NEW YORK (Reuters Health)—Levels of two bone markers currently recommended for evaluating postmenopausal women with osteoporosis have no association with hip fracture risk, according to a new study using Women’s Health Initiative data.
“At least in these postmenopausal women, it was not a useful endeavor to check bone turnover markers to predict hip-fracture risk. That doesn’t mean it wouldn’t apply to men or people who were taking therapy for osteoporosis,” Dr. Carolyn J. Crandall, a professor at David Geffen School of Medicine at the University of California, Los Angeles, tells Reuters Health by phone.
The International Osteoporosis Foundation/International Federation of Clinical Chemistry and Laboratory Medicine (IOF/IFCC) Bone Markers Working Group stated in 2011 that C-terminal telopeptide of type I collagen (CTX) and procollagen type 1 aminoterminal propeptide (PINP) were the “most promising markers” of bone turnover, Dr. Crandall and her team note in the Journal of Bone and Mineral Research, online June 19.1 The IOF/IFCC recommends that serum CTX, a bone resorption marker, and serum PINP, a bone formation marker, be measured by standardized assays and used as reference markers in research.
Studies to date looking at bone turnover markers have focused on fragility or osteoporotic fractures in general, and no studies focusing on hip fracture have required that samples be taken in a fasting state, the authors note. “Because hip fractures are a substantial cause of increased morbidity and mortality, it is of clinical importance to elucidate the ability of serum bone turnover markers to predict hip fracture risk,” they add.
Dr. Crandall and her team reviewed data from the WHI study, which included measurements of fasting serum PINP and CTX. Women were followed for about seven years, on average, and self-reported hip fractures were confirmed by physician report. They compared 400 women with incident hip fracture who were not taking osteoporosis medication and 400 controls matched by age, race/ethnicity and blood sampling date.
Multivariate analysis showed no significant association between serum CTX or PINP and hip fracture risk.
The authors note that the findings are clinically relevant, given that the American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis recommend, based on Grade B evidence, that clinicians “consider using bone turnover markers in the initial evaluation of osteoporosis patients. Elevated levels can predict higher fracture risk.”
Clinicians are using serum CTX and PINP to predict fracture risk in osteoporosis, Dr. Crandall noted, but this practice is not evidence-based. Some also test for additional bone turnover markers, she adds. “Even those have not really been standardized yet across laboratories in the way that they should be.”
The next steps will be to determine if the bone markers are useful in predicting fracture risk in older men, she added, whether they can predict other types of fracture, and whether they are useful for monitoring people who are stopping their osteoporosis therapy for a drug holiday.
“Those are all very important questions that I think need to be addressed,” she says. “For the time being it doesn’t look like there are clear indications of roles for turnover markers in those settings, but we need to do some methodologically good research to really get solid answers about that.”
- Crandall CJ, Vasan S, LaCroix A, et al. Bone turnover markers are not associated with hip fracture risk: A case-control study in the Women’s Health Initiative. J Bone Miner Res. 2018 Jul;33(7):1199–1208.