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Association of Beta Blocker Use With Bone Mineral Density in the Framingham Osteoporosis Study: A Cross?Sectional Study

ABSTRACT: ABSTRACT Some, but not all, prior observational studies have shown that beta blocker (BB) use is associated with lower fracture risk and higher bone mineral density (BMD). Rodent studies show the mechanism to involve the reduction in the effects of beta?adrenergic signaling on bone remodeling. Because previous studies did not have detailed information on dose, duration, and beta?1 selectivity, we examined these in a cross?sectional analysis of the association between BB use and hip and spine BMD using DXA with the Offspring Cohort of the Framingham Heart Study. The sample size was n = 1520, and 397 individuals used BBs. We used propensity score modeling to balance a comprehensive set of covariates using inverse probability of treatment weighting (IPTW) to minimize bias due to treatment indication. We found significant differences in BMD between BB users and non?users for three of four BMD measurements (femoral neck: 3.1%, 95% CI, 1.1% to 5.0%; total femur: 2.9%, 95% CI, 0.9% to 4.9%; femoral trochanter: 2.4%, 95% CI, ?0.1% to 5.0%; and lumbar spine: 2.7%, 95% CI, 0.2% to 5.0%). Results were found to be similar between sexes although the magnitude of association was larger for women. Similar differences were estimated for beta?1 selective and nonselective BBs compared with no BB use. We modeled dose in categories (no BB use, low?dose, high?dose) and as a continuous variable and found an increasing dose response that levels off at higher doses. Finally, associations were similar for short?term versus long?term (?4?years versus >4?years) use. In summary, this large comprehensive study shows that BB use is associated with higher BMD in a dose?related manner regardless of beta?1 specificity and duration of use, which supports the conduct of a randomized clinical trial of BBs for achieving improvements in BMD for individuals at risk of bone loss with aging. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research. Predicted bone mineral density (BMD) in g/cm2 as a function of standardized dose (defined daily dose [DDD]) in polynomial dose response models with sample weighing by inverse probability of treatment weights (IPTW).

SUBMITTER: Lary C

PROVIDER: S-EPMC7507481 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Project description:ObjectiveUndercarboxylated osteocalcin (ucOC) is one form of osteocalcin lacking full carboxylation, which plays an important role in bone homeostasis, glucose homeostasis, and energy metabolism. Our aim is to obtain the profile of serum ucOC level according to gender and age and explore its associations with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteopenia and osteoporosis in the Chinese population.MethodsThis is a cross-sectional study with 900 subjects, composed of 431 men and 469 women. Clinical information was collected, and BMD values of the lumbar spine (L1-4), left femoral neck, and total hip were scanned. Biochemical markers including hepatic and renal function, serum calcium, serum phosphorus, procollagen type 1 N-propeptide (P1NP) β-CrossLaps of type I collagen-containing cross-linked C-telopeptide (β-CTX) intact parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and ucOC were measured.ResultsWe found that the median ucOC level was higher in men than women [men, 2.6 ng/ml; women, 1.6 ng/ml; p < 0.001]. The profile according to age showed that ucOC levels were the lowest at the age of 40-49 years in both men [2.55 ng/ml (95% CI = 1.96-3.13 ng/ml)] and women [1.57 ng/ml (95% CI = 1.12-2.03 ng/ml)]; in patients younger than 49 years, they decreased with age; then over 50 years, they quickly increased. Furthermore, we found that a higher ucOC level was correlated with lower BMD values at the lumbar spine (men, r = -0.128, p = 0.013; women, r = -0.321, p < 0.001), femoral neck (men, r = -0.095, p = 0.062; women, r = -0.260, p < 0.001), and total hip (men, r = -0.123, p = 0.015; women, r = -0.209, p < 0.001) and higher P1NP (men, r = 0.307, p < 0.001; women, r = 0.239, p < 0.001) and β-CTX (men, r = 0.169, p = 0.001; women, r = 0.354, p < 0.001) levels in both men and women. Furthermore, we also showed that a 1 - SD increase in ucOC was associated with an odds ratio (OR) of 1.63 and 1.70 for having osteopenia or osteoporosis in men and women, respectively (men, 95% CI = 1.25-2.13, p = 0.004; women, 95% CI = 1.19-2.42, p = 0.004).ConclusionsWe first revealed the profile of serum ucOC levels according to gender and age in the Chinese population and demonstrated the associations of ucOC with BMD and BTMs and the risk of prevalent osteopenia or osteoporosis. Our findings provide a clue to elucidate the function of ucOC in bone metabolism.

Project description:BackgroundDietary protein is beneficial to bone health; however, dietary patterns of protein intake and their relationship with bone mineral density (BMD) have not been evaluated.ObjectiveTo examine the relationship of dietary protein food clusters with BMD at the femoral neck, trochanter, total femur, and lumbar spine among middle-aged and older men and women.DesignCross-sectional study.Participants and settingTwo thousand seven hundred fifty-eight community-dwelling individuals from the Framingham Offspring Study.MethodsBMD was measured by Lunar DPX-L (Lunar Radiation Corporation) in 1996-2001. Dietary intakes were estimated using the Willett food frequency questionnaire in either 1995-1998 or 1998-2001, and the exam closest to a participant's BMD measurement was used. Cluster analysis (FASTCLUS procedure, k-means method) was used to classify participants into groups, determined by major sources of protein. Generalized linear regression was used to compare adjusted least-squares mean BMD across protein food clusters for all pairwise comparisons.ResultsFrom 2,758 participants (44% men; mean age 61±9 years, range=29 to 86 years), five protein food clusters were identified (chicken, fish, processed foods, red meat, and low-fat milk). Three of these food clusters showed associations with BMD. The red meat protein food cluster presented with significantly lower femoral neck BMD compared with the low-fat milk cluster (red meat 0.898±0.005 g/cm(2) vs low-fat milk 0.919±0.007 g/cm(2); P=0.04). Further, the processed foods protein cluster presented with significantly lower femoral neck BMD compared with the low-fat milk cluster (processed foods 0.897±0.004 g/cm(2) vs low-fat milk 0.919±0.007 g/cm(2); P=0.02). A similar, yet nonsignificant, trend was observed for other BMD sites examined.ConclusionsDiets with the greatest proportion of protein intake from red meat and processed foods may not be as beneficial to the skeleton compared with dietary patterns where the highest proportion of protein is derived from low-fat milk.

Project description:BackgroundOsteoporosis is diagnosed by the measurement of bone mineral density, which is a highly heritable and multifactorial trait. We aimed to identify genetic loci that are associated with bone mineral density.MethodsIn this genome-wide association study, we identified the most promising of 314 075 single nucleotide polymorphisms (SNPs) in 2094 women in a UK study. We then tested these SNPs for replication in 6463 people from three other cohorts in western Europe. We also investigated allelic expression in lymphoblast cell lines. We tested the association between the replicated SNPs and osteoporotic fractures with data from two studies.FindingsWe identified genome-wide evidence for an association between bone mineral density and two SNPs (p<5x10(-8)). The SNPs were rs4355801, on chromosome 8, near to the TNFRSF11B (osteoprotegerin) gene, and rs3736228, on chromosome 11 in the LRP5 (lipoprotein-receptor-related protein) gene. A non-synonymous SNP in the LRP5 gene was associated with decreased bone mineral density (rs3736228, p=6.3x10(-12) for lumbar spine and p=1.9x10(-4) for femoral neck) and an increased risk of both osteoporotic fractures (odds ratio [OR] 1.3, 95% CI 1.09-1.52, p=0.002) and osteoporosis (OR 1.3, 1.08-1.63, p=0.008). Three SNPs near the TNFRSF11B gene were associated with decreased bone mineral density (top SNP, rs4355801: p=7.6x10(-10) for lumbar spine and p=3.3x10(-8) for femoral neck) and increased risk of osteoporosis (OR 1.2, 95% CI 1.01-1.42, p=0.038). For carriers of the risk allele at rs4355801, expression of TNFRSF11B in lymphoblast cell lines was halved (p=3.0x10(-6)). 1883 (22%) of 8557 people were at least heterozygous for these risk alleles, and these alleles had a cumulative association with bone mineral density (trend p=2.3x10(-17)). The presence of both risk alleles increased the risk of osteoporotic fractures (OR 1.3, 1.08-1.63, p=0.006) and this effect was independent of bone mineral density.InterpretationTwo gene variants of key biological proteins increase the risk of osteoporosis and osteoporotic fracture. The combined effect of these risk alleles on fractures is similar to that of most well-replicated environmental risk factors, and they are present in more than one in five white people, suggesting a potential role in screening.

Project description:BackgroundLow bone mineral density (BMD) and subsequent skeletal fragility have emerged as a long-term complication of phenylketonuria (PKU).ObjectiveTo determine if there are differences in BMD and body composition between male and female participants with PKU.MethodsFrom our randomized, crossover trial [1] of participants with early-treated PKU who consumed a low-phenylalanine (Phe) diet combined with amino acid medical foods (AA-MF) or glycomacropeptide medical foods (GMP-MF), a subset of 15 participants (6 males, 9 females, aged 15-50 y, 8 classical and 7 variant PKU) completed one dual energy X-ray absorptiometry (DXA) scan and 3-day food records after each dietary treatment. Participants reported lifelong compliance with AA-MF. In a crossover design, 8 participants (4 males, 4 females, aged 16-35 y) provided a 24-h urine collection after consuming AA-MF or GMP-MF for 1-3 weeks each.ResultsMale participants had significantly lower mean total body BMD Z-scores (means ± SE, males = - 0.9 ± 0.4; females, 0.2 ± 0.3; p = 0.01) and tended to have lower mean L1-4 spine and total femur BMD Z-scores compared to female participants. Only 50% percent of male participants had total body BMD Z-scores above - 1.0 compared to 100% of females (p = 0.06). Total femur Z-scores were negatively correlated with intake of AA-MF (r = - 0.58; p = 0.048). Males tended to consume more grams of protein equivalents per day from AA-MF (means ± SE, males: 67 ± 6 g, females: 52 ± 4 g; p = 0.057). Males and females demonstrated similar urinary excretion of renal net acid, magnesium and sulfate; males showed a trend for higher urinary calcium excretion compared to females (means ± SE, males: 339 ± 75 mg/d, females: 228 ± 69 mg/d; p = 0.13). Females had a greater percentage of total fat mass compared to males (means ± SE, males: 24.5 ± 4.8%, females: 36.5 ± 2.5%; p = 0.047). Mean appendicular lean mass index was similar between males and females. Male participants had low-normal lean mass based on the appendicular lean mass index.ConclusionsMales with PKU have lower BMD compared with females with PKU that may be related to higher intake of AA-MF and greater calcium excretion. The trial was registered at www.clinicaltrials.gov as NCT01428258.

Project description:BackgroundThe association between lipid and bone metabolism, particularly the role of high-density lipoprotein cholesterol (HDL-C) in regulating bone mineral density (BMD), is of significant interest. Despite numerous studies, findings on this relationship remain inconclusive, especially since evidence from large, sexually diverse Chinese populations is sparse. This study, therefore, investigates the correlation between HDL-C and lumbar BMD in people of different genders using extensive population-based data from physical examinations conducted in China.MethodsData from a cross-sectional survey involving 20,351 individuals aged > = 20 years drawn from medical records of health check-ups at the Health Management Centre of the Henan Provincial People's Hospital formed the basis of this study. The primary objective was to determine the correlation between HDL-C levels and lumbar BMD across genders. The analysis methodology included demographic data analysis, one-way ANOVA, subgroup analyses, multifactorial regression equations, smoothed curve fitting, and threshold and saturation effect analyses.ResultsMultifactorial regression analysis revealed a significant inverse relationship between HDL-C levels and lumbar BMD in both sexes, controlling for potential confounders (Male: β = -8.77, 95% CI -11.65 to -5.88, P < 0.001; Female: β = -4.77, 95% CI -8.63 to -0.90, P = 0.015). Subgroup and threshold saturation effect analyses indicated a stronger association in males, showing that increased HDL-C correlates with reduced lumbar BMD irrespective of age and body mass index (BMI). The most significant effect was observed in males with BMI > 28 kg/m2 and HDL-C > 1.45 mmol/L and in females with a BMI between 24 and 28 kg/m2.ConclusionElevated HDL-C is associated with decreased bone mass, particularly in obese males. These findings indicate that individuals with high HDL-C levels should receive careful clinical monitoring to mitigate osteoporosis risk.Trial registrationThe research protocol received ethics approval from the Ethics Committee at Beijing Jishuitan Hospital, in conformity with the Declaration of Helsinki guidelines (No. 2015-12-02). These data are a contribution of the China Health Quantitative CT Big Data Research team, registered at clinicaltrials.gov (code: NCT03699228).

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Association of Beta Blocker Use With Bone Mineral Density in the Framingham Osteoporosis Study: A Cross?Sectional Study

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