Alendronate with and without cholecalciferol for osteoporosis: results of a 15-week randomized controlled trial.
OBJECTIVE
Many osteoporosis patients have low 25-hydroxyvitamin D (25OHD) and do not take recommended vitamin D amounts. A single tablet containing both cholecalciferol (vitamin D3) and alendronate would improve vitamin D status concurrently, with a drug shown to reduce fracture risk. This study assessed the efficacy, safety, and tolerability of a once-weekly tablet containing alendronate 70 mg and cholecalciferol 70 microg (2800 IU) (ALN + D) versus alendronate 70 mg alone (ALN).


METHODS
This 15-week, randomized, double-blind, multi-center, active-controlled study was conducted during a season when 25OHD levels are declining, and patients were required to avoid sunlight and vitamin D supplements for the duration of the study. Men (n = 35) and postmenopausal women (n = 682) with osteoporosis and 25OHD >or= 9 ng/mL were randomized to ALN + D (n = 360) or ALN (n = 357).


METHODS
Serum 25OHD, parathyroid hormone, bone-specific alkaline phosphatase (BSAP), and urinary N-telopeptide collagen cross-links (NTX).


RESULTS
Serum 25OHD declined from 22.2 to 18.6 ng/mL with ALN (adjusted mean change = -3.4; 95% confidence interval [CI]: -4.0 to -2.8), and increased from 22.1 to 23.1 ng/mL with ALN + D (adjusted mean change = 1.2; 95% CI: 0.6 to 1.8). At 15 weeks, adjusted mean 25OHD was 26% higher (p < 0.001, ALN + D versus ALN), the adjusted relative risk (RR) of 25OHD < 15 ng/mL (primary endpoint) was reduced by 64% (incidence 11% vs. 32%; RR = 0.36; 95% CI: 0.27 to 0.48 [p < 0.001]), and the RR of 25OHD < 9 ng/mL (a secondary endpoint) was reduced by 91% (1% vs. 13%; RR = 0.09; 95% CI: 0.03 to 0.23 [p < 0.001]). Antiresorptive efficacy was unaltered, as measured by reduction in bone turnover (BSAP and NTX).


CONCLUSIONS
In osteoporosis patients who avoided sunlight and vitamin D supplements, this once-weekly tablet containing alendronate and cholecalciferol provided equivalent antiresorptive efficacy, reduced the risk of low serum 25OHD, improved vitamin D status over 15 weeks, and was not associated with hypercalcemia, hypercalciuria or other adverse findings, versus alendronate alone.
Recker
Robert
R
Creighton University, Osteoporosis Research Center, Omaha, NE, USA. RRecker@creighton.edu
Lips
Paul
P
Felsenberg
Dieter
D
Lippuner
Kurt
K
Benhamou
Laurent
L
Hawkins
Federico
F
Delmas
Pierre D
PD
Rosen
Clifford
C
Emkey
Ronald
R
Salzmann
Gretel
G
He
Weili
W
Santora
Arthur C
AC
D000368:Aged; D019386:Alendronate / Q000008:administration & dosage* / Q000009:adverse effects; D001842:Bone and Bones / Q000378:metabolism; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D017698:Postmenopause; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
D004338:Drug Combinations; D010281:Parathyroid Hormone; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D; D019386:Alendronate