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Early Bone Loss Marker Predicts Fracture Risk Later
  By Michael Smith, North American Correspondent, MedPage Today
Published: October 20, 2010
Action Points
* Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
* Explain that having a high level of cross-linked N-telopeptide of type 1 collagen (NTx) was linked to about a 50% increase in the risk of later fracture.
* Note that NTx is a marker of bone resorption.
TORONTO -- A marker of bone resorption before menopause is associated with risk of fracture later, a researcher said here.
Having a high level of cross-linked N-telopeptide of type 1 collagen (dubbed NTx, for short) was linked to about a 50% increase in the risk of later fracture, according to Jane Cauley, DPhil, of the University of Pittsburgh.
The finding comes from an analysis of 2,406 women taking part in the so-called SWAN study (for Study of Women's health Across the Nation), Cauley reported here at the annual meeting of the American Society for Bone and Mineral Research.
Participants were eligible to take part in the study if they were between the ages of 42 and 52, were not taking oral contraceptives or on hormone therapy, and had menstruated within three months of the date of enrollment, Cauley said.
The researchers measured osteocalcin (involved in bone-building) at baseline and urinary NTx (a breakdown product of bone) every year for an average of 7.6 years. They also measured lumbar spine and hip bone mineral density every year, using dual energy x-ray absorptiometry. New fractures were identified through self-report and later verified by radiology.
Over the study period, there were 184 fractures, and women who had broken bones were significantly heavier (at P=0.005), more likely to have a history of previous fractures (at P=0.001), and had significantly lower spine bone mineral density (at P=0.005).
However, the change in spine bone mineral density over time was not significantly different between the groups, Cauley said.
Analysis of the bone turnover markers showed:
* Baseline osteocalcin was not significantly related to later fracture risk.
* Baseline NTSACx above the median (a ratio of nanomoles of bore collagen equivalent to minimoles of creatinine of more than 31.9) was associated with a significant 49% increase in risk of later fracture in a multivariate analysis.
* In the fully adjusted model, an NTx increase of one standard deviation was associated with a significant 35% increase in risk.
* Women who had an NTx level above the median at any clinic visit had a significant 55% increase in fracture risk in the multivariate model.
Cauley cautioned that osteocalcin was available only at baseline, so the study might underestimate its predictive value. Also, she noted, newer markers of bone formation might be more sensitive.
It's also not clear, she said, if urinary NTx and serum NTx would yield similar results.
If the finding can be confirmed, it might have a clinical implication, said Elizabeth Barrett-Connor, MD, of University of California San Diego, who moderated the session at which the study was presented.
"If you can identify women with rapid bone loss," she told MedPage Today, "you might be vigorous in getting them into a lifestyle program."
But Barrett-Connor said it's unlikely that medication would play a role. "I'm not ready to treat 51-year-old women to prevent osteoporosis," she said.

The study was supported by the NIH and Swiss Precision Diagnostics. Cauley made no disclosures.
Barrett-Connor had no disclosures.
Primary source: American Society for Bone and Mineral Research
Source reference:
Cauley JA, et al "Bone resorption and fracture across the menopausal transition: The Study of Women's Health Across the Nation (SWAN)" ASBMR 2010; Abstract 1093.
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