bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluoxetine Administration During Lactation Impacts the Bone Health of the Dam and the Offspring in Mice
Authors: Fricke Hannah P , Krajco Chandler J , Sheftel Celeste M , Charles Julia F , Hernandez Laura L
Published: May 2021

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressants during pregnancy and lactation. SSRIs decrease bone mineral density (BMD) across all ages and sexes. Lactation is also characterized by increased bone resorption to mobilize calcium 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. Our lab has previously shown that administration of the SSRI fluoxetine (FLX) during both gestation and lactation results in compromised bone health of the dam, which is characterized by a decreased bone mineral density (BMD). Along with this, we have also shown a decrease in BMD and femoral length in the offspring of the FLX-treated dams at weaning. We hypothesize that FLX usage during lactation only will impact the bone health of the dam as well as the bone health of her offspring due to exposure to FLX via the dam’s milk. Female C57BL/6 mice were randomized to receive the SSRI fluoxetine hydrochloride (20 mg/kg) or saline daily from the beginning of lactation (D0) through the end of lactation (D21), resulting in the following treatments: FLX dams (n=13) and control dams (n=13). The offspring of the treated dams were then harvested at weaning (3 weeks of age). During the peripartal period, the BMD of the dam was monitored via dual x-ray absorptiometry (DEXA). A baseline scan was taken at 6 weeks of age, at the end of pregnancy (E17.5), the beginning of lactation (D2), peak lactation (D10), and at the end of lactation (D21). There was no significant difference in the BMD of the FLX dams compared to the control dams at 6 weeks of age (p=0.9992), E17.5 (p=0.9995), D2 (p>0.9999), or D10 (p>0.9999). However, at D21, the FLX dams had a decreased BMD compared to the control dams (p=0.0493). Along with the decreased BMD of the FLX dams at weaning, there was a significant decrease in femur length in the pups of the FLX dams (p=0.0040). When the pups were separated by sex, the decreased femur length was observed in both the male (p=0.0413) and female (p=0.0047) offspring. These data suggest that fluoxetine use during lactation only results in a decreased BMD of the treated dams, as well as decreased femur length in the exposed offspring in both sexes.
PTH Protects Osteocytes From Oxidative Stress and Cellular Senescence
Authors: Uda Yuhei , Santos Roberto , Kochen Alejandro , Newell Carly , Huang Tim Y , Pajevic Paola Divieti
Published: May 2021

Age-induced osteoporosis is characterized by a progressive decline in bone formation and increase in bone resorption with uncoupled activities of osteoblasts and osteoclasts. Parathyroid hormone (PTH) is used in the clinic to treat osteoporosis due to its anabolic actions on bone via binding to the PTH receptor (PPR). The receptor is highly expressed in cells of the osteoblastic lineage, including osteocytes. Osteocytes are the most abundant cells in bone and serve as a key regulator of bone remodeling. Despite the significant role of PPR signaling in skeletal homeostasis, its function in osteocytes during aging remains unclear. We have gathered preliminary data demonstrating that mice lacking PPR predominantly in osteocytes (Dmp1-PPRKO) have marked age-induced bone loss due to increased bone resorption and suppressed bone formation. These mice, with aging, develop characteristics of skeletal senescence: a decrease in osteoprogenitors and an increase in bone marrow adiposity and p16Ink4a/Cdkn2a expression in bone. Since senescence of cells in the bone microenvironment has been reported as a cause of age-induced bone loss, we hypothesized that PPR signaling protects osteocytes from senescence. To test this hypothesis, we generated osteocytes (Ocy454-12H), in which the PPR expression was ablated using CRISPR/Cas9 technique. Ocy454-12H-PPRKO and Ocy454-12H-PPRCtrl cells were treated with PTH followed by an exposure to hydrogen peroxide (H2O2). High levels of intracellular reactive oxygen species (ROS), including H2O2, promote protein and DNA oxidation, resulting in cell death and senescence. PTH treatment significantly suppressed the increase in H2O2-induced cell death, measured by resazurin-based assays, in PPRCtrl but not in PPRKO cells. We analyzed intracellular ROS levels using a fluorescent probe and found that PTH treatment significantly suppressed the increase in ROS upon H2O2 exposure, suggesting an antioxidant function of PTH in osteocytes. To further investigate if PTH prevents osteocytes from oxidative stress-induced senescence, we examined senescence-associated β-galactosidase (SA β-gal) activity in cells that were treated with PTH followed by an exposure to low doses of H2O2. Compared to untreated and PPRKO groups, treatment with PTH significantly decreased the number of SA β-gal positive cells, demonstrating that PPR signaling protects osteocytes, and possibly other osteoblastic cells, from H2O2-induced cellular senescence. PTH treatment reduced mRNA expression of p21/Cdkn1a. Taken together these results demonstrate that PPR signaling is important to protect osteocytes from cellular senescence.
Sarcopenic Obesity Indices Are Major Determinants of Bone Strength in Older Adults With Obesity
Authors: Gregori Giulia , Paudyal Arjun , Barnouin Yann , Celli Alessandra , Villareal Reina Condevillamar , Qualls Clifford , Villareal Dennis Tan
Published: May 2021

Background: The increasing number of older adults with obesity is a growing public health problem because of increased risk of fractures especially at the ankle and upper leg despite normal or high bone mineral density. Among the contributory factors for fracture risk in this population may be aging- and obesity- associated physical frailty and impaired bone quality. However, how the adverse changes in physical function and body composition in this aging and obese population contribute to bone quality as assessed by finite element analyses (FEA) of bone strength has not been determined. Methods: One-hundred sixty-nine older (age ≥ 65 yrs.) adults with obesity (BMI ≥ 30 kg/m2) were recruited to participate in lifestyle intervention trials at our Medical Center. All underwent baseline measurements of bone strength (failure load [N] and stiffness [N.mm-1]) as estimated using FEA from high-resolution peripheral quantitative tomography (HR-pQCT) of the distal radius and tibia. In addition, body composition (appendicular lean mass/BMI [ALMBMI], fat mass/height2 [FMI]) was assessed by dual-energy x-ray absorptiometry (DXA) and physical function by the modified physical performance test (PPT), knee extension strength (isokinetic dynamometry), hand grip strength, and 4-meter gait speed. Results: Bivariate analyses showed that ALMBMI (r=.57 to .58), FMI (r=-.16 to -.17), gait speed (r=.20 to .21), grip strength (.56 to .57), and knee extension strength (r=.40 to .42) correlated with stiffness and failure load at the distal radius (all P<0.05). In addition, ALMBMI (r=.65 to .67), FMI (r=-.22 to .23), gait speed (r+.18 to .19), grip strength (r=.58 to .59), and knee extension strength (r=.44 to .45) correlated with stiffness and failure load at the distal tibia (all P<0.05). Controlling for age and sex, multiple regression analyses revealed that ALMBMI (β=.34 to .35) and grip strength (β=.28 to .29) were the independent predictors of stiffness and failure load at the distal radius, explaining 45% to 46% of the variance in stiffness and failure load (P<0.001). On the other hand, multiple regression analyses revealed that ALMBMI (β=.45 to .52), grip strength (β=.27 to .28), and FMI (β=.17 to .18) were the independent predictors of stiffness and failure load at the distal tibia, explaining 74% to 75% of the variance in stiffness and failure load (P<0.001). Conclusions: These findings suggest the importance of preserving muscle mass while reducing fat mass and improving physical function to maintain bone quality and decrease the risk of fractures when older adults with obesity undergo lifestyle intervention.
Aromatase Inhibitor Induced Bone Loss: Do International Guidelines Accurately Stratify Fracture Risk and Selection of Anti-Osteoporosis Treatment?
Authors: Gandhi Shriya , Bullock Cydney A , Ritz Ethan M , Beck Todd , Baim Sanford
Published: May 2021

Introduction: Aromatase inhibitors (AI) are used for adjunctive treatment of estrogen receptor-positive (ER+) breast cancer. Aromatase converts androgens to estrogens in the ovaries and peripheral tissues such as adipose, liver, muscle, and breast. In breast, estrogens increase cell proliferation in both normal and ER+ malignant tissue. AIs globally suppress estrogen production, and thereby can decrease tumor progression. However, in bone, estrogens suppress osteoclast activity and decrease bone resorption so AI use results in increased bone resorption and decreased bone mineral density (BMD). Several guidelines exist to direct management of AI-associated bone loss, but it is unclear whether adherence to these guidelines translates to decreased fracture risk. The International Osteoporosis Foundation (IOF) et al 2017 guidelines for the prevention of osteoporotic fractures in patients treated with AI recommended BMD measurement at the onset of AI use and use of anti-osteoporosis therapy (anti-OP) in those who met T-score and clinical risk factor (CRF) criteria. Hypothesis: We explored application of these guidelines and whether they were able to stratify patients according to risk, initiation of treatment, and fracture outcomes. Methods: 1517 charts were extracted from the electronic medical record (EMR) of a tertiary academic medical center based on history of breast cancer and use of AIs between 2008 and 2017. Charts were retrospectively analyzed to determine baseline BMD, osteoporosis risk factors, duration of AI use, duration of anti-OP therapy, and fractures. The IOF criteria were applied to each patient to determine applicability of anti-OP therapy. Fracture rates were compared using chi square test or Fisher’s exact test. Results: 1517 patients were included in the analysis. Regardless of whether criteria were met for treatment based on baseline BMD and CRF, the fracture rate was significantly higher in the treated versus the untreated group, 13.78% (CI: 9.56–18.99) versus 2.24% (p < 0.0001, CI: 1.51–3.21). Similarly, among those that met criteria, the fracture rate was significantly higher in the treated versus the untreated group, 10.24% (CI: 5.56–16.87) versus 2.61% (p = 0.0005, CI: 1.20–4.89). There was no significant difference in fractures between those who did versus did not meet treatment criteria, 4.66% (CI: 2.94–6.97) versus 3.64% (p = 0.34, CI 2.59–4.96). Conclusions: This retrospective EMR analysis of 1517 breast cancer patients on AIs between 2008 and 2017 observed a higher fracture incidence in patients who received anti-OP treatment compared to those who did not, regardless of meeting criteria for treatment per the IOF guidelines. It is possible that patients who initiated anti-OP therapy had additional CRFs not captured in the EMR and not factored into our analyses.
Fall Patterns Are Independent Risk Factors for Mortality After Hip Fracture in Older Adults
Authors: Hong Namki , Burm Seungwon , Rhee Yumie
Published: May 2021

Hip fracture is becoming a major health problem with high mortality and morbidity in older adults. However, whether specific fall patterns could act as independent risk factors for predicting mortality after hip fracture remains unknown. We aimed to investigate whether fall patterns can serve as an independent risk factor for mortality after hip fracture. Electronic medical records (EMR) of individuals who visited emergency room or admitted to the Severance hospital, Seoul, Korea, between January 2005 to December 2019 were reviewed to categorize fall patterns. Fall patterns were categorized upon review of explanatory description in EMR, using modified classification based on motion analysis of video-captured falls in a prior study. Among 1,991 study subjects (mean age 77 years, 71% women), 211 patients died (10.6%; median survival 296 days). Fall location was divided into home (67.4%) and outdoor (32.6%) with mortality rate of 11.9% and 8.0% (p=0.009), respectively. Fall patterns were specified by “cause of fall” (6 categories; slip [29.6%], trip or stumble [17.5%], etc.) and by “activity at time of fall” (6 categories; walking [54.8%], getting up or rising [14.1%], etc). Among the combinations of both causes and activities, individuals who sustained hip fracture during “incorrect weight shift while sitting down or lowering”(hazard ratio [HR] 3.35, p=0.003), “collapsed during unclassified activity”(HR 2.37, p=0.006), “incorrect weight shift while getting up or rising”(HR 2.13, p=0.003), and “slipped while walking”(HR 1.83, p=0.004) had increased mortality after hip fracture compared to those with outdoor falls, after adjustment for age, sex, and Charlson comorbidity index. Specific fall patterns in individuals who sustained hip fracture predicted excess mortality in older adults, independent of age, sex, and comorbidities. Acknowledgement: We thank Doori Cho of the the SENTINEL (Severance ENdocrinology daTa scIeNcE pLatform) team (4-2018-1215) for the data acquisition process. Conflict of Interest: SB, NH, and YR have nothing to declare.
Targeting the Fragility Fracture Prevention Message
Authors: Blank Robert Daniel , Choi Yoonah , Song Hae-Jin , (Derrick) Chan Ding-Cheng , Lee Joon Kiong
Published: May 2021

Background: The impact of fragility fractures on human suffering is underappreciated. Fragility fractures increase mortality and the risk of recurrent fracture. Notwithstanding these facts, only a minority of patients suffering osteoporotic fractures receive fracture preventing therapy. Education about the burden of disease and the benefits of prompt treatment are important means to increase the treatment rate. We propose that the focus of the educational message should be varied for distinct audiences.

Method: We searched existing literature to determine perceptions about the importance of treating fractures and osteoporosis among the following groups: the general population, primary care physicians, specialist physicians, hospital administrators, and government health officials.

Result: Extensive data focusing on patients and primary care physicians exist about barriers to treatment initiation. In these groups, lack of perceived treatment benefit is a widespread, common finding. To address this gap, we have produced a primary care education toolkit, patient booklet and education directory as Asia Pacific Fragility Fracture Alliance (APFFA)-sponsored initiatives.

Data are more limited for specialist physicians, hospital administrators, and government officials. Health economic arguments have been found to be persuasive among policy makers.

Conclusion: Information about the importance of treating fragility fractures and osteoporosis is far more abundant with reference to patients and primary care providers than to specialty physicians, hospital administrators, and government officials. Understanding the state of knowledge and belief is an essential first step in developing educational materials that address the concerns and misperceptions of each key constituency. Existing data suggest that patients will be more receptive to materials emphasising independence and quality of life, while policy makers will be more receptive to materials highlighting the burden of disease.
Basal Ganglia Calcification in Hypoparathyroidism Is Associated With Low Serum Calcium/Phosphate Ratio
Authors: Zavatta Guido , Tebben Peter J , Clarke Bart Lyman
Published: May 2021

Background: Basal ganglia calcification (BGC) is a well-known complication of hypoparathyroidism. It is currently thought that increased serum phosphate or calcium x phosphate product may be major risk factors. However, the pathophysiology of BGC is still unclear, since the literature is largely based on limited case series or case reports. Methods: We identified a large cohort of patients with hypoparathyroidism diagnosed between 2000 and 2020 and evaluated those with head CT scans performed over this interval. Etiology and date of onset of hypoparathyroidism were determined by medical records review. All head CT scan images were reviewed to confirm radiology reports reporting BGC. We retrieved laboratory data within 10 years before the first head CT that showed incident BGC. Three age- and sex- matched controls with head CT scans were selected for each patient, and compared to the patients with hypoparathyroidism. Results: Of 1014 unique patients with a verified diagnosis of hypoparathyroidism, 142 had a head CT scan performed between 2000 and 2020. Head CT scans were performed for reasons unrelated to hypoparathyroidism in 96.5% of patients. In this cohort, 80.3% of patients (n=114) had post-surgical hypoparathyroidism. Age at which the first head CT in patients was done was 62±20.6 (range 11–97), and duration of hypoparathyroidism at the time of first head CT was 11.0±14.4 years (0–71). Prevalence of BGC in patients with hypoparathyroidism was 25.4% (n=36), as compared with 7.3% in the control group (31/426) (P<0.001). Patients and controls were similar in terms of cardiovascular risk factors (diabetes, hypertension, dyslipidemia, alcohol consumption, smoking status and BMI). In patients with non-surgical hypoparathyroidism (n=28), prevalence of BGC was 71.4% vs. 14.0% in the postsurgical cohort (OR 15.4; 95% CI 5.8–40, P<0.001). Compared to patients with hypoparathyroidism without BGC, those with BGC had lower time-weighted average serum calcium (8.4±0.8 vs. 8.8±0.8, P=0.002; normal range, 8.6–10.2 mg/dL), and lower time-weighted average calcium/phosphate ratio (Ca/P) (1.83±0.52 vs. 2.13±0.47, P=0.007). Conclusions: Basal ganglia calcification in hypoparathyroidism is associated with low serum calcium and low Ca/P ratio. This may allow increased bioavailability of phosphate in the extracellular space, leading to calcium phosphate crystal formation within the basal ganglia. Assessing Ca/P ratio may be useful to identify patients at risk for BGC. Prevalence of BGC is significantly higher in patients with non-surgical hypoparathyroidism.
Creation of an Evidence-Based Physical Therapy Program for Adults with XLH: Translational Application of an Interprofessional Clinical Study
Authors: Kanamalla Karthik , Fuchs Rebekah , Herzog Casey , Steigbigel Keith , Macica Carolyn Marie
Published: May 2021

X-linked hypophosphatemia (XLH) arises due to inactivating mutations of the PHEX gene resulting in elevated circulating levels of the hormone FGF23, producing phosphaturia and impaired intestinal phosphate absorption. XLH is a lifelong metabolic disease with musculoskeletal comorbidities that dominate the adult clinical picture, and are resistant to standard therapies. We have previously reported the physical and functional impact of the adult disorder (J Clin Endocrinol Metab. 2020 Apr 1;105(4)). Bilateral and diffuse enthesophytes, degenerative arthritis and osteophytes were reported at the spine and synovial joints across subjects. Passive range of motion (ROM) was decreased at the spine, hips, knees, and ankles compared to controls. Gait analysis, relative to controls, revealed increased step width, markedly increased lateral trunk sway, and physical restriction at the hip, knees and ankle joints that translated into limitations through the gait cycle. These studies have been translated into an evidence-based physical therapy (PT) intervention study to address these major physical and functional comorbidities. Participants were enrolled in a remote 12-week PT program consisting of balance exercises and basic stretches with/without resistance. Subjects were evaluated at baseline and at every 4-weeks to assess ROM, gait, and functional ability. Several validated tools were employed to assess overall function: Berg Balance Scale, the Timed Up and Go (TUG) Test, and the Five Times Sit to Stand Test (5XSST). Subjective questionnaires, including the Lower Extremity Functional Scale (LEFS) and Activities-Specific Balance Confidence (ABC) Scale, were administered along with a weekly survey. At the conclusion of the study, minimal to modest improvements were seen in active ROM for the upper and lower extremity which reflect the significant bony restriction caused by XLH. However, improvements were seen in functional measures including the Berg Balance Scale, TUG, 5XSST, LEFS, and ABC. Weekly surveys indicated that participants improved their ability to balance, perform activities of daily living (ADLs), walk, and bend down to reach the ground. Results from this study will be applied to the creation of an evidence-based PT program to maintain functional capacity and improved ability to perform ADLs across the lifespan.
Improving Knowledge of MRONJ Risk Among Singapore Dental Practitioners Using an Educational Lecture With an Incorporated Quiz
Authors: Gani Linsey , Chionh Siok Bee
Published: May 2021

Background: Fear of rare medication side effects, such as medication related osteonecrosis of the jaw (MRONJ) in patients and dentists remains a major reason for the low rate of antiresorptive initiation for osteoporosis, and for the poor adherence after starting treatment. In this study, we assessed the understanding of osteoporosis treatment and its risk in dental professionals pre and post an education lecture. Method: Dental professionals were invited to an educational lecture on osteoporosis treatment and benefits. 2 lectures were conducted over the course of a year, with the 2nd lecture conducted virtually due to physical meeting restrictions in place for the COVID 19 pandemic. Attendees were invited to submit responses to a pre- and post- lecture survey assessing their knowledge of the current osteoporosis treatments and MRONJ. Results: There were 126 responses to the survey conducted. Majority (87%) of responders were dentists in private, including group dental practices, with 74% having more than 11 years of working experience. Most (81 %) have not had any encounters with patients with MRONJ. The pre-lecture survey showed that 60% of responders expressed slight or no confidence at all in treating patients who are on osteoporosis treatment. Only 19% of all responders were able to correctly identify the risk of MRONJ in patients on osteoporosis treatment. Majority of responders tended to inflate MRONJ risk by as much as 100 times the quoted baseline risk in the literature. One third of dentists would not perform any invasive treatments on patients on osteoporosis treatment. Post-lecture, the percentage of responders with slight and no confidence at all in treating patients who are on osteoporosis treatment decreased to 18%. 65% of responders were able to correctly identify the risk of MRONJ in patients on osteoporosis treatment as quoted in the literature. Only 3% of dentists would not perform any invasive treatments on patients on osteoporosis treatment. 95% of responders correctly stated that maintenance of good oral hygiene is the most important measure to prevent MRONJ. Attendees suggested the creation of a joint guidance from local osteoporosis and dental societies may better improve knowledge and instill confidence in treating osteoporosis patients. Conclusion: There is a significant knowledge gap within the dental practitioners in Singapore on the risk of MRONJ associated with osteoporosis treatments. This may result in dentists discouraging patients from starting osteoporosis medications and dentists not performing necessary dental treatments on patients on osteoporosis treatment. Both physical and virtual dental education lectures are effective in increasing the level of confidence and in correcting misconceptions on MRONJ risk. Continued engagement of the dental community would be important in reducing fear of MRONJ and facilitate treatment of osteoporosis in the population.
Patients With Primary Hyperparathyroidism Have Shorter QT/QTc Intervals
Authors: Stewart Latoya A , Steinl Gabrielle K , Huang Bernice L , McManus Catherine , Lee James A , Walker Marcella D , Kuo Jennifer H
Published: May 2021

Background: Previous studies suggest that patients with primary hyperparathyroidism (PHPT) have subclinical cardiovascular disease, but data regarding cardiac conduction abnormalities are limited. The aim of this study was to assess cardiac conduction abnormalities in patients with PHPT compared to controls with thyroid disease (TD).

Method: We conducted a retrospective analysis of patients over 40 years of age who underwent parathyroidectomy or thyroidectomy at a single tertiary institution between 2013 and 2018. Demographics and EKG parameters from pre-operative EKG reports were compared using the Mann-Whitney U and Chi Square tests. Regression was used to compare EKG differences between the PHPT and control groups adjusted for sex, age, and other variables found to be significant on univariate analysis.

Results: A total of 1181 patients were analyzed, 51% in the PHPT group (n=602) and 49% in the TD group (n=579). The median age was 60.5 years (IQR 53.5–67.9) and there was no difference in sex between the cohorts. PHPT patients had a higher prevalence of hyperlipidemia (HLD, 49% vs 36%, p<0.001) and hypertension (HTN, 50.7% vs 42.1%, p<0.01), but had no differences in EKG rhythm patterns or prevalence of arrhythmia compared to TD patients. As expected, mean serum calcium levels were higher for the PHPT group, 10.74 (0.66) vs 9.53 (0.44). However, the PHPT group included both normocalcemic and hypercalcemic patients. The PHPT group had a lower median QT interval compared to the TD group, 386ms (IQR 368–406) vs 398ms (IQR 376–418), p<0.001 and a higher median PR value, 158ms (IQR 144–174.5) vs 156ms (IQR 143.5–171), p<0.05. More PHPT patients (n=21, 3.5%) had a short QTc interval (<360ms males/<370ms females), compared to TD controls (n=1, 0.2%). Among PHPT patients with a short QT interval, the proportion of patients with hypercalcemia (95%) was higher than that of the PHPT group overall (75%). On multivariable analysis, PHPT patients had a shorter QT interval than TD controls after controlling for sex, age, HLD, HTN. There was no difference between PHPT and TD when serum calcium was included in the model, suggesting that calcium mediates the relationship between QT interval and disease status.

Conclusion: PHPT patients have shorter QT/QTc intervals compared to TD controls, but no increased prevalence of arrythmia at baseline. While the QT interval was associated with degree of serum calcium elevation, these findings in a large cohort suggest that PHPT is not associated with arrythmia at baseline among those undergoing parathyroidectomy.
Dress-Style Effect on Vitamin D3 Metabolic Profile
Authors: Odhaib Samih A , Alibrahim Nassar T Y , Zaboon Ibrahim A , Mansour Abbas A
Published: May 2021

Background and Objectives:Conservative clothing like niqab and hijab dress-style may affect the vitamin D metabolic parameters even in the predominantly sunny areas of the world, with adequate sunlight exposure throughout the year. Our objective is to evaluate the effect of wearing the niqab or hijab style on different vitamin D3 metabolic parameters in a sample of premenopausal women from Basrah. Methods: This was a cross-sectional observational study on premenopausal women who wore a niqab (n=64), with a comparable age-matched group of women who wore the hijab dress-style (n=60). Biochemical evaluation of the vitamin D3 metabolic profile involved 25-OH-vitamin D, corrected serum calcium, parathyroid hormone, phosphorus, and alkaline phosphatase estimation. Statistical comparison of these parameters was made using the independent sample t-test and Mann-Whitney-U test.

Results: The two groups of women were age- and weight-matched, with a median age was 39 years, and median body mass index (BMI) of 31.8 kg/m2. Overall, age, marital status, and BMI of women in both groups had no significant relationship to the vitamin D3 metabolic parameters (low 25-OH-vitamin D, low corrected calcium, and high parathyroid hormone). The subgroup analysis for women with the niqab showed the same results. Conclusions: Wearing niqab or hijab dress-style by the premenopausal women was not associated with any significant statistical relationship or difference in vitamin D3 metabolic parameters.
Vitamin D and Muscle Health: A Systematic Review and Metaanalysis of Randomized Placebo-Controlled Trials
Authors: Bislev Lise Sofie , Grove-Laugesen Diana , Rejnmark Lars
Published: May 2021

Background: Data regarding effects of vitamin D on muscle function are inconsistent. Discrepancies between observational and placebo-controlled studies are an indisputable fact. Objective: To investigate effects of vitamin D supplementation vs placebo on muscle health. Data Sources: A systematic research of published randomized controlled trials published until October 2020 has been conducted on Medline, Cochrane Database of Systematics Reviews, Embase and Google Scholar. Study Selection: Participants treated with vitamin D2 or vitamin D3 supplementation vs placebo, with or without calcium co-supplementation. All studies despite administration form (daily, bolus and duration) and populations, except athletes, were included. The pre-defined end-points were maximum muscle strength (Newton) measured as handgrip, elbow flexion, elbow extension, knee flexion, and knee extension. Physical performance reported as Timed Up and Go test (s), Chair Rising Test (s), 6 minutes walking distance (m) and Standard Physical Performance Battery (points). Finally, muscle mass in term of total lean mass (kg) was included. As the end-point measures were standardized, we apriori used random model effects and mean difference. Data Synthesis: In total, 51 randomized controlled trials involving 7798 individuals were included. Of included studies, 14 studies included participants with vitamin D insufficiency (25(OH)D<50 nmol/l) as inclusion criteria (19% of individuals). Outlier studies (N=1) were excluded. Analyses revealed a significant negative effect of vitamin D supplementation on knee flexion strength, mean difference -3.3 N, 95% CI (-6.63 to -0.03), I2=0%, n=765. The majority (8/12) of the studies used dosages > 2800 IU/day. Time spend performing the TUG test was also significant longer in individuals treated with vitamin D as compared with placebo, mean difference at 0.15 s (95% CI 0.04 to 0.26), I2=0%, n=5175. Excluding studies using bolus therapy or daily dosages > 2800 IU, the negative findings were no longer significant. No significant effect was found on the other measures of muscle strength, physical performance or muscle mass. In the minority of studies using vitamin D insufficiency as inclusion criteria, subgroup analysis revealed comparable effects of vitamin D and placebo. Conclusions: Overall, vitamin D do not have a beneficial effect on muscle health in non-athletes and may in some cases even have a negative effect. Subgroup analysis suggest that this finding may be dose-dependent. Our data do not support a beneficial effect on muscle health in vitamin D insufficient individuals, albeit only a minority of included studies investigated individuals suffering from vitamin D insufficiency. As an increasing number of studies report negative musculoskeletal effects including an increased fall risk, this study support the theory, that vitamin D should be dosed with care.
Black Women Have a Worse Cardio-Metabolic Risk Profile Compared to White Women with Polycystic Ovary Syndrome in the United States: A Systematic Review and Meta-Analysis
Authors: Kazemi Maryam , Kim Joy Y , Parry Stephen A , Azziz Ricardo , Lujan Marla E
Published: May 2021

Health disparities may influence cardio-metabolic risk in women with polycystic ovary syndrome (PCOS). The magnitude and direction of differences in cardio-metabolic risk between Black and White women with PCOS remain uncertain due to inconsistent reports. We conducted a systematic review and meta-analysis to evaluate evidence on cardio-metabolic health disparities between Black and White women with PCOS in the US in response to the call for further delineation of these disparities by the International Evidence-based Guideline for the Assessment and Management of PCOS. Databases of MEDLINE, Web of Science, and Scopus were searched (January 1990 to September 2020) to identify observational studies documenting cardio-metabolic risk profile (glucoregulatory, lipid profile, anthropometric, blood pressure status) in Black and White women with PCOS. The primary outcome was fasting glucose. Further, cardiovascular events (stroke, coronary heart disease, heart failure) and mortality rate (cardiovascular death, total mortality) data were evaluated between groups. Studies on children (< 17 yrs.), pregnant or menopausal-aged (> 50 yrs.) women were excluded. Data were pooled by random-effects models and expressed as weighted mean differences and 95% confidence intervals. Eleven studies (n = 2,821; [626 Black; 2,195 White women]) evaluated cardio-metabolic risk profile, yet none reported on cardiovascular events/mortality rate. Black women had comparable fasting glucose (-0.61 [-1.69, 2.92] mg/dL; I2 = 62.5%), yet exhibited increased fasting insulin (6.76 [4.97, 8.56] µIU/mL; I2 = 59.0%); homeostatic model assessment of insulin resistance (HOMA-IR; 1.47 [0.86, 2.08]; I2 = 83.2%); systolic blood pressure (SBP, 3.32 [0.34, 6.30] mmHg; I2 = 52.0%) and decreased triglyceride (-32.56 [-54.69, -10.42] mg/dL; I2 = 68.0%) when compared to White women with PCOS (All: P ≤ 0.03). Groups were comparable in total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and diastolic blood pressure (All: P ≥ 0.06). Paucity in the number of studies that evaluated cardiovascular events or mortality limits any conclusions about potential disparities. Overall, Black women with PCOS have a greater tendency for an adverse cardio-metabolic risk profile (increased insulin, HOMA-IR, SBP), despite lower triglyceride levels than White women. Our observations support consideration of these disparities for diagnostic, monitoring, management, and public health practices, and for future guideline recommendations. Heterogeneity among studies warrants future research to address the relative contributions of biological, environmental, socioeconomic, and healthcare factors to the observed disparities. Longitudinal research should address cardiovascular events and mortality rate in Black women with PCOS (www.crd.york.ac.uk/PROSPERO ID, CRD42020183485).
Impact of Hypertriglyceridemia on Outcome of Adult Patient Admitted With Hyperthyroidism: Analysis of the National Inpatient Sample 2016–2017
Authors: Asemota Iriagbonse , Akuna Emmanuel , Shaka Hafeez , Edigin Ehizogie , Velazquez Genaro , Ojemolon Pius , Asotibe Jennifer Chiagoziem
Published: May 2021

Introduction: Thyroid dysfunction has a great impact on lipids as well as a number of other cardiovascular risk factors. Though the effect of thyroid hormones on plasma cholesterol concentrations are well-recognized, however, there are conflicting reports about the effect of thyroid hormone on the metabolism of plasma triglycerides. We sought to determine the effect of hypertriglyceridemia on patient admitted with hyperthyroidism. Methods: We queried the National Inpatient Sample (NIS) databases from 2016 to 2017 for adults aged 18 and above with hypertriglyceridemia as a principle diagnosis with and without hyperthyroidism using ICD-10 codes. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. Results: There were over 71 million discharges in the combined 2016 and 2017 NIS database. Out of 17,705 hyperthyroidism hospitalizations, 15% had hypertriglyceridemia. Hypertriglyceridemia with hyperthyroidism had a similar odds of inpatient mortality (AOR 0.37, CI 0.06–1.99, P=0.246), acute kidney injury (AOR 1.03, CI 0.706–1.510, P=0.868) and cardiogenic shock (AOR 0.96, CI 0.134–6.72, P=0.963). There was a statistically significant increase in odds of acute respiratory failure (AOR 0.46, CI- 0.21- 0.99, P=0.048) in those hospitalized with hyperthyroidism and hypertriglyceridemia compared to those with hyperthyroidism alone. Conclusion: Hypertriglyceridemia is associated with similar outcomes in patient admitted for hyperthyroidism in terms of mortality, acute kidney injury and acute cardiogenic shock with an increased odd of acute respiratory failure. More research is needed to explain the pathophysiologic mechanism underlying the effect of hypertriglyceridemia on hyperthyroidism.
The Relationship Between the Aldosterone-to-Renin Ratio and Blood Pressure in Young Adults: A Longitudinal Study
Authors: Yang Jun , Gwini StellaMay , Beilin Lawrence J , Schlaich Markus , Stowasser Michael , Young Morag J , Fuller Peter J , Mori Trevor
Published: May 2021

Background: Hypertension tracks throughout childhood into adulthood. Aldosterone excess, or primary aldosteronism, has been reported as the most common secondary cause of hypertension in adults. Elevated aldosterone in the setting of low renin predicts incident hypertension in normotensive adults. However, the relationship between aldosterone and blood pressure in adolescents and young adults is unclear. Objectives: To evaluate the relationship between aldosterone, renin and the aldosterone:renin ratio (ARR) and blood pressure (BP) at age 17y as well as BP at age 27y in a community-based population. Methods: This is a prospective birth cohort study. Young adult offspring (Gen2) of women enrolled during pregnancy into the Raine Study, with 1239 at age 17y and 1006 at age 27y, were evaluated. Females taking hormonal contraception and participants without BP data were excluded from the current analysis. A generalised linear model was used to examine the relationship between BP and aldosterone, renin and ARR over time. The median aldosterone, renin and ARR was compared between sexes using quantile regression. Results: At 17y, females had similar aldosterone (349 vs 346 pmol/L, p=0.833) but significantly lower renin (20.6 vs 25.7 mU/L, p<0.001) and thus a higher ARR (18.3 vs 13.5, p<0.001) compared to males. However, they had lower systolic BP (109 vs 118 mmHg, p< 0.001) versus males. A significant correlation between ARR and systolic BP was detected in 17y males when adjusted for alcohol consumption, physical activity, urinary sodium and body mass index. This was true when the ARR was expressed as a continuous variable (β-coefficient 0.1, p=0.009) or categorical variable (highest quartile, β-coefficient 3.15, p=0.003). A similar correlation was not observed in females at 17y. However, the ARR at 17y was significantly associated with both systolic (β-coefficient 0.15, p=0.009) and diastolic BP (β-coefficient 0.14, p=0.003) at 27y in females, but not males. Conclusion: A relationship between ARR and BP are observed at both 17 and 27 years but with distinct age-related sex differences. Further evaluation of the relationship between ARR and surrogate markers of cardiovascular disease such as vascular reactivity will improve our understanding of aldosterone as a cardiovascular risk factor young people.
Tolerability and Efficacy of Long-Term Medical Therapy in Primary Aldosteronism
Authors: Puar Troy , Tang Fengjie , Loh Lih-Ming , Foo Roger , Loh Wann Jia , Khoo Joan , Kek Peng Chin
Published: May 2021

Introduction: Patients with primary aldosteronism (PA) have increased cardiovascular risk and studies have found that medical therapy fails to ameliorate this. This may be due to side effects and limited efficacy of medications at tolerable doses. Methods: We conducted a retrospective study on 201 patients with PA treated with medical therapy (spironolactone, eplerenone or amiloride) for PA from 2000–2020 at two tertiary centres. Patients were assessed for efficacy to achieve clinical and biochemical control, and for side effects. Results: 53.7% of patients achieved blood pressure <140/90mmHg, 44.6% achieved serum potassium ≥4.3mmol/L, and 63.2% achieved renin levels >1ng/ml/hr. Concordance between biochemical control as assessed by potassium and renin levels was 49%. 45.3% of patients experienced side effects, with 8.5% switching to another medication, 18.9% decreasing dose, and 10.0% stopping medications altogether. Risk factors for side effects were spironolactone use, dose ≥50mg, duration of treatment ≥1 year, male gender and unilateral PA. Patients with unilateral PA, compared to bilateral PA, used higher median doses of spironolactone, 75mg vs 50mg, P<0.001, but more had persistent hypokalemia, 20.5% versus 6.4%, P=0.007. 44 patients with unilateral PA underwent surgery after initial medical therapy, which further improved systolic and diastolic BP, from 142 to 134mmHg, P<0.001, and from 85 to 79mmHg, P<0.001, respectively. Conclusion: Dose-dependent side effects limit the efficacy of medical therapy in PA. Future prospective studies should assess the best monitoring strategy for biochemical control during long-term medical therapy. In patients with unilateral PA, surgery remains a better option compared to life-long medications.
Trends in Serum Lipid Profiles and Lifestyle Factors Among Korean Adolescents, 2007–2018
Authors: Kim Shin-Hye , Park Mi-Jung
Published: May 2021

Objectives: Trends in serum lipids among teenagers would be crucial predictors of potential cardiovascular disease in adults. We aimed to investigate the trends in lipid profiles and related factors, including obesity, smoking, exercise, alcohol use, and total fat intakes in Korean adolescents from 2007 to 2018. Methods: We analyzed 5,967 participants aged 12–19 yrs from the Korea NHANES 2007–2018. Fasting total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) levels were measured. Results: All kinds of lipid profiles, except TG, showed increasing trends from 2007 to 2018 (P<0.01). Nevertheless, the prevalence of dyslipidemia showed a trend of decreasing in boys (from 33.3 to 26.6%; P=0.002) and maintained in girls (from 28.4 to 30.2%; P=0.465), mainly due to a substantial decrease in hypo-HDL-cholesterolemia (9% reduction in boys, 5% reduction in girls). This occurred amid an increasing trend of central obesity in boys (P<0.001). In lifestyle factors, there were no significant changes in alcohol use and muscle-strengthening exercise, while a substantial decrease in smoking rate was observed. A favorable effect of muscle-strengthening exercise on both TG and HDL-C and an unfavorable impact of smoking on HDL-C were observed. Alcohol use was associated with higher HDL-C in both genders, but it showed opposite associations with TG between boys (unfavorable) and girls (favorable). Regarding dietary factors, there were increasing trends in total fat intakes and the percentage of energy supply from total dietary fat (〔total fat (%E)〕 in both genders. In boys, an increase in total fat (%E) was related to the higher HDL-C in normal-weight subjects (P<0.01 in both genders); however, it was associated with higher LDL-C in overweight girls (P=0.001). Conclusions: Increases in fat intakes and a decline in smoking rates appeared to have positively impacted HDL-C in Korean adolescents over the past 12 years. We confirmed a rise in fat intakes was linked with the increase in LDL-C among overweight adolescents. Therefore, close monitoring for the dyslipidemia prevalence is essential in Korean adolescents whose obesity prevalence is on the rise.
A Case of Fishy Smell-Fish Malodor Syndrome
Authors: Wang Ally W , Greenberg Pietra D , Saul Shira R
Published: May 2021

Introduction: Primary trimethylaminuria (TMAU), also known as fish malodor syndrome is a rare condition that is characterized by trimethylamine excess. The hallmark of this condition is a body malodor similar to decaying fish. As this metabolic disorder is uncommon, this case highlights the management options for an endocrinologist.

Case presentation: A 56-year-old man was referred to the endocrine clinic for TMAU. Starting in puberty, the patient’s family and friends noted a malodor that he has never been able to detect. After several decades, the patient was diagnosed clinically by a dermatologist. Since then, the patient’s management had included avoiding cholines in his diet, which included egg yolks and salt-water fish. Additionally, for severe episodes occurring once to twice a year, he took a cup of charcoal daily plus Metronidazole 500 mg twice a day for ten days. The patient was the only member of his family with this condition. Physical exam was unremarkable expect for a faint malodor. Metronidazole, charcoal, and a genetics consult were ordered.

Discussion: TMAU is a rare metabolic disorder in which an individual is not able to convert trimethylamine into trimethylamine N-oxide due to a defect in the hepatic oxidase system. It results from a mutation in the flavin-containing monooxygenase 3 gene (FMO3) that is inherited via autosomal recessive pattern. An excess excretion of trimethylamine in the urine, breath, sweat, and reproductive fluids results in a body malodor similar to that of decaying fish. The odor may be exacerbated by increase in body temperature, emotional changes, puberty, and prior to and during menstruation in women and often results in distressing psychosocial difficulties. Thus, early institution of dietary and pharmacological measures will likely have a major impact on quality of life.

Treatment options are limited and include topical, dietary, and medications. Topical approaches include antiperspirants, deodorants, and pH-balanced soap. A diet low in choline-containing foods such as dairy, beans, and marine fish is beneficial as choline is metabolized to trimethylamine by the intestinal bacteria. For severe cases, antibiotics such as Metronidazole, Rifaximin, and Neomycin sulfate are helpful to reduce the intestinal bacterial load. Other therapeutic strategies consist of activated charcoal (750 mg twice a day for ten days) and copper chlorphyllin (60 mg three times a day for three weeks); both reduce urinary free trimethylamine and increase the concentration of trimethylamine N-oxide.
Tyhroid Storm-Induced Worsening Acute Myocardial Infarction: A Case Report
Authors: Diba Sonya Farah
Published: May 2021

Background: As a true endocrine emergency, thyroid storm is rarely associated with acute myocardial infarction. However Graves’ disease is the most common underlying cause of thyroid storm. Clinical Case: A 47-year women experienced typical chest pain since 30 minutes before visited emergency room. The patient had type two diabetes as a cardiovascular risk factor and regularly took metformin thrice daily. The electrocardiogram showed non-ST segment elevation in leads I, V4-V6. Coronary arteriography showed stenosis in the three and left main vessels (70% stenosis of right coronary, 80% stenosis of left circumflex, 90% stenosis of left anterior descendent, and 90% stenosis of mid distal, in left main stem) then the patient was planned to do bypass surgery. At day 6 of hospitalization, the typical chest pain was worsening, epigastric pain became more painful, had 5 times diarrhea per day, high grade fever (>38.5oC), severe nausea and vomiting, then generalized tonic clonic seizure and respiratory failure was occurred. The patient was intubated in intensive care unit. Through a detail physical examination, a diffuse palpable thyroid enlargement and class I ophthalmopathy were found. Laboratory findings of free T4 was 2.23 ng/dL and Thyroid Stimulating Hormone (TSH) was 0.003 µIU/mL. The patient was assessed as thyroid storm then immediately, treated with three times of 100 mg hydrocortisone, two times of 20 mg of propranolol, and three times of 400 mg propylthiourasil. The patient’s clinical appearance was gradually recovered. After 3 days of treatment, she was extubated from ventilator. Two weeks later, no complaint of chest pain or epigastric pain in observation. Conclusion: Our case highlight the possibility that hyperthyroidism may be involved in the development of acute myocardial infarction.