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PHARMACOTHERAPEUTICSJ Korean Med Assoc 2019 October; 62(10):542-550
pISSN 1975-8456 / eISSN 2093-5951
https://doi.org/10.5124/jkma.2019.62.10.542
542 대한의사협회지
서론
골다공증은 가장 흔한 대사성 골질환의 하나로 골강도의
손상으로 골절의 위험이 증가하는 전신성 골격계질환으로
정의할 수 있다[1]. 특히 폐경 여성에서 폐경 후 급격한 골소
실로 인하여 발생하며, 이러한 골소실은 피질골이 많은 장골
보다는 척추, 골반, 손목 말단 부위 등 해면골이 많은 뼈에
서 더욱 심하게 나타난다. 폐경 초기의 이러한 급격한 골소
실 단계가 지나고 폐경 후 4-8년이 지나고 나면 폐경 초기
에 비하여 보다 완만하고 지속적인 골소실이 일어나는데, 이
단계에서 골 소실은 고령 남성에서 보이는 골소실과 유사한
양상으로 진행된다[2].
골다공증성 골절의 발생으로 인한 개인의 건강위해, 장애
와 삶의 질 저하, 그리고 사회적인 비용의 증가와 같은 문제
를 고려할 때, 골다공증에 사용되는 여러 약제들을 이해하
고, 환자에 맞는 적절한 약제를 선택하며, 치료반응을 확인
하는 것은 매우 중요하다. 본 연제에서는 골다공증의 약물치
골다공증의 약물치료전 성 욱 | 인제대학교 의과대학 해운대백병원 산부인과
Pharmacological treatment of osteoporosis Sungwook Chun, MD
Department of Obstetrics and Gynecology, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
Received: August 21, 2019 Accepted: August 26, 2019
Osteoporosis is a skeletal disorder characterized by compromised bone strength resulting in a predisposition to fracture. Osteoporosis-related fractures can lead to pain, disability, and increased healthcare costs. This study aimed to explore different pharmacological treatments for osteoporosis. Various treatments are used to prevent and treat osteoporosis, particularly in postmenopausal women and elderly men, but the approach needs to be individually tailored. Bisphosphonates are most commonly used to treat osteoporosis. Bisphosphonates and denosumab are mainly used during the initial phase of therapy for most patients with osteoporosis, including those with a high risk of fracture. In younger postmenopausal women, menopausal hormone therapy (including tibolone) and selective estrogen receptor modulators may be considered as alternatives for fracture prevention. Parathyroid hormone therapy is recommended for osteoporosis treatment in elderly patients with an increased risk of multiple vertebral fractures. Dual energy X-ray absorptiometry (DXA) is the mainstay for monitoring the treatment response, and clinicians may consider alternative treatments if a significant decrease in bone mineral density is detected (using DXA or bone turnover markers) or if recurrent fractures occur during treatment. For postmenopausal women undergoing long-term bisphosphonate treatment, the risk of fracture should be reassessed after 3 to 5 years, and a “drug holiday” should be considered if the risk of fracture is low-to-moderate. Therapy should be continued for patients who continue to exhibit a high risk of fracture, or alternatively, switching to other treatments may be considered. Key Words: Osteoporosis; Fracture; Pharmacotherapy
골다공증 치료 543
Chun S·Osteoporosis treatment
료에 대해서 전반적으로 살펴보고, 올바른 약제 선택의 기준
과 치료 모니터링에 대하여 알아보고자 한다.
골다공증 약물치료의 기준
대한골대사학회에서 권고하는 폐경 후 여성 및 50세
이상 남성의 골다공증 약물치료 기준은 1) 대퇴골 골절 또는
척추골절이 있거나, 2) 이차성 원인이 배제된 대퇴골경부,
총대퇴골, 요추의 골다공증(T-값 -2.5 이하)이 있는 경우,
그리고 3) 골감소증 환자에서 과거 기타 골절력이 있거나,
골절 위험이 증가된 이차성 원인이 있거나, 또는 세계보건
기구에서 제시한 FRAX 모델을 이용했을 때 10년 내 대퇴골
절의 위험도가 3% 이상 또는 주요 골다공증 골절위험도(임
상적 척추, 전완, 상완골 포함)가 20% 이상인 경우이다[3].
FRAX (Fracture Risk Assessment Tool)는 세계보건기구
에서 여러 입증된 골절 위험인자를 종합하여 10년 내 골절
위험도 또는 절대위험도를 산출하도록 개발되었다. 해당 위
험인자들은 연령과 대퇴골 경부 골밀도 이외에 연령, 성별,
신체질량지수, 과거 골절력, 부모의 대퇴골절, 병력, 흡연력,
이차성 골다공증 유무, 경구 글루코르티코이드 복용력, 음
주력 및 류마티스 관절염 여부로 구성
되어 있다. FRAX 홈페이지(https://
www.shef.ac.uk/FRAX/)에 들어가면
여러 인종별로 다양한 절대위험도를 산
출할 수 있으며, 한국어 서비스도 제공
된다.
골다공증 치료약제의 종류
1. 비스포스포네이트
비스포스포네이트(bisphosphonate)
는 골다공증 예방 및 치료 목적으로 사
용되는 강력한 골흡수억제제로 골다공
증 치료의 일차 선택제이며, 골다공증
의 치료 목적으로 전 세계적으로 가장 많이 처방되는 약
제이다[3-5]. 현재 골다공증 치료 목적으로 사용하는 비
스포스포네이트는 경구제로 알렌드로네이트(alendronate,
ALN), 리세드로네이트(risedronate, RIS), 이반드로네
이트(ibandronate, IBN), 주사제로 IBN과 졸레드로네
이트(zoledronat, ZOL)가 있으며, 그 외 파미드로네이트
(pamidronate)의 경우 미국에서는 골다공증 치료 목적으
로는 승인되지 않은 반면, 한국에서는 골칼슘 함량의 불균
형에 기인한 폐경 후 골다공증의 치료 목적으로 승인되어
있다. ALN, RIS, ZOL의 경우 척추골절과 비척추골절 및
대퇴골절의 위험도를 모두 유의하게 감소시키는 반면, IBN
의 경우 척추골절 감소효과만 보인다[4,6]. 비스포스포네
이트의 제제별 투여 경로 및 방법은 Table 1과 같다. 경구
제제의 경우 위장관에서의 낮은 흡수율을 극복하기 위하여
기상 후 아침 식전 최소 30분 전에 200 mL 이상의 충분한
양의 물과 함께 복용하도록 하며, 우유나 유제품, 오렌지주
스, 커피, 칼슘, 철분제, 제산제 등 약물 흡수 저해의 우려
가 있는 것들은 최소 1시간이 경과한 이후에 섭취하도록 한
다[3]. 위염, 식도염을 일으킬 수 있으며, 고농도 경구제제
는 주사제의 경우와 마찬가지로 관절통, 두통, 근육통, 발
열 등의 급성반응이 가능하므로 소염진통제의 처방이 도
Table 1. Approved bisphosphonates used in the prevention and treatment of osteoporosis in Korea
Class Molecule Route Usage
Bisphosphonates Alendronate Oral 10 mg daily
Oral 70 mg weekly
Alendronate + calcitriol Oral 5 mg + 0.5 μg daily
Alendronate + cholecalciferol Oral 70 mg + 2,800 IU weekly
70 mg + 5,800 IU weekly
Risedronate Oral 5 mg daily
Oral 35 mg weekly
Oral 35 mg (enteric coated) weekly
Oral 150 mg monthly
Risedronate + cholecalciferol Oral 35 mg + 5,600 IU weekly
Oral 150 mg + 30,000 IU monthly
Ibandronate Oral 150 mg monthly
Intravenous 3 mg q 3 months
Ibandronate + cholecalciferol Oral 150 mg + 24,000 IU monthly
Conflict of InterestNo potential conflict of interest relevant to this article was reported.
Younger postmenopausal women with high risk of fracture
VMS (+), low breast cancer risk VMS (-), high breast cancer risk
MHT SERMs
Bisphosphonates Denosumab
Elder postmenopausal women with high risk of fracture
Low risk
Drug holiday
Re-assessment: Fracture, BMD , BTM , …
Teriparatide
After 3-5 yr
High risk Non-responder
If ‘target’ is met after treatment for 5-10 yr
Switching
After 2 yr
Antiresorptives
Adding
Intolerant or InappropriateIncreased fracture risk
Oral Intravenous
Non-responder
Figure 2. Algorithm for the pharmacological treatment of osteoporosis in postmenopausal women. VMS, vasomotor symptom; MHT, menopausal hormone therapy; SERM, selective estrogen receptor modulator; BMD, bone mineral density; BTM, bone turnover marker.
Figure 1. Algorithm for the drug holiday period during the long-term bispho-sphonate therapy in postmenopausal women. IV, intravennous; BMD, bone mineral density. Reproduced from Korean Society for Bone and Mineral Re-saerch. Physician’s guide for diagnosis and treatment of osteoporosis 2015 [Internet]. Seoul: Korean Society for Bone and Mineral Research; 2015, accord-ing to the Creative Commons license [3].
High risk1. T-score still ≤-2.5, after
bisphosphonate therapy2. Previous fracture of the
hip or spine3. 2ndary osteoporosis
from chronic diseases or medication
Continue therapy and annual BMD measurement.
Alternative therapymay be offered.
Patients with high risk Patients with high risk
Consider drug holiday
Annual BMD measurement
If new fracture occurs,BMD decrease, or
T-score reaches ≤-2.5,restart therapy.
Patients with oral bisphophonate for
5 years or with IV zoldedronic acid for 3 years
골다공증 치료 549
Chun S·Osteoporosis treatment
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