PTH PTH PTH D PTH PTH PTH CHIN J OSTEOPOROSIS & BONE MINER RES Vol. 5 No. 2 June

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1 151 DOI /j. issn * PTH rhpth PTH rhpth R681 A The progression of PTH supplements on osteoporosis LIU Ming PAN Wei CHEN De-cai * Department of Endocrinology West China Hospital Sichuan University Chengdu China Abstract Parathyroid hormone PTH and recombinant human parathyroid hormone rhpth as bone formation a- gents are receiving increasing attention. This review is mean to illustrate its basic research animal experiment and clinical observation briefly. Key words osteoporosis parathyroid hormone bone formation agents PTH PTH PTH D PTH 10 ~ 50 ng /L PTH camp PTH PTH PTH * cdecai@ yahoo. com. cn

2 152 OH 2 -Vit D OH 2 -Vit D 3 Ca 2 + OB PTH OB OC PTH 1ɑ- OB PTH 25-OH-VitD Ⅰ IGF-Ⅰ PTH B G TGF-β Pfalschifter 2 PTH 2 PTH 1 PTH 2 OB TGF-β TGF-β 6 PTH 1 PTH IL-6 Gs AC ATP- PG Mg 2 + camp A PTH OC PTH OB PKA PTH 1 Gq OC 3 - C PKC DG IP 3 C 4 PKC Ca 2 + PTH 2 camp PTH PTH PTH PTH PTH 1-34 PTH 1-84 PTH 1-84 PTH hpth 2-34 hpth hpth 1-34 N Ser1 Val2 anabolic window 6 1 < 24 PTH PTH hrpth1-84 preotact hrpth1-34 teriparatide 1 Preotact PTH OC β Prank 1 PTH PTH 2 PTH PTH 1 PTH Fig 1 The effects of PTH on bone formation and bone resorption

3 153 PTH 100 μg /d Teriparatide PTH 18 ~ 24 Preotact PTH PTHR1 55% 90 min FDA 20 μg /d Teriparatide FDA % 75 min Table 1 1 hrpth 1-84 hrpth 1-34 The relative comparison between hrpth 1-84 and hrpth 1-34 min % min μg /d hrpth 1-84 preotact % hrpth 1-34 teriparatide % ~ 30% 1935 PTH 25% 70% ~ 80% PTH > 70% β Reeve 7 PTH 1-34 PTH PTH PTH Wistar % 0. 2 ml / PTHrP 1 ~ μg /d PTHrP 1 ~ μg /d PTHrP 1 ~ μg /d Sato PTH 1-34 BMD 18 X PTHrP ± g /cm 2 PTHrP μg PTH ± g /cm 2 P < BMD 9% BMD 3% BMD PTHrP 20 BMD 40 μg PTH BMD ± g /cm % PTH /d 15 20% ~ 1-34 BMD 13% ± g /cm 2 BMD 6% BMD BMD Lindsay 12 Moselilde μg PTH

4 154 13% PTH1-34 n = 14 PTH % 1% PTH n = GIOP BMD % 7. 9 % BMD P < BMD 5% ~ 10% PTH Neer PTH n = 17 n = PTH % PTH % 20 μg /d 5% 2. 7% 8. 0% BMD 65% PTH μg /d Black ~ 85 4% 3 1 PTH 69% 6% μg /d 2 PTH 1-84 PTH 3% 100 μg /d Alendronate 10 mg /d 3 Alendronate 10 mg /d 500 mg /d Vit D U /d % Ⅰ 16 rhpth BMD 4. 9% 2 1 BMD 1. 7% rhpth 2 3 Alendronate 10 mg /d 1 1 ~ 4 μg /kg BMD 4. 6% 5 μg /kg 6 4 PTH 3 μg /kg d 7 d 8 1 PTH 4 μg /kg d 7 d rhpth Paget's rhpth 2 BMD Lindsay 12 > % 4. 6% Alendronate 10 mg /d 1 rhpth rhpth T T < rhpth - 3 Paget's rhpth rhpth Hodsman ~ 24 20

5 155 Cosman 21 PTH Johannes PD Elisabeth Z Eleftherios P et al. Treatment 5 PTH1-34 of osteoporosis with parathyroid hormone and teriparatide μg /d 20 μg /d PTH Rubin MR Bilezikian JP. New anabolic therapies inosteoporosis J. Curr Opin Rheumatol P < PTH μg /d 7 Reeve J Meunier PJ Parsons JA et al. The anabolic 20 μg /d P < effect of human parathyroid hormone fragment hpth 1-34 on trabecular bone volume in involutional osteoporosis report of a multiple centre trial J. Br Med P < J PTH 9 Mosekilde L Sogaard CH McLsker JE et al. PTH has PTH more pronounced effect on vertebral bone mass and biomechanical competence than antiresorptive agents esteogen 18 ~ 24 and bisphosphonate vassessed in sexually mature ovariectomized rats J. Bone PTH 10 Hayashi K Yamaguchi T Yano S et al. BMP /Wnt antagonists are upregulated by dexamethasone in osteoblasts and reversed by alendronate and PTH potential therapeutic targets for glucocorticoid-induced osteoporosis J. PTH BBRC Sato M Westmore M Yanfei L Ma et al. Teriparatide PTH 1-34 strengthens the proximal femur of ovariectomized nonhuman primates despite increasing porosity 1 Prank K Noelan SJ Hanns HM et al. Tine series prdiction of plasma hormone concentrayion J. Clinical mvest Pfeilschifter J Mundy GR. Modulation of type beta transforming growth factor activity in bone cultures by osteotropic hormones J. Proc Natl Acad Sci USA Hock JM Centrella M Canalis E. Insulin2like growth factor2i IGF2I has independent effects on bone matrix formation and cellreplication J. Endocrinology Rosen D Miller SC Deleon E et al. Systemic administra- PTH tion of re 2 combinant transforming growth factor beta 2 rhpth rtgf2β2 stimulatesparameters of cancellous bone formation in juvenile and adult rats J. Bone J. Calcif Tissue Int J. J. JBMR Lindsay R Nieves J Formica C et al. Randomised con2 trolled study of effect of parathyroid hormone on vertebral2 bone mass and fracture incidence among postmenopausalwomen on estrogen with osteoporosis J. Lancet Orwoll ES Scheele WH Adami S et al. The effect of teriparatide human parathyroid hormone 1-34 therapy on bone density in men with osteoporosis J. Bone Miner Res Lane NE Sanchez S Modin GW et al. Parathyroid hormone treatment can reverse corticosteroid-inducedosteoporosis. Results of a randomised controlled clinical trial J. ClinInvest

6 Neer RM Arnaud CD Zanchetta JR et al. Effect of parathyroid hormone 1-34 on fractures andbone mineral density in post-menopausal women with osteoporosis J. N Engl J Med Debiais F. Efficacy data on teriparatide parathyroid hormone in patients with postmenopausal osteoporosis J. Joint Bone Spine Lane NE Kimmel DB Magnus HL et al. Bone-selective analogs of human PTH 1-34 increase bone formation in an ovariectomized rat model J. Bone Miner Res Hodsman AB Fraher LJ Watson PH et al. A randomized controlled trial to compare the efficacy of cyclical parathyroid hormone versus cyclical parathyroidhormon and sequential calcitonin to improve bone mass inpostmenopausal women with osteoporosis J. Clin Endocrinol Metab Black DM Greenspan SL Ensrud KE et al. The effects of parathyroid hormone and alendronate aloneor in combination in postmenopausal osteoporosis. J N Engl J Med Cosman F Greenspan S. Parathyroid Hormone Treatment for Osteoporosis J /OL http / /onlinelibrary. wiley. com / doi / / ch51 / summary 21 Cosman F Lane NE Bolognese MA et al. Effect of transdermal teriparatide administration on bone mineral density in postmenopausal women J. JCEM

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