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Journal of Orthopaedic Surgery and... Jun 2024Facet joint degeneration (FJD) is a major cause of low back pain. Parathyroid hormone (PTH) (1-34) is commonly used to treat osteoporosis. However, little is known about...
PURPOSE
Facet joint degeneration (FJD) is a major cause of low back pain. Parathyroid hormone (PTH) (1-34) is commonly used to treat osteoporosis. However, little is known about its effects on FJD induced by estrogen deficiency. This study aims to investigate the effects of PTH (1-34) on FJD induced by estrogen deficiency and the underlying pathogenesis of the disease.
METHODS
Forty 3-month-old female Sprague-Dawley rats were randomly divided into four groups: 30 received bilateral ovariectomy (OVX) followed by 12 weeks of treatment with normal saline, PTH (1-34) or 17β-estradiol (E2), and 10 received sham surgery followed by administration of normal saline. Status and Wnt/β-catenin signaling activity in the cartilage and subchondral bone of the L4-L5 FJs and serum biomarkers were analyzed.
RESULTS
Administration of PTH (1-34) and E2 ameliorated cartilage lesions, and significantly decreased MMP-13 and caspase-3 levels and chondrocyte apoptosis. PTH (1-34) but not E2 significantly increased cartilage thickness, number of chondrocytes, and the expression of aggrecan. PTH (1-34) significantly improved microarchitecture parameters of subchondral bone, increased the expression of collagen I and osteocalcin, and decreased RANKL/OPG ratio. E2 treatment significantly increased the OPG level and decreased the RANKL/OPG ratio in the subchondral bone of ovariectomized rats, but it did not significantly improve the microarchitecture parameters of subchondral bone. Wnt3a and β-catenin expression was significantly reduced in the articular cartilage and subchondral bone in OVX rats, but PTH (1-34) could increase the expression of these proteins. E2 significantly increased the activity of Wnt/β-catenin pathway only in cartilage, but not in subchondral bone. The restoration of Wnt/β-catenin signaling had an obvious correlation with the improvement of some parameters associated with the FJs status.
CONCLUSION
Wnt/β-catenin signaling may be a potential therapeutic target for FJD induced by estrogen deficiency. PTH (1-34) is effective in treating this disease with better efficacy than 17β-estradiol, and the efficacy may be attributed to its restoration of Wnt/β-catenin signaling.
Topics: Animals; Female; Ovariectomy; Rats, Sprague-Dawley; Wnt Signaling Pathway; Parathyroid Hormone; Zygapophyseal Joint; Lumbar Vertebrae; Rats; Estradiol
PubMed: 38877549
DOI: 10.1186/s13018-024-04817-6 -
Brain & Development Jun 2024To investigate whether patients with severe motor and intellectual disability (SMID) have nutritional vitamin D and K insufficiencies and clarify the required vitamin...
PURPOSE
To investigate whether patients with severe motor and intellectual disability (SMID) have nutritional vitamin D and K insufficiencies and clarify the required vitamin supplementation.
METHODS
This prospective observational study enrolled Japanese adults with SMID receiving institutionalized care who underwent blood sampling between February 2020 and February 2022 during annual medical checkups. Serum vitamin K and 25-hydroxy vitamin D (25(OH)D) levels were measured to determine their relationship with serum uncarboxylated osteocalcin (ucOC) levels. Vitamin D and K intake was compared among tube-fed and oral-intake patients with SMID and control participants using corresponding serum levels.
RESULTS
The study included 124 patients with SMID (56 men and 68 women; mean age: 53.0 years) and 20 control participants. Serum 25(OH)D levels were significantly higher in the SMID group than in the control group and the oral intake SMID group than in the tube-fed SMID group. In the tube-fed SMID group, vitamin D intake was lower than the daily recommended intake and correlated with serum 25(OH)D levels. Daily vitamin K intake in the tube-fed group was lower than recommended but not correlated with serum vitamin K levels. Serum ucOC levels were significantly higher in the SMID group than in the control group. Tube feeding was significantly and positively correlated with serum 25(OH)D levels. Serum 25(OH)D levels were not correlated with serum vitamin K levels.
CONCLUSIONS
The SMID group had higher ucOC levels than the control group, possibly owing to daily vitamin K and D deficiencies. Vitamin D supplementation is recommended to decrease ucOC levels.
PubMed: 38876823
DOI: 10.1016/j.braindev.2024.06.001 -
Nanoscale Jun 2024Titanium-based orthopedic implants are gaining popularity in recent years due to their excellent biocompatibility, superior corrosion resistance and lightweight...
Titanium-based orthopedic implants are gaining popularity in recent years due to their excellent biocompatibility, superior corrosion resistance and lightweight properties. However, these implants often fail to perform effectively due to poor osseointegration. Nanosurface modification approaches may help to resolve this problem. In this work, TiO nanotube (NT) arrays were fabricated on commercially available pure titanium (Ti) surfaces by anodization and annealing. Then, zinc (Zn) and strontium (Sr), important for cell signaling, were doped on the NT surface by hydrothermal treatment. This very simple method of Zn and Sr doping takes less time and energy compared to other complicated techniques. Different surface characterization tools such as scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDS), static water contact angle, X-ray diffraction (XRD) and nanoindentation techniques were used to evaluate the modified surfaces. Then, adipose derived stem cells (ADSCs) were cultured with the surfaces to evaluate cell adhesion, proliferation, and growth on the surfaces. After that, the cells were differentiated towards osteogenic lineage to evaluate alkaline phosphatase (ALP) activity, osteocalcin expression, and calcium phosphate mineralization. Results indicate that NT surfaces doped with Zn and Sr had significantly enhanced ADSC adhesion, proliferation, growth, and osteogenic differentiation compared to an unmodified surface, thus confirming the enhanced performance of these surfaces.
PubMed: 38874593
DOI: 10.1039/d4nr01123f -
BMC Endocrine Disorders Jun 2024The aim was to evaluate the effect of metabolic control on bone biomarkers in children with type I diabetes.
BACKGROUND
The aim was to evaluate the effect of metabolic control on bone biomarkers in children with type I diabetes.
MATERIALS AND METHODS
The children were divided into two groups according to their glycated hemoglobin (HbA1c) (%) levels: a group with HbA1c levels < 8% (n = 16) and: a group with HbA1c levels > 8% (n = 18). The serum total oxidative status (TOS) (µmol/L), total antioxidant status (TAS) (mmol/L), alkaline phosphatase (ALP) (IU/L), osteocalcin (OC) (ng/ml), procollagen type-1-N-terminal peptide (P1NP) (ng/ml), and vitamin D (IU) levels and food consumption frequencies were determined.
RESULTS
When patients were classified according to HbA1c (%) levels, those with HbA1c levels < 8% were found to have lower TOS (µmol/L) values (8.7 ± 6.16, 9.5 ± 5.60) and higher serum OC (ng/mL) (24.2 ± 16.92, 22.0 ± 6.21) levels than those with HbA1c levels > 8% (p < 0.05). Regardless of the level of metabolic control, there was a statistically significant association between serum TOS (µmol/L) and P1NP (ng/ml) (p < 0.05) levels, with no group-specific relationship (HbA1c levels <%8 or HbA1c levels >%8).
CONCLUSION
HbA1c and serum TOS levels had an effect on bone turnover biomarkers in individuals with type I diabetes.
Topics: Humans; Diabetes Mellitus, Type 1; Child; Male; Female; Biomarkers; Bone Remodeling; Glycated Hemoglobin; Turkey; Adolescent; Osteocalcin; Alkaline Phosphatase; Procollagen; Prognosis; Peptide Fragments; Oxidative Stress; Vitamin D; Follow-Up Studies
PubMed: 38872156
DOI: 10.1186/s12902-024-01553-0 -
Frontiers in Endocrinology 2024Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially... (Review)
Review
INTRODUCTION
Liraglutide (Lrg), a novel anti-diabetic drug that mimics the endogenous glucagon-like peptide-1 to potentiate insulin secretion, is observed to be capable of partially reversing osteopenia. The aim of the present study is to further investigate the efficacy and potential anti-osteoporosis mechanisms of Lrg for improving bone pathology, bone- related parameters under imageology, and serum bone metabolism indexes in an animal model of osteoporosis with or without diabetes.
METHODS
Eight databases were searched from their inception dates to April 27, 2024. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately.
RESULTS
Seventeen eligible studies were ultimately included in this review. The number of criteria met in each study varied from 4/10 to 8/10 with an average of 5.47. The aspects of blinded induction of the model, blinding assessment of outcome and sample size calculation need to be strengthened with emphasis. The pre-clinical evidence reveals that Lrg is capable of partially improving bone related parameters under imageology, bone pathology, and bone maximum load, increasing serum osteocalcin, N-terminal propeptide of type I procollagen, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P<0.05). Lrg reverses osteopenia likely by activating osteoblast proliferation through promoting the Wnt signal pathway, p-AMPK/PGC1α signal pathway, and inhibiting the activation of osteoclasts by inhibiting the OPG/RANKL/RANK signal pathway through anti-inflammatory, antioxidant and anti-autophagic pathways. Furthermore, the present study recommends that more reasonable usage methods of streptozotocin, including dosage and injection methods, as well as other types of osteoporosis models, be attempted in future studies.
DISCUSSION
Based on the results, this finding may help to improve the priority of Lrg in the treatment of diabetes patients with osteoporosis.
Topics: Liraglutide; Animals; Osteoporosis; Disease Models, Animal; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents; Diabetes Mellitus, Experimental; Bone Density
PubMed: 38868747
DOI: 10.3389/fendo.2024.1378291 -
BMC Endocrine Disorders Jun 2024Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of...
Identification of novel risk factors for postoperative severe hypocalcemia in patients with primary hyperparathyroidism undergoing parathyroidectomy: a case control study.
BACKGROUND
Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of SH. We aimed to identify risk factors for early postoperative SH after PTX in patients with PHPT and to evaluate the predictive value of clinical parameters.
METHODS
A retrospective review of patients with PHPT who underwent PTX between January 2010 and December 2022 was performed. A total of 46 patients were included in the study, with 15 (32.6%) experiencing postoperative SH, 19 (41.3%) having calculi in the ureter or kidney, and 37 (80.4%) having osteoporosis. Patients were divided into SH and non-SH groups based on postoperative serum calcium levels. Preoperative biochemical indicators, bone turnover markers, and renal function parameters were analyzed and correlated with postoperative SH.
RESULTS
Statistically significant (P < 0.05) differences were found in preoperative serum calcium (serum Ca), intact parathyroid hormone, serum phosphorus (serum P), serum Ca/P, percentage decrease of serum Ca, total procollagen type 1 intact N-terminal propeptide, osteocalcin (OC), and alkaline phosphatase levels between the two groups. Multivariate analysis showed that serum P (odds ratio [OR] = 0.989; 95% confidence interval [95% CI] = 0.981-0.996; P = 0.003), serum Ca (OR = 0.007; 95% CI = 0.001-0.415; P = 0.017), serum Ca/P (OR = 0.135; 95% CI = 0.019-0.947; P = 0.044) and OC levels (OR = 1.012; 95% CI = 1.001-1.024; P = 0.036) were predictors of early postoperative SH. The receiver operating characteristic curve analysis revealed that serum P (area under the curve [AUC] = 0.859, P < 0.001), serum Ca/P (AUC = 0.735, P = 0.010) and OC (AUC = 0.729, P = 0.013) had high sensitivity and specificity.
CONCLUSION
Preoperative serum P, serum Ca/P and osteocalcin levels may identify patients with PHPT at risk for early postoperative SH after PTX.
Topics: Humans; Hyperparathyroidism, Primary; Female; Male; Parathyroidectomy; Middle Aged; Risk Factors; Retrospective Studies; Case-Control Studies; Hypocalcemia; Postoperative Complications; Aged; Calcium; Prognosis; Biomarkers; Adult; Follow-Up Studies; Parathyroid Hormone
PubMed: 38867205
DOI: 10.1186/s12902-024-01620-6 -
Nutrition Research and Practice Jun 2024This study evaluated the beneficial effects of an ethanol extract of gum resin (FJH-UBS) in osteoporosis.
BACKGROUND/OBJECTIVES
This study evaluated the beneficial effects of an ethanol extract of gum resin (FJH-UBS) in osteoporosis.
MATERIALS/METHODS
MC3T3-E1 osteoblastic cells and RAW 264.7 osteoclastic cells were treated with FJH-UBS. The alkaline phosphatase (ALP) activity, mineralization, collagen synthesis, osteocalcin content, and Runt-related transcription factor 2 (RUNX2) and Osterix expression were measured in MC3T3-E1 cells. The actin ring structures, tartrate-resistant acid phosphatase (TRAP) activity, and the nuclear factor of activator T-cells, cytoplasm 1 (NFATc1) expression were evaluated in RAW 264.7 cells. Ovariectomized ICR mice were orally administered FJH-UBS for eight weeks. The bone mineral density (BMD) and the serum levels of osteocalcin, procollagen 1 N-terminal propeptide (P1NP), osteoprotegerin, and TRAP 5b were analyzed.
RESULTS
FJH-UBS increased the ALP activity, collagen, osteocalcin, mineralization, and RUNX2 and osterix expression in MC3T3-E1 osteoblastic cells, whereas it decreased the TRAP activity, actin ring structures, and NFATc1 expression in RAW 264.7 osteoclastic cells. In ovariectomy-induced osteoporosis mice, FJH-UBS positively restored all of the changes in the bone metabolism biomarkers (BMD, osteocalcin, P1NP, osteoprotegerin, and TRAP 5b) caused by the ovariectomy.
CONCLUSION
FJH-UBS has anti-osteoporotic activity by promoting osteoblast activity and inhibiting osteoclast activity and , suggesting that FJH-UBS is a potential functional food ingredient for osteoporosis.
PubMed: 38854466
DOI: 10.4162/nrp.2024.18.3.309 -
Clinical and Experimental Reproductive... Jun 2024Osteocalcin (OCN) influences spermatogenesis in conjunction with testosterone and estrogen. OCN facilitates the secretion of testosterone by engaging with G...
OBJECTIVE
Osteocalcin (OCN) influences spermatogenesis in conjunction with testosterone and estrogen. OCN facilitates the secretion of testosterone by engaging with G protein-coupled receptor class C group 6 member A (GPRC6A) on Leydig cells and with androgen receptors on Sertoli cells.
METHODS
Adult mice were assigned to the following groups: control; sham I, which received dimethyl sulfoxide for 5 weeks followed by phosphate-buffered saline for 1 month; azoospermia, which was treated with busulfan (40 mg/kg); sham II, which consisted of azoospermic animals that received phosphate-buffered saline for 1 month beginning at the 5-week mark; and the experimental group, which included azoospermic mice treated with OCN (3 ng/g/day) for 1 month.
RESULTS
In the mice receiving OCN treatment, immunohistochemical analysis revealed increased expression of androgen receptors and GPRC6A, indicative of enhanced spermatogenesis. Additionally, the expression levels of the cyclic adenosine monophosphate-responsive element binding protein 1, steroidogenic acute regulatory protein, and cytochrome P450 family 11 genes were elevated. However, testosterone levels exhibited no significant differences across groups. Morphometric analysis suggests that OCN may play a crucial role in spermatogenesis, as evidenced by its positive effects on germinal cells and the germinal epithelium in the azoospermia group (p<0.05).
CONCLUSION
We conclude that OCN may serve as a beneficial therapeutic agent for male infertility.
PubMed: 38853130
DOI: 10.5653/cerm.2023.06674 -
Applied Radiation and Isotopes :... May 2024In addition to generalised of bone loss and a higher fracture risk, rheumatoid arthritis (RA) causes periarticular bone erosions. Improvements in bone density/erosion...
In addition to generalised of bone loss and a higher fracture risk, rheumatoid arthritis (RA) causes periarticular bone erosions. Improvements in bone density/erosion and turnover may not go hand in hand with a positive clinical response to biological anti-inflammatory drugs assesed by disease activity score 28 (DAS28) in RA patients. This study aimed to understand how biologic anti-inflammatory drugs affect bone density, erosion, and turnover in RA patients. We examined bone mineral density (BMD) and bone turnover biomarkers. The study population consisted of 62 RA patients, 49 (79%) of whom were female and 13 (21%) of whom were male. The patients ranged in age from 40 to 79 years old. The patients' BMD was measured using a DEXA scan, and their plasma levels of bone turnover biomarkers CTX and osteocalcin were quantified utilizing an ELISA. BMD of the hip and lumbar spine in responder patients rose after therapy by 0.001g/cm (0.11 percent, p0.001 vs. before treatment) and 0.0396g/cm (3.96 percent, p0.001 vs. before treatment), respectively. Clinically non-responder patients' DAS28 revealed minor reductions in hip BMD values of -0.008g/cm (-0.78 percent, p0.001 vs. before therapy), as well as an improvement in lumbar spine BMD of 0.03g/cm2 (3.03 percent, p0.001 vs. before treatment). After 12 weeks of therapy, the CTX levels in responder patients dropped from 164 125 pg/ml to 131 129 pg/ml. Osteocalcin levels in non-responder patients increased substantially from 11.6 ng/ml to 14.9 ng/ml after 12 weeks of therapy compared to baseline (p = 0.01). Treatment with biologic anti-inflammatory medicines decreases widespread bone loss in RA patients' hip and lumbar spine. The beneficial effects of therapy on BMD were not associated with changes in disease activity of RA patients. Changes in plasma levels of bone turnover biomarkers such as sCTX and osteocalcin confirmed the treatment's beneficial effects.
PubMed: 38851075
DOI: 10.1016/j.apradiso.2024.111373 -
Chinese Journal of Integrative Medicine Jun 2024To explore the potential of metanephric mesenchymal cells (MMCs) for osteogenesis and naringin's ability to enhance this process and its molecular mechanism.
OBJECTIVE
To explore the potential of metanephric mesenchymal cells (MMCs) for osteogenesis and naringin's ability to enhance this process and its molecular mechanism.
METHODS
Porcine MMCs at 70 days of gestation were used as tool cells, cultured in osteogenic induction medium, identified by immunocytochemistry staining. Osteogenic potential of porcine MMCs and naringin's ability to enhance this process was tested by detecting changes in cell viability, alkaline phosphatase (ALP) activity, the expression of runt-related transcription factor 2 (Runx2), osteopontin (OPN) and osteocalcin (OCN), and the formation of mineralized nodules, and the application of the p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin.
RESULTS
Immunocytochemical staining showed that the cells were Vimentin and Six2(+), E-cadherin and CK-18(-). Naringin can activate the p38 signaling pathway to enhance the osteogenesis of porcine MMCs by increasing cell viability, ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05). The application of p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin, manifested by decreased ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05).
CONCLUSION
Naringin, the active ingredient of Chinese herbal medicine Rhizoma Drynariae for nourishing Shen (Kidney) and strengthening bone, enhances the osteogenic differentiation of renal MMCs through the p38 signaling pathway.
PubMed: 38850479
DOI: 10.1007/s11655-024-3761-1