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Summary  The risk of osteoporosis increases in inflammatory disorders. In cell‐mediated immune activation, interferon ( IFN )‐γ stimulates macrophage release of neopterin and increases the activity of indoleamine 2,3‐dioxygenase ( IDO ), thereby stimulating tryptophan degradation along the kynurenine pathway. Plasma levels of neopterin and the kynurenine/tryptophan ratio ( KTR ) are thus markers of  IFN ‐γ‐mediated inflammation. Several kynurenine pathway metabolites (kynurenines) possess immunomodulatory properties. The aim of this study was to investigate associations between markers of  IFN ‐γ‐mediated inflammation and kynurenines with bone mineral density ( BMD ). The community‐based  H ordaland  H ealth  S tudy ( HUSK ), with middle‐aged (46–49 years) and older (71–74 years) participants, was conducted from 1998 to 2000 ( n  = 5312). Hip  BMD  in relation to neopterin,  KTR  and kynurenines were investigated, using linear and logistic regression analyses. In the oldest group, neopterin ( P  ≤ 0·019) and  KTR  ( P  ≤ 0·001) were associated inversely with  BMD  after multiple adjustment. Comparing the highest to the lowest quartiles, the odds ratios of low  BMD  (being in the lowest quintile of  BMD ) in the oldest cohort were for neopterin 2·01 among men and 2·34 among women ( P  ≤ 0·007) and for  KTR  1·80 for men and 2·04 for women ( P  ≤ 0·022). Xanthurenic acid was associated positively with  BMD  in all sex and age groups while 3‐hydroxyanthranilic acid was associated positively with  BMD  among women only ( P  ≤ 0·010). In conclusion, we found an inverse association between  BMD  and markers of  IFN ‐γ‐mediated inflammation in the oldest participants.  BMD  was also associated with two kynurenines in both age groups. These results may support a role of cell‐mediated inflammation in bone metabolism.

Interferon ( IFN )‐γ‐mediated inflammation and the kynurenine pathway in relation to bone mineral density: the H ordaland H ealth S tudy