Vietnam Osteoporosis Workshop, HCM Cty 2006 Secondary Osteoporosis Tuan Van Nguyen and Nguyen Dinh Nguyen Bone and Mineral Research Program Garvan Institute of Medical Reseach Sydney, Australia

Vietnam Osteoporosis Workshop, HCM Cty 2006 Overview Definitions Causes Corticosteroid Induced Osteoporosis: –Machanism –Magnitude of the problem –Patient managements

Vietnam Osteoporosis Workshop, HCM Cty 2006 Secondary osteoporosis Results from chronic conditions that contribute significantly to accelerated bone loss. Treatment of secondary osteoporosis is more complex than that of primary osteoporosis. Prognosis depends on the underlying disease.

Vietnam Osteoporosis Workshop, HCM Cty 2006 Secondary Osteoporosis Endocrine or Metabolic causes Medications Collagen/genetics disorders Nutritional disorders Forms of secondary osteoporosis

Vietnam Osteoporosis Workshop, HCM Cty 2006 Endocrine or metabolic causes Hypogonadism Hyperparathyroidism Cushing-syndrome Acidosis Diabetes (type I) Androgen insensitivity Hemochromatosis Gaucher’s disease

Vietnam Osteoporosis Workshop, HCM Cty 2006 Medications Corticosteroids Thyroid GnRH antagonists Anti-neoplastic agents Cyclosporin, methotrexate Phenobarbital Phenothiazines, Phenytoin

Vietnam Osteoporosis Workshop, HCM Cty 2006 Collagen/genetic disorders Ehler-Danlos syndrome Glycogen storage diseases Homocysturina Hypophosphatasis Marfan syndrome Osteogenesis Imperfecta

Vietnam Osteoporosis Workshop, HCM Cty 2006 Nutritional Alcoholism Calcium deficiency Chronic liver disease Gastric operations Malabsorption syndromes Vitamin D deficiency

Vietnam Osteoporosis Workshop, HCM Cty 2006 Corticosteroid-induced Osteoporosis (CIOP)

Vietnam Osteoporosis Workshop, HCM Cty 2006 Corticosteroid-induced osteoporosis CS used in many underlying diseases Benefits effects on the underlying disease vs. detrimental effects on bone. High percentage of osteoporosis and fracture Dose-dependent effect  difficult to define

Vietnam Osteoporosis Workshop, HCM Cty 2006 CIPO-Epidemiology Prevalence of use of oral corticosteroids: – Population: 0.5% – Among women aged ≥ 55: 1.7% L J Walsh et al, BMJ 1996;313:344-6 Main indications: – Rheumatoid arthritis – Polymyalgia – COPD 14% of patients taking any treatment of osteoporosis

Vietnam Osteoporosis Workshop, HCM Cty 2006 CIPO: Burden Most common of drug-related osteoporosis in men and women Occur at any age, in both sexes, across races Up to 50% patient of chronic steroid therapy sustain osteoporotic fractures and/or develop osteonecrosis. Significant bone loss can occur in as little as 3 months. 50% chance of developing osteoporosis if on steroid for 6 mo.

Vietnam Osteoporosis Workshop, HCM Cty 2006 Corticosteroids-effect on bone Corticosteroids Osteoblast Inhibition enhancement Bone resorption Calcium loss increase Calcium absorption Inhibition Gonadal hormone

Vietnam Osteoporosis Workshop, HCM Cty 2006 Who is at high-risk of CIPO? Eastell R et al, J Intern Med 1998;244: Tobias JH, Rheumatology 1999;38: Prior fracture - Premature menaupause at < 45y - Age > 65 y - Planned or current use CS > 6 mo - Low weight - Other causes of Osteoporosis

Vietnam Osteoporosis Workshop, HCM Cty 2006 CIPO and fracture (Source: van Staa TP et al., 2000)

Vietnam Osteoporosis Workshop, HCM Cty 2006 Patient assessment Eastell R et al, J Intern Med 1998;244: BMD measurement BMD-Tscores? High-risk of CIOP? >1 0 to -1.5 < -1.5 or with CS >15mg/d or with CS 7.5mg/d x 6mo -Thoracic and lumbar spine X-ray -FBC, ESR & S-Electrophoresis if necessary -Serum Ca, P, AP, Albumin -Thyroid function -Men: testosterone an women: FSH, LH In 3-5 y After 1 y Lifestyle modification advice: -Smoking -Alcohol -Physical activity -Prevent fall

Vietnam Osteoporosis Workshop, HCM Cty 2006 CIOP-Management Primary prevention, PP (treatment started at the time initiation up to 3 mo of CS therapy) Secondary prevention, SP (treatment started >1y after the time initiation of CS therapy)

Vietnam Osteoporosis Workshop, HCM Cty 2006 Pharmacological therapy AgentPPSPDose Calcium &Vit Dvv1000mg/d & 50000U/w CalcitrolvNA0.6µg/d AlfacalcidiolvNA1µg/d CalcitoninvNAConflicting results (200U/d, nasal) Fluoridevv25mg BID plus Calcium Etidronatevvmarginal effect Alendronatevv5mg/d PamidronatevvIntermittent IV Risedronatevv5mg/d HRTNAv Testosterone (men)NAv

Vietnam Osteoporosis Workshop, HCM Cty 2006 Key messages Secondary osteoporosis is common Patients on CS therapy should be consider the need for therapy to prevent or treat CIOP Data on CIOP fracture reduction with treatment remain sparse

Vietnam Osteoporosis Workshop, HCM Cty 2006 Lời Cảm tạ Chúng tôi xin chân thành cám ơn Công ty Dược phẩm Bridge Healthcare, Australia là nhà tài trợ cho hội thảo.

Vietnam Osteoporosis Workshop, HCM Cty 2006 Thank you!