Effects of oral alendronate on BMD in adult patients with osteogenesis imperfecta: a 3-year randomized placebo-controlled trial.
A 3-year, randomized, double-blind, placebo-controlled trial evaluated the effect of oral alendronate on the BMD of 64 adult patients with osteogenesis imperfecta. The mean increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7 +/- 5.7% in the alendronate and placebo groups, respectively. Oral alendronate increases BMD in adult patients with osteogenesis imperfecta.


BACKGROUND
This study evaluated the effect of oral alendronate on the BMD of adult patients with osteogenesis imperfecta.


METHODS
We carried out a 3-year, randomized, double-blind, placebo-controlled trial of oral alendronate in 64 adult patients with osteogenesis imperfecta. The primary endpoint was the difference between the groups in the mean percent change in lumbar spine BMD at 3 years. Secondary outcomes included changes in BMD of total hip, vertebral and peripheral fracture incidence, pain, hearing loss, and bone turnover biochemical markers. Patients were treated daily with either placebo or 10 mg alendronate. All received 1 g of calcium and 800 IU of vitamin D daily.


RESULTS
The mean +/- SD increases in the lumbar spine BMD were 10.1 +/- 9.8% (p < 0.001) and 0.7 +/- 5.7% in the alendronate and placebo groups, respectively. Hip BMD increased in the alendronate group by 3.3 +/- 0.5% (p = 0.001) and decreased in the placebo group by 0.3 +/- 0.6%. The sample size was not sufficient to determine an effect of alendronate on fracture rate. A significant increase of the pain score was noted in the alendronate group (p = 0.04) in the intent-to-treat analysis but not in the per protocol analysis. There was no change in hearing in either group. Bone resorption and formation biochemical markers were significantly decreased in the alendronate group (p < 0.001). There were no differences in severe adverse effects between the groups, but there was an increase in nonsevere upper gastrointestinal effects in the alendronate group (p = 0.003).


CONCLUSIONS
Oral alendronate increases BMD and increase nonsevere gastrointestinal adverse effects but does not modify the hearing loss in adult patients with osteogenesis imperfecta. More studies are needed to evaluate an effect on the fracture rate.
Chevrel
Guillaume
G
Department of Rheumatology and Bone Diseases, Edouard Herriot Hospital, Lyon France.
Schott
Anne-Marie
AM
Fontanges
Elisabeth
E
Charrin
Jeanne E
JE
Lina-Granade
Geneviève
G
Duboeuf
François
F
Garnero
Patrick
P
Arlot
Monique
M
Raynal
Claude
C
Meunier
Pierre J
PJ
D015502:Absorptiometry, Photon; D000284:Administration, Oral; D000328:Adult; D019386:Alendronate / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016723:Bone Remodeling; D003094:Collagen / Q000097:blood / Q000652:urine; D024042:Collagen Type I; D005260:Female; D050723:Fractures, Bone / Q000000981:diagnostic imaging; D034381:Hearing Loss / Q000175:diagnosis; D006615:Hip / Q000000981:diagnostic imaging; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D010013:Osteogenesis Imperfecta / Q000188:drug therapy*; D010146:Pain / Q000175:diagnosis; D010455:Peptides / Q000097:blood / Q000652:urine; D010919:Placebos; D016103:Spinal Fractures / Q000000981:diagnostic imaging; D016896:Treatment Outcome
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D010455:Peptides; D010919:Placebos; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D019386:Alendronate