Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Osteopenia.
Treatment: Genetic Testing (collagen cross links, any method (82523). 

The insurer denied the Genetic Testing (collagen cross links, any method (82523).  The denial is overturned.

The patient is a female diagnosed with Osteopenia. This request is for Collagen cross links testing. As reported, she is postmenopausal with a history of breast cancer. She was started on Anastrazole as part of the therapy for the breast cancer. This class of drugs is known to cause bone loss. She was being treated for hypercalciuria but despite that has continued to lose bone. The CTX (carboxy-terminal telopeptide of type 1 collagen) and NTX (amino-terminal telopeptide of type 1 collagen) were elevated and high normal.

Yes, the health plan should cover the Collagen crosslink testing, as it is medically appropriate, as described below.

Yes, the Collagen crosslink testing is more beneficial.

Collagen Crosslinks are not investigational, as there is evidence that examining Collagen crosslinks changes management and improves outcomes. There is a relationship between normalization of bone markers and clinical outcomes (1-9). Collagen crosslinks are used to determine bone turnover in patients with osteopenia or osteoporosis (1, 10, 11). Measures of bone turnover are useful in osteopenia and osteoporosis in determining the course and efficacy of treatment (1-3, 12, 13).

It is standard of care for patients being followed on treatment with anti-resorptive agents for osteopenia and osteoporosis and in whom a secondary cause of osteoporosis is suspected.

The American Association of Clinical Endocrinologists (AACE) Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis published in 2011, supports the use of collagen Crosslinks when secondary causes of osteoporosis are suspected, when patients are being treated with antiresorptive agents, assessing fracture risk in elderly patients, and identifying patients with high bone turnover (to predict rapid bone loss) (14, 15).

The national osteoporosis foundation also supports the use of collagen Crosslinks (16).

Biochemical markers of bone turnover may:  1) Predict risk of fracture independently of bone density, 2) Predict extent of fracture risk reduction when repeated after 3-6 months of treatment with FDA (United States Food and Drug Administration)-approved therapies. 3) Predict magnitude of BMD (bone mineral density) increases with FDA (United States Food and Drug Administration)-approved therapies, 4) Predict rapidity of bone loss, 5)  Help determine adequacy of patient compliance and persistence with osteoporosis therapy, and 6) Help determine duration of 'drug holiday' and when and if medication should be restarted.

It states, "Biochemical markers of bone remodeling [e.g., resorption markers serum C-telopeptide (CTX) and urinary N-telopeptide (NTX) and formation markers serum bone specific alkaline phosphatase (BSAP) and osteocalcin] can be measured in the serum and urine in untreated patients to assess risk of fracture. They may predict bone loss and, when repeated after 3-6 months of treatment with FDA (United States Food and Drug Administration) approved antiresorptive therapies, may be predictive of fracture risk reduction."

This patient has postmenopausal osteopenia and may have a secondary cause of this bone loss. She meets the above described criteria for use of collagen crosslinks.

There are no other tests that can be done that provide the same information. The test is expected to be health beneficial for the patient.