Mendelian randomization analysis: exploring the causal relationship between menstrual cycle length and bone mineral density

Osteoporosis (OP) arises from an imbalance between bone resorption and formation, leading to diminished bone mass and weakened bone structure [1].It is the most prevalent bone ailment globally, with over 37.5 million individuals affected in the European Union (EU) and the United States of America (USA) alone by 2010 [2].Particularly prevalent among postmenopausal women, nearly one in three women over the age of 50 are afflicted by this condition.Therefore, it is essential to recognize potential factors that could impact the onset of OP, and further research into the pathogenesis, prevention, and treatment principles of OP holds significant medical and social value.Menstrual cyclicity serves as a visible indicator of both health and fertility.The length of the menstrual cycle refers to the duration between the initial day of menstrual bleeding in one cycle and the commencement of menses in the subsequent cycle [3].Typically, the median duration of a menstrual cycle is 28 days, with most cycles between 25 and 30 days [4].Individuals experiencing menstrual cycles lasting fewer than 21 days are categorized as polymenorrheic, while those with cycles lasting longer than 35 days are termed oligomenorrheic.Studies indicate that the menstrual cycle entails consistent, cyclic variations in estrogen and progesterone levels, and these hormones are pivotal in bone metabolism, remodeling, and BMD [5,6].Mendelian randomization (MR) offers a risk-free method for examining causal effects.It functions as an analytical method that uses genetic traits as instrumental variables (IVs) to explore causal relationships between exposure and result [7].Our aim was to explore the association between menstrual cycle length and BMD, and to substantiate this relationship through a two-sample MR analysis.Methods.Study design.This study strictly adhered to the three assumptions of MR analysis: (1) The selected IVs were related to the exposure.(2) IVs were not associated with any confounding factors.(3) IVs can influence outcomes solely through the exposure.All datasets utilized in this study are openly accessible.Leveraging these premises, we proceeded to estimate the causal association between menstrual cycle length and total body BMD (TB-BMD), lumbar spine BMD (LS-BMD), femoral neck BMD (FN-BMD), and TB-BMD 0-15 years, TB-BMD 15-30 years, TB-BMD 30-45 years, TB-BMD 45-60 years, and TB-BMD over 60 years.GWAS Summary Data.