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中國醫藥大學機構典藏 China Medical University Repository, Taiwan:Item 310903500/25715

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  ! "Parathyroid hormone restores bone mass for osteopenia in the

spontaneously hypertensive rat #$NSC87-2314-B-039-017 %&'(86/08/01~87/07/31 )*+,-. %&/0123456789:58;<= E-mail[email protected] > ? 19 @A

(spontaneously hypertensive rat, SHR)BCD /EFGHI 4 JBK-LMNOPQR HSTUHVWX 0Y4Y8 Z 16 [\/100g  + ]  (human parathyroid hormone, hPTH1-34)B^_ 14 -BL`a XbcdefghiB21 @jkl hPTH  SHRBmnopq

Xrstu Wistar Kyoto (WKY rat) vwxByg0z{rIq|f}~q €‚ƒ„…€†‡ˆ‰Š ‹BŒ€Žj‘bf’ hPTH  JB“mnopqX1 €‚‡Š‹Bs~”•–1 “—9˜€™šŠ‹def› ˜œ™šžHŸ1 •–¡Š ‹B¢’ 16 [\ hPTH  J£xB Œ¤J¥j¦§¨©fªz«B hPTH¬Š‹€­®¯°B œ±²j¦§Š‹B³´XŠ‹ µhfˆ¶MNOP hPTH ·Š‹ X/¸B޹º»¼½fŒ¾J¿e À7ÁÂÃiBhPTH ˜J¿ Ä­Å®ÆÇ±²B)ÈÉÊc…Ë ̔•–ÍΐÏf    Abstract

Daily subcutaneous injection of graded doses of 0, 4, 8, or 16Ðg / 100g hPTH 1-34 of 19-week-old male spontaneously hyperten- sive rat (SHR) of five rats in each group for 14 days were done. The 21-week-old SHR exhibited a significant lower metaphyseal trabecular bone volume osteopenia accompanied by poor trabecular architecture than in Wistar-Kyoto (WKY) rats were observed in the study. The preservation of trabecular bone volume in the PTH-treated rats was associated with an increase in number of osteoblasts, bone surface extent of osteoblasts, double labelled bone surface, mineral apposition rate and trabecular thickness. Trabecular number remained comparable to control. Measurements of resorption such as percent eroded surface and numbers of osteoclasts also remained comparable to control values. These dual effects increase the bone formation rate and in the absence of significant resorption, result in a net increase in bone mass. The above findings of histomorphometric data support the hypothesis that the PTH increase bone mass by specific effects on osteoblast activation and function.

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Key word: Parathyroid hormone, osteo-porosis, spontaneous hypertensive rat, osteopenia, bone cell.

ÑY !" ? ÒÓ4’ÔÕ+Ö×ØÙ 1990 ڛ 2036ÚuˆB+Ö˜ 65 ÛŸ°¬× 6%Š› 20.5%Bܾ 123 ݊› 517 Ý(1)f Þ}B˜ßqà1áâQš !…ã Bäåæ»çèf ßqà(osteoporosis)å>éêë    ì í î B ¾ ˜  X ƒ „ (osteopenia)Bçï­á (2)f1993 Ú ,-.ðñBòØÙ 2020 Ú ó4’Ô ÕôõöÚ+ÖÞßqà÷”® áø²BKÚùúøûÔü 1600 ýÙ (3)f¾Lz«Bßqàþ »·f          (spontaneously hypertensive rat, SHR)…

(Wistar-Kyoto WKY, rat)å ¾ Wistar   ÷®fSHR ˜ 4 @t ¬ ŒB÷ WKY ¥}> ifÞ}BWKY ·˜®I SHR¤J(5)f +] (hPTH)¬Š‹ XB‚¬Š‹(6)fÞ}B !’`aßqà  R…hPTHSHRJ¿!"def #Y#$ %& $>%YÉ&'ubc ? SHR 1 WKY ’ 5 @¹B ? ()¦§¨©f*+D,Út ? Š‹B{-,zfWKY  ? ’ 10 @L B(.*>/B ? »01SHR u¥»2Š ? f20 @L BSHR .*’ ? 9'f’ 10-25 @:»s@t; ? SHR ¦§Ÿst WKY ? vwf hPTH  14 - ?  SHR (Éj  SHR JŸrB)¦§¨©f ? WKY u&'B§,˜st ? ; SHR &'f hPTH   ? SHR &'B{rj  SHR J ? vwf $Ñ%Y­cÁH< IY=…>?@A‚bc W K Y     = ? @ A ‚ r SHRByBC7z¨©f hPTH  : SHR J=?@ A‚Éj  SHR ŸrBD) ¦§¨©fWKY > ?@A‚É SHR ŸrBD)¦§ bcf  : SHR J>?@ A‚¦§˜j  SHR Jf IIYE>FGA‚bc WKY ¼E>FG É SHR HŸrB)¦§bcf  : SHR JE>FG A‚˜ WKY J…j  SHRJf¢I’ 8 Z 16 [\ hPTH  JBBC7zJKf I I IYL M…NFOA‚bc W K Y   L MA‚É SHR ŸrBDj¦§bcf  : SHR JL MA‚¦ §˜ WKY J…j  SHR Jf¢:JˆBNFOA‚Dj ¦§¨©f (# ) Y k P  § [ Q PR!SuH< SHR É WKY qX ŸrB¦§ƒ„if HV

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qXÉj  SHR JŸrB ‡¦§Š‹deByD  WXŠ‹B÷ŠâTUf (V)Ymnop­WX:Ábc IY ­WX‚WKY …:  SHR J§,˜j   SHR Jf IIY­WXY•–Z‰‚WKY …: SHRJ¦§ ˜j  SHR Jf IIIYŠ •–WKY … :  SHR J¦§â˜j  SHR Jf IVY[\­W¯°WKY  …: SHRJ¦§˜j  SHR Jf (])Ymnop•–:Ábc IY23W‚”•–WKY  …: SHRJ¦§â˜ j  SHR Jf IIY 23W‚ •–WKY  ¦§â˜ SHRfL 4 Z 8 [ \ hPTH  SHR JB¦§ ˜j  SHR JfŒ’ 16 [ \ JÉj  SHR JŸ rB¥)¦§¨©f IIIY •–1”•–uŸ SHR ¦§˜ WKY fj  SHR JB{˜ hPTH : SHR Jf IVY  •–†‡^_WKY  ¦§˜ SHRfL 4 Z 8 [ \ hPTH  SHR JB¦§ ˜j  SHR JfŒ’ 16 \  SHR JÉj  SHR JŸrB¥)C7z¨©f VY  •–œ™šWKY  ¦§˜ SHRfL 4 Z 8 [ \ hPTH  SHR J¦§ ˜j  SHR JfŒ’ 16 [ \  SHR JÉj  SHR JŸrB¥)C7z¨©f $`%YmnopaÀÁbc IY žHŸWKY ¦§ SHRfL hPTH : SHR J ‡¦§˜j  SHR JBy DWXŠ‹÷Š‹TUf IIY €†‡‚WKY ¦ §˜ SHRfL hPTH : SHR J‡¦§˜j  SHR Jf“L 16 [\ hPTH J €†‡‚Š‹Ibâf IIIY€†‡Ž:JˆcjB C7z¨©f IVY €†‡ˆ‰WKY  ¦§x˜ SHRfL hPTH : SHRJ‡x˜¤JByDWX Š‹B÷ƒ„TUf (d)YmnopÀÁbc qefg¯°Y™š hijkB™šhijkžHŸ1 €­®¯°B’ WKY ¦§ ˜ SHRf÷L hPTH : SHR JB‡¦§˜j  SHR JB yDWXŠ‹B÷Š‹if VY%& ? SHR’ 21 @¼B=?@1>? @A‚rst WKY ¤Jxf}g hÉ Bindels l’ 1987 Úmngh os(7)fTU hPTH  B>? @A‚Š‹f}p·ÎÉqŠ‹>? @œZŠ‹rs>?@'œ ±²(8)Ïf E>FGA‚B·t±”

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•–ÍÎuj(marker)f“A‚D,” •–Ž…ÊŠ‹÷Š‹By ÉHc®”•–Ï(9)f hPTH v   SHR JB¼E>FG¦§ Š‹BI”•–Ž…ÊŠ‹ ðw>xyzf ¼L M…NFOA‚Æ™rÍ ÎujB’Ÿr SHR É WKY {JˆD )¦§bcf}ghÉ McCarron l+ ios(10)fL å&|}~FB …r€M±²B“uj·‚ñ ƒ…rƒÍÎ(11)fÞ}B hPTH  B¼L MA‚÷NF D)„SbcB·ÎåÍΩZå &|…ÆÇ±²†‡³f SHR ’mnoˆGpq XB¦§iB÷ ‰ hPTH v 14 - B“Xܐ¦§Š‹± ²f“ghÉ˜Š‹Œ ” ®X(12)…ßqàH(13) l hPTH  B‡¬Š‹q Xghå>³f SHR   ­ ® Î Ž (bone-forming activity)Ÿ WKY ¤JxB}ghÉ, -.l(14) 26 @ SHR mJ¿ o‘if hPTH v 14 -  SHRJB“­®ÎŽcŸjkl hPTH v SHR JvwByDWXŠ‹ TUf}p’¦ hPTH ¬Ë Ì9”•–(osteo-progenitor cells) Š …Hc±²(15)f hPTH v B“ •–o ÏÁB‡Ÿjkl hPTH v SHR J1Œ’ SHR+16Ðg hPTH JÉj  SHR J)¦§¨©f¾}«B »sWX hPTH  •–¬Ä­» s±²By’rxWX(SHR+4 or 8Ðg Š‹ •–ÍÎB÷’rWX (SHR+16Ðg hPTH )~B¬“k”•  •–ÍÎf hPTH v  SHR JB“ €aÀÁbcghÉGunnessl(16) –² hPTH v Š‹Œ gho—fhPTH ¬´€†‡‚Š ‹…g0˜™rš›B*åLfg QRŠ‹qXBs~{¬´ W   ­  œ Ž (biomechanical competence)Š‹f hPTH v SHR JB€e fg¯°¦§˜jkl hPTH  SHR Jf}ghɊ‹Œ  B hPTH B·Lie fg¯°Š‹i(12)o—f}p’ ¦ hPTH ž­®±²f '()*$+ , ž&~B×vB:x ÁuXŸ±BòCH< ¡ –BL³gh ¢£f !®h¤B 7¥Á¦§(B·ÉL™˜ Y|H¨…©J¿loÏ57ª« zf '-./ 1.ÒÓ4ÔÕôõÓ479 ڛ 80 Ú+ Ö¬­B&®8 ¯:°±¬+Ž ²³v#´B1992f

2.Consensus Development Conference: Diagnosis, prophylaxis, and treatment of osteoporosis. Am. J. Med. 94: 646- 650,1993.

3.Wang, T.M. : Report of 4th International Convention of Osteoporosis. Science Development, Monthyl, NSC, ROC

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4.Okamoto K and Aoki K: Development of a strain of spontaneously hypertensive rats. Jpn. Circ. J. 27:282-293, 1963. 5.Yamori Y.: Handbook of Hypertension :

Experimental and Genetic Models of Hypertension. Elsevier Science Publishers BV, 1984.

6.Moseki L, Sogaard CH, Danielsen CC, Torring O and Nilsson MHL: The anabolic effects of hPTH on rat vertebral body mass are also reflected in the quality of bone, assessed by biomechanical testing : a comparison study between hPTH-(1-34) and -(1-84). Endocrinology 129:421-428, 1991. 7.Bindels RJM, Brock LAM, Jongen MJM,

Hackeng WHL and Lowik WJM: Increased plasma calcitonin levels in young spontaneously hypertensive rats: Role in disturbed phosphate homeostasis. Pflugers Arch. 408: 395-400, 1987. 8.Bindels RJM, Geertsen JA and Os CH:

Increased transport of inorganic phos-phate in renal brush broders of spontaneously hypertensive rats. Am.J. physiol. 250: F470-F475, 1986.

9.Hanazawa S, Ohmori Y, Amano S, Hirose K, and Kitano S: Human purified interleukin-1 inhibits DNA synthesis and cell growth of osteoblastic cell line, but enhance alkaline phosphatase activity in the cells, FEBS Letters 203: 279-284, 1986.

10.McCarron D, Yung NN, Ugoretz BA and Krutzik S: Disturbances of calcium m e t a b o l i s m i n the spontaneously hypertensive rat : Attenuation of hyper- tension by calcium supplementation.

Hypertension 43: 1162-1167, 1981. 11.Stern N, Lee DBN, Silis V, Beck FWJ, Deftos L and Sowers JR : Effects of high calcium intake on blood pressure and calcium intake on blood pressure and calcium metabolism metabolism in

young SHR. Hypertension 6: 639-646, 1984.

12.Gasser JA and Jerome CP: Parathyroid hormone : a cure for osteoporosis? Triangle 31: 111-121, 1992.

13.Reeve J, Williams D, Hesp R, Hulme P, Kleneman L, Zanelli JM and Parsons

JA : Anabolic effect of low doses of a fragment of human parathyroid hormone on the skeleton in postmenopausal osteoporosis. Lancet 1:1035-1038, 1976.

14.Wang TM, Hsu JF, Jee WSS and Matthews JL : Evidence for reduced c a n c e l l o u s b o n e m a s s i n t h e spontaneously hypertensive rat. Bone

Miner. 20:251-264, 1993.

15.Owen M: Cellular dynamics of bone. In: Bourne GH (ed) The biochemistry and physiology of bone, 2nd ed., Vol.3. Academic Press, New York, 1971, pp. 271-298.

16.Gunness M and Hock JM: Anabolic effect of parathyroid hormone on cancellous and cortical bone histology.

Bone 14: 277-281, 1993.

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