Nulliparity and Fracture Risk in Older Women: The Study of Osteoporotic Fractures

Hillier, Teresa A.; Rizzo, Joanne; Pedula, Kathryn L.; Stone, Katie L.; Cauley, Jane A.; Bauer, Doug C.; Cummings, Steven R.

doi:10.1359/jbmr.2003.18.5.893

Cited by 69 publications

(85 citation statements)

References 39 publications

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“…Such relationship has been reported before in most (but not all) prior studies that examined the association between parity and fracture risk. (22)(23)(24) The most frequently discussed hypothesis underlying such association between parity and fracture risk would be that each additional pregnancy contribute to increase the accumulated lifetime exposure to estrogen and thus reduce the subsequent risk of fracture.…”

Section: Discussionmentioning

confidence: 99%

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

Trémollières

Pouillès

Drewniak

et al. 2010

Journal of Bone and Mineral Research

179

114

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The aim of this prospective study was (1) to identify significant and independent clinical risk factors (CRFs) for major osteoporotic (OP) fracture among peri-and early postmenopausal women, (2) to assess, in this population, the discriminatory capacity of FRAX and bone mineral density (BMD) for the identification of women at high risk of fracture, and (3) to assess whether adding risk factors to either FRAX or BMD would improve discriminatory capacity. The study population included 2651 peri-and early postmenopausal women [mean age (AE SD): 54 AE 4 years] with a mean follow-up period of 13.4 years (AE1.4 years). At baseline, a large set of CRFs was recorded, and vertebral BMD was measured (Lunar, DPX) in all women. Femoral neck BMD also was measured in 1399 women in addition to spine BMD. Women with current or past OP treatment for more than 3 months at baseline (n ¼ 454) were excluded from the analyses. Over the follow-up period, 415 women sustained a first low-energy fracture, including 145 major OP fractures (108 wrist, 44 spine, 20 proximal humerus, and 13 hip). In Cox multivariate regression models, only 3 CRFs were significant predictors of a major OP fracture independent of BMD and age: a personal history of fracture, three or more pregnancies, and current postmenopausal hormone therapy. In the subsample of women who had a hip BMD measurement and who were not receiving OP therapy (including hormone-replacement therapy) at baseline, mean FRAX value was 3.8% (AE2.4%). The overall discriminative value for fracture, as measured by the area under the Receiver Operating Characteristic (ROC) curve (AUC), was equal to 0.63 [95% confidence interval (CI) 0.56-0.69] and 0.66 (95% CI 0.60-0.73), respectively, for FRAX and hip BMD. Sensitivity of both tools was low (ie, around 50% for 30% of the women classified as the highest risk). Adding parity to the predictive model including FRAX or using a simple risk score based on the best predictive model in our population did not significantly improve the discriminatory capacity over BMD alone. Only a limited number of clinical risk factors were found associated with the risk of major OP fracture in peri-and early postmenopausal women. In this population, the FRAX tool, like other risk scores combining CRFs to either BMD or FRAX, had a poor sensitivity for fracture prediction and did not significantly improve the discriminatory value of hip BMD alone. ß

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Section: Discussionmentioning

confidence: 99%

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

Trémollières

Pouillès

Drewniak

et al. 2010

Journal of Bone and Mineral Research

179

114

View full text Add to dashboard Cite

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“…This has been examined through numerous epidemiological studies that have ascertained whether parity confers any risk of lower BMD, an osteoporotic level of BMD, or fragility fractures. The majority of such studies have found either a neutral effect of parity (16, (384,397,421,460,625,689,869,997). One of the studies reporting a protective effect of parity was particularly strong because it involved 1,852 twins and their female relatives, including 83 identical twins who were discordant for ever being pregnant (700).…”

Section: Human Datamentioning

confidence: 99%

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

Kovacs

2016

Physiological Reviews

383

524

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During pregnancy and lactation, female physiology adapts to meet the added nutritional demands of fetuses and neonates. An average full-term fetus contains ϳ30 g calcium, 20 g phosphorus, and 0.8 g magnesium. About 80% of mineral is accreted during the third trimester; calcium transfers at 300-350 mg/day during the final 6 wk. The neonate requires 200 mg calcium daily from milk during the first 6 mo, and 120 mg calcium from milk during the second 6 mo (additional calcium comes from solid foods). Calcium transfers can be more than double and triple these values, respectively, in women who nurse twins and triplets. About 25% of dietary calcium is normally absorbed in healthy adults. Average maternal calcium intakes in American and Canadian women are insufficient to meet the fetal and neonatal calcium requirements if normal efficiency of intestinal calcium absorption is relied upon. However, several adaptations are invoked to meet the fetal and neonatal demands for mineral without requiring increased intakes by the mother. During pregnancy the efficiency of intestinal calcium absorption doubles, whereas during lactation the maternal skeleton is resorbed to provide calcium for milk. This review addresses our current knowledge regarding maternal adaptations in mineral and skeletal homeostasis that occur during pregnancy, lactation, and post-weaning recovery. Also considered are the impacts that these adaptations have on biochemical and hormonal parameters of mineral homeostasis, the consequences for long-term skeletal health, and the presentation and management of disorders of mineral and bone metabolism.

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“…

We now have several additional years of follow-up of the Study of Osteoporotic Fractures cohort (SOF), which now makes the age of our cohort more closely comparable with what Robbins et al presented with EPIDOS.

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confidence: 61%

“…We thank Drs Robbins, Schott, and Meunier for validating our results that nulliparity increases the risk of hip fracture in older women (1) among their large EPIDOS cohort. The importance of replication among different study settings is a critical piece for scientific proof of causality of any study's initial findings which we endorse.…”

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confidence: 61%

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Nulliparity and Osteoporotic Fracture Risk

Hillier¹,

Rizzo²,

Pedula³

et al. 2004

Journal of Bone and Mineral Research

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We thank Drs Robbins, Schott, and Meunier for validating our results that nulliparity increases the risk of hip fracture in older women (1) among their large EPIDOS cohort. The importance of replication among different study settings is a critical piece for scientific proof of causality of any study's initial findings which we endorse.We now have several additional years of follow-up of the Study of Osteoporotic Fractures cohort (SOF), which now makes the age of our cohort more closely comparable with what Robbins et al. presented with EPIDOS. We have done additional analyses to allow better comparison between the two cohorts. Among our 9704 SOF women, with now an average of 12.8 years of follow-up available for analysis, there were 926 fractures. The average age of the SOF cohort was 71.7 years at the baseline exam, and thus the average age of survivors after 13 years of follow-up is essentially identical to Drs Robbins, Schott, and Meunier's findings from EPIDOS. Furthermore, both cohorts are of primarily Northern European ancestry-the highest risk group for osteoporosis-although environmental and/or lifestyle differences may be likely between their cohort and ours.We first did age-and weight-adjusted Cox proportional hazards models to mirror the EPIDOS analysis, and nulliparous women in SOF had an increased risk of hip fracture (HR 1.20; 95% CI, 1.03-1.41). As the issue raised by Robbins et al. is the contribution of bone mineral density (BMD) to this risk of hip fracture among nulliparous women, we next limited our analyses to the 7928 SOF women who also had BMD measured at our second visit in 1989 -1990. Among this group, there were 754 hip fractures-the strong relationship of nulliparity to increase hip fracture remained significant after adjustment for BMD (HR 1.26; 95% CI, 1.06 -1.49). Further multivariate adjustment for covariates used in our original paper (1) with BMD was similar (HR 1.31; 95% CI, 1.10 -1.55).We would like to note that when we initially tested for a relationship between parity and hip fracture with BMD in SOF, this relationship was borderline significant after multivariate adjustment (mean duration of follow-up at that time was 4.1 years).(2) However, with longer follow-up and additional hip fracture cases, the effect of nulliparity on increasing hip fracture risk became evident. We would argue that the effect size did not change appreciably in the EPIDOS study with the addition of BMD (HR decreased from 1.38 to 1.31), and that it is very possible with additional follow-up that the EPIDOS study will also find this increased risk is significant after adjustment for BMD.We completely agree with Drs Robbins, Schott, and Meunier that the clinically important time for hip fractures is in older women of ages similar to the women in the SOF and EPIDOS cohorts. However, we respectfully disagree that clinicians should consider only BMD when assessing a women's risk of hip fracture-our results would suggest increasing parity operates through a different mechanism than is detected by BMD to incr...

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Nulliparity and Fracture Risk in Older Women: The Study of Osteoporotic Fractures

Cited by 69 publications

References 39 publications

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

Nulliparity and Osteoporotic Fracture Risk

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