Indian Journal of Rheumatology 2011 June Guidelines Volume 6, Number 2; pp. 68–75 Indian rheumatology association guidelines for management of glucocorticoid-induced osteoporosis Endorsed by: Endocrine Society of India and Indian Society for Bone & Mineral Research Venkataraman Krishnamurthy 1 *, Aman Sharma 2 , Amita Aggarwal 3 , Uma Kumar 4 , Sanjiv Amin 5 , Uppuluri Ramakrishna Rao 6 , Gumdal Narsimulu 7 , Rohini Handa 8 , Ambrish Mithal 9 , Shashank Joshi 10 INTRODUCTION Glucocorticoids have revolutionized the treatment of inflammatory diseases in the past 60 years. The beneficial anti-inflammatory effects are associated with various side- effects. Osteoporosis resulting in fractures at spine and hips is one of the significant adverse effects with long-term use. Other adverse effects include precipitation of diabetes, hypertension, cataract formation, skin thinning, osteonecro- sis and Cushingoid appearance. Around 1% of adult popu- lation chronically ingests glucocorticoids on long-term basis and the percentage is higher in the elderly. In one of the largest studies having included more than 250,000 glu- cocorticoid users and same number of age matched controls, the incidence of hip and vertebral fractures was increased 2–4 fold amongst patients taking daily doses of prednisolone more than 2.5 mg. 1 After discontinuation of glucocorticoids, the bone loss is at least partially reversed. 2 PATHOGENESIS Bone is a dynamic tissue wherein pockets of resorption and formation are coupled under normal physiological condi- tions. These processes are uncoupled during glucocorticoid treatment, the bone formation being inhibited and resorp- tion unchanged or accelerated. Trabecular bone is initially affected and with prolonged use the cortical bone such as femoral neck can also get involved. Glucocorticoids stimulate apoptosis of osteoblasts and osteocytes, and they prolong the lifespan of osteoclasts. 3 Glucocorticoids preferentially stimulate the differentiation of mesenchymal stem cells into adipocytes pathway over the differentiation to osteoblasts. The intestinal absorption of calcium is also reduced and urinary calcium loss is increased. 4 Oral glucocorticoids inhibit fol- licle stimulating hormone-induced estrogen production in women and suppress testosterone levels in men. These nega- tive effects on gonadal hormones contribute to increased bone resorption. 4 Other than these direct effects on bone, gluco- corticoids induce muscle wasting and consequently muscle weakness and increased susceptibility to physical falls. Although decline in bone mineral density is correlated with fracture risk, the glucocorticoid-induced micro- architectural changes of collagen content and cross-linking are also important determinants of fracture risk. Analysis of placebo groups from randomized trials indicate that for the same bone mineral density the incidence of vertebral frac- tures is higher in glucocorticoid patients than in no-users, suggesting that the increased fracture risk is only partly explained by measuring bone mineral density. 5 The underlying disease for which the glucocorticoid is prescribed also contributes to the increased risk of fracture. Inflammatory processes, through pro-inflammatory cytokines contribute to systemic bone loss. 5 Although glucocorticoids reduce systemic inflammation, there is evidence of higher risks of fractures on oral glucocorticoid users compared to non-users with similar underlying disease. 1 The relative contribution of the different mechanisms to development of fractures is not known, and there exists 1 Consultant Rheumatology, Apollo Speciality Hospital, Chennai & Meenakshi Multispecialty Hospital, Chennai, 2 Assistant Professor (Rheumatology), Department of Internal Medicine, PGIMER, Chandigarh, 3 Additional Professor, Department of Clinical Immunology, SGPGI, Lucknow, 4 Additional Professor of Medicine Head, Clinical Immunology & Rheumatology, AIIMS, New Delhi, 5 Consultant Rheumatology, Mumbai, 6 Director & Consultant Rheumatology, Sri Deepti Rheumatology Centre, Hyderabad, 7 Professor & Head, Department of Rheumatology, Nizam’s Institute of Medical Sciences, Hyderabad, 8 Senior Consultant Rheumatologist, Apollo Indraprastha Hospitals, New Delhi, 9 Chairman & HOD, Division of Endocrinology and Diabetes, Medanta, the Medicity, 10 Senior Consultant (Endocrinologist), Lilavati Hospital and Research Center, Mumbai. Correspondence: Venkataraman Krishnamurthy, email: vk23@hotmail.com