Osteoporosis

Osteoporosis

1. OSTEOPOROSIS Dr Rohil Singh Kakkar PG Resident Department of Orthopaedics RHC, India

2. DEFINITION Osteoporosis is a diffuse reduction in bone density that results when the rate of bone resorption exceeds the rate of bone absorption. Histologically , this is apparent by either diminished osteoblastic activity or excessive osteoclastic activity.

3. Osteoporosis by WHO B M D (Bone Mineral Density ) 2. 5 SD or mo r e be l o w th e mea n f o r y ou n g heal t h y adult of same gender( T-score is equal to or less than -2.5 ).

4. WHO CRITERIA FOR OSTEOPOROSIS BMD compare d with young adult T score Normal < 1 SD below >/= -1 Low bone mass ( Osteopenia ) 1-2.5 SD below < -1 > -2.5 Osteoporosis >/= 2.5 SD below </= -2.5 Severe osteoporosis >/= 2.5 SD below PLUS Fracture

5. CLASSIFICATION RIGGS AND MELTON CLASSIFICATION : a.Primary osteoporosis – T ype 1 : P ost menopausal T ype 2 : Age Related Osteoporosis b.Secondary osteoporosis

6. . POST MENOPAUSAL OSTEOPOROSIS (TYPE 1) Caused by lack of estrogen Causes PTH to overstimulate osteoclast AGE RELATED OSTEOPOROSIS (TYPE 2 ) Bone loss due to increased bone turnover Malabsorption Mineral and vitamin deficiency Patients usually present with fractures of the hip , spine and forearm. 23

7. SECONDARY OSTEOPOROSIS ENDOCRINE : Cushing’s syndrome , Hypogonadism , Thyrotoxicosis , Hyperparathyroidism DRUGS : Glucocorticoids , Heparin , Phenytoin , Immunosuppressants CHRONIC DISEASES : Renal impairment , Liver cirrhosis , Malabsorption , Rheumatoid Arthritis OTHERS :Nutritional , Multiple Myeloma , Malignancy

8. Epidemiology In women it is 3 times more common than men due to Low peak bone mass (PBM) H ormonal changes at menopause 1 in 3 women over 50 years suffer from osteoporosis. 1 in 5 men over 50 years suffer from osteoporosis. 15% - 30% men and 30%- 50% women suffer fractures related to osteoporosis in their life time. Peak incidence : western countries – 70 - 80 years india – 50 – 60 years

9. Hormones & Growth factors regulating bone formation Factor Target cells & tissue Effect Interleukins (IL-l, IL-3, lL-6, IL-ll) Bone marrow, osteoclasts Stimulate osteoclast formation & resorption Tumor necrosis factor (TNF-a) ; Granulocyte macrophage stimulating factor (GM-CSF) Osteoclasts Stimulates bone resorption Leukemic inhibitory Factor (LIF) Osteoblasts, osteoclasts Stimulates osteoblast and Osteoclast formation in marrow

10. Factor Target cells Effect Parathyroid Hormone (PTH) Kidney & Bone Stimulate production of Vit-D & helps resorption of calcium Calcitonin Bone osteoclasts Inhibits resorptive action of osteoclasts: lowers circulating Calcium. Calcitriol (1.25-dihydroxy vit-D3) Bone Osteoblasts Bone Osteoclasts, Kidney, Intestine -Stimulates collagen, osteopontin, osteocalcin synthesis; -stimulates cell differentiation; -Stimulates Calcium retention -Stimulates calcium absorption Estrogen Bone Stimulates formation of calcitonin receptors, inhibiting resorption,; Stimulate bone formation Testosterone Muscle, Bone Muscle growth, placing stress on bone to stimulate bone formation Prostaglandins Osteoclasts Stimulate resorption and bone formation Bone Morphogenic protein Mesenchyme Stimulate cartilage protein & bone matrix formation; replication

11. CLINICAL FEATURES A ka SILENT DISEASE. Low back ache- usually mild. Loss of height KYPHOSIS Fractures- m / c at the level of Dorso -Lumbar junction , Hip and Wrist Joint

12. MANAGEMENT INCLUDES : DIAGNOSIS PREVENTION TREATMENT

13. A. DIAGNOSIS INVESTIGATIONS : 1.ROUTINE INVESTIGATIONS TO RULE OUT SECONDARY OSTEOPOROSIS 2. Plain Radiography 3. PHYSICAL EXAMINATION 4. DEXA (GOLD STANDARD FOR MEASURING BMD ) 5.QUANTITATIVE ULTRASOUND 6. BONE TURN OVER MARKERS (BTM)

14. ROUTINE INVESTIGATIONS : THE PRIMARY AIM IS TO EXCLUDE SECONDARY CAUSES OF OSTEOPOROSIS WHICH INCLUDES : COMPLETE BLOOD COUNT ERYTHROCYTE SEDIMENTATION RATE (ESR) SR. CALCIUM , PHOSPHATASE , ALBUMIN ALKALINE PHOSPHATASE PARATHYROID HORMONE (PTH) IF SERUM CALCIUM LEVEL IS HIGH THAN 10.5 mg %

15. X - r a y Post menopausal osteoporosis : Trabecular resorption and cortical resorption Senile osteoporosis: Endosteal resorption Hyperparathyroidism: Sub periosteal resorption Osteoporosis produces increased radiolucency of vertebral bone. Approximately 30 to 80 per cent of bone tissue must be lost before a recognizable abnormality can be detected on spinal radiographs. The main radiographic features of generalized osteoporosis are cortical thinning and increased radiolucency .

16. CONVENTIONAL RADIOGRAPHY LS SPINE- Generalized osteopenia Thining and accentuation of cortex Accentuation of primary trabeculae and thinning of secondary trabaculae. Vertically striated appearance vertebral body.

17. KLEER KOPER score Osteoporosis produces increased radiolucency of vertebral bone. Approximately 30 to 80 per cent of bone tissue must be lost before a recognizable abnormality can be detected on spinal radiographs .

18. PHYSICAL EXAMINATION For Osteoporosis A.Height loss B.Kyphosis C.Humped back For Vertebral fracture A.Wall - occiput distance Test B.Rib -pelvis distance Test

19. Dual Energy X-ray A bsorptiometry (DEXA) Commercially introduced in 1987. Principle – 2 x ray of 70Kv and 140kv are fired on site of measurement with lag time o f 4ms. Detector detects accentuation of 2 beams. C alculates BMD . SITES- Central dexa- lumbar spine, hip, whole body. Peripheral dexa- forearm , calcaneum.

20. Dual Energy X-ray A bsorptiometry (DEXA) - 2-dimensional study BMD = Amount of mineral Area Accuracy at hip > 90% Low radiation exposure Error in Osteomalacia Osteoarthritis Previous fracture

21. BMD Interpretation T score: standard deviation of the BMD from the average sex matched 35-year-old Z score: standard deviation score compared to age matched control For every 1 decrease in T score, double risk of fracture Regardless of BMD, patients with prior osteoporotic fracture have up to 5 times risk of future fracture.

22. INDICATIONS FOR BMD TESTING In females 6 0 yrs + and in men 65 yrs + In postmenopausal women above age 5 5 based on risk factor profile and symptoms. In postmenopausal women and men age 50 and older who have had an adult age fracture, to diagnose and determine degree of osteoporosis At dual-energy X-ray absorptiometry (DXA) facilities using accepted quality assurance measures

23. Sites of measurement are the spine, the hip, calcaneum and the wrists.

24. CONTRAINDICATIONS- PREGNANCY. RECENT ADMINISTRATION OF CONTRAST. AGENT,NUCLEAR MEDICINE SCAN. RADIOPAQUE IMPLANT IN MEASUREMENT AREA. MARKED OBESITY.

25. Ultrasonic measurement Broad-band ultrasound attenuation No radiation exposure Preferred use in assessment of fracture risk

26. Calcaneum is the most common skeletal site for quantitative ultrasound assessment because It has a high percentage of trabecular bone that is replaced more often than cortical bone, providing early evidence of metabolic change. B. The calcaneus is fairly flat and parallel, reducing repositioning errors.

27. The McCue CUBA Ultrasonometry Technology That Can Assess Osteoporosis

28. CT scan True volumetric study Quantitative Computed Tomography (QCT) utilizes CT technology to detect low bone mass and monitors the effects of therapy in patients undergoing treatment. It is a fast, non-invasive exam that detects low bone mass earlier and more accurately than other bone density exams

29. The trabecular BMD is indicated as the most important parameter, and interpreted using the Felsenberg classification based on the following cut-off values: Normal BMD > 120 mg/cc Osteopenia < 120 mg/cc Osteoporosis < 80 mg/cc Very high fracture risk < 50 mg/cc

30. Advantages of CT scan over D E XA : Ability to separate cortical and trabecular bone Provides true volumetric density in units of mg/cc No errors due to spinal degenerative changes or aortic calcification Clinicians and researchers favor DXA because -Scanners are readily available and relatively inexpensive. -The radiation dose is negligible -The T-score scale, defined by the WHO specifically for DXA, provides a standardized classification.

31. BIOCHEMICAL MARKERS OF BONE TURNOVER PREDICT THE RISK OF FRACTURE INDEPENDENTLY OF BONE DENSITY IN UNTREATED PATIENTS PREDICT RAPIDITY OF BONE LOSS IN UNTREATED PATIENTS PREDICT EXTENT OF FRACTURE RISK REDUCTION WHEN REPEATED AFTER 3-6 MONTHS OF TREATMENT PREDICT MAGNITUDE OF INCREASE IN BMD HELP DETERMINE DURATION OF DRUG HOLIDAY AND WHEN AND IF MEDICATION SHOULD BE RESTARTED

32. BONE TURN OVER MARKERS

33. Risk Factors for Fracture (Major) with relative risk >2 (Minor) with relative risk 1-2 Age >70 Estrogen deficiency Menopause Calcium intake <500mg/day Hypogonadism Primary hyperparathyroidism Rheumatoid arthritis Hip fracture h/o in parents Hypercalciuria Glucocorticoids Anticonvulsants High bone turnover Diabetes mellitus Anorexia nervosa Smoking BMI < 18 Alcohol Immobilisation/sedentary life Chr. Renal failure Transplantation Chronic Inflammatory diseases

34. DIFFERENTIAL DIAGNOSIS HYPERPARATHYROIDISM PAGETS DISEASE OSTEOMALACIA OSTEOGENESIS IMPERFECTA MULTIPLE MYELOMA SECONDARY TUMOURS

35. 1.NON PHARMACOLOGICAL – PREVENTION OF OSTEOPOROSIS AND OSTEOPOROTIC FARCTURE. A.NUTRITION B.LIFE STYLE MODIFICATIONS C.PREVENTION OF FALL D.HIP PROTECTORS 2. BASIC THERAUPETIC MEASURES VIT D AND CALCIUM SU P P L EMEN T A T I O N ESTEROGEN AND HRT 3.ANTI RESORBTIVE AGENTS A.CALCITONIN B. BISPHOSHPHANTES C.SERM (SELECTIVE ESTROGEN RECEPTOR MODULATOR ) D.DONESUMAB 4. DRUGS STIMULATE BONE FORMATION 1.TERIPARATIDE 2. STRONTIUM RANELATE TREATMENT

36. LIFESTYLE MODIFICATIONS- a.Physical activity-weight bearing and muscle strengthing exercises. Exercise improves bone strength by 30%to 50%. Exercise should be life long. b.Cessation of smoking,alcohol,high caffeine intake. c.Adequate sunexposure

37. HIP PROTECTORS PREVENT S DIRECT IMPACT ON PELVIS . TYPES : 1.Energy absorption type 2.Energy shunting types 3.Crash helmet type 4.Airbag type

38. ca Men age 50–70 should consume 1000 mg/day of calcium. Women age 51 and older and men age 71 and older consume 1200 mg/day of calcium. Intakes in excess of 1200 to 1500 mg/day may increase the risk of developing kidney stones, cardiovascular disease, and stroke. PHARMACOLOGICAL PREVENTION OF OSTEOPOROSIS CALCIUM

39. VIT D 3 800 to 1000 international units (IU) of vitamin D per day for adults age 50 and older. Treatment of vitamin D deficiency- Adults should be treated with 6 0,000 IU once a week ) for 4-6 weeks to achieve a level of approximately 30 ng/ml. This regimen should be followed by maintenance therapy of 1500–2000 IU/day.

40. Pharmacologic therapy All patients being considered for treatment of osteoporosis should also be counseled on risk factor reduction including the importance of calcium, vitamin D, and exercise as part of any treatment program for osteoporosis. Prior to initiating treatment, patients should be evaluated for secondary causes of osteoporosis and have BMD measurements by central DXA, when available, and vertebral imaging studies when appropriate. Biochemical marker levels should be obtained if monitoring of treatment effects is planned.

41. Who should be considered for treatment? Postmenopausal women and men age 50 and older presenting with the following should be considered- A hip or vertebral fracture (clinically apparent or found on vertebral imaging). T-score ≤−2.5 at the femoral neck , hip joint , or lumbar spine. Low bone mass (T-score between −1.0 and −2.5 at the femoral neck or lumbar spine) a 10-year probability of a hip fracture ≥3 % or a 10-year probability of a major osteoporosis-related fracture ≥20 %.

42. Bisphosphonates Are analogues of pyrophosphates. Cause apoptosis of osteoclasts by disrupting cytoskeleton.

43. 1. Alendronate- prevention -5 mg daily and 35 mg weekly tablets. treatment -10 mg daily tablet, 70 mg weekly tablet . Alendronate is also used in treatment of osteoporosis in men and women taking glucocorticoids. 2.Ibandronate- 2.5 mg daily for 3 years 3.Risedronate- prevention and treatment -5 mg daily tablet; 35 mg weekly tabletfor 6 months.

44. 4.Zoledronic acid prevention and treatment -5 mg by intravenous infusion over at least 15 min once yearly for treatment and once every 2 years for prevention.

45. Drug safety Side effects for all oral bisphosphonates gastrointestinal problems such as difficulty swallowing and oesophagitis and gastritis. All bisphosphonates are contraindicated in patients with estimated GFR below 30–35 ml/min. osteonecrosis of the jaw (ONJ) can occur with long- term use of bisphosphonates (>5year). Although rare, low-trauma atypical femur fractures may be associated with the long-term use of bisphosphonates (e.g., >5 years of use).

46. T eriparatide Teriparatide is approved for the treatment of osteoporosis in postmenopausal women and men at high risk for fracture. It is also approved for treatment in men and women at high risk of fracture with osteoporosis associated with sustained systemic glucocorticoid therapy. DOSE-20 μg daily subcutaneous injection for 18 months. Regular monitoring of sr. calcium and uric acid at 1,6 and 12 months.

47. Calcitonin Treatment of osteoporosis in women who are at least 5 years postmenopausal when alternative treatments are not suitable. 200 IU delivered as a single daily intranasal spray. Intranasal calcitonin can cause rhinitis, epistaxis, and allergic reactions. Very small increase in the risk of certain cancers.

48. SERM (SELECTIVE ESTROGEN RECEPTOR MODULATOR) U sed for both prevention and treatment of osteoporosis. RALOXIFENE-60mg/day .

49. DONESUMAB[RANKL INHIBITOR ] Dose- 60mg every 6months S.C Used in postmenopausal women.

50. HORMONE REPLACEMENT THERAPHY Esterogen with or without progestin is used. Also relieves symptoms of postmenopausal symptoms, vulvovaginal atrophy. Dose-0.625mg daily. Routes –oral,transdermal

51. PREVENTATION TREATMENT Calcium 500mg to 1500 mg 1000 to 1500 Vit – D 400IU 400IU – 800IU Bi phosphonates 1. Alendronate 5mg/day 10mg/day 2. Ibandronate - 150mg/month 3. Rsidronate - 5mg/day 4. Zolendronic acid 5mg once in 2 year 5mg once / 1 year SERMS Rolaxifen 5mg/day 10mg/day Calcitonin 200 IU 200IU Teriparatide 20ug/d 20-40ug/d Donesumab - 60mg/6 months

52. SURGERY IN VERTEBRAL FRACTURES Vertebroplasty T o reduce vertebral fracture–associated pain Kyphoplasty T o restore height or to treat the deformity associated with osteoporotic vertebral fractures P edicle sc rew fixation In progressive vertebral collapse or deformity

53. Role of Orthopaed ic Surgeons The goals of surgical treatment of osteoporotic fractures include R apid mobilization and return to normal function and activities . Back / Bowel / Bladder care. Avoid too much manipulations . Progressive physio therapy .

54. Thank You