Could a fatty acid in the bloodstream be associated with bone density—and could that relationship change depending on which part of the skeleton is measured? This study finds different patterns for different fatty acids and bones.

Osteoporosis is a degenerative skeletal disorder involving disruption of bone microstructure and reduced bone mass, resulting in decreased bone strength and higher fracture risk. Approximately 10 million Americans over the age of 50 years are affected by osteoporosis, according to a report by the US Surgeon General.

Osteoporosis-related fragility fractures can lead to poor quality of life, severe economic burden, and significantly elevated mortality, especially hip fractures. That is why exploring factors associated with osteoporosis is important.

Diet and nutrients, as nongenetic factors, have attracted more attention because of their impact on osteoporosis. Polyunsaturated fatty acids, or PUFAs, consist of two subtypes, n-3 and n-6, and are essential fatty acids acquired mainly through fish and vegetable oils.

Previous studies have shown that PUFAs are associated with cardiovascular events, diabetes, depressive disorders, osteoarthritis, and osteoporosis. Bone mineral density, or BMD, is widely used to evaluate bone mass and diagnose osteoporosis.

However, research evidence for the relationship between dietary PUFAs and BMD remains equivocal. One cohort study found a negative association between dietary PUFA intake and femoral neck BMD in premenopausal women, while a cross-sectional study found a positive correlation with total BMD among adults aged 20 to 59 years.

NHANES is a health project that investigates the health and nutrition status of the US population, and data from the 2011 to 2014 cycle were used to evaluate serum PUFAs and BMD. Subjects younger than 20 years were eliminated, and participants without complete information on serum PUFAs, BMD measures, sample weights, or covariates were excluded.

The final analysis included 1,979 participants. The NHANES study received approval from the NCHS Ethics Review Board, and all participants provided written informed consent. Figure one traces how the NHANES twenty-eleven to twenty-fourteen sample was narrowed for analysis.

From nineteen thousand nine hundred thirty-one participants, the authors excluded individuals younger than twenty, then removed records missing bone mineral density or polyunsaturated fatty-acid data, followed by exclusions for missing sample weights or covariates. The final analytic sample contained one thousand nine hundred seventy-nine subjects, clarifying which participants contributed to the weighted regression analyses.

Serum specimens were processed, stored, and shipped to the Division of Laboratory Sciences at the National Center for Environmental Health, Centers for Disease Control and Prevention, in Atlanta for analysis. Fatty acids were detected using electron capture negative-ion mass spectrometry within 34 minutes.

Finally, 11 PUFAs were selected for further analysis, including alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. Dual-energy X-ray absorptiometry, or DXA, is widely used for evaluating BMD because it is rapid, simple, and involves minimal radiation exposure.

Trained and certified radiology technologists administered DXA examinations using QDR 4500A fan-beam densitometers, and whole-body scans provided BMD data for the head, lumbar spine, thoracic spine, trunk, and total body. Trunk BMD was defined as measurements for trunk bone, including the thoracic and lumbar spine, left and right ribs, and pelvis.

The analysis included confounding factors potentially associated with BMD, including age, sex, race, and educational level. BMI was defined as weight in kilograms divided by the square of height in meters. The analysis also included moderate recreational activities and smoking data, defined as having smoked at least 100 cigarettes in life.

Laboratory data included alkaline phosphatase, serum phosphorus, serum calcium, serum bilirubin, uric acid, total cholesterol, triglyceride, glycohemoglobin, and urine albumin creatinine ratio collected from fasting blood samples. A weighted multiple linear regression model was used to determine the relationship between serum PUFAs and BMD.

Model 1 adjusted no covariates, while Model 2 adjusted age, gender, and race. Model 3 adjusted age, gender, race, educational level, BMI, moderate recreational activities, smoking, laboratory measures, and urine albumin creatinine ratio.

Subgroup analysis was conducted by age, gender, and race, with P less than zero point zero five considered statistically significant. After all covariates were adjusted in Model 3, serum DPA was positively associated with head BMD and lumbar spine BMD. Serum EDA was negatively associated with thoracic spine BMD.

No relationship was observed between serum PUFAs and trunk BMD or total BMD. Table two reports regression coefficients and p-values linking serum PUFAs with bone mineral density across five skeletal regions. Most associations have p-values above zero point zero five, while EDA shows a negative association with thoracic spine BMD, with b equal to negative zero point zero zero zero eight, a ninety-five percent confidence interval from negative zero point zero zero one six to negative zero point zero zero zero zero, and p equal to zero point zero four five three five five.

This table supports the authors’ broader focus on potentially different n-six and n-three PUFA relationships with bone health. Smoothed curve fitting revealed a linear association between serum DPA and head BMD, and between serum EDA and thoracic spine BMD. A nonlinear association was found between serum DPA and lumbar BMD.

Threshold effect analysis indicated that the turning point for serum DPA was 81.4 micromoles per liter. Below 81.4 micromoles per liter, serum DPA was positively associated with lumbar spine BMD; above 81.4 micromoles per liter, the relationship was not significant.

Figure four examines serum DPA against lumbar spine bone mineral density. Panel A shows individual samples, while panel B shows a smoothed association with dotted ninety-five percent confidence bands after adjustment for demographic, lifestyle, metabolic, and laboratory factors.

The curve is not simply linear: the paper reports a turning point at eighty-one point four micromoles per liter, with a positive association below that level, supporting the need to assess possible threshold effects. Subgroup analysis was conducted by age, gender, and race.

For serum DPA and head BMD, a positive association was observed in participants aged 50 to 59 years. Serum DPA was also positively associated with head BMD in females. The study used the NHANES database to evaluate the association between serum PUFAs and BMD.

It demonstrated a nonlinear positive association between serum DPA and lumbar spine BMD, a linear positive relationship between serum DPA and head BMD, and a linear negative correlation between serum EDA and thoracic spine BMD in US adults. The study therefore speculated that serum n-3 PUFAs were beneficial for BMD, while n-6 PUFAs had the opposite effect.

The research data were extracted from the NHANES database, and covariates potentially associated with BMD were adjusted to improve the reliability of the study. However, because this was a cross-sectional study, it could not draw causal inferences regarding serum PUFAs and BMD.

The participants were 20 to 59 years of age, so the conclusions cannot be directly extrapolated to older populations or adolescents. The relationship between serum PUFAs and BMD was weak, and the study lacked experimental validation. In US adults aged 20 to 59 years, the study demonstrated a linear positive relationship between serum DPA and head BMD, a nonlinear positive association between serum DPA and lumbar spine BMD, and a linear negative correlation between serum EDA and thoracic spine BMD.

In US adults aged 20 to 59, serum DPA was positively associated with head and lumbar spine BMD, while EDA was negatively associated with thoracic spine BMD. But the cross-sectional design and weak relationships mean these are associations, not proof of cause.