-
Bauer DC, Black D, Ensrud K, Thompson D, Hochberg M, Nevitt M, Musliner T, Freedholm D. Upper gastrointestinal tract safety profile of alendronate - the fracture intervention trail. Arch Intern Med 2000;160:517-525. PubMed
| Level of Evidence |
1b |
| Study Design |
Randomized, Double-blind, Placebo-controlled Trial
|
| Sample Size |
- N =
2,207 vertebral fracture group
- N = 4,432 clinical fracture group
|
| Interventions |
- Alendronate
5 mg daily (after 2 years, alendronate dose increased to 10 mg daily)
- Placebo
|
| Follow Up |
Interview
follow-up every 3 months
Duration
dependent on study arm:
- 3
yrs for vertebral fracture group
- 4.5 yrs for clinical fracture group
|
| Primary Endpoint |
Incidence of upper GI tract events
|
| Secondary Endpoint |
Further
examination of GI tract events looking at particular areas of GI tract
-
Stomach:
gastritis, hemorrhage, gastric ulcer
- Duodenum:
duodenitis, hemorrhage, duodenal ulcer
- Esophagus: acid regurgitation, reflux
esophagitis, esophagitis, Barrett esophagus, erosive esophagitis, esophageal ulcer, esophageal
stricture, dysphagia, odynophagia, esophagalgia
|
| Results |
- Incidence
of upper GI tract events: alendronate (47.5%; 1,536/3,236) vs placebo (46.2%;
1,490/3,223) with RR of 1.02 (95% CI, 0.95 - 1.10)
- Incidence
of esophageal events: alendronate (10%;
322/3,236) vs placebo (9.4%; 303/3,223) with a RR 1.06 (95% CI, 0.91 - 1.24)
- Esophageal ulcers: alendronate 0.2% vs placebo 0.2%
|
| Conclusions |
Both
active and placebo groups frequently experienced upper GI tract events, but the
events were not significantly greater in the active group. The rate of esophageal ulcer occurrence was infrequent,
and the results were similar between groups. |
| Location |
11 U.S. Clinical Centers
|
| Funding |
Merck Research Laboratories |
| Comments |
Many of the diagnoses of the secondary endpoints were subjective which
could have created skewed data given the trial occurred in 11 clinical centers.
|
-
McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY. Effect of risedronate on the risk of hip fracture in elderly women. N Engl J Med. 2001;344(5):333-340. PubMed
| Level of Evidence |
1b |
| Study Design |
Prospective, Multicenter, Randomized, Placebo-Controlled Trial |
| Sample Size |
N = 5,445 women
|
| Interventions |
- Risedronate 2.5 mg or 5 mg by mouth daily
- Placebo
|
| Other Treatments |
- Calcium
carbonate 1000 mg of elemental calcium daily
- Vitamin D (< 500 IU daily) if serum
25-hydroxyvitamin D concentration < 16 mg/mL at screening
|
| Follow-Up |
3 - years
|
| Primary Endpoint |
Occurrence of hip fracture |
| Secondary Endpoint |
Incidence
of nonvertebral osteoporotic fractures, bone
mineral density, and ssessment of adverse events |
| Results |
- The
overall incidence of hip fracture was 2.8% (137/6197) risedronate vs placebo
3.9% (95/3134) with RR 0.7 (95% CI, 0.6 - 0.9; p = 0.02)
- The
incidence of hip fractures in women 70-79 yrs with osteoporosis was 1.9%
(55/3624) vs placebo 3.2% (46/1821) with RR 0.6 (95% CI, 0.4-0.9; p = 0.009)
- The
incidence of hip fractures in women > 80 yrs and with > 1 risk factor for
hip fracture was 4.2% (82/2573) for risedronate vs placebo 5.1% (49/1313) with
RR 0.8 (95% CI, 0.6-1.2; p = 0.35)
- The
incidence of nonvertebral fractures was 9.4% for risederonate vs 11.2% for
placebo, RR 0.8 (95% CI, 0.7-1.0; p = 0.03)
- Esophageal ulceration occurred in 0.3% with
risedronat 2.5 mg vs 0.03% with risderonate 5 mg, and 0.4% with placebo.
|
| Conclusions |
Incidence
of esophageal ulcer was similar between risedronate and placebo groups. Incidence of hip fracture in women aged 70-79
years of age with a diagnosis of osteoporosis
was significantly reduced with bisphosphonate use compared to placebo. |
| Location |
183 study centers in North America, Europe, New Zealand, and Australia
|
| Funding |
Procter & Gamble Pharmaceuticals
|
| ClinicalTrials.gov |
|
| Comments |
Effects of calcium and vitamin D could contribute to results.
|
|
