Medical Drug Criteria (MDC)
Policy Num: M5.001.028
Policy Name: Denosumab Products and its biosimilars
Policy ID: [M5.001.028] [Ac/MA/ M+ P-] [0.00.00]
Last Review: January 14, 2026
Next Review: January 20, 2027
Related Policies:
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Denosumab is a fully human monoclonal antibody against receptor activator of nuclear factor κ-β ligand (RANKL) and inhibits its action on the surface receptors expressed on osteoclasts. This causes reduced osteoclast formation, function and survival, consequently decreasing bone resorption, increasing bone mass, and strengthening both cortical and trabecular bone. The role of excessive RANKL as a contributor to conditions characterized by bone loss or bone destruction has been well studied. A comprehensive clinical development program for denosumab resulted in a robust data set that supported global and regulatory approvals of the RANKL-targeted antibody denosumab in the bone loss and cancer inducted bone destruction settings.
To define the clinical criteria, coverage parameters, and utilization requirements for denosumab products, including biosimilars, to ensure their appropriate, evidence-based, and medically necessary use. This policy aims to promote safe and effective patient care while supporting consistent decision-making, regulatory compliance, and responsible resource utilization in accordance with current clinical guidelines and approved indications.
| Indications and Specific Criteria | ||
| Indication | Criteria | Agents |
| Postmenopausal Osteoporosis Osteoporosis in biological males | When ALL of the following are met:
i. FRAX10-year probability of major osteoporotic fracture ≥ 20%2
c. The dose does not exceed 60 mg SQ every 6 months d. ONE of the following: i. Member had an inadequate response or intolerance to bisphosphonate therapy (oral or IV) ii. Member is not a candidate for bisphosphonate therap iii. Member has a history of a fragility or osteoporotic fracture iv. Member is at high risk of falls or has a history of falls v. Member has a BMD T-score of -3.0 or lower[a] vi. FRAX 10-year probability of major osteoporotic fracture ≥ 30%2 vii. FRAX 10-year probability of hip fracture ≥ 4.5%2 | Prolia Osvyrti Enoby Bosaya Bildyos Conexxence Stoboclo Ospomyv Jubbonti Boncressa |
| Non-metastatic Prostate Cancer-Increase | When ALL of the following are met: 1. Member is diagnosed with non-metastatic prostate cancer 2. Member is receiving androgen deprivation therapy (e.g., surgical castration, medical castration, gonadotropin-releasing hormone agonist) 3. Member meets ONE of the following: a. Pre-treatment BMD T-score of -1 or lower[a] b. Member has a history of a fragility fracture 4. Denosumab will not be used in combination with other antiresorptive or anabolic agents (e.g., bisphosphonates, parathyroid hormone analogs, or romosozumab) 5. The dose does not exceed 60 mg SQ every 6 months | Prolia Osvyrti Enoby Bosaya Bildyos Conexxence Stoboclo Ospomyv Jubbonti Boncressa |
| Breast Cancer-Increase bone mass | When ALL of the following are met: 1. Member is receiving concomitant aromatase inhibitor therapy (e.g., anastrozole [Arimidex], letrozole [Femara], exemestane [Aromasin]) as adjuvant therapy 2. Denosumab will not be used in combination with other antiresorptive or anabolic agents (e.g., bisphosphonates, parathyroid hormone analogs, or romosozumab) 3. Dose does not exceed 60 mg SQ every 6 months 4. EITHER of the following: a. Member had an inadequate response or intolerance to bisphosphonate therapy (oral or IV) b. Member is not a candidate for bisphosphonate therapy | Prolia Osvyrti Enoby Bosaya Bildyos Conexxence Stoboclo Ospomyv Jubbonti Boncressa |
| Glucocorticoid-induced osteoporosis | When ALL of the following are met: 1. History of prednisone or its equivalent at a dose of 2.5 mg/day or greater for 3 months or more 2. Member meets ONE of the following: a. Member has a diagnosis of osteoporosis b. Member has a BMD T-score between - 1.0 and -2.5[a] and ONE of the following1 i. FRAX 10-year probability of major osteoporotic fracture ≥ 20%2 ii. FRAX 10-year probability of hip fracture ≥ 3%2 iii. Fragility fracture 3. Denosumab will not be used in combination with other antiresorptive or anabolic agents (e.g., bisphosphonates, parathyroid hormone analogs, or romosozumab) 4. The dose does not exceed 60 mg SQ every 6 months 5. ONE of the following: a. Member had an inadequate response or intolerance to bisphosphonate therapy (oral or IV) b. Member is not a candidate for bisphosphonate therapy c. Member has a history of a fragility fracture d. Member is at high risk of falls or has a history of falls e. Member has a BMD T-score of -2.5 or lower[a] f. FRAX 10-year probability of major osteoporotic fracture ≥ 20%2 g. FRAX 10-year probability of hip fracture ≥ 3%2 h. High dose glucocorticoid use with prednisone equivalent of greater than or equal to 30 mg/day for 30 days or cumulative doses of greater than or equal to 5 grams per year | Prolia Osvyrti Enoby Bosaya Bildyos Conexxence Stoboclo Ospomyv Jubbonti Boncressa |
| Systemic Mastocytosis | When ALL of the following are met: 1. Member is diagnosed with systemic mastocytosis 2. Denosumab will not be used in combination with other antiresorptive or anabolic agents (e.g., bisphosphonates, parathyroid hormone analogs, or romosozumab) 3. Dose does not exceed 60 mg SQ every 6 months 4. Member is not a candidate for, or had an inadequate response or intolerance to zoledronic acid (Reclast®) | N/A |
| Bone metastases secondary to breast cancer | When ALL of the following are met: 1. Member is diagnosed with breast cancer 2. Member has bone metastases 3. Denosumab will be used in conjunction with standard antineoplastic therapy (i.e., chemotherapy or endocrine therapy) 4. Denosumab will not be used in combination with other antiresorptive or anabolic agents (e.g., bisphosphonates, parathyroid hormone analogs, or romosozumab) 5. Dose does not exceed 120 mg SQ every 4 weeks | Aukelso Bilprevda Bomyntra Osenvelt Wyost Xbryk |
| Bone metastases secondary to lung cancer | When ALL of the following are met: 1. Member is diagnosed with lung cancer 2. Member has bone metastases 3. Denosumab will not be used in combination with other antiresorptive or anabolic agents (e.g., bisphosphonates, parathyroid hormone analogs, or romosozumab) 4. Dose does not exceed 120 mg SQ every 4 weeks | Xgeva Jubereq Xtrenbo Aukelso Bilprevda Bomyntra Osenvelt Xbryk Wyost Oziltus |
| Bone metastases secondary to castrate recurrent prostate cancer | When ALL of the following are met: 1. Member is diagnosed with castrate-recurrent prostate cancer 2. Member has bone metastases 3. Denosumab will not be used in combination with other antiresorptive or anabolic agents (e.g., bisphosphonates, parathyroid hormone analogs, or romosozumab) 4. Dose does not exceed 120 mg SQ every 4 weeks | Xgeva Jubereq Xtrenbo Aukelso Bilprevda Bomyntra Osenvelt Xbryk Wyost Oziltus |
| Bone metastases secondary to solid tumor (other than breast cancer, | When ALL of the following are met: 1. Member has a solid tumor cancer diagnosis (e.g., thyroid cancer, kidney cancer) 2. Member has bone metastases 3. Denosumab will not be used in combination with other antiresorptive or anabolic agents (e.g., bisphosphonates, parathyroid hormone analogs, or romosozumab) 4. Dose does not exceed 120 mg SQ every 4 weeks | Xgeva Jubereq Xtrenbo Aukelso Bilprevda Bomyntra Osenvelt Xbryk Wyost Oziltus |
| Giant Cell Tumor of the Bone | When BOTH of the following are met: 1. Denosumab will not be used in combination with other antiresorptive or anabolic agents (e.g., bisphosphonates, parathyroid hormone analogs, or romosozumab) 2. Dose does not exceed 120 mg every 4 weeks (Note: an additional dose of 120 mg on days 8 and 15 will be permitted for the first cycle only) | Xgeva Jubereq Xtrenbo Aukelso Bilprevda Bomyntra Osenvelt Xbryk Wyost Oziltus |
| Hypercalcemia of Malignancy | When ALL of the following are met: 1. Member has a cancer diagnosis with tumor related hypercalcemia (albumin corrected calcium± of 12 mg/dL or greater) 2. Denosumab will not be used in combination with other antiresorptive or anabolic agents (e.g., bisphosphonates, parathyroid hormone analogs, or romosozumab) 3. Dose does not exceed 120 mg every 4 weeks (Note: an additional dose of 120 mg on days 8 and 15 will be permitted for the first cycle only) | Xgeva Jubereq Xtrenbo Aukelso Bilprevda Bomyntra Osenvelt Xbryk Wyost Oziltus |
| Multiple myeloma, prevention of skeletalrelated events | When ALL of the following are met: 1. Member is diagnosed with active (symptomatic) multiple myeloma [i.e., NOT smoldering (asymptomatic) myeloma] 2. Denosumab will be used in combination with primary myeloma therapy 3. Denosumab will not be used in combination with other antiresorptive or anabolic agents (e.g., bisphosphonates, parathyroid hormone analogs, or romosozumab) 4. Dose does not exceed 120 mg SQ every 4 weeks | Xgeva Jubereq Xtrenbo Aukelso Bilprevda Bomyntra Osenvelt Xbryk Wyost Oziltus |
| BMD, bone mineral density; IV, intravenous
| ||
Triple-S uses the following criteria and clinical compendia in its determination of a "Medically-Accepted Indication":
An FDA approved, labeled indication or a use supported in the American Hospital Formulary Service Drug Information (AHFS-DI), NCCN Drugs and Biologics Compendium, Truven Health Analytics Micromedex DrugDex®, Elsevier/Gold Standard Clinical Pharmacology and Wolters Kluwer Lexi-Drugs® as the acceptable compendia based on CMS' Change Request 6191 (Compendia as Authoritative Sources for Use in the Determination of a "Medically Accepted Indication" of Drugs and Biologicals Used Off-Label in an Anti-Cancer Chemotherapeutic Regimen)
The compendia listed above will be accepted at the following levels;
· American Hospital Formulary Service-Drug Information (AHFS-DI) –indication is supportive
· NCCN Drugs and Biologics Compendium - indication is a Category 1, 2A or 2B
· Micromedex DrugDex® – indication is Class I, Class IIa, or Class IIb or
· Clinical Pharmacology – indication is supportive
· Lexi-Drugs - indication is rated as “Evidence Level A”
| FDA-approved indications and dosage | |
| Prolia and biosimilars (Bildyos, Bosaya, Conexxence, Jubbonti, Ospomyv, Stoboclo) | |
| Indication | Dose/Administration |
| Treatment of postmenopausal women with | · 60 mg SQ every 6 months3 · Inject into upper arm, upper thigh, or abdomen (administered by a healthcare professional) · Concomitant therapy with calcium 1000 mg and at least 400 IU vitamin daily is recommended · Pregnancy must be ruled out prior to administration in all biological females of reproductive potential |
| Treatment to increase bone mass in men with | |
| Treatment of glucocorticoid-incuded | |
| Treatment to increase bone mass in men at | |
| Treatment to increase bone mass in women at | |
| Xgeva and biosimilars (Aukelso, Bilprevda, Bomyntra, Osenvelt, Wyost, Xbryk) | |
| Indication | Dose/Administration |
| Prevention of skeletal-related events in | · 120 mg SQ every 4 weeks3 · Inject into upper arm, upper thigh, or abdomen · Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia |
| Giant cell tumor of bone | · 120 mg SQ every 4 weeks with additional 120 mg doses on days 8 and 15 of the first cycle3 · Inject into upper arm, upper thigh, or abdomen · Concomitant therapy with calcium and vitamin D as necessary to treat or prevent hypocalcemia |
| (3) SQ; subcutaneously | |
Bildyos and Bilprevda are considered as covered agents when the criteria for medical necessity established in this policy are met.
Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.
Prolia, Xgeva and other approved biosimilars are excluded from coverage under the Medical Benefit. Coverage, if applicable, is subject to the member’s Pharmacy Benefit plan design and applicable formulary requirements.
Any prescription for Prolia or Xgeva will be interchangeble for Bildyos or Bilprevda as applicable and according to Puerto Rico applicable regulations.
1. ACOG Practice Bulletin on Osteoporosis. American Family Physician. 2013; 88(4): 273 – 275.
2. Aukelso (denosumab-kyqq) [package insert]. Biocon Biologics Inc, Cambridge (MA): September 2025.
3. Bildyos (denosumab-nxxp) [package insert]. Organon & Co. Jersy City (NJ): August 2025.
4. Bilprevda (denosumab-nxxp) [package insert]. Organon & Co. Jersy City (NJ): August 2025.
5. Bomyntra (denosumab-bnht) [package insert]. Fresenius Kabi USA. Lake Zurich, IL. March 2025.
6. Bosaya (denosumab-kyqq) [package insert]. Biocon Biologics Inc, Cambridge (MA): September 2025.
7. Buckley L, Guyatt G, Fink HA et al. 2017 American College of Rheumatology Guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis & Rheumatology. 2017: 69: 1521- 1537.
8. 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. Endocr Pract. 2016; 22: Suppl 4;1-42.
9. 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 – 2020 Update. Endocr Pract. 2020; 26: Suppl 1;1-46.
10. Chawla S, Henshaw R, Seeger L, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumor of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol 2013:14:901-08.
11. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.;2025. URL www.clinicalpharmacilogy-ip.com Accessed 08/31/25.
12. Cohen SB, Dore RK, Lane NE, et al. Denosumab Treatment Effects on Structural Damage, Bone Mineral Density, and Bone Turnover in Rheumatoid Arthritis. Arthritis Rheum 2008;58:1299-1309.
13. Conexxence (denosumab-bnht) [package insert]. Fresenius Kabi USA. Lake Zurich, IL. March 2025.
14. Cosman F, de Beur SJ, LeBoff MS, et al. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014; 25 (10): 2359-81.
15. Cummins SR, San Martin J, McClung MR, et al. Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis. N Engl J Med 2009;361:756-65.
16. Denosumab. In: McEvoy GK, editor. AHFS drug information 2016[monograph on the Internet]. Bethesda (MD): American Society of Health-System Pharmacists; 2016 [cited 2016 Dec 16]. Available from: http://online.statref.com. Subscription required to view
17. Eastell R, Rosen CJ, Black DM et al. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society clinical practice guideline. 2019; 104: 1595 – 1622.
18. Ellis GK, Bone HG, Chlebowski, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol 26:4875-82.
19. FRAX® Fracture Risk Assessment Tool. https://www.sheffield.ac.uk/FRAX/index.aspx
20. Humphrey MB, Russell L, Danila M et al. 2022 American College or Rheumatology for the prevention and treatment of Glucocorticoid-induced osteoporosis. Arthritis Rheumatol. 2023 75 (12): 2088-2102.
21. Jubbonti (denosumab-bbdz) [package insert]. Sandoz Inc. Princeton (NJ): October 2024.
22. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 08/31/25.
23. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 08/31/25.
24. North American Menopause Society (NAMS) Position Statement. Management of osteoporosis in postmenopausal women: 2010 position statement of the NAMS. Menopause. 2010; 17(1): 25-54.
25. NOF: fast facts on osteoporosis [Internet]. Washington DC: National Osteoporosis Foundation; c2010 [cited 2012 Dec 3]. Available from: http://www.NOF.org.
26. Osenvelt (denosumab-bmwo) [package insert]. Celtrion Inc. Jersy City (NJ). February 2025. 27. Ospomyv (denosumab-dssb) [package insert]. Samsung Bioepis Co, Ltd, Republic of Korea: October 2025.
28. Prolia (denosumab) [package insert]. Amgen Inc. Thousand Oaks (CA): May 2025.
29. Scagliotti GV, Hirsh V, Siena S, et al. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid; a subgroup analysis from a randomized phase 3 study. J Thorac Oncol 2012;7:1823-29.
30. Shoback D, Rosen CJ, Black DM et al. Pharmacological management of osteoporosis in postmenopausal women: an endocrine society guideline update. J Clin Endocrinol Metab. 2020; 105: 1-8.
31. Smith MR, Egerdie B, Toriz NH, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 2009;361:745-55.
32. Stoboclo (denosumab-bmwo) [package insert]. Celtrion Inc. Jersy City (NJ). February 2025.
33. Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advance breast cancer: a randomized, double-blind study. J Clin Oncol 2010.
34. Watts NB, Adler RA, Bilezikan JP, Drake MT, et al. Osteoporosis in men: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2012;97(6):1802-22.
35. Watts NB, Bilezkian JP, Camacho PM et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocrine Practice. 2010; 16 (Suppl 3): 1-37.
36. Wyost (denosumab-bbdz) [package insert]. Sandoz Inc. Princeton (NJ): March 2024.
37. Xbryk (denosumab-dssb) [package insert]. Samsung Bioepis Co, Ltd, Republic of Korea: October 2025.
38. Xgeva (denosumab) [package insert]: Amgen Inc. Thousand Oaks (CA): May 2025.
| Codes | Number | Description |
|---|---|---|
| HCPCS | J0897 | Injection, denosumab, 1 mg (PROLIA, XGEVA) |
| J3590 | Bildyos® SC (denosumab-nxxp), Bilprevda® SC (denosumab-nxxp), Bosaya® (denosumab-kyqq) | |
| Q5136 | Injection, denosumab-bbdz (jubbonti/wyost), biosimilar, 1 mg | |
| Q5157 | Injection, denosumab-bmwo (stoboclo/osenvelt), biosimilar, 1 mg | |
| Q5158 | Injection, denosumab-bnht (bomyntra/conexxence), biosimilar, 1 mg | |
| Q5159 | Injection, denosumab-bnht (ospomyv/xbryk), biosimilar, 1 mg | |
| ICD10-CM | C50.011 – C50.929 | Malignant neoplasm of breast |
| C61 | Malignant neoplasm of prostate | |
| C94.30 – C94.32 | Mast cell leukemia | |
| C96.20 – C96.29 | Malignant mast cell neoplasm | |
| D47.02 | Systemic mastocytosis | |
| M80.00XA – M80.00XS M80.011A – M80.011S M80.012A – M80.012S M80.019A – M80.019S M80.021A – M80.021S M80.022A – M80.022S M80.029A – M80.029S M80.031A – M80.031S M80.032A – M80.032S M80.039A – M80.039S M80.041A – M80.041S M80.042A – M80.042S M80.049A – M80.049S M80.051A – M80.051S M80.052A – M80.052S M80.059A – M80.059S M80.061A – M80.061S M80.062A – M80.062S M80.069A – M80.069S M80.071A – M80.071S M80.072A – M80.072S M80.079A – M80.079S M80.08XA – M80.08XS M80.0AXA – M80.0AXS M80.0B1A – M80.0B1S M80.0B2A – M80.0B2S M80.0B9A – M80.0B9S | Age-related osteoporosis with current pathological fracture | |
| M80.80XA – M80.80XS M80.811A – M80.811S M80.812A – M80.812S M80.819A – M80.819S M80.821A – M80.821S M80.822A – M80.822S M80.829A – M80.829S M80.831A – M80.831S M80.832A – M80.832S M80.839A – M80.839S M80.841A – M80.841S M80.842A – M80.842S M80.849A – M80.849S M80.851A – M80.851S M80.852A – M80.852S M80.859A – M80.859S M80.861A – M80.861S M80.862A – M80.862S M80.869A – M80.869S M80.871A – M80.871S M80.872A – M80.872S M80.879A – M80.879S M80.88XA – M80.88XS M80.8AXA – M80.8AXS M80.8B1A – M80.8B1S M80.8B2A – M80.8B2S M80.8B9A – M80.8B9S | Other osteoporosis with current pathological fracture | |
| M81.0 | Age-related osteoporosis without current pathological fracture | |
| M81.6 | Localized osteoporosis (Lequesne) | |
| M81.8 | Other osteoporosis without current pathological fracture | |
| M89.9 | Disorder of bone, unspecified | |
| M94.9 | Disorder of cartilage, unspecified | |
| N95.1 | Menopausal and female climacteric states | |
| T38.0X5A – T38.0X5S | Adverse effect of glucocorticoids and synthetic analogues | |
| T38.6X5A – T38.6X5S | Adverse effect of antigonadotrophins, antiestrogens, antiandrogens, not elsewhere classified | |
| T38.7X5A – T38.7X5S | Adverse effect of androgens and anabolic congeners | |
| Z78.0 | Asymptomatic menopausal state | |
| Z79.811 | Long term (current) use of aromatase inhibitors | |
| Z79.818 | Long term (current) use of other agents affecting estrogen receptors and estrogen levels | |
| C33 | Malignant neoplasm of trachea | |
| C34.00 – C34.02 | Malignant neoplasm of unspecified main bronchus | |
| C34.10 – C34.12 | Malignant neoplasm of upper lobe, unspecified bronchus or lung | |
| C34.2 | Malignant neoplasm of middle lobe, bronchus or lung | |
| C34.30 – C34.32 | Malignant neoplasm of lower lobe, unspecified bronchus or lung | |
| C34.80 – C34.82 | Malignant neoplasm of overlapping sites of unspecified bronchus and lung | |
| C34.90 – C34.92 | Malignant neoplasm of unspecified part of unspecified bronchus or lung | |
| C40.00 – C40.92 | Malignant neoplasm of bone and articular cartilage of limbs | |
| C41.0 – C41.9 | Malignant neoplasm of bone and articular cartilage of other and unspecified sites | |
| C50.011 – C50.929 | Malignant neoplasm of breast | |
| C64.1 – C64.9 | Malignant neoplasm of unspecified kidney, except renal pelvis | |
| C73 | Malignant neoplasm of thyroid gland | |
| C79.51 – C79.52 | Secondary malignant neoplasm of bone and bone marrow | |
| C90.00 – C90.32 | Multiple myeloma | |
| D48.0 | Neoplasm of uncertain behavior of bone and articular cartilage | |
| E83.52 | Hypercalcemia |
| Date | Action | Description |
|---|---|---|
| 1/14/2026 | New Medical Drug Coverage Guideline | Bildyos and Bilprevda are considered covered agents. Prolia, Xgeva and other approved biosimilars are excluded from coverage under the Medical Benefit. |