549 Form

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Medical Policy Bone Turnover Markers for Diagnosis and Management of Osteoporosis and Diseases Associated with High Bone Turnover Table of Contents • Policy: Commercial • Description • Information Pertaining to All Policies
• Authorization Information • Policy History

• Coding Information • References

Policy Number: 549 BCBSA Reference Number: 2.04.15 (For Plan internal use only) Related Policies
• Bone Mineral Density Studies, #450 • Vertebral Fracture Assessment with Densitometry, #449 Policy Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity

Measurement of bone turnover markers is considered INVESTIGATIONAL to determine fracture risk in individuals with osteoporosis or with age-related risk factors for osteoporosis.

Measurement of bone turnover markers is considered INVESTIGATIONAL in the management of individuals with conditions associated with high rates of bone turnover, including but not limited to Paget’s disease, primary hyperparathyroidism and renal osteodystrophy.

Measurement of bone turnover markers is considered INVESTIGATIONAL to determine response to therapy in individuals who are being treated for osteoporosis. Prior Authorization Information Inpatient • For services described in this policy, precertification/preauthorization IS REQUIRED for all products if the procedure is performed inpatient.
Outpatient • For services described in this policy, see below for products where prior authorization might be required if the procedure is performed outpatient.

Outpatient Commercial Managed Care (HMO and POS) This is not a covered service. Commercial PPO and Indemnity This is not a covered service.

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CPT Codes / HCPCS Codes / ICD Codes Inclusion or exclusion of a code does not constitute or imply member coverage or provider reimbursement. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage as it applies to an individual member.

Providers should report all services using the most up-to-date industry-standard procedure, revenue, and diagnosis codes, including modifiers where applicable.

The following codes are included below for informational purposes only; this is not an all-inclusive list. The following CPT code is considered investigational for Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity:

CPT Codes CPT codes:

Code Description 82523 Collagen cross-links, any method

The following CPT code is considered investigational for Commercial Members: Managed Care (HMO and POS), PPO, Indemnity, Medicare HMO Blue and Medicare PPO Blue:

CPT Codes CPT codes:

Code Description 83937 Osteocalcin (bone g1a protein)

Description Bone Turnover After cessation of growth, bone is in a constant state of remodeling (or turnover), with initial absorption of bone by osteoclasts followed by deposition of new bone matrix by osteoblasts.1, This constant bone turnover is critical to the overall health of the bone, by repairing microfractures and remodeling the bony architecture in response to stress. Normally, the action of osteoclasts and osteoblasts is balanced, but bone loss occurs if the 2 processes become uncoupled. Bone turnover markers can be categorized as bone formation markers or bone resorption markers and can be identified in serum and/or urine.2, There is interest in the use of bone turnover markers to evaluate age-related osteoporosis, a condition characterized by slow, prolonged bone loss, resulting in an increased risk of fractures at the hip, spine, or wrist. Measurement of bone turnover markers may aid in the diagnosis (by determining fracture risk) and therapeutic monitoring (by determining response to treatment) of osteoporosis. Bone turnover markers may also be used for the management of other diseases associated with high bone turnover (eg, primary hyperparathyroidism, Paget disease, renal osteodystrophy). Table 1 summarizes the various bone turnover markers.3,

Table 1. Bone Turnover Markers Formation Markers Resorption Markers Serum osteocalcin Serum and urinary hydroxyproline Serum total alkaline phosphatase Urinary total pyridinoline Serum bone-specific alkaline phosphatase Urinary total deoxypyridinoline Serum procollagen I carboxyterminal propeptide Urinary-free pyridinoline (also known as Pyrilinks) Serum procollagen type 1 N-terminal propeptide Urinary-free deoxypyridinoline (also known as Pyrilinks- D) Bone sialoprotein Serum and urinary collagen type I cross-linked N- telopeptide (also referred to as Osteomark)

Serum and urinary collagen type I cross-linked C- telopeptide (also referred to as CrossLaps)

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Serum carboxy-terminal telopeptide of type I collagen

Tartrate-resistant acid phosphatase

Summary Description Bone turnover markers are biochemical markers of either bone formation or bone resorption. Commercially available tests are available to assess some of these markers in urine and/or serum by high-performance liquid chromatography or immunoassay. Assessment of bone turnover markers is proposed to supplement bone mineral density measurement in the diagnosis of osteoporosis and to aid in treatment decisions. Bone turnover markers could also potentially be used to evaluate treatment effectiveness before changes in bone mineral density can be observed.

Summary of Evidence For individuals with osteoporosis or risk factors for age-related osteoporosis who receive a measurement of bone turnover markers to determine fracture risk, the evidence includes observational studies on the association between markers and osteoporosis and fracture risk, and systematic reviews of those studies. Relevant outcomes are test validity and morbid events. Few studies have directly addressed whether any bone turnover markers beyond bone mineral density (BMD) measurements are independent predictors of fracture risk. One meta-analysis investigated the independent role of bone turnover markers in fracture risk prediction and found a statistically significant but modest association between bone turnover markers (specifically, PINP and CTX) and future fracture risk after adjusting for BMD and clinical risk factors. Other studies have suggested that bone turnover marker levels may be independently associated with osteoporosis and fracture risk in some groups, but there is insufficient evidence reporting on an association with any specific marker. Questions remain whether bone turnover markers are sufficiently sensitive to determine reliably individual treatment responses. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. For individuals who are being treated for osteoporosis who receive a measurement of bone turnover markers to determine response to therapy, the evidence includes an observational studies, randomized controlled trials (RCTs), and a systematic review of these RCTs. Relevant outcomes are test validity and morbid events. There is limited evidence on the impact of bone turnover markers on the management of osteoporosis. Individual RCTs and a systematic review of these RCTs have not found that feedback on bone turnover markers improves treatment adherence rates. No studies were identified that evaluated whether the use of bone turnover markers leads to management changes that are expected to improve outcomes. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. For individuals with conditions associated with high rates of bone turnover other than age-related osteoporosis (eg, primary hyperparathyroidism, Paget disease, renal osteodystrophy) who receive a measurement of bone turnover markers, the evidence includes observational studies on the association between markers and disease activity and a systematic review of those studies. Relevant outcomes are test validity and morbid events. The largest amount of evidence has been published on Paget disease; a systematic review found correlations between several bone turnover markers and disease activity prior to and/or after bisphosphonate treatment. There is a lack of evidence on how the measurement of bone turnover markers can change patient management or improve health outcomes. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Policy History Date Action 2/2026 Annual policy review. Policy updated with literature review through October 22, 2025; references added. Policy statements unchanged.
3/2025 Annual policy review. References updated. Policy statements unchanged. 3/2024 Annual policy review. Description, summary, and references updated. Policy statements unchanged.

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3/2023 Annual policy review. Minor editorial refinements to policy statements; intent unchanged. 2/2022 Annual policy review. Policy statements unchanged. 3/2021 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 1/2021 Medicare information removed. See MP #132 Medicare Advantage Management for local coverage determination and national coverage determination reference.
6/2020 Annual policy review. New investigational indications described. Effective 6/1/2020. 2/2019 Annual policy review. Description, summary, and references updated. Policy statements unchanged. 3/2018 Annual policy review. New references added. 11/2015 Annual policy review. New references added. 7/2015 Clarified coding information. 6/2014 Updated Coding section with ICD10 procedure and diagnosis codes, effective 10/2015. 1/2014 Annual policy review. New references added. 11/2013 Added ICD-9 diagnosis code 256.9 to be in alignments with the NCD. 10/2013 Added ICD-9 diagnosis codes 252.00-252.02, 252.08 to be in alignment with the NCD. 6/2013 Annual policy review. New investigational indications described. Effective 6/1/2013.
11/2011-4/2012 Medical policy ICD 10 remediation: Formatting, editing and coding updates.
No changes to policy statements.
1/1/2011 New policy effective 1/1/2011 describing covered and non-covered indications. Information Pertaining to All Blue Cross Blue Shield Medical Policies Click on any of the following terms to access the relevant information: Medical Policy Terms of Use Managed Care Guidelines Indemnity/PPO Guidelines Clinical Exception Process Medical Technology Assessment Guidelines

References

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