Collagen Crosslinks, any Method — NCD 96 | CMS Coverage Update

TL;DR: The Centers for Medicare & Medicaid Services modified NCD 96 for collagen crosslinks testing, effective March 7, 2026. Here's what billing teams need to know before submitting claims.

CMS collagen crosslinks coverage policy under NCD 96 has been updated. This National Coverage Determination governs Medicare coverage of collagen crosslink assays — biochemical markers used to measure bone resorption in patients with or at risk for osteoporosis. The policy does not list specific CPT or HCPCS codes in the current data release, but the coverage criteria and medical necessity standards have been modified, and those changes directly affect what claims will pay.

Quick-Reference Table

CMS Collagen Crosslinks Coverage Criteria and Medical Necessity Requirements 2026

NCD 96 is the National Coverage Determination governing Medicare coverage of collagen crosslinks testing for bone resorption assessment. CMS defines collagen crosslinks as biochemical markers — specifically pyridinoline crosslinks and associated telopeptides — measured in urine via immunoassay or high performance liquid chromatography (HPLC). Elevated urinary collagen crosslinks signal elevated bone resorption, which contributes to osteoporosis and fracture risk.

The CMS collagen crosslinks coverage policy recognizes three covered indications. First, identifying individuals with elevated bone resorption who have osteoporosis and are being monitored for treatment response. Second, predicting response to FDA-approved antiresorptive therapy in postmenopausal women, as assessed by bone mass measurements. Third, assessing treatment response in patients with osteoporosis.

Medical necessity is the central issue here. CMS is explicit: collagen crosslinks testing is most useful in "fast losers" of bone. By age 65, most fast losers will have already been stabilized by therapy or will have lost so much bone mass that further testing provides no clinical value. That's a narrowing frame for a Medicare population.

Coverage can still be established for younger Medicare beneficiaries. It also extends to men and women who become fast losers because of another therapy — glucocorticoids being the clearest example. Secondary osteoporosis caused by long-term glucocorticosteroid administration, endocrine-related disorders other than menopause-driven estrogen loss, or certain bone diseases like bone cancer all fall within the covered scope.

The real exposure for billing teams is repeat testing. CMS states directly: if bone resorption is not elevated, repeat testing is not medically necessary. A single test that shows normal resorption closes the door on follow-up claims. Document the initial result and make sure the ordering physician's notes justify any subsequent orders.

The policy also calls for safeguards against excessive testing in patients for whom the test has no clinical relevance. That language signals that CMS expects payers and MACs to scrutinize patterns of high-volume collagen crosslinks billing. If your practice or lab bills this test frequently, expect closer review.

Prior authorization is not explicitly required under this NCD, but that doesn't mean your MAC won't have a local coverage determination (LCD) that adds prior auth requirements on top of this national policy. Check with your Medicare Administrative Contractor before assuming national coverage translates directly to local reimbursement without additional steps.

CMS Collagen Crosslinks Exclusions and Non-Covered Indications

CMS draws a clear line here. Testing in patients without elevated bone resorption is not covered for repeat claims. The policy is unambiguous on this point.

Testing in patients for whom the test has no clinical relevance is also excluded. CMS's language about "safeguards" is a direct message to MACs and reviewers: watch for claims that don't fit a clinically appropriate patient profile.

Routine monitoring in stable patients who are not on antiresorptive therapy is not supported by the NCD. The clinical trigger for covered testing is active treatment monitoring or a diagnostic workup where bone resorption status will change clinical management.

The policy also implies that patients who are well past the "fast loser" window — elderly Medicare beneficiaries who have been stable on therapy for years — are unlikely to meet medical necessity for new collagen crosslinks orders. This isn't absolute, but the clinical logic CMS uses points strongly in that direction. If you're billing for these patients, make sure the chart supports a clear reason why the test will change management.

Coverage Indications at a Glance

CMS Collagen Crosslinks Billing Guidelines and Action Items 2026

These are the steps your billing team and clinical staff need to take before and after the effective date of March 7, 2026.

CPT, HCPCS, and ICD-10 Codes for Collagen Crosslinks Under NCD 96

Note on Code Availability

The current NCD 96 policy data does not list specific CPT, HCPCS, or ICD-10 codes. This is a known limitation of some NCD releases — CMS sometimes publishes coverage criteria without explicit code-level assignments, leaving code selection to the MAC level or to standard lab coding conventions.

Do not infer codes from this blog post. Collagen crosslinks testing billing codes should be confirmed directly with your lab, your MAC's published LCD, or your coding team's current reference materials. The method of testing — immunoassay versus HPLC — typically drives the CPT code assignment, and that distinction needs to be verified against current AMA CPT guidance and your MAC's fee schedule.

If your billing team is uncertain which codes apply to your specific test methodology, contact your Medicare Administrative Contractor directly or consult a coding specialist before the March 7, 2026 effective date.