Dairy Food Intake Is Not Associated with Measures of Bone Microarchitecture in Men and Women: The Framingham Osteoporosis Study

Abstract Objectives Previous studies reported that dairy foods are associated with higher areal bone mineral density (BMD) in older adults. However, data on bone strength and bone microarchitecture are lacking. The objective of this study was to determine the association of milk, yogurt, cheese, cream, milk + yogurt and milk + yogurt + cheese intakes with high resolution peripheral quantitative computed tomography (HR-pQCT) measures of bone in older adults from the Framingham Offspring study. Methods This cross-sectional study included 532 men and 694 women (aged 32–81y, mean 64y) with measures of dairy food intake (servings/wk.) from a food frequency questionnaire. Cortical and trabecular BMD and microarchitecture at the distal tibia and radius were measured using HR-pQCT. We focused on five bone parameters: 1) Bone strength assessed via failure load from micro–finite element analysis, 2) Two cortical bone measures: cortical BMD and cortical thickness; and 3) Two trabecular bone measures: trabecular bone density and trabecular number. Sex-combined and sex-specific multivariable linear regression was used to estimate the association of dairy food intake (energy adjusted) with each bone measure adjusting for covariates (sex, age, height, weight, current smoking, energy intake, calcium supplement use, vitamin D supplement use, physical activity and multivitamin use). Results Over 90% of the participants consumed the recommended ≥ 3 servings of dairy per day. Mean milk intake ± SD was 5.5 servings/week in both men and women. In sex combined analyses, only cheese intake was associated with cortical BMD at the radius and tibia (Table). None of the other dairy foods were significantly associated with any of the bone measures. In sex-stratified analysis higher cheese intake was associated with lower cortical BMD at the radius and tibia in women alone (radius: β = −9.61 ± 2.73, P = 0.001, tibia: β = −9.41 ± 3.10, P = 0.001). In men, higher cream intake was associated with higher trabecular number (radius: β = 0.021 ± 0.011, P = 0.02, tibia: β = 0.024 ± 0.012, P = 0.05). Higher yogurt intake was also associated with higher trabecular volumetric BMD at the tibia in men alone (tibia: β = 4.86 ± 2.00, P = 0.02). Conclusions In this cohort of primarily healthy older men and women with high dairy food consumption, specific dairy foods seem to be more beneficial in men than women. Negative associations for cheese intake and cortical BMD in women should be further confirmed in longitudinal studies. Funding Sources NIH AR # 053205; FHS N01-HC-25195 R01 AR/AG 41398 and unrestricted institutional research grant from Dairy Management Inc. Supporting Tables, Images and/or Graphs

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Bone Metabolism in Adolescents Undergoing Bariatric Surgery

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa836 ◽

2020 ◽

Author(s):

Madhusmita Misra ◽

Miriam A Bredella

Keyword(s):

Bariatric Surgery ◽

Sleeve Gastrectomy ◽

Lumbar Spine ◽

Bone Loss ◽

Bone Microarchitecture ◽

Quantitative Computed Tomography ◽

Areal Bone Mineral Density ◽

Mineral Density ◽

Cross Sectional ◽

Peripheral Skeleton

Abstract Purpose The prevalence of childhood obesity has increased over past decades with a concomitant increase in metabolic and bariatric surgery (MBS). While MBS in adults is associated with bone loss, only a few studies have examined the effect of MBS on the growing skeleton in adolescents. Methods This mini-review summarizes available data on the effects of the most commonly performed MBS (sleeve gastrectomy and gastric bypass) on bone in adolescents. A literature review was performed using PubMed for English-language articles. Results Dual-energy x-ray absorptiometry (DXA) measures of areal bone mineral density (aBMD) and BMD Z scores decreased following all MBS. Volumetric BMD (vBMD) by quantitative computed tomography (QCT) decreased at the lumbar spine while cortical vBMD of the distal radius and tibia increased over a year following sleeve gastrectomy (total vBMD did not change). Reductions in narrow neck and intertrochanteric cross-sectional area and cortical thickness were observed over this duration, and hip strength estimates were deleteriously impacted. Marrow adipose tissue (MAT) of the lumbar spine increased while MAT of the peripheral skeleton decreased a year following sleeve gastrectomy. The amount of weight loss and reductions in lean and fat mass correlated with bone loss at all sites, and with changes in bone microarchitecture at peripheral sites. Conclusion MBS in adolescents is associated with aBMD reductions, and increases in MAT of the axial skeleton, while sleeve gastrectomy is associated with an increase in cortical vBMD and decrease in MAT of the peripheral skeleton. No reductions have been reported in peripheral strength estimates.

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High Cortico-Trabecular Transitional Zone Porosity and Reduced Trabecular Density in Men and Women with Stress Fractures

Journal of Clinical Medicine ◽

10.3390/jcm10051123 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1123

Author(s):

Afrodite Zendeli ◽

Minh Bui ◽

Lukas Fischer ◽

Ali Ghasem-Zadeh ◽

Wolfgang Schima ◽

...

Keyword(s):

Lower Limb ◽

Quantitative Computed Tomography ◽

Distal Tibia ◽

Transitional Zone ◽

Peripheral Quantitative Computed Tomography ◽

Stress Fractures ◽

Cross Sectional ◽

Men And Women ◽

Trabecular Microstructure ◽

Trabecular Density

To determine whether stress fractures are associated with bone microstructural deterioration we quantified distal radial and the unfractured distal tibia using high resolution peripheral quantitative computed tomography in 26 cases with lower limb stress fractures (15 males, 11 females; mean age 37.1 ± 3.1 years) and 62 age-matched healthy controls (24 males, 38 females; mean age 35.0 ± 1.6 years). Relative to controls, in men, at the distal radius, cases had smaller cortical cross sectional area (CSA) (p = 0.012), higher porosity of the outer transitional zone (OTZ) (p = 0.006), inner transitional zone (ITZ) (p = 0.043) and the compact-appearing cortex (CC) (p = 0.023) while trabecular vBMD was lower (p = 0.002). At the distal tibia, cases also had a smaller cortical CSA (p = 0.008). Cortical porosity was not higher, but trabecular vBMD was lower (p = 0.001). Relative to controls, in women, cases had higher distal radial porosity of the OTZ (p = 0.028), ITZ (p = 0.030) not CC (p = 0.054). Trabecular vBMD was lower (p = 0.041). Distal tibial porosity was higher in the OTZ (p = 0.035), ITZ (p = 0.009), not CC. Stress fractures are associated with compromised cortical and trabecular microstructure.

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Bone Microarchitecture, Volumetric or Areal Bone Mineral Density for Discrimination of Vertebral Deformity in Adults: A Cross-sectional Study

Journal of Clinical Densitometry ◽

10.1016/j.jocd.2020.05.005 ◽

2020 ◽

Author(s):

Canchen Ma ◽

Feitong Wu ◽

Feng Pan ◽

Laura Laslett ◽

Anuj Shah ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Vertebral Deformity ◽

Bone Microarchitecture ◽

Cross Sectional Study ◽

Areal Bone Mineral Density ◽

Sectional Study ◽

Mineral Density ◽

Cross Sectional

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Effect of Testosterone treatment on bone microarchitecture and bone mineral density in men: a two-year RCT

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab149 ◽

2021 ◽

Author(s):

Mark Ng Tang Fui ◽

Rudolf Hoermann ◽

Karen Bracken ◽

David J Handelsman ◽

Warrick J Inder ◽

...

Keyword(s):

Bone Mineral Density ◽

Fracture Risk ◽

Bone Mineral ◽

Bone Microarchitecture ◽

Quantitative Computed Tomography ◽

Distal Tibia ◽

Mineral Density ◽

Testosterone Undecanoate ◽

Testosterone Treatment ◽

Bone Remodeling Markers

Abstract Context Testosterone treatment increases bone mineral density (BMD) in hypogonadal men. Effects on bone microarchitecture, a determinant of fracture risk, are unknown. Objective Determine the effect of testosterone treatment on bone microarchitecture using high resolution-peripheral quantitative computed tomography (HR-pQCT). Design, Setting, Participants Men>50 years were recruited from six Australian centres. Interventions Injectable testosterone undecanoate or placebo over 2 years on the background of a community-based lifestyle program. Main outcomes Primary endpoint was cortical volumetric BMD (vBMD) at the distal tibia, measured using HR-pQCT in 177 men (one centre). Secondary endpoints included other HR-pQCT parameters and bone remodelling markers. Areal BMD (aBMD) was measured by dual energy X-ray absorptiometry (DXA) in 601 men (five centres). Using a linear mixed model for repeated measures, the mean adjusted differences (MAD) [95% CI] at 12 and 24 months between groups are reported as treatment effect. Results Over 24 months, testosterone treatment, compared to placebo, increased tibial cortical vBMD), 9.33mgHA/cm 3[3.96;14.71],p<0.001 or 3.1%[1.2;5.0], radial cortical vBMD, 8.96mgHA/cm 3[3.30;14.62],p=0.005 or 2.9%[1.0;4.9], total tibial vBMD, 4.16mgHA/cm 3[2.14;6.19],p<0.001 or 1.3%[0.6;1.9] and total radial vBMD, 4.42mgHA/cm 3[1.67;7.16],p=0.002 or 1.8%[0.4;2.0]. Testosterone also significantly increased cortical area and thickness at both sites. Effects on trabecular architecture were minor. Testosterone reduced bone remodeling markers CTX, -48.1ng/L[-81.1;-15.1],p<0.001, and P1NP, -6.8μg/L[-10.9;-2.7], p<0.001. Testosterone significantly increased aBMD at the lumbar spine, 0.04 g/cm 2[0.03;0.05],p<0.001, and the total hip, 0.01g/cm 2[0.01;0.02],p<0.001. Conclusions In men>50 years, testosterone treatment for 2 years increased volumetric bone density, predominantly via effects on cortical bone. Implications for fracture risk reduction require further study.

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The Effects of Ivacaftor on Bone Density and Microarchitecture in Children and Adults with Cystic Fibrosis

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa890 ◽

2020 ◽

Author(s):

Melissa S Putman ◽

Logan B Greenblatt ◽

Michael Bruce ◽

Taisha Joseph ◽

Hang Lee ◽

...

Keyword(s):

Cystic Fibrosis ◽

Bone Density ◽

Outcome Measures ◽

Bone Microarchitecture ◽

Medical Center ◽

Academic Medical Center ◽

Quantitative Computed Tomography ◽

Areal Bone Mineral Density ◽

Mineral Density ◽

The Impact

Abstract Context Cystic fibrosis (CF) transmembrane conductance (CFTR) dysfunction may play a role in CF-related bone disease (CFBD). Ivacaftor is a CFTR potentiator effective in improving pulmonary and nutritional outcomes in patients with the G551D-CFTR mutation. The effects of ivacaftor on bone health are unknown. Objective To determine the impact of ivacaftor on bone density and microarchitecture in children and adults with CF. Design Prospective observational multiple cohort study. Setting Outpatient clinical research center within a tertiary academic medical center. Patients or Other Participants Three cohorts of age-, race-, and gender-matched subjects were enrolled: 26 subjects (15 adults and 11 children) with CF and the G551D-CFTR mutation who were planning to start or had started treatment with ivacaftor within 3 months (Ivacaftor cohort), 26 subjects with CF were not treated with ivacaftor (CF Control cohort), and 26 healthy volunteers. Interventions All treatments, including Ivacaftor, were managed by the subjects’ pulmonologists. Main Outcome Measures Bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT), areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) and bone turnover markers at baseline, 1, and 2 years. Results Cortical volume, area, and porosity at the radius and tibia increased significantly in adults in the Ivacaftor cohort. No significant differences were observed in changes in aBMD, trabecular microarchitecture, or estimated bone strength in adults or in any outcome measures in children. Conclusions Treatment with ivacaftor was associated with increases in cortical microarchitecture in adults with CF. Further studies are needed to understand the implications of these findings.

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Spectrum of microarchitectural bone disease in inborn errors of metabolism: a cross-sectional, observational study

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01521-6 ◽

2020 ◽

Vol 15 (1) ◽

Cited By ~ 1

Author(s):

Karamjot Sidhu ◽

Bilal Ali ◽

Lauren A. Burt ◽

Steven K. Boyd ◽

Aneal Khan

Keyword(s):

Bone Density ◽

Short Stature ◽

Inborn Errors Of Metabolism ◽

Bone Microarchitecture ◽

Quantitative Computed Tomography ◽

Distal Tibia ◽

Secondary Outcome ◽

Mineral Density ◽

Inborn Errors ◽

Skeletal Pathology

Abstract Background Patients diagnosed with inborn errors of metabolism (IBEM) often present with compromised bone health leading to low bone density, bone pain, fractures, and short stature. Dual-energy X-ray absorptiometry (DXA) is the current gold standard for clinical assessment of bone in the general population and has been adopted for monitoring bone density in IBEM patients. However, IBEM patients are at greater risk for scoliosis, short stature and often have orthopedic hardware at standard DXA scan sites, limiting its use in these patients. Furthermore, DXA is limited to measuring areal bone mineral density (BMD), and does not provide information on microarchitecture. Methods In this study, microarchitecture was investigated in IBEM patients (n = 101) using a new three-dimensional imaging technology high-resolution peripheral quantitative computed tomography (HR-pQCT) which scans at the distal radius and distal tibia. Volumetric BMD and bone microarchitecture were computed and compared amongst the different IBEMs. For IBEM patients over 16 years-old (n = 67), HR-pQCT reference data was available and Z-scores were calculated. Results Cortical bone density was significantly lower in IBEMs associated with decreased bone mass when compared to lysosomal storage disorders (LSD) with no primary skeletal pathology at both the radius and tibia. Cortical thickness was also significantly lower in these disorders when compared to LSD with no primary skeletal pathology at the radius. Cortical porosity was significantly greater in hypophosphatasia when compared to all other IBEM subtypes. Conclusion We demonstrated compromised bone microarchitecture in IBEMs where there is primary involvement of the skeleton, as well as IBEMs where skeletal complications are a secondary outcome. In conclusion, our findings suggest HR-pQCT may serve as a valuable tool to monitor skeletal disease in the IBEM population, and provides insight to the greatly varying bone phenotype for this cohort that can be used for clinical monitoring and the assessment of response to therapeutic interventions.

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Association of bone microarchitecture with parathyroid hormone concentration and calcium intake in men: the STRAMBO study

Acta Endocrinologica ◽

10.1530/eje-11-0184 ◽

2011 ◽

Vol 165 (1) ◽

pp. 151-159 ◽

Cited By ~ 27

Author(s):

A Chaitou ◽

S Boutroy ◽

N Vilayphiou ◽

A Varennes ◽

M Richard ◽

...

Keyword(s):

Vitamin D ◽

Parathyroid Hormone ◽

Bone Turnover ◽

Calcium Intake ◽

Bone Microarchitecture ◽

Quantitative Computed Tomography ◽

Distal Tibia ◽

Volumetric Bone Mineral Density ◽

Mineral Density ◽

Low Calcium

ObjectiveIn the elderly, vitamin D deficit, low calcium intake, and impaired bone microarchitecture are associated with higher risk of hip fracture. We assessed the association of bone microarchitecture with calcium intake and serum concentrations of 25-hydroxycholecalciferol (25OHD) and parathyroid hormone (PTH) in men.DesignCross-sectional analysis was performed in 1064 men aged 20–87 years not taking vitamin D or calcium supplements.MethodsDaily calcium intake was assessed using a food frequency questionnaire. Bone microarchitecture was assessed at distal radius and tibia by high-resolution peripheral quantitative computed tomography. We measured serum and urinary levels of biochemical bone turnover markers (BTMs). Statistical models were adjusted for age, weight, height, and glomerular filtration rate.ResultsIn 500 men aged <65 years, lower 25OHD levels and low calcium intake were associated with lower trabecular volumetric bone mineral density (Dtrab) at the distal tibia, due to lower trabecular number (Tb.N). Low calcium intake was associated with lower cortical thickness (Ct.Th). Higher PTH level was associated with higher BTM levels. In 563 men aged ≥65 years, the highest PTH quartile was associated with lower Ct.Th (tibia), lower Dtrab (both sites), and lower Tb.N (radius) compared with the lowest quartile. Low calcium intake was associated with lower Tb.N and more heterogenous trabecular distribution. BTM positively correlated with the PTH concentration.ConclusionIn older men, elevated PTH concentration is associated with high bone turnover, poor trabecular microarchitecture (radius and tibia), and, at the distal tibia, lower Ct.Th. Low calcium intake is associated with lower Tb.N and more heterogenous trabecular distribution.

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Serum levels of sclerostin reflect altered bone microarchitecture in patients with hepatic cirrhosis

Wiener klinische Wochenschrift ◽

10.1007/s00508-019-01595-8 ◽

2020 ◽

Vol 132 (1-2) ◽

pp. 19-26 ◽

Cited By ~ 1

Author(s):

Robert Wakolbinger ◽

Christian Muschitz ◽

Jacqueline Wallwitz ◽

Gerd Bodlaj ◽

Xaver Feichtinger ◽

...

Keyword(s):

Bone Mineral Density ◽

Patient Group ◽

Bone Mineral ◽

Hepatic Cirrhosis ◽

Bone Microarchitecture ◽

Quantitative Computed Tomography ◽

Areal Bone Mineral Density ◽

Receptor Interaction ◽

Mineral Density ◽

Increased Risk

Summary Background Patients with hepatic cirrhosis are at increased risk of bone loss. Recent work on areal bone mineral density has reported contradictory findings. As the assessment of bone microarchitecture is complex, a search was made for correlations with new serum markers of bone turnover. Current data on serum sclerostin levels in patients with increased fracture risk are divergent and to date only one study has examined patients with hepatic cirrhosis. Therefore, the aim of this study was to evaluate serum sclerostin levels and to test for correlations with microarchitecture. Methods This study was performed in 32 patients with recently diagnosed hepatic cirrhosis and 32 controls. The parameters of bone microarchitecture were assessed by high-resolution peripheral quantitative computed tomography. Sclerostin was detected via a new ELISA that detects the active receptor interaction site at loop 2 of the sclerostin core region. Results Sclerostin levels were slightly, but not significantly lower in the patient group, compared to controls. In contrast, patients with alcoholic liver cirrhosis had significantly lower levels than the controls. A significant correlation with areal bone mineral density (BMD) and trabecular microarchitecture was observed in the patient group. However, there was hardly any correlation between sclerostin and bone microarchitecture in the controls. Conclusion In hepatic cirrhosis, sclerostin is related to altered bone microarchitecture and lower areal BMD. In alcoholic liver disease, low sclerostin concentrations were seen.

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Spectrum of microarchitectural bone disease in inborn errors of metabolism: a cross-sectional, observational study

10.21203/rs.3.rs-28436/v1 ◽

2020 ◽

Author(s):

Karamjot Sidhu ◽

Bilal Ali ◽

Lauren A Burt ◽

Steven K Boyd ◽

Aneal Khan

Keyword(s):

Bone Density ◽

Short Stature ◽

Inborn Errors Of Metabolism ◽

Bone Microarchitecture ◽

Quantitative Computed Tomography ◽

Distal Tibia ◽

Secondary Outcome ◽

Mineral Density ◽

Inborn Errors ◽

Skeletal Pathology

Abstract Background Patients diagnosed with inborn errors of metabolism (IBEM) often present with compromised bone health leading to low bone density, bone pain, fractures, and short stature. Dual-energy X-ray absorptiometry (DXA) is the current gold standard for clinical assessment of bone in the general population and has been adopted for monitoring bone density in IBEM patients. However, IBEM patients are at greater risk for scoliosis, short stature and often have orthopedic hardware at standard DXA scan sites, limiting its use in these patients. Furthermore, DXA is limited to measuring areal bone mineral density (BMD), and does not provide information on microarchitecture. Methods In this study, microarchitecture was investigated in IBEM patients (n = 101) using a new three-dimensional imaging technology high-resolution peripheral quantitative computed tomography (HR-pQCT) which scans at the distal radius and distal tibia. Volumetric BMD and bone microarchitecture were computed and compared amongst the different IBEMs. For IBEM patients over 16 years-old (n = 67), HR-pQCT reference data was available and Z-scores were calculated. Results Cortical bone density was significantly lower in IBEMs associated with decreased bone mass when compared to lysosomal storage disorders (LSD) with no primary skeletal pathology at both the radius and tibia. Cortical thickness was also significantly lower in these disorders when compared to LSD with no primary skeletal pathology at the radius. Cortical porosity was significantly greater in hypophosphatasia when compared to all other IBEM subtypes. Conclusion We demonstrated compromised bone microarchitecture in IBEMs where there is primary involvement of the skeleton, as well as IBEMs where skeletal complications are a secondary outcome. In conclusion, our findings suggest HR-pQCT may serve as a valuable tool to monitor skeletal disease in the IBEM population, and provides insight to the greatly varying bone phenotype for this cohort that can be used for clinical monitoring and the assessment of response to therapeutic interventions.

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