LRP5 gene polymorphisms and idiopathic osteoporosis in men

• Published in: Bone (New York, N.Y.) Vol. 37; no. 6; pp. 770 - 775
• Main Authors: Ferrari, S.L., Deutsch, S., Baudoin, C., Cohen-Solal, M., Ostertag, A., Antonarakis, S.E., Rizzoli, R., de Vernejoul, M.C.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-12-2005; Elsevier Science
• Subjects: Adult; Aged; Amino Acid Substitution; Biological and medical sciences; Case-Control Studies; Diseases of the osteoarticular system; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Haplotypes; Humans; LDL-Receptor Related Proteins - genetics; Low Density Lipoprotein Receptor-Related Protein-5; LRP5; Male; Medical sciences; Men; Middle Aged; Mutation, Missense; Osteoporosis; Osteoporosis - genetics; Osteoporosis. Osteomalacia. Paget disease; Polymorphism; Polymorphism, Genetic; Vertebrates: anatomy and physiology, studies on body, several organs or systems; BMD; LRP5; Osteoporosis; Men; Polymorphism; Human; LDL receptor-related protein 5; Morphology; Diseases of the osteoarticular system; Idiopathic
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2005.06.017

Mutations in the low-density lipoprotein receptor-related protein 5 gene (
LRP5) have demonstrated the role of LRP5 in bone mass acquisition.
LRP5 variants were recently reported to contribute to the population-based variance in vertebral bone mass and size in males. To investigate whether
LRP5 variants are implicated in idiopathic male osteoporosis, we studied 78 men with low BMD (<2.5
T score or < −2
Z score) aged less than 70 years (mean ± SD: 50 ± 16 years) in whom secondary causes of osteoporosis had been excluded and 86 controls (51 ± 10 years). Genotypes and haplotypes were based on
LRP5 missense substitutions in exons 9 (c.2047G > A, p.V667M) and 18 (c.4037C > T, p.A1330V), and their association with osteoporosis evaluated after adjustment for multiple clinical and environmental variables using logistic regression. The presence of osteoporosis was significantly associated with
LRP5 haplotypes (
P = 0.0036) independent of age (
P = 0.006), weight (
P = 0.004), calcium intake (
P = 0.002), alcohol (
P = 0.005) and tobacco (
P = 0.004) consumption. Accordingly, the odds ratio for osteoporosis was 3.78 (95% CI 1.27–11.26,
P < 0.001) in male carriers of haplotype 3 (c.2047A–4037T,
n = 20 cases and 12 controls) versus homozygous carriers of haplotype 1 (c.2047G–4037C,
n = 42 cases and 61 controls). In conclusion, these data indicate beyond a significant role for environmental factors, an association between
LRP5 variants and idiopathic osteoporosis in males, pointing to a role of LRP5 in this disease.