TY - JOUR
T1 - The detrimental effects of kynurenine, a tryptophan metabolite, on human bone metabolism
AU - Kim, Beom Jun
AU - Hamrick, Mark W
AU - Yoo, Hyun Ju
AU - Lee, Seung Hun
AU - Kim, Su Jung
AU - Koh, Jung Min
AU - Isales, Carlos M
N1 - Funding Information:
This paper was supported by grants from the Bio & Medical Technology Development Program of the National Research Foundation, funded by the Korean Government, MSIP (2016M3A9E8941329) (to B.-J.K.) and from the National Institute on Aging, US National Institutes of Health (AG036675) (to C.M.I.).
Funding Information:
Financial Support: This paper was supported by grants from the Bio & Medical Technology Development Program of the National Research Foundation, funded by the Korean Government, MSIP (2016M3A9E8941329) (to B.-J.K.) and from the National Institute on Aging, US National Institutes of Health (AG036675) (to C.M.I.).
Publisher Copyright:
Copyright © 2019 Endocrine Society
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Context: Studies in aged mice support a role for kynurenine, a tryptophan metabolite, in age-induced bone loss; however, the role of kynurenine in human bone metabolism is not well understood. Objective: To assess whether the kynurenine level in bone marrow (BM) aspirates, directly reflecting the bone microenvironment, is associated with osteoporosis-related phenotypes and bone biochemical markers. Design and Setting: A case-control study conducted in a clinical unit. Participants and Main Outcome Measures: BM samples were collected from 72 patients at the time of hip surgery for either fragility hip fracture (HF) (n = 27) or for other causes (n = 45). In these samples, kynurenine was measured by liquid chromatography-tandem mass spectrometry, and the levels of tartrate-resistant acid phosphatase 5b (TRAP5b), bone-specific alkaline phosphatase (BSALP), receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) were measured by immunoassay. Results: Age was positively correlated with BM kynurenine level. After adjustment for confounders, subjects with fragility HF had a 39.7% higher BM kynurenine level than those without, and the OR per SD increment in BM kynurenine level for fragility HF was 3.80. The BM kynurenine level was inversely associated with bone mass at the total femur. Higher kynurenine concentrations were significantly associated with higher TRAP-5b and RANKL levels, but not with BSALP and OPG levels, in BM plasma. Conclusion: These results suggest that increased kynurenine levels during aging may contribute to the bone fragility seen in the elderly through increased bone resorption, with a resultant imbalance in bone remodeling.
AB - Context: Studies in aged mice support a role for kynurenine, a tryptophan metabolite, in age-induced bone loss; however, the role of kynurenine in human bone metabolism is not well understood. Objective: To assess whether the kynurenine level in bone marrow (BM) aspirates, directly reflecting the bone microenvironment, is associated with osteoporosis-related phenotypes and bone biochemical markers. Design and Setting: A case-control study conducted in a clinical unit. Participants and Main Outcome Measures: BM samples were collected from 72 patients at the time of hip surgery for either fragility hip fracture (HF) (n = 27) or for other causes (n = 45). In these samples, kynurenine was measured by liquid chromatography-tandem mass spectrometry, and the levels of tartrate-resistant acid phosphatase 5b (TRAP5b), bone-specific alkaline phosphatase (BSALP), receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) were measured by immunoassay. Results: Age was positively correlated with BM kynurenine level. After adjustment for confounders, subjects with fragility HF had a 39.7% higher BM kynurenine level than those without, and the OR per SD increment in BM kynurenine level for fragility HF was 3.80. The BM kynurenine level was inversely associated with bone mass at the total femur. Higher kynurenine concentrations were significantly associated with higher TRAP-5b and RANKL levels, but not with BSALP and OPG levels, in BM plasma. Conclusion: These results suggest that increased kynurenine levels during aging may contribute to the bone fragility seen in the elderly through increased bone resorption, with a resultant imbalance in bone remodeling.
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U2 - 10.1210/jc.2018-02481
DO - 10.1210/jc.2018-02481
M3 - Article
C2 - 30715395
AN - SCOPUS:85065559761
SN - 0021-972X
VL - 104
SP - 2334
EP - 2342
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 6
ER -