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- Disease review - Approach to the patients with secondary osteoporosis R3 강 경 환 Bone resorption Bone formation Primary osteoporosis (more common) Secondary osteoporosis (less common) : occurring as a result of menopause or the aging process : accounting for approximately 80% of cases of osteoporosis in women : is becoming more frequently recognized (especially in men and premenopausal women) : accounts for 40% to 60% of all cases of osteoporosis : due to underlying disease or concurrent medication : require specific diagnostic tests : response to osteoporosis therapy may be limited if the underlying disorder goes unrecognized N Engl J Med 2008;358:1474-82 소아, 청소년, 폐경기전 여성, 50세 이하 남성 Z score <-2.0 (below the expected range for age) → secondary cause? N Engl J Med 2008;358:1474-82 Harrison’s principle of internal medicine, 17th edition Harrison’s principle of internal medicine, 17th edition N Engl J Med 2005;353:164-71. . N Engl J Med 2008;358:1474-82 Harrison’s principle of internal medicine, 17th edition N Engl J Med 2008;358:1474-82 European Journal of Endocrinology (2010) 162 1009–1020 이차성 골다공증을 의심해야 하는 경우 1. 이차적 원인이 이미 있는 환자에서 골다공증 병발 확인 2. 골량의 감소 정도가 기대치보다 현저한 경우 - Z-점수 < –2 (연령 기대치 이하) - 골다공증성 골절의 병력 (폐경 전 여성, 남성) 3. 치료에 대한 반응이 적절하지 않은 경우 4. 골다공증 발생 위험 인자가 적은데도 불구하고 현저하게 골밀도가 감소되어 있는 경우 5. 기타 의심되는 경우 골다공증 진단 및 치료 지침 2008 European Journal of Endocrinology (2010) 162 1009–1020 European Journal of Endocrinology (2010) 162 1009–1020 Mechanism Glucocorticoid excess - serum estrogen & testosterone↓ ,Ca absorption↓ urine Ca↑ serum Ca↓ → bone resorption↑, bone formation↓ - an increased risk of falls due to muscular atrophy and altered neuromuscular function Hyperthyroidism - activation of thyroid hormone receptor α on osteoblasts and osteoclasts → enhanced bone resorption and bone loss (TSH level <0.1 mU/l was associated with a four- and fivefold risk of hip and vertebral fractures respectively) Primary hyperparathyroidism - chronic effects of PTH are to increase the number both osteoblasts and osteoclasts - continuous exposure to elevated PTH leads to increased osteoclast-mediated bone resorption → affects cortical rather than cancellous bone European Journal of Endocrinology (2010) 162 1009–1020 Pregnancy-associated osteoporosis - preexisting vitamin D deficiency - low intake of calcium and protein - low bone mass, increased PTH-related protein, high bone turnover - unfractionated heparins for thromboembolic disorders Hypogonadisim - through disruption of HPA or through gonadal function - androgens are crucial for the accrual of peak bone mass - use of androgen ablation Tx or GnRH agonist for prostate ca., tamoxifen for breast ca. Diabetes mellitus type 1 - lack of the bone anabolic actions of insulin & β-cell-derived proteins (amylin) → contribute to low BMD - diabetic complications (retinopathy, polyneuropathy, and nephropathy) : major determinants of low bone mass and increased fracture risk - type 2 diabetes mellitus with TZD → associated with fractures of the hip, humerus GH deficiency - GH→stimulation of hepatic receptor→production of IGF-1 and IGF-binding protein : a potent stimulator of osteoblastic functions and bone formation European Journal of Endocrinology (2010) 162 1009–1020 GI disease Disease Celiac disease Pancreatic insufficiency Inflammatory bowel disease Treatment gluten-free diet exocrine pancreatic enzymes modify the immunosuppressive regimen to control inflammatory activity and to reduce the glucocorticoid dose Endocrinologic disorder Disease Treatment Cushing’s syndrome - surgically treated if osteoporosis is present Primary hyperparathyroidism - surgically treated if osteoporosis is present Hyperthyroidism - endogenous : anti-thyroid drugs, radioiodine therapy, or surgery - exogenous : adjustment of the L-T4 dosage with a target serum thyrotropin level within the normal range Sex hormone deficiency (premenopausal women and men) - should be replaced, if signs and symptoms of hormone deficiency are present (decreased libido, sarcopenia, visceral obesity) GH deficiency - GH replacement therapy increases BMD Diabetes mellitus - intensive insulin therapy - aggressive prevention of diabetic vascular complications Anorexia nervosa - estrogen replacement therapy : resulted in variable increase in BMD N Engl J Med 2008;358:1474-82 N Engl J Med 2005;353:595-603