Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Relationship Between the Effect of Denosumab On Bone Turnover Markers and Change in Bone Mineral Density in Postmenopausal Osteoporosis

McClung1,  M., Christiansen2,  C., Grauer3,  A., Kutilek4,  S., Libanati3,  C., Resch5,  H., Reid6,  I.

Oregon Osteoporosis Center, Portland, OR,
SFCC, CPMC Research Institute & UCSF, San Francisco, CA,
University of Sheffield, Sheffield, United Kingdom
CCBR, Ballerup, Denmark,
Amgen Inc., Thousand Oaks, CA,
CCBR, Pardubice, Czech Republic,
St. Vincent Hospital Vienna, University of Vienna, Vienna, Austria,
University of Auckland, Auckland, New Zealand,
Columbia University Medical Center, New York, NY,
University Hospital of Zurich, Zurich, Switzerland,
CHU de Nancy, Vandoeuvre, France,

Purpose:

Denosumab (DMAb), an investigational human monoclonal antibody to RANKL, reduced the risk of vertebral, nonvertebral and hip fractures in the FREEDOM trial. With DMAb treatment, levels of bone resorption markers (BRM) were reduced below the premenopausal reference range in all women tested. In a subset of women, the level of BRM reduction attenuated at the end of the 6-month dosing interval, while other women had sustained BRM reduction throughout the study. We evaluated the relationship between change in bone turnover markers (BTM) and change in BMD and if there were similar BMD increases in women with sustained BTM reduction vs those with a transient attenuation of BTM.

Methods:

FREEDOM was a phase 3 trial in women ages 60–90 years with postmenopausal osteoporosis randomized to sc DMAb 60mg or placebo (Pbo) every 6 months for 36 months with daily calcium (1000mg) and vitamin D supplements (400–800 IU). Osteoporosis was defined as a T-score <-2.5 at the spine or hip but not <-4 at either site. We measured BTM (serum CTX [ELISA, Osteometer] and PINP [RIA, Orion]) in 944 women (505 DMAb, 439 Pbo) at baseline, 1, 6, 12, 24 and 36 months, and BMD of the proximal femur annually and lumbar spine at baseline and 36 months.

Results:

DMAb decreased CTX and PINP at 6 months and increased BMD at the lumbar spine and total hip at 36 months (Table). Overall, BTM changes in DMAb and Pbo groups at 6 months were negatively correlated with BMD changes at 36 months (Table). Mean (SD) BMD changes with DMAb at 36 months were identical (+0.08 [0.04] g/cm2 at the lumbar spine, and +0.04 [0.02] g/cm2 at the total hip) in women treated with DMAb who had sustained reduction in BTM (n=146 CTX, n=103 PINP) vs those who had transient attenuation of BTM levels before repeat dosing (n=359 CTX, n=402 PINP).

 PlaceboDMAb
CTX Absolute Change (ng/mL) at 6 mo, median (interquartile range)-0.07 (-0.20 to +0.04)-0.40 (-0.59 to -0.26)†††
PINP Absolute Change (ng/mL) at 6 mo, median (interquartile range)-14 (-26 to -5)-39 (-54 to -25)†††
Lumbar Spine BMD Change (g/cm2) at 36 mo, mean (SD)0.00 (0.04)+0.08 (0.04)†††
Total Hip BMD Change (g/cm2) at 36 mo, mean (SD)-0.01 (0.03)+0.04 (0.02)†††
Correlation Between CTX at 6 mo and Lumbar Spine BMD Change at 36 mo-0.09-0.20***
Correlation Between PINP at 6 mo and Lumbar Spine BMD Change at 36 mo-0.07-0.31***
Correlation Between CTX at 6 mo and Total Hip BMD Change at 36 mo-0.16**-0.34***
Correlation Between PINP at 6 mo and Total Hip BMD Change at 36 mo-0.09-0.39***
††† p < 0.001 indicates the difference in BTM/BMD changes between treatment groups is different from zero.
**p < 0.01 and*** p < 0.001 indicate the correlation between BTM change at 6 months and BMD change at 36 months is different from zero.

Conclusion:

There were weak to modest correlations between changes in BTM and changes in BMD. Additionally, there were similar increases in BMD whether or not BTM remained below the premenopausal reference range throughout the study or showed attenuation of BTM before the next dose.

To cite this abstract, please use the following information:
McClung, M., Christiansen, C., Grauer, A., Kutilek, S., Libanati, C., Resch, H., et al; Relationship Between the Effect of Denosumab On Bone Turnover Markers and Change in Bone Mineral Density in Postmenopausal Osteoporosis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :870
DOI: 10.1002/art.25950

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