scholarly journals Impact of serum calcium levels on local and total body bone mineral density: A Mendelian randomization study and an age stratum analysis

2019 ◽  
Author(s):  
Jing-yi Sun ◽  
Haihua Zhang ◽  
Yan Zhang ◽  
Longcai Wang ◽  
Jin Rok Oh ◽  
...  

AbstractObjectivesUntil recently, randomized controlled trials and meta-analyses have not demonstrated convincing conclusions regarding the association of calcium intake with bone mineral density (BMD). Until now, it remains unclear whether high serum calcium levels are causally associated with BMD. This study aimed to investigate the genetic association between serum calcium levels and BMD using a large-scale serum calcium GWAS dataset and four large-scale BMD GWAS datasets in individuals of European descent.MethodsWe performed a Mendelian randomization study to investigate the association of increased serum calcium levels with BMD using a large-scale serum calcium genome-wide association study (GWAS) dataset (including up to 61,079 individuals) and four large-scale BMD GWAS datasets (including minimum 4,180 individuals and maximum 142,487 individuals) regarding the total body, forearm, femoral neck, lumbar spine, and heel BMD. Here, we selected three Mendelian randomization methods including inverse-variance weighted meta-analysis (IVW), weighted median, and MR-Egger.ResultsIn specific site analysis, we found that increased serum calcium levels could reduce BMD at forearm (OR=0.59, 95% CI: 0.36-0.95, P=0.029) and lumbar spine (OR=0.65, 95% CI: 0.49-0.86, P=0.002). We did not identify any suggestive association of genetically increased serum calcium levels with BMD of total body, femoral neck, and heel BMD. In specific age stratum analysis, we found that genetically increased serum calcium levels were statistically significantly associated with reduced total body BMD in age stratum 60 or more years (OR=0.58, 95% CI: 0.41-0.82, P=0.002).ConclusionsWe provide genetic evidence that increased serum calcium levels could not improve BMD in the general population. The elevated serum calcium levels in generally healthy populations, especially adults older than 60 years, may even reduce the BMD, and further cause osteoporosis.

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Lv ◽  
Pengfei Wu ◽  
Shipeng Xiao ◽  
Wan Zhang ◽  
Yawei Li ◽  
...  

Background: We aimed at investigating causal associations between matrix metalloproteinases (MMPs) and bone mineral density (BMD) by the Mendelian randomization (MR) analysis.Methods: From genome-wide association studies of European ancestry, we selected instrumental variables for MMP-1, MMP-3, MMP-7, MMP-8, MMP-10, and MMP-12. Accordingly, we retrieved summary statistics of three site-specific BMD, namely, forearm, femoral neck, and lumbar spine. We conducted an inverse variance weighted MR as the primary method to compute overall effects from multiple instruments, while additional MR approaches and sensitivity analyses were implemented. Bonferroni-adjusted significance threshold was set at p < 0.05/18 = 0.003.Results: Totally, there was no evidence for causal effects of genetically-predicted levels of MMPs on BMD measurement at three common sites. MR results indicated that there were no causal associations of circulating MMPs with forearm BMD (all p ≥ 0.023) by the inverse variance weighted method. Similarly, there were no causal effects of MMPs on femoral neck BMD (all p ≥ 0.120) and MR results did not support causal relationships between MMPs and lumbar spine BMD (all p ≥ 0.017). Multiple sensitivity analyses suggested the robustness of MR results, which were less likely to be biased by unbalanced pleiotropy or evident heterogeneity.Conclusion: We found no evidence for the causal relationship between MMPs and BMD in the European population.


2005 ◽  
Vol 90 (4) ◽  
pp. 2022-2028 ◽  
Author(s):  
M. G. Murphy ◽  
K. Cerchio ◽  
S. A. Stoch ◽  
K. Gottesdiener ◽  
M. Wu ◽  
...  

Abstract The αVβ3 integrin (vitronectin receptor) plays a pivotal role in bone resorption. We hypothesized that L-000845704, an αVβ3 integrin antagonist, would potently inhibit bone resorption, thereby increasing bone mass as assessed by bone mineral density (BMD) in women with postmenopausal osteoporosis. In a multicenter, randomized, double-blind, placebo-controlled, 12-month study, 227 women (average 63 yr) with low lumbar spine or femoral neck BMD were randomly assigned to receive 100 or 400 mg L-000845704 once daily (qd), 200 mg L-000845704 twice daily (bid), or placebo. L-000845704 increased lumbar spine BMD (2.1, 3.1, and 3.5% for the 100-mg-qd, 400-mg-qd, and 200-mg-bid treatment groups, respectively, vs. −0.1% for placebo; P < 0.01 all treatments vs. placebo). Only 200 mg L-000845704 bid significantly increased BMD at the hip (1.7 vs. 0.3% for placebo; P < 0.03) and femoral neck (2.4 vs. 0.7% for placebo; P < 0.05). No L-000845704 group increased total body BMD. All doses of L-000845704 resulted in a similar approximately 42% decrease from baseline of N-telopeptide cross-links (P < 0.001 vs. placebo). L-000845704 was generally well tolerated; adverse events resulting in discontinuation from the study were relatively infrequent. In conclusion, the antiresorptive effect of the αVβ3 integrin antagonist L-000845704 translated into significant increases in lumbar spine BMD. Furthermore, 200 mg L-000845704 bid provided efficacy at the hip sites. These data suggest that the αVβ3 integrin antagonist L-000845704 could be developed as an effective therapeutic agent for osteoporosis.


2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Maryna Bystrytska ◽  
Vladyslav Povoroznyuk ◽  
Nataliia Grygorieva ◽  
Iryna Karaban ◽  
Nina Karasevich

Osteoporosis and Parkinson’s disease (PD) are two important age-related diseases, which have an influence on pain, physical activity, disability, and mortality. The aim of this research was to study the parameters of bone mineral density (BMD), frequency, and 10-year probability of osteoporotic fractures (OFs) in females with Parkinson’s disease (PD). We have examined 113 postmenopausal women aged 50–74 years old which were divided into 2 groups (I, control group (CG), n = 53 and II, subjects with PD, n = 60). Bone mineral density of lumbar spine, femoral neck, distal radius, and total body were measured, and quantity and localization of vertebral deformities were performed by the vertebral fracture assessment (VFA). Ten-year probability of OFs was assessed by Ukrainian version of FRAX®. It was established that BMD of lumbar spine, femoral neck, distal radius, and total body in PD women was reliably lower compared to CG. The frequency of OFs in PD subjects was higher compared to CG (51.7 and 11.3%, respectively) with prevalence of vertebral fractures (VFs) in women with PD (52.6% among all fractures). 47.4% of the females had combined VFs: 74.2% of VFs were in thoracic part of the spine and 73.7% were wedge ones. Ten-year probability of major OFs and hip fracture were higher in PD women compared to CG with and without BMD measurements. Inclusion of PD in the FRAX calculation increased the requirement of antiosteoporotic treatment from 5 to 28% (without additional examination) and increased the need of additional BMD measurement from 50 to 68%. Anterior/posterior vertebral height ratios (Th8-Th11) measured by VFA in PD females without confirmed vertebral deformities were lower compared to indices of CG. In conclusion, women with PD have lower BMD indices, higher rate of osteoporosis, and risk of future low-energy fractures that should be taken into account in the assessment of their osteoporosis risk and clinical management.


1998 ◽  
Vol 83 (11) ◽  
pp. 3845-3851 ◽  
Author(s):  
Mohamed Abdelhadi ◽  
Jörgen Nordenström

Patients with hyperparathyroidism (HPT) generally display reduced bone mass due to excessive PTH activity. The effect of parathyroidectomy on bone mass changes in different types of HPT, however, is not well understood. Bone mineral density (BMD) was measured in the distal radius, total body, femoral neck, and lumbar spine by dual energy x-ray absorptiometry in four groups of patients with different hyperparathyroid conditions: primary symptomatic HPT (n = 54), primary asymptomatic (mild) HPT (n = 24), HPT associated with hemodialysis (n = 20), and HPT associated with renal transplant (n = 30). Subsets of patients with primary symptomatic HPT (n= 52), HPT associated with hemodialysis (n = 19), and HPT associated with renal transplant (n = 15) underwent parathyroidectomy, and bone density was measured longitudinally for 3 yr. Patients with primary asymptomatic (mild) HPT did not undergo surgery and were followed prospectively. Before surgery, all groups showed a greater reduction of bone mineral density in cortical bone (distal radius) than in predominantly trabecular bone (lumbar spine). In primary symptomatic HPT, the BMD z-score of the distal radius was −1.80 ± 0.21 (±sem), and the corresponding figures for the total body, femoral neck, and lumbar spine were −0.60 ± 0.15, −0.54 ± 0.14, and −0.53 ± 0.18 compared with those of an age- and sex-matched reference group. In renal HPT BMD z-scores were −2.51± 0.38 (hemodialysis patients) and −2.83 ± 0.43 (renal transplant patients) for the distal radius and between −0.81 and− 1.46 for the other measured sites. After parathyroidectomy, BMD increased by 1–8% at all sites in patients with primary symptomatic HPT and HPT associated with renal transplant. The largest increase in bone mass was observed in patients with HPT associated with hemodialysis, in whom the improvement amounted to 7–23%. In patients with primary HPT and HPT associated with hemodialysis, this increase in bone density resulted in virtual recovery from their preoperative bone loss. The majority of patients with asymptomatic primary HPT disease (n = 21) maintained their bone density during the follow-up period and have not shown evidence of increases in serum calcium or PTH levels, but three patients followed conservatively underwent parathyroidectomy due to progressive deterioration of BMD. We conclude that, regardless of the etiology, a large proportion of HPT patients show reduced bone density. In patients with primary symptomatic HPT and patients with HPT associated with hemodialysis, bone density increases after parathyroidectomy to an extent that largely restores the preoperative bone loss. However, no anabolic effect of parathyroidectomy on bone mass was observed in patients with HPT associated with renal transplant, probably because of their immunosuppressive therapy.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Vladyslav Povoroznyuk ◽  
Maryna Bystrytska ◽  
Nataliia Grygorieva ◽  
Iryna Karaban ◽  
Nina Karasevich

Introduction. Current research studies demonstrate the changes of bone mineral density (BMD) in subjects with Parkinson’s disease (PD); however, data about bone quality and body composition (BC) indexes are insufficient. The aim of the study was to assess the parameters of BMD, ВС, and trabecular bone score (TBS) in PD males. Materials and Methods. We performed a cross-sectional case-control research design and examined 76 males aged 50–77 years old, who were divided into two groups: first group including men without PD n=38 and the second group including subjects with PD n=38. Disease duration was at least 5 years; all PD participants were at levodopa therapy. BMD of lumbar spine, femoral neck, total femur, radius, and total body and TBS Ll−L4 were measured using the DXA method. Whole-body DXA measures were also used for the study of total, lean, and fat masses, skeletal muscle index (SMI), appendicular lean mass index (ALMI), and fat mass index (FMI). Results. Our study showed an increased incidence of osteoporosis and significantly lower total body BMD (respectively, 1.20 ± 0.13 and 1.26 ± 0.10 g/cm2, p=0.05), but not lumbar spine and femoral neck BMDs, and higher TBS value in PD men comparing to the control group (respectively, 1.33 ± 0.12 and 1.22 ± 0.18 un., p=0.005). Also, we established significantly decreased lower extremities BMD indexes, but not upper extremities, spine, and trunk BMDs in PD males. The femoral neck, proximal femur, and lower extremities BMD indexes in PD men were reliably lower at the side of predominance of clinical symptoms. Parameters of appendicular lean mass and ALMI in PD males were reliably higher, but fat mass values and FMI were lower compared to the control group in the absence of significant differences in lean mass values and SMI in weight-matched control. Conclusion. Due to low BMD values, changes in BC are present in PD males, and appropriate screening and preventive strategies should be instigated to maintain bone health in PD subjects.


2019 ◽  
Vol 49 (4) ◽  
pp. 1221-1235 ◽  
Author(s):  
Gloria Hoi-Yee Li ◽  
Ching-Lung Cheung ◽  
Philip Chun-Ming Au ◽  
Kathryn Choon-Beng Tan ◽  
Ian Chi-Kei Wong ◽  
...  

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is suggested to play a role in osteoporosis but its association with bone metabolism remains unclear. Effects of LDL-C-lowering drugs on bone are also controversial. We aim to determine whether LDL-C is linked causally to bone mineral density (BMD) and assess the effects of LDL-C-lowering drugs on BMD. Methods Association between blood lipid levels and BMD was examined by epidemiological observation analyses in a US representative cohort NHANES III (n = 3638) and the Hong Kong Osteoporosis Study (HKOS; n = 1128). Two-sample Mendelian randomization (MR), employing genetic data from a large-scale genome-wide association study (GWAS) of blood lipids (n = 188 577), total body BMD (TB-BMD) (n = 66 628) and estimated BMD (eBMD) (n= 142 487), was performed to infer causality between LDL-C and BMD. Genetic proxies for LDL-C-lowering drugs were used to examine the drugs’ effects on BMD. Results In the NHANES III cohort, each standard deviation (SD) decrease in LDL-C was associated with a 0.045 SD increase in femoral neck BMD (95% CI: 0.009 − 0.081; P = 0.015). A similar increase in BMD was observed in the HKOS at femoral neck and lumbar spine. In MR analysis, a decrease in genetically predicted LDL-C was associated with an increase in TB-BMD {estimate per SD decrease, 0.038 [95% confidence interval (CI): 0.002 − 0.074]; P = 0.038} and eBMD [0.076 (0.042 − 0.111); P = 1.20x10−5]. Reduction in TB-BMD was causally associated with increased LDL-C [0.035 (0.033 − 0.066); P = 0.034]. Statins’ LDL-C-lowering proxies were associated with increased TB-BMD [0.18 (0.044 − 0.316); P = 9.600x10−3] and eBMD [0.143 (0.062 − 0.223); P = 5.165x10−4]. Conclusions Negative causal association exists between LDL-C level and BMD. Statins’ LDL-C-lowering effect increases BMD, suggesting their protective effect on bone.


Author(s):  
Tathyane Krahenbühl ◽  
Juliano Henrique Borges ◽  
Antonio de Azevedo Barros-Filho ◽  
Gil Guerra-Junior ◽  
Ezequiel Moreira Gonçalves

Optimizing bone mass gain during childhood and adolescence may help prevent bone diseases in advanced ages. The aim of this study was to verify the bone mineral density (BMD) and bone mineral content (BMC) in female adolescent’s handball players. This is a cross-sectional study where 68 female adolescents (12–17 years) were allocated into two groups: handball players (n = 29) (HG) and control group (n = 39) (CG). BMC and BMD from total body (TB), total body less head (TBLH), lumbar spine (L1–L4), femoral neck (FN), Ward’s triangle (WT) and respectively Z-scores were measured using dual-energy X-ray absorptiometry (DXA). Sexual maturity, menarche, PHV, time of sun exposure, physical activity level and Calcium and vitamin D intake were assessed. The HG showed significantly higher BMC, BMD as well Z-scores values (p≤0.05) of total body, TBLH, femoral neck, hip and lumbar spine than the CG. When the values were adjusted for lean soft tissue (LST) the HG showed significantly higher BMC of femoral neck (p≤0.05), as well as BMD of TBLH and femoral neck (p≤0.05) and Z-score values all bone sites except hip, than the CG. We conclude that handball players have significantly higher bone mass values compared to group of girls of the same age.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1757.2-1757
Author(s):  
T. Raskina ◽  
I. Grigoreva ◽  
J. Averkieva ◽  
A. Kokov ◽  
V. Masenko

Objectives:To examine bone mineral density (BMD) in men with coronary heart disease (CHD), depending on the state of the muscle mass, strength and function.Methods:79 men aged over 50 years with verified CHD were examined (mean age 63 (57; 66) years).The BMD and T-criterion (standart deviation, SD) of the femoral neck and lumbar spine (L1-L4) were evaluated using dual-energy x-ray absorptiometry (DXA) on the Lunar Prodigy Primo bone densitometer (USA). The following reference intervals were used: normal BMD values (T-criterion ≥-1), osteopenia (OPe) (T-criterion from -1 to -2.5), and osteoporosis (OP) (T-criterion <-2.5).To assess muscle mass, the total area (cm2) of the lumbar muscles of the axial section at the level of the 3rd lumbar vertebra (L3) was determined using multispiral computed tomography on a 64-slice computer tomograph “Somatom Sensation 64” (Siemens AG Medical Solution, Germany). The ratio of the obtained index of the area of skeletal muscle to the square of the patient’s growth index determined the “ skeletalmuscular index L3” (SMI). The media considered the threshold value to be 52.4 cm2/m2.Results:The femoral neck BMD in the examined patients was 0.96 (0.89; 1.03) g/cm2, which corresponds to -0.50 (-1.00; 0) SD according to the T-criterion, in the lumbar spine -1.23 (1.11; 1.32) g/cm2and 0.4 (-0.50; 1.20) SD according to the T-criterion.In accordance with the recommendations of the European working group on sarcopenia in Older people (EWGSOP, 2010, 2018), the patients were divided into 3 groups: 31 patients without sarcopenia (group 1), 21 patients with isolated muscle loss (presarcopenia) (group 2) and 27 patients with sarcopenia (group 3).BMD in the femoral neck in the group of patients without sarcopenia was 0.96 (0.72; 1.26) g/cm2, which corresponds to -0.50 (-0.8; 0.2) SD according to the T-criterion, in the lumbar spine – 1.19 (1.10; 1.275) g/cm2and 0.1 (-0.6; 0.8) SD according to the T-criterion. BMD in the femoral neck in the group of patients with presarcopenia (group 2) – 0.995 (0.94; 1.04) g/cm2and -0.3 (-0.70; 0) SD according to the T-criterion, in the lumbar spine – 1.32 (1.24; 1.40) g/cm2and 1.20 (0.50; 1.90) SD according to the T-criterion. In patients with established sarcopenia (group 3), the following indicators of BMD and T-criterion were recorded: 0.95 (0.845; 0.98) g/cm2and -0.60 (-1.40; -0.40) SD and 1.23 (0.085; 1.31) g/cm2and 0.4 (-0.8; 1.1) SD in the femoral neck and lumbar spine, respectively.A comparative analysis of the results of the DXA found that patients with sarcopenia had a significant decrease in the BMD and T-criterion in the femoral neck compared to patients with presarcopenia (p=0.039 and p=0.040, respectively). There were no differences between the groups of patients without sarcopenia and with sarcopenia and presarcopenia (p>0.05).It was found that patients with sarcopenia had significantly lower BMD and T-criterion in the lumbar spine compared to patients with presarcopenia (p=0.017 and p=0.0165, respectively). The values of the BMD and T-criterion in the groups of patients without sarcopenia and with presarcopenia and sarcopenia in the lumbar spine were comparable (p>0.05).Conclusion:The presence of sarcopenia is associated with loss of BMD in the femoral neck and in the lumbar spine. The results obtained confirm the high probability of common pathogenetic links between OP and sarcopenia.Disclosure of Interests:None declared


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stefana Catalina Bilha ◽  
Letitia Leustean ◽  
Cristina Preda ◽  
Dumitru D. Branisteanu ◽  
Laura Mihalache ◽  
...  

Abstract Background Despite the increased fracture risk, bone mineral density (BMD) is variable in type 1 (T1D) and type 2 (T2D) diabetes mellitus. We aimed at comparing independent BMD predictors in T1D, T2D and control subjects, respectively. Methods Cross-sectional case-control study enrolling 30 T1D, 39 T2D and 69 age, sex and body mass index (BMI) – matched controls that underwent clinical examination, dual-energy X-ray absorptiometry (BMD at the lumbar spine and femoral neck) and serum determination of HbA1c and parameters of calcium and phosphate metabolism. Results T2D patients had similar BMD compared to T1D individuals (after adjusting for age, BMI and disease duration) and to matched controls, respectively. In multiple regression analysis, diabetes duration – but not HbA1c- negatively predicted femoral neck BMD in T1D (β= -0.39, p = 0.014), while BMI was a positive predictor for lumbar spine (β = 0.46, p = 0.006) and femoral neck BMD (β = 0.44, p = 0.007) in T2D, besides gender influence. Age negatively predicted BMD in controls, but not in patients with diabetes. Conclusions Long-standing diabetes and female gender particularly increase the risk for low bone mass in T1D. An increased body weight partially hinders BMD loss in T2D. The impact of age appears to be surpassed by that of other bone regulating factors in both T1D and T2D patients.


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