Cigna denosumab (Prolia) Coverage Update

Coverage Criteria

1. Bone loss in breast cancer patients receiving aromatase inhibitors (FDA-approved)

Covered when ALL of the following are met

Breast cancer bone loss: A. Patient has breast cancer that is not metastatic to bone; AND B. Patient is receiving aromatase inhibitor therapy (examples: anastrozole, letrozole, exemestane)

Dosing: 60 mg subcutaneously once every 6 months; Approve for 1 year.

2. Bone loss in nonmetastatic prostate cancer receiving androgen deprivation therapy (FDA-approved)

Covered when ALL of the following are met

Prostate cancer bone loss: A. Patient has prostate cancer that is not metastatic to bone; AND B. Patient meets ONE of the following: (i) Patient is receiving androgen deprivation therapy (examples: leuprolide depot, leuprolide acetate injectable, triptorelin, goserelin, relugolix); OR (ii) Patient has undergone bilateral orchiectomy

Dosing: 60 mg subcutaneously once every 6 months; Approve for 1 year.

3. Glucocorticoid-induced osteoporosis — treatment (FDA-approved)

Covered when ALL of the following are met

GIO treatment: A. Patient is initiating or continuing chronic systemic glucocorticoids (example: prednisone); AND B. Patient meets ONE of the following: (i) tried zoledronic acid IV infusion (Reclast); OR (ii) tried ≥1 oral bisphosphonate or oral bisphosphonate-containing product and, per prescriber, had inadequate efficacy after a 12-month trial OR significant intolerance; OR (iii) cannot take oral bisphosphonates due to inability to swallow, inability to remain upright after administration, or a pre-existing GI condition; OR (iv) patient has severe renal impairment (e.g., creatinine clearance <35 mL/min) with evaluation for CKD-MBD to reduce hypocalcemia risk OR has had an osteoporotic/fragility fractureglucocorticoid ≥7.5 mg prednisone equivalent daily; oral bisphosphonate trial 12 months

Dosing: 60 mg subcutaneously once every 6 months; Approve for 1 year.

4. Osteoporosis treatment — postmenopausal (FDA-approved)

Covered when BOTH of the following are met

Postmenopausal osteoporosis: A. Patient meets ONE: (i) T-score ≤ -2.5 at lumbar spine, femoral neck, total hip and/or 33% radius; OR (ii) prior osteoporotic/fragility fracture; OR (iii) low bone mass (T-score between -1.0 and -2.5) AND prescriber-assessed high fracture risk; AND B. Patient meets ONE: (i) tried ibandronate IV injection or zoledronic acid IV infusion; OR (ii) tried ≥1 oral bisphosphonate or oral bisphosphonate-containing product and, per prescriber, had inadequate efficacy after a 12-month trial OR significant intolerance; OR (iii) cannot take oral bisphosphonates (cannot swallow, cannot remain upright, or pre-existing GI condition); OR (iv) severe renal impairment with CKD-MBD evaluation OR prior fractureT-score ≤ -2.5 where applicable; oral bisphosphonate trial 12 months

Dosing: 60 mg subcutaneously once every 6 months; Approve for 1 year.

5. Osteoporosis treatment in men (FDA-approved)

Covered when BOTH of the following are met

Male osteoporosis: A. Patient meets ONE: (i) T-score ≤ -2.5 at lumbar spine, femoral neck, total hip and/or 33% radius; OR (ii) prior osteoporotic/fragility fracture; OR (iii) low bone mass AND prescriber-assessed high fracture risk; AND B. Patient meets ONE: (i) tried zoledronic acid IV infusion; OR (ii) tried ≥1 oral bisphosphonate or oral bisphosphonate-containing product and, per prescriber, had inadequate efficacy after a 12-month trial OR significant intolerance; OR (iii) cannot take oral bisphosphonates; OR (iv) severe renal impairment with CKD-MBD evaluation OR prior fractureT-score criteria where applicable; oral bisphosphonate trial 12 months

Dosing: 60 mg subcutaneously once every 6 months; Approve for 1 year.

6. Treatment of bone loss in prostate cancer receiving ADT (alternate listing)

Covered when the patient is receiving androgen deprivation therapy

ADT-associated bone loss: Patient is receiving androgen deprivation therapy (examples: leuprolide depot, leuprolide acetate injectable, triptorelin, goserelin, relugolix)

Dosing: 60 mg subcutaneously once every 6 months; Approve for 1 year.

7. Increase bone mineral density in patients with breast cancer

Covered when ONE of the following is met

Breast cancer BMD increase: i) Patient is postmenopausal AND receiving aromatase inhibitor therapy (examples: anastrozole, letrozole, exemestane); OR ii) Patient is premenopausal AND receiving estrogen deprivation therapy (examples: leuprolide, triptorelin, goserelin, anastrozole, letrozole, exemestane)

Dosing: 60 mg subcutaneously once every 6 months; Approve for 1 year.

8. Not Medically Necessary Uses

Denosumab products are considered not medically necessary for the following uses unless specific policy criteria are met elsewhere in the policy:

Concurrent therapy exclusion: Denosumab products (Prolia, biosimilars) used concurrently with other osteoporosis medications (e.g., teriparatide, abaloparatide, oral bisphosphonates, IV bisphosphonates, calcitonin nasal spray, romosozumab) are not covered.

Calcium and/or vitamin D supplements are allowed in combination.

Giant cell tumor of bone: Use of Prolia dosing for giant cell tumor of bone is not covered; studies for giant cell tumor used Xgeva dosing and Xgeva (higher-dose denosumab) is the indicated product.

Osteoporosis prevention: Denosumab products (Prolia, biosimilars) are not indicated for prevention of osteoporosis and therefore are not covered for prevention use.

9. Added Covered Indications

Newly added conditions considered medically necessary when full policy criteria are met:

Bone loss in prostate cancer on ADT: Treatment of bone loss in patients with prostate cancer receiving androgen deprivation therapy was added as a covered condition with dosing.

Examples of androgen deprivation therapy were added.

Increase BMD in breast cancer on AI therapy: Use to increase bone mineral density in patients with breast cancer at high risk for fracture receiving adjuvant aromatase inhibitor therapy was added as a covered condition with dosing.

Examples of aromatase inhibitor therapy were added.

Use of denosumab products (Prolia and biosimilars) concurrently with other osteoporosis agents is considered not medically necessary. Examples of agents that should NOT be administered together with denosumab products include teriparatide (Forteo), abaloparatide (Tymlos), oral bisphosphonates (e.g., alendronate, risedronate, ibandronate), intravenous bisphosphonates (e.g., zoledronic acid [Reclast], IV ibandronate), calcitonin nasal spray (Miacalcin/Fortical), and romosozumab (Evenity). Calcium and/or vitamin D supplementation may be used in combination with denosumab products.

Giant cell tumor of bone is treated with a higher-dose denosumab product (Xgeva) using dosing regimens distinct from Prolia. Use of Prolia or its biosimilars at Prolia dosing for giant cell tumor of bone is not covered; Xgeva (and its biosimilars where indicated) is the product studied and indicated for unresectable giant cell tumor of bone or when surgery would cause severe morbidity.

Operationally, denosumab products (Prolia and biosimilars) are not covered when used concurrently with other osteoporosis medications, and Prolia dosing should not be used to treat giant cell tumor of bone because the GCT-B indication was studied with and is indicated for Xgeva. Additionally, denosumab products are not indicated for osteoporosis prevention and therefore are not covered for prevention-only use.

Any use of denosumab products (Prolia and biosimilars) for indications other than those explicitly listed as covered in this policy is considered not medically necessary. This includes, but is not limited to, concurrent combination therapy with other osteoporosis agents as described in the policy.

Summary of coverage exclusions: denosumab products (Prolia and biosimilars) are not covered for concurrent use with other osteoporosis medications (examples: teriparatide, abaloparatide, oral or IV bisphosphonates, calcitonin nasal spray, romosozumab), for treatment of giant cell tumor of bone using Prolia dosing (Xgeva is the indicated product), and for use solely for osteoporosis prevention.

Initial Therapy Criteria

inv-34: Initial therapy — glucocorticoid-induced osteoporosis

Initial therapy rules for glucocorticoid-induced osteoporosis

GIO initial therapy: Patient is initiating or continuing systemic glucocorticoids (example: prednisone) and meets trial/intolerance/prerequisite criteria for bisphosphonates or listed exceptions as specified in the GIO criteria.glucocorticoid ≥7.5 mg prednisone equivalent daily; oral bisphosphonate trial 12 months

Dosing: 60 mg subcutaneously once every 6 months; Approve for 1 year.

inv-35: Initial Therapy Prerequisites

Initial therapy prerequisite updates

Oral bisphosphonate trial: A 12-month trial of an oral bisphosphonate or oral bisphosphonate-containing product is required as a prerequisite in applicable indications unless inadequate efficacy or significant intolerance is documented (examples of inadequate efficacy and intolerance were added).

Continuation of Therapy

inv-36: Continuation of therapy

Extended approvals are allowed if the patient continues to meet the Criteria and Dosing

Continuation: Extended approvals are allowed when the patient continues to meet the applicable medical necessity criteria and dosing requirements.

Approvals are provided for 1 year.

inv-37: Continuation / Prerequisite Requirements

Continuation and prerequisite trial clarifications in selected revisions

Prerequisite bisphosphonate trial: Clarified that the oral bisphosphonate or oral bisphosphonate-containing prerequisite trial should be for 12 months; examples of inadequate efficacy and intolerance were added.12 months

Zoledronic acid IV infusion was added as a prerequisite option in some indications; IV bisphosphonates were removed as prerequisite options in other places per revisions.

Step Therapy Requirements

Step requirement	Coverage label
Patient must have tried or be unable to take oral or IV bisphosphonates per indication-specific criteria (examples include prior trial of zoledronic acid IV, trial of ≥1 oral bisphosphonate with documented inadequate efficacy after a 12-month trial, significant intolerance to oral bisphosphonates, inability to swallow or remain upright, or severe renal impairment with evaluation for CKD-MBD).
Coverage requires meeting the bisphosphonate step requirement as described; denosumab is covered with criteria met.

Prerequisite trial	Coverage label
Trial of an oral bisphosphonate or an oral bisphosphonate–containing product for 12 months is required in applicable indications unless there is documented inadequate efficacy or significant intolerance (examples of inadequate efficacy include ongoing significant BMD loss, lack of BMD increase, or occurrence of an osteoporotic/fragility fracture; examples of intolerance include severe GI or musculoskeletal adverse events).
Coverage requires fulfillment of the 12-month oral bisphosphonate prerequisite when applicable; denosumab is covered if prerequisite met or appropriate exception documented.

Prerequisite trial

Coverage label

Trial of an oral bisphosphonate or an oral bisphosphonate–containing product for 12 months is required in applicable indications unless there is documented inadequate efficacy or significant intolerance (examples of inadequate efficacy include ongoing significant BMD loss, lack of BMD increase, or occurrence of an osteoporotic/fragility fracture; examples of intolerance include severe GI or musculoskeletal adverse events).

Coverage requires fulfillment of the 12-month oral bisphosphonate prerequisite when applicable; denosumab is covered if prerequisite met or appropriate exception documented.

Coding

Covered HCPCS (medical benefit) - exampleHCPCSCovered

J0897

Injection, denosumab, 1 mg (example HCPCS used commonly for Prolia)

Considered Medically Necessary HCPCS/CodesHCPCSCovered

C9399	Unclassified drugs or biologicals (Effective until 09/30/2025)
J0897	Injection, denosumab, 1 mg
J3490	Unclassified drugs (Effective until 09/30/2025)
J3590	Unclassified drugs or biologicals (Effective until 09/30/2025)
Q5136	Injection, denosumab-bbdz (jubbonti/wyost), biosimilar, 1 mg
Q5157	Injection, denosumab-bmwo (stoboclo/osenvelt), biosimilar, 1 mg (Effective Date 10/01/2025)

Glucocorticoid threshold (GIO)

Glucocorticoid dose threshold≥ 7.5 mg prednisone equivalent daily

Glucocorticoid duration contextPatient expected to remain on glucocorticoids for at least 6 months

Applies toMen and women at high risk of fracture initiating or continuing systemic glucocorticoids

T-score threshold

T-score threshold for osteoporosisT-score ≤ -2.5 at lumbar spine, femoral neck, total hip, and/or 33% (one-third) radius

Alternative diagnosisPrior osteoporotic/fragility fracture qualifies regardless of T-score

Provider Actions & Authorization

Prior Authorization

Prior Authorization Recommended

Prior Authorization is recommended for medical benefit coverage of denosumab products (Prolia and biosimilars). Approvals are granted for 1 year when the patient meets the policy Criteria and Dosing. Requests for doses outside the dosing documented in this policy will be reviewed case-by-case by a clinician (Medical Director or Pharmacist).

All approvals provided for 1 year in duration
Out-of-range doses considered case-by-case by clinician

Billing Rule

Codes Requiring Authorization

Prior authorization is required for denosumab products billed with the listed HCPCS/NDC-like codes. Note that certain miscellaneous/unclassified codes are effective only through 09/30/2025; a new HCPCS (Q5157) becomes effective 10/01/2025.

Quantity Limits & Dosing

Denosumab (Prolia and biosimilars) — standard dose

Denosumab standard dose60 mg subcutaneously once every 6 months

Typical approval durationApprove for 1 year when criteria met

Applies to productsProlia and listed biosimilars (same dosing and criteria)

Site of Care

Note

Site of care options

Site of care options include office, infusion center, or home; the site should be reasonable and clinically appropriate and adjusted based on severity and prior response.

Coding and drug supply codes for infusion center billing are provided elsewhere in the policy.

Billing Rule

Site of care coding note (infusion center)

Infusion center is an available site of care; the policy provides coding and drug supply codes for billing denosumab in applicable settings.

Biosimilars

Billing Rule

Prolia and biosimilars covered with same criteria

Prolia and listed biosimilars (Jubbonti, Stoboclo) are covered denosumab products and are subject to the same dosing and criteria in this policy.

Standard dosing for covered indications is 60 mg subcutaneously once every 6 months.

Billing Rule

Jubbonti added and covered

Jubbonti (denosumab‑bbdz) was added to the policy and is covered with the same criteria and dosing as Prolia.

Billing Rule

Stoboclo added and Q5157 effective 10/01/2025

Stoboclo (denosumab‑bmwo) was added to the policy and is covered with the same criteria and dosing as Prolia; HCPCS Q5157 references this biosimilar and becomes effective 10/01/2025.

Q5157 (Injection, denosumab‑bmwo) effective date: 10/01/2025.

Definitions

High risk of fracture

Definition of high fracture riskHistory of osteoporotic fracture, multiple risk factors for fracture, or failure/intolerance to other available osteoporosis therapy

Clinical implicationsUsed to identify candidates for denosumab when low bone mass alone may not suffice

Applies to indicationsPostmenopausal women, men, and cancer therapy–related bone loss contexts

Advanced chronic kidney disease risk

Advanced CKD riskPatients with advanced chronic kidney disease or CKD-MBD are at greater risk of severe hypocalcemia after denosumab

Pre-initiation actionEvaluate for presence of CKD-MBD before starting denosumab

Background

Denosumab products (Prolia and biosimilars) are monoclonal antibody RANKL inhibitors indicated to increase bone mass and reduce fracture risk across multiple settings, including postmenopausal osteoporosis, osteoporosis in men at high fracture risk, bone loss related to androgen deprivation or aromatase inhibitor therapy, and glucocorticoid-induced osteoporosis. The typical Prolia dosing is 60 mg subcutaneously every 6 months with approvals generally granted for 1 year when criteria are met.

Revision History

2025-10-01coding_update

HCPCS code Q5157 (denosumab biosimilar Stoboclo) added with effective date 10/01/2025; descriptions for C9399, J3490, and J3590 updated to note effectiveness until 09/30/2025.

2025-08-15policy_revision

Policy title updated to 'Bone Modifiers - Denosumab Products (Prolia)'; biosimilars Jubbonti and Stoboclo added and aligned with Prolia criteria; documentation requirements removed; examples of aromatase inhibitor and androgen deprivation therapies added.

2025-01-15annual_revision