Disclosures: The authors report no relevant financial disclosures.
July 02, 2021
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Birth weight, genetic risk score may predict osteoporosis risk

Disclosures: The authors report no relevant financial disclosures.
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An above average birth weight is associated with lower bone mineral density and higher fracture risk later in life, according to data published in the Journal of Bone and Mineral Research.

“These findings provide the clues that early birth weight control is helpful for the prevention of osteoporosis later in life,” Shu-Feng Lei, PhD, professor in the School of Public Health, Medical College of Soochow University in Suzhou, Jiangsu, China, told Healio. “Further research is needed to investigate the functional mechanism underlying the causal associations between birth weight and risk for osteoporosis, but such research is very difficult to move forward.”

Lei is a professor in the School of Public Health, Medical College of Soochow University in Suzhou, Jiangsu, China.

Lei and colleagues conducted a genetic risk score analysis based on individual-level data from the UK Biobank (n = 340,000), as well as a comprehensive Mendelian randomization analysis based on summary-level data available from large genome-wide association studies (n = 300,000 for birth weight; n = 400,000 for estimated BMD).

“Compared with prior studies, the key strength of our work is the ability to distinguish the fetal and maternal effect of birth weight when evaluating its causal effect on BMD or osteoporosis, providing an in-depth insight into the origin of the relationship,” the researchers wrote.

Researchers assessed whether there was a nonlinear relationship between birth weight and estimated BMD using a restricted cubic spline analysis; results were stratified by sex due to different scales of birth weight and estimated BMD for males and females.

Researchers then assessed the relationship between birth weight and estimated BMD while additionally adjusting for age, smoking status, alcohol consumption, age at menarche, height and weight.

Within the cohort, males on average had higher birth weight and BMD compared with females; average birth weight was 3.45 kg for boys and 3.24 kg for girls (P < .001). Average estimated BMD was 0.57 g/cm² for boys and 0.52 g/cm² for girls (P < .001).

Sex-stratified restricted cubic spline analysis showed birth weight is negatively associated with estimated BMD for males and females, indicating an interaction between sex and birth weight (P < .001).

Restricted cubic spline analysis also showed an “obvious nonlinear relationship” between birth weight and estimated BMD even in age-stratified subgroups (aged 30-40, 40-50 and 50-60 years). Results persisted for both sexes after adjustments for all covariates.

In a mediation analysis with height and weight as mediators, researchers observed significant indirect influences on estimated BMD for weight (P < .001) and height (P < .001), which account for 62.2% or 40.6% of the total effect of birth weight on estimated BMD, respectively.

Restricted cubic spline analysis showed a positive correlation between birth weight and the calculated genetic risk score in the UK Biobank (beta = 0.167; 95% CI, 0.163-0.171), “implying that the genetically determined birth weight can explain some phenotypic variation of its observed counterpart.”

Researchers also found a negative association between estimated BMD and genetic risk score in the total samples (beta = –0.021; 95% CI, –0.025 to –0.018) among females (beta = –0.026; 95% CI, –0.03 to –0.022) and males (beta = –0.016; 95% CI, –0.021 to –0.011).

“The association between fracture and genetic risk score of birth weight is also significant, indicating that genetically determined birth weight can increase the risk of fracture,” the researchers wrote.

Researchers noted that data sets with DXA-derived BMD measurements were not available, and an age- or sex-stratified Mendelian randomization analysis cannot be done due to the lack of a relevant data set.

“This multistage systematic study found consistent causal associations between birth weight and osteoporosis risk, fetal origin of genetic effects underlying the associations, and several mediation factors on the detected associations,” the researchers wrote. “The results enhanced our understanding of the effects of fetal original phenotypes on outcomes in late adulthood and provided helpful clues for early prevention research on osteoporosis.”

For more information:

Shu-Feng Lei, PhD, can be reached at leisf@suda.edu.cn.