Osteoporosis

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Osteoporosis is a poorly recognized entity in India, especially among the non-endocrine physicians. Talk given to chest physicians focusing on glucocorticoid induced osteoporosis

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  • Osteoporosis for Chest Physicians Mathew John, MD, DM, DNB Providence Endocrine & Diabetes Specialty Centre www.endocrinologydiabetes.com
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Osteoporosis

  1. 1. Osteoporosis for Chest Physicians Mathew John, MD, DM, DNB Providence Endocrine & Diabetes Specialty Centre www.endocrinologydiabetes.com
  2. 2. Agenda Osteoporosis • Definition, diagnosis, management Glucocorticoid induced osteoporosis • Diagnosis, management, prevention
  3. 3. Definition Systemic skeletal disease characterized by low bone mass and microarchitectural deterioration, with consequent increase in fragility and susceptibility to fracture Or BONE DEFICIENCY National Osteoporosis Foundation. Physician's guide to prevention and treatment of osteoporosis. Washington, DC: National Osteoporosis Foundation, 1998
  4. 4. Epidemiology • Osteoporosis is responsible for more than 1.5 million fractures annually (300,000 hip fractures; 700,000 vertebral fractures; 250,000 wrist fractures; and 300,000 fractures at other sites) • Half of all women over age 50 will have an osteoporosis-related fracture • 24 % of individuals over age 50 die within a year following a hip fracture • 25 % become disabled after a hip fracture
  5. 5. Osteoporosis in India 26 million Indians suffer from osteoporosis, and this number is expected to reach 36 million by 2013 Action Plan Osteoporosis: Consensus Statement of an Expert Group, Osteoporosis Society of India, New Delhi, 2003 Estimated number of hip fractures projected for 2020 and 2050 2009 IOF Asian Audit
  6. 6. Osteoporosis : a comparison 2,000,000 2,000,000 Osteoporosis Fracture Incidence * > 1,500,000 Heart Attack + Stroke + Breast Cancer 1,500,000 1,500,000 1,000,000 250,000250,000 forearm hip 250,000 other sites § 250,000 500,000other sites 750,000 ‡ vertebral 513,000 228,000 184,300 750,000 0 vertebral Osteoporotic fractures Osteoporotic Heart Stroke Breast fractures Attack Cancer
  7. 7. Normal and Osteoporotic Bone
  8. 8. Determinants of bone mass PEAK BONE Calcium MASS Vit D intake Physical activity Gonadal steroid Physical activity Gonadal steroid Calcium Vit D intake Genetics 20 –30 yrs
  9. 9. Who are at risk for osteoporosis ? Age ≥ 65 years Low trauma vertebral compression fracture MAJOR Low trauma fracture over age 40 RISK Family history of osteoporotic fracture FACTORS Current systemic glucocorticoid therapy Malabsorption syndrome Primary hyperparathyroidism Hypogonadism Early menopause (before age 45)
  10. 10. Who are at risk for osteoporosis ? • Chronic anticonvulsant therapy • Low dietary calcium intake • Smoking MINOR • Excessive alcohol intake RISK • Excessive caffeine intake (e.g.. > 4 cups FACTORS coffee/day) • Weight < 57 kg • Short term weight loss > 10% from weight at age 25 • Chronic heparin therapy • Rheumatoid arthritis
  11. 11. Diagnosing osteoporosis DXA • Dual energy x-ray absorptimetry • Rapid & precise • Less radiation than a chest x-ray • Measures BMD at hip, spine and wrist
  12. 12. Reading DXA reports •Normal: T-score > -1 •Osteopenia: T-score -1 -- 2.5) •Osteoporosis: T-score <-2.5 •Severe Osteoporosis: one or more fractures
  13. 13. What is a T score ? From healthy white women Calculate: Mean ( M) & SD(sd) T score: Patient’s BMD- M SD Mean -1SD -2.5SD 1-SD decrease in BMD is associated with a doubled risk of fracture
  14. 14. Quantitative CT ( qCT) http://www.uic.edu/orgs/heart/EBT.htm
  15. 15. FRAX: WHO Fracture Risk Assessment Tool
  16. 16. Clinical features Ca/Vit D intake Loss High risk of fall Eye sight Of height Medications Muscle incordination Neuropathy Kyphosis Proximal Muscle weakness Fragility fracture Defined as a fracture occurring on minimal trauma after age 40 years and includes forearm, spine, hip, ribs and pelvis
  17. 17. Osteoporotic fractures http://www.learningradiology.com/archives06/ COW%20213-Hip%20fracture-intertrochanteric/hipfxtrochcorrect.htm http://www.szote.u-szeged.hu/radio/trauma2/a2trau1c.htm
  18. 18. Why is osteoporosis important for chest physicians ? • One of the most common cause of use of systemic steroids • Kyphosis secondary to osteoporosis can adversely affect lung function • Lung diseases can cause osteoporosis • Current use of anti –osteoporosis medication less among chest physicians
  19. 19. Use of systemic steroid • Pulmonary diseases : 2 nd most common cause of systemic steroid use • Three or more vertebral fractures were associated with a restrictive ventilatory defect (mean total lung capacity of 75% predicted and mean FVC of 68% predicted) • Rib mobility and inspiratory muscle function may also be impaired in patients with kyphosis Leech JA, Dulberg C, Kellie S, et al. Relationship of lung function to severity of osteoporosis in women. Am Rev Respir Dis 1990; 141:68–71 Lisboa C, Moreno R, Fava M, et al. Inspiratory muscle function in patients with severe kyphoscoliosis. Am Rev Respir Dis 1985; 132:48–52
  20. 20. Lung diseases linked to osteoporosis • COPD • Cystic fibrosis • Sarcoidosis • Pre lung transplantation
  21. 21. Glucocorticoid induced Osteoporosis Reduced Osteoblast Reduced function Calcium absorption Glucocorticoid Hypercalciuria + secondary hyperparathyroidism Enhanced Osteoclastic activity Reduced gonadotropin Reduced matrix protein secretion synthesis
  22. 22. Who is at risk ? Every patient receiving either oral or inhaled glucocorticoid therapy is at risk for bone loss regardless of age, ethnicity, gender, or other risk factors for non glucocorticoid-induced osteoporosis Fracture risk declines after oral glucocorticoids are stopped, reaching a relative risk of 1 approximately 2 years later. Ledford D, Apter A, Brenner AM, et al. Osteoporosis in the corticosteroid-treated patient with asthma. J Allergy Clin Immunol 1998; 102:353–362 van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 2002; 13:777–787
  23. 23. Dose of glucocorticoids and bone loss Prednsolone > 7.5 mg/day Prednisolone < 5 mg /day Inhaled steroids Wong CA, Walsh LJ, Smith CJ, et al. Inhaled corticosteroid use and bone-mineral density in patients with asthma. Lancet 2000; 355:1399–1403 van Staa TP, Leufkens HG, Abenhaim L, Begaud B, Zhang B, Cooper C. Use of oral corticosteroids in the United Kingdom. QJM 2000; 93:105–111.
  24. 24. Management of Osteoporosis Anti resorptive Bone anabolic agents agents SERMS Teripartide ( PTH 1-34) Bisphosphonates Strontium ranelate Calcitonin HRT All medical therapies to be supplemented with Calcium & Vitamin D
  25. 25. Management of osteoporosis Prevention of GIOP • Calcium+ Vitamin D, Bisphosphonates, Teripartide Treatment of GIOP • Calcium + Vitamin D, Bisphosphonates, Teriparatide
  26. 26. Approved Pharmacological Agents for the Management of GIO Intervention Dosing regimen Route of administration Alendronate 5 or 10 mg once daily Oral 70 mg once weekly* Etidronate‡ 400 mg daily for 2 weeks every 3 Oral months Risedronate 5 mg once daily Oral 35 mg once weekly* Zoledronate 5 mg once yearly Intravenous infusion Teriparatide 20 µg once daily Subcutaneous injection *Only once-daily dosing regimens are approved for GIO. ‡Etidronate is only approved in Europe and Canada. Abbreviation: GIO, glucocorticoid-induced osteoporosis. Nat Rev Rheumatol. 2010;6(2):82-88
  27. 27. General measures • A daily calcium intake of around 1200-1500 gm • Good nutrition • Maintenance of a normal BMI • Stop smoking • Stop alcohol
  28. 28. Bisphosphonates • Molecules: Alendronate, Risedronate, Ibandronate, Zoledronic acid, Pamidronate • Bind to active bone remodeling sites and inhibit osteoclasts • Dose : Alendronate 10 mg/day or 70 mg/week Risedronate 5 mg/day or 35 mg/week
  29. 29. Bisphosphonates: adverse effects • Gastrointestinal effects: esophageal irritation,nausea, hypocalcemia, bone pain • Contraindicated: esophageal dysmotility, significant renal dysfunction, hypocalcemia • High dose IV bisphosphonates can have adverse skeletal profile
  30. 30. Zoledronic Acid in GIOP: HORIZON study Prevention Subpopulation Lancet. 2009 Apr 11;373(9671):1253-63.
  31. 31. Zoledronic Acid in GIOP: HORIZON study Treatment Subpopulation Lancet. 2009 Apr 11;373(9671):1253-63.
  32. 32. Recombinant PTH • Teriparatide( PTH 1-34 ) • Bone anabolic agent • Dose: 20 mcg daily as subcutaneous injection Contraindications •Hypercalcemia •Hyperparathyroidism •Unexplained increased alkaline phosphatase •Paget’s disease
  33. 33. Effect of teriparatide 20 µg on skeletal architecture 0 months 21 months Microcomputed tomographic scan
  34. 34. Teriparatide vs. Alendronate Lumbar spine BMD Arthritis Rheum. 2009 Nov;60(11):3346-55.
  35. 35. Teriparatide vs. Alendronate Femoral neck and total Hip BMD Arthritis Rheum. 2009 Nov;60(11):3346-55.
  36. 36. Teriparatide vs. Alendronate Fracture data Arthritis Rheum. 2009 Nov;60(11):3346-55.
  37. 37. Calcitonin • 32 AA polypeptide • Indication: post menopausal osteoporosis( >5 years, unable to tolerate other agents) Vertebral fracture pain • Intranasal salmon calcitonin • Dosage: 200 IU • Significant reduction in vertebral fractures ( 33%) • Not much effect on non vertebral fractures
  38. 38. Risk stratification: postmenopausal women and men over age 50 years Low Risk: FRAX <10% for 10 year major osteoporotic fracture Medium Risk: FRAX 10-20% for 10 year major osteoporotic fracture High Risk: FRAX >20% for 10 year major osteoporotic fracture AMERICAN COLLEGE OF RHEUMATOLOGY 2010 RECOMMENDATIONS FOR THE PREVENTION AND TREATMENT OF GLUCOCORTICOID-INDUCED OSTEOPOROSIS A rthritis Care & Research DOI 10.1002/acr.20295
  39. 39. Low Risk: FRAX <10% for 10 year major osteoporotic fracture If glucocorticoids < 7.5 mg per day- no pharmacologic treatment recommended If glucocorticoids ≥7.5 mg per day:alendronate, risedronate or zoledronic acid Arthritis Care & Research DOI 10.1002/acr.20295
  40. 40. Medium Risk: FRAX 10-20% for 10 year major osteoporotic fracture If glucocorticoids <7.5 mg per day:alendronate, risedronate or zoledronic acid If glucocorticoids ≥7.5 mg per day:alendronate, risedronate or zoledronic acid Arthritis Care & Research DOI 10.1002/acr.20295
  41. 41. High Risk: FRAX >20% for 10 year major osteoporotic fracture If glucocorticoids <5 mg daily for 1 month or less: alendronate, risedronate, or zoledronic acid If glucocorticoids ≥5 mg daily for 1 month or less or any dose of glucocorticoids used for > 1 month: alendronate, risedronate, zoledronic acid or teriparatide
  42. 42. Clinical factors that may shift an individual to a greater risk category • Low body mass index • Parental history of hip fracture • Current smoking • 3 or more alcoholic drinks daily • Higher daily glucocorticoid dose • Higher cumulative glucocorticoid dose • Intravenous pulse glucocorticoid usage • Declining central BMD measurement that exceeds the least significant change
  43. 43. Approach to premenopausal women and men under age 50 years starting or on glucocorticoid therapy Arthritis Care & Research DOI 10.1002/acr.20295
  44. 44. AMERICAN COLLEGE OF RHEUMATOLOGY 2010 RECOMMENDATIONS FOR THE PREVENTION AND TREATMENT OF GLUCOCORTICOID-INDUCED OSTEOPOROSIS Limitations • Uses FRAX to classify risk in patients Limited use in busy OPD settings Needs more familiarity with non-endocrine physicians • Uses fragility fracture presence to decide on prophylaxis for premenopausal women and men < 50 Difficulty in vertebral fracture assessment Miss a high risk population with low BMD
  45. 45. Who should go on calcium/vitamin D ? At 2 years after starting calcium and vitamin D, there was a significant weighted mean difference of 2.6% (95% confidence interval [CI] 0.7–4.5) between the treatment and control groups in lumbar spine bone mineral density. All patients starting glucocorticoids should go on Calcium( 1000 -1500 mg/day) and Vitamin D 800 U/day Homik J, Suarez-Almazor ME, Shea B, Cranney A, Wells G, Tugwell P. Calcium and vitamin D for corticosteroid induced osteoporosis. Cochrane Database Syst Rev 2000; (2):CD000952.
  46. 46. Who should be started on bisphosphonates ? Patients starting long-term glucocorticoid treatment (i.e., expected to last 3 months or more) in doses of 5 mg or more per day of prednisone or its equivalent , irrespective of bone mineral density values Limited data in premenopausal women and men less than 50 American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid- induced osteoporosis: 2001 update. Arthritis Rheum 2001; 44:1496–1503.
  47. 47. Patient already on steroids? Treat with Bisphosphonates irrespective of BMD
  48. 48. Patient already on steroids? No high risk features T score > -1 : T Score -1 to -2.5: T score < -2.5 : r PTH if fractures calcium and bisphosphonates bisphosphonates present * Vitamin D American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid- induced osteoporosis: 2001 update. Arthritis Rheum 2001; 44:1496–1503. *: not in recommendation
  49. 49. Other medications • Calcitonin: limited effects on BMD • Active Vitamin D e.g. Alfacalcidiol, Calcitriol : modest benefits • Hormone replacement therapy : limited evidence in GIO
  50. 50. ‘‘ It is never too early and never too late to treat’’
  51. 51. Disclaimer The material for these slides were derived from various sources including pictures and cartoons from the world wide web. I have tried my best to acknowledge all possible sources and references. However, if I have overlooked any particular reference, it is not done intentionally. Anyone reproducing materials from this presentations should acknowledge the author of the original work.

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