Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

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


Relationship of Baseline Bone Turnover Marker Levels and Month 12 Bone Mineral Density Change in Postmenopausal Women Transitioned From Alendronate to Denosumab

Bolognese1,  M.A., Roux2,  C., Bianchi3,  G., Supronik4,  J., Valter5,  I., de Vernejoul6,  M.C., Kendler7,  D.L.

Bethesda Health Research Center, Bethesda, MD,
Amgen Inc., Thousand Oaks, CA,
Azienda Ospedaliera Careggi, Firenze, Italy
Paris Descartes University Hôpital Cochin, Paris, France,
Azienda Sanitaria Genovese, Genova, Italy,
Niepubliczny Zaklad Opieki Zdrowotnej Centrum Medyczne, Bialystok, Poland,
Center for Clinical and Basic Research. Tallinn, Estonia,
Hôpital Lariboisiere, Paris, France,
Clinical Research Centre, Vancouver, BC,
Michigan Bone and Mineral Clinic. Detroit, MI,
Istituto Auxologico Italiano, Milan, Italy,

Purpose:

Denosumab is an investigational fully-human monoclonal antibody that reduces bone resorption by inhibiting RANKL, an essential mediator of osteoclast formation, function, and survival. In previous studies in postmenopausal women, denosumab increased bone mineral density (BMD) and reduced the risk of fracture.

Methods:

Subjects were eligible for this randomized, double-blind, double-dummy study if they were postmenopausal women >=55 with a lumbar spine or total hip T-score <=-2.0 and >=-4.0 and were receiving generic or branded alendronate for >=6 months. After a 1-month alendronate run-in phase, subjects were randomized to treatment with continued alendronate (70 mg weekly) or denosumab (60 mg every 6 months subcutaneously) and the effects on BMD were compared. The relationship between baseline bone turnover marker levels and month 12 percent changes in BMD at the total hip or lumbar spine was also evaluated.

Results:

The 504 enrolled women (251 alendronate, 253 denosumab) had a baseline mean age of 68, a mean lumbar spine BMD T-score of –2.63, and a median sCTX-I level of 0.20 ng/mL (range, 0.05–0.89 ng/mL). As previously reported, transition to denosumab resulted in greater increases in total hip, lumbar spine, femoral neck, and 1/3 radius BMD compared with continued alendronate (P<=0.012). For subjects receiving alendronate, month 12 BMD gains were generally similar across quartiles of baseline bone turnover marker levels. For subjects transitioned to denosumab, month 12 BMD gains at the total hip and lumbar spine were largest and significantly differed from the alendronate group among subjects in the 2 highest quartiles of baseline sCTX-I or PINP levels (Table– total hip vs. sCTX-I).

Table. Percent Change in Month 12 Total Hip BMD by Baseline sCTX-I

Baseline sCTX-I (ng/mL) AlendronateDenosumab
<0.128N5662
 BMD % Change1.241.58
 95% CI0.66, 1.821.03, 2.12
0.128–<0.202N5762
 BMD % Change1.241.38
 95% CI0.61, 1.870.78, 1.97
0.202–<0.308N5863
 BMD % Change1.152.16*
 95% CI0.56, 1.741.57, 2.74
>=0.308N6254
 BMD % Change0.682.65**
 95% CI0.12, 1.232.05, 3.24
*P = 0.015 vs alendronate;**P < 0.0001 vs. alendronate

Conclusion:

In postmenopausal women with low bone mass who were previously receiving alendronate, transition to denosumab 60 mg every 6 months increased BMD. The greatest BMD increases as compared with continued alendronate occurred among women with the two highest quartiles of baseline levels of bone turnover markers.

To cite this abstract, please use the following information:
Bolognese, M.A., Roux, C., Bianchi, G., Supronik, J., Valter, I., de Vernejoul, M.C., et al; Relationship of Baseline Bone Turnover Marker Levels and Month 12 Bone Mineral Density Change in Postmenopausal Women Transitioned From Alendronate to Denosumab [abstract]. Arthritis Rheum 2009;60 Suppl 10 :871
DOI: 10.1002/art.25951

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