Androgen receptor CAG repeat size is associated with stress fracture risk: A pilot study

Background: Stress fractures commonly affect military recruits during basic training. Several lines of evidence suggest genetic factors are involved in stress fracture predisposition. As gender steroid hormone levels and activity have been implicated in affecting bone strength, one of the candidate genes likely to be involved is the androgen receptor gene. Questions/purposes: We assessed the possible involvement of the androgen receptor gene in stress fracture predisposition in Israeli soldiers. Patients and Methods: Between January 2007 and December 2009, we collected clinical and imaging data from 454 Israeli soldiers referred for bone scans with clinical symptoms compatible with stress fractures: 171 soldiers (154 men, 17 women) (patients) with bone scan-proven stress fractures and 283 soldiers (242 men, 41 women) with normal bone scans (control subjects). All participants were genotyped for the length of the CAG (cytosine-adenine-guanine) repeat in exon 1 of the androgen receptor gene using PCR and subsequent fragment analysis on sequence analyzer. Results: The androgen receptor gene CAG repeat was ranged between six and 31 (mean ± SD, 20.6 ± 4.3) among patients and between 11 and 32 (mean ± SD, 20.0 ± 3.8) among control subjects. Smaller-sized (< 16) androgen receptor CAG repeats were more prevalent among control subjects (23%) than among patients (13%); the risk for having SFs was almost halved if the size of the repeat was shorter than 16 repeats. Conclusions: The androgen receptor gene CAG repeat has a different allele distribution among Israeli soldiers with stress fractures than in control subjects. While our finding must be validated, it could be used for screening individuals at risk for stress fractures. Level of Evidence: Level II, prognostic study. See the Guidelines for Authors complete description of levels of evidence.