟ࡟㏲

(3)

ḟ㔜ᅇᖐศᯒࢆ⾜࠸㸪$'7 ࡢ἞⒪ᮇ㛫ࡣ⭜᳝࠾ࡼࡧ኱⭣㦵㢁㒊ࡢ㦵ᐦᗘ࡟ᙳ㡪ࢆཬࡰࡍ᭷ព࡞ᅉ Ꮚࡢࡦ࡜ࡘ࡛࠶ࡿࡇ࡜ࢆ☜ㄆࡋࡓ㸦S 㸧ࠋ ⭜᳝࠾ࡼࡧ኱⭣㦵㢕㒊ࡢ㦵ᐦᗘࢆࡶ࡜࡟ :+2 ࡢ㦵⢒㧼⑕デ᩿ᇶ‽࡟ᚑࡗ࡚ศ㢮ࡍࡿ࡜㸪ṇᖖ㸪 㦵ῶᑡ㸪㦵⢒㧼⑕ࡀࡑࢀࡒࢀ  ே㸦㸧㸪 ே㸦㸧㸪 ே㸦㸧࡛࠶ࡗࡓࠋ$'7 ࡢ ἞⒪ᮇ㛫ࡀ㛗ࡃ࡞ࡿ࡟ᚑ࠸㸪㦵⢒㧼⑕ࡢ᭷⑓⋡ࡣ᭷ព࡟ቑຍࡋ㸦S 㸧㸪$'7 㛤ጞ๓ࡢ  ࡛࠶ࡗࡓ㦵⢒㧼⑕ࡢ᭷⑓⋡ࡣ㸪 ᖺ௨ୖࡢ $'7 ࡢ⥅⥆࡛ ࡟ୖ᪼ࡋࡓࠋ༢ኚ㔞ゎᯒ࡟࠾࠸࡚㸪 㦵⢒㧼⑕ࡢデ᩿࡟ᙳ㡪ࢆ୚࠼ࡿ᭷ព࡞ᅉᏊࡣ㸪$'7 ࡢ἞⒪ᮇ㛫㸪%0,㸪ᖺ㱋㸪; ⥺⏬ീୖࡢ᳝య㦵 ᢡ࠾ࡼࡧ %$3 ࡛࠶ࡗࡓࠋࡑࡇ࡛ከኚ㔞ࣟࢪࢫࢸࢵࢡᅇᖐศᯒࢆ⾜࠸㸪$'7 ࡢ἞⒪ᮇ㛫ࡣ㦵⢒㧼⑕ デ᩿࡟ᙳ㡪ࢆཬࡰࡍ᭷ព࡞ᅉᏊࡢࡦ࡜ࡘ࡛࠶ࡿࡇ࡜ࢆ☜ㄆࡋࡓ㸦S 㸧ࠋ  ࠙⪃ᐹࠚ  すὒㅖᅜ࠿ࡽࡢሗ࿌࡜ẚ㍑ࡋ㸪᪥ᮏேࡢ㠀㌿⛣ᛶ๓❧⭢⒴ᝈ⪅࡟࠾࠸࡚ $'7 㛤ጞ᫬ࡢ᳝య㦵ᢡࡸ㦵 ⢒㧼⑕ࡢ᭷⑓⋡ࡣప࠸ഴྥ࡟࠶ࡗࡓࡀ㸪$'7 ࡢ἞⒪ᮇ㛫ࡀ㛗ࡃ࡞ࡿ࡟ᚑ࠸㦵ᐦᗘࡣపୗࡋ㸪㦵⢒㧼⑕ ࡢ᭷⑓⋡ࡣቑຍࡍࡿ࡜࠸࠺⤖ᯝࡣྠࡌ࡛࠶ࡗࡓࠋከኚ㔞ゎᯒ࡟࠾࠸࡚࢔ࢪ࢔ே࡟࠾ࡅࡿ $'7 ࡢ἞⒪ᮇ 㛫࡜㦵⢒㧼⑕᭷⑓⋡ࡢ㛫ࡢ᭷ព࡞ṇࡢ㛵ಀࢆド᫂ࡋࡓࡢࡣ㸪ᮏ◊✲ࡀึࡵ࡚࡛࠶ࡿࠋ୍᪉㸪ᮏ◊✲࡟ ࠾࠸࡚㸪㦵ᐦᗘࡸ㦵⢒㧼⑕デ᩿࡟᭱ࡶᙉࡃᙳ㡪ࢆ୚࠼ࡓᅉᏊࡣ $'7 ࡢ἞⒪ᮇ㛫࡛ࡣ࡞ࡃ㸪%0, ࡛࠶ࡾ㸪 すὒㅖᅜ࠿ࡽࡢሗ࿌࡜ࡣ␗࡞ࡿ⤖ᯝ࡛࠶ࡗࡓࠋ%0, ࡣ㦵ᐦᗘ࡟ᙳ㡪ࢆ୚࠼ࡿᅉᏊ࡜ࡋ࡚ࡼࡃ▱ࡽࢀ࡚ ࠾ࡾ㸪%0, ࡀప࠸࡯࡝㦵ᐦᗘࡣపࡃ㸪ࡲࡓ㸪㦵ᐦᗘῶᑡࡀ኱ࡁ࠸࡜ሗ࿌ࡉࢀ࡚࠸ࡿࠋᮏ◊✲ࡢᑐ㇟ᝈ ⪅ࡢ %0, ࡣすὒㅖᅜࡢᑐ㇟ᝈ⪅ࡢ %0, ࡜ẚ㍑ࡋ࡚᫂ࡽ࠿࡟పࡃ㸪%0, ࡀ㦵ᐦᗘ࡟ࡼࡾᙉࡃᙳ㡪ࡋࡓྍ ⬟ᛶࡀ࠶ࡿࠋ࢔ࢪ࢔ே࡟࠾࠸࡚ࡣ $'7 ࡜࡜ࡶ࡟ %0, ࡶ㦵ᐦᗘ࡜㦵⢒㧼⑕デ᩿࡟ᙳ㡪ࢆ୚࠼ࡿ㔜せ࡞ᅉ Ꮚ࡛࠶ࡿ࡜⪃࠼ࡽࢀࡓࠋ  ࠙⤖ㄽࠚ ᪥ᮏேࡢ㠀㌿⛣ᛶ๓❧⭢⒴ᝈ⪅࡟࠾࠸࡚㸪$'7 ࡣ⭜᳝࠾ࡼࡧ኱⭣㦵㢁㒊ࡢ㦵ᐦᗘ࡟㈇ࡢᙳ㡪ࢆ ୚࠼㸪ࡲࡓ㸪἞⒪ᮇ㛫ࡢᘏ㛗࡟ᚑ࠸㸪㦵⢒㧼⑕ࡢ᭷⑓⋡ࡶቑຍࡍࡿࡇ࡜ࡀ♧ࡉࢀࡓࠋ ㄽ ᩥ ᑂ ᰝ ࡢ ⤖ ᯝ ࡢ せ ᪨  ⏦ㄳ⪅ ຍ⸨ᡂ୍ࡣ, 㠀㌿⛣ᛶ๓❧⭢⒴ࢆ᭷ࡍࡿ᪥ᮏே⏨ᛶ࡛㸪࢔ࣥࢻࣟࢤࣥ㝖ཤ⒪ἲ㸦௨ୗ ADT㸧 ࢆ ᣢ ⥆ ⓗ ࡟ ཷ ࡅ ࡚ ࠸ ࡿ ᝈ ⪅ ࡜ ࡇ ࢀ ࠿ ࡽ ཷ ࡅ ࡿ ண ᐃ ࡢ ᝈ ⪅ ࢆ ᑐ ㇟ ࡜ ࡋ, Dual-energy X-ray absorptiometry ἲࢆ⏝࠸࡚⭜᳝ཬࡧ኱⭣㦵㢕㒊ࡢ㦵ᐦᗘࢆ ᐃࡋ, ADT ἞⒪ᮇ㛫ࡸ Bone mass index,ࡀ㦵ᐦᗘ࡟㈇ࡢᙳ㡪ࢆ୚࠼㸪㦵⢒㧼⑕᭷⑓⋡ࡀቑຍࡍࡿࡇ࡜ࢆ᫂ࡽ࠿࡟ࡋࡓࠋADT ࡢ἞⒪ᮇ㛫 ཬࡧBone mass index, X ⥺⏬ീୖࡢ᳝య㦵ᢡ࡞࡝ࡀᙳ㡪ࢆ୚࠼ࡿ᭷ព࡞ᅉᏊ࡛࠶ࡿࡇ࡜ࡶ᫂ࡽ࠿࡟ ࡋࡓࠋᮏ◊✲ࡢᡂᯝࡣ㠀㌿⛣ᛶ๓❧⭢⒴ࢆ᭷ࡍࡿ᪥ᮏே⏨ᛶ࡟࠾ࡅࡿ࢔ࣥࢻࣟࢤࣥ㝖ཤ⒪ἲ࡜㦵⢒㧼 ⑕ࡢ㛵ࢃࡾࢆ᫂ࡽ࠿࡟ࡋ, Ἢᒀჾ⛉ᏛࡢⓎᒎ࡟ᑡ࡞࠿ࡽࡎᐤ୚ࡍࡿࡶࡢ࡜ㄆࡵࡽࢀࡿࠋ

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