Trigger 4

1. Trigger 4 Group B A.A. NgurahAgungWigantara, Ahmad Pasha Natanegara, Christopher Khorazon, Dina Rahmatika, IvanaYapiy, Lia Amanda, M. ShafiqAdvani, NurEulisPujiastutiNahdiyat, Putra RizaPratama, SherinPai, VanesiaStevianyDiauw

2. Trigger • MsWiwi, 73 years old, came to the clinic complaining of back pain that hinder her daily activities since 2 weeks ago. The pain intensifies with change of body position, movement, even during sleeping. She was brought to a 24 hour clinic and the doctor gave her pain killers and calcium tablets. However, the back pain persists. MsWiwi told the doctor that she had felt sore in her bones since 4 years ago and to relieve some of the soreness, she often drank medicine she bought at a small stall. The doctor observed that MsWiwi was slightly hunchbacked. The doctor performed a thorough physical examination, then recommended some blood tests, x-ray of the spinal column and pelvis, and bone densitometry.

3. Step 1 • Difficult terms: • none • Keywords • 73 years old female • Lower back pain since 2 weeks ago • Pain intensifies with change of body position, movement, and sleeping • Back pain persists after given the pain killers and Ca tablet • Sore in her bone since 4 years ago • Medicine from small stall  relieve some soreness • Slightly hunchbacked • Examination: physical, blood tests, X-ray of spinal column and pelvis, and bone densitometry • Identification of problem • What causes the pain in her right knee since 2 years ago and the last 2 weeks?

4. Step 2 – Analysis of Problem Taking medicine from small stall Sore in her bone since 4 years ago Female, 73 years old Given painkillers and Ca tablets Back pain since 2 weeks ago Intensifies with change of body position, movement, and sleeping Back pain persists Bone densitometry Examination Blood test Slightly hunchbacked Radiology Physical Spinal column Pelvic area Etiology & pathophysiology Osteoporosis Other disease (differential diagnosis) Complications Epidemiology, risk factors, prevention Treatment

5. Differential diagnosis • Signs and symptoms • Similarity • Epidemiology Step 5 - Identification of knowledge already known • Pathophysiology of pain • Radiology • Pharmacodynamics of analgesics • Histology of bone Step 6 - Identification of appropriate learning resources • Textbooks • Anatomy • Pharmacology • Pathophysiology • Medical Rehabilitation • Nutrition • Radiology • Reliable internet sources • Medical journal • Resource person (lecture) Step 3 - Development of hypothesis • Osteoporosis causes the persistent back pain Step 4 - Identification of knowledge needed • Anatomy • Vertebrae • Pelvic area • Osteoporosis • Pathophysiology • Etiology • Risk factors, prevention, epidemiology • Treatment and management • Pharmacology • Non-pharmacology • Examination • Physical • Radiology • Laboratory • Bone densitometry

6. Step 7 – Collection of new information Anatomy of vertebrae and pelvic area

9. Etiology & Pathophysiology • Age-related changes • Osteoblast from elderly individuals have reduced proliferative and biosynthetic potentials • Protein bound to the extracellular matrix: growth factors (both mitogenic to osteoprogenitor cells, stimulate osteoblastic synthetic activity)  loose their biologic punch over time Senile Osteoporosis • Reduced Physical Activity • Mechanical forces stimulate normal bone remodeling • Muscle contraction is the dominant source of skeletal loading  resistance exercise (weight training) are more effective stimuli for increasing bone mass than repetitive endurance activities (jogging)

10. Genetic factors • 60% - 80% of the variation in bone density is genetically determined • Top associated genes: RANKL, OPG, and RANK (encode key regulators of osteoclasts) • Calcium nutritional state • Adolescent girl tend to have insufficient calcium intake in the diet  these individuals have greater risk of developing osteoporosis • Calcium deficiency, increased PTH concentrations, reduced level of vitamin D  may contribute to senile osteoporosis • Hormonal Influence • Decreased estrogen level  increased secretion of inflammatory cytokines by blood monocytes and bone marrow  stimulate osteoclast recruitment and activity (by increasing level of RANKL while diminishing expression of OPG)  compensatory osteoblastic activity occurs, but does not keep pace  high-turnover form of osteoporosis

11. Epidemiology

12. Risk Factor Major Minor Rheumatoid arthritis Low calcium Chronic anticonvulsant therapy History of hyperthyroidism Smoking Excessive Alcohol Excessive Caffeine Low weight (<57 kg) Chronic heparin therapy Sudden weight loss (>10%) at age 25 • Age >65yr • Early menopause (<45yr) • Natural tendency to fall • Compression fracture at vertebrae • Fragility Fracture (>40 yr) • OP history in family • Systemic glucocorticoid therapy (>3 months) • Malabsorption syndrome • Primary hyperparathyroidism • Hypogonadism

13. Nutrition

14. Sign & Symptoms • Acute insufficiency fractures : • Minimal or no trauma resulting in pain. • Fall from a standing or sitting position. • Compression fractures • Thoracic kyphosis  iliocostalfriction with associated abdominal protrusion, decreased tolerance for oral intake, and breathing difficulties. • Hip, pelvic, or sacral fractures  worse pain with weight-bearing. • Sustained a vertebral compression • Progressive kyphosis with loss of height. • Acute back pain after bending, lifting, or coughing. • Asymptomatic.

15. Differential Diagnosis of Osteoporosis • Paget Disease • Found in > 3% in over 40 patient in North America, UK, western Europe, and Australia • Results in thick bone with weak structure • Renal Osteodystrophy • Combination of secondary hyperparathyroidism, rickets, osteomalacia, and osteoporosis • Most likely to occur on children • Clinical features: stunted, pasty-faced, rachitic deformities with myopathy

16. Multiple Myeloma • Most likely to occur on elderly • Malignant B-cell lymphoproliferative disorder of the marrow • Have effect on bone (osteoporosis & discrete lytic lesions on skeleton) & tumor (plasmacytoma accumulation of plasma cells) • Homocystinuria/Homocysteinemia • Due to high level of homocystein in blood and urine • Associated with osteoporosis and muscle weakness, and have similar clinical appearance to Marfan’s disease.

17. Hyperparathyroidism • Parathyroid hormone (PTH)-> maintain extracellular calcium concentrations. • Hyperparathyroidism-> characterized by excessive secretion of PTH (polypeptide hormone, 84aa) • PTH >>> -> increase the concentration of plasma calcium (increase the calcium reabsorption in the kidney, increase the release of phosphate and calcium from bone matrix, and increase 1,25-dihydroxyvitamin D-3 (calcitriol)-> increase intestinal absorption of calcium. • Divide into two : primary and secondary hyperparathyroidism.

18. Primary Hyperparathyroidism Causes : adenoma (benign tumor of parathyroid gland) 75%-80%, primary hyperplasia/ multiple adenoma 10-15%, parathyroid carcinoma <5%). Secondary Hyperparathyroidism • Causes: Hypocalcemia or Chronic renal failure, vitamin D deficiency can elevate PTH levels, Not enough calcium in the diet, too much calcium lost in urine , vitamin D disorders, and problem absorbing nutrients from food (malabsorption) can cause this diseases.

19. Scurvy Osteomalacia Softening of the bones-> lacks of vitamin D In osteomalacia-> have normal amount of collagen ( give the structure of the bone) In children, it is called rickets. Causes: Not enough vitamin D in the diet, not enough exposure to sunlight, which produces vitamin D in the body, and malabsorption of vitamin D. • Deficiency of vitamin C (ascorbic acid). • Scurvy is caused by a prolonged dietary deficiency of vitamin C • Symptoms: muscle and joint pain, tiredness, Presence of red dots on the skin and bleeding and swelling of the gums. • Vitamin C is essential cofactor for synthesis of collagen-> bone strength (can resist compression force and against torsion) Vitamin C deficiency -> impaired collagen synthesis.

20. Non pharmacology Treatment and Management • Weight bearing exercise improve muscle mass,strength & balance, at least 3x/week • Nutritions • calcium ( 1200-1500), diet & supplements • vit D (800-2000 IU/day), esp for men>65 yo • Use of fall-prevention programs, inc home-based interventions,visual assessment, balance exercise, tai chi

21. Pharmacology • Anti-resorptive therapy, increase bone strength. reducing osteoclasticresorption of bone. • Bisphosphonates • Estrogens • selective estrogen receptor modulators (SERMs) • Calcitonin

22. Pharmacology • Hormon Replacement Therapy • Not recommended, because might increasedthe risk of: • Breast cancer • Stroke • Heartdisease. • Blood clots. • Dementia in women 65 and older. • The WHI study also found that HRT may reduce the risk of: • Colorectal cancer • The number of broken bones in women who are past menopause

23. Complications • Osteoporosis causes the weakening of the bone, making it brittle. • The bone density loss from osteoporosis is a major cause for the patient becoming prone to have bone fractures. • The bones, particularly vertebrae, may crumple, which can result in back pain, lost of height and a hunched forward posture. • Facts: • Osteoporosis causes more than 1.5 million fractures annually. • About 50% of women and 25% of men over age 50 will suffer an osteoporosis-related fracture during their lifetime. • Each year, there are about 700,000 spinal fractures, 300,000 hip fractures, 250,000 broken wrists and more than 300,000 fractures of other bones. • About 80% of the fractures occur after relatively minor falls or accidents.

24. Facts • Osteoporosis causes more than 1.5 million fractures annually. • About 50% of women and 25% of men over age 50 will suffer an osteoporosis-related fracture during their lifetime. • Each year, there are about 700,000 spinal fractures, 300,000 hip fractures, 250,000 broken wrists and more than 300,000 fractures of other bones. • About 80% of the fractures occur after relatively minor falls or accidents.

25. Laboratory test - CBC • Laboratory Exam • Complete Blood Count • Every part of blood will be analyzed • Component: • Red Blood Cells (RBCs)• Hematocrit (Hct)• Hemoglobin (Hgb)• Mean Corpuscular Volume (MCV)• Mean Corpuscular Hemoglobin Concentration (MCHC) • Red cell distribution width (RDW) • White Blood Cells (WBCs) • Platelet • Physical Examination: look, feel, move

26. Range

27. X-Ray Imaging Radiological and Bone Densitometry • Firing electrons  rotating anode • The more dense = whiter it will be • Metal • SF  Radioluscent • The patient, The soft tissues, The bones, The joints

28. X-Ray Contrast Media

30. BMD • Radiographic absorptiometry • Quantitative commuted tomography • Quantitative ultrasonometry • Dual energy x-ray absorption (DXA) • Low dose of x-ray beams • 2 different energy • International database

31. Kyphosis • Exaggerated rounding of the upper spine • 3 types of kyphosis: • postural kyphosis • Poor posture & weakening of muscles and ligments in the back (paraspinous muscle) pain and muscle fatigue • Does not continue to become more progressively worse • Scheuermann’s kyphosis • Structural deformity of the vertebrae:wedging together of several bones of the spine (vertebrae) in a row • Congenital kyphosis • Failure formation or segmentation in the anterior vertebral body

32. Causes • Certain endocrine diseases • Connective tissue disorders • Infection (such as tuberculosis) • Muscular dystrophy • Neurofibromatosis • Paget's disease • Polio • Spina bifida • Tumors • Degenerative diseases of the spine (arthritis or disk degeneration) • Fracturescaused by osteoporosis (osteoporotic compression factors) • Injury (trauma) • Slipping of one vertebra forward on another (spondylolisthesis)

33. Pathophysiology of Back Pain Etiology • Degenerative causes • osteoarthritis, degenerative disk disease, spondylolisthesis • Muscular causes • myofascial pain, paraspinal muscle strain • Mechanical causes • postural disorder, prolapsed intervertebral disk, strain and sprain • Referred pain • endometriosis, hip joint pain, abdominal aortic aneurysm • Vertebral fracture  Osteoporosis

34. Pathophysiology – Disc degeneration • Intervertebral disc materials (nucleus pulposus and anulus fibrosis) herniate into spinal canal  pain in extremities  sciatica • Late stage of disc degeneration  deflation of the disc and rise of the outer rim  spinal nerve and nerve channels become narrow (spinal stenosis)  back and extremity pain • Discs degenerate further  unstable and susceptible toward repeated painful sprains from normal activities • Final stage of disc degeneration  discs becomes stiff  fused together by bone spurs (osteophytes) on the margin of vertebrae  narrowing of spinal nerve channels  nerve pain Taken from http://www.energycenter.com/anatomy.html

35. Step 8 – Synthesis of Old and New Knowledge • Female and elderly are more prone to suffer OP • Calcium and vitamin D intake, plus physical exercise are vital to prevent OP • The best drug to treat OP has not yet been found, but drug that can manage the OP are anti resorptive, hormone replacement therapy. OP can also be treated through weight bearing exercise. • One of the complication of OP is back pain which happens due to vertebral fractures. • The best way to measure BMD is using DXA • Differential diagnosis for osteoporosis are Paget’s disease, multiple myeloma, homocysteinemia, renal osteodystrophy, osteomalacia, scurvy, and hyperparathyroidism

36. Step 9 - Repetition: none Step 10 - Knowledge not known: none Step 11 - Summary • We accept our hypothesis because back pain and kyphosis are the complications of osteoporosis.

37. References • Tortora GJ, Derrickson B. Principles of anatomy & physiology volume 1: organization, support and movement, and control systems of the human body. 13th ed. New Jersey: John Willey & Son; 2011. • Kumar, Abbas, Fausto, Aster. Robbins and Cotran Pathologic Basis of Disease. 8th ed. Philadelphia: Saunders, an imprint of Elsevier Inc; 2010: p1214-1215 • Terris DJ, Gourin CG. Thyroid and Parathyroid Diseases: Medical and Surgical Management. New York; Thieme Medical Publishers, Inc: 2009. • National Center for Biotechnology Information, U.S. National Library of Medicine. Hyperparathyroidism. [online]. [updated 2012 July 19; cited 2012 December 19]. Available from: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002195/ • Taniegra ED. Hyperparathyroidsm. Am Fam Physician. 2004 Jan 15;69(2):333-339 • Vigorita VJ. Orthopaedic Pathology. 2nd ed. United States of America; Lippincott Williams & Wilkins; 2008. • Bone Density Scan. RadiologyInfo. [homepage on the internet]. Available on: http://www.radiologyinfo.org/en/info.cfm?pg=dexa • Solomon W, Warwick D, Nayagam S. Apley’s System of Orthopaedics and Fractures. 9th ed. 2010. London: Hodder Arnold. p 15-25. • Rizer M. Osteoporosis. Prim Care Clin Office Pract 2006; 33:943-951. • Kamal AF. Osteoporosis: definition until management. Faculty of Medicine Universitas Indonesia, Department of Orthopedic and Traumatology. 2011. • Sambrook P, Cooper C. Osteoporosis. Lancet 2006;367:2010-18 • SIGN. Management of Osteoporosis.USA : June,2003 • Simon, H. Osteoporosis: medication [homepage on the Internet].18 november 2008 [cited on 19 desember 2012]. Available at : http://www.umm.edu/patiented/articles/what_medications_osteoporosis_000018_8.htm • National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis -- 2008. Washington, DC. • Brown MD. Conquer back and neck pain: walk it off!. 1st ed. Sunrise River Press: USA; 2008. • Clinical Key. Back pain. [internet. 2012 [cited 19 Dec 2012]. Available from: https://www.clinicalkey.com/topics/rheumatology/back-pain.html • Simon H. Osteoporosis - Complications. [homepage on the Internet]. 2008 [cited 2012 Dec 18]. Available from: University of Maryland Medical Center, Web site: http://www.umm.edu/patiented/articles/how_serious_osteoporosis_000018_4.htm • Solomon L, Warwick D & Nayagam S Apley’s System of Orthopaedics and Fractures. 9th ed. Bristol: Hodder Arnold; 2010. • Rizer M. Osteoporosis. Prim Care Clin Office Pract 2006; 33:943-951. • Kamal AF. Osteoporosis: definition until management. Faculty of Medicine Universitas Indonesia, Department of Orthopedic and Traumatology. 2011. • Sambrook P, Cooper C. Osteoporosis. Lancet 2006;367:2010-18

38. Q & A • Karina: OP needs to be examined first, so how can you conclude it? • If compared to the other differential diagnoses, the symptoms of the woman is more suited as OP • Azka: Which pharmacology treatment is the most commonly used? Why? • Depends on the patient’s condition and side effect. Bisphosphonates are the most common used. • Leo: What exercise affect the muscle strength? • Proper weight bearing exercises • Leo: What is the correlation of testosterones to OP? • Testosterones influence the BMD, for a better bone • Jason: OP and hunchback, which causes which? • \We cant really determine, because of abundant etiologies