Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Denosumab Decreases Cortical Porosity in Postmenopausal Women with Low Bone Mineral Density.

Libanati1,  C., Boyd2,  S. K., Nishiyama2,  K. K., Zebaze3,  R. M., Hanley2,  D. A., Zanchetta4,  J. R., Thomas5,  Thierry

Amgen Inc., Thousand Oaks, CA
University of Calgary, Calgary, AB
University of Melbourne, Melbourne, Australia
Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina
INSERM U1059 and University Hospital, Saint-Étienne, France
INSERM U831 and Université de Lyon, Lyon, France
Austin and Repatriation Medical Centre, University of Melbourne, Melbourne, Australia

Background/Purpose:

Intracortical remodeling, particularly in the cortex adjacent to the marrow cavity, is responsible for most of the bone lost during advancing age.1,2 Indeed, patients who suffer a hip fracture have large coalescent pores that precipitously compromise bone strength as porosity increases.3 Denosumab reduces bone remodeling and ovariectomy-induced intracortical porosity in subhuman primates. In postmenopausal women, denosumab rapidly reduces bone remodeling intensity and increases cortical density.4–6 We propose that this increase in cortical density is the result of (i) partial reversal of intracortical porosity that is present prior to treatment, (ii) reduction in the appearance of new pores by suppression of remodeling, and (iii) more complete secondary mineralization of osteons (which would be removed had remodeling continued at the same intensity). We now present evidence to support several of these mechanisms.

Methods:

Postmenopausal women (N=247) aged 61 ± 5 years with low bone mineral density were randomized in a double-blind, double-dummy fashion to denosumab 60 mg every 6 months (N=83), alendronate 70 mg weekly (N=82), or placebo (N=82). Porosity was evaluated in the compact-appearing cortex of the distal radius at baseline and month 12 from HRpQCT scans using an enhanced method that accurately7 and reproducibly8 identifies the cortex with automatic threshold segmentation.9 Pores above ~82 mm were quantifiable; porosity was expressed as a percent of the total cortical volume.

Results:

Baseline cortical porosity at the distal radius was 2.6%. Over 12 months, cortical porosity (mean [95% CI]) increased with placebo (5.19%[1.41, 8.98]) and alendronate (2.86%[–2.32, 8.04]) but decreased with denosumab (–2.98%[–6.39, 0.43]) (Figure). Denosumab reduced cortical porosity by 8.18% (P < 0.01) compared with placebo and by 5.84% (P= 0.06) compared with alendronate.

Figure. Denosumab Decreases Cortical Porosity at the Distal Radius in Postmenopausal Women With Low Bone Mineral Density

Conclusion:

In summary, denosumab prevented the progression of porosity seen with placebo, an effect that differs from that of alendronate. The changes in porosity are likely to partly reverse bone fragility and prevent its progression and thus reduce fracture risk. Ongoing work exploring non-threshold methods and assessing porosity over the entire cortex, including the trabecularized cortex is underway and may improve quantification of bone morphology and differences between therapies.

References:

1Zebaze, , Lancet 2010;

2Holzer, , JBMR 2009,

3Bell, , Bone 2000;

4Seeman, , JBMR 2010;

5Genant, , Bone 2010;

6Baron, , Bone 2011;

7Nishiyama, , JBMR 2010;

8Burghardt, , Bone 2010;

9Buie, , Bone 2007

To cite this abstract, please use the following information:
Libanati, C., Boyd, S. K., Nishiyama, K. K., Zebaze, R. M., Hanley, D. A., Zanchetta, J. R., et al; Denosumab Decreases Cortical Porosity in Postmenopausal Women with Low Bone Mineral Density. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1631
DOI:

Abstract Supplement

Meeting Menu

2011 ACR/ARHP