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Cureus Oct 2021Nowadays, chronic kidney disease (CKD) and osteoporosis have become crucial health-related issues globally. CKD-induced osteoporosis is a systemic disease characterized... (Review)
Review
Nowadays, chronic kidney disease (CKD) and osteoporosis have become crucial health-related issues globally. CKD-induced osteoporosis is a systemic disease characterized by the disruption of mineral, hormone, and vitamin homeostasis that elevates the likelihood of fracture. Here, we review recent studies on the association of CKD and osteoporosis. In particular, we focus on the pathogenesis of CKD-associated osteoporosis, including the homeostasis and pathways of several components such as parathyroid hormone, calcium, phosphate, vitamin D, fibroblast growth factor, and klotho, as well as abnormal bone mineralization, remodeling, and turnover. In addition, we explore the diagnostic tools and possible therapeutic approaches for the management and prevention of CKD-associated osteoporosis. Patients with CKD show higher osteoporosis prevalence, greater fracture rate, increased morbidity and mortality, and an elevated occurrence of hip fracture. We also rule out that increased severity of CKD is related to a more severe condition of osteoporosis. Furthermore, supplements such as calcium and vitamin D as well as lifestyle modifications such as exercise and cessation of smoking and alcohol help in fracture prevention. However, new approaches and advancements in treatment are needed to reduce the fracture risk in patients with CKD. Therefore, further collaborative multidisciplinary research is needed in this regard.
PubMed: 34692259
DOI: 10.7759/cureus.18488 -
Reviews in Endocrine & Metabolic... Jun 2022Cinacalcet, a positive allosteric modulator of the calcium sensing receptor (CaSR) reduces parathyroid hormone (PTH) secretion by increasing the sensitivity of the CaSR... (Meta-Analysis)
Meta-Analysis Review
Cinacalcet, a positive allosteric modulator of the calcium sensing receptor (CaSR) reduces parathyroid hormone (PTH) secretion by increasing the sensitivity of the CaSR on parathyroid cells. We conducted a systematic review and meta-analysis on the safety and efficacy of cinacalcet in Primary Hyperparathyroidism (PHPT). MEDLINE, Embase, BIOSIS, and the Cochrane Library were searched for published articles (from database inception to Sept 2020). All double-blind RCTs and cohort studies that reported data on the efficacy and safety of cinacalcet therapy in individuals ≥ 18 with PHPT were included. Random effect meta-analysis was performed to estimate the efficacy of cinacalcet in lowering serum calcium and PTH levels compared with placebo. 4 RCTs (177 participants) and 17 cohort studies (763 participants) were eligible for final analysis. Pooled results from the RCTs suggest that, when compared to placebo and administered for up to 28 weeks, cinacalcet normalizes serum calcium (≤ 10.3 mg/dl) in patients with PHPT [RR 20 (95% CI 6.04 - 68.52, I = 0%, p < 0·00001)]. Serum PTH levels decreased significantly after 2 weeks and up to 28 weeks after treatment with cinacalcet. In the pooled analysis of the 17 cohort studies, serum calcium levels normalized in 76% (95% CI 66% to 86%; I = 92%, p < 0·00001) of patients regardless of the duration of treatment. In most studies, PTH levels decreased by 13% to 55%. No RCT reported on BMD as a primary or secondary outcome, and no improvement in BMD was noted in the 2 non-randomized studies that reported densitometric findings. No significant difference in urinary calcium was noted with cinacalcet therapy in either the RCTs or non-randomized studies. There was no significant difference in overall adverse events (AE) (RD 0.01, 95% CI -0.07 to 0.26) compared to placebo noted in the RCTs. In the non-randomized studies, pooled weighted AE rate was 45% (95% CI 32 to 59%). Risk of bias was low in 2/4 RCTs and 6/17cohort studies; risk was intermediate in 2/4 RCTs and 8/17 cohort studies, and risk was high in 3/17 cohort studies. In PHPT, cinacalcet lowers serum calcium and PTH with greater effects on calcium than on PTH in the short term. In the doses reported, the drug is safe with tolerable side effects. These findings can help inform targeted medical therapy of PHPT in those for whom lowering the serum calcium is indicated and for whom parathyroidectomy is not an option.
Topics: Cinacalcet; Humans; Hyperparathyroidism, Primary; Randomized Controlled Trials as Topic
PubMed: 35041148
DOI: 10.1007/s11154-021-09694-6 -
Diabetes & Metabolic Syndrome Aug 2023Studies have suggested that high parathyroid hormone (PTH) was associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH),... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Studies have suggested that high parathyroid hormone (PTH) was associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), although the results from existing studies are inconsistent. Using systematic review and meta-analysis, we aimed to determine the association of PTH with NAFLD and NASH.
METHODS
Potentially eligible studies were identified from Embase and Medline databases from using search strategy consisting of terms for "NAFLD/NASH", and "PTH". Eligible study must consist of one group of patients with NAFLD/NASH and another group without NAFLD/NASH. The study must provide mean ± SD PTH in both groups. We extracted such data to calculate mean difference (MD). Pooled MD was then calculated by combining MDs of each study using random-effects model. Funnel plot was used to assess for the presence of publication bias.
RESULTS
A total of 388 articles were identified. After systematic review, 12 studies fulfilled the eligibility criteria and were included into the meta-analysis. The meta-analysis of 10 studies revealed the significant association between high PTH and NAFLD, with the pooled MD of 5.479 (95%CI 0.947-10.011, I 82.4%). The funnel plot was symmetric and did not suggest publication bias. The meta-analysis of 4 studies revealed the non-significant association between high PTH and NASH, with the pooled MD of 11.955 (95%CI -4.703 - 28.614, I 81.0%).
CONCLUSIONS
High PTH level is significantly associated with NAFLD and can be used as a marker of NAFLD. However, high PTH level is non-significantly associated with NASH. Further studies are needed to increase the sample size and eliminate the confounding factors.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Parathyroid Hormone
PubMed: 37451113
DOI: 10.1016/j.dsx.2023.102827 -
Bone Mar 2024Neurofibromatosis type 1 (NF1) is a genetic autosomal neurocutaneous syndrome correlated with skeletal dysplasia and defects in the osseous microarchitecture. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Neurofibromatosis type 1 (NF1) is a genetic autosomal neurocutaneous syndrome correlated with skeletal dysplasia and defects in the osseous microarchitecture. The physiological mechanism for the development of NF1-related bone abnormal turnover is still unclear.
OBJECTIVES
A meta-analysis was performed to investigate the effects of NF1 on bone mineral density (BMD) and osseous metabolic indices in order to provide clinical evidence for the pathogenesis of the associated skeletal deformities.
METHODS
A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed/Medline and Web of Science databases from the date of inception of each database through to 10 September 2023. Specific inclusion and exclusion criteria were applied for the identification of studies examining the effects of NF1 on bone strength and metabolism. The Newcastle-Ottawa and Jadad scales were applied to assess the quality of the included studies. RevMan 5.3 software was used for the analysis of the data, and MedCalc was applied to examine publication bias.
RESULTS
Overall, 13 studies met the inclusion criteria comprised of 5 cross-sectional, 6 case-control and 2 retrospective studies. 703 patients and 973 healthy subjects formed the NF1 and control group, respectively. The results of the meta-analysis displayed that lumbar (SMD = -3.85, 95%CI = -7.53 to -0.18, Z = 2.05, p = 0.04) and femoral (SMD = -4.78, 95%CI = -8.86 to -0.69, Z = 2.29, p = 0.02) BMD was reduced in the NF1 group. Both in children and adults the serum levels of 25 hydroxyvitamin D3 were also decreased in NF1 group, but without any statistical significance (SMD = -0.62, 95%CI = -1.34 to -0.11, Z = 1.66, p = 0.10). Serum Parathyroid hormone (PTH) (SMD = 0.73, 95%CI = 0.31 to 1.15, Z = 3.43, p = 0.0006) and C-telopeptide of type 1 collagen (CTX) (SMD = 0.82, 95%CI = 0.33 to 1.30, Z = 3.29, p = 0.001) were elevated in NF1 patients, while serum calcium (SMD = -0.10, 95%CI = -0.74 to 0.53, Z = 0.32, p = 0.75) phosphorous (SMD = 0.33, 95%CI = -0.38 to 1.05, Z = 0.92, p = 0.36), alkaline phosphatase (ALP) (SMD = -0.36, 95%CI = -0.77 to 0.05, Z = 1.71, p = 0.09), osteocalcin (SMD = 1.81, 95%CI = -0.37 to -3.98, Z = 1.63, p = 0.10) and bone formation markers (SMD = 0.28, 95%CI = -0.37 to -0.94, Z = 0.85, p = 0.39) were not.
CONCLUSION
NF1 is associated with decreased BMD at the lumbar spine and femur. Taking into account that the serum levels of PTH, CTX were increased whereas the concentrations of vitamin D, calcium, phosphorous, ALP, osteocalcin and bone formation markers were not altered significantly in the NF1 patients compared with the healthy subjects, a vitamin D independent dysregulated bone cellular activity could be considered.
STUDY REGISTRATION
Registered on PROSPERO (CRD42023424751).
Topics: Adult; Child; Humans; Bone Density; Vitamin D; Neurofibromatosis 1; Calcium; Retrospective Studies; Cross-Sectional Studies; Osteocalcin; Parathyroid Hormone; Vitamins
PubMed: 38141750
DOI: 10.1016/j.bone.2023.116992 -
Orthopaedic Journal of Sports Medicine Jan 2024Deficiency in vitamin D has been shown to increase the risk of injury. (Review)
Review
BACKGROUND
Deficiency in vitamin D has been shown to increase the risk of injury.
PURPOSE
To synthesize current placebo-controlled randomized trials investigating the effect of vitamin D supplementation in elite athletes on (1) aerobic capacity; (2) anaerobic measures, such as strength, speed, and anaerobic power; (3) serum biomarkers of inflammation; and (4) bone health.
STUDY DESIGN
Systematic review; Level of evidence, 1.
METHODS
A literature search was conducted on November 30, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included were randomized, placebo-controlled studies of longer than 2 weeks on subjects with active participation in organized sport. Excluded were nonrandomized controlled trial study designs, vitamin D administration routes other than oral, studies that did not use vitamin D supplementation as the sole intervention, and studies with nonathletic or military populations.
RESULTS
Out of 2331 initial studies, 14 studies (482 athletes) were included. Of the 3 studies that assessed aerobic capacity, 2 demonstrated significantly greater improvements in maximal oxygen uptake and physical working capacity-170 ( < .05) in supplemented versus nonsupplemented athletes. Measurements of anaerobic power and strength were consistently increased in supplemented groups compared with nonsupplemented groups in 5 out of the 7 studies that assessed this. Of the 6 studies that assessed sprint speed, 4 found no significant difference between supplemented and nonsupplemented groups. Aside from 1 study that found significantly lower interleukin-6 levels in supplemented athletes, measures of other inflammatory cytokines were not affected consistently by supplementation. The 4 studies that assessed markers of bone health were conflicting regarding benefits of supplementation. One study found demonstrated improvements in bone mineral density in response to supplementation ( = .02) compared with control whereas another found no significant difference between supplemented and nonsupplemented groups. However, in 3 other studies, serum biomarkers of bone turnover such as bone-specific alkaline phosphatase, parathyroid hormone, and N-terminal telopeptide appeared to be higher in subjects with lower serum vitamin D levels ( < .05).
CONCLUSION
Results of this systematic review indicated that the greatest benefit of vitamin D supplementation in elite athletes may be improving aerobic endurance, anaerobic power, and strength. More research is needed to determine the effect of vitamin D supplementation on bone health and injury risk in this population.
PubMed: 38188620
DOI: 10.1177/23259671231220371 -
Endocrine Dec 2023To understand the pathophysiology of idiopathic osteoporosis (IOP) better, we conducted a systematic review and meta-analysis of bone mineral density (BMD), hormones,... (Meta-Analysis)
Meta-Analysis
PURPOSE
To understand the pathophysiology of idiopathic osteoporosis (IOP) better, we conducted a systematic review and meta-analysis of bone mineral density (BMD), hormones, and bone turnover markers (BTMs) between IOP patients and healthy controls.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, an appropriate search query was created, and three databases, including PubMed, ScienceDirect, and Google Scholar, were searched for screening relevant original articles. Feasible information, both qualitative and quantitative, was extracted and used to conduct meta-analyses. Publication bias and heterogeneity among studies were evaluated using appropriate statistical tools.
RESULTS
A total of 21 studies were included in the meta-analysis. There was reduced BMD at the lumbar spine (LS) (pooled: SDM: -2.38, p-value: 0.0001), femoral neck (FN) (pooled: SDM: -1.75 p-value: 0.0001), total hip (TH) (pooled: SDM: -1.825, p-value: 0.0001) and distal radius (DR) (pooled: SDM of -0.476, p-value: 0.0001), of which LS was the most affected site. There was no significant change in BTMs compared with healthy controls. Total estradiol (SDM: -1.357, p-value: 0.003) was reduced, and parathyroid hormone (PTH) (SDM: 1.51, p-value: 0.03) and sex hormone-binding globulin (SHBG) (SDM: 1.454, p-value: 0.0001) were elevated in IOP patients compared with healthy controls.
CONCLUSION
Our meta-analysis, the first of its kind on IOP, defines it as showing BMD decline maximally at LS compared with healthy controls without any alterations in the BTMs. Further studies are required to understand gender differences and the significance of altered hormonal profiles in this condition.
Topics: Humans; Osteoporosis; Bone Density; Parathyroid Hormone; Estradiol; Femur Neck
PubMed: 37733181
DOI: 10.1007/s12020-023-03505-5 -
Frontiers in Physiology 2023In vertebrates fibroblast growth factor 23 (FGF23) is a phosphate regulating hormone closely linked to calcium regulation by vitamin D and parathyroid hormone (PTH)....
In vertebrates fibroblast growth factor 23 (FGF23) is a phosphate regulating hormone closely linked to calcium regulation by vitamin D and parathyroid hormone (PTH). Although phosphorus, calcium and vitamin D are important for poultry well-being, relatively little is known about their levels of FGF23. Our objective was to quantitatively estimate the blood FGF23 level in birds, and to examine its relationship to diet and blood levels of other components of phosphate and calcium homeostasis. A systematic search of Agricola, Embase and Medline identified 86 studies focused on FGF23 in birds, from which 12 manuscripts reporting data for 60 independent groups of chickens were included in the analysis. FGF23 levels were 256 pg/ml (Confidence interval (CI): 215, 297) in broilers (39 datasets containing 435 birds), and 256 pg/ml (CI: 178, 339) in egg-laying hens (21 datasets containing 208 birds). FGF23 levels did not correlate with dietary phosphorus, calcium or vitamin D, or with plasma calcium or PTH. FGF23 levels demonstrated a trend to positively correlate with plasma phosphate and a strongly and positive correlation with plasma vitamin D. This study provides normative estimates of FGF23 levels in poultry birds and new insights into the regulation of calcium and phosphate homeostasis.
PubMed: 37908340
DOI: 10.3389/fphys.2023.1279204 -
BMC Nutrition Nov 2023Vitamin D, one of the most essential micronutrients, is crucial in various health outcomes. However, previous studies showed conflicting results and uncertainty about...
Evaluating the effect of vitamin D supplementation on serum levels of 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, parathyroid hormone and renin-angiotensin-aldosterone system: a systematic review and meta-analysis of clinical trials.
BACKGROUND
Vitamin D, one of the most essential micronutrients, is crucial in various health outcomes. However, previous studies showed conflicting results and uncertainty about vitamin D supplementation's optimal dosage and duration. In this study, we aimed to evaluate the vitamin D supplements efficiency on serum levels of 25-hydroxy vitamin D (25(OH)D), 1,25-dihdroxy vitamin D (1,25(OH)2D), parathyroid hormone (PTH) and renin-angiotensin-aldosterone system (RAAS) in adults.
METHODS
A systematic analysis of eligible and relevant randomized-controlled trials (RCT) published before April 2023 assessing the effect of vitamin D supplementations applied. The studies were identified by searching several databases, including Pubmed, Scopus, Web of Science, ProQuest, and Cochrane Register of controlled trials.
RESULTS
Five eligible RCTs with 346 participants in the intervention and 352 participants in the control group were assessed in our project. According to the results, there was a substantial change in 25(OH)D (SMD: 2.2, I: 92.3, 95% Confidence Interval (CI): 1.38-3.02, P-value: 0.048) and 1,25(OH)2D (SMD:1.23, I: 86.3, 95% CI: 0.01- 2.44, P-value < 0.010) affected by vitamin D intervention. Regarding Parathyroid hormone (PTH), however, vitamin D intervention showed a remarkable decrease (SMD: -0.75, I: 82.4, 95% CI: (-1.3)-(-0.18), P-value < 0.010). Moreover, sensitivity analysis showed significant publication bias in terms of 25(OH)D.
CONCLUSION
Vitamin D supplements significantly increase the serum levels of 25(OH)D and 1,25(OH)2D and decrease PTH levels. While some studies reported decreasing effect of vitamin D supplements on RAAS activity, some reported no changes.
PubMed: 37968749
DOI: 10.1186/s40795-023-00786-x -
Evidence-based Complementary and... 2021Despite the proposed role of the gut microbiota-bone axis, findings on the association between probiotic consumption and bone health are conflicting. This systematic... (Review)
Review
Despite the proposed role of the gut microbiota-bone axis, findings on the association between probiotic consumption and bone health are conflicting. This systematic review aimed to assess the effect of probiotic consumption on bone health parameters. A systematic literature search of relevant reports published in PubMed/Medline, Web of Science, SCOPUS, EMBASE, and Google scholar before December 2020 was conducted. All clinical trials or experimental studies, which examined the relationship between probiotic consumption and bone health parameters, were included. No limitation was applied during the search. After screening articles based on inclusion criteria, 44 studies remained. In clinical trials, probiotic consumption affects bone health parameters such as serum calcium levels (3.82; 95% CI: 1.05, 6.59 mmol/l), urinary calcium levels (4.85; 95% CI: 1.16, 8.53 mmol/l), and parathyroid hormone (PTH) levels (-5.53; 95% CI: -9.83, -0.86 ng/l). In most studies, species such as , and were consumed and women aged 50 years or older were assessed. Spinal and total hip bone mineral density (BMD) was not affected significantly by probiotic consumption. In 37 animal experiments, probiotic or symbiotic feeding mostly had effects on bone health parameters. Some strains of and including . , , and have indicated beneficial effects on bone health parameters. In conclusion, this systematic review and meta-analysis indicate that probiotic supplementation might improve bone health. Further studies are needed to decide on the best probiotic species and appropriate dosages.
PubMed: 34394379
DOI: 10.1155/2021/3582989 -
Archives of Oral Biology Dec 2020The purpose of this systematic review was to determine the potential interest of parathyroid hormone (PTH) as an adjunct to periodontal treatment based on studies...
OBJECTIVES
The purpose of this systematic review was to determine the potential interest of parathyroid hormone (PTH) as an adjunct to periodontal treatment based on studies performed in rodents.
MATERIALS & METHODS
Electronic databases (MEDLINE, Web of Science) were searched up to December 2019. Studies assessing the impact of PTH administration in experimental periodontitis in rodents have been identified.
RESULTS
Amongst the 247 identified articles, 10 met the inclusion criteria and were included in this systematic review. Experimental periodontitis was mainly induced by ligature placement or surgically with a dental bur. All studies considered bone healing after PTH administration at different frequencies as primary outcome. Results showed that an intermittent administration of PTH promoted bone healing and neovascularization. Nevertheless, a decrease of soft tissue inflammation was also observed.
CONCLUSION
Intermittent administration of PTH appears to enhance significantly periodontal healing and to promote alveolar bone regeneration. However, due to the risk of side effects, the development of scaffolds allowing its local and time-controlled delivery is of importance.
Topics: Alveolar Bone Loss; Animals; Bone Regeneration; Disease Models, Animal; Parathyroid Hormone; Periodontitis; Wound Healing
PubMed: 33113458
DOI: 10.1016/j.archoralbio.2020.104932