SGH Rheum Rapid Review Series GLUCOCORTICOIDINDUCED OSTEOPOROSIS Dr

SGH Rheum Rapid Review Series GLUCOCORTICOID-INDUCED OSTEOPOROSIS Dr Nur Emillia Roslan Dr Warren Fong SGH Department of Rheumatology & Immunology

Learning objectives • • • Definition Epidemiology Pathophysiology Investigations and assessment tools Management strategies and algorithms

Osteoporosis definition • WHO: a generalized bone disease characterized by a decreased bone mass and a deterioration of bone microarchitecture resulting in an increased fracture risk. • NIH: a disease of compromised bone strength, with bone strength made up of both bone mass and bone quality, resulting in an increased risk of fracture.

Epidemiology • Approximately 0. 5% of the population may be taking glucocorticoid for a period of at least 3 months. • A rapid decline in bone mineral density begins within the first 3 months of glucocorticoid use, and peaks at 6 months, followed by a slower steady loss with continued use.

• An increased risk of both vertebral and nonvertebral fractures has been reported with prednisolone dosages as low as 2. 5 - 7. 5 mg a day, or its equivalent. • 30% of individuals taking long-term glucocorticoids for more than 3 years will have evidence of osteoporotic fractures.

• Consequences of fractures: Ø pain, decreased quality of life, functional decline, psychosocial decline Ø Increased risk for new fractures Ø Increased mortality

Pathophysiology Glucocorticoid-Induced Bone Disease. Robert S. Weinstein, M. D. N Engl J Med 2011; 365: 62 -70

Factors that increase the risk of glucocorticoid-induced osteoporosis • • • Low body mass index Parental history of hip fracture Current smoking Three or more alcoholic drinks a day Higher daily glucocorticoid dose Intravenous pulse glucocorticoid usage

Clinical features • Bone loss is asymptomatic • A fracture is suspected when there is acute pain, loss of height, hyperkyphosis

Investigations • Bone Mineral Density • X-rays

Bone Mineral Density • Normal bone density: BMD T score above -1 SD (standard deviation) • Osteopenia: BMD T score between -1 and -2. 5 SD • Osteoporosis: BMD T score below -2. 5 SD

FRAX 10 year probability for major osteoporotic fracture Risk classification FRAX < 10% Low risk FRAX 10 - 20% Medium risk FRAX >20% High risk

Examples of osteoporotic fractures

Aim of treatment: prevention of fragility fracture.

Pharmacological management • Calcium intake of at least 1 g a day • Correction of Vitamin D deficiency or insufficiency • Reduce dose and duration of glucocorticoid where possible

Bisphonates Ø Inhibit osteoclast activity and induce osteoclast apoptosis, thereby reducing bone resorption and increasing BMD. Glucocorticoid-induced osteoporosis: hope on the HORIZON-COMMENT once yearly infusion therapy better than once weekly. The Lancet, Volume 373, Issue 9671, Pages 1225 - 1226, 11 April 2009 doi: 10. 1016/S 0140 -6736(09)60704 -2

Ø examples: Weekly oral alendronate, risedronate Yearly intravenous zoledronic acid

PTH family • increases number and activity of osteoblasts, thus increasing bone mass and improving skeletal architecture at both cancellous and cortical skeletal sites. Glucocorticoid-induced osteoporosis: hope on the HORIZON-COMMENT once yearly infusion therapy better than once weekly. The Lancet, Volume 373, Issue 9671, Pages 1225 - 1226, 11 April 2009

Ø Example: Daily subcutaneous Teriparatide

Treatment algorithms for premenopausal women and men under the age of 50 years, with a history of fragility fractures 1 - 3 months of glucocorticoids 3 or more months of glucocorticoids Alendronate or Risedronate if receiving prednisolone 5 mg or more a day Alendronate, Risedronate, Zoledronic acid or Teriparatide for any dose Zoledronic acid if receiving prednisolone 7. 5 mg or more a day

Treatment algorithms for post-menopausal women and men aged 50 or more Low risk Medium risk Alendronate, Risedronate or Zoledronic acid if receiving prednisolone 7. 5 mg or more a day Alendronate or Alendronate, Risedronate for any dose of Zoledronic acid or glucocorticoid Teriparatide for any dose Zoledronic acid if receiving prednisolone 7. 5 mg or more a day High risk

Other treatment strategies • Exercises such as walking, weight-bearing, aerobics and resistance exercises • Smoking cessation • Reducing alcohol intake • Fall-prevention: home modification, reducing medications that can reduce alertness, improving vision

Summary • Stratify patients on glucocorticoids with regards to risk for osteoporotic fractures • Prescribe the recommended treatment for prevention of fractures • Include non-pharmacological management

References • EULAR textbook on Rheumatic Diseases • American College of Rheumatology 2010 Recommendations for the Prevention and Treatment of Glucocorticoid-induced Osteoporosis • Online FRAX calculator: http: //www. shef. ac. uk/FRAX/tool. jsp? location. Value=9

• Glucocorticoid-induced osteoporosis: hope on the HORIZONCOMMENT once yearly infusion therapy better than once weekly. The Lancet, Volume 373, Issue 9671, Pages 1225 1226, 11 April 2009 • Glucocorticoid-Induced Bone Disease. Robert S. Weinstein, M. D. N Engl J Med 2011; 365: 62 -70