研究背景：骨關節炎的藥物治療主要分為「緩解症狀的藥物」與「改變病程的藥物(DMOAD)」。雖然現階段已開發出許多DMOAD，但因證據仍不充足，所以尚無藥物確定可以改變骨關節炎的病程。而目前已有數個體外試驗與動物實驗顯示，teriparatide可促進軟骨基質的合成、減少軟骨細胞的凋亡，因此可能具有改變骨關節炎病程發展的潛力 ─ 由於至今尚未有臨床研究探討teriparatide對骨關節炎的療效，所以本研究希望藉由回溯性病例回顧，評估膝關節或髖關節骨關節炎患者在使用teriparatide前後其關節空隙變化速率和NSAIDs暴露時間的變化程度。
研究方法：本研究屬於回溯性病例回顧。分析2006年1月1日至2011年1月31日間有、無使用teriparatide的膝關節或髖關節骨關節炎病患，比較兩組的關節空隙變化速率的差異﹝主要結果變項﹞；另外分析有使用teriparatide的膝關節或髖關節骨關節炎患者其NSAIDs暴露時間在teriparatide使用前、後一年內的差異﹝次要結果變項﹞。
結果：本研究收入有、無使用teriparatide的膝關節或髖關節骨關節炎病患各27位。在膝關節骨關節炎病患中，有使用teriparatide者其膝關節內側腔室的關節空隙變化速率為+1.77 mm/yr / +1.80 mm/yr﹝若某病患收入兩側關節，則進行統計分析時單取一側，以「/」作為分隔表示「單取右側之數值/單取左側之數值」﹞，而沒有使用teriparatide者則為–0.17 mm/yr / +0.11 mm/yr ─ 顯示有使用者其關節空隙變化速率增加的幅度比無使用者高，但兩組之間無達到顯著的差異﹝p = 0.33 / 0.41﹞；在髖關節骨關節炎病患中，有使用teriparatide者其髖關節空隙變化速率為+0.38 mm/yr / +0.38 mm/yr，而沒有使用teriparatide者則
為+0.22 mm/yr / –0.13 mm/yr ─ 顯示有使用者其關節空隙變化速率增加的幅度比無使用者高，但兩組之間無達到顯著的差異﹝p = 0.77 / 0.22﹞。而在次要結果分析中，有使用teriparatide的27位膝關節與髖關節骨關節炎病患裡，各有8位與10位的膝關節與髖關節骨關節炎患者於開始使用teriparatide前一年內曾領用過NSAIDs，而後一年內則各有5位與3位。且在開始使用teriparatide的前一年內，NSAIDs的暴露時間於膝關節與髖關節骨關節炎患者各為6.5與3.7個月，而後一年內則各為1.8與0.2個月，但膝關節與髖關節骨關節炎患者其前後一年內的NSAIDs暴露時間無達到顯著的差異﹝p = 0.21與0.11﹞。
結論：本研究沒有觀察到teriparatide對膝關節或髖關節骨關節炎具有改變關節空隙變化速率的療效，且本研究中作為對照組的OA Non-user其關節空隙變化速率和其他研究的數據有所出入，可能會對teriparatide對骨關節炎療效的評估造成影響。另外，在次要結果分析中，本研究無觀察到teriparatide使用前、後NSAIDs的暴露時間有顯著地減少，雖然領用NSAIDs的人數與NSAIDs的暴露時間在teriparatide使用之後皆有降低的趨勢。因此teriparatide對膝關節或髖關節骨關節炎究竟是否具有改變結構型態或改善疼痛症狀的療效，需其他研究作進一步的探討。

Background: Management of osteoarthritis (OA) requires a comprehensive therapy consists of pharmacological and non-pharmacological elements to relieve pain and to maintain joint mobility. Many attempts have been made to find treatments that can alter the course of OA. But only a few disease-modifying osteoarthritis drugs (DMOADs) have been recognised by clinical trials to potentially influence the course of OA beneficially. Teriparatide has been shown to modify the chondrocyte apoptosis process, and to increase the synthesis of the cartilage matrix. The aim of current study was to assess the effect of teriparatide on joint space narrowing and the effect on reducing consumption period of NSAIDs in patients with knee and hip OA.
Methods: The current study was a retrospective case review. Patients who had knee or hip OA and ever received teriparatide ≥ 1 times from 2006.1.1 to 2011.1.31 were included (set as Knee or Hip OA Forteo user). And age-, sex-, region of OA- matched patients who had knee or hip OA but never received teriparatide were included as controls (set as Knee or Hip OA Non-user).
Primary outome was the difference of joint space narrowing rate between OA Forteo user and OA Non-user. Secondary outcome was the difference of consumption period of NSAIDs one year before and after receiving teriparatide in OA Forteo user.
Results: Primary outcome: Twenty seven OA Forteo users and 27 OA Non-users were included. The joint space narrowing rate in the medial compartments of the knee was +1.77 mm/yr / +1.80 mm/yr in Knee OA Forteo users and –0.17 mm/yr / +0.11 mm/yr in Knee OA Non-users (If the patietnt had both right and left joints included, we took only one joint per statistics calculation. The “/” was used to separate the data of right joint and left joint). Although there was no significant difference (p = 0.33 / 0.41), but the increase of joint spaces was wider in Knee OA Forteo users than that in Knee OA Non-users. The joint space narrowing rate of the hip was +0.38 mm/yr / +0.38 mm/yr in Hip OA Forteo users and +0.22 mm/yr / –0.13 mm/yr in Hip OA Non-users. Although there was no significant difference (p = 0.77 / 0.22), but the increase of joint spaces was wider in Hip OA Forteo users than that in Hip OA Non-users. Secondary outcome: There were 8 Knee OA Forteo users and 10 Hip OA Forteo users took NSAIDs one year before receiving teriparatide, and the number decreased to 5 and 3 one year after receiving teriparatide. The consumption period of NSAIDs was 6.5 months in Knee OA Forteo users and 3.7 months in Hip OA Forteo users one year before receiving teriparatide, and then the period decreased to 1.8 and 0.2 months one year after receiving teriparatide. But there was no significant difference between the consumption period before and after receiving teriparatide (p = 0.21 and 0.11).
Conclusion: The slowing or reversing in joint space narrowing was not observed in current sutdy, and there was a discrepancy in the joint space narrowing rate of OA Non-user between current study and other studies. The effect of teriparatide on reducing consumption period of NSAIDs was also not observed. Further studies with more patients are needed. New clinical trials are also necessary.

第一部：以關節空隙變化速率評估Teriparatide於膝關節或髖關節骨關節炎病患之療效
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第二部：骨質疏鬆患者對Teriparatide治療的順從性
1. De Bari C, Kurth TB, Augello A. Mesenchymal stem cells from development to postnatal joint homeostasis, aging, and disease. Birth Defects Research Part C: Embryo Today: Reviews. 2010;90(4):257-271.
2. Felson DT. Chapter 326. Osteoarthritis. In: Anthony S. Fauci EB, Dennis L. Kasper, Stephen L. Hauser, Dan L. Longo, J. Larry Jameson, and Joseph Loscalzo, ed. Harrison's Principles of Internal Medicine, 17e: http://www.accessmedicine.com/content.aspx?aID=2897738. New York McGraw-Hill; 2008.
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