Bone turnover markers (BTMs) are gaining traction as a tool for identifying osteoporosis in its earliest stages, as well as providing key information for monitoring and treating patients with the disease. Updating its 2012 guidance, the Japan Osteoporosis Society offers a detailed tutorial on the types of assays and algorithms for measuring BTMs, reflecting new types of drugs and therapies that have been approved over the last 7 years. The updated guidelines appear in the journal Clinica Chimica Acta.
Effectively treating osteoporosis before it progresses helps patients maintain their quality of life while avoiding medical expenses associated with fractures, according to the guideline authors. “To achieve this effect, the early diagnosis of osteoporosis, the effective treatment of existing osteoporosis and highly precise treatment monitoring, and the assessment of fracture risk are all essential,” they wrote.
The society had initially developed guidelines for BTM in 2001, updating them periodically every few years. Since the 2001 edition, the number of BTMs in Japan has grown to 2.6 million a year, evolving into an important clinical test, Masakazu Miura, PhD, MBA, a board member of both the Japan Osteoporosis Society and Japan Society of Clinical Chemistry, and corresponding author of the guidelines, told CLN Stat. “BTM is used in the treatment of osteoporosis to determine the drug for osteoporosis and to monitor the therapeutic effect,” Miura said.
Clinicians often use bone biopsy or bone mineral density measurements to help diagnose disease. Biopsy is invasive and in some ways limited, however, and bone mineral density isn’t that practical a choice in monitoring bone turnover on a daily basis, to inform treatment. “Studies have found that BTMs can accurately express the state of daily bone turnover and are thus more useful as dynamic indices,” wrote Miura and his co-authors.
With new drug formulations changing the landscape of osteoporosis management, “two issues must now be addressed: what significance should currently be allotted to drug turnover markers, and the fact that the guidelines were formulated only for the treatment of primary osteoporosis, whereas, in clinical practice today, secondary osteoporosis is also a target of treatment,” the authors explained.
The guideline identifies 26 assays that measure 14 different analytes in three categories: bone formation markers; bone resorption markers; and bone matrix-related markers. Specifically, it highlights BTM tests that are either currently available or under development in Japan, said Miura. The most popular bone resorption marker is tartrate-resistant acid phosphatase (TRACP)-5b, developed by Nittobo Medical in Japan, representing 34% of all BTM usage.
Total Type I procollagen-N- propeptide (Total P1NP), developed by Roche, and bone alkaline phosphatase (BAP), developed by Beckman Coulter, represent the most popular bone formation markers. Other frequently used tests include: type I collagen cross-linked N-telopeptide; deoxypyridinoline; type I collagen cross-linked C-telopeptide; Intact P1NP; and undercarboxylated osteocalcin (ucOC).
The guideline also includes algorithms for using these markers to guide testing following diagnosis, selecting therapy, and to evaluate response after treatment begins.
In the event that no drugs are affecting bone metabolism or recent fractures, the guideline recommends which biomarker assays clinicians should use for various treatments. For example, if a patient is receiving vitamin K2, the recommendation is to measure for ucOC, whereas patients undergoing daily teriparatide treatments should be measured for BAP or P1NP. If no treatment has been decided, the recommendation is to measure seven different markers including TRACP-5b, BAP, and P1NP.
When selecting a drug treatment for osteoporosis, clinicians should check for drugs that affect bone metabolism. Patients taking such drugs should discontinue them for one month. The next course of action is to measure a series of bone resorption markers and bone formation markers. The guideline authors recommended several different courses of action on drug treatments, depending on whether a patient’s bone resorption or formation markers were above or below upper reference limits. For example, if a patient’s bone resorption markers are below their respective reference limits, clinicians in selecting drug treatment should consider variables such as fractures, bone mineral density, risk factors, and comorbidities.
To evaluate patient response after the start of osteoporosis treatment, clinicians should measure a bone resorption marker and bone formation marker before the start of treatment and 3 to 6 months after treatment starts. The algorithm also describes what courses of action a clinician should take under two scenarios: If a “minimum significant change” has or hasn’t has been exceeded for either bone resorption or formation markers; or whether or not these markers are within or not within the reference limits for premenopausal women.
“The main reasons for testing BTMs in osteoporosis are to evaluate the status of bone metabolism in patients with a clinical diagnosis of osteoporosis, select therapeutic drugs, and assess response to treatment,” the authors summarized.