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Summary

Pregnancy has been considered a risk factor for developing osteoporosis. Although there has been much research in the field of bone health, the relationship between parity and bone mineral density (BMD) is still controversial. Recently, Yang et al. [1] reported the results of a cross-sectional study that used data from the National Health and Nutrition Examination Survey (NHANES) in order to investigate the relationship between parity and BMD of the femoral neck and lumbar spine in 924 postmenopausal women aged 45 to 65. The authors applied three linear regression models, Model 1 (unadjusted), Model 2 (adjusted for age and body mass index, and Model 3 (adjusted for all covariates). Also, the p value trend of BMD in the different parity groups was mutually verified with the results of multiple regression. Multiple logistic regression models were used to assess the relationship between parity and osteoporosis. After adjustment for potential confounders, women with a parity of ≥ 6 had significantly lower BMD at the lumbar spine than women with a parity of 1-2 (β = – 0.072, 95% CI: – 0.125, – 0.018, p = 0.009). Despite this, there was no correlation found between parity and femoral neck BMD in any of the three regression models. Furthermore, parity of ≥ 6 was associated with a significantly higher prevalence of lumbar spine osteoporosis compared to parity 1-2 (OR = 3.876, 95% CI: 1.637, 9.175, p = 0.002). The authors conclude that after adjusting for BMD-related risk factors, in postmenopausal women, a parity of 6 or more was associated with decreased lumbar spine BMD but not femoral neck BMD. Authors suggest that postmenopausal women with high parity are at increased risk of lumbar osteoporotic fractures and should pay more attention to their bone health.

Commentary

Osteoporosis is one of the most common chronic metabolic skeletal diseases, that increases the risk of bone fragility and fracture due to low bone mass and the destruction of bone microstructure. Women who are postmenopausal women are at high risk for osteoporosis due to the fact that estrogen deficiency accelerates bone turnover with net bone loss [2]. One study of the National Health and Nutrition Examination Survey (NHANES) showed that among older US adults the prevalence of osteoporosis and low bone mass (femoral neck or lumbar spine) was significantly higher in women than in men [3]. BMD, as an index to evaluate the mineral content in bone, has often been used for the diagnosis of osteoporosis. Low BMD is strongly associated to a higher risk of fracture, which in turn increases morbidity and mortality rate for older women [2]. Pregnancy has been reported as a risk factor for developing osteoporosis, theoretically, because bone mass may decrease due to calcium requirements during pregnancy, while contrary to this, bone mass may increase due to higher estrogen levels in the third trimester of pregnancy and the increased bone load caused by weight gain during pregnancy [4]. The present commented study of Yang et al. [1] used data of the NHANES, very widely used in epidemiological research, nutritional status assessments, and disease risk factor investigations. Interestingly the authors found that by using three linear regression models women with a parity of 6 or more displayed lower BMD at the lumbar spine, but not at the femoral neck, than women with a parity of 1-2. With logistic regression models, same higher parity was associated with a higher prevalence of lumbar spine osteoporosis. Controversial data has emerged when investigating the impact of female parity on their future bone health. Indeed, while studies similar to the present one of Yang et al. [1] confirm that higher parity correlates with lower BMD and/or higher rate osteoporosis; others do not display this same correlation. I agree with the authors that these conflicts may be due to the data analysis management: the control of confounding factors, different ethnic groups, lifestyles, recall data, nutritional status and so on.

The demand of calcium is high during pregnancy and breastfeeding in order to help fetal and neonatal bone growth. If the only source of calcium is maternal, women will lose approximately 3% (30 to 1,000 gr) of the mineral with each pregnancy. Hence, with more pregnancies there will be more calcium loss. Of course, as other authors have reported, not only is the loss of calcium due to fetal demand, yet also with more pregnancies women will spend more time breastfeeding, another identified factor related to loss calcium and osteoporosis. Now, whether higher parity is related directly to lower bone mass in the future or indirectly to a higher time breastfeeding is still be determined. Animal studies have shown that as the number of litters increases, the decrease in trabecular bone density becomes irreversible [5]. In any case, the mechanisms underlying the effects of parity on the skeleton are complex, and more basic and clinical studies are needed.

The present study has various strengths: first it uses data of the NHANES for analysis and second it applies three linear regression models of merged data from three cycles 2005-2006, 2007-2008 and 2009-2010, and taking into account many confounders. Despite this, it presents several limitations: i) recall biases, despite the fact that the questionnaire data were obtained from face-to-face interviews; ii) the disease history was based on self-reports and was not cross-checked with medical records; iii) due to lack of reproductive information such as twins, abortions, stillbirths, and breastfeeding duration, the impact of these factors on BMD was not considered; iv) although the authors combined data from three cycles, the number of eligible nulliparous women was too small to be included in the analysis and v) the cross-sectional design does not allow determining causality yet only association. I agree, as the authors that there is a need that future studies be longitudinal with a larger sample size that involves also nulliparous women.

In conclusion, higher parity in postmenopausal women was associated to lower lumbar spine BMD but not femoral neck BMD, and a higher rate of osteoporosis; hence they are at higher risk of osteoporotic fractures and should pay more attention to their bone health. There is a need to promote educational programs that improve the awareness among women during their reproductive phase of the fact that parity may have a negative impact on their future bone health. These programs should promote healthy lifestyle and dietary habits (i.e abstinence of tobacco and alcohol consumption, increase in physical activity, intake of calcium and vitamin D, etc). These are cost-effective ways to decrease the risk of fractures among vulnerable populations. There is a need for further longitudinal studies to deeper explore the association of parity with postmenopausal osteoporosis.

Peter Chedraui, MD, PhD
Instituto de Investigación e Innovación en Salud Integral
Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador

References

  1. Yang Y, Wang S, Cong H. Association between parity and bone mineral density in postmenopausal women. BMC Womens Health. 2022;22(1):87.
    https://pubmed.ncbi.nlm.nih.gov/35321721/
  2. Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2013;24(1):23-57.
    https://pubmed.ncbi.nlm.nih.gov/23079689/
  3. Looker AC, Sarafrazi Isfahani N, Fan B, Shepherd JA. Trends in osteoporosis and low bone mass in older US adults, 2005-2006 through 2013-2014. Osteoporos Int. 2017;28(6):1979-1988.
    https://pubmed.ncbi.nlm.nih.gov/28315954/
  4. Alderman BW, Weiss NS, Daling JR, Ure CL, Ballard JH. Reproductive history and postmenopausal risk of hip and forearm fracture. Am J Epidemiol. 1986;124(2):262-7.
    https://pubmed.ncbi.nlm.nih.gov/3728442/
  5. Gu A, Sellamuthu R, Himes E, Childress PJ, Pelus LM, Orschell CM, Kacena MA. Alterations to maternal cortical and trabecular bone in multiparous middle-aged mice. J Musculoskelet Neuronal Interact. 2017;17(4):312-318.
    https://pubmed.ncbi.nlm.nih.gov/29199192/

 


If you would like to add a comment or contribute to a discussion based on this issue, please contact Menopause Live Editor, Peter Chedraui at peter.chedraui@cu.ucsg.edu.ec

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