Comparison of Meds for Osteoporosis

Transcription

1 PL Detail-Document # This PL Detail-Document gives subscribers additional insight related to the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER July 2012 Comparison of Meds for Osteoporosis Bone mineral density (BMD) determination should be offered to all patients at high risk of osteoporosis. Recommendations vary by guideline. In general, candidates include men age 70 and older, women 65 and older, and postmenopausal women under 65 who are thin, who smoke, or who have a family history of fracture. 4,15 Also screen men age 50 to 69 with risk factors. 15 Other reasons to check BMD in postmenopausal women under 65 include vision impairment, repeated falls, lifetime low calcium intake, inactivity, and poor health. Other indications for screening are history of lowtrauma fracture, radiographic osteopenia, vertebral deformity, alcoholism, immobility, organ transplant, chronic corticosteroid use, chronic illness associated with bone loss (e.g., rheumatoid arthritis, hyperthyroidism, etc), or menopause before age Treatment is indicated for postmenopausal women, and men age 50 and older, with a T-score of -2.5 or lower (i.e., osteoporosis) or previous hip or spine facture. 2,15 It is also indicated for osteopenia (T-score -1 to -2.5) in patients with a 10-year hip fracture risk of 3% or higher or a 10-year risk of major osteoporotic fracture of 20% or higher per the FRAX tool (available at 2 Also consider treatment for patients with low-trauma fracture. 2,4 Ensure all patients get adequate calcium and vitamin D. Consider estrogen therapy for prematurely menopausal women less than 50 years old for osteoporosis prevention. 4 Otherwise, estrogen therapy is not indicated solely for prevention of osteoporosis. 4 Treating 10,000 women 50 to 79 years of age with estrogen/progestin for one year prevents six spine and six hip fractures. However, there will be eight more cases of breast cancer, nine more strokes, and 21 more thromboembolic events. 13 For patients with low fracture risk, adequate calcium and vitamin D, and estrogen if appropriate, may be all that is needed for osteoporosis prevention. 2,4 Use the chart below to help individualize pharmacotherapy choice based on efficacy, safety, cost, and convenience. All numbers needed to treat (NNT) are in comparison to placebo. These medications haven t been directly compared. Abbreviations: GI = gastrointestinal; RANK= receptor activator of nuclear factor kappa-b ligand; SERM = selective estrogen receptor modifier Bisphosphonates, oral (alendronate [Fosamax, generics, etc], ibandronate [Boniva (U.S.), generics], risedronate [Actonel, generics (Canada), etc]) Continued Vertebral fracture: Alendronate 15 (16 over 2 years for men 21 ) Ibandronate 21 Risedronate 20 Hip fracture: Alendronate 91 Risedronate 91 Most patients firstline 2.,3 Prevention of postmenopausal osteoporosis or corticosteroid-induced Treatment of postmenopausal Patient who cannot remain upright for at least 30 minutes 2 esophageal or swallowing disorder 2 Patient unable or unwilling to follow dosing instructions 2 Daily, weekly, or monthly dosing a GI side effects: esophagitis, dysphagia, abdominal pain, diarrhea, upset stomach, heartburn 2,4 May cause musculoskeletal pain 4 Associated rarely with jaw osteonecrosis and atypical thigh fracture 4 May reduce risk of breast cancer 2 Consider stopping after 5 years unless

2 (PL Detail-Document #280704: Page 2 of 5) Bisphosphonates, oral, Continued Bisphosphonates, intravenous (zoledronic acid [Reclast, Aclasta (Canada)], ibandronate [Boniva; U.S.]) Raloxifene (Evista)/SERM Vertebral fracture: 14 Hip fracture: 91 (for zoledronic acid) Vertebral fracture: 29 (16 to 46; NNT decreases as risk increases) osteoporosis, corticosteroid-induced osteoporosis, or osteoporosis in men 4 Patient unable to take oral bisphosphonates due to gastrointestinal issues 2 Patient unwilling to follow oral bisphosphonate dosing instructions 2 Prevention and treatment in: 2 postmenopausal women at high risk of breast cancer 2 postmenopausal women who cannot take bisphosphonate therapy 2 women in their 50s or 60s with concerns about long-term bisphosphonate safety 2,19 hypocalcemia 2 renal insufficiency 2,4 hypocalcemia 2 renal insufficiency 2 hot flashes 2 history of venous thromboembolism 2 Patients in whom hip fracture is the primary concern. high risk (e.g., femoral neck T-score <-2.5 or previous vertebral fracture and femoral neck T-score -2 or lower) 7 Zoledronic acid given once a year for treatment, once every 2 years for prevention (single dose for prevention in Canada) 10,11 Ibandronate given once every 3 months for treatment (postmenopausal women) 20 Associated rarely with jaw osteonecrosis and atypical thigh fracture 4 Consider stopping after 3 years unless high risk (e.g., femoral neck T-score <-2.5 or previous vertebral fracture and femoral neck T-score -2 or lower). 7 Acute renal failure reported 2 Acute flu-like reaction 4,20 May cause musculoskeletal pain 4,20 Analgesic effect 2 May reduce risk of breast cancer 2 Expensive (about $2000 per year U.S.; $740 per year Canada) Higher risk of vertebral fracture than hip fracture in women in their 50s or 60s. 19

3 (PL Detail-Document #280704: Page 3 of 5) Calcitonin nasal spray (Miacalcin, generics; Fortical [U.S.]) Vertebral fracture : 12 (in patients with prior vertebral fracture) Treatment in postmenopausal women: 3 who cannot take bisphosphonates 2 with bone pain from vertebral compression fractures 2 Patients in whom hip fracture is the primary concern Women less than 5 years postmenopausal (not proven effective) 16 Side effects include nausea, flushing, and runny nose 4 Not a first-line drug for osteoporosis. It does not have strong fracture efficacy and it has less effects on BMD than other osteoporosis meds. 16 Clinical significance of its relief of vertebral fracture pain unclear 18 Teriparatide (Forteo)/Parathyroid Hormone Vertebral fracture: 11 b Hip fracture: 200 b Treatment in patients with high fracture risk (e.g., previous vertebral fracture, multiple risk factors, very low BMD): 2,4 with postmenopausal with primary or hypogonadal osteoporosis (men) 4 with corticosteroidinduced especially those who have failed or cannot take other agents 4 metabolic bone disease 2 Paget s disease 4 previous skeletal irradiation 4 Elevated alkaline phosphatase of unknown etiology 4 Severe renal impairment 2 Daily subcutaneous injection 2 Side effects include nausea, dizziness, headache, and leg cramps 2 Use for max of 2 years 2,14,17 2-yr treatment course may be followed by bisphosphonate 2 Associated with osteosarcoma in rats 2 Analgesic effect 2 Caution with moderate renal impairment 2 Expensive (about $15,000 per year U.S.; $12,800 per year Canada)

4 (PL Detail-Document #280704: Page 4 of 5) Denosumab (Prolia)/RANKL inhibitor Vertebral fracture: 21 Hip fracture: 200 Treatment in patients with high fracture risk (e.g., previous fracture, multiple risk factors): 2,9 with postmenopausal osteoporosis, especially those who have failed or can t/won t take bisphosphonates, such as those with renal insufficiency 2,4,9 with prostate cancer, receiving androgen deprivation therapy for prostate cancer 8 with breast cancer, receiving an aromatase inhibitor 8 hypocalcemia 2 Subcutaneous injection every 6 mos 2 Dermatologic reactions and cellulitis reported 2 Potential for jaw osteonecrosis and atypical fractures unknown 2 Expensive (about $2000 per year U.S.; $740 per year in Canada) a. Alendronate does not have monthly dosing. Ibandronate does not have weekly dosing. b. Over 19 months 14 c. All numbers needed to treat (NNT) are in comparison to placebo. These medications haven t been directly compared to one another. Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication.

5 (PL Detail-Document #280704: Page 5 of 5) Project Leader in preparation of this PL Detail- Document: Melanie Cupp, Pharm.D., BCPS References 1. Ringe JD, Doherty JG. Absolute risk reduction in osteoporosis: assessing treatment efficacy by number needed to treat. Rheumatol Int 2010;30: Silverman S, Christiansen C. Individualizing osteoporosis therapy. Osteoporos Int 2012;23: Maclaughlin EJ, Sleeper RB, McNatty D, Raehl CL. Management of age-related osteoporosis and prevention of associated fractures. Ther Clin Risk Manag 2006;2: Institute for Clinical Systems Improvement (ICSI). Health care guideline: diagnosis and treatment of osteoporosis. Seventh edition. July ment_of_osteoporosis 3.html. (Accessed June 1, 2012). 5. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361: Chestnut CH, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. Am J Med 2000;109: Black DM, Bauer DC, Schwartz AV, et al. Continuing bisphosphonate treatment for osteoporosis--for whom and for how long? N Engl J Med 2012;366: Product information for Prolia. Amgen Inc. Thousand Oaks, CA May Product monograph for Prolia. Amgen Canada Inc. Mississauga, ON L5N 0A4. October Prescribing information for Reclast. Novartis Pharmaceuticals Corporation. East Hanover, NJ August Product monograph for Aclasta. Novartis Pharmaceuticals Canada. Dorval, QC H9S 1A9. December Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA 1999;282: Nelson HD, Walker M, Zakher B, Mitchell J. Menopausal hormone therapy for the primary prevention of chronic conditions: a systematic review to update the U.S. Preventive Services Task Force recommendations. May /menohrt/menohrtart.htm. (Accessed June 4, 2012). 14. Product information for Forteo. Lilly USA, LLC. Indianapolis, IN March Watts NB, Adler RA, Bilezikian JP, et al. Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97: Management of osteoporosis in postmenopausal women: 2010 position statement of the North American Menopause Society. Menopause 2010;17: Product monograph for Forteo. Eli Lilly Canada Inc. Toronto, ON M1N 2E8. February Bandolier. Calcitonin for pain relief following acute osteoporotic vertebral fractures. g/chronrev/muscskel/cp104.html. (Accessed June 18, 2012). 19. Skugor M. Osteoporosis. Cleveland Clinic. Center for Continuing Education. seasemanagement/endocrinology/osteoporosisdisease/. (Accessed June 19, 2012). 20. Prescribing information for Boniva injection. Genentech. South San Francisco, CA January Orwoll E, Ettinger M, Weiss S, et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med 2000;343: Cite this document as follows: PL Detail-Document, Comparison of Medications for Osteoporosis. Pharmacist s Letter/Prescriber s Letter. July Evidence and Recommendations You Can Trust 3120 West March Lane, P.O. Box 8190, Stockton, CA ~ TEL (209) ~ FAX (209) Subscribers to the Letter can get PL Detail-Documents, like this one, on any topic covered in any issue by going to or