Alendronate Trial In Adults With Osteogenesis Imperfecta (OI): Characteristics Of The Population At Baseline.

P.J. Meunier, G. Chevrel, J.E. Charrin, E. Fontanges
Department of Rheumatology and Bone Diseases,
Edouard Herriot Hospital, 69437 Lyon Cedex 3, France.

The term OI is used to designate a group of diseases characterized by brittle bones that fracture with minimal trauma, leading to skeletal deformities. Although useful advances have been made in our understanding of OI and its treatment in children, the efficacy of systemic drugs currently used to treat this disease remains unproven in adult. The purpose of our study is to determinate the effects on bone mineral density and safety of alendronate, a potent amino-bisphosphonate, in adults with OI in a single-centre, randomised, double-blind, placebo-controlled trial with parallel groups. The inclusion criteria are: women (pre- or postmenopausal) and men, outpatients, >= 20 years, suffering from OI arbritrarly defined by the association of 3 criteria:

1. A typical personal history of bone fragility fractures before 20 years with at least 3 successive fractures,
2. One criterion in the following list: blue sclerae; scoliosis (COBB method and angle > 10° and < 40°); hearing disorder defined by a decrease of 10 dB of the average Rinne; hyperlaxity defined by at least 3 criteria of Carter and Wilkinson; dentinogenesis imperfecta defined by at least one yellow to brown tooth; at least one family member with osteogenesis imperfecta.
3. A low bone mineral density (BMD) of lumbar spine or total hip measured by dual energy X-ray absorptiometry (DXA) with a T score >= - 2.5 on one site (WHO threshold for osteoporosis definition).

The treatment consists in one tablet of alendronate 10 mg or placebo, taken orally each day, half an hour before breakfast and a daily supplement of 1 g of elemental calcium and 800 IU of vitamin D3. The main efficacy endpoint is the change in the lumbar bone mineral density after three years of treatment, with an interim analysis at 2 years. The main secondary end points are: the changes in bone mineral density of the total hip; the incidence and rate of vertebral and peripheral fractures; the level of pain; the everyday activity; the changes in biochemial markers of bone turnover assessed by measuring serum osteocalcin, serum and urinary crosslaps and type I collagen propeptide.

The clinical, biochemical and densitometric characteristics at baseline of the recruited population will be described.

Supported by: Association de l'Ostéogenèse Imparfaite, Hospices Civils de Lyon (Programme Hospitalier de Recherche Clinique n° 97. 058), Merck Sharp & Dohme-Chibret Laboratories and I.N.S.E.R.M. Unit 403.

Reference: Proceedings of the 7th International Conference on Osteogenesis Imperfecta. Montreal, Canada, 1999.