Effects of odanacatib on BMD and safety in the treatment of osteoporosis in postmenopausal women previously treated with alendronate: a randomized placebo-controlled trial.
BACKGROUND
Odanacatib (ODN) is a selective cathepsin K inhibitor being developed to treat osteoporosis.


OBJECTIVE
The effects of ODN were evaluated on bone mineral density (BMD), biochemical markers of bone turnover, and safety in patients previously treated with alendronate.


METHODS
This was a randomized, double-blind, placebo-controlled, 24-month study.


METHODS
The study was conducted at private or institutional practices.


METHODS
Postmenopausal women (n = 243) ≥ 60 years of age with low BMD at the total hip, femoral neck, or trochanter (T-score ≤-2.5 but >-3.5 without prior fracture or ≤-1.5 but >-3.5 with prior fracture) on alendronate for ≥ 3 years.


METHODS
The intervention included ODN 50 mg or placebo weekly.


METHODS
The primary end point was percentage change from baseline of femoral neck BMD at month 24. BMD was assessed by dual-energy x-ray absorptiometry at baseline and 6, 12, and 24 months. Biochemical markers of bone turnover (serum C-telopeptides of type 1 collagen, urinary N-telopeptides of type 1 collagen, serum bone specific alkaline phosphatase, and serum N-terminal propeptide of type 1 collagen) were measured at baseline and 3, 6, 12, 18, and 24 months.


RESULTS
In the ODN group, BMD changes from baseline at the femoral neck, trochanter, total hip, and lumbar spine at 24 months (1.7%, 1.8%, 0.8%, and 2.3%, respectively) were significantly different from the placebo group. ODN significantly decreased urinary N-telopeptides of type 1 collagen to creatinine ratio and significantly increased serum N-terminal propeptide of type 1 collagen compared with placebo. Serum C-telopeptides of type 1 collagen was unexpectedly increased with ODN treatment. The safety profile appeared similar between groups.


CONCLUSIONS
ODN provided incremental BMD gains in osteoporotic women after alendronate treatment.
MD, PhD, 126 East Lincoln Avenue, Rahway, NJ 07065-0900. deborah.gurner@merck.com.
Sydney
S
Bonnick
Tobias
T
De Villiers
Alberto
A
Odio
Santiago
S
Palacios
Roland
R
Chapurlat
Carolyn
C
DaSilva
Boyd B
BB
Scott
Celine
C
Le Bailly De Tilleghem
Albert T
AT
Leung
Deborah
D
Gurner
D000368:Aged; D019386:Alendronate / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002136:Calcium, Dietary / Q000627:therapeutic use; D056657:Cathepsin K / Q000037:antagonists & inhibitors*; D002762:Cholecalciferol / Q000627:therapeutic use; D003131:Combined Modality Therapy; D019587:Dietary Supplements; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D055118:Medication Adherence; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy* / Q000378:metabolism; D010352:Patient Dropouts; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*
D015415:Biomarkers; D001713:Biphenyl Compounds; D050071:Bone Density Conservation Agents; D002136:Calcium, Dietary; D011480:Protease Inhibitors; D002762:Cholecalciferol; D056657:Cathepsin K; C527128:odanacatib; D019386:Alendronate