core_course_lecture_-_osteoprosis_2010.ppt
- 1. Quality Education for a Healthier Scotland Pharmacy Current updates and new horizon in osteoporosis management Emad Elbanna (MD) Assistant professor of orthopaedic surgery Beni Suef University
- 2. Quality Education for a Healthier Scotland Pharmacy Definition 1. Osteoporosis is a progressive systemic skeletal disease characterised by low bone mass and micro- architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. 2. .
- 3. Quality Education for a Healthier Scotland Pharmacy • Trabecular bone is more susceptible to the effects of osteoporosis • Most osteoporotic fractures occur where there are high levels of trabecular bone eg the vertebrae, the neck of femur (hip) and the wrist
- 4. Quality Education for a Healthier Scotland Pharmacy Bone tissue cells Basically three : • Osteoclasts- large multi-nuclear cells which release enzymes and acids that digest protein and mineral components of bone (resorption) • Osteoblasts- bone builders, synthesize and secrete collagen and other components to create a matrix which is laid down in the bone. They initiate calcification of the matrix and hence bone formation • Osteocytes- mature bone cells (osteoblasts encased in matrix secretions) responsible for exchange of waste and nutrients.
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- 6. Quality Education for a Healthier Scotland Pharmacy Pathophysiology • Bone is constantly re-modelled and repaired due to damage caused by daily use • Osteoclasts “cut” into old bone (resorption) and osteoblasts fill with organic matrix which becomes mineralised (bone formation or ossification) • In osteoporosis the net rate of bone resorption exceed rate of bone formation- normally matched. • Results in a decrease in bone mass and quality
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- 8. Quality Education for a Healthier Scotland Pharmacy -Cathepsin K :very potent protease secreted by the activated osteoclast Resulting in degradation of bone matrix and breakdown of mineral component of bone tissue. -Oxidative stress in bone :Imbalance between production of reactive oxygen species (ROS) and antioxidant Resulting in decreased bone mass formation,osteoblast formation,number and dysfunction
- 9. Quality Education for a Healthier Scotland Pharmacy • One in 3 women and one in 12 men over 50 will sustain an osteoporotic fracture in their lifetime
- 10. Quality Education for a Healthier Scotland Pharmacy Risk factors for Osteoporosis • Age • Premature menopause or hysterectomy Gender • Genetic factors Smoking –Alcohol Obesity Low Vitamin D and calcium level
- 11. Quality Education for a Healthier Scotland Pharmacy Secondary causes of osteoporosis • Long term corticosteroid use ie 5mg or more prednisolone daily for 3 months or more • Aromatase inhibitor treatment • Hyperparathyroidism • Hyperthyroidism • Coeliac disease, malabsorption syndromes, inflammatory bowel disease,IBS • Anorexia • Renal disease • Rheumatoid arthritis • Other drugs- PPI’S, SSRI’s, Anti-epileptics
- 12. Quality Education for a Healthier Scotland Pharmacy -Asymptomatic disease -Generalized bony pain -Fragility fractures (vertebrae,rib,hip and wrist) Diagnosis of osteoporosis
- 13. Quality Education for a Healthier Scotland Pharmacy DEXA scan DEXA is the most popular method for measurig Bone Mineral Density(BMD) Osteoporosis is diagnosed when BMD is less than or equal to 2.5 standard deviation below that of young age (30-40 years old)
- 14. Quality Education for a Healthier Scotland Pharmacy Management -The aim of treatment is to prevent fractures -Non pharmacological measures -Pharmacological agents
- 15. Quality Education for a Healthier Scotland Pharmacy Pharmacological agents Traditional drugs -Antiresorptive measures: Bisphsphanate Estrogen agonists Calcitonin Denosumab -Anabolic agents: Teriparatide
- 16. Quality Education for a Healthier Scotland Pharmacy -Cathepsin K inhibitor (Odanacatib) -Anti-sclerostin antibodies (Romozumab) -Regulating activin signaling (under research) -Insulin like growth factor 1 (under research) New agents
- 17. Quality Education for a Healthier Scotland Pharmacy Vitamin K Folic acid Vitamin B12 supplementations Androgen Fluoride Cytokines and cytokine antagonists (under research) Other therapies
- 18. Quality Education for a Healthier Scotland Pharmacy The aim of combintion is synergistic and additive antiresorptive effect Combined agents of different mechanisms as antiresorptive and anabolic agents like combination of Bisphosphonate and Teriparatide Combined agents of the same mechanisms as combination of Bisphosphonate and Estrogen Combination of anti-inflamatory agents (anti TNF) with anti sclerostin antibodies Combination therapy
- 19. Quality Education for a Healthier Scotland Pharmacy Bisphosphonates • First line treatment • inhibit action of osteoclasts • Available as daily, weekly and monthly oral preparations and 3 monthly and yearly injections • Daily and weekly- alendronate, risedronate, etidronate • Monthly- ibandronate • 3 monthly IV- ibandronate infusion • Yearly IV- zoledronate infusion
- 20. Quality Education for a Healthier Scotland Pharmacy Bisphosphonates cont. -Oral bisphosphonates have complicated dosage regimes and poor bioavailability -Strong evidence to support their use -Accumulates in skeleton -Alendronate usually first choice due to cost -GI Side effects are fairly common with oral bisphosphonates -Recent concerns regarding osteonecrosis of the jaw especially with high dose intravenous versions -Increased risk of low trauma atypical subtrochanteric fracture femur -
- 21. Quality Education for a Healthier Scotland Pharmacy Strontium • Reduce bone resorption and increas bone formation by its action on osteoclasts and osteoblasts • Available as a powder for reconstitution and taken daily usually bedtime • Avoidance of food required 2 hours before and after administration • GIT side effects of nausea and diarrhoea but usually transient • Possible slight increase in risk of venous thromboembolism (VTE) • Possibility of DRESS syndrome occurring (rare)
- 22. Quality Education for a Healthier Scotland Pharmacy • Raloxifene- selective oestrogen receptor modulator (SERM) which selectively binds to oestrogen receptors on bone. • Reduces incidence of vertebral fractures but no effect on non- vertebral or hip fractures. Carries risk of VTE. Not for postmenopausal women for primary prevention. • Teriparatide- a fragment of recombinant human parathyroid hormone. High levels of parathyroid hormone usually cause bone resorption but pulsed doses cause formation. Daily injection. Reduces vertebral and non-vertebral fractures but not hip. Expensive and usually initiated by specialists.
- 23. Quality Education for a Healthier Scotland Pharmacy Calcium and Vitamin D3 - has an important role on bone formation and remodelling. Calcium is required for bone mineralization and vitamin D keeps parathyroid hormone secretion under control (esp elderly & housebound) • Consider using alone or in combination with biphosphonates Calcitonin- hormone produced by thyroid gland. Given as a nasal spray of synthetic calcitonin. Reduces risk of vertebral fracture only
- 24. Quality Education for a Healthier Scotland Pharmacy The first biological agent Inhbits RANKL Administrated every 6 months S.C Not cleared by the kidney Possible increased adherence to rgimen But impact immune system infection Marked suppression of bone remodeling Long term safety and efficacy unknown Denosumab
- 25. Quality Education for a Healthier Scotland Pharmacy Oral bioavalability Weekly administration do not accumulate in skeletal tissues good effect on mineral density Biopsy suggest bone safety Cathepsin K
- 26. Quality Education for a Healthier Scotland Pharmacy Emerging drug Inhibits sclerostin which secreted by osteoclast to reduce bone formation by interfering with proliferation and function of osteoblast FDA has rejected approval of Romosuzamb due to high rate of serious cardiovascular complication(july 2017) Other antibodies developed and tested as Blosozumab Antisclerosin antibodies
- 27. Quality Education for a Healthier Scotland Pharmacy -Enhance the differntaited function of the osteoclast and bone formation -Parenteral administration -High adverse effects -Lack of tissue specificity -Possible role in some malignancies All these factors are concern for development of IGF1 as a theapeutic agent for osteoporosis Insulin like growth factor
- 28. Quality Education for a Healthier Scotland Pharmacy More studies needed to be conducted for understanding : -signaling pathway -Prevention of osteoporosis -Safety and efficacy of pharmacological agents -Drug discovery -Antioxidative measurement Recommendations for future research
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