Context: The adverse skeletal effects of type 1 diabetes (T1D) include deficient bone accrual and lifelong increased fracture risk. The contributors to impaired bone accrual in people with T1D are incompletely understood.
Objective: To determine if urinary calcium excretion is associated with impaired bone accrual in youth with T1D and to characterize the contribution of glycemic control and markers of bone mineral metabolism to urinary calcium excretion.
Design: Observational study.
Participants: 50 participants with T1D aged 6-20 years completed a 12-month longitudinal study of bone accrual. A second cohort of 99 similarly aged participants with T1D completed cross-sectional 24-hr urine and blood collections.
Main Outcome Measure: Whole body less head bone mineral content (WBLH BMC) velocity Z-score and fractional excretion of calcium (FeCa).
Results: Participants in the bone accrual cohort had lower WBLH BMC velocity compared to a healthy reference dataset (Z-score -0.3 ± 1.0, p=0.03). FeCa was negatively associated with WBLH BMC velocity Z-score, ρ= -0.47, p=0.001. In the urinary calcium excretion cohort, intact parathyroid hormone (β= -0.4, p=0.01), beta c-telopeptide (β=0.35, p=0.007), and either hemoglobin A1c (HbA1c, β=0.08, p=0.03) or urine fractional glucose excretion (β=0.07, p=0.03) were associated with FeCa in multivariable regression models that included known determinants of urinary calcium excretion.
Conclusions: Urinary calcium excretion was negatively associated with bone accrual in this cohort of youth with T1D. Mechanistic studies are needed to determine if interventions to reduce urinary calcium excretion could increase bone accrual and reduce skeletal fragility in people with T1D.
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http://dx.doi.org/10.1210/clinem/dgae660 | DOI Listing |
J Pediatr (Rio J)
January 2025
Faculdade de Medicina da Universidade de São Paulo (FMUSP), Instituto da Criança, Unidade de Endocrinologia Pediátrica, São Paulo, São Paulo, Brazil.
Objective: Discontinuation of growth hormone therapy (rhGH) upon completion of linear growth may adversely affect bone mineral density and content (BMD/BMC) in adolescents with childhood-onset GH deficiency (CO-GHD) and predisposition to osteoporosis. Although the benefits of weight-dependent somatropin high doses over bone gain are established, little is known about fixed low doses. We analyzed the impact of non-weight-based low-dose somatropin on bone accrual during the transition among CO-DGH patients, treated since childhood.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Department of Bioactive Material Sciences, Research Center of Bioactive Materials, Jeonbuk National University, Jeonju 54896, South Korea; Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Jeonbuk National University, Jeonju 54896, South Korea. Electronic address:
Dysregulated Wnt signaling causes age-related characteristics such as oxidative stress, stem cell senescence, and abnormal bone homeostasis. Here we explored whether supplemental n-acetyl-l-cysteine (NAC) recovers the age-associated complications relative to osteoblastic Wntless (Wls) ablation and examined the possible mechanisms therein. For this work, we administered Col2.
View Article and Find Full Text PDFPLoS One
December 2024
Department of Biology, Indiana University Indianapolis, Indianapolis, Indiana, United States of America.
Studies with genetically modified mice have implicated the transcriptional regulator STAT3 as a key modulator of bone development. STAT3-OKO knockout mouse lines were generated in two genetic backgrounds, pure C57BL/6 (STAT3-OKO-BL) and mixed C57BL/6, CD1 (STAT3-OKO-M). Both lines exhibited defective postnatal bone development resulting in reduced body weight and shortened femurs that displayed low bone mineral density as well as cortical widening and thinning in the diaphyseal region.
View Article and Find Full Text PDFJBMR Plus
January 2025
Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
The R47H variant of the triggering receptor expressed on myeloid cells 2 (TREM2) is a risk factor for Alzheimer's disease in humans and leads to lower bone mass accrual in female but not male 12-mo-old mice. To determine whether, as with aging, gonadectomy results in sex-specific musculoskeletal effects, gonad removal or SHAM surgery was performed in 4-mo-old TREM2 mice and WT male and female littermates ( = 10-12/group), with sexes analyzed separately. Body weight was lower in males, but higher in females after gonadectomy, independently of their genotype.
View Article and Find Full Text PDFLancet Oncol
January 2025
Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence, Florence, Italy; Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.
Background: Optimal therapy following breast-conserving surgery in older adults with low-risk, early-stage breast cancer remains uncertain. The EUROPA trial aims to compare the effects of radiotherapy and endocrine therapy as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population.
Methods: This non-inferiority, phase 3, randomised study was conducted at 18 academic hospitals across Italy (17 centres) and Slovenia (one centre).
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