The requirements of the Horizon BCBSNJ Denosumab (Prolia, Xgeva) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

1. Denosumab (Prolia, Xgeva) should be administered by a healthcare professional AND the prescriber is a specialist in the area of the patient’s diagnosis (e.g. endocrinologist, rheumatologist, oncologist) or has consulted with a specialist in the area of the patient’s diagnosis.

2. Prolia (denosumab) is considered medically necessary for the following FDA approved indications:

A. Treatment of postmenopausal women with osteoporosis at high risk for fracture when ALL of the following are met:
• Patient age at least 18 years
• Patient is postmenopausal with a diagnosis of osteoporosis defined as:
  • T-score -2.5 or below in the lumbar spine, femoral neck, total, and /or 33% (one-third) radius; or
  • Low-trauma spine or hip fracture (regardless of BMD); or
  • Osteopenia or low bone mass (T-score between -1 and -2.5) with a fragility fracture of proximal humerus, pelvis, or possibly distal forearm; or
  • Low bone mass or osteopenia and high FRAX® fracture probability based on country-specific thresholds; AND
• Patient is at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture (e.g. premature ovarian failure, low body mass, smoking, rheumatoid arthritis, alcohol intake of 3 or more drinks/day, vitamin D deficiency, hyperkyphosis, parental hip fracture, multiple falls, history of oral glucocorticoids ≥ 5 mg/day of prednisone (or equivalent) for > 3 months)
• Patient has tried and failed or had an inadequate response to a 12 or more months trial of 1 bisphosphonate OR patient is intolerant to or has a contraindication to other oral and IV osteoporosis therapy (e.g. alendronate, risedronate, ibandronate, and zoledronic acid). (Contraindications include esophageal ulceration, esophageal strictures, Barrett's esophagitis, active ulcers and an inability to stand or sit upright for 30 minutes.)
• Patient has no known contraindications to Prolia including hypocalcemia, pregnancy, and known hypersensitivity to Prolia
• Patient will be taking a daily supplement of calcium 1000 mg daily and at least 400 IU vitamin D
• Patient is not concurrently on a bisphosphonate, parathyroid hormone (e.g. Forteo, Tymlos) or Evenity (romosozumab-aqqg) with the requested agent

[INFORMATIONAL NOTE: As per the 2016 AACE Guidelines for Diagnosis and Treatment of Post-Menopausal Osteoporosis:

Table 4 World Health Organization Criteria for Classification of Osteoporosis and Osteopenia
Category	T-score
Normal	-1.0 or above
Low bone mass (osteopenia)*	Between -1.0 and -2.5
Osteoporosis	-2.5 or below
*Fracture rates within this category vary widely. The category of “osteopenia” is useful for epidemiology studies and clinical research but is problematic when applied to individual patients and must be combined with clinical information to make clinical decisions.

Table 5 2016 AACE Diagnosis of Osteoporosis in Postmenopausal Women

1. T-score –2.5 or below in the lumbar spine, femoral neck, total, and/or 33% (one-third) radius 2. Low-trauma spine or hip fracture (regardless of BMD) 3. Osteopenia or low bone mass (T-score between –1 and –2.5) with a fragility fracture of proximal humerus, pelvis, or possibly distal forearm 4. Low bone mass or osteopenia and high FRAX® fracture probability based on country-specific thresholds]

B. Treatment to increase bone mass in men with osteoporosis at high risk for fracture when ALL of the following are met:
• Patients age 30 to 85 years,
• Patient is with bone mineral density (BMD) of -2.5 or below OR -1.0 to -2.5 with prior major osteoporotic fracture
• Patient is at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture (e.g. hypogonadism, low body mass, smoking, rheumatoid arthritis, alcohol intake of 3 or more drinks/day, vitamin D deficiency, hyperkyphosis, parental hip fracture, multiple falls, history of oral glucocorticoids > 5 mg/day or prednisone for > 3 months)
• Patient has tried and failed or had an inadequate response to a 12 or more months trial of 1 bisphosphonate OR patient is intolerant to or has a contraindication to other oral and IV osteoporosis therapy (e.g. alendronate, risedronate, ibandronate, and zoledronic acid). (Contraindications include esophageal ulceration, esophageal strictures, Barrett's esophagitis, active ulcers and an inability to stand or sit upright for 30 minutes.)
• Patient has no known contraindications to Prolia including hypocalcemia and known hypersensitivity to Prolia
• Patient will be taking a daily supplement of calcium 1000 mg daily and at least 400 IU vitamin D
• Patient is not concurrently on a bisphosphonate or parathyroid hormone (e.g. Forteo, Tymlos) with the requested agent
• 
  
[INFORMATIONAL NOTE: Risk factors for bone fractures are from the 2012 Treatment To Prevent Fractures in Men and Women With Low Bone Density or Osteoporosis report from the Agency for Healthcare Research and Quality (US)]

C. Treatment of bone loss in men at high risk for fracture receiving androgen deprivation therapy (ADT) for prostate cancer when ALL of the following are met:
• Patient is a male with a diagnosis of non-metastatic prostate cancer
• Patient is expected to continue ADT therapy for > 12 months
• Patient is at high risk for fracture, defined as a history of osteoporotic fracture, or multiple factors, defined as:
  1. Age > 70 years; OR
  2. Age < 70 years PLUS T score < -1.0;
• Patient has tried and failed or had an inadequate response to a 12 or more months trial of 1 bisphosphonate OR patient is intolerant to or has a contraindication to other oral and IV osteoporosis therapy (e.g. alendronate, risedronate, ibandronate, and zoledronic acid)
• Patient has no known contraindications to Prolia including hypocalcemia and known hypersensitivity to Prolia
• Patient will be taking a daily supplement of calcium 1000 mg daily and at least 400 IU vitamin D
• Patient is not concurrently on a bisphosphonate or parathyroid hormone (e.g. Forteo) with the requested agent

[INFORMATIONAL NOTE: Denosumab was studied by Smith et al (2009) for the prevention of bone loss in men receiving androgen deprivation therapy (ADT) for prostate cancer. The study included patients with histologically confirmed prostate cancer who were receiving ADT with an expected duration of treatment for 12 or more months of the study period. Men were 70 years of age or older, or were younger than 70 but had low BMD (T score at lumbar spine, total hip and femoral neck of between -1.0 and 4.0) at baseline or history of osteoporotic fracture. Patients were excluded if they had taken oral bisphosphonates for more than 3 years or were exposed to IV bisphosphonates in the last 5 years, but were included if they had taken oral bisphosphonates previously for 3 months to 3 years, provided they had been bisphosphonate free for > 1 year prior to enrollment. ]

D. Treatment of bone loss in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer when ALL of the following are met:
• Patient is a female with a diagnosis of nonmetastatic breast cancer
• Patient has one or more of the following risk factors for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture (e.g. hypogonadism, low body mass, smoking, rheumatoid arthritis, alcohol intake of 3 or more drinks/day, vitamin D deficiency, hyperkyphosis, parental hip fracture, multiple falls, history of oral glucocorticoids > 5 mg/day or prednisone for > 3 months)
  Documented Hip DXA (femoral neck or total hip) or lumbar spine T-score ≤-1
• Patient has tried and failed or had an inadequate response to a 12 or more months trial of 1 bisphosphonate OR patient is intolerant to or has a contraindication to other oral and IV osteoporosis therapy (e.g. alendronate, risedronate, ibandronate, and zoledronic acid)
• Patient has no known contraindications to Prolia including hypocalcemia, pregnancy, and known hypersensitivity to Prolia
• Patient will be taking a daily supplement of calcium 1000 mg daily and at least 400 IU vitamin D

[INFORMATIONAL NOTE: Denosumab was studied by Ellis et al (2008) for the prevention of bone loss in women receiving aromatase inhibitor therapy oir nonmetastatic breast cancer. The study included patients who were > 18 years with early-stage histologically or cytologically confirmed breast cancer that was hormone-receptor positive, had evidence of low bone mass (lumbar spine, total hip, or femoral neck BMD corresponding to T score of -1.0 to -2.5. Patients with T score < -2.5, current use of bisphosphonates or prior vertebral fracture were excluded. 63% of patients had been on aromatase inhibitor therapy for > 6 months prior to enrollment. 63% of patients had been on aromatase inhibitor therapy for > 6 months prior to enrollment.
There are many safety concerns with denosumab. In a trial of over 7,800 post menopausal women with osteoporosis, the incidence of nonfatal serious infection was 4.0% in the denosumab group and 3.3% in the placebo. Patients receiving denosumab has a statistically significant greater number of skin and soft tissue related adverse events than placebo at 10.8% vs. 8.2%, respectively. Pancreatitis was reported in 4 patients (0.1%) in the placebo and 8 patients (0.2%) in the Prolia group. There was also an increase incidence of cancer during a three year trial period and the long term carcinogenic effect of denosumab has not been established.]

E. Treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture when ALL of the following are met:
• Patient age at least 18 years
• Patient is with a diagnosis of osteoporosis with documented bone mineral density (BMD) T-score < -2.5.
• Patient has one or more of the following risk factors for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture (e.g. hypogonadism, low body mass index (BMI), smoking, rheumatoid arthritis, alcohol intake of 3 or more drinks/day, vitamin D deficiency, hyperkyphosis, parental hip fracture, multiple falls, history of oral glucocorticoids > 5 mg/day or prednisone for > 3 months)
• Patient will be initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone
• Patient will be on systemic glucocorticoid therapy for at least 6 months
• Patient has tried and failed or had an inadequate response to a 12 or more months trial of 1 bisphosphonate OR patient is intolerant to or has a contraindication to other oral and IV osteoporosis therapy (e.g. alendronate, risedronate, ibandronate, and zoledronic acid). (Contraindications include esophageal ulceration, esophageal strictures, Barrett's esophagitis, active ulcers and an inability to stand or sit upright for 30 minutes.)
• Patient has no known contraindications to Prolia including hypocalcemia, pregnancy (in women), and known hypersensitivity to Prolia
• Patient will be taking a daily supplement of calcium 1000 mg daily and at least 400 IU vitamin
• Patient is not concurrently on a bisphosphonate or parathyroid hormone (e.g. Forteo) with the requested agent

A. Prevention of skeletal-related events in patients with bone metastases from solid tumors
• Patient is ≥ 18 years of age
• Pre-existing hypocalcemia has already been addressed and corrected
• For patient diagnosed with bone metastases secondary to solid tumor (other than breast cancer or castrate-recurrent prostate cancer), patient has an inadequate response, contraindication, or intolerance to zoledronic acid

B. Treatment of adults and skeletally mature adolescents > 13 years old with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
• Pre-existing hypocalcemia has already been addressed and corrected

C. Hypercalcemia of malignancy
• Patients must be > 18 years old; AND
• Patient must have a diagnosis of cancer (malignancy); AND
• Patient must have a diagnosis of refractory hypercalcemia of malignancy defined as an albumin-corrected calcium of >12.5 mg/dL (3.1 mmol/L) despite treatment with a minimum seven (7) day trial on previous therapy with intravenous (IV) bisphosphonate such as zoledronic acid; OR
• Patient has a documented contraindication or intolerance to intravenous (IV) bisphosphonate such as zoledronic acid

D. Prevention of skeletal-related events in patients with multiple myeloma patients
• Patients must be ≥ 18 years old; AND
• Patient must have a diagnosis of multiple myeloma; AND
• Pre-existing hypocalcemia has already been addressed and corrected; AND
• Patient does not have a prior history or current evidence of osteonecrosis/osteomyelitis of the jaw, and does not have any active dental or jaw condition which requires an invasive dental procedure
• Patient has an inadequate response, contraindication, or intolerance to zoledronic acid unless the patient has renal insufficiency

[INFORMATIONAL NOTES Based on FDA approved package insert,
• Patients should be instructed to take calcium 1000 mg daily and at least 400 units of vitamin D daily.
• Patients with creatinine clearance less than 30 mL/min or receiving dialysis are at risk for hypocalcemia. Adequately supplement with calcium and vitamin D.
• Xgeva can cause harm when administered to a pregnant woman. Based on findings in animals, Xgeva is expected to result in adverse reproductive effects and therefore should not be used in pregnant patients. Females of reproductive potential should use effective contraception in order to prevent the potential risk to the fetus.]

• Prolia (denosumab) will be eligible at the FDA approved dose of 60 mg administered subcutaneously every 6 months.
• Xgeva (denosumab) will be eligible at the FDA approved dose of 120 mg administered subcutaneously every four weeks. Giant cell tumor of bone and hypercalcemia of malignancy have additional doses on Days 8 and 15 of the first month of therapy.

There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage will follow the Horizon Policy.

Medicaid Coverage

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Denosumab (Prolia, Xgeva)
Prolia (Denosumab)
Xgeva (Denosumab)

References:
1. Amgen Inc. Prolia (denosumab) prescribing information. Thousand Oaks, CA. March 2020.

2. Amgen Inc. Prolia Risk Evaluation and Mitigation Strategy (REMS) Materials (US). Available at: http://wwwext.amgen.com/media/prolia_in_the_news.html

3. U.S. Department of Health and Human Services (DHHS), Food and Drug Administration (FDA). Background Document for Meeting of Advisory Committee for Reproductive Health Drugs (August 13, 2009) Denosumab. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM176595.pdf

4. Cummings S, Martin J, McClung M, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. NEJM 2009. 361:756-65.

5. ClinicalTrials.gov. An open-label, single arm, extension study to evaluate the long term safety of denosumab (AMG 162) in the treatment of bone loss in subjects undergoing androgen-deprivation therapy for non-metastatic prostate cancer. Available from: http://clinicaltrials.gov/ct2/show/NCT00838201?term=denosumab&rank=2

6. Clinical Trials.gov. Study to compare the efficacy and safety of denosumab versus placebo in males with osteoporosis- the ADAMO trial. Available from: http://clinicaltrials.gov/ct2/show/NCT00980174?term=denosumab&rank=4

7. ClinicalTrials.gov. Study of denosumab in the treatment of hypercalcemia of malignancy in subjects with elevated serum calcium. Available from: http://clinicaltrials.gov/ct2/show/NCT00896454?term=denosumab&rank=10

8. ClinicalTrials.gov. Study of denosumab as adjuvant treatment for women with high early risk breast cancer receiving neoadjuvant or adjuvant therapy (D-Care). Available from: http://clinicaltrials.gov/ct2/show/NCT01077154?term=denosumab&rank=12

9. ClinicalTrials.gov. Safety study of denosumab in subjects with recurrent or unresectable giant cell tumor of bone. Available from: http://clinicaltrials.gov/ct2/show/NCT00680992?term=denosumab&rank=13

10. ClinicalTrials.gov. Study to evaluate the safety and efficacy of denosumab and Actonel® in postmenopausal women transitioned from alendronate therapy. Available from: http://clinicaltrials.gov/ct2/show/NCT00919711?term=denosumab&rank=28

11. ClinicalTrials.gov. Efficacy, safety and tolerability of denosumab in the treatment of rheumatoid arthritis. Available from: http://clinicaltrials.gov/ct2/show/NCT00095498?term=denosumab&rank=20

12. ClinicalTrials.gov. AMG 162 in bisphosphonate naïve metastatic breast cancer. Available from: http://clinicaltrials.gov/ct2/show/NCT00091832?term=denosumab&rank=35

13. ClinicalTrials.gov. A study comparing denosumab vs. zoledronic acids in treatment of bone metastases in breast cancer subjects. Available from: http://clinicaltrials.gov/ct2/show/NCT00321464?term=denosumab&rank=29

14. ClinicalTrials.gov. Double-blind study of denosumab compared with zoledronic acid in treatment of bone metastases in subjects with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. Available from: http://clinicaltrials.gov/ct2/show/NCT00330759?term=denosumab&rank=19

15. ClinicalTrials.gov. Safety and efficacy study of denosumab in subjects with recurrent or unresectable giant cell tumor of bone. Available from: http://clinicaltrials.gov/ct2/show/NCT00396279?term=denosumab&rank=22
16. ClinicalTrials.gov. Open-label, Phase 2, Proof of concept study in Multiple Myeloma- Denosumab. Available from: http://clinicaltrials.gov/ct2/show/NCT00259740?term=denosumab&rank=24

17. ClinicalTrials.gov. AMG 162 in the treamtent of bone loss in subjects undergoing androgen-deprivation for non-metastatic prostate cancer. Available from: http://clinicaltrials.gov/ct2/show/NCT00089674?term=denosumab&rank=31

18. ClinicalTrials.gov. Study on prolonging bone metastasis-free survival in men with hormone refractory prostate cancer. Available from: http://clinicaltrials.gov/ct2/show/NCT00286091?term=denosumab&rank=36

19. Stopeck A, Body JJ, Fujiwara Y, et al. Denosumab versus zoledronic acid for the treatment of breast cancer patients with bone metastases: results of a randomized phase 3 study. Eur J Can Suppl. 2009; 7(3):2. Abstract 2LBA.

20. Stopeck A, Body JJ, Fujiwara Y, et al. Denosumab versus zoledronic acid for the treatment of breast cancer patients with bone metastases: results of a randomized phase 3 study. Presented at: 2009 Annual Meeting of the European Cancer Organisation and European Society for Medical Oncology; September 20-24, 2009. Berlin, Germany.

21. Lipton A, Steger GG, Figueroa J, et al. Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol. 2007; 25:4431-4437.

22. Fizazi K, Lipton A, Mariette X, et al. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol. 2009; 27:1564-1571.

23. Ellis GK, Bone HG, Chlebowski R, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol. 2008. 26: 4875-4882.

24. Ellis GK, Bone HG, Chlebowski R, et al. Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer : subgroup analyses of a phase 3 study. Breast Cancer Res Treat. 2009; 118: 81-87.

25. Smith MR, Egerdie B, Hernandez Toriz N, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. NEJM 2009; 361: 745-755.

26. Smith MR. Saad F, Egerdie B, et al. Effects of denosumab on bone mineral density in men receiving androgen deprivation therapy for prostate cancer. J Urol. 2009; 182: 2670-2676.

27. Henry D, von Moos R, Vadhan-Raj S, et al. A double-blind, randomized study of denosumab versus zoledronic acid for the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. Eur J Can Suppl. 2009; 7(3): 11. Abstract 20LBA.

28. Cohen S, Dore R, Lane N, et al. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis. Arthritis & Rheumatism. 58(5): 1299-1309.

29. Sharp JT, Tsuji W, Ory P, et al. Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid arthritis. Arthritis Care Res. 2010; 62: 537-544.

30. National Institute of Clinical Health and Excellence. Denosumab for the prevention of osteoporotic fractures in postmenopausal women: appraisal consultation document. Available online at: http://guidance.nice.org.uk/TA/Wave20/75/Consultation/DraftGuidance. Last viewed June 2010.

31. Cummings SR, et al. Twice Yearly Denosumab, a Monoclonal Antibody to RANK-ligand, for Prevention of Fractures in Postmenopausal Women with Osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65.

32. Kendler D, Roux C, Benhamou C, et al. Effects of Denosumab on Bone Mineral Density Turnover in Postmenopausal women transitioning from Alendronate Therapy. Journal of Bone and Minderal Research. 2010 Jan; vol 25, No.1:72-81.

33. Brown J, Prince R, Deal C, et al. Comparison of the Effect of Denosumab and alendronate on BMI and biochemical markers of Bone turnover in Postmenopausal Women with Low Bone Mass: A Randomized, Blinded, Phase 3 Trial. J Bone Miner Res 2009;24:153-161.

34. Bone H, Bolognese M, Yuen C, et al. Effects of Denosumab on Bone Mineral Density and Bone Turnover in Postmenopausal Women. J.Clin Endocrinol. Metab. 2008;93:2149-2157.

35. Lafleur J, McAdam-Marx C, Kirkness C, et al. Clinical Risk Factors for Fracture in Postmenopausal Osteoporotic Women: A Review of the Recent Literature. The Annals of Pharmacotherapy. 2008 March; 42 [published online.]

36. Stopeck AT, Lipton A, Body JJ, et al. Denosumab Compared with Zolendronic Acid for the Treatment of Bone Metastases in Patients With Advanced Breast Cancer: A Randomized, Double-Blind Study. J Clin Oncol. 2010;28: 1-10.

37. Amgen, Inc. Xgeva [prescribing information]. Thousand Oaks, CA. March 2016. Updated February 2020.

38. MICROMEDEX® 1.0 (Healthcare Series). DRUGDEX® Evaluations. Denosumab (Xgeva) Available at: http://www.thomsonhc.com. Accessed February 2, 2013

39. MICROMEDEX® 1.0 (Healthcare Series). DRUGDEX® Evaluations. Denosumab (Prolia). Available at: http://www.thomsonhc.com. Accessed February 2, 2013

40. Smith M, Egerdie B, Toriz N, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med, 2009;361(8):745-55.

41. Ellis GK, Bone HG, Chlebowski R, et al. Randomized Trial of Denosumab in Patients Receiving Adjuvant Aromatase Inhibitors for Nonmetastatic Breast Cancer. J Clin Oncol, 2008; 26:4875-4882.

42. Orwoll E., Teglbjaerg CS., Langdahl BL., et al. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab, September 2012, 97(9):3161-3169.

43. National Comprehensive Cancer Network (NCCN): Drugs and Biologics Compendium. Denosumab. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=36. [Accessed on May 30, 2020].

44. Treatment To Prevent Osteoporotic Fractures: An Update. Effective Health Care Program, Agency for Healthcare Research and Quality. May 2012. [Accessed on January 17, 2014]. Available at http://www.effectivehealthcare.ahrq.gov/ehc/products/160/1048/lbd_clin_fin_to_post.pdf

45. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2014.

46. T. Lin, C. Wang, X.-Z. Cai, et al. Comparison of Clinical Efficacy and Safety Between Denosumab and Alendronate in Postmenopausal Women With Osteoporosis. Int J Clin Pract. 2012;66(4):399-408.

47. Bone HG, Bolognese MA, Yuen CK, et al: Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab 2008.

48. Crandall CJ, Newberry SJ, Diamant A, et al. Treatment To Prevent Fractures in Men and Women With Low Bone Density or Osteoporosis: Update of a 2007 Report [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Mar. (Comparative Effectiveness Reviews, No. 53.).

49. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice
Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis 2016. Endocr Pract 2016; 22(Suppl 4):1-42. September 2016.

50. Gnant M, Pfeiler G, Dubsky PC,et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 Aug 1;386(9992):433-43.

51. Henry D, Costa L, Goldwasser F, et al. Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma. J Clin Oncol. 2011;29:1125-1132.

52. ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Denosumab Compared With Risedronate in Individuals Taking Glucocorticoids (GIOP). Available at: https://clinicaltrials.gov/ct2/show/NCT01575873. Accessed June 2018.

53. Buckley L, Guyatt G, Fink HA, et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis & Rhetumatology 2017; Vol 69, No. 8, pp 1521-1537. DOI 10.1002/art.40137

54. Evenity [package insert]. Thousand Oaks, Ca: Amgen Inc ; April 2019.

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

J0897