ModifiedUnitedHealthcarePolicy CS021NM.C

Collagen Crosslinks and Biochemical Markers of Bone Turnover (New Mexico)

Policy governing the medical necessity and coverage stance for serum or urine collagen crosslinks and biochemical bone turnover markers for assessment of fracture risk, bone loss prediction, and monitoring response to antiresorptive therapy in New Mexico members.

Policy Summary

PayerUnitedHealthcare

PolicyCollagen Crosslinks and Biochemical Markers of Bone Turnover (New Mexico)

Policy CodePolicy CS021NM.C

Change TypeContent update and archival of prior version

Effective DateFeb 1, 2026

Next Review Date

Key ActionVerify plan-specific prior authorization requirements and include clinical documentation when submitting requests for biochemical bone turnover marker testing.

SourceLink

POLICY UPDATE CHANGES

Updated Description of Services, Clinical Evidence, FDA, and References sections to reflect the most current information and archived previous policy version CS021NM.B.

1state-specific (NM)

82523CPT code listed

35systematic review RCTs cited

3-4primary BTMs mentioned

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Not medically necessary — general

Covered when ALL of the following are met

Primary coverage stance: Serum or urine collagen crosslinks and biochemical markers of bone turnover are considered unproven and not medically necessary for assessing fracture risk, predicting bone loss, or assessing response to antiresorptive therapy.

Policy statement — tests are not medically necessary pending further evidence.

Coverage rationale

Clinical utility summarized from systematic reviews and society guidelines

General findings: BTMs cannot be used alone to diagnose osteoporosis; they may provide dynamic assessment of skeletal activity, predict rate of bone loss and may be useful for monitoring therapy response or adherence in selected patients

Supported by guideline statements and systematic review findings noting assay and preanalytical variability and limited prospective outcome data.

When BTMs may be used: Use PINP and β-CTX as reference markers to monitor response to therapy, assess adherence (eg, CTX for antiresorptives, PINP for anabolics), or as adjunctive information for fracture risk in appropriate patients

Recommendation reflected in ES/ESCEO/IOF/IFCC and BHOF guidance endorsing PINP and CTX as reference markers and potential roles in monitoring adherence and treatment effect.

When BTMs are not recommended for routine use: Routine use of BTMs for diagnosis or for population-level fracture risk prediction is not recommended due to assay variability, preanalytical factors, and inconclusive evidence; BTMs are not included in FRAX

Reflected in ISCD/IOF and NAMS positions and systematic review conclusions urging caution and noting lack of evidence-based thresholds for clinical decision-making.

This policy addresses the use of serum or urine collagen crosslinks and other biochemical bone turnover markers (BTMs) for clinical purposes including assessment of fracture risk, prediction of bone loss, diagnosis of osteoporosis, and monitoring response to antiresorptive therapy. Based on the available evidence, these tests are considered unproven and not medically necessary for those indications because prospective, well-designed trials demonstrating clinical benefit and improved patient outcomes are lacking.

Clinical society guidance and position statements do not support routine inclusion of BTMs in established fracture-risk tools. Notably, the 2023 ISCD/IOF position states that evidence is inconclusive that BTMs predict fracture risk independent of bone mineral density, and therefore BTMs are not included in FRAX. Professional groups such as NAMS also advise against routine use of BTMs in clinical practice for fracture prevention decisions.

The FDA regulates commercially marketed tests and test systems for BTMs but has not identified biochemical markers as diagnostic tools for osteoporosis nor as criteria for selecting, dosing, or administering FDA-approved osteoporosis treatments. The FDA consumer-facing guidance on osteoporosis does not list BTMs among diagnostic tests, underscoring that FDA approval or marketing clearance of a test is not sufficient to establish clinical utility for these clinical decisions.

In summary, serum or urine collagen crosslinks and other BTMs are considered unproven and not medically necessary for assessment of fracture risk, prediction of bone loss, diagnosis of osteoporosis, or routine monitoring of response to osteoporosis treatment. Use of these markers for these purposes may be denied as not medically necessary in the absence of robust evidence demonstrating improvement in clinically meaningful outcomes.

Higher-quality observational and systematic evidence does not support reliable prediction of hip fracture by commonly measured BTMs. The prospective case-control study by Crandall et al. (800 participants) found that fasting serum CTX and PINP were not significantly associated with hip fracture risk. Systematic reviews and technology assessments (including an ECRI HTA and a systematic review of 35 RCTs and 36,706 individuals) reported mixed results, study limitations, and risk of bias, concluding that evidence is insufficient to establish BTMs as predictors of fracture outcomes.

For informational purposes, the FDA consumer-focused osteoporosis information does not include biochemical bone markers in its list of diagnostic tests, reflecting the absence of an FDA-recognized role for BTMs in the diagnosis or management of osteoporosis in consumer guidance.

Provider Actions, Prior Authorization, and Billing

Prior Authorization

Prior authorization may be required for BTM-driven treatment decisions

Because the FDA has not endorsed BTMs for diagnosis or for selecting or dosing osteoporosis drugs, payers may require prior authorization when BTMs are used to support nonstandard treatment decisions.

FDA has no identified guidance endorsing BTMs for selection, dosing, or administration of osteoporosis drugs.
Coverage decisions that rely on BTMs for nonstandard treatment may trigger PA requirements.

Prior Authorization

Verify prior authorization per member contract

Verify prior authorization requirements per the member's contract and applicable federal, state, or contractual benefit terms before ordering or submitting claims for BTMs.

This policy assists interpretation of UnitedHealthcare standard benefit plans but plan-specific terms govern.
In the event of conflict, federal/state/contractual requirements control coverage.

Step Therapy

Step therapy: none specified in this policy excerpt

No step therapy requirements are specified in this portion of the policy.

Step Therapy

Operational note: follow plan and decision‑support tools for step therapy

Step therapy is not specified in this excerpt; use applicable plan rules and any third-party decision-support tools when making treatment decisions.

UnitedHealthcare may use third-party tools (e.g., InterQual) to assist in administration of benefits.

Billing Rule

Coding and documentation: include procedure code and clinical justification

When submitting claims, use the referenced procedure code(s) (e.g., CPT 82523) for collagen crosslinks and include clinical documentation that justifies the use of biochemical bone turnover markers; listing a code does not imply coverage.

Include clinical rationale tying testing to patient management decisions.
Document that listing a code is for reference only and does not guarantee payment.

Documentation Required

Testing methods: document assay and specimen details

Studies measured serum or urinary BTMs (for example, serum PINP, serum CTX, urinary CTX, NTx, bone alkaline phosphatase) using standardized assays such as ELISA or automated immunoassays; document assay type, specimen timing, and preanalytical controls when reporting results.

Common analytes: CTX, PINP, NTx, bALP.
Assay methods include HPLC, immunoassay, automated electrochemiluminescence immunoassays.

Documentation Required

Plan-specific benefit documentation required

Reference the member's federal, state, or contractual benefit requirements and document applicable plan terms when submitting requests for coverage of BTMs.

Plan-specific terms may differ from UnitedHealthcare standard benefits; in conflicts, federal/state/contractual terms govern.

Denial Risk

Denial risk: tests considered unproven and not medically necessary

Claims for serum or urine collagen crosslinks or biochemical bone turnover markers may be denied as not medically necessary because these tests are considered unproven for assessing fracture risk, predicting bone loss, or monitoring response to antiresorptive therapy.

Policy states BTMs are unproven and not medically necessary for fracture risk assessment, bone loss prediction, or monitoring antiresorptive therapy.

Note

Coverage note: FDA approval alone does not establish coverage

FDA approval or marketing clearance alone is not a basis for coverage; the policy notes absence of FDA labeling or guidance endorsing BTMs for diagnostic selection, dosing, or administration of osteoporosis treatments.

FDA consumer-facing materials do not list biochemical markers among diagnostic tests for osteoporosis.

Denial Risk

Denial risk if only FDA approval is cited

If coverage is supported only by FDA clearance or approval for a test, absence of evidence of medical necessity consistent with this policy may lead to denial; provide policy‑consistent clinical evidence when seeking coverage.

Policy explicitly states FDA approval alone is not a basis for coverage and that no FDA guidance was identified linking BTMs to drug selection/dosing.

Definitions and Key Terms

Bone turnover markers (BTMs) — formation vs resorption examples

Formation markers (examples)Osteocalcin; bone alkaline phosphatase (bALP); P1NP

Resorption markers (examples)Pyridinoline; telopeptides (including CTX); urinary N-telopeptide (NTx)

Assay methodsMeasured in serum or urine by high-performance liquid chromatography or immunoassay; assay variability limits clinical use

Reference BTMs — PINP and β-CTX-I recommended as reference markers

Reference formation markerSerum P1NP recommended as a reference marker for monitoring anti-osteoporosis therapy

Reference resorption markerSerum/plasma β-CTX-I (CTX) recommended as a reference resorption marker for monitoring therapy

Guideline sourcesRecommendations from AACE/ACE and BHOF (also endorsed by ESCEO/IOF/IFCC/ISCD statements)

Least significant change (LSC) — ~40% for CTX per BHOF

LSC magnitudeApproximately a 40% reduction in serum CTX is cited as the least significant change (BHOF)

Purpose of LSCUsed to characterize adherence to antiresorptive therapy and to interpret meaningful change over time

Measurement intervalBHOF references repeated measurements after 3–6 months to assess treatment-related change

FDA / CLIA regulatory note — FDA regulation and CLIA categories for test systems

FDA regulationFDA regulates commercially marketed tests and test systems such as bone markers; 510(k)-cleared systems are listed in FDA databases

CLIA categoriesTest systems are categorized per CLIA as waived, moderate, or high complexity based on potential public health risk

Laboratory-developed tests (LDTs)Laboratories using their own (in-house) tests are subject to CLIA standards but not to FDA marketing regulations

OpenPayer

Collagen Crosslinks and Biochemical Markers of Bone Turnover (New Mexico)

Coverage Criteria — Medical Necessity

Coding and Test Codes

Provider Actions, Prior Authorization, and Billing

Background and Clinical Context

Definitions and Key Terms

Policy Revision History