Osteoporosis

Osteoporosis is a skeletal disorder in association with compromised bone strength predisposing individuals to an increased fracture risk.
Osteoporosis occurs when there is imbalance between resorption and formation of bone, if resorption is often quicker and formation is slower, or for both reasons. This presentation includes definition, classification, diagnosis, treatment prevention and complications associated with osteoporosis.Osteoporosis can be prevented by properly awarening people about the facts of it. If etiological factors are minimized then the condition can be well regulated. Lifestyle changes like advising physical activities, prohibiting addictions like tobacco, smoking, alcohol, proper diet which in rich in calcium, phosphorus, salt restriction, getting exposure to sunlight. Intrinsic factors including poor vision, musculoskeletal and neurological disease and medications, whereas extrinsic or environmental factors including trailing wires, loose carpets, and ill fitting footwear assessment should be done for reducing fall complication risks.if dietary intake of calcium cannot be achieved then calcium supplementation should be provided. Caffeine intake should be properly regulated since it plays role in calcium excretion. Weight-bearing aerobic and strengthening exercises can decrease the risk of falls and fractures by improving muscle strength, coordination, balance, and mobility.

1. Osteoporosis Dr. Chavan P. R.

2. Terms Osteopenia - bone loss Osteopetrosis –bones become dense and prone to breakage Osteoporosis – bones become weak and brittle

3. Functions of bone Support Protection Movement Blood cells Mineral storage Fat storage PH balance Detoxification Endocrine function

4. Bone Composition Osteoclast Osteoblast Osteoid Osteocytes Inorganic mineral salts Cartilage Endosteum & periosteum

5. OSTEOCLASTS  Are large cells that dissolve the bone. Come from the bone marrow and are related to white blood cells. Have more than one nucleus. Found on the surface of the bone mineral next to the dissolving bone.

6. OSTEOBLASTS  Are the cells that form new bone. Also called  lining cells. Come from the bone marrow Produce new bone called "osteoid" which is made of bone collagen and other protein. Then they control calcium and mineral deposition. Found on the surface of the new bone.

7. OSTEOCYTES   Are cells inside the bone. Come from osteoblasts. These cells can sense pressures or cracks in the bone and help to direct where osteoclasts will dissolve the bone.

8. Definition Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing individuals to an increased fracture risk.

9. Classification

10. Etiology Primary Causes Genetic Factors Hypogonadal State Endocrine Disorders Gastrointestinal Disorders Age Sex Low body mass index (≤19 kg/m2) Previous fragility fracture, particularly of the hip, wrist and spine including morphometric vertebral fracture Cystic fibrosis Homocystinuria Osteogenesis imperfecta Ehlers- Danlos Hypophosphatasia Parental history of hip fracture Gaucher’s disease Idiopathic hypercalciuria Porphyria Glycogen storage diseases Marfan syndrome Riley-Day syndrome Hemochromatosis Menkes steely hair syndrome Androgen insensitivity Anorexia nervosa and bulimia Athletic amenorrhea Hyperprolactinemia Panhypopituitarism Premature ovarian failure Turner syndrome, Klinefelter syndrome Adrenal insufficiency Cushing syndrome Diabetes mellitus Hyperparathyroidism Thyrotoxicosis Celiac disease Gastric bypass Inflammatory bowel disease Malabsorption Pancreatic disease Previous gastrointestinal surgery Primary biliary cirrhosis

11. Hematologic disorders Rheumatic and autoimmune diseases Miscellaneous conditions and diseases Medications Lifestyle factors Hemophilia Leukemia and lymphomas Multiple myeloma Sickle cell disease Systemic mastocytosis Thalassemia Ankylosing spondylitis Lupus Rheumatoid arthritis Other rheumatic and autoimmune diseases Alcoholism Amyloidosis Chronic metabolic acidosis Congestive heart failure Depression Emphysema End-stage renal disease Epilepsy Idiopathic scoliosis Multiple sclerosis Muscular dystrophy Parenteral nutrition Posttransplant bone disease Prior fracture as an adult Sarcoidosis Anticoagulants (heparin) Anticonvulsants Aromatase inhibitors Barbiturates Chemotherapeutic agents Cyclosporine A Depo -medroxyprogesterone Glucocorticoids (‡5mg/day of prednisone or equivalent for ‡3 months) Gonadotropin-releasing hormone agonists Lithium Oral hypoglycemics Proton pump inhibitors Tacrolimus Selective serotonin reuptake inhibitors Alcohol Abuse High salt intake Falling Low calcium intake Inadequate physical activity Excessive thinness Vitamin D insufficiency Immobilization Excess vitamin A Smoking (active or passive)

12. Pathophysiology

13. Clinical presentations Occurrence of Fractures after bending, lifting, or falling, or independent of any activity. Fractures mainly involving the vertebrae, proximal femur, and distal radius (wrist or Colles ’ fracture). Patients with vertebrae fracture show moderate to severe back pain radiating down a leg after a new vertebral fracture. Though pain subsides significantly after 2 to 4 weeks, residual, chronic, low-back pain may persist. Decrease in height and curve the spine due to Multiple vertebral fractures (kyphosis or lordosis) with or without significant back pain. Severe pain, swelling, and reduced function and mobility at the fracture site can be associated with Patients of nonvertebral fracture.

14. Diagnosis History and physical examination Bone parameter assessment Dexa scan T score findings

15. Fracture Risk Assessment Tool Model 10-year probability of hip fracture or a major osteoporotic fracture (clinical spine, hip, forearm, or humerus). Biochemical bone turnover marker - serum C-terminal telopeptide type-I collagen (s-CTX) and urinary N- telopeptide (NTX), and formation markers, such as serum procollagen type-I N-terminal propeptide (s-PINP),

16. Other diagnostic tests includes Complete blood count (CBC) Serum creatinine, calcium, phosphorus, and magnesium Alanin aminotransferase (ALT), aspartat aminotransferase (AST), and alkaline phosphatase (AP) Thyroid-stimulating hormone (TSH) and free T4 Vitamin D (V-D) (25 (OH) D) Parathyroid hormone (PTH) Total testosterone and gonadotropin in younger men BTMs Serum protein electrophoresis (SPEP), serum immunofixation, and serum-free light chains Tissue transglutaminase antibodies (IgA and IgG) Iron and ferritin level Homocysteine Prolactin Tryptase 24-h urinary calcium Urinary protein electrophoresis (UPEP) Urinary-free cortisol level Urinary histamine

17. Desired outcomes Prevention of disease development. Optimization of skeletal development and peak bone mass accrual in childhood, adolescence, and early adulthood will reduce the future incidence of osteoporosis. After disease development stabilization and improvement of bone mass and strength and prevention of fractures. Reducing future falls and fractures, Improving functional capacity, Reducing pain and deformity, and Improving quality of life.

18. Complications Limited mobility - Due to Osteoporosis there is limitation to physical activity resulting in weight gain and further complications associated with obesity like heart diseases, hyperlipidemia , diabetes mellitus etc. again severe stress on bone can increase risk of fractures.

19. Depression -Reduced mobility can increase selfing create stressful conditions about health and develop fear of fracture risk can affect mental health of patient leading to depression.

20. Pain -Persistent back and neck pain can result from the fracture. Also pain at the site of fracture always be there.

21. Hospital admission -Some fractures need surgical interventions and thus the hospital stay and cost of hospitalization gets increased. Again risks of hospital acquired infections and cardiovascular complications can be observed due to longer stay in bedridden patients.

22. Evaluation of Therapeutic Outcomes Patients with low bone mass should be examined at least annually. Patients should be asked about possible fracture symptoms (e.g., bone pain, disability) at each visit. Medication adherence and tolerance evaluation must be done Central dual X-ray absorptiometry Bone Mineral Density measurements should be done for 1-2 years. Frequent monitoring for assessment of bone loss has to be carried out.

23. Treatment Non Pharmac treatment Prevention by awareness Rule out cause Lifestyle changes Physical activity prohibiting addictions like tobacco, smoking, alcohol

24. proper diet which in rich in calcium, phosphorus salt restriction, getting exposure to sunlight Intrinsic and extrinsic factor assessment caffeine

25. Biphosphonates binds to hydroxyapatite that helps to build up integrity and to increase the bone mineral density and also prevent resorption by inhibing the osteoclasts and thus increase the life of bones upto 10 years. The risk of fracture also gets reduced.

26. Rising of bone mineral density begins with dose administration can increase it upto 6-12 months with therapy. After discontinuation of therapy also the benefits lasts for the duration depending on the therapy administration.

27. IV ibandronate and zoledronic acid are only used to treat postmenopausal osteoporosis while other class of drugs like Alendronate, risedronate, and oral ibandronate can also be considered for cure purpose.

28. The oral tablets should be taken in the morning with at least 6 oz of plain tap water at least 30 minutes (60 minutes for oral ibandronate) before consuming any food, supplement, or medication. As drugs are having risks of precipitation of esophageal irritation and ulceration, patient should be advised to remain upright (sitting or standing) for at least 30 minutes after alendronate and risedronate and 1 hour after ibandronate administration

29. If doses are missed they should be taken as per next mentioned schedule. The adverse effects associated with class are nausea, abdominal pain, dyspepsia. Esophageal, gastric, or duodenal irritation, perforation, ulceration or bleeding, fever, flu-like symptoms, and local injection-site reactions, Osteonecrosis of the jaw.

30. Romosozumab is a monoclonal antibody acting on sclerostin found to inhibit bone resorption and increases bone formation. It proved helpful in combination with alendronate for increasing bone mass. But it has property to affect vascular network and can increase risk of cardiac complications and also can worsen the osteoporotic state

31. Mixed Estrogen Agonists/Antagonists Drugs bind to selective estrogen receptors and agonize or antagonize the activity of different tissues. Raloxifen is an agonist at bone and antagonist at uterus and breast. It can be used to treat hip, spine fractures as well as in breast cancer also. They can alter lipoprotein levels also but are not used clinically.

32. Adverse effects include hot flushes in women finishing menopause or those discontinuing estrogen therapies. Endometrial bleeding can occur rarely. It is contraindicated in women with venous thromboembolism.

33. Calcitonin Thyroid gland releases calcitonin that increases calcium levels showing antiresorptive properties. After menopause it should be given atleast upto 5years. Its efficiency is only associated with vertebral fracture.

34. It is given as a short therapy that is for 4 weeks. It is prescribed by intranasal way 200 units daily every alternate day and 100 units daily can be given subcutaneously but is rarely prescribed because of its adverse effects and cost.

35. Estrogen therapy Estrogen work by inhibiting osteoclasts cytokine release and inducing osteoclasts death. Estrogen is required for postmenopausal women and can reduce the risk of fracture than other agents but with discontinuation of therapy bone loss accelerates and fracture risk get increased.

36. Testosterone Testosterone increases bone density specially spine bone density. It decreases bone loss in case of Hypogonadal diseased states of men. Methyl testosterone with dose 1.25-2.5mg daily or testosterone implants with dose 50mg daily for 3 months can be proved helpful for rising the bone mineral density in some women. Testosterone is available in various forms like oral, gel, transdermal, intramuscular and pellet preperation .

37. Thiazide Diuretics Thiazide diuretics can decrease the urinary excretion of calcium by increasing its reabsorption. It’s mainly prescribed for the patients on glucocorticoid therapy showing 24hr urinary calcium excretion >300mg.

38. Anabolic Therapy Teriparatide is a recombinant product of parathyroid hormone. It increases bone density, integrity and strength of bone and reduces bone loss. Mainly used for managing lumbar spine bone mineral density. It is given with dose of 20mcg subcutaneously in thigh or abdominal area. Transient hypercalcemia may develop rarely. It is contraindicated in osteosarcoma.

39. Surgery As per some studies Vertebroplasty or kyphoplasty may prove effective inselected patients. Patients with vertebral fracture with severe pain can suffer may get benefitted from vertebral augmentation or vertebroplasty .

40. Treatment of glucocorticoid induced osteoporosis

41. Glucocorticoids resultantly decrease bone formation, calcium balance, bone quality, bone mass and increases resorption with risk of fracture. Such complications will develop only with long term use of these agents that’s why monitoring is required. Patients with long term therapy of Glucocorticoids should follow lifestyle modification and should receive calcium (1500mg) and vitamin d (800-1200 units) supplementation to cope up the loss.

42. Alendronate and risedronate show maximum efficacy with glucocorticoid induced osteoporosis, further as per the american college of rheumatology guidelines patients receiving systemic glucocorticoids for more than 3 months should receive bisphosphonates, if bisphosphonates are not tolerated or contraindicated then teriparatide can be used. Testosterone replacement can also be followed in case of male and high dose oral contraceptives can also be utilized in premenopausal females.

43. Thank you