Recent advances in management - Osteoporosis

1. Recent advances in management - Osteoporosis MEDICINE UPDATE

2. Definition Osteoporosis is defined as a reduction in the strength of bone leading to increased risk of fracture. WHO operationally defines osteoporosis as bone density that falls 2.5 SD below the mean for young healthy adults of same gender – also reffered to as T- Score of – 2.5. Harrison’s 17 th edition

3. osteoporosis Reduced BMD Micro-architectural deterioration Increased risk of fracture

4. Risk factors – non modifiable Female sex Advanced age Caucasian race

5. Risk factors -potentially modifiable Cigarette smoking Low body weight Estrogen deficiency : early menopause (<45y) or b/l ovariectomy prolonged premenstrual amenorrhea ( > 1y ) Low calcium intake Alcoholism Inadequate physical activity Poor health

6. Sedentary occupation Use of systemic corticosteroids Long term heparin therapy Pregnancy Lack of hormone replacement therapy

7. pathogenesis Post menopausal osteoporosis Osteoporosis in men Secondary osteoporosis Corticosteroid induced osteoporosis

8. Post menopausal osteoporosis Causes : low peak bone mass accelerated bone loss after menopause a combination of both factors After menopause , d/t oestrogen def – uncoupling of bone resorption & bone formation – such that the amount of bone removed during bone remodelling exceeds that which is replaced. Genetic & environmental factors – regulate bone mass and bone loss.

9. Osteoporosis in men Less common Secondary cause – 50 % cases – hypogonadism, alcoholism, corticosteroid usage.

10. Secondary osteoporosis Endocrine : hypogonadism hyperparathyroidism hyperthyroidism cushings syn Inflammatory ds : inflammatory bowel ds RA Ankylosing spondylitis Drugs: corticosteroids thyroxine heparin alcohol cancer chemotherapy Git causes : malabsorption chronic liver ds Chronic renal failure Misc : myeloma anorexia nervosa homocystinuria gauchers immobilization poor diet / low bd.wt

11. Corticosteroid induced osteoporosis Directly related to dose & duration of therapy Risk becomes substantial dose of prednisolone>7.5mg daily & continued for >3 months. Adv effects of cal.met : intestinal cal absorption decreased & renal cal excretion increased – sec.hyperparathyroidism & increased bone turn over. Direct inhibitory effect on osteoblast activity and stimulation of osteoblast death via apoptosis.

12. Clinical features Fragility fractures Back pain Ht loss Kyphosis Many are asymptomatic

13. investigations X ray – low specificity & sensitivity S. Ca , S.Phos , ALP – NORMAL BMD – DXA Indications : low trauma # clinical features of osteoporosis osteopenia on x ray corticosteroid Rx f/h osteoporotic # low bd.wt early menopause <45 yrs assessing response of osteoporosis to Rx

14. FDA approved indications for BMD testing Estrogen deficient women at risk of clinical osteoporosis Vertebral abnormalities on Xray suggestive of osteoporosis ( osteopenia / vertebral fractures ) Glucocorticoid therapy equivalent > 7.5 mg of prednisolone or duration of therapy more than 3 months

15. FDA approved indications for BMD testing Primary hyperparathyroidism Monitoring response to FDA- approved medication for osteoporosis Repeat BMD evaluations at > 23 month interval or more frequently if medically justified

16. WHO Osteoporosis criteria Typical sites examined are lumbar spine, hip. Also heel ( calcaneus ) , forearm ( radius, ulna ) , fingers ( phalanges ) BMD in g/cm2 is compared with that of young healthy adult. T score – no of SD the BMD from the avg If T score : > 0 – BMD better than reference 0 to -1 – top 84%, no evidence of osteoporosis -1 to -2.5 – osteopenia -2.5 or worse - osteoporosis

17. Management T Score > -1 : reassure T Score -1 to -2 : mild osteopenia : life style advice T Score -2 to -2.5 : mod osteopenia : life style advice and reassess after 3 -5 yrs T Score < -2.5 : life style adv & drug Rx

18. Treatment should also be considered in postmenopausal women with risk factors ( age, family history, low body weight, steroid use, RA ) , even if BMD is not in osteoporotic range.

19. Management of osteoporotic fractures Management of underlying disease

20. Management – osteoporotic fractures Frequently requires management of fracture and also the underlying disease Hip fractures – almost always require surgical repair ( open reduction and internal fixation , hemiarthroplasty, total arthroplasty )

21. Long bone fracture – external / internal fixation other fractures ( vertebral, rib, pelvic ) – supportive care, no specific orthopedic treatment.

22. Only 25 -30 % of vertebral compression fractures present with sudden onset back pain Acutely symptomatic : NSAIDS, Codeine Percutaneous injection of artificial cement ( polymethylmethacrylate ) into the vertebral body – significant immediate pain relief Short periods of bed rest Early mobilization

23. Management of underlying disease Non pharmacological Pharmacological

24. Non pharmacological management Adequate diet – in proteins, calories, calcium, Vitamin D High impact physical activity : Jogging – increases bone density Stair climbing – increases bone density Regular exercises – helps to increase strength and reduce risk of falling Weight training – helpful to increase muscle strength & bone density Balanced exercises – reduce falls

25. Adequate spinal support – avoid braces or corsets, rigid and excessive immobilization Vertebroplasty Kyphoplasty Cessation of smoking Stop or reduce alcohol

26. Pharmacological Anti resorptive drugs : Bisphosphonates SERM – Raloxifene Estrogen Calcitonin Calcium , vit D Anabolic agents : PTH - Teriparatide

27. Calcium Calcium rich foods : dairy products, fortified food ( cereals, snacks ) ESTIMATED ADEQUATE INTAKE young children( 1-3 y ) – 500 mg/day older children ( 4 – 8 y ) – 800 mg/day Adolescents,young adults(9-18y) 1300mg/day Men, women ( 19-50 y) – 1000mg/day Men, women ( > 51 y ) – 1200 mg/day

28. Calcium supplementation Calcium citrate – 60mg/300mg Calcium lactate – 80mg/600mg Calcium gluconate – 40mg/500mg Calcium carbonate 400mg/g Calcium carbonate + 5ug Vit D2 – 250mg/ tab Calcium carbonate – 500mg/tablet

29. Vit D < 50 y : 200 IU /day 50 – 70 y : 400 IU/day > 70 y : 600 IU/day Multivitamin tablets usually contain 400 IU VitD

30. Bisphosphonates Impair osteoclast function Reduce osteoclast number by induction of apoptosis

31. Etidronate Alendronate Risedronate Ibandronate Zoledronic acid

32. etidronate Ist bisphosphonate to be approved Initially used in pagets disease, hypercalcemia Reduces incidence of vertebral fractures when given in cyclical regime ( 2 weeks on , 2 and ½ months off )

33. alendronate 70 mg once weekly dose 10 mg OD Preventive dose : 35 mg once weekly 5 mg OD Rapid antifracture effect

34. risedronate An aminobisphosphonate Prevent vertebral and non vertebral fractures Treatment / prevention Women : 5 mg OD 35 mg once weekly 75 mg 2 consecutive days monthly 150mg once monthly Men : 35 mg once weekly

35. ibandronate Reduces vertebral fractures Has no protective effect on non vertebral fractures Approved for postmenopausal osteoporosis Treatment or prevention : Oral : 150 mg once monthly , 2.5 mg OD IV : 3 mg IV every 3 monthly

36. Zoledronic acid Most potent bisphosphonate available IV 5 mg over 15 min once yearly

37. calcitonin FDA approved for use in pagets disease hypercalcemia osteoporosis in women > 5 yrs past menopause

38. calcitonin Nasal spray containing calcitonin ( 200IU/day) Dose : 2oo IU ( 1 puff ) once daily in alternating nostrils 100 mg IM /SC once daily

39. teriparatide Biological product that contains a portion of HUMAN PARATHYROID HORMONE Increases bone remodelling with net effect of increased bone mass and bone micro architecture Approved for post menopausal osteoporosis and male osteoporosis Dose : 20 mcg SC once daily For about 2 years

40. Strontium Ranelate Oral therapy Composed of 2 atoms of stable non radioactive strontium coupled with ranelic acid. It has both antiresorptive and anabolic effects Decreases both vertebral and non vertebral fractures

41. SERM - raloxifene Dose : 60 mg OD Useful for treating and preventin postmenopausal osteoporosis Additional benefits : Reduces total and LDL Cholesterol Reduces cardiovascular disease s/e : thromboembolic phenomenon when combined with bisphosphonates

42. Hormone replacement - estrogen Esterified estrogen 0.3 mg OD continously or cyclical regime ( 25 days on , 5 days off ) Adjust to lowest level that will provide effective control Conjugated estrogen– 0.625mg/day Ethinyl estradiol – 5 ug /day

43. Trial Patients received 0.625 mg of conjuagated equine estrogen with 2.5 mg medroxyprogesterone acetate or placebo daily . At 5.2 yrs , relative risk of clinical, vertebral, hip fractures were reduced by 34 %

44. In comparision to placebo, HRT was associated with 29 % increased incidence cardiac events 41 % increased risk of stroke Doubling of thromboembolic events 20 % increase in breast cancer So overall risk out weigh the benefits HRT – at present is recommended primarily for Menopausal and Vasomotor symptoms

45. Thank you