bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethnicity, Ethnic Language, and Fracture Risk Conditions in Women Initiating Osteoporosis Therapy
Authors: Lo Joan Chia-Mei , Chandra Malini , Darbinian Jeanne A , Hui Rita L , Gordon Nancy P 
Published: May 2021

Abstract
Introduction: The ethnic diversity of women with osteoporosis has increased, but data on acculturation and health remain limited. Having a primary language (PL) other than English may reflect acculturation level and/or immigration as an adult. We used electronic health record (EHR) data from a large US health plan to examine the association of baseline clinical risk conditions and PL among US Chinese and US Hispanic women who initiated osteoporosis therapy. Methods: We identified women age 65-74y who initiated osteoporosis therapy in 2002–2014, excluding those with skeletal disorders, advanced kidney disease and metastatic cancer. PL was ascertained from the EHR. The study included 1676 Chinese women with English-PL (50%) vs Chinese-PL (50%); 3453 Hispanic women with English-PL (72%) vs Spanish-PL (28%); and 20,289 non-Hispanic White (White) women with English-PL. Clinical conditions assessed included: current smoking; BMI &lt;19 kg/m2; Charlson-Deyo Comorbidity Index (CCI); diabetes (DM) based on diagnosis with treatment; rheumatoid arthritis (RA) based on 2 diagnoses; and fracture diagnosis in the prior 5 years. Language subgroups (* denotes significant difference by PL, p&lt;.05) and ethnic groups (all ethnic differences cited are significant at p&lt;.05) were compared using chi-square tests. Results: Mean age was (69±3y) for Chinese, Hispanics, Whites, and PL subgroups. Prior fracture was lower in Chinese (12.8%) and Hispanics (25.6%) vs Whites (29.7%), with Chinese lower than Hispanics. Smoking was lower in Chinese (1.6%) and Hispanics (6.7%) vs Whites (11.3%). CCI score ≥3 was lower in Chinese (5.2%) and higher in Hispanics (13.0%) vs Whites (10.4%). RA was low overall and lowest in Chinese, especially Chinese-PL. More Chinese (4.2%) and fewer Hispanics (0.8%) had a BMI &lt;19 vs Whites (2.2%). DM was higher in Hispanics (14.8%) and Chinese (8.2%) compared to Whites (5.7%). Significant and non-significant differences by PL were observed for current smoking (0.8%* vs 2.4% for Chinese-PL vs English-PL; 4.0% vs 7.8% for Spanish-PL vs English-PL), prior fracture (11.4%* vs 14.2% for Chinese-PL vs English-PL; 24.3% vs 26.1% for Spanish-PL vs English-PL) and DM (10.5%* vs 5.8% for Chinese-PL vs English-PL; 24.3% vs 26.1% for Spanish-PL vs English-PL) in Chinese and Hispanic women. Conclusion: Among older women initiating osteoporosis therapy, US Chinese women have lower comorbidity but a higher DM prevalence compared to white women, especially those with Chinese-PL. Hispanic women have higher comorbidity and higher DM prevalence than White women, with no differences by PL. Variation in prior fracture, low BMI, RA, and smoking were also seen. These findings highlight ethnic differences in women receiving osteoporosis care, including differences by primary language in Chinese women. Future studies should examine fracture risk factors and outcomes in US immigrant populations, especially Asians.
Impact of Thyroid Disease on Bone Mineral Density Preservation in Patients With Osteoporosis and Idiopathic Hypercalciuria
Authors: Chu James W 
Published: May 2021

Abstract
Background: Idiopathic hypercalciuria (IHC) is associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fractures. It is not known if thyroid disease impacts the degree of urine and bone mineral abnormalities in patients with IHC and osteoporosis (OPO).
Methods: Retrospective chart review from a private endocrinology clinic identified 62 consecutive patients with OPO (fragility fracture and/or t-score ≤-2.5 on bone density scan) and concomitant diagnosis of IHC (urine calcium &gt; 4.0 mg/kg weight/d when intaking low-moderate calcium amounts). Patients were classified into two groups: those with thyroid disease (Thy+, if presence of autoimmune thyroid disease [AITD] with high antibody titers and/or long-term thyroid medication use) and those without (Thy-). Comparisons were made between the two groups for severity of renal disease (urine calcium) and bone disease (number of fragility fractures, and BMD response to therapy).
Results: Of 55 women and 7 men identified with both OPO and IHC, 30 were Thy+ (4 with Graves’, 11 with confirmed Hashimoto’s, 13 taking levothyroxine for presumed Hashimoto’s and 2 with thyroid cancer), and 32 were Thy- (including 2 with type 1 DM, 1 with vitiligo, and 6 with non-toxic nodular goiters requiring biopsies). Thy+ were compared to Thy- with respect to: mean age (70.7 ± 7.3 vs. 70.8 ± 9.3 y), sex (97% vs. 81% women), 24-hr urine calcium at diagnosis (317 ± 75 vs. 311 ± 68 mg), presence of fragility fracture (50% vs. 59%), use of thiazide (83% vs. 78%), and use of anti-fracture pharmacotherapy (73% vs. 84%).
50 patients had adequate comparative longitudinal BMD data. A (+) BMD response was based on consistent increases in BMD and/or t-scores across all spine and hip sites, and a (-) BMD response was classified by decreased BMD and/or t-scores across all sites. For Thy+ vs. Thy- patients, there were 25% vs. 69% (+) BMD response, 38% vs. 12% (-) BMD response, 21% vs. 4% with no significant BMD response, and 17% vs. 15% with mixed BMD responses.
Conclusions: In this group at high risk for future fragility fractures, much lower rates of BMD preservation was seen in the Thy+ as compared to the Thy- patients. Overall, AITD and medical thyroid disease was very common (48%) in this cohort of patients with IHC and OP. However, this high rate may be confounded by the selective nature of the specialty clinic population. Further research needs to delineate the impact of AITD and thyroid medication use on the progression and treatment of patients with IHC and OPO.
Radiofrequency Multi Echographic Spectrometry (REMS) Technology in Patients With Bone Artifacts
Authors: Tomai Pitinca Maria Dea , Caffarelli Carla , Gonnelli Stefano 
Published: May 2021

Abstract
Introduction: Dual-energy X-ray Absorptiometry (DXA) is considered the gold standard examination for the evaluation of bone mineral density (BMD). However, it is known that some conditions, such as arthrosis, vertebral collapse, or vertebroplasty, result in an overestimation of the BMD measured by DXA. Conversely, Radiofrequency Echographic Multi-Spectrometry (REMS) technology is able to automatically discard signals related to bone artifacts, such as calcifications or osteophytes, thanks to the identification of unexpected spectral features (Diez-Perez et al. 2019). The aim of this work is to assess the performance of REMS technology in patients with bone alterations that could alter the densitometric examination. Materials: The bone densitometry exams, both REMS and DXA, of patients with evidences of bone alterations at lumbar vertebrae or femoral neck were analysed. Written patient informed consent was obtained before the scans. Results: Eighty-seven patients with spinal artifacts, including 22 patients with vertebroplasty, 26 patients with bone fracture and 38 patients with osteo-arthrosis were considered. At lumbar spine, the mean BMD and T-score values assessed by REMS was lower than the ones measured by DXA. Moreover, the results obtained by the two technologies were not correlated. On the contrary, the BMD and T-score values measured by REMS and DXA at the femoral site were highly correlated (p&lt;0.01), as well as BMD and the T-score values measured by DXA at the femoral neck and by REMS at the lumbar spine (p&lt;0.01). As concerning artifacts involving femoral site, a patient with an intramedullary gamma nail positioned following a displaced pertrochanteric fracture of the left femur underwent a DXA scan of the right femur and a REMS scan of both femurs. A diagnosis of osteoporosis at the right femur was posed by both technologies. At the left femur with intramedullary gamma nail, REMS only made a diagnosis of osteoporosis highly corresponding with the one performed at right femur. Conclusions: The results from the patient series with spinal artifacts and the clinical case with femoral intramedullary gamma nail show the ability of REMS to evaluate anatomical sites that would not be assessable by DXA, such as in case of implanted nails, or that would give unreliable higher BMD values, such as in case of vertebroplasty, osteo-arthrosis and bone fracture. References: Diez-Perez et al. Aging Clin Exp Res 2019;31(10):1375–89
A Phase 2B, Open-Label, Dose-Ranging Study of Encaleret (CLTX-305) in Autosomal Dominant Hypocalcemia Type 1 (ADH1)
Authors: Gafni Rachel Ilana , Hartley Iris Ruth , Roszko Kelly Lauter , Nemeth Edward F , Pozo Karen A , Sani-Grosso Ramei , Sridhar Ananth , Fox Jonathan C , Collins Michael T 
Published: May 2021

Abstract
Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism caused by gain-of-function pathogenic variants in the gene encoding the calcium-sensing receptor (CaSR). It is characterized by variable degrees of hypocalcemia, hyperphosphatemia, and hypomagnesemia, with inappropriately low levels of parathyroid hormone (PTH) and hypercalciuria. Conventional therapy includes oral calcium and activated Vitamin D supplementation, which can lead to or exacerbate hypercalciuria. As a result, patients may develop nephrolithiasis and/or nephrocalcinosis, which can progress to renal insufficiency. Calcilytics (antagonists of the CaSR) have demonstrated in in vitro and in vivo models of ADH1, as well as in a small clinical trial (Roberts et al, JBMR 2019), the ability to shift the dose-response relationship between extracellular calcium and the cellular response of cells bearing the mutant CaSR towards normal. This shift has the potential to increase endogenous PTH secretion which in turn may promote skeletal release of calcium into the bloodstream, production of endogenous calcitriol, renal excretion of phosphate, and renal reabsorption of calcium. Additionally, direct effects of calcilytics on renal CaSRs may further reduce renal calcium and magnesium excretion in ADH1. Taken together, this class of drugs has the capacity to restore normal mineral homeostasis, without calcium and activated vitamin D supplements and without attendant risks of iatrogenic hypercalciuria. This Phase 2b, open-label, dose-ranging study will evaluate the safety, tolerability, pharmacodynamics, and pharmacokinetics of the calcilytic encaleret (CLTX-305) in up to 16 participants with ADH1 (NCT04581629). The study will consist of 3 periods. In periods 1 and 2, participants will undergo a 1-week inpatient evaluation to study the safety and tolerability of daily and twice-daily doses of encaleret. Period 3 will follow participants for up to 24 weeks of continuous outpatient dosing, with periodic inpatient and outpatient assessments. The primary endpoint of period 3 is the change from baseline in albumin-corrected blood calcium concentration. Secondary endpoints of the study include the change in urine calcium (fractional and 24-hour excretion), 1,25-dihydroxy-Vitamin D, phosphate, magnesium, and other blood/urine biomarkers. Enrollment for this study at the National Institutes of Health (NIH) began in September 2020 with topline results expected in 2021. This study is supported by Calcilytix Therapeutics, Inc. and the NIH Intramural Research Program.
Circulating MicroRNA-23a-5p Is a Potential Biomarker for Recovery of Bone Mass After Parathyroidectomy in Primary Hyperparathyroidism
Authors: Lee Seunghyun , Hong Namki , Kim Kyoung Jin , Jeong Jong Ju , Rhee Yumie 
Published: May 2021

Abstract
Circulating microRNA (miRNA), a non-coding RNA molecule, is the potential biomarker for bone and mineral metabolism. Primary hyperparathyroidism (PHPT) is one of the leading causes of secondary osteoporosis. After parathyroidectomy, BMD improves as parathyroid hormone (PTH) decreases in patients with PHPT but degree of recovery in BMD vary greatly among patients. Biomarkers which are able to predict postoperative bone response may facilitate individualized approach to PHPT treatment. In this study, we aimed to investigate whether changes of miRNA related to PHPT can predict postoperative BMD recovery. A total 12 patients (10 women) who underwent parathyroidectomy for PHPT at Severance hospital from 2016 to 2019 were analyzed. A total of 15 selected miRNAs (miR-19b-3p, miR-21-5p, miR-23a-3p, miR-152-3p, miR-335-5p, miR-375, miR-532-3p, miR-24-3p, miR-100-5p, miR-125b-5p, miR-24-5p, miR-93-5p, miR-122-5p, miR-124-3p, and miR-148a-3p) from literature review were measured from pre- and pot-operative serum samples. Among pre-, post-operative level, and fold changes [the normalized gene expression(2-ΔCt) in postoperative period divided the normalized gene expression (2-ΔCt) in pre-operative period] of each miRNA, potential predictors of femoral neck BMD changes (%) as primary outcome were selected by univariable regression. The mean age of patients during parathyroidectomy was 56±16 years. PTH level and calcium level restored to normal range after parathyroidectomy in all subjects. (pre to postoperative: PTH, median 113 to 42; calcium, mean 10.6 to 9.2). Circulating level of miR-19b-3p, miR-21-5p, miR-100-5p, miR-125-5p, miR-152-3p and miR-335-5p dropped significantly after parathyroidectomy (p&lt;0.05 for all). A fold change in miR-23a-5p showed a negative correlation with changes (%) in femur neck BMD (β coefficient=-10.58, 95% CI=-19.84 to -1.31, p=0.029). The association remained robust (β coefficient=-7.25, 95% CI=-14.17 to -0.34, p=0.042) even after adjustment for gender, age, and preoperative PTH level in multiple linear regression model. Preoperative miR-124-3p showed a positive correlation with changes in total hip BMD (β coefficient=-9.748, 95% CI= 3.740 to 15.755, p=0.005), but there was no association after adjustment for gender, age, and preoperative PTH level. In conclusion, a fold change in circulating miRNA-23a-5p predict the degree of improvement for femoral neck BMD. MiRNA have potential to serve as novel biomarker to predict treatment response in patients with PHPT, which merits further investigation.
Risk of Chronic Kidney Disease in Adult Patients With Chronic Hypoparathyroidism Treated With rhPTH(1–84) Compared With a Historical Control Cohort
Authors: Gosmanova Elvira , Ayodele Olulade , Sherry Nicole , Mu Fan , Briggs Allie , Swallow Elyse , Rejnmark Lars 
Published: May 2021

Abstract
Patients (pts) with chronic hypoparathyroidism are at increased risk of renal complications. This study evaluated chronic kidney disease (CKD) outcomes over a period of up to 5 years in adult pts with chronic hypoparathyroidism treated with recombinant human parathyroid hormone (1–84), rhPTH(1–84), compared with a historical control cohort of pts who did not receive rhPTH(1–84). The cohort of pts with chronic hypoparathyroidism treated with rhPTH(1–84) was derived from the NCT00732615 (REPLACE), NCT01268098 (RELAY), NCT01297309 (RACE) and NCT01199614 (HEXT) clinical trials. The control cohort of adult pts who did not receive rhPTH(1–84) or rhPTH(1–34) was selected from the US Explorys electronic medical record database (Jan 2007−Aug 2019), using criteria similar to the enrollment criteria used in the trials. Index date was the day after treatment initiation for the rhPTH(1–84) cohort, and the day after the first calcitriol prescription for the control cohort. Pts with CKD at baseline (defined as estimated glomerular filtration rate [eGFR] &lt;60 mL/min/1.73 m2 at the closest eGFR measurement before the index date) were excluded. All included pts had ≥1 eGFR measurement within 6 months before the index date and ≥2 eGFR measurements ≥3 months apart during the 5 years on or after the index date. The CKD outcome was defined as first occurrence of eGFR &lt;60 mL/min/1.73 m2 confirmed by a second measurement ≥3 months after. Risk of CKD was assessed in a Kaplan-Meier analysis and a Cox proportional hazards model adjusted for demographic characteristics, baseline clinical conditions (including acute manifestations of hypoparathyroidism), and baseline laboratory measurements. The analysis included 118 pts in the rhPTH(1–84) cohort and 478 pts in the control cohort. Pts in the rhPTH(1–84) cohort, compared with pts in the control cohort, were younger (mean ± SD age, 45.3±11.4 vs 51.5±16.2 years; P&lt;0.001), a higher proportion were White (97.5% vs 81.6%; P&lt;0.001), and a lower proportion had acute manifestations of hypoparathyroidism before the index date (15.3% vs 73.2%; P&lt;0.001). In a Kaplan-Meier analysis, rhPTH(1–84)-treated pts had a significantly reduced risk of developing CKD compared with pts in the control cohort, with 11.0% and 27.0% of pts in each cohort, respectively, developing CKD during follow-up (P&lt;0.01). The adjusted hazard ratio of developing CKD associated with rhPTH(1–84) treatment vs no rhPTH(1–84) treatment was 0.47 (95% CI, 0.25−0.88; P&lt;0.05). Pts with chronic hypoparathyroidism treated with rhPTH(1–84) in long-term clinical trials had a significantly reduced risk of developing CKD compared with pts in a control cohort who did not receive rhPTH(1–84). These results should be viewed in light of possible treatment differences in the studied cohorts (ie, predefined trial protocols vs real-word practice for the control cohort).
Body Composition And Bone Mineral Differences According to Lamin A (LMNA) Genotype in Familial Partial Lipodystrophy Type 2
Authors: de Freitas Maria Cristina Foss , Akinci Baris , Corsa Callie , Rothberg Amy E , MacDougald Ormond A , Oral Elif A 
Published: May 2021

Abstract
Phenotypic heterogeneity is well known in Familial Partial Lipodystrophy Type 2 (FPLD2), a rare form of adipose tissue disorder caused by pathogenic mutations in LMNA gene. Animal studies from our group have identified an association between adipose tissue loss and an increase in bone mineral density (BMD) in a mouse model with adipose tissue specific knockout of LMNA gene. Aiming to translate this observation to patients with FPLD2, we analyzed body composition data obtained by dual X-ray absorptiometry from 61 patients diagnosed with FPLD2 and 61 individuals with no diagnosis of FPLD (nFPLD) matched for sex, age and body mass index. As expected, we observed lower total fat mass in FPLD2 patients compared to nFPLD (15.8±9.3 kg vs. 28.5±12.4 kg, p=0.001), as well as lower fat mass in regions of arms, legs and trunk. Interestingly, patients with FPLD2 showed lower bone mineral density (BMD) compared to nFPLD 1.0±0.2 g/cm3 vs 1.2±0.1 g/cm3, p=0.01) and lower t-score (0.2±1.8 vs.1.5±1.2). We then aimed to determine if the patients with FPLD2 displayed differences with respect to genotype. For these analyses, the FPLD2 group was divided according to the pathogenic variant; 42 with mutations on the hot spot codon of the LMNA gene (R482: 50.2 ± 164.8 years, 76% women) and 19 with non-hot spot codon mutations (nR482: 44.8 ± 12.8 years, 78% women). Patients in the R482 group were older when they were first diagnosed with lipodystrophy (39.6 ± 18.6 years vs. 36.5 ± 12.3 years, p=0.05). Also, nR482 group presented with more progeroid characteristics. Patients in n-R482 group also had lower weight compared to R482 and nFPLD groups (64.4±14.4 vs. 73.3±18.5 and 77.6±16.6 kg, p=0.01), as well as lower total fat mass (15.3±5.1 vs. 15.8±9.3 and 25.7±11.4 kg, p=0.01) and fat mass ratio (5.8±1.9 vs. 5.9±3.1 and 9.0±4.1, p= 0.01). Control group bone mass was significantly higher in arms, legs and trunk compared to the R482 and nR482 groups. Moreover, the R482 group had lower bone mass in the legs compared to nR482 (690.5±227.2 vs.703.5±95.3 g, p=0.01), while showing higher trunk bone mass (676.4±266.7 vs. 674.1±79.3, p=0.04), in addition to greater fat mass in the legs (3.3±1.6 vs. 2.6±0.7 kg, p=0.05) and trunk areas (10.3±6.1 vs. 10.0±4.2 kg, p=0.03). There were no differences in total bone mass, BMD, and t-scores, according to genotype. Our data showed more fat preservation in LMNA R482 than nR482, presumably leading to a later lipodystrophy diagnosis. Furthermore, bone mass in different regions may be affected by LMNA genotype; however, more studies are needed to define the bone phenotype and fracture risk in FPLD2 population fully.
Effects of the Rate of Impaired Insulin Secretion on Bone Mineral Density in Type 1 Diabetes
Authors: Suzuki Masaki , Urai Shin , Fukuoka Hidenori , Hirota Yushi , Yamamoto Masaaki , Yamamoto Naoki , Shichi Hiroki , Fujita Yasunori , Kanie Keitaro , Iguchi Genzo , Takahashi Yutaka , Wataru Ogawa 
Published: May 2021

Abstract
Background: Type 1 Diabetes mellitus (T1DM) is a well-known condition associated with low bone mineral density (BMD) and bone fracture, in which one of the risk factor is impaired endogenous insulin secretion. However, the association between the rate of impaired insulin secretory capacity in T1DM and BMD remains to be elucidated. Objective: To clarify the effect of the rate of impaired insulin secretion on BMD in T1DM. Patients and Methods: This a retrospective single-center cross-sectional study, in which consecutive one-hundred seventy Japanese patients with T1DM at Kobe University Hospital were registered. According to the diagnostic criteria of The Japan Diabetes Society, patients were stratified into three subtypes; acute-onset (AO) (n =51, male 25%, 39 ± 15 years), slowly-progressive (SP) (n =37, male 37%, 57 ± 14 years), and fulminant (F) (n =12, male 33%, 51 ± 15 years) mainly by insulin secretory capacity at onset of T1DM. Lumbar spine (LS) and femoral neck (FN) BMD Z-score between three groups were evaluated. Results: The LS BMD is lower in AO than SP (p =0.03), while no differences were observed compared to F (SP/AO/F; 0.38 ± 1.08/-0.25 ± 0.96/-0.35 ± 1.01). The FN BMD also tended to be lower in AO than in SP (p =0.08) and in F (p =1.00) (SP/AO/F;0.03 ± 1.01/-0.44 ± 0.96/-0.35 ± 0.70). To identify the factors associated with decreased BMD, the multivariate regression analysis was performed using AO and SP. The LS BMD was associated with the pathogenic group (p =0.01). Since a negative correlation was seen between durations and CPR both in AO and SP group (p &lt;0.01, p &lt;0.01), we divided these subjects into following 5 groups; 1 to 4, 5 to 9, 10 to 14, 15 to 19, and more than 20 years. In these groups, the CPR was lower in AO than in SP in 1 to 4 years (p &lt;0.01). Intriguingly, LS BMD was started to decline in 5 to 9 years (p =0.03) and was still continued in 10 to 14 years (p =0.01). In FN, BMD was started to decline in 10 to 14 years (p =0.01), suggesting the BMD decline followed by impaired insulin secretion. However, the difference of both BMD and CPR between AO and SP groups were not seen in more than 15 years group, indicating this tangent BMD difference is link to the difference of insulin secretion. Conclusions: This study firstly showed that pathogenic subtypes of T1DM differently affected on BMD. A detailed examination of each disease period showed that BMD continued to decrease as impaired insulin secretion.