Bone Turnover Markers for Diagnosis and Management of Osteoporosis and Diseases Associated with High Bone Turnover

POLICY NUMBER

A.2.04.15

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.

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. 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 two 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. 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). The table below summarizes the various bone turnover markers.

Bone Turnover Markers

Several tests for bone turnover markers have been cleared for marketing by the U.S. Food and Drug Administration through the 510(k) process. Examples are listed in the table below. FDA product codes: NEO, JMM, CIN.

FDA-Cleared Tests for Bone Turnover Markers

ELISA: enzyme-linked immunosorbent assay; FDA: U.S. Food and Drug Administration.

Related Policies:

• Bone Mineral Density Studies

• Vertebral Fracture Assessment with Densitometry or Biomechanical Computed Tomography

POLICY

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 to determine response to therapy in individuals who are being treated 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 disease, primary hyperparathyroidism, and renal osteodystrophy.

POLICY EXCEPTIONS

Federal Employee Program (FEP): FEP may dictate that laboratory tests approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational and thus these devices may be assessed only on the basis of their medical necessity.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting. 

POLICY HISTORY

1/5/2007: Policy added.

3/22/2007: Reviewed and approved by the Medical Policy Advisory Committee (MPAC).

5/9/2008: Policy reviewed, no changes.

12/11/2009: Policy Description revised to add additional information on bone turnover markers, their definition, and additional indications for testing. FDA approved collagen cross-links and other bone turnover tests added. Links to related policies added. Policy Exceptions revised to add FEP verbiage.

10/21/2010: Policy title changed from "Collagen Cross Links as Markers of Bone Turnover" to "Bone Turnover Markers for the Diagnosis and Management of Osteoporosis." This terminology was changed throughout the policy. Intent of policy statement unchanged.

10/05/2011: Policy reviewed. Deleted "or other conditions associated with increased bone turnover" from the policy statement. Intent unchanged.

01/09/2013: Added "and Diseases Associated with High Bone Turnover" to the policy title. Added the following investigational policy statement:  Measurement of bone turnover markers is considered investigational in the management of patients with conditions associated with high rates of bone turnover, including but not limited to Paget’s disease, primary hyperparathyroidism and renal osteodystrophy. Added 83937 to the Code Reference section as non-covered.

12/13/2013: Policy reviewed; no changes.

11/11/2014: Policy reviewed; description updated. Added "markers" to first investigational policy statement. Intent unchanged.

07/08/2015: Code Reference section updated for ICD-10.

11/16/2015: Policy description updated. Policy statements unchanged. Investigative definition updated in policy guidelines section.

06/06/2016: Policy number A.2.04.15 added.

01/16/2017: Policy description updated. Policy statements unchanged.

01/15/2018: Policy description updated. Policy statements unchanged.

01/14/2019: Policy reviewed; no changes.

03/05/2020: Policy description updated to remove information regarding bone density. First policy statement separated into two statements. The policy intent is unchanged. The first statement is regarding determining fracture risk, and the second statement is regarding monitoring response to therapy. It previously stated: Measurement of bone turnover markers is considered investigational in the diagnosis and management of osteoporosis.

03/02/2021: Policy description updated. Policy statements unchanged.

02/10/2022: Policy reviewed; no changes.

02/14/2023: Policy description updated regarding bone turnover and FDA cleared tests for bone turnover markers. Policy statements updated to change "patients" to individuals."

02/09/2024: Policy description updated. Policy statements unchanged.

03/12/2025: Policy reviewed; no changes.

SOURCE(S)

Blue Cross Blue Shield Association Policy # 2.04.15

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy. 

Investigational Codes

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