Find policies, billing codes, payers, states, and providers
Biochemical Markers of Bone Remodeling
Customize your policy alerts
Sign up for Aetna Policy 0562 alerts
Get alerted when Policy 0562 changes without checking for updates manually.
Monitor payer policy activity
This Aetna clinical policy bulletin governs the use and coverage stance for measurement of biochemical markers of bone remodeling for evaluation, diagnosis, monitoring, and related indications in members covered by Aetna.
No material clinical or coverage changes in this revision.
Coverage Criteria and Policy Stance
Callout: Provider Actions
Prior Authorization Required: Prior authorization is required for claims for experimental or investigational biochemical marker tests listed below. Providers should obtain authorization before ordering these tests to avoid claim denials.
- Prior authorization is required for experimental/non-covered biochemical marker tests.
- Document the specific marker selected and the clinical rationale for ordering, including the clinical question the test is intended to answer.
- If measuring parathyroid hormone (PTH), document trends over time rather than reliance on a single value; include dates and values of prior measurements when available.
- Do not order BTMs for routine screening, routine monitoring to replace BMD/DXA, or for selection of osteoporosis therapy — these are not supported by current evidence and may be denied.
- Non-covered experimental markers include (but are not limited to): bone sialoprotein; cathepsin K; cobalamine; dickkopf-related protein 1; hydroxyproline; insulin-like growth factor-1 (IGF-1); osteocalcin; osteoprotegerin; procollagen type 1 amino-terminal propeptide (P1NP) when used outside specified, evidence-based indications; pyridinium crosslinks (pyridinoline, deoxypyridinoline); receptor activator of nuclear factor kappa-B ligand (RANKL); sclerostin; tartrate-resistant acid phosphatase; telopeptides of type 1 collagen (CTX, NTX); serum microRNAs; serum tumor necrosis factor-alpha and interleukin-6 for Charcot osteoarthropathy; plasma homocysteine for fracture risk evaluation; and collagen crosslinks for bisphosphonate-related osteonecrosis of the jaw or other non-established indications.
- When submitting prior authorization requests or claims, include supporting documentation: pertinent clinical history, relevant imaging (e.g., recent BMD/DXA if applicable), prior laboratory results, and the intended clinical use and interpretation plan for the marker results.
Policy Scope and Disclaimer
Policy Documentation and History: This Clinical Policy Bulletin is descriptive and not a contract. It may be updated and is subject to change. Providers are responsible for ensuring documentation supports medical necessity for non-routine or experimental tests. Prior authorization decisions and coverage determinations are based on current evidence and guideline synthesis and may be revised as new evidence emerges.
- Clinical Policy Bulletins are developed to assist in administering plan benefits and do not constitute medical advice or a guarantee of coverage.
- Providers remain responsible for medical decision-making and for maintaining documentation in the medical record to support testing.
- This policy may be updated; prior authorization and coverage positions reflect the policy effective on the date of service and are subject to change.
Monitoring and Step-Therapy Guidance
Monitoring and Step Therapy Notes: Routine monitoring with BTMs after initiation of bisphosphonate therapy is not recommended for most patients because bisphosphonates produce predictable BMD increases in the majority of patients and routine monitoring has not been shown to improve outcomes. If BTMs are used for monitoring in selected clinical situations, document the planned monitoring interval, the specific assay to be used, how results will influence management, and ensure repeat measurements account for assay and biological variability.
- Routine BMD or BTM monitoring within the first three years after initiating potent bisphosphonate therapy is generally unnecessary and may be misleading.
- If BTMs are measured for monitoring (e.g., suspected non-response, research, or specialized clinical scenarios), specify the marker, assay method, sampling timing (e.g., fasting, morning), and target change thresholds that would trigger a management change.
- Document persistence/adherence interventions (e.g., follow-up visit at ~3 months) rather than relying solely on biomarker results to address non-adherence.
Coding — CPT, ICD-10, and Imaging Codes
| 82523 | Collagen cross links, any method |
| 82607 | Cyanocobalamin (Vitamin B-12) |
| 82608 | Cyanocobalamin (Vitamin B-12); unsaturated binding capacity |
| 83090 | Homocysteine |
| 83500 | Hydroxyproline; free |
| 83505 | Hydroxyproline; total |
| 83937 | Osteocalcin (bone g1a protein) |
| 88319 | Special stain including interpretation and report; Group III, for enzyme constituents [tartrate-resistant acid phosphatase testing] |
| F32.00 - F33.9 | Major depressive disorder [for persons receiving serotonergic anti-depressants] |
| M14.671 - M14.679 | Charcot's joint, ankle and foot (range indicated) |
| M80.00X+ - M81.8 | Age-related osteoporosis with or without current pathological fracture |
| M87.08 | Idiopathic aseptic necrosis of bone, other site [jaw] |
| N18.1 - N18.9 | Chronic kidney disease (CKD) |
| N25.0 | Renal osteodystrophy |
| Q78.0 | Osteogenesis imperfecta |
| T84.030+ - T84.039+ | Mechanical loosening of internal prosthetic joint |
| T84.050+ - T84.058+ | Periprosthetic osteolysis of internal prosthetic joint |
| Z13.820 | Encounter for screening for osteoporosis |
Provider Actions, Prior Authorization, and Documentation
Prior authorization expectation for routine monitoring
Routine use of biochemical markers to monitor osteoporosis or to guide therapy is not supported by randomized trial evidence showing improved fracture outcomes; therefore routine or repeated testing for monitoring purposes may require justification or prior authorization.
Prior authorization requirements (none specified here)
No specific prior authorization processes, requirements, or billing codes are specified in the cited portions of this policy.
Routine monitoring discussion — not a step therapy directive
Discussion in this policy notes that routine monitoring after initiation of potent bisphosphonate therapy (e.g., early BMD monitoring) is generally unnecessary; this portion does not impose step therapy requirements.
Step therapy — not applicable
This policy does not include step therapy directives for biochemical marker testing; no step therapy requirements are specified in the cited sections.
Step therapy rules — none specified
No step therapy rules for biochemical marker testing are specified in the referenced portions of this policy.
Coding and indication mapping for non-covered indications
The policy lists CPT procedure codes and ICD-10 diagnosis codes associated with non-covered indications; map ordered tests to these codes when documenting clinical indications to align with the policy's non-coverage examples.
- Use CPT codes listed in the CPB when submitting claims for biochemical marker assays.
- Document the clinical indication with the corresponding ICD-10 code when the test is for an indication noted as not covered.
Document marker selection and interpretation (PINP and serum CTX)
If bone turnover markers are reported, document that PINP (formation marker) and serum CTX (resorption marker) are the recommended reference markers and note that short-term changes correlate with BMD variation but do not predict individual fracture benefit.
- Document selection of PINP and serum CTX when used as reference markers.
- Document that short-term changes relate to group-level BMD variation and do not reliably predict individual fracture outcomes.
Document PTH trends (avoid single-value interpretation)
When evaluating suspected renal osteodystrophy, document serial PTH trends rather than relying on a single PTH value; inconsistent PTH trends may warrant consideration of bone biopsy if results would change therapy.
- Record and review longitudinal PTH trend data in the medical record.
- Consider bone biopsy when PTH trends are inconsistent and biopsy results could alter management.
Reference policy documentation and review history
Refer to the Clinical Policy Bulletin Notes and Review History links for policy history, last review date, and next scheduled review when documenting coverage rationale or appeal information.
- Check the CPB Notes and Review History for last review (07/27/2023) and next review date.
- Use policy history links when preparing coverage appeals or clinical justification.
Denial risk — non-covered experimental markers and related CPTs
Measurements of the biochemical markers listed in the policy and the associated CPT codes are considered experimental/investigational for the specified indications and are not covered; claims for these tests for the listed purposes may be denied.
Denial risk for routine monitoring
There is no trial evidence that treatment monitoring by any method reduces fracture rates; lack of demonstrated clinical benefit for routine monitoring may lead to denial of testing ordered for routine monitoring purposes.
Renal osteodystrophy diagnostic note — trends preferred
One-time biochemical marker values have limited diagnostic utility for renal osteodystrophy; document trends in PTH and consider bone biopsy when trends are inconsistent and results may alter management.
Administrative disclaimer — CPB not an offer of coverage
Clinical Policy Bulletins are developed to assist in administering plan benefits and do not constitute offers of coverage or medical advice; plan or program provisions govern coverage decisions and providers remain responsible for medical care.
Background and Rationale
Bone strength is determined by a combination of bone mass, microarchitecture/macrogeometry, and the rate of bone turnover. Biochemical markers of bone remodeling measure processes of formation and resorption and can be obtained from serum or urine; they often change more rapidly than bone mineral density after intervention.
Markers of bone formation include bone‑specific alkaline phosphatase, osteocalcin, and procollagen peptides (e.g., PINP), while markers of bone resorption include collagen telopeptides (serum CTX, urinary NTX) and collagen crosslinks. Although BTMs reflect skeletal biology and treatment effects at a group level, high biological and analytical variability and lack of standardized assays limit their reliability for individual diagnostic or therapeutic decisions.
Definitions and Reference Markers
OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.