Background: Advanced glycation end-products (AGEs), that bind to type 1 collagen in bone and skin, have been implicated in reduced bone quality. The AGE reader^TM measures skin autofluorescence (SAF), which might be regarded as a marker of long-term AGEs accumulation in tissues. We investigated the association of SAF with bone mineral density (BMD) and fractures in the general population.

Methods: We studied 2853 individuals from the Rotterdam Study with available SAF measurements (mean age 74.1 years) and with data on prevalent major osteoporotic (MOFs: hip, humerus, wrist, clinical vertebral) and vertebral fractures (VFs: clinical + radiographic Genant’s grade 2 and 3). Radiographs were assessed 4-5 years before SAF. Multivariate regression models were performed adjusted for age, sex, BMI, creatinine, smoking status and diabetes and additionally for BMD with interaction terms to test for effect modification.

Results: Prevalence of MOFs was 8.5% and of VFs 7%. SAF had a curvilinear association with prevalent MOFs and VFs and therefore, age-adjusted, sex stratified SAF quartiles were used. The odds ratio (OR) (95% confidence interval) of the second, third and fourth quartiles of SAF for MOFs were 1.60(1.08-2.35, p=0.02); 1.30(0.89-1.97, p=0.20) and 1.40(0.95-2.10, p=0.09), respectively, with first (lowest) quartile as reference. For VFs the OR were 1.69(1.08-2.64, p=0.02), 1.74(1.11-2.71, p=0.01) and 1.73(1.12-2.73, p=0.02) for second, third and fourth quartiles respectively. When comparing the top three quartiles combined with the first quartile, the OR (95% CI) for MOFs was 1.43(1.04-2.00, p=0.03) and for VFs 1.72(1.18-2.53, p=0.005).  Additional  adjustment for BMD did not change the associations.

Conclusion: In conclusion, there is evidence of presence of a threshold of skin AGEs below which there is distinctly lower prevalence of fractures. Longitudinal analyses are needed to confirm our cross-sectional findings.