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Journal of Dairy Science Dec 2023Many multiparous dairy cows experience subclinical hypocalcemia (SCH) in the immediate postpartum period as they adapt to the demands of lactation. Furthermore,...
Many multiparous dairy cows experience subclinical hypocalcemia (SCH) in the immediate postpartum period as they adapt to the demands of lactation. Furthermore, differing dynamics of SCH in the days following parturition are associated with varied health and production outcomes, with cows experiencing transient SCH producing more milk and facing fewer negative health events than cows with delayed or persistent SCH. Our objectives were to describe differences in mediators of calcium (Ca) homeostasis between cows experiencing differing Ca dynamics postpartum. A prospective cohort of 89 multiparous Holstein cows from 2 herds in New York were classified into 1 of 4 SCH groups based on mean serum total Ca (tCa) at 1 and 4 d in milk (DIM): normocalcemic (NC; [tCa] >1.89 mmol/L at 1 DIM and >2.25 mmol/L at 4 DIM, n = 30); transient SCH (tSCH; [tCa] ≤1.89 mmol/L at 1 DIM and >2.25 mmol/L at 4 DIM, n = 12); delayed SCH (dSCH; [tCa] >1.89 mmol/L at 1 DIM and ≤2.25 mmol/L at 4 DIM, n = 23); and persistent SCH (pSCH; [tCa] ≤1.89 mmol at 1 DIM and ≤2.25 mmol/L at 4 DIM, n = 24). Blood samples were collected at -5, -1, 1 through 5, 7, and 10 DIM and analyzed for tCa, parathyroid hormone (PTH), and serotonin. Repeated measures ANOVA models were used to analyze differences between SCH groups and changes over time for tCa, PTH, and serotonin. During the prepartum period, tCa was greater in the NC, tSCH, and dSCH cows as compared with the pSCH cows and there was marginal evidence for a difference in PTH between SCH groups. Postpartum tCa varied over time between SCH groups. Mean postpartum (95% confidence interval) tCa for respective SCH groups were NC = 2.32 (2.28, 2.35) mmol/L; tSCH = 2.20 (2.14, 2.25) mmol/L; dSCH = 2.17 (2.13, 2.21) mmol/L; and pSCH = 2.03 (1.99, 2.07) mmol/L. Mean concentrations of PTH in the postpartum period were NC = 70.1 (66.2, 74.4) pmol/L; tSCH = 72.1 (66.1, 79.2); dSCH = 75.8 (70.8, 81.5) pmol/L; and pSCH = 77.7 (72.4, 83.9) pmol/L. Serotonin was similar between SCH groups pre- and postpartum and followed a cyclical pattern from 1 to 10 DIM. Our results agreed with our hypothesis that differences in postpartum PTH might exist between cows experiencing different dynamics of SCH in the early lactation period; however, further studies are needed to confirm this difference. If true, this would suggest that Ca homeostasis may be disrupted in cows with dSCH and pSCH. Gaining a better understanding of these modulatory differences may aid in the prevention, management, and treatment of SCH.
Topics: Animals; Cattle; Female; Pregnancy; Calcium; Cattle Diseases; Hypocalcemia; Lactation; Milk; Parathyroid Hormone; Postpartum Period; Prospective Studies; Serotonin
PubMed: 37690732
DOI: 10.3168/jds.2022-23175 -
Cytopathology : Official Journal of the... Nov 2023The cytomorphological features of parathyroid tissue (PTT) may overlap with those of thyroid lesions, thus posing a diagnostic challenge. In this retrospective study, we... (Review)
Review
OBJECTIVE
The cytomorphological features of parathyroid tissue (PTT) may overlap with those of thyroid lesions, thus posing a diagnostic challenge. In this retrospective study, we reviewed our institutional experience in using parathyroid hormone (PTH) immunocytochemistry (ICC) to substantiate the diagnosis of PTT on fine needle aspiration (FNA).
METHODS
Our pathology database was searched for FNA cases in which PTH ICC was performed between 1 January 2015 and 31 March 2022. PTH ICC was performed on a ThinPrep slide in cases with a clinical suspicion of PTT or with cytomorphological features raising the possibility of PTT. Patients' clinicopathological characteristics, PTH ICC results, cytological diagnoses, and surgical follow-ups, if available, were reviewed and analysed.
RESULTS
The study cohort included 103 cases clinically designated as thyroid (n = 85, 82.5%), parathyroid (n = 11, 10.7%) and neck soft tissue (n = 7, 6.8%). PTH immunostaining was negative, positive, and indeterminate in 53 (51.5%), 27 (26.2%), and 23 (22.3%) cases, respectively. Surgical follow-up was available in 27 (26.2%) cases, including 17 thyroid lesions and 10 PTT cases. All positive PTH cases were confirmed to be PTT, while all but one of the negative PTH cases were non-PTT on follow-up. The calculated sensitivity, specificity, positive and negative predictive values were 85.7%, 100%, 100% and 93.3%, respectively.
CONCLUSION
Our study demonstrates that PTH ICC performed on additional ThinPrep slides is a valuable adjunct test in FNA samples with a differential diagnosis of PTT vs non-PTT. Low cellularity may be a limiting factor in the accurate assessment of PTH by ICC.
Topics: Humans; Parathyroid Hormone; Biopsy, Fine-Needle; Immunohistochemistry; Retrospective Studies; Parathyroid Neoplasms
PubMed: 37534757
DOI: 10.1111/cyt.13283 -
Frontiers in Cellular and Infection... 2023Diabetes mellitus (DM) impairs fracture healing and is associated with susceptibility to infection, which further inhibits fracture healing. While intermittent...
INTRODUCTION
Diabetes mellitus (DM) impairs fracture healing and is associated with susceptibility to infection, which further inhibits fracture healing. While intermittent parathyroid hormone (1-34) (iPTH) effectively improves fracture healing, it is unknown whether infection-associated impaired fracture healing can be rescued with PTH (teriparatide).
METHODS
A chronic diet-induced type 2 diabetic mouse model was used to yield mice with decreased glucose tolerance and increased blood glucose levels compared to lean-fed controls. Methicillin-resistant (MRSA) was inoculated in a surgical tibia fracture model to simulate infected fracture, after which mice were treated with a combination of antibiotics and adjunctive teriparatide treatment. Fracture healing was assessed by Radiographic Union Scale in Tibial Fractures (RUST), micro-computed tomography (μCT), biomechanical testing, and histology.
RESULTS
RUST score was significantly poorer in diabetic mice compared to their lean nondiabetic counterparts. There were concomitant reductions in micro-computed tomography (μCT) parameters of callus architecture including bone volume/total volume, trabecular thickness, and total mineral density in type 2 diabetes mellitus (T2DM) mice. Biomechanicaltesting of fractured femora demonstrated diminished torsional rigidity, stiffness, and toughness to max torque. Adjuvant teriparatide treatment with systemic antibiotic therapy improved numerous parameters of bone microarchitecture bone volume, increased connectivity density, and increased trabecular number in both the lean and T2DM group. Despite the observation that poor fracture healing in T2DM mice was further impaired by MRSA infection, adjuvant iPTH treatment significantly improved fracture healing compared to antibiotic treatment alone in infected T2DM fractures.
DISCUSSION
Our results suggest that teriparatide may constitute a viable adjuvant therapeutic agent to improve bony union and bone microarchitecture to prevent the development of septic nonunion under diabetic conditions.
Topics: Mice; Animals; Fracture Healing; Methicillin-Resistant Staphylococcus aureus; Teriparatide; Diabetes Mellitus, Type 2; Diabetes Mellitus, Experimental; X-Ray Microtomography; Parathyroid Hormone
PubMed: 37829606
DOI: 10.3389/fcimb.2023.1230568 -
Clinica Chimica Acta; International... Aug 2023Chronic kidney disease-mineral bone disease (CKD-MBD) is a major complication of CKD. Bone turnover markers (BTMs) are important for clinicians to evaluate and manage...
BACKGROUND
Chronic kidney disease-mineral bone disease (CKD-MBD) is a major complication of CKD. Bone turnover markers (BTMs) are important for clinicians to evaluate and manage patients with CKD-MBD. This study aimed to assess BTMs in patients with CKD and their correlation with parathyroid hormone (PTH) and other clinical characteristics of CKD.
METHODS
A total of 408 subjects were included in this study. The serum BTMs including N-terminal midfragment osteocalcin (N-MID OC), β-isomerized C-terminal telopeptides (β-CTX), and total procollagen type 1 amino-terminal propeptide (tPINP) were measured. Spearman correlation and multiple stepwise regression models were used to investigate the association of N-MID OC, β-CTX, and tPINP with the clinical characteristics of CKD patients.
RESULTS
BTMs was no significant difference between non-CKD and CKD stages 1, 2, and 3. However, N-MID OC, β-CTX were significantly increased in patients with CKD stage 4 compared to non-CKD patients and patients with CKD stages 1, 2, and 3. Compared with non-dialysis dependent (NDD)-CKD stage 5, BTMs were significantly higher in dialysis patients. The estimated glomerular filtration rate was negatively associated with N-MID OC (r = -0.479, P < 0.001), β-CTX (r = -0.474, P < 0.001), and tPINP (r = -0.375, P < 0.001). Multiple analysis showed that N-MID OC (β = 0.67, P < 0.001), β-CTX (β = 0.64, P < 0.001), and tPINP (β = 0.81, P < 0.001) were independently associated with PTH. CKD patients with secondary hyperparathyroidism (SHPT) have higher β-CTX (P < 0.05), and N-MID OC (P < 0.05) than patients with non-SHPT.
CONCLUSIONS
BTMs in advanced CKD stages were significantly higher than in the early disease stages. PTH level was independently and positively associated with the BTM levels in patients with CKD. In the advanced stage of CKD, β-CTX and N-MID OC levels were significantly higher in those with SHPT than those with non-SHPT.
Topics: Humans; Bone Diseases; Bone Remodeling; Chronic Kidney Disease-Mineral and Bone Disorder; Kidney Failure, Chronic; Parathyroid Hormone
PubMed: 37619948
DOI: 10.1016/j.cca.2023.117518 -
BMC Nephrology Sep 2023Patients with kidney failure experience derangements of circulating markers of mineral metabolism and dysregulation of skeletal and cardiovascular physiology which... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with kidney failure experience derangements of circulating markers of mineral metabolism and dysregulation of skeletal and cardiovascular physiology which results in high mortality rate in these patients. This study aimed to evaluate the effect of intradialytic exercise on regulation of these abnormalities in patients receiving chronic hemodialysis (HD).
METHODS
In this randomized controlled trial conducted in an HD center in Iran, adult patients receiving chronic HD were randomized to intradialytic exercise (60 min) in the second hour of thrice weekly dialysis for 6 months (intervention) or no intradialytic exercise (control). The primary outcomes were serum calcium, serum phosphorous and parathyroid hormone levels. Secondary outcomes were serum alkaline phosphatase and calcium-phosphorous product.
RESULTS
The study included 44 participants randomized to intervention (n = 22) or control (n = 22). During the 6-month intervention period, significant between-group changes were observed in all primary and secondary outcomes between the intervention and control groups. Statistical analyses reveal a significant increase in serum calcium (P < 0.05) as well as a significant decrease in serum phosphorous, parathyroid hormone, alkaline phosphatase and calcium-phosphorous product (P < 0.05).
CONCLUSION
Intradialytic exercise performed for at least 60 min during thrice weekly dialysis sessions improves bone mineral metabolism in adult patients receiving HD. Further studies should focus on observing and comparing the effect of different types of exercise on bone mineral disorders and all-cause mortality in HD patients.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04916743, Registered on 08/06/2021. Registered trial name: The Effect of Intradialytic Exercise on Calcium, Phosphorous and Parathyroid Hormone: A Randomized Controlled Trial.
Topics: Adult; Humans; Calcium; Parathyroid Hormone; Phosphorus; Alkaline Phosphatase; Renal Dialysis; Calcium, Dietary; Bone Diseases
PubMed: 37730530
DOI: 10.1186/s12882-023-03327-7 -
Parathyroid-on-a-chip simulating parathyroid hormone secretion in response to calcium concentration.Lab on a Chip Jun 2024The parathyroid gland is an endocrine organ that plays a crucial role in regulating calcium levels in blood serum through the secretion of parathyroid hormone (PTH)....
The parathyroid gland is an endocrine organ that plays a crucial role in regulating calcium levels in blood serum through the secretion of parathyroid hormone (PTH). Hypoparathyroidism is a chronic disease that can occur due to parathyroid defects, but due to the difficulty of creating animal models of this disease or obtaining human normal parathyroid cells, the evaluation of parathyroid functionality for drug development is limited. Although parathyroid-like cells that secrete PTH have recently been reported, their functionality may be overestimated using traditional culture methods that lack similarities, particularly vascularization. To overcome these limitations, we obtained parathyroid organoids from tonsil-derived mesenchymal stem cells (TMSCs) and fabricated a parathyroid-on-a-chip, capable of simulating PTH secretion based on calcium concentration. This chip exhibited differences in PTH secretion according to calcium concentration and secreted PTH within the range of normal serum levels. In addition, branches of organoids, which are difficult to observe in animal models, were observed in this chip. This could serve as a guideline for successful engraftment in implantation therapies in the future.
Topics: Parathyroid Hormone; Calcium; Humans; Lab-On-A-Chip Devices; Parathyroid Glands; Mesenchymal Stem Cells; Organoids; Cells, Cultured
PubMed: 38836406
DOI: 10.1039/d4lc00249k -
Ultrasonics Jul 2023Due to aging and long-term estrogen deficiency, postmenopausal women suffer muscle atrophy (MA), which is characterized by decreased muscle mass and muscle quality....
Due to aging and long-term estrogen deficiency, postmenopausal women suffer muscle atrophy (MA), which is characterized by decreased muscle mass and muscle quality. Low-intensity pulsed ultrasound (LIPUS) is an acoustic wave inducing biological effects mainly by the mechanical stimulation and used as a non-invasive physical therapy for muscle repair. Parathyroid hormone (PTH) is an 84-amino-acid polypeptide, and its bioactive fragment [PTH (1-34)] has potential application in the treatment of MA. We speculate that the combination of physical therapy (i.e., the LIPUS) and regulatory hormone (i.e., the PTH) would be more effective in the treatment of MA. The objective of this study was to evaluate the individual and combined effects of LIPUS and PTH therapy on MA in estrogen deficiency mice. Seventy 8-week-old female C57BL/6J mice were used in this study and the MA model was induced by an intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD) for 20 consecutive days. The VCD-induced MA mice were randomly divided into MA, LIPUS, PTH and LIPUS + PTH (Combined) groups (n = 10/group). In the LIPUS group, the mice were treated by LIPUS in bilateral quadriceps muscles for 20 min, five times a week for 6 weeks. In the PTH group, the mice received subcutaneous injection of PTH (1-34) (80 ug/kg/d) five times a week, for 6 weeks. In the Combined group, the PTH was administrated 30 min before each LIPUS session. Hematoxylin-eosin (H&E) staining, serum biochemical analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to evaluate the therapeutic effects of related treatments. The results showed that the MA mice had a disordered estrus cycle, significantly decreased muscle mass and myofibers cross-sectional area (CSA). After treatments, LIPUS, PTH and Combined groups had a significantly increased CSA, compared with the MA mice without treatment. In addition, Combined group had a significantly increased mRNA expression of Pax7, MyoD and MyoG, compared with LIPUS and PTH monotherapy groups. Our findings indicated that the combination of LIPUS and PTH treatment improves muscle regeneration ability, which might have potential for treating MA in postmenopausal women.
Topics: Mice; Female; Animals; Parathyroid Hormone; Mice, Inbred C57BL; Muscular Atrophy; Ultrasonic Waves; Ultrasonic Therapy; Estrogens
PubMed: 36944299
DOI: 10.1016/j.ultras.2023.106984 -
Advanced Biology Dec 2023Osteocytes have recently been identified as a new regulator of bone remodeling, but the detailed mechanism of their differentiation from osteoblasts remains unclear. The...
Osteocytes have recently been identified as a new regulator of bone remodeling, but the detailed mechanism of their differentiation from osteoblasts remains unclear. The purpose of this study is to identify cell cycle regulators involved in the differentiation of osteoblasts into osteocytes and determine their physiological significance. The study uses IDG-SW3 cells as a model for the differentiation from osteoblasts to osteocytes. Among the major cyclin-dependent kinases (Cdks), Cdk1 is most abundantly expressed in IDG-SW3 cells, and its expression is down-regulated during differentiation into osteocytes. Inhibition of CDK1 activity reduces IDG-SW3 cell proliferation and differentiation into osteocytes. Osteocyte and Osteoblast-specific Cdk1 knockout in mice (Dmp1-Cdk1 ) results in trabecular bone loss. Pthlh expression increases during differentiation, but inhibiting CDK1 activity reduces Pthlh expression. Parathyroid hormone-related protein concentration is reduced in the bone marrow of Dmp1-Cdk1 mice. Four weeks of Parathyroid hormone administration partially recovers the trabecular bone loss in Dmp1-Cdk1 mice. These results demonstrate that Cdk1 plays an essential role in the differentiation from osteoblast to osteocyte and the acquisition and maintenance of bone mass. The findings contribute to a better understanding of the mechanisms of bone mass regulation and can help develop efficient therapeutic strategies for osteoporosis treatment.
Topics: Animals; Mice; Cell Differentiation; Cell Proliferation; Osteoblasts; Osteocytes; Parathyroid Hormone
PubMed: 37424388
DOI: 10.1002/adbi.202300136 -
Current Rheumatology Reports May 2024The purpose of this literature review was to determine if medications used to treat osteoporosis are also effective for treating osteoarthritis (OA). (Review)
Review
PURPOSE OF REVIEW
The purpose of this literature review was to determine if medications used to treat osteoporosis are also effective for treating osteoarthritis (OA).
RECENT FINDINGS
A total of 40 relevant articles were identified. Studies were categorized into those (1) discussing estrogen and selective estrogen receptor modulators (SERMs), (2) bisphosphonates, (3) parathyroid hormone (PTH) analogs, and (4) denosumab, and (5) prior review articles. A large amount of evidence suggests that estrogen and SERMs are effective at reducing OA symptoms and disease progression. Evidence suggests that bisphosphonates, the most common medications used to treat osteoporosis, can reduce OA symptoms and disease progression. In vivo studies suggest that PTH analogs may improve the cartilage destruction associated with OA; however, few human trials have examined its use for OA. Denosumab is approved to treat osteoporosis, bone metastases, and certain types of breast cancer, but little study has been done with respect to its effect on OA. The current evidence indicates that medications used to treat osteoporosis are also effective for treating OA. Estrogen, SERMs, and bisphosphonates have the most potential as OA therapies. Less is known regarding the effectiveness of PTH analogs and denosumab in OA, and more research is needed.
Topics: Humans; Disease Progression; Osteoarthritis; Bone Density Conservation Agents; Female; Diphosphonates; Denosumab; Selective Estrogen Receptor Modulators; Osteoporosis, Postmenopausal; Parathyroid Hormone; Estrogens; Antibodies, Monoclonal, Humanized; Treatment Outcome
PubMed: 38372871
DOI: 10.1007/s11926-024-01139-8 -
Frontiers in Endocrinology 2024Magnesium (Mg), a nutritional element which is essential for bone development and mineralization, has a role in the progression of osteoporosis. Osteoporosis is a... (Review)
Review
Magnesium (Mg), a nutritional element which is essential for bone development and mineralization, has a role in the progression of osteoporosis. Osteoporosis is a multifactorial disease characterized by significant deterioration of bone microstructure and bone loss. Mg deficiency can affect bone structure in an indirect way through the two main regulators of calcium homeostasis (parathyroid hormone and vitamin D). In human osteoblasts (OBs), parathyroid hormone regulates the expression of receptor activator of nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) to affect osteoclast (OC) formation. In addition, Mg may also affect the vitamin D3 -mediated bone remodeling activity. vitamin D3 usually coordinates the activation of the OB and OC. The unbalanced activation OC leads to bone resorption. The RANK/RANKL/OPG axis is considered to be a key factor in the molecular mechanism of osteoporosis. Mg participates in the pathogenesis of osteoporosis by affecting the regulation of parathyroid hormone and vitamin D levels to affect the RANK/RANKL/OPG axis. Different factors affecting the axis and enhancing OC function led to bone loss and bone tissue microstructure damage, which leads to the occurrence of osteoporosis. Clinical research has shown that Mg supplementation can alleviate the symptoms of osteoporosis to some extent.
Topics: Humans; Osteoporosis; Magnesium; Animals; Parathyroid Hormone; RANK Ligand; Osteoblasts; Bone Remodeling; Vitamin D; Magnesium Deficiency; Osteoclasts; Osteoprotegerin
PubMed: 38904051
DOI: 10.3389/fendo.2024.1406248