Maternal Bone Mineral Density Research Articles

Markers of Maternal Bone and Renal Toxicity Through 50 Weeks Postpartum: IMPAACT 2010 (VESTED) Trial.

Safety data from randomized trials of antiretrovirals in pregnancy are scarce. We evaluated maternal bone and renal data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 trial, which compared the safety and efficacy of 3 antiretroviral therapy regimens started in pregnancy: dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF), dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). A subset of participants underwent dual-energy X-ray absorptiometry scans at postpartum week 50 only. Maternal bone mineral density (BMD) Z-scores were compared between arms. Maternal creatinine was measured at enrolment and periodically through week 50 postpartum, and by-arm differences in average weekly change in estimated creatinine clearance were compared. Six hundred forty-three participants were randomized to DTG + FTC/TAF (N = 217) or DTG + FTC/TDF (N = 215) or EFV/FTC/TDF (N = 211). Median age = 27 years (IQR 23, 32), median CD4 count = 466 cells/mm3 (IQR 308, 624); 564 (88%) women enrolled in Africa and 479 (74%) breastfed. Week 50 postpartum dual-energy X-ray absorptiometry results from 154 women were included in the analysis. Hip and spine BMD was on average higher in women in the DTG + FTC/TAF and lower in the DTG + FTC/TDF and EFV/FTC/TDF arms, but no significant differences in BMD Z-scores were observed between treatment groups. The weekly rate of change in estimated creatinine clearance differed among treatment groups during the antepartum period, but not over the full study follow-up. Markers of bone and renal toxicity did not differ significantly through week 50 postpartum among women randomized to start DTG + FTC/TAF or DTG + FTC/TDF or EFV/FTC/TDF in pregnancy.

Factors Affecting Postpartum Bone Mineral Density in a Clinical Trial of Vitamin D Supplementation.

Background: Few studies evaluate the effects of vitamin D status and supplementation on maternal bone mineral density (BMD) during lactation and further lack inclusion of diverse racial/ethnic groups, body mass index (BMI), or physical activity. Objective: Determine the effects of vitamin D treatment/status, feeding type, BMI, race/ethnicity, and physical activity on postpartum women's BMD to 7 months. Methods: Women with singleton pregnancies beginning 4-6 weeks' postpartum were randomized into two treatment groups (400 or 6400 IU vitamin D/day). Participant hip, spine, femoral neck, and whole-body BMD using Dual-energy X-ray absorptiometry (DXA Hologic), serum 25-hydroxyvitamin D [25(OH)D] (RIA; Diasorin), BMI, and physical activity were measured at 1, 4, and 7 months postpartum. A general linear mixed modeling approach was undertaken to assess the effects of vitamin D status [both serum 25(OH)D concentrations and treatment groups], feeding type, race/ethnicity, BMI, and physical activity on BMD in postpartum women. Results: During the 6-month study period, lactating women had 1-3% BMD loss in all regions compared with 1-3% gain in nonlactating women. Higher maternal BMI was associated with less bone loss in femoral neck and hip regions. Black American women had less BMD loss than White/Caucasian or Hispanic lactating women in spine and hip regions. Exclusively breastfeeding women in the 6400 IU vitamin D group had less femoral neck BMD loss than the 400 IU group at 4 months sustained to 7 months. Physical activity was associated with higher hip BMD. Conclusion: While there was BMD loss during lactation to 7 months, the loss rate was less than previously reported, with notable racial/ethnic variation. Breastfeeding was associated with loss in BMD compared with formula-feeding women who gained BMD. Higher BMI and physical activity independently appeared to protect hip BMD, whereas higher vitamin D supplementation appeared protective against femoral neck BMD loss.

Longitudinal changes of the femoral bone mineral density from first to third trimester of pregnancy: bone health assessment by means of non-ionizing REMS technology

BackgroundThroughout the pregnancy, there is a substantial transfer of calcium from the maternal skeleton to the fetus, which leads to a transient net reduction of the maternal bone mineral density.AimsTo assess longitudinally the changes in the bone mineral density at the femoral neck between the first and third trimester of pregnancy in a cohort of healthy participants using Radiofrequency Echographic Multi Spectrometry (REMS) technology.MethodsProspective, cohort study conducted at the University hospital of Parma, Italy between July 2022 and February 2023. We recruited healthy participants with an uncomplicated singleton pregnancy before 14 completed weeks of gestation. All included participants were submitted to a sonographic examination of the femoral neck to assess the bone mineral density (and the corresponding Z-score values) using REMS at 11–13 and 36–38 weeks of pregnancy. The primary outcome was the change in the bone mineral density values at the maternal femoral neck between the first and third trimester of pregnancy.ResultsOver a period of 7 months, a total of 65 participants underwent bone mineral density measurement at the femoral neck at first and third trimester of the pregnancy using REMS. A significant reduction of the bone mineral density at the femoral neck (0.723 ± 0.069 vs 0.709 ± 0.069 g/cm2; p < 0.001) was noted with a mean bone mineral density change of − 1.9 ± 0.6% between the first and third trimester of pregnancy. At multivariable linear regression analysis, none of the demographic or clinical variables of the study population proved to be independently associated with the maternal bone mineral density changes at the femoral neck.ConclusionsOur study conducted on a cohort of healthy participants with uncomplicated pregnancy demonstrates that there is a significant reduction of bone mineral density at femoral neck from early to late gestation.

Association between Dietary Inflammatory Index and Bone Mineral Density Changes among Pregnant Women: A Prospective Study in China.

This study aims to examine the relationship between dietary inflammatory index (DII) and bone mineral density (BMD) changes among Chinese pregnant women, offering valuable insights for dietary guidance during pregnancy. 289 pregnant women were enrolled in this cohort. Serum inflammatory factors and ultrasonic BMD were measured at the first, second, and the third trimesters. DII scores were calculated based on a semi-quantitative food frequency questionnaire (FFQ) and divided into tertiles. We compared the differences in inflammatory factors in serum across the tertiles of DII and changes in BMD at the second and third trimesters across the tertiles. The participants with higher DII scores had higher total energy intakes than those with lower DII scores. The serum level of interleukin-6 (IL-6) was significantly different across the tertiles of the DII. Women who had lower DII scores had higher T-scores and Z-scores in the BMD assessment. In the test of trends, after adjusting potential covariates, including educational level, physical activity, body mass index, and calcium, vitamin D, or multivitamin supplements, DII values were determined to be positively related to the maternal BMD lost. DII was positively associated with serum IL-6. Meanwhile, higher DII scores were associated with more bone mass loss in pregnant women. We recommend adhering to a lower-DII diet to preserve BMD during pregnancy.

Impact of Tenofovir Disoproxil Fumarate Use During Pregnancy on Maternal Bone Mineral Density.

Impact of Tenofovir Disoproxil Fumarate Use During Pregnancy on Maternal Bone Mineral Density.

Fractures following pregnancy in Osteogenesis imperfecta - A self-controlled case series using Danish Health Registers.

Osteogenesis imperfecta (OI) is a rare inherited connective tissue disorder with considerable clinical and genetic heterogeneity. The clinical hallmark of OI is liability to fractures due to reduced bone strength. Pregnancy and lactation are periods of increased calcium demand resulting in a decrease in maternal bone mineral density (BMD). This self-controlled case series evaluates fracture risk 12- and 19-months prior to conception compared to a period of 12- and 19months following childbirth in women with OI. This study is based on data from the Danish National Patient Register collected between 1995 and 2018. Modified Poisson models were fitted to estimate Incidence Rate Ratio in the post/pre-pregnancy period/s, adjusted by parity and age. The 12-month observation group included 111 women with 205 pregnancies, and the 19-month observation 108 women with 197 pregnancies. We calculated fracture rates (IR) of 48.78 [95%CI 18.55-79.01] per 1000 person years 12months prior to conception, and of 27.87 [95%CI 10.60-45.14] in the 12months post-delivery. Comparing pre- and post-pregnancy period we found an incidence rate ratio (IRR) of 1.00 [95%CI 0.42-2.40]. When adjusting for parity and age at delivery no significant change in the IRR was noted. In the 19months observation-period, the IR per 1000 person years prior to conception was 74.84 [95%CI 44.25-105.43] and the IR postpartum was 36.86 [95%CI 17.55-56.17], leading to an IRR of 0.61 [95%CI 0.31-1.18]. We could not identify any increased risk of fractures when comparing fracture rates during pregnancy and 12 or 19months postpartum to fracture rates 12 or 19months prior to conception.

Pregnancy and Lactation in Sprague-Dawley Rats Result in Permanent Reductions of Tibia Trabecular Bone Mineral Density and Structure but Consumption of Red Rooibos Herbal Tea Supports the Partial Recovery.

During pregnancy and lactation, maternal bone mineral density (BMD) is reduced as calcium is mobilized to support offspring bone development. In humans, BMD returns to pre-pregnancy levels shortly after delivery, shifting from a high rate of bone resorption during pregnancy and lactation, into a rapid phase of bone formation post-lactation. This rapid change in bone turnover may provide an opportunity to stimulate a greater gain in BMD and stronger trabecular and cortical structure than present pre-pregnancy. Providing polyphenols present in red rooibos herbal tea may promote such an effect. In vitro, red rooibos polyphenols stimulate osteoblast activity, reduce osteoclastic resorption, and increase mineral production. The study objective was to determine if consuming red rooibos from pre-pregnancy through to 4 months post-lactation resulted in a higher BMD and improved trabecular and cortical bone structure in a commonly used rat model. Female Sprague-Dawley rats (n = 42) were randomized to one of the following groups: PREG TEA (pregnant, received supplemental level of red rooibos in water: ~2.6 g /kg body weight/day in water), PREG WATER (pregnant, received water), or NONPREG CON (age-matched, non-pregnant control, received water) from 2 weeks pre-pregnancy (age 8 weeks) through to 4 months post-lactation. Rats were fed AIN-93G (pre-pregnancy through to the end of lactation) and AIN-93M (post-lactation onwards). BMD and trabecular structure (bone volume fraction, trabecular number, trabecular separation) were improved (p < 0.05) by 1- or 2-months post-lactation when comparing PREG TEA to PREG CON, though neither group recovered to the level of NONPREG CON. Cortical outcomes (cortical area fraction, cortical thickness, tissue mineral density) for PREG TEA and PREG CON were reduced (p < 0.05) following lactation but returned to the level of NONPREG CON by 2-months post-lactation, with the exception of cortical thickness. The lack of recovery of BMD and key outcomes of trabecular bone structure was unexpected. While consumption of red rooibos did not result in stronger bone post-lactation, red rooibos did support the partial recovery of trabecular BMD and bone structure following pregnancy and lactation. The findings also provide insight into the timing and dose of polyphenols to study in future interventions.

Calcium supplementation during pregnancy and maternal and offspring bone health: a systematic review and meta-analysis.

Insufficient calcium intake during pregnancy may lead to maternal bone resorption and lower bone density of offspring. We evaluated the impact of supplementary calcium with or without vitamin D during pregnancy on maternal and offspring bone mineral density (BMD) and teeth firmness of the offspring. Randomized controlled trials (RCTs) were searched systematically in 11 databases. Two researchers independently screened the titles and abstracts of 3555 records and the full texts of 31 records to examine eligibility. The search yielded seven RCTs (11 reports, n = 1566). No advantage of calcium supplementation was found on maternal BMD after delivery or during breastfeeding, or on offspring BMD, even when dietary calcium intake was low. The results were neither modified by the dose of calcium nor concomitant vitamin D administration. A suspicion of some long‐term harm of the intervention on maternal BMD and growth of female offspring was raised based on the data. One study suggested some benefit of high‐dose calcium supplementation on offspring teeth firmness at 12 years old. A low number of the studies and abundant missing data reduced the quality of the findings. The impact of calcium supplementation on maternal and offspring bone health was deemed unknown because of inconclusive research results.

Effect of Low Dietary Vitamin D Fed Prior to and During Pregnancy and Lactation on Maternal Bone Mineral Density, Structure, and Strength in C57BL/6 Mice.

ABSTRACTSeveral studies have shown that diets containing lower vitamin D than in the AIN-93G diet do not compromise bone structure, bone mineral density (BMD), and/or bone strength in male and female mice. This study determined if a diet containing low vitamin D from prepregnancy through to the end of lactation maintained these bone outcomes to a similar extent as a high vitamin D diet. Mice were fed an AIN-93G diet with 25 (LD diet) or 5000 (HD diet) IU vitamin D/kg diet from premating through to lactation (n = 15/group). Of the major structure outcomes, only cortical area fraction of the distal femur was lower (P <0.05) with the LD diet. Lumbar vertebra BMD was lower (P <0.05) with LD whereas distal femur BMD and bone strength at 3 sites did not differ. Dams fed an LD diet premating through to the end of lactation had largely similar bone outcomes to dams fed a HD diet.

P79: Calcium, phosphorus, and niacin intakes during late pregnancy are positively associated with maternal bone mineral density: A pilot study

P79: Calcium, phosphorus, and niacin intakes during late pregnancy are positively associated with maternal bone mineral density: A pilot study

Bone resorption and dietary calcium in pregnancy-a window to future maternal bone health.

Pregnancy is characterized by increased bone turnover and reversible loss of bone mineral density (BMD) to meet fetal calcium demands. The long-term effect of bone turnover and maternal diet in pregnancy on maternal bone is not well established. We aimed to determine if an association exists between [1] bone resorption, [2] dietary calcium, and [3] serum 25-hydroxyvitamin D in pregnancy with maternal BMD 5-year postpartum. This is a prospective, longitudinal study of 107 women recruited to the ROLO low glycemic index dietary intervention trial in pregnancy and followed-up at 13, 28, and 34weeks' gestation and 5years' postpartum. At 13 and 28weeks' gestation, a biomarker of bone resorption, urine cross-linked N-telopeptide of type I collagen (uNTX), was measured. At the 5-year follow-up BMD was measured using dual-energy X-ray absorptiometry. Anthropometry, dietary intakes, and serum 25-hydroxyvitamin D were measured in pregnancy and at 5years. Multiple linear regression, controlling for confounders, was used for analysis. Mean BMD at 5years was 1.208g/cm2. In pregnancy, 24-34% reported dietary calcium intakes <800mg/day. Vitamin D deficiency (< 30nmol/L) was observed in 38-41% of women in pregnancy and in 29% of women at the 5-year follow-up. At 13 and 28weeks' gestation, uNTX levels greater than the median were associated with 0.060 and 0.050g/cm2 lower BMD 5years later, respectively. Dietary calcium <800mg/day in trimester 3 was associated with 0.072g/cm2 lower BMD 5years later. Vitamin D deficiency at 5years, but not in pregnancy, was associated with lower BMD. Higher bone resorption and low dietary calcium in pregnancy were associated with lower BMD 5years later. These findings could enable the identification of women at risk of declining of BMD in later life, but further research is needed. Adequate dietary calcium should be advised in the antenatal setting to promote lifelong maternal bone health.

Impact of postpartum tenofovir-based antiretroviral therapy on bone mineral density in breastfeeding women with HIV enrolled in a randomized clinical trial.

We set out to evaluate the effect of postnatal exposure to tenofovir-containing antiretroviral therapy on bone mineral density among breastfeeding women living with HIV. IMPAACT P1084s is a sub-study of the PROMISE randomized trial conducted in four African countries (ClinicalTrials.gov number NCT01066858). IMPAACT P1084s enrolled eligible mother-infant pairs previously randomised in the PROMISE trial at one week after delivery to receive either maternal antiretroviral therapy (Tenofovir disoproxil fumarate / Emtricitabine + Lopinavir/ritonavir-maternal TDF-ART) or administer infant nevirapine, with no maternal antiretroviral therapy, to prevent breastmilk HIV transmission. Maternal lumbar spine and hip bone mineral density were measured using dual-energy x-ray absorptiometry (DXA) at postpartum weeks 1 and 74. We studied the effect of the postpartum randomization on percent change in maternal bone mineral density in an intention-to-treat analysis with a t-test; mean and 95% confidence interval (95%CI) are presented. Among 398/400 women included in this analysis, baseline age, body-mass index, CD4 count, mean bone mineral density and alcohol use were comparable between study arms. On average, maternal lumbar spine bone mineral density declined significantly through week 74 in the maternal TDF-ART compared to the infant nevirapine arm; mean difference (95%CI) -2.86 (-4.03, -1.70) percentage points (p-value <0.001). Similarly, maternal hip bone mineral density declined significantly more through week 74 in the maternal TDF-ART compared to the infant nevirapine arm; mean difference -2.29% (-3.20, -1.39) (p-value <0.001). Adjusting for covariates did not change the treatment effect. Bone mineral density decline through week 74 postpartum was greater among breastfeeding HIV-infected women randomized to receive maternal TDF-ART during breastfeeding compared to those mothers whose infants received nevirapine prophylaxis.

Modulatory role of genistein on placenta and maternal bone minerals composition: further insight into its influence on pregnancy and foetal development

Pregnancy is a crucial period with an increased need to supply necessary minerals for both the mother and the developing foetus and with a tendency of altering the maternal bone mineral density when there is no balance between demand and supply of these minerals. This study evaluated the influence of genistein on the maternal bone and placenta mineral composition. Pregnant rats were grouped into control, 2mg/kg and 4mg/kg genistein groups, dosed accordingly till sacrificed at different gestation days (GD). Body and placenta weights, right femur bone and placenta mineral composition were analysed. A significant decrease in body weight and percentage relative right femur bone weight at GD-20 was recorded in the 2-mg group with the reverse occurring in the 4-mg genistein group. The right femur bone Ca2+ and Zn2+ was reduced towards GD-20 in both 2-mg and 4-mg genistein groups. Genistein had no influence on placenta selenium and cadmium level, but significantly decreased zinc and lead level concentration as the gestation progressed towards GD-20. Copper level was increased at GD-16 at the doses used. Genistein modulated maternal bone mineral composition and placenta capability in retaining some heavy metals at various stages of pregnancy.

Calcium, Phosphorus, and Niacin Intakes During Late Pregnancy Are Positively Associated with Maternal Bone Mineral Density: A Pilot Study

Abstract Objectives The adequate calcium intake during pregnancy on postpartum bone mineral density (BMD) and neonatal outcomes are unknown as results of recent intervention trials are inconsistent. We investigated the relationship between maternal nutrient intake and maternal BMD at delivery, newborn birth outcomes, and maternal bone loss during lactation in Korean mothers. Methods Thirty Korean pregnant women (mean age: 34 years) were enrolled before delivery. Maternal food and supplement intake and BMD were assessed twice: at delivery (T1) and at weaning or 6 months postpartum (T2). Third trimester and postpartum food intake was assessed by food frequency questionnaire at T1 and T2, respectively, and analyzed for intake of calcium and 22 major nutrients. Calcium intake was assessed as a continuous variable or categorized as &amp;lt; or ≥500 mg/d. Maternal lumbar spine (LS), femoral neck (FN), trochanter, and intertrochanter BMD were measured by dual energy X-ray absorptiometry. Birth length, birth weight, and head circumference of neonates were collected. Participants were categorized according to duration of lactation. General linear models were adjusted for covariates. Results Mean ± STD calcium intake was 905 ± 430 mg/d at T1 and 608 ± 227 at T2 (change: P = 0.05). Women with calcium intakes &amp;lt;500 mg/d had lower LS BMD at T1 (P = 0.026). No difference was detected at other study sites. Phosphorus and niacin intakes during the third trimester were positively correlated with T1 LS BMD (ß: 0.162 and 0.088, respectively; both P &amp;lt; 0.05). Birth weight and head circumference were negatively associated with T1 iron intake(ß: −9.065 and −0.0292, respectively; both P &amp;lt; 0.05). Intake of other nutrients during late pregnancy were not associated with maternal T1 BMD or neonatal outcomes. Among the 10 participants that completed the second visit, 6 women breastfed. Postpartum bone change was not associated with breastfeeding. Energy intake at T2 was negatively associated with change in FN BMD (ß: −0.007, P &amp;lt; 0.001). Postpartum intake of other nutrients was not associated with change of BMD at any site. Conclusions Intakes of calcium, phosphorus, and niacin during the third trimester are positively associated with maternal LS BMD, but not neonatal birth outcomes, in Koreans. Breastfeeding and postpartum calcium intake may not affect bone after birth. Funding Sources National Research Foundation of Korea.

SAT-009 SSRI Use in the Peripartum Period Regulates Mammary Gland Parathyroid Hormone Related Protein (PTHrP) by a Serotonylation-Dependent Mechanism

During lactation, a woman experiences a considerable amount of bone loss and recent studies suggest bone deficits persist years postpartum. Furthermore, selective serotonin uptake inhibitors (SSRIs), which are often prescribed to women experiencing peripartum depression, have been linked to osteopenia. Serotonin signaling can increase parathyroid hormone related protein (PTHrP), a bone remodeling protein which liberates calcium for the milk. Additionally, fluoxetine (a common SSRI) results in increased mammary gland serotonin content and PTHrP, and treatment during the peripartal period reduced maternal bone mineral density. One proposed mechanism of serotonin action is by its covalent addition to proteins by transglutaminase (TG2), termed serotonylation. We therefore investigated whether the combination of fluoxetine and lactation can exacerbate maternal bone loss and the underlying mechanism. We hypothesized that SSRI-induced serotonin signaling in the lactating mammary gland increases PTHrP through a serotonylation-dependent mechanism. Treatment of mouse mammary epithelial cells (HC11) with fluoxetine significantly upregulates PTHrP gene expression and the concentration of its downstream effector, cAMP, over control (P < 0.0004). Furthermore, treatment of the HC11 cells with fluoxetine in addition to a TG2 inhibitor, monodansylcadaverine, restores PTHrP mRNA expression to levels observed in the control. Small g-proteins have emerged as a common target protein for serotonylation. Currently, our data suggest that the g-proteins, RhoA and Rab4, are potential serotonylation targets in the mammary gland. Together these data suggest that the molecular process of serotonyation in HC11 cells links serotonin signaling to increased PTHrP expression. Future work is directed at using the cre-lox system to genetically ablate serotonylation using a WAPCre/TG2Flox transgenic mouse to determine whether decreasing serotonylation in vivo in the mammary gland during lactation improves maternal bone mass.

MON-001 Peripartum Sertraline (Zoloft®) Increases Pup Mortality Immediately Postpartum

Peripartum and postpartum depression can be detrimental to both the mother and the developing child. Use of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), is common during the peripartal period and SSRIs have been the leading prescribed antidepressant to treat maternal depression. One of the most commonly prescribed SSRIs is sertraline (Zoloft®) because of the limited fetal teratogenic effects observed, unlike maternal paroxetine (Paxil®) usage which can manifest in fetal cardiovascular defects. Fluoxetine (Prozac®), like sertraline, has previously been shown to have limited teratogenic effects, however, we have shown treatment with fluoxetine for the entire period of pregnancy and lactation in mice compromises pup bones at weaning resulting in decreased long bone length and head circumference. Furthermore, maternal fluoxetine usage results in a sustained reduction in maternal bone mineral density post weaning, which may lead to long-term osteopenia, putting the mother at risk for bone-related disorders later in life. We hypothesized sertraline, like fluoxetine, will compromise maternal bone postpartum and fetal bone development at weaning. Treatment with sertraline in C57BL/6 dams throughout pregnancy and lactation reduced litter size (5.4 pups/dam) and increased pup mortality during the first 24 hours postpartum (20% dead pups/litter) compared to controls (6.8 pups/dam, 5% dead pups/litter, respectively; P < 0.018). Maternal calcium transporters (Orai1 and Serca2) were downregulated in the mammary gland in sertraline-treated dams on day 21 of lactation (P < 0.0032). Together, our data suggests in utero pharmacological exposure to sertraline may induce a failure to thrive in the pups and alters calcium metabolism in the dam. SSRI exposure during pregnancy and lactation may adversely affect the developing neonate(s) as well as have lasting impacts on the mother.

SAT-020 Fluoxetine Administration Influences Serotonin-Driven Bone Remodeling During Lactation and Pregnancy Outcome in Mice

Selective serotonin reuptake inhibitors (SSRI) are the most commonly prescribed class of antidepressants during pregnancy and lactation. SSRI decrease bone mineral density (BMD) across all ages and sexes. Lactation is also characterized by increased bone resorption to mobilize calcium due to the demands of lactation and achieves this via a serotonin-induced hormonal cascade. This serotonin-mediated bone loss is normally restored after weaning but is persistent when an SSRI is administered during the peripartum period. We hypothesize that the long-term BMD loss associated with fluoxetine administration during lactation will be seen in two sequential lactations and will have a more dramatic effect on maternal bone loss after the second lactation at both weaning and 3 months post-weaning. Female C57BL/6 mice were randomized to receive the SSRI fluoxetine hydrochloride (20 mg/kg) or saline daily from the beginning of pregnancy (E0), determined by the presence of a vaginal mucous plug, through the end of lactation (D21). They were then given a 3-week rest period before undergoing a second lactation with the same study design. Each group is paired to an age-matched virgin cohort to provide a non-lactating control. This created the following treatments: saline dam (S), fluoxetine dam (F), saline virgin pair (SV), and fluoxetine virgin pair (FV). Dual-energy X-ray absorptiometry (DEXA) was used to measure BMD of all groups throughout the peripartum period. At the end of gestation (E17.5), BMD was decreased in both the F and FV groups, and the BMD of the FV group remained persistently lower than the SV group across all timepoints. Both the F and S groups exhibited a dramatic decrease in BMD between E17.5 and the beginning of lactation (D2), then a slight increase between mid-lactation (D10) and at weaning (D21). There was an overall interaction between treatment and time for all groups across the peripartum period (p<0.0001). During the first peripartum period, the F dams that were mated had significantly increased pregnancy loss (p=0.0041) and pup mortality post-parturition compared to S mice. Of the dams that were inseminated, determined by the presence of a mucus plug, 63% of successfully mated S dams (n=19) resulted in a full-term pregnancy. Of those S dams (n=12), 25% lost their entire litter at the beginning of lactation, and 75% maintained their litter until weaning. In the F dams that were successfully mated (n=37), only 35% resulted in a full-term pregnancy. We conclude that fluoxetine administration during the peripartum period decreases long-term maternal BMD and that fluoxetine exhibits a drug-specific effect on the dam resulting in a notably decreased incidence of a successful pregnancy.

Association between maternal smoking and child bone mineral density: a systematic review and meta-analysis.

Maternal smoking during pregnancy has detrimental effects on fetal development. The current review examined the differences in offspring's bone mineral density (BMD) between mothers smoked during pregnancy and those who did not. A systematic review and meta-analysis on the studies investigating the influence of maternal smoking during pregnancy on children or neonates' bone measures published up to October 30, 2018, was performed. BMD results measured at different body sites were pooled and then fixed or random effect models were used based on the presence of heterogeneity. The desired pooled effect size was the offspring's BMD mean difference with 95% confidence interval between smoker and non-smoker mothers. Sensitivity analysis was performed for birth weight and current weight, two important mediator/confounders causing heterogeneity. Overall, eight studies consisting of 17,931 participants aged from infancy to 18years were included. According to the fixed effect model, the mean of BMD in offspring whose mothers smoked during pregnancy was 0.01g/cm2 lower than those with non-smoker mothers (95% CI = - 0.02 to - 0.002). However, subgroup meta-analysis adjusted for birth weight and current weight demonstrated no significant mean difference between BMD of children with smoker and non-smoker mothers (d = 0.06, 95% CI = -0.04 to 0.16, p value = 0.25 and d = - 0.005, 95% CI = - 0.01 to 0.004, p value = 0.28, respectively). According to available studies, it is suggested that maternal smoking during pregnancy does not have direct effect on the offspring's BMD. Instead, this association might be confounded by other factors such as placental weight, birth weight, and current body size of children.

Maternal mortality, marital status and bone mineral density in young women from the Coimbra identified skeletal collection.

In contemporary populations, pregnancy and lactation are usually followed by transient bone loss. The observation of reduced bone mass in young females from archaeological sites has sometimes been interpreted as an outcome of reproductive stress. In order to evaluate the overall effect of reproductive dynamics on bone mass in a historical skeletal sample, bone mineral density (BMD) at the proximal femur was assessed by dual-energy X-ray absorptiometry in 78 young women (17-39 years) from the Coimbra Identified Skeletal Collection. BMD was compared within the skeletal sample ("maternal deaths" [ICD - 10: chapter XV] vs. "other causes of death", and "married/widowed women" vs. "single women"). Results revealed that mean BMD differences among groups are non-significant, suggesting that a strict reproductive interpretation of premature bone loss in young women from archaeological contexts is not sustained by empirical evidence. Bone mass in young women from archaeological sites should be interpreted as a complex trait stemming from the interplay between reproductive factors, genetics, nutrition, physical activity, and age at menarche.

Changes in maternal volumetric bone mineral density in the peripheral skeleton during pregnancy as determined by single-slice peripheral Quantitative Computed Tomography

Changes in maternal volumetric bone mineral density in the peripheral skeleton during pregnancy as determined by single-slice peripheral Quantitative Computed Tomography