scholarly journals Genetic predisposition to increased serum calcium, bone mineral density, and fracture risk in individuals with normal calcium levels: mendelian randomisation study

BMJ ◽  
2019 ◽  
pp. l4410 ◽  
Author(s):  
Agustin Cerani ◽  
Sirui Zhou ◽  
Vincenzo Forgetta ◽  
John A Morris ◽  
Katerina Trajanoska ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Serum Calcium ◽  
Genetic Predisposition ◽  
Calcium Supplementation ◽  
Meta Analysis ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Mineral Density ◽  
The Uk

Abstract Objective To determine if genetically increased serum calcium levels are associated with improved bone mineral density and a reduction in osteoporotic fractures. Design Mendelian randomisation study. Setting Cohorts used included: the UK Biobank cohort, providing genotypic and estimated bone mineral density data; 25 cohorts from UK, USA, Europe, and China, providing genotypic and fracture data; and 17 cohorts from Europe, providing genotypic and serum calcium data (summary level statistics). Participants A genome-wide association meta-analysis of serum calcium levels in up to 61 079 individuals was used to identify genetic determinants of serum calcium levels. The UK Biobank study was used to assess the association of genetic predisposition to increased serum calcium with estimated bone mineral density derived from heel ultrasound in 426 824 individuals who had, on average, calcium levels in the normal range. A fracture genome-wide association meta-analysis comprising 24 cohorts and the UK Biobank including a total of 76 549 cases and 470 164 controls, who, on average, also had calcium levels in the normal range was then performed. Results A standard deviation increase in genetically derived serum calcium (0.13 mmol/L or 0.51 mg/dL) was not associated with increased estimated bone mineral density (0.003 g/cm 2 , 95% confidence interval −0.059 to 0.066; P=0.92) or a reduced risk of fractures (odds ratio 1.01, 95% confidence interval 0.89 to 1.15; P=0.85) in inverse-variance weighted mendelian randomisation analyses. Sensitivity analyses did not provide evidence of pleiotropic effects. Conclusions Genetic predisposition to increased serum calcium levels in individuals with normal calcium levels is not associated with an increase in estimated bone mineral density and does not provide clinically relevant protection against fracture. Whether such predisposition mimics the effect of short term calcium supplementation is not known. Given that the same genetically derived increase in serum calcium is associated with an increased risk of coronary artery disease, widespread calcium supplementation in the general population could provide more risk than benefit.

scholarly journals Association between calcium supplementation and bone mineral density in children: a systematic review and meta-analysis

2021 ◽  
Vol 8 (2) ◽  
pp. 169-176
Author(s):  
Jin-Ping Gao ◽  
Hong-Xia Ren ◽  
Yan-Fei Wang ◽  
Shi-Fan Han ◽  
Chang-Tai Zhu
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Randomized Clinical Trials ◽  
Calcium Supplementation ◽  
Meta Analysis ◽  
Lumbar Vertebrae ◽  
Whole Body ◽  
Cochrane Library ◽  
Mineral Density ◽  
Standard Mean Difference

Abstract Objective To evaluate the effects of calcium supplementation on bone mineral density in children. Methods The PubMed, Embase, and Cochrane library were systematically searched. The retrieve inception date was between October 2001 and October 2019. Two reviewers independently performed the data extraction and assessed methodology quality. Studies were limited to randomized clinical trials comparing calcium supplement with a placebo for bone mineral density in children. A meta-analysis was performed to calculate standard mean difference (SMD) and 95% confidence interval (CI). Results A total of 6 randomized controlled trials involving 408 participants (calcium supplementation group: 198; placebo group: 210) were finally included in this study. The meta-analysis revealed that, compared with placebos, calcium supplementation had no effect on the bone mineral densities [the whole-body: SMD with CI = 0.43 (−0.05–0.91), P=0.08, I 2 = 75%; the 2nd–4th lumbar vertebrae: SMD with 95% CI = 0.27 (−0.17 to 0.70), P = 0.07, I 2 = 0%)]. Sensitivity analysis revealed that the results of the whole-body bone mineral density were unstable and that the bone density of the 2nd–4th lumbar spine was robust. Conclusions The results of this meta-analysis suggested that calcium supplementation did not improve bone mineral density in children. However, there continues to be a need for more high-quality studies to verify this fact in the future.

scholarly journals The effect of calcium and vitamin D on bone mineral density in patients taking glucocorticoid therapies: Protocol for a systematic review and network meta-analysis

2020 ◽  
Author(s):  
Jiawen Deng
Keyword(s):  
Bone Mineral Density ◽  
Systematic Review ◽  
Vitamin D ◽  
Bone Mineral ◽  
Inflammatory Diseases ◽  
Calcium Supplementation ◽  
Meta Analysis ◽  
Vitamin D Metabolites ◽  
Mineral Density ◽  
Autoimmune And Inflammatory Diseases

ABSTRACTGlucocorticoid (GC) administration is an effective therapy commonly used in the treatment of autoimmune and inflammatory diseases. However, the use of GC can give rise to serious complications. The main detrimental side effect of GC therapy is significant bone loss, resulting in glucocorticoid-induced osteoporosis (GIOP).We performed a systematic review and network meta-analysis (NMA) to evaluate whether the use of calcium supplementation, with or without vitamin D, vitamin D metabolites and vitamin D analogues is capable of increasing bone mineral density (BMD) at the lumbar spine, femoral neck, and hip in adult patients undergoing glucocorticoid therapies compared to no treatment.

scholarly journals Mendelian Randomization analysis reveals a causal influence of circulating sclerostin levels on bone mineral density and fractures

2018 ◽  
Author(s):  
Jie Zheng ◽  
Winfried Maerz ◽  
Ingrid Gergei ◽  
Marcus Kleber ◽  
Christiane Drechsler ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Femoral Neck ◽  
Fracture Risk ◽  
Bone Mineral ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Mendelian Randomisation ◽  
Adaptive Responses ◽  
Mineral Density ◽  
A Genome

ABSTRACTIn bone, sclerostin is mainly osteocyte-derived and plays an important local role in adaptive responses to mechanical loading. Whether circulating levels of sclerostin also play a functional role is currently unclear, which we aimed to examine by two sample Mendelian Randomisation (MR). A genetic instrument for circulating sclerostin, derived from a genome wide association study (GWAS) meta-analysis of serum sclerostin in 10,584 European-descent individuals, was examined in relation to femoral neck bone mineral density (BMD; n= 32,744) in GEFOS, and estimated BMD by heel ultrasound (eBMD; n=426,824), and fracture risk (n=426,795), in UK Biobank. Our GWAS identified two novel serum sclerostin loci, B4GALNT3 (standard deviation (SD)) change in sclerostin per A allele (β=0.20, P=4.6×10−49), and GALNT1 (β=0.11 per G allele, P=4.4×10−11). B4GALNT3 is an N-acetyl-galactosaminyltransferase, adding a terminal LacdiNAc disaccharide to target glycocoproteins, found to be predominantly expressed in kidney, whereas GALNT1 is an enzyme causing mucin-type O-linked glycosylation. Using these two SNPs as genetic instruments, MR revealed an inverse causal relationship between serum sclerostin and femoral neck BMD (β= −0.12, 95%CI= −0.20 to −0.05) and eBMD (β= −0.12, 95%CI= −0.14 to −0.10), and a positive relationship with fracture risk (β= 0.11, 95%CI= 0.01 to 0.21). Colocalization analysis demonstrated common genetic signals within the B4GALNT3 locus for higher sclerostin, lower eBMD, and greater B4GALNT3 expression in arterial tissue (Probability>99%). Our findings suggest that higher sclerostin levels are causally related to lower BMD and greater fracture risk. Hence, strategies for reducing circulating sclerostin, for example by targeting glycosylation enzymes as suggested by our GWAS results, may prove valuable in treating osteoporosis.

scholarly journals Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study

Diabetologia ◽  
2021 ◽  
Author(s):  
Adam Mitchell ◽  
Susanna C. Larsson ◽  
Tove Fall ◽  
Håkan Melhus ◽  
Karl Michaëlsson ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Fasting Glucose ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Mendelian Randomisation ◽  
Bone Area ◽  
Mineral Density ◽  
Total Hip ◽  
Glucose Levels

Abstract Aims/hypothesis Observational studies indicate that type 2 diabetes mellitus and fasting glucose levels are associated with a greater risk for hip fracture, smaller bone area and higher bone mineral density (BMD). However, these findings may be biased by residual confounding and reverse causation. Mendelian randomisation (MR) utilises genetic variants as instruments for exposures in an attempt to address these biases. Thus, we implemented MR to determine whether fasting glucose levels in individuals without diabetes are causally associated with bone area and BMD at the total hip. Methods We selected 35 SNPs strongly associated with fasting glucose (p < 5 × 10−8) in a non-diabetic European-descent population from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 133,010). MR was used to assess the associations of genetically predicted fasting glucose concentrations with total hip bone area and BMD in 4966 men and women without diabetes from the Swedish Mammography Cohort, Prospective Investigation of Vasculature in Uppsala Seniors and Uppsala Longitudinal Study of Adult Men. Results In a meta-analysis of the three cohorts, a genetically predicted 1 mmol/l increment of fasting glucose was associated with a 2% smaller total hip bone area (−0.67 cm2 [95% CI −1.30, −0.03; p = 0.039]), yet was also associated, albeit without reaching statistical significance, with a 4% higher total hip BMD (0.040 g/cm2 [95% CI −0.00, 0.07; p = 0.060]). Conclusions/interpretation Fasting glucose may be a causal risk factor for smaller bone area at the hip, yet possibly for greater BMD. Further MR studies with larger sample sizes are required to corroborate these findings. Graphical abstract

Relationship between serum calcium levels and bone mineral density in liver transplant receipients

2001 ◽  
Vol 120 (5) ◽  
pp. A564-A564
Author(s):  
K ISLAM ◽  
S CREECH ◽  
R SOKHI ◽  
R KONDAVEETI ◽  
A NADIR ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Liver Transplant ◽  
Bone Mineral ◽  
Serum Calcium ◽  
Mineral Density
Sign in / Sign up

Export Citation Format

Share Document