Treatment of osteoporosis

1. Treatment of osteoporosis

2. US FDA-APPROVED DRUGS FOR OSTEOPOROSIS • Bisphosphonates (alendronate, ibandronate,risedronate and zoledronate) • Calcitonin • Estrogens (estrogen and/or hormone therapy) • Parathyroid hormone [PTH (1-34), teriparatide] • Selective estrogen receptor modulators or SERMs (raloxifene).

3. Bisphosphonates • AlendronateFosamax® • Alendronate sodium is approved by the FDA for the prevention (5 mg daily and 35 mg weekly) and treatment (10 mg daily and 70 mg weekly) of osteoporosis in postmenopausal women.

4. Alendronate reduces the incidence of spine, hip and wrist fractures by about 50% over 3 years in patients with a prior spine fracture. It reduces the incidence of spine fractures by 48% over 3 years in patients without a prior spine fracture.

5. IbandronateBoniva® • Ibandronate sodium, in a once monthly tablet of 150 mg, is approved by the FDA for the prevention and treatment of postmenopausal osteoporosis.

6. Ibandronate reduces the incidence of spine fractures by about 50% over 3 years

7. RisedronateActonel® • Risedronate sodium (5 mg daily dose, and 35 mg weekly dose) is approved by the FDA for the prevention and treatment of postmenopausal osteoporosis.

8. Risedronate reduces the incidence of spine fractures by 41-49% and non-spine fractures by 36% over 3 years in patients with a prior spine fracture.

9. Zolendronic Acid (Aclasta®) • Approved for treatment of osteoporosis in postmenopausal women in 2007 • Single 5 mg infusion given IV over > 15 minutes, once yearly • Should still supplement with calcium/vitamin D • May be ideal for those with GI contraindications to the oral formulations

10. Side Effects and Administration of Bisphosphonates • Gastrointestinal problems such as difficulty swallowing, inflammation of the esophagus and gastric ulcer.

11. There have been a few reports of osteonecrosis of the jaw (particularly following intravenous bisphosphonate treatment) and of visual disturbances, which should be reported to the healthcare provider as soon as possible.

12. Alendronate and risedronate must be taken on an empty stomach, first thing in the morning, with 8 ounces of water (no other liquid), at least 30 minutes before eating or drinking. • Patients should remain upright (sitting or standing) during this interval as well.

13. Ibandronate should be taken on the same day each month, at least 60 minutes before first food, drink (other than water) or medication of the day. Ibandronate must be taken on an empty stomach, first thing in the morning, with a glass of tap water. Patients must remain upright for at least one hour after taking medication.

14. CalcitoninMiacalcin® • Salmon calcitonin is FDA-approved for the treatment of osteoporosis in women who are at least 5 years postmenopausal.

15. Intranasal spray that provides 200 (IU). Subcutaneous administration is available. Safe (rhinitis and, rarely, epistaxis.)

16. Estrogen/Hormone Therapy (ET/HT) Premarin® • Approved by the FDA for the prevention of osteoporosis, relief of vasomotor symptoms and vulvovaginal atrophy associated with menopause.

17. The Woman’s Health Initiative (WHI) found that 5 years of HT reduced the risk of clinical vertebral fractures and hip fractures by 34% and other osteoporotic fractures by 23%.

18. The WHI reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli and deep vein phlebitis during 5 years of treatment with Estrogen/Hormone Therapy

19. Because of the risks, ET/HT should be used in the lowest possible doses for the shortest duration to meet treatment goals

20. Parathyroid hormone [PTH(1-34), teriparatide] Forteo® • Approved by the FDA • Daily subcutaneous injection.

21. 20 µg daily : decrease the risk of spine fractures by 65% and non-spine fractures by 53% in patients with osteoporosis, after an average of 18 months of therapy.

22. Well tolerated ( leg cramps and dizziness.) • Because PTH (1-34) caused an increase in the incidence of osteosarcoma in rats, patients with an increased risk of osteosarcoma(e.g., patients with Paget’s disease of bone, prior radiation therapy of the skeleton, bone metastases, hypercalcemia, or a history of skeletal malignancy) should not receive PTH (1-34) therapy.

23. RaloxifeneEvista® • Raloxifene, a SERM, is approved by the FDA for both prevention and treatment of osteoporosis in postmenopausal women.

24. Raloxifene reduces the risk of spine fracture by 30% in patients with and by 55% in patients without a prior spine fracture, over 3 years.

25. Raloxifeneincreases the risk of deep vein thrombosis to a degree similar to that observed with estrogen. It also increases hot flashes (6% over placebo).

26. NON-FDA-APPROVED DRUGS FOR OSTEOPOROSIS • Other bisphosphonates (etidronate, pamidronate, tiludronate). Most of these medications are currently approved for other conditions including Paget's disease, hypercalcemia of malignancy, and myositisossificans

27. Sodium fluoride • Sodium fluoride stimulates the formation of new bone. • The quality of bone mass thus developed is also uncertain, and the evidence that fluoride reduces fracture risk is conflicting and controversial

28. Strontium ranelate • Alternative to bisphosphonates • Particularly in the elderly • If potential for upper gastrointestinal complications • Failed (intolerance or inadequate response) to treatment with other osteoporosis therapies • Beware rash and VTE

29. DENOSUMAB:A NEW TREATMENT

30. Denosumab • Monoclonal Ab to RANKL which drives osteoclasts • Subcutaneous every 6/12 month 60mg • Dramatic and quick effect • Fracture reduction similar to Zoledronate • Cost similar to Risedronate

31. Proven osteoporotic fracture reductionthroughout the skeleton 6 P