Wednesday, April 29, 2009

Your Bones: Role of Bone Turnover Markers

Here's a post from the latest North American Menopause Society's First to Know site. Bruce Ettinger is an osteoporosis expert. See what you think of his comments about this recent article. -- SG

BTMs to predict BMD response

Burnett-Bowie SA, Saag K, Sebba A, et al. Prediction of

changes in bone mineral density in postmenopausal

women treated with once-weekly bisphosphonates. 

J Clin Endocrinol Metab 2009 Jan 13 [Epub ahead of

print] Level of evidence: II-2.


Abstract copyright © 2009 The Endocrine Society. All

rights reserved. Used with permission.


BACKGROUND: In clinical practice, bone

mineral density (BMD) determined by DXA is

used to monitor response to osteoporosis

therapy. However, 1 to 2 years are usually

required to assess patients’ BMD responses.

The possibility of earlier indicators of a

response or non-response to treatment, such as

changes in bone turnover markers (BTMs), is

of interest to physicians and patients.

METHODS: In this post-hoc analysis of

women treated with once-weekly bis-

phosphonates, we examined the association of

tertile percent change from baseline in BTMs at

3 or 6 months, and association of several

baseline clinical characteristics, with 24-month

percent change from baseline in BMD, and

with percentage of patients showing BMD non-

response (defined as BMD loss at 2 or more of

4 sites) at 24 months. Multivariable analysis

was performed to determine which factors were

associated with BMD non-response.

RESULTS: Patients in the tertile with the

greatest decrease in each of the BTMs had the

greatest mean increase in BMD and the lowest

percentage of BMD nonresponders at 24

months. Several characteristics were

independently associated with BMD non-

response including smaller 3-month reductions from baseline in CTX, bone ALP, and PINP,

younger age of menopause, a family history of

osteoporosis, and higher baseline trochanteric

BMD. Baseline BTMs were not predictive of 24-

month BMD response to therapy. The strongest

associations were for changes in BTMs with

treatment. CONCLUSION: In groups of patients,

short term changes in markers of bone turnover

appear to be predictors of longer term BMD

response and non-response to bisphosphonate



Comment. It has been over 15 years that BTMs

have been commercially available—yet few

practitioners ever use these tests in management

of osteoporosis. There was high hope that BTMs

would be useful for individual patients in several

ways including: 1) determining fracture risk and

need for treatment; 2) determining what kind of

drug to use; and 3) encouraging adherence and

persistence with therapy. 


This report adds to our general skepticism about

application of BTMs to individual patients. Even

using group data (with more power to find

associations), the authors failed to find that

baseline BTM values predicted response to

bisphosphonate (BP) treatment among compliant

users after 2 years. Furthermore, change between

baseline and 3-6 month BTM values showed only

weak associations with 2-year bone density



Typically, studies of BMD in clinical trials of BP

indicate a 90% response rate; in this paper,

alendronate users had an 88% BMD response

rate. Thus, the number of poor responders that

could ideally be found by a perfect BTM test


would be about 1 in 10. But, as the current article

shows, BTM tests have poor specificity and

sensitivity when applied to patients starting BPs.

This is not new. Delmas et al,1 using NTx, found

that about one third of patients starting on BP did

not decrease NTx the expected 30%—a lot of

false positives.


BTMs have been useful in research, but for

several reasons are not worth the trouble in

practice. First, the cost: in the range of $140 to

$150 per test (double this when getting baseline

and 3-6 month follow-up). Second, the

inconvenience for patients: requiring morning

12-hour fasting blood sampling. Third, the low

predictive value: in this paper, the correlation

coefficient between BTM and BMD was only 

-0.25, meaning that only 6% of the variance in

the BMD increase could be predicted from the

BTM decrease. Finally, investigators who have

examined feedback of BTM results on patients’

drug persistence have found no difference

between giving BTM results and simply

contacting and supporting those patients newly



It is no wonder that NAMS and other expert

societies have not recommended to clinicians

that they use BTMs to make early treatment

decisions in individual patients.


Bruce Ettinger, MD

Clinical Professor of Medicine and Radiology

University of California, San Francisco

San Francisco, CA

Certified NAMS Menopause Practitioner



Delmas PD, Vrijens B, Eastell R, et al. Effect of

monitoring bone turnover markers on persistence with

risedronate treatment of postmenopausal osteoporosis. 

J Clin Endocrinol 2007;92:1296-1304. 

1 comment:

Aubrey Blumsohn said...

I agreed with Ettinger, and to make it worse much of the data in this niche area is frankly fraudulent

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