A high activity index of stearoyl-CoA desaturase is associated with increased risk of fracture in men.
The activity index of stearoyl-CoA desaturase (SCD), a key enzyme in lipogenesis, was associated with increased risk of fracture in a longitudinal population-based cohort of men. This indicates that elevated levels of endogenous lipogenesis increase the risk of fracture and suggest a role for saturated fat in the pathogenesis of osteoporosis.


BACKGROUND
Osteoblasts and marrow adipocytes are derived from a common mesenchymal progenitor, and experimental studies have indicated that increased adipogenesis can occur at the expense of osteoblasts, leading to bone loss. Stearoyl-CoA desaturase (SCD) converts saturated to monounsaturated fatty acids and is a key enzyme in lipogenesis.


METHODS
Analysis was performed in a population-based, longitudinal cohort study of men (n = 2009). A product-to-precursor index (palmitoleic acid/palmitic acid) was used to estimate SCD activity in fasting serum analyzed in samples obtained at enrollment at age 50 years. Fractures were documented in 422 men during 35 years of follow-up. Cox regression analysis was used to determine the risk of fracture according to SCD activity index.


RESULTS
The risk of fracture was highest among men with the highest levels of SCD activity index. Multivariable analysis of the risk of fracture in the highest quintile as compared to the lowest one showed that the rate ratio was 1.71 (95% CI 1.26-2.33) for any fracture, with an estimated population attributable risk of 15%. The risk was further increased within the highest quintile.


CONCLUSIONS
Our results indicate that elevated levels of endogenous lipogenesis increase the risk of fracture and suggest a role for saturated fat in the pathogenesis of osteoporosis.
Melhus
H
H
Department of Medical Sciences, University Hospital, Entrance 61, 4th floor, SE-751 85, Uppsala, Sweden. Hakan.Melhus@medsci.uu.se
Risérus
U
U
Warensjö
E
E
Wernroth
L
L
Jensevik
K
K
Berglund
L
L
Vessby
B
B
Michaëlsson
K
K
D015415:Biomarkers / Q000378:metabolism; D050723:Fractures, Bone / Q000201:enzymology* / Q000453:epidemiology; D006801:Humans; D050155:Lipogenesis / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D018570:Risk Assessment; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism*
D015415:Biomarkers; D013230:Stearoyl-CoA Desaturase