ModifiedPremera BluecrossPolicy G2051

Bone Turnover Markers Testing

This policy governs reimbursement and clinical use of biochemical bone turnover marker (BTM) testing for assessment, monitoring, and management of bone metabolic conditions (primarily osteoporosis) for Premera Bluecross members.

Policy Summary

PayerPremera Bluecross

PolicyBone Turnover Markers Testing

Policy CodePolicy G2051

Change TypeModified — new reimbursable schedule and clarified non‑reimbursable uses

Effective DateFeb 6, 2026

Next Review Date

Key ActionFollow the reimbursable testing schedule for members on bisphosphonate therapy: baseline before treatment, every 3 months during the first year after initiation/change, then every 2 years if unchanged.

SourceLink

POLICY UPDATE CHANGES

For individuals on bisphosphonate therapy, bone turnover marker testing is reimbursable to establish baseline before treatment, every three months during the first year after initiation or change, and every two years if therapy is unchanged.

Bone turnover marker testing is not reimbursable for monitoring teriparatide treatment, diagnosing osteoporosis, or managing other high bone turnover conditions.

New policy approved October 14, 2025 effective for dates of service on or after February 6, 2026 following 90-day provider notification.

baseline, q3m, q2yReimbursable schedule (bisphosphonates)

teriparatideExplicit non-reimbursable indication

6CPT codes listed

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Preferred markers cited

limit certain BTMsCKD-specific guidance

Coverage Criteria

Not reimbursable indications

The following uses of bone turnover marker testing are considered not reimbursable.

For individuals with osteoporosis, measurement of bone turnover markers to monitor teriparatide treatment is not reimbursable.

Measurement of bone turnover markers as a diagnostic test for osteoporosis is not reimbursable.

Measurement of bone turnover markers for the diagnosis and management of patients with other conditions associated with high rates of bone turnover is not reimbursable.

Coding

Covered CPT CodesCPTCovered

82523	Collagen cross links, any method
83500	Hydroxyproline; free
83505	Hydroxyproline; total
83937	Osteocalcin (bone gla protein)
84080	Phosphatase, alkaline; isoenzymes

Examples of FDA-cleared / Commercial BTM assays (examples)mixed

Osteomark NTX Urine ELISA (Abbott)	Measures cross-linked N-telopeptides of type I collagen (NTx) — urine NTX assay
Serum Crosslaps One-step ELISA	Measures hydroxyproline / C-terminal telopeptides (CTX) in serum
Access Ostase (Beckman Coulter)	Measures bone-specific alkaline phosphatase (B-ALP)
NMID Osteocalcin One-step ELISA (Osteometer/Nordic Biotech)	Measures osteocalcin (OC)
Elecsys N-MID Osteocalcin Immunoassay (Roche Diagnostics)	Measures N-MID osteocalcin

Referenced assays and coding notemixed

FDA-cleared assays (examples)	Osteomark NTX (Abbott); Serum Crosslaps One-step ELISA; Access Ostase (Beckman Coulter); NMID Osteocalcin (Osteometer/Nordic Biotech); Elecsys N-MID Osteocalcin (Roche)
Laboratory-developed tests (LDTs)	May be used by individual labs; these are CLIA-regulated high-complexity tests and are not FDA-cleared

Provider Actions and Billing Guidance

Billing Rule

Billing codes affected for BTM testing

CPT codes associated with bone turnover marker testing listed in the policy: 82523, 83500, 83505, 83937, 84080. Use these CPT codes on claims for BTM assays per payer coding guidance.

82523 — Collagen cross links, any method
83500 — Hydroxyproline; free
83505 — Hydroxyproline; total
83937 — Osteocalcin (bone gla protein)
84080 — Phosphatase, alkaline; isoenzymes

Prior Authorization

Prior authorization: required information

If prior authorization is requested or required for BTM assays, include the clinical indication for testing, which specific marker will be measured (for example PINP, CTX, or B‑ALP), and the timing of the test relative to therapy initiation or monitoring.

Background

Bone turnover markers (BTMs) are biochemical measures of bone formation or resorption that have been proposed for predicting bone loss, fracture risk, and for monitoring response to osteoporosis therapies. Analytical and biological variability and limited assay standardization constrain their routine clinical use; several guideline groups identify PINP (formation) and CTX (resorption) as preferred reference markers, and consensus reports note BTMs may be useful in selected situations such as monitoring adherence or early treatment response, assessing change after cessation of certain agents, or when BMD is unavailable.

Definitions

Bone turnover markers (BTMs) — formation and resorption marker examples

Formation markers (examples)Serum bone-specific alkaline phosphatase (BSAP/BALP); Serum osteocalcin (OC); Serum type I procollagen (C1NP or P1NP)

Resorption markers (examples)Urinary hydroxyproline (HYP); Urinary total pyridinoline (PYD); Urinary free deoxypyridinoline (DPD); Urinary or serum NTX; Urinary or serum CTX

Additional markers listedBone sialoprotein (BSP); Serum TRACP5b; Cathepsin K

PINP — Procollagen type I N-terminal propeptide (preferred formation marker)

Full nameProcollagen type I N-terminal propeptide (PINP)

RolePreferred serum bone formation marker cited by multiple guideline groups for evaluating bone formation and monitoring response to therapy

Revision History

2025-10-14approval

New policy approved.

2026-02-06effectiveLatest

Policy effective for dates of service; reimbursable schedule added for bisphosphonate therapy (baseline; every 3 months first year after initiation/change; every 2 years if unchanged) and explicit non‑reimbursable uses specified (monitoring teriparatide, diagnosing osteoporosis, managing other high bone‑turnover conditions).

The policy history adds an operational reimbursement schedule for members on bisphosphonate therapy and restates explicit non-reimbursable items. Specifically, for individuals on bisphosphonate therapy the policy now reimburses BTM testing to establish a baseline before treatment, every 3 months during the first year after initiation or change, and every 2 years if therapy is unchanged. It also explicitly notes that BTM testing is not reimbursable for monitoring teriparatide treatment, diagnosing osteoporosis, or managing other high bone turnover conditions. Providers should follow documentation and claims submission guidance when requesting reimbursement.

Policy Summary

PayerPremera Bluecross

PolicyBone Turnover Markers Testing

Policy CodePolicy G2051

Change TypeModified — new reimbursable schedule and clarified non‑reimbursable uses

Effective DateFeb 6, 2026

Next Review Date

SourceLink

On This Page

State the clinical indication (e.g., baseline before bisphosphonate initiation; monitoring at specified intervals).
Specify which BTM analyte will be measured (preferred markers: PINP for formation, CTX for resorption; B‑ALP may be used in renal insufficiency).
Report timing of testing relative to treatment (e.g., baseline, 3 months, 6 months, 12 months as applicable) and whether the assay is FDA 510(k)-cleared or an LDT.

Billing Rule

Reimbursable schedule for bisphosphonate therapy

For members on bisphosphonate therapy the policy permits reimbursement for BTM testing to establish a baseline before treatment, every three months after initiation or change during the first year, and every two years if therapy remains unchanged.

Baseline before initiating bisphosphonate treatment
Every 3 months after initiation or change of therapy for the first year
Every 2 years when no medication changes have occurred

Documentation Required

Provider actions — documentation and billing

Document the clinical indication for BTM testing on the chart and submit appropriate CPT codes and laboratory documentation with claims to support reimbursement.

Include indication and which marker was measured on the clinical note.
Use the policy-listed CPT codes on the claim and attach lab documentation per payer procedures.

Denial Risk

Provider actions — avoid non‑reimbursable indications

Do not submit claims for BTM testing when used to monitor teriparatide treatment or when used as a diagnostic test for osteoporosis or for diagnosis/management of other high bone‑turnover conditions; these uses are non‑reimbursable and may be denied.

Measurement of BTMs to monitor teriparatide treatment — not reimbursable.
BTMs used as a diagnostic test for osteoporosis or to manage other high‑turnover conditions — not reimbursable.

Note

Provider actions — follow payer procedures

Follow payer procedures for claims submission and any applicable prior authorization processes per the member's benefit plan when requesting reimbursement for BTM testing.

Adhere to member benefit limitations and contact member services if coverage is uncertain.
Follow the policy's operational reimbursement schedule when billing for bisphosphonate monitoring.

Documentation Required

Provider actions — indicate indication and timing in documentation

Chart documentation should state the indication for testing (for example, baseline prior to bisphosphonate initiation or monitoring at specified intervals) and link the test timing to the treatment plan.

Indicate baseline testing when performed before starting bisphosphonates.
Document planned monitoring intervals (e.g., every 3 months first year, then every 2 years if unchanged).

Documentation Required

Recommended documentation elements to support BTM testing

Support the clinical rationale for BTM testing with documentation that includes the indication (e.g., monitoring adherence or early response), baseline and follow‑up timing, and which marker is being used (preferably PINP for formation and CTX for resorption).

Clinical reason for testing (e.g., adherence monitoring, early therapeutic response).
Baseline and specified follow‑up times (examples: baseline, 1–3, 3, 6, and 12 months depending on agent).
Specify the analyte used (PINP, CTX, or B‑ALP when appropriate).

Documentation Required

Laboratory test documentation — cleared assays vs LDTs

When submitting lab documentation, note whether the BTM assay is an FDA 510(k)-cleared commercial test or a laboratory‑developed test (LDT) performed under CLIA, and include the appropriate CPT code(s) on the claim.

FDA 510(k)-cleared assays (examples listed in policy) versus LDTs must be identified in documentation.
LDTs are regulated under CLIA as high‑complexity tests; include supporting lab paperwork when requesting reimbursement.

Denial Risk

Provider actions — do not use BTMs as diagnostic tests for osteoporosis

Do not bill for BTM tests when the sole purpose is diagnosis of osteoporosis or diagnosis/management of other high bone‑turnover conditions; such uses are excluded from reimbursement and may be denied.

Diagnostic use for osteoporosis — excluded and not reimbursable.
Diagnosis/management of other high‑turnover bone conditions — excluded and not reimbursable.

Denial Risk

CKD-related limitation for BTM measurement

Be aware that KDIGO guidance suggests not to routinely measure collagen‑derived BTMs (such as PINP, CTX, NTX) in patients with CKD stages G3a–G5D; routine CKD testing contexts may be limited or denied.

KDIGO suggests using PTH or bone‑specific alkaline phosphatase rather than routine collagen‑derived BTMs in CKD G3a–G5D.
Consider documenting CKD stage and rationale if requesting BTMs in CKD patients.

Denial Risk

Denial triggers for BTM claims

Claims for BTM testing submitted for monitoring teriparatide treatment, for diagnosing osteoporosis, or for managing other high bone turnover conditions are denial risks because these uses are listed as not reimbursable.

Monitoring teriparatide — not reimbursable; expect denial risk.
Diagnosing osteoporosis or managing other high‑turnover conditions — not reimbursable; expect denial risk.

Documentation Required

Provider actions — document indication and timing

Ensure clinical notes specify the indication for testing and the timing relative to therapy (for example baseline before bisphosphonate initiation or scheduled monitoring intervals) to support reimbursement.

Document the specific indication (baseline, monitoring interval) and the BTM analyte measured.
Link testing to the treatment plan (e.g., bisphosphonate initiation and follow‑up schedule).

Guideline notesIdentified alongside serum CTX as among the most informative biochemical markers for monitoring osteoporosis in joint IOF/ESCEO guidance and consensus reports

CTX — C-terminal telopeptide of type I collagen (preferred resorption marker)

Full nameC-terminal telopeptide of type I collagen (CTX)

RolePreferred serum bone resorption marker cited by multiple guideline groups for evaluating resorption and monitoring response to therapy

Guideline notesRecommended with PINP as the reference resorption/formation pair; both have prognostic significance for fracture when BMD unavailable

B-ALP — Bone-specific alkaline phosphatase, formation marker useful in CKD contexts

AbbreviationB-ALP (Bone-specific alkaline phosphatase)

Clinical utilityBone formation marker noted as less affected by renal failure and useful in certain CKD contexts

Example cleared assayAccess Ostase (Beckman Coulter) measures B-ALP and is FDA 510(k)-cleared

Bone turnover markers (BTMs) definition — biochemical markers measured in blood or urine reflecting bone turnover and treatment response

DefinitionBiochemical markers measured in blood or urine that reflect bone formation or resorption and may change in response to osteoporosis treatment

Sample typesSerum (e.g., PINP, CTX, B-ALP, osteocalcin) and urine (e.g., HYP, PYD, DPD, NTX)

Clinical usesProposed uses include assessing bone turnover, monitoring therapy effectiveness/adherence, and research; guideline groups note limited value for routine individual patient monitoring due to variability and standardization issues

Laboratory-developed tests (LDTs) — CLIA-regulated high-complexity tests note

Regulatory statusLaboratory-developed tests (LDTs) are regulated by CMS as high-complexity tests under CLIA '88 and are not FDA-cleared

FDA-cleared examplesSeveral BTM assays have FDA 510(k) clearance (e.g., Osteomark NTX urine ELISA; Serum Crosslaps; Access Ostase; NMID Osteocalcin; Elecsys N-MID Osteocalcin)

Clinical implicationMany labs perform their own validated LDTs for BTMs; providers should document assay type (cleared assay vs LDT) when submitting claims