Korean J Fam Pract. 2013;3:25-32 기타골다공증치료제의효과와문제점 Symposium 박주성 * 동아대학교의과대학가정의학교실 Anti-Osteoporotic Effect, Extra-Skeletal Benefits and Risks of Other Agents Joosung Park* Department of Family Medicine, Dong-A University College of Medicine, Busan, Korea Selective estrogen receptor modulators have an agonistic and antagonistic effect on estrogen receptors and reduce the risk of vertebral fracture and invasive breast cancer. Estrogen with or without progestin reduces the risk of vertebral, nonvertebral and hip fracture, and colorectal cancer. Tibolone is a synthetic steroid with estrogenic properties, and it reduces the risk of vertebral and non-vertebral fracture and postmenopausal symptoms. Isoflavone derivative ipriflavone does not reduce fracture risk. Intranasal calcitonin reduces the risk of vertebral fracture and pain in acute vertebral fracture. The purely anabolic teriparatide is available for extremely severe osteoporotic patients and for those who do not respond to other types of therapy. It reduces the risk of vertebral and non-vertebral fracture, and is effective in the treatment of glucocorticoid induced osteoporosis. Strontium ranelate reduces the risk of vertebral and non-vertebral fracture, and may be effective for the management of osteoarthritis. The fully human monoclonal antibody denosumab neutralizes the receptor activator of nuclear factor kappa B ligand, and reduces the risk of vertebral, non-vertebral and hip fracture. These agents have variable extra-skeletal side effects. Keywords: Osteoporosis; Contraindications; Selective Estrogen Receptor Modulators; Estrogens; Tibolone; Calcitonin; Teriparatide; Denosumab; Strontium Ranelate 서론 우리나라에서는남성및여성모두에서골다공증치료의 1차선택약제가 bisphosphonate 제재이다. 장기간의투약이나부작용때문에 bisphosphonate 제재를사용할수없는경우, 혹은특정적응증이있는다른약제가있는경우에는다른약제를선택해야한다. Denosumab은폐경후골다공증여성의골다공증 1차치료제및 androgen depravation 치료를받고있는전립선암환자의골다공증치료제로일부나라에서 Received: February 4, 2013, Accepted: March 8, 2013 *Corresponding Author: Joosung Park Tel: 051-240-2870, Fax: 051-255-8282 E-mail: jspark@dau.ac.kr 승인을받았다. 여기에서는골다공증의치료제중선택적에스트로겐수용체조절제, 에스트로겐, 부갑상선호르몬유사체인 teriparatide, calcitonin, 국민건강보험공단에서아직승인하지않은 strontium ranelate와 denosumab, 그리고 tibolone 및 ipriflavone의효과및부작용에대해서알아보고자한다. 선택적에스트로겐수용체조절제 선택적에스트로겐수용체조절제 (selective estrogen receptor modulators) 는비스테로이드성물질로서에스트로겐수용체에결합하여각각의조직에따라에스트로겐작용제역할도하고길항제역할도한다. 2차혹은 3차치료제로사용하도록권장된다. 1) 골밀도를증가시키지는못하나척추골절을예방하는효과는있다는것을미리환자에게알리는것이좋다. Korean Journal of Family Practice Copyright 2013 by The Korean Academy of Family Medicine 가정의학 Vol. 3, No. 1 Mar 2013 25
Joosung Park: Anti-Osteoporotic Effect, Extra-Skeletal Benefits and Risks of Other Agents 1. 효과폐경후골다공증의예방및치료에가장널리사용되는선택적에스트로겐수용체조절제는 raloxifene이다. 하루 60 mg의 raloxifene은골약화증및골다공증을가진폐경후여성의골소실 2) 을줄여주고, 척추골절위험을감소시킨다. 3) 1. 효과에스트로겐은척추골절및골반골절을포함한비척추골절을감소시킨다. 14,15) 투여를중단하면폐경때와같은속도로골감소가일어난다. 논란은있지만골절방지효과는수년간지속할수있다. 16,17) 2. 기타효과 Raloxifene은침습성유방암위험을약 60% 정도감소시키며, 4,5) 사망위험을 10% 줄인다. 6) 또총콜레스테롤및저밀도콜레스테롤을감소시킨다. 7) 2. 기타효과갱년기증상을완화시키고대장직장암의위험을감소시킨다. 18) 폐경증상을호소하는여성에게되도록적은용량으로단기간사용하도록대부분의나라에서권장하고있다. 3. 부작용 1) 안면홍조및하지통증일부연구에서는안면홍조빈도가증가하지않았으나, 8,9) 다른연구들에서는안면홍조빈도가증가하였고, 하지통증빈도도증가하였다. 4) 2) 정맥혈전색전증 Raloxifene은발생빈도는드물지만, 정맥혈전색전증위험을 54%, 폐동맥색전증위험을 91% 증가시켰다. 10) 3) 관상동맥질환, 뇌졸중심혈관질환위험이높은폐경후여성에서 raloxifene 복용군은심혈관질환으로인한사망, 그리고관상동맥질환및뇌졸중빈도에서는차이가없었으나, 치명적인뇌졸중빈도가대조군보다높았으며 (0.22% vs. 0.15%), 현재흡연자에서뇌졸중위험이높았다. 11) 반면에 lasofoxifene은관상동맥질환발생위험은감소시켰으나, 관상동맥질환으로인한사망이나심근경색위험을감소시키지못했고, 12) 뇌졸중위험은줄였다. 13) 에스트로겐 에스트로겐은폐경에의해가속화되는뼈교체율을감소시키고, 나이와치료기간에관계없이모든뼈의소실을예방한다. 미국식품의약품안전청에서는다른골다공증치료제를사용할수없는폐경여성중골다공증위험이높은경우에만골다공증예방약제로사용할수있도록승인하였다. 1) 자궁이있는여성에서는자궁내막의증식및암의위험을증가시킬수있으므로프로제스테론을추가하여야한다. 3. 부작용 Women s Health Initiative 연구 18-21) 에따르면 conjugated estrogen과 medroxyprogesteronacetate를사용했을때혈전색전증, 관상동맥질환, 뇌졸중, 유방암, 그리고치매위험이증가했다. 그러나전체적으로이익에비해서위험이증가하지는않았다. 자궁이없어서에스트로겐만투여한경우뇌졸중위험은증가했지만, 관상동맥질환및유방암위험은증가하지않았다. 22) 그러나최근의한연구 23) 는에스트로겐의긍정적인효과를보고하고있는데, 폐경직후의여성에게호르몬대체요법을 11년간실시했더니사망혹은심부전이나심근경색으로인한입원위험은감소했고, 유방암혹은유방암으로인한사망, 그리고심부정맥혈전색전증위험은증가하지않았다. 또투약중단후 5년간추적했을때도사망, 혹은심부전이나심근경색으로인한입원위험이낮았고, 유방암혹은유방암으로인한사망, 그리고심부정맥혈전색전증위험은증가하지않았다. 부갑상선호르몬유사체 (Teriparatide) 재조합형사람부갑상선호르몬펩타이드이며, 골다공증치료제로승인을받은유일한골형성촉진제로여성과남성모두에게사용할수있다. 부갑상선호르몬이지속적으로높으면뼈를약화시키지만, 간헐적으로투여하면 ( 예 : 하루 1회의피하주사 ) 골아세포의수및활성도를증가시키고골량을증가시키고, 뼈의구조를향상시킨다. 24) 골절의위험이아주높은사람및 bisphosphonate 등의다른치료에실패한사람에게권장되고, 부신피질호르몬사용으로인한골다공증및남성골다공증치료제로승인을받았으며, 2년이상사용하지않도록한다. 1) 26 Vol. 3, No. 1 Mar 2013 Korean J Fam Pract
박주성 : 기타골다공증치료제의효과와문제점 1. 효과 Teriparatide 20 μg을매일주사하면척추골절및비척추골절위험이감소하며, 25) 투약을중지해도 30개월까지효과가지속된다. 26) 사용중지후골소실이빠르게일어나므로중지후알렌드로네이트를사용하면이러한골소실을막을수있고, 일부에서는골밀도가더증가하기도한다. 27) 2. 부작용 1. 효과하루에 200 IU을투여했을때척추의골밀도가약간증가하고, 새로운척추골절위험이감소하였다. 30) 여성과남성모두에게사용가능하다. 31) 2. 기타효과 Calcitonin은급성척추골절로인한통증치료에효과가있다. 32) 1) 흔한부작용가장흔한부작용은구역, 두통, 어지럼증, 하지통증이다. 어지럼증및하지통증빈도가의의있게증가하며, 주사후첫수시간이내에나타난다. 주사부위에피부자극및홍반이나타날수있다. 28) 2) 혈청칼슘농도증가정상칼슘혈증인사람에서혈청칼슘농도가일시적으로약간증가한다. 4 6시간사이에최고조에달하고 16 24시간에원래대로돌아간다. 이러한변화는작기때문에, 치료전검사에서혈청칼슘, 부갑상선호르몬, 25(OH)-비타민 D검사에서정상인사람은혈청칼슘치를검사할필요는없다. 29) 그러나소변을통한칼슘배출을증가시킬가능성이있어서현재의혹은최근의요로결석환자에게는주의해서사용해야한다. 비정상적으로골교체가증가한경우및심한신기능장애가있으면사용할수없다. 29) 3) 요산증가약 3% 의환자에서경미한요산치증가가나타나므로통풍환자에게는주의해서사용해야한다. 28) 3. 부작용비강분무시비염, 비점막자극, 비출혈등이생길수있다. 주사했을때는구역, 주사부위에국소염증반응, 홍조및발한등의혈관운동성증상이나타날수있다. 31) Strontium Ranelate Strontium ranelate는스트론튬원자 2개에 ranelic acid가결합된것이다. 골흡수를감소시키고골형성을증가시킨다. 33) 스트론튬은 2 g을경구로섭취한다. 음식이나유제품에의해섭취가감소하기때문에식사중간에섭취해야한다. 이상적으로는식사후 2시간이지난후자기전에먹는것이가장좋다. 심한신기능장애환자에게는권장되지않는다 (creatinine clearance<30 ml/ 분 ). 31) 남성에게도사용할수있다. 34) 1. 효과 Strontium ranelate는골약화증과다양한골다공증환자의척추및비척추골절을비스포스포네이트제재만큼감소시킨다. 35,36) 그리고 10년을써도골밀도증가는계속되며, 척추골절과비척추골절의빈도는위약군보다유의하게낮다. 37) 4) 체위성저혈압아주소수의환자에서일시적인체위성저혈압이발생했다는보고가있지만, 이것은수분이내에사라지기때문에투약을중단할필요는없다. 29) Calcitonin Calcitonin은파골세포에있는 calcitonin 수용체에결합하여파골세포의활성을감소시킨다. 재조합형혹은합성칼시토닌중에서가장널리쓰이는것은비강으로분무하는 salmon calcitonin으로하루 1회 (200 IU) 비강에분무한다. 다른약제를사용할수없는경우에최후의치료제로사용하도록권장한다. 1) 2. 기타효과연골형성을증가시키며, 3년간사용시골관절염점수가감소하고, 추간판간격및요통도감소하는효과가있었다. 38) 3. 부작용 1) 흔한부작용가장흔한부작용은구역과설사이다. 대개치료시작시에호소하며세달정도계속해서복용하면대부분없어진다. 31) 2) 정맥혈전색전증정맥혈전색전증위험이약간증가한다는보고 39) 가있지 가정의학 Vol. 3, No. 1 Mar 2013 27
Joosung Park: Anti-Osteoporotic Effect, Extra-Skeletal Benefits and Risks of Other Agents 만, 골다공증여성에서정맥혈전색전증을증가시키지않았다. 40) 정확한인과관계는밝혀지지않았지만혈전정맥염의과거력이있는사람에게는금기이다. 적절한예방적조치가없이장기간움직일수없는환자와같은정맥혈전색전증위험이높은환자에게는투약을중단해야한다. 31) 3) 기타부작용아주드물지만 drug reaction with eosinophilia and systemic symptoms 41) 혹은독성표피괴사를일으킬수있다. 42) Denosumab Denosumab은인간단클론항체이다. Receptor activator of nuclear factor kappa B (RANK) 의 ligand인 RANKL에강한친화력을가진항체로파골세포의분화, 활성화및생존을감소시킨다. 폐경후골다공증여성의골다공증 1차치료제 1) 및 androgen depravation 치료를받고있는전립선암환자의골다공증치료제 34) 로승인을받았다. 저칼슘혈증은치료전반드시교정해야한다. 1) 2. 기타효과폐경증상을완화시키는효과가있으며, 에스트로겐에비해유방압통및질출혈빈도가적다. 50,51) 노인폐경여성에서유방암의위험을감소시켰다. 49) 3. 부작용및금기사항노인폐경여성에서뇌졸중의위험을증가시켰다. 정맥혈전색전증위험을증가시킨다는근거는아직없지만, 노인, 고혈압, 흡연, 당뇨병, 그리고심방세동과같은강력한위험인자를가진사람에게는주의해서사용해야한다. 49) Ipriflavone Ipriflavone (7-isopropoxyisoflavone) 은 isoflavone 유도체이다. 1. 효과동물실험에서볼때골흡수를감소시키고골형성을촉진시키는효과가있을것으로기대되지만, 52) 3년간복용했을때골손실을예방하지못했다. 53) 1. 효과폐경후골다공증여성에게 denosumab 60 mg을 6개월마다한번씩 3년간피하로주사했을때새로운척추골절, 비척추골절, 대퇴경부골절위험이감소했다. 2년간더투여하면요추및골반총골밀도는더증가한다. 43,44) 2. 부작용습진과봉와직염의위험이증가하지만, 45,46) 전체피부감염은증가하지않는다. 47) 증상이심하면투약을중지하는것이좋다. 턱뼈괴사가발생했다는보고가있다. 44) Tibolone Tibolone은에스트로겐의특성을가진합성스테로이드호르몬으로, 에스트로겐수용체에결합하여효과를나타낸다. 48) Tibolone은미국과캐나다를제외한많은나라에서골다공증예방제로승인을받았다. 1. 뼈에대한효과골다공증이있는노인여성의척추및비척추골절위험을감소시킨다. 49) 2. 부작용상당수의환자에서무증상의백혈구감소증을일으킨다. 53) 각약제의금기사항 결론 각약제별금기사항은다음의 Table 1 에정리하였다. 1,31,54) 선택적에스트로겐수용체조절제인 raloxifene, 그리고 calcitonin은척추골절, teriparatide는척추골절과비척추골절, strontium ranelate는척추골절과비척추골절 ( 일부환자의골반골절포함 ), denosumab은척추골절, 비척추골절, 그리고골반골골절위험을의미있게감소시킨다. Denosumab 은 bisphosphonate와함께 1차치료제로승인을받았다. Teriparatide는골절위험이아주높은환자혹은 bisphosphonate 등의치료가실패한환자에게권장된다. Teriparatide는 bisphosphonates와함께당류코티코스테로이드사용으로인한골다공증치료제로승인을받았다. 가장많이사용되고있는 bisphosphonates 외의약물을처방하고자할때에는, 상기약물의효과, 부작용, 그리고금기사항을고려하여환자의상태에 28 Vol. 3, No. 1 Mar 2013 Korean J Fam Pract
박주성 : 기타골다공증치료제의효과와문제점 Table 1. Contraindications for each agents Agents Raloxifene Estrogen, tibolone Calcitonin Teriparatide Strontium ranelate Denosumab Contraindications Pregnancy, history of venous thromboembolism, hypersensitivity, nursing Pregnancy, active thrombophlebitis or history of thromboembolic disorders, breast cancer (except appropriately selected patients treated for metastatic disease), estrogen dependent neoplasia, undiagnosed abnormal vaginal bleeding, hypersensitivity, active or recent (within one year) liver dysfunction or disease, stroke or myocardial infarction Hypersensitivity Paget s disease, prior therapeutic radiation therapy involving the skeleton, bone metastases or history of skeletal malignancies, metabolic bone disease (other than osteoporosis), hypercalcemia, pregnant and nursing women, unexplained elevated alkaline phosphatase, hypersensitivity, and pediatric population or young adults with open epiphyses History of thrombophlebitis, high-risk situations for venous thromboembolism such as prolonged immobilisation without appropriate preventive measures taken Uncorrected pre-existing hypocalcemia 맞는적절한약제를선택하여야한다. 또한국민건강보험공단의급여인정기준에도적절히맞추어야하겠다. 국민건강보험공단의급여인정기준에도적절히맞추어야하겠다. 요약 우리나라에서는남성및여성골다공증치료의일차선택약제가 bisphosphonate 제재이다. 장기간의투약이나부작용때문에 bisphosphonate 제재를사용할수없는경우, 혹은특정적응증이있는다른약제가있는경우에는다른약제를선택해야한다. Denosumab은폐경후골다공증여성의골다공증일차치료제및 androgen depravation 치료를받고있는전립선암환자의골다공증치료제로일부나라에서승인을받은약제이다. 선택적에스트로겐수용체조절제인 raloxifene 은에스트로겐수용체에따라작용제역할도하고길항제역할도한다. 척추골절및진행성유방암의위험을감소시키는효과가있다. Teriparatide는척추골절과비척추골절, strontium ranelate는척추골절과비척추골절 ( 일부환자의골반골절포함 ), denosumab은척추골절, 비척추골절, 그리고골반골골절위험을의의있게감소시킨다. Calcitonin은척추골절위험을감소시킨다. Teriparatide는골절위험이아주높은환자혹은 bisphosphonate 등의치료가실패한환자에게권장된다. Teriparatide는 bisphosphonates와함께당류코티코스테로이드사용으로인한골다공증치료제로도승인을받았다. 가장많이사용되고있는 bisphosphonates 외의약물을처방하고자할때에는, 상기약물의효과, 부작용, 그리고금기사항을고려하여환자의상태에맞는적절한약제를선택하여야한다. 또한 중심단어 : 골다공증 ; 금기 ; 선택적에스트로겐수용체조절제 ; 에스트로겐 ; 티볼론 ; 칼시토닌 ; 부갑상선호르몬유사체 ; 데노수맙 ; 스트론튬라넬레이트 REFERENCES 1. Watts NB, Bilezikian JP, Camacho PM, Greenspan SL, Harris ST, Hodgson SF, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract 2010;16 Suppl 3:1-37. 2. Delmas PD, Genant HK, Crans GG, Stock JL, Wong M, Siris E, et al. Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 2003;33:522-32. 3. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999;282:637-45. 4. Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, et al. The effect of raloxifene on risk of breast cancer 가정의학 Vol. 3, No. 1 Mar 2013 29
Joosung Park: Anti-Osteoporotic Effect, Extra-Skeletal Benefits and Risks of Other Agents in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 1999; 281:2189-97. 5. Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, et al. Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006;295:2727-41. 6. Grady D, Cauley JA, Stock JL, Cox DA, Mitlak BH, Song J, et al. Effect of Raloxifene on all-cause mortality. Am J Med 2010;123: 469.e1-7. 7. Delmas PD, Bjarnason NH, Mitlak BH, Ravoux AC, Shah AS, Huster WJ, et al. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997;337:1641-7. 8. Palacios S, Farias ML, Luebbert H, Gomez G, Yabur JA, Quail DC, et al. Raloxifene is not associated with biologically relevant changes in hot flushes in postmenopausal women for whom therapy is appropriate. Am J Obstet Gynecol 2004;191:121-31. 9. Gordon S, Walsh BW, Ciaccia AV, Siddhanti S, Rosen AS, Plouffe L Jr. Transition from estrogen-progestin to raloxifene in postmenopausal women: effect on vasomotor symptoms. Obstet Gynecol 2004;103:267-73. 10. Adomaityte J, Farooq M, Qayyum R. Effect of raloxifene therapy on venous thromboembolism in postmenopausal women. A meta-analysis. Thromb Haemost 2008;99:338-42. 11. Barrett-Connor E, Mosca L, Collins P, Geiger MJ, Grady D, Kornitzer M, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006;355:125-37. 12. Ensrud K, LaCroix A, Thompson JR, Thompson DD, Eastell R, Reid DM, et al. Lasofoxifene and cardiovascular events in postmenopausal women with osteoporosis: Five-year results from the Postmenopausal Evaluation and Risk Reduction with Lasofoxifene (PEARL) trial. Circulation 2010;122:1716-24. 13. Cummings SR, Ensrud K, Delmas PD, LaCroix AZ, Vukicevic S, Reid DM, et al. Lasofoxifene in postmenopausal women with osteoporosis. N Engl J Med 2010;362:686-96. 14. Torgerson DJ, Bell-Syer SE. Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials. JAMA 2001;285:2891-7. 15. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, et al. Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women s Health Initiative randomized trial. JAMA 2003;290:1729-38. 16. Sornay-Rendu E, Garnero P, Munoz F, Duboeuf F, Delmas PD. Effect of withdrawal of hormone replacement therapy on bone mass and bone turnover: the OFELY study. Bone 2003;33:159-66. 17. Bagger YZ, Tanko LB, Alexandersen P, Hansen HB, Mollgaard A, Ravn P, et al. Two to three years of hormone replacement treatment in healthy women have long-term preventive effects on bone mass and osteoporotic fractures: the PERF study. Bone 2004;34:728-35. 18. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women s Health Initiative randomized controlled trial. JAMA 2002;288:321-33. 19. Wassertheil-Smoller S, Hendrix SL, Limacher M, Heiss G, Kooperberg C, Baird A, et al. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women s Health Initiative: a randomized trial. JAMA 2003;289:2673-84. 20. Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women s Health Initiative Randomized Trial. JAMA 2003; 289:3243-53. 21. Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women s Health Initiative Memory Study: a randomized controlled trial. JAMA 2003;289:2651-62. 22. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women s Health Initiative randomized controlled trial. JAMA 2004;291:1701-12. 23. Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ 2012;345:e6409. 24. Pleiner-Duxneuner J, Zwettler E, Paschalis E, Roschger P, Nell- Duxneuner V, Klaushofer K. Treatment of osteoporosis with parathyroid hormone and teriparatide. Calcif Tissue Int 2009;84: 30 Vol. 3, No. 1 Mar 2013 Korean J Fam Pract
박주성 : 기타골다공증치료제의효과와문제점 159-70. 25. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001;344:1434-41. 26. Prince R, Sipos A, Hossain A, Syversen U, Ish-Shalom S, Marcinowska E, et al. Sustained nonvertebral fragility fracture risk reduction after discontinuation of teriparatide treatment. J Bone Miner Res 2005;20:1507-13. 27. Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, et al. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med 2005;353:555-65. 28. Hodsman AB, Bauer DC, Dempster DW, Dian L, Hanley DA, Harris ST, et al. Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. Endocr Rev 2005;26:688-703. 29. Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2013;24:23-57. 30. Chesnut CH 3rd, Silverman S, Andriano K, Genant H, Gimona A, Harris S, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med 2000;109:267-76. 31. Chesnut CH 3rd, Azria M, Silverman S, Engelhardt M, Olson M, Mindeholm L. Salmon calcitonin: a review of current and future therapeutic indications. Osteoporos Int 2008;19:479-91. 32. Plosker GL, McTavish D. Intranasal salcatonin (salmon calcitonin): a review of its pharmacological properties and role in the management of postmenopausal osteoporosis. Drugs Aging 1996;8:378-400. 33. Marie PJ, Felsenberg D, Brandi ML. How strontium ranelate, via opposite effects on bone resorption and formation, prevents osteoporosis. Osteoporos Int 2011;22:1659-67. 34. Watts NB, Adler RA, Bilezikian JP, Drake MT, Eastell R, Orwoll ES, et al. Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97:1802-22. 35. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004;350:459-68. 36. Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study. J Clin Endocrinol Metab 2005;90:2816-22. 37. Reginster JY, Kaufman JM, Goemaere S, Devogelaer JP, Benhamou CL, Felsenberg D, et al. Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis. Osteoporos Int 2012;23:1115-22. 38. Bruyere O, Delferriere D, Roux C, Wark JD, Spector T, Devogelaer JP, et al. Effects of strontium ranelate on spinal osteoarthritis progression. Ann Rheum Dis 2008;67:335-9. 39. Stevenson M, Davis S, Lloyd-Jones M, Beverley C. The clinical effectiveness and cost-effectiveness of strontium ranelate for the prevention of osteoporotic fragility fractures in postmenopausal women. Health Technol Assess 2007;11:1-134. 40. Osborne V, Layton D, Perrio M, Wilton L, Shakir SA. Incidence of venous thromboembolism in users of strontium ranelate: an analysis of data from a prescription-event monitoring study in England. Drug Saf 2010;33:579-91. 41. Jonville-Bera AP, Crickx B, Aaron L, Hartingh I, Autret-Leca E. Strontium ranelate-induced DRESS syndrome: first two case reports. Allergy 2009;64:658-9. 42. Lee HY, Lie D, Lim KS, Thirumoorthy T, Pang SM. Strontium ranelate-induced toxic epidermal necrolysis in a patient with post-menopausal osteoporosis. Osteoporos Int 2009;20:161-2. 43. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009; 361:756-65. 44. Papapoulos S, Chapurlat R, Libanati C, Brandi ML, Brown JP, Czerwinski E, et al. Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension. J Bone Miner Res 2012;27: 694-701. 45. Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, Siddhanti S, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 2010;25:72-81. 46. Brown JP, Prince RL, Deal C, Recker RR, Kiel DP, de Gregorio LH, et al. Comparison of the effect of denosumab and 가정의학 Vol. 3, No. 1 Mar 2013 31
Joosung Park: Anti-Osteoporotic Effect, Extra-Skeletal Benefits and Risks of Other Agents alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res 2009;24:153-61. 47. Miller PD, Wagman RB, Peacock M, Lewiecki EM, Bolognese MA, Weinstein RL, et al. Effect of denosumab on bone mineral density and biochemical markers of bone turnover: six-year results of a phase 2 clinical trial. J Clin Endocrinol Metab 2011; 96:394-402. 48. Huang KE, Baber R; Asia Pacific Tibolone Consensus Group. Updated clinical recommendations for the use of tibolone in Asian women. Climacteric 2010;13:317-27. 49. Beardsworth SA, Kearney CE, Purdie DW. Prevention of postmenopausal bone loss at lumbar spine and upper femur with tibolone: a two-year randomised controlled trial. Br J Obstet Gynaecol 1999;106:678-83. 50. Berning B, Kuijk CV, Kuiper JW, Bennink HJ, Kicovic PM, Fauser BC. Effects of two doses of tibolone on trabecular and cortical bone loss in early postmenopausal women: a two-year randomized, placebo-controlled study. Bone 1996;19:395-9. 51. Cummings SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos V, Verweij P, et al. The effects of tibolone in older postmenopausal women. N Engl J Med 2008;359:697-708. 52. Arjmandi BH, Birnbaum RS, Juma S, Barengolts E, Kukreja SC. The synthetic phytoestrogen, ipriflavone, and estrogen prevent bone loss by different mechanisms. Calcif Tissue Int 2000;66:61-5. 53. Alexandersen P, Toussaint A, Christiansen C, Devogelaer JP, Roux C, Fechtenbaum J, et al. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA 2001;285:1482-8. 54. Institute for Clinical Systems Improvement. Diagnosis and treatment of osteoporosis [Internet]. Bloomington: Institute for Clinical Systems Improvement; 2011 [cited 2013 Feb 25]. Available from: http://guidelines.gov/content.aspx?f=rss&id=34270. 32 Vol. 3, No. 1 Mar 2013 Korean J Fam Pract