OSTEOPOROSIS (대한골다공증학회지)

The Korean Society of Osteoporosis (대한골다공증학회)
권호 표지

Glucocorticoid-induced Osteoporosis: From Pathogenesis to Treatment

스테로이드 유발성 골다공증: 병인에서 치료까지

  • Jeong, Yun-Seok (Department of Endocrinology and Metabolism, Ajou University School of Medicine)
  • 정윤석 (아주대학교 의과대학 내분비대사내과학교실)
  • Published : 2009.12.31

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Abstract

Glucocorticoid-induced osteoporosis (GIO) is the most common type of secondary osteoporosis. However, the mechanism responsible for GIO and the appropriate treatment for this problem remain poorly understood. The pathogenesis of GIO can be explained by a traditional model and a scientific model of bone cells. According to the traditional model, glucocorticoids decrease intestinal calcium absorption and increase urinary calcium excretion, and the negative calcium balance induces secondary hyperparathyroidism. In the more recent scientific model of bone cells, glucocorticoids stimulate osteoclast cells directly and increase osteoclast cell activity and survival during early accelerated bone loss this activity induces high bone turnover and rapid bone loss. Glucocorticoids suppress osteoblast cell activity directly and suppress osteoblast cell activity indirectly by osteoclast-mediated osteoblast recruitment during late decelerated continuous sustained bone loss. This results in low bone turnover and slow bone loss. A more detailed action mechanism of glucocorticoids in osteoblasts may include: (1) Runx2 expression, (2) PPAR gamma expression, and (3) Wnt /$\beta$-catenin signaling. Glycogen synthase kinase-3$\beta$(GSK3$\beta$) also plays a role in osteoblast apoptosis. Traditional general guidelines and life style modifications for GIO are: (1) doses of glucocorticoids as low as possible (2) duration of steroid administration as short as possible (3) topical rather than systemic glucocorticoid treatment, if possible (4) smoking cessation (5) reduction of alcohol; (6) weight -bearing exercise (7) adequate amounts of calcium and vitamin D intake (8) and the prevention of falls. Medical treatment options for GIO are sex hormones, calcitonin, bisphosphonate, and parathyroid hormone. In some studies, estrogen/progestin therapy in postmenopausal women and testosterone therapy in hypogonadal men have shown a beneficial effect on bone mineral density (BMD) of the spine. Calcitonin treatment may have the additional benefit of relieving the pain associated with vertebral fractures. Bisphosphonates reduce early accelerated bone loss, prevents bone resorption by inflammatory cytokines, and demonstrates anti-apoptotic effects on osteoblasts and osteocytes. In many studies, bisphosphonates have shown significant increase in the BMD of the spine and reduction of the risk of vertebral fractures in GIO. Parathyroid hormone (PTH) might be a better treatment option than bisphosphonate therapy, because PTH (1) targets osteoblasts, (2) increases osteoblast recruitment, activity, and survival, and (3) does not suppress osteoclasts. PTH treatment significantly increased lumbar spine BMD and total hip BMD and prevented vertebral fractures compared to alendronate therapy in patients with GIO. Future therapy targeting osteoblasts include: (1) the GSK3$\beta$ inhibitor, (2)Dickkopf antibody, (3) Sclerostin antibody.

스테로이드에 의한 골다공증 (GIO)은 이차성 골다공증의 가장 흔한 원인이다. 그러나 아직까지 그 기전은 명확하게 밝혀지지 않았으며, 치료 또한 쉽지 않다. GIO의 병인기전은 표적기관에 초점을 둔 전통적 모델과 골세포에 초점을 둔 과학적 모델이 있다. 과거의 전통적 모델에서는 스테로이드는 장에서 칼슘 흡수를 억제하고 소변으로의 칼슘 배출을 촉진하여, 이러한 음의 칼슘 균형이 이차성 부갑상선기능항진증을 일으키는 것으로 설명하고 있다. 그러나 이러한 과거 모델에 대한 반론과 문제점이 제기되고 있다. 최근의 과학적 모델에서는 스테로이드가 초기 (투여 1년 이내) 가속화된 골소실에서 파골세포를 직접적으로 자극하고, 파골세포의 활성도와 생존을 증가시켜, 골전환을 증가시키고 골소실을 촉진한다. 후기 감속화된 지속적 골소실에서는 스테로이드는 조골세포를 직접적으로 억제할 뿐만 아니라 파골세포에 의해 매개된 조골세포 동원을 간접적으로 억제한다. 이에 따라 느린 골전환 및 골소실을 유도한다. 이밖에 조골세포에 대한 스테로이드의 작용기전은 Runx2 발현, PPAR gamma 발현, Wnt /$\beta$-catenin 신호 등이 있다. 저자등은 glycogen synthase kinase-3$\beta$(GSK3$\beta$)의 역할을 최근 보고한 바 있다. GIO의 일반적 치료 지침과 생활 개선 요법으로 가능한 최소 용량의 스테로이드 사용, 짧은 기간의 스테로이드 사용,국소 스테로이드 요법, 금연, 알코올 섭취 감소, 체중부하 운동, 적절한 칼슘 섭취, 비타민 D 섭취, 낙상 예방이 있다. 약물 치료는 성호르몬 요법, 칼시토닌, 비스포스포네이트, 부갑상선호르몬 요법이 있다. 비스포스포네이트는 염증 사이토카인에 의한 골흡수를 억제하고, 조골세포와 골세포에 대한 세포사멸 억제 효과를 보인다. 이를 통해 요추의 골밀도를 증가시키고 척추골절의 위험을 감소시키는 것으로 보고되고 있다. 부갑상선호르몬은 조골세포에 대해 동원,활성화, 생존을 증가시키고, 파골세포를 억제하지 않아 비스포스포네이트보다 치료 효과가 좋을 것으로 예상된다. 부갑상선호르몬은 알렌드로네이트에 비해 요추 및 고관절 골밀도를 증가시키고, 척추골절을 감소시키는 것으로 보고되었다. 향후 가능성 있는 치료제로서 GSK3$\beta$ 억제제, Dickkopf 항체, Sclerostin 항체 등이 연구되고 있다.

Keywords

References

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