Relationship between serum nutritional factors and bone mineral density: a Mendelian randomization study

Author(s):  
Zihao Qu ◽  
Fangkun Yang ◽  
Yishang Yan ◽  
Jianqiao Hong ◽  
Wei Wang ◽  
...  

Abstract Purpose Multiple risk factors have been implicated in the development of osteoporosis. This study examined potential associations between serum nutritional factors and bone mineral density (BMD). Methods Six nutritional factors were selected as exposures. Outcomes included total body BMD (n = 66 945); BMD at the forearm (FA), femoral neck (FN) and lumbar spine (LS) (n = 8143, 32 735 and 28 498, respectively); estimated heel BMD (HL eBMD) (n = 394 929); and HL eBMD stratified by sex (n = 206 496). A two-sample Mendelian randomization (MR) approach was adopted to estimate the association between serum nutritional factors and BMD. The threshold for adjusted p-value was 1.39×10 -3. Results Serum calcium levels were inversely associated with LS BMD (effect = -0.55; 95% CI, -0.86 to -0.24; P = 0.001), whereas serum selenium levels were positively correlated with HL eBMD (effect = 0.22; 95% CI, 0.10 to 0.33; P = 1.70×10 -4). Regarding nominal significance, there was a positive association between serum selenium levels and FA BMD. Nominally significant results were also obtained for serum retinol as well as vitamin E levels and HL eBMD. Moreover, sex-specific effects of serum retinol and vitamin E levels on BMD were observed in men. Main Conclusions Serum calcium and selenium levels influence BMD at specific skeletal sites. This implies that these nutritional factors play crucial roles in bone metabolism.

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.


2001 ◽  
Vol 120 (5) ◽  
pp. A564-A564
Author(s):  
K ISLAM ◽  
S CREECH ◽  
R SOKHI ◽  
R KONDAVEETI ◽  
A NADIR ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1626
Author(s):  
Catalina Ballestero-Fernández ◽  
Gregorio Varela-Moreiras ◽  
Natalia Úbeda ◽  
Elena Alonso-Aperte

The only available treatment for celiac disease is life-long gluten exclusion. We conducted a cross-sectional age- and gender-matched study in 64 celiac adults on a long-term (>1 year) gluten-free diet and 74 non-celiac volunteers from Spain, using dietary, anthropometric, and biochemical parameters, as well as assessing bone mineral density and physical activity. Celiac adults had deficient intake (below 2/3 of the recommended intake) for folates, vitamin E, and iodine and low intake of calcium (below 80% of the recommended intake). Iron intake was also below 2/3 of the recommended intake in celiac women. Vitamin D intake was extremely low, and 34% of celiac patients had moderately deficient plasma levels. According to bone mineral density, celiac women may be more prone to osteopenia and osteoporosis. However, we found a perfectly analogous nutritional status scenario in celiac as compared to healthy volunteers, with the dietary deviations found being similar to those of the Spanish population, i.e., both groups followed a high-lipid, high-protein, and low-carbohydrate diet. Values for biochemical parameters were found within the reference ranges. Celiac disease had no influence on body weight, but body fat in celiac patients tended to be higher. According to our results, vitamin D, calcium, folates, vitamin E, iodine, and iron nutritional status should be specifically assessed and monitored in the celiac population.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1940
Author(s):  
Karl Michaëlsson ◽  
Susanna C. Larsson

Recent cohort studies indicate a potential role of the antioxidant α-tocopherol in reducing bone loss and risk of fractures, especially hip fractures. We performed a Mendelian randomization investigation of the associations of circulating α-tocopherol with estimated bone mineral density (eBMD) using heel ultrasound and fractures, identified from hospital records or by self-reports and excluding minor fractures. Circulating α-tocopherol was instrumented by three genetic variants associated with α-tocopherol levels at p < 5 × 10−8 in a genome-wide association meta-analysis of 7781 participants of European ancestry. Summary-level data for the genetic associations with eBMD in 426,824 individuals and with fracture (53,184 cases and 373,611 non-cases) were acquired from the UK Biobank. Two of the three genetic variants were strongly associated with eBMD. In inverse-variance weighted analysis, a genetically predicted one-standard-deviation increase of circulating α-tocopherol was associated with 0.07 (95% confidence interval, 0.05 to 0.09) g/cm2 increase in BMD, which corresponds to a >10% higher BMD. Genetically predicted circulating α-tocopherol was not associated with odds of any fracture (odds ratio 0.97, 95% confidence interval, 0.91 to 1.05). In conclusion, our results strongly strengthen a causal link between increased circulating α-tocopherol and greater BMD. Both an intervention study in those with a low dietary intake of α-tocopherol is warranted and a Mendelian randomization study with fragility fractures as an outcome.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Mahrukh Khalid ◽  
Vismay Deshani ◽  
Khalid Jadoon

Abstract Background/Aims  Vitamin D deficiency is associated with more severe presentation of primary hyperparathyroidism (PTHP) with high parathyroid hormone (PTH) levels and reduced bone mineral density (BMD). We analyzed data to determine if vitamin D levels had any impact on PTH, serum calcium and BMD at diagnosis and 3 years, in patients being managed conservatively. Methods  Retrospective analysis of patients presenting with PHPT. Based on vitamin D level at diagnosis, patients were divided into two groups; vitamin D sufficient (≥ 50 nmol/L) and vitamin D insufficient (≤ 50 nmol/L). The two groups were compared for age, serum calcium and PTH levels at diagnosis and after mean follow up of 3 years. BMD at forearm and neck of femur (NOF) was only analyzed in the two groups at diagnosis, due to lack of 3 year’s data. Results  There were a total of 93 patients, 17 males, mean age 70; range 38-90. Mean vitamin D level was 73.39 nmol/L in sufficient group (n = 42) and 34.48 nmol/L in insufficient group (n = 40), (difference between means -38.91, 95% confidence interval -45.49 to -32.33, p &lt; 0.0001). There was no significant difference in age, serum calcium and PTH at the time of diagnosis. After three years, there was no significant difference in vitamin D levels between the two groups (mean vitamin D 72.17 nmol/L in sufficient group and 61.48 nmol/L in insufficient group). Despite rise in vitamin D level in insufficient group, no significant change was observed in this group in PTH and serum calcium levels. BMD was lower at both sites in vitamin D sufficient group and difference was statistically significant at NOF. Data were analyzed using unpaired t test and presented as mean ± SEM. Conclusion  50% of patients presenting with PHPT were vitamin D insufficient at diagnosis. Vitamin D was adequately replaced so that at 3 years there was no significant difference in vitamin D status in the two groups. Serum calcium and PTH were no different in the two groups at diagnosis and at three years, despite rise in vitamin D levels in the insufficient group. Interestingly, BMD was lower at forearm and neck of femur in those with sufficient vitamin D levels and the difference was statistically significant at neck of femur. Our data show that vitamin D insufficiency does not have any significant impact on PTH and calcium levels and that vitamin D replacement is safe in PHPT and does not impact serum calcium and PTH levels in the short term. Lower BMD in those with adequate vitamin D levels is difficult to explain and needs further research. Disclosure  M. Khalid: None. V. Deshani: None. K. Jadoon: None.


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