Design of a pragmatic approach to evaluate the effectiveness of concurrent treatment for the prevention of osteoporotic fractures: rationale, aims and organization of a Japanese Osteoporosis Intervention Trial (JOINT) initiated by the Research Group of Adequate Treatment of Osteoporosis (A-TOP).
The aim of osteoporosis treatment is to prevent future fractures. Although concurrent treatment has been used very frequently for osteoporosis in clinical practice, there are no data on accurate and verified effectiveness of concurrent treatment for fracture prevention in patients with osteoporosis. To clarify the clinical usefulness of concurrent treatment, the Japan Osteoporosis Society has authorized the establishment of the A-TOP (Adequate Treatment of Osteoporosis) research group. The objective of this research is to establish a design for a clinical trial to prove whether concurrent treatment using both alfacalcidol (1-alpha-hydroxycholecalciferol) and alendronate is more effective as compared to treatment using alendronate alone in terms of fracture prevention. The present study was named JOINT (Japanese Osteoporosis Intervention Trial) and is based on a method using national, prospective, randomized, open-labeled, blinded endpoints focusing on postmenopausal osteoporosis with a high risk for fracture. The patients were mainly selected by practitioners and allocated randomly by a central registration system into two groups, of which one received 5 mg/day of alendronate alone, and the other received 1 μg/day of 1-alpha-hydroxycholecalciferol (alfacalcidol) in addition to the alendronate. The endpoints focused primarily on fracture prevention, and the patients' quality of life (QOL) and change in body height, as well as adherence and the adverse events of the treatments were evaluated secondarily. To obtain sufficient statistical power in the events during a 2-year observation period, the patients who are expected to have higher risk were selected to participate in this study, and it was decided that the final plan would involve 890 patients per group (two-sided alpha = 0.05, power = 0.8). Data collection began in November 2003. Correspondence regarding the registration of the investigator and the progress of the study was conducted through a web system from the Public Health Research Foundation to practitioners.
Shiraki
Masataka
M
Department of Internal Medicine, Research Institute and Practice for Involutional Diseases, 1610-1 Meisei, Misato, Azumino, Nagano, Japan. ripid@fc4.so-net.ne.jp
Kuroda
Tatsuhiko
T
Miyakawa
Nobuaki
N
Fujinawa
Naohito
N
Tanzawa
Kazumasa
K
Ishizuka
Akiko
A
Tanaka
Shiro
S
Tanaka
Yukari
Y
Hosoi
Takayuki
T
Itoi
Eiji
E
Morimoto
Shigeto
S
Itabashi
Akira
A
Sugimoto
Toshitsugu
T
Yamashita
Toshihiko
T
Gorai
Itsuo
I
Mori
Satoshi
S
Kishimoto
Hideaki
H
Mizunuma
Hideki
H
Endo
Naoto
N
Nishizawa
Yoshiki
Y
Takaoka
Kunio
K
Ohashi
Yasuo
Y
Ohta
Hiroaki
H
Fukunaga
Masao
M
Nakamura
Toshitaka
T
Orimo
Hajime
H
D015502:Absorptiometry, Photon; D000368:Aged; D019386:Alendronate / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use*; D007564:Japan; D010024:Osteoporosis / Q000188:drug therapy*; D058866:Osteoporotic Fractures / Q000517:prevention & control
D050071:Bone Density Conservation Agents; D006887:Hydroxycholecalciferols; C008088:alfacalcidol; D019386:Alendronate
J Bone Miner Res. 2003 Jun;18(6):1051-6
12817758
BMJ. 1996 Jan 13;312(7023):71-2
8555924
J Bone Miner Res. 2000 Jul;15(7):1384-92
10893688
Expert Opin Pharmacother. 2009 Oct;10(14):2303-15
19640210
Osteoporos Int. 2003 Dec;14(12):965-8
14504697
Osteoporos Int. 1999;10(3):183-92
10525709
Bone. 2004 Apr;34(4):599-604
15050889
J Bone Miner Metab. 2004;22(2):104-10
14999520
J Bone Miner Res. 2008 Oct;23(10):1569-75
18505366
Lancet. 1996 Dec 7;348(9041):1535-41
8950879
JAMA. 1998 Dec 23-30;280(24):2077-82
9875874
J Bone Miner Metab. 2006;24(3):219-25
16622735
JAMA. 2004 Sep 15;292(11):1363-4
15355936
J Bone Miner Metab. 2001;19(6):331-7
11685647
JAMA. 1999 Aug 18;282(7):637-45
10517716
J Bone Miner Metab. 2004;22(5):462-8
15316867
J Bone Miner Res. 1996 Jul;11(7):984-96
8797120
JAMA. 1999 Oct 13;282(14):1344-52
10527181
Endocr Rev. 2002 Aug;23(4):570-8
12202472
JAMA. 2001 Feb 14;285(6):785-95
11176917
J Bone Miner Metab. 2007;25(5):302-9
17704995
J Bone Miner Res. 2004 Feb;19(2):323-9
14969403