Causal Effect of Blood Pressure on Bone Mineral Density and Fracture: A Mendelian Randomization Study

Abstract

BackgroundHypertension may have some association with osteoporosis. This Mendelian randomization (MR) study aimed to explore the causal effect of blood pressure (BP) on bone mineral density (BMD), fall, and fracture.MethodsWe used the genome-wide association study (GWAS) summary data among 330,956 European-descent individuals to identify 107 single-nucleotide polymorphisms (SNPs) as the instrumental variables of BP. MR analyses of these instruments were performed on 53,236 European individuals for the association with forearm BMD (FA-BMD), femoral neck BMD (FN-BMD), and lumbar spine BMD (LS-BMD); 451,179 European individuals for fall susceptibility; and up to 1.2 million individuals from European descent for fracture. Conventional inverse variance weighted (IVW) method was adopted to obtain the causal estimates of BP on different outcomes, while weighted median, MR-egger, and MR pleiotropy residual sum and outlier (MR-PRESSO) test were used for sensitivity analyses.ResultsGenetically high pulse pressure (PP) could significantly improve FA-BMD (beta-estimate: 0.038, 95% confidence interval [CI]: 0.013 to 0.063, SE:0.013, P-value=0.003<Bonferroni correction P) in the IVW analysis, indicating that 1-SD increase in PP was associated with the improvement in FA-BMD levels by 0.038 g/cm2 (95% CI: 0.013 to 0.063). This positive finding was also confirmed by weighted-median analysis (beta-estimate: 0.034, 95% CI: 0.000 to 0.067, SE:0.017, P-value=0.046) and MR-Egger analysis (beta-estimate: 0.117, 95% CI: 0.026 to 0.208, SE:0.046, P-value=0.011). However, there was no remarkable MR association between BP and other outcomes (i.e., FN-BMD, LS-BMD, fall, and fracture).ConclusionsOur findings reveal a potentially causal relationship between high PP and improved FA-BMD, which may provide new sights for the treatment of osteoporosis.

Investigating the effect of history of fractures and hypertension on the risk of all-cause death from osteoporosis: A retrospective cohort study

“…Previous studies have shown that hypertension could increase risk of osteoporosis and osteoporotic fracture, which greatly increased the incidence of fracture or re-fracture in patients with osteoporosis and caused the higher mortality ultimately. [ 16 , 17 ] In the study of Chai et al, [ 18 ] hypertension has been confirmed to be significantly associated with osteoporosis in Chinese postmenopausal women; However, this study displayed that there was no significant association between hypertension and the all-cause death risk of osteoporosis, the possible reason was related with the included sample size. There was no doubt that the history of fractures was identified to be correlated with higher all-cause death risk osteoporosis, which was mostly consistent with the result of prior research.…”

Hipertensión arterial asociada a osteoporosis en pacientes mujeres del hospital del Seguro Social, Trujillo

“…El resultado reveló que las pacientes en el grupo de osteoporosis tuvieron una mayor prevalencia de HTA (p < 0,05), asociándose significativamente. Sin embargo, He et al (26) realizaron un estudio de aleatorización mendeliana (RM) para poder hallar el efecto causal de la presión arterial (PA) sobre la densidad mineral ósea. Se realizaron análisis de RM en 53 236 genomas de individuos europeos para la asociación con la DMO del antebrazo (FA-DMO), la DMO del cuello femoral (FN-DMO) y la DMO de la columna lumbar (LS-DMO).…”

Efficacy of magnetic therapy for osteoporotic patients: A meta-analysis of randomized controlled studies

“…[9] Many factors can improve the incidence of osteoporosis, and mainly include elderly, postmenopausal women, steroid drugs, and hyperthyroidism. [10][11][12][13][14] The decrease in calcitonin secretion after complete or subtotal thyroidectomy was proven to cause osteoporosis. [15] Increased awareness of side effects of main osteoporosis drugs such as bisphosphonates caused decreased adherence to pharmacotherapy regimes, which was highlighted as "a crisis in the treatment of osteoporosis."…”