Determinants of Peak Bone Mass in Men

Objective: The aim of this thesis was to identify, investigate and evaluate hereditary and environmental factors associated with peak bone mass or bone development in men. Method: All studies in the thesis were performed within a well-characterized population-based cohort of 1068 men between 18 to 20 years of age at baseline (the Gothenburg Obesity and Osteoporosis Determinants (GOOD) study). Measurements of bone mass, bone geometry, microstructure and estimated bone strength were assessed using dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and high-resolution pQCT with applied finite element analysis. A self-administered questionnaire was used to collect information about physical activity, calcium intake, smoking and fracture prevalence. For evaluation of heredity and maternal factors, various Swedish registers were used, and fracture prevalence was verified in local hospital X-ray records. Results: Family history of a grandfather with hip fracture was associated with reduced areal bone mineral density (aBMD) and cortical bone size in 19-year-old men. Advancing maternal age was a negative predictor of lumbar spine aBMD in 19-year-old men, independently of the possible confounders known to affect bone mass in late adolescence. Young men who started to smoke in young adulthood developed lower aBMD at several sites as well as lower trabecular density and smaller cortical cross-sectional area, than their nonsmoking peers. Prevalent fractures in young adult men were associated with impaired trabecular microstructure at the radius, independently of aBMD and cortical thickness. Conclusion: We identified heredity over two generations, high maternal age, smoking and prevalent fractures as predictors of low peak bone mass. We suggest that these factors could possibly affect the risk of osteoporosis and fracture later in life

X‐ray–verified fractures are associated with finite element analysis–derived bone strength and trabecular microstructure in young adult men

It has been suggested that fracture during childhood could be a predictor of low peak bone mass and thereby a potential risk factor for osteoporosis and fragility fractures later in life. The aim of this cross‐sectional, population‐based study was to investigate whether prevalent fractures, occurring from birth to young adulthood, were related to high‐resolution peripheral quantitative computed tomography (HR‐pQCT)–derived trabecular and cortical microstructure, as well as bone strength estimated by finite element (FEA) analysis of the radius and tibia in 833 young adult men around the time of peak bone mass (ages 23 to 25 years). In total, 292 subjects with prevalent X‐ray–verified fractures were found. Men with prevalent fractures had lower trabecular bone volume fraction (BV/TV) at the radius (5.5%, p < 0.001) and tibia (3.7%, p < 0.001), as well as lower cortical thickness (5.1%, p < 0.01) and cortical cross‐sectional area (4.1%, p < 0.01) at the tibia. No significant differences were seen for the cortical porosity or mean pore diameter. Using a logistic regression model (including age, smoking, physical activity, calcium intake, height, and weight as covariates), every SD decrease of FEA‐estimated failure load was associated with an increased prevalence of fractures at both the radius (odds ratio [OR] 1.22 [1.03–1.45]) and tibia (OR 1.32 [1.11–1.56]). Including dual‐energy X‐ray absorptiometry (DXA)–derived radius areal bone mineral density (aBMD), cortical thickness, and trabecular BV/TV simultaneously in a logistic regression model (with age, smoking, physical activity, calcium intake, height, and weight as covariates), BV/TV was inversely and independently associated with prevalent fractures (OR 1.28 [1.04–1.59]), whereas aBMD and cortical thickness were not (OR 1.19 [0.92–1.55] and OR 0.91 [0.73–1.12], respectively). In conclusion, prevalent fractures in young adult men were associated with impaired trabecular BV/TV at the radius, independently of aBMD and cortical thickness, indicating that primarily trabecular bone deficits are of greatest importance for prevalent fracture in this population. © 2013 American Society for Bone and Mineral Research

X-ray-verified fractures are associated with finite element analysis-derived bone strength and trabecular microstructure in young adult men

It has been suggested that fracture during childhood could be a predictor of low peak bone mass and thereby a potential risk factor for osteoporosis and fragility fractures later in life. The aim of this cross‐sectional, population‐based study was to investigate whether prevalent fractures, occurring from birth to young adulthood, were related to high‐resolution peripheral quantitative computed tomography (HR‐pQCT)–derived trabecular and cortical microstructure, as well as bone strength estimated by finite element (FEA) analysis of the radius and tibia in 833 young adult men around the time of peak bone mass (ages 23 to 25 years). In total, 292 subjects with prevalent X‐ray–verified fractures were found. Men with prevalent fractures had lower trabecular bone volume fraction (BV/TV) at the radius (5.5%, p < 0.001) and tibia (3.7%, p < 0.001), as well as lower cortical thickness (5.1%, p < 0.01) and cortical cross‐sectional area (4.1%, p < 0.01) at the tibia. No significant differences were seen for the cortical porosity or mean pore diameter. Using a logistic regression model (including age, smoking, physical activity, calcium intake, height, and weight as covariates), every SD decrease of FEA‐estimated failure load was associated with an increased prevalence of fractures at both the radius (odds ratio [OR] 1.22 [1.03–1.45]) and tibia (OR 1.32 [1.11–1.56]). Including dual‐energy X‐ray absorptiometry (DXA)–derived radius areal bone mineral density (aBMD), cortical thickness, and trabecular BV/TV simultaneously in a logistic regression model (with age, smoking, physical activity, calcium intake, height, and weight as covariates), BV/TV was inversely and independently associated with prevalent fractures (OR 1.28 [1.04–1.59]), whereas aBMD and cortical thickness were not (OR 1.19 [0.92–1.55] and OR 0.91 [0.73–1.12], respectively). In conclusion, prevalent fractures in young adult men were associated with impaired trabecular BV/TV at the radius, independently of aBMD and cortical thickness, indicating that primarily trabecular bone deficits are of greatest importance for prevalent fracture in this population. © 2013 American Society for Bone and Mineral Research

A high amount of local adipose tissue Is associated with high cortical porosity and low bone material strength in older women

Obesity is associated with increased risk of fractures, especially at skeletal sites with a large proportion of cortical bone, such as the humerus and ankle. Obesity increases fracture risk independently of BMD, indicating that increased adipose tissue could have negative effects on bone quality. Microindentation assesses bone material strength index (BMSi) in vivo in humans. The aim of this study was to investigate if different depots of adipose tissue were associated with BMSi and cortical bone microstructure in a population based group of 202 women, 78.2 ± 1.1 (mean ± SD) years old. Bone parameters and subcutaneous (s.c.) fat were measured at the tibia with an XtremeCT device. BMSi was assessed using the OsteoProbe device, and based on at least 11 valid reference point indentations at the mid‐tibia. Body composition was measured with dual X‐ray absorptiometry. BMSi was inversely correlated to body mass index (BMI) (r = –0.17, p = 0.01), whole body fat mass (r = –0.16,p = 0.02), and, in particular, to tibia s.c. fat (r = –0.33, p < 0.001). Tibia s.c. fat was also correlated to cortical porosity (Ct.Po; r = 0.19, p = 0.01) and cortical volumetric BMD (Ct.vBMD; r = –0.23, p = 0.001). Using linear regression analyses, tibia s.c. fat was found to be independent of covariates (age, height, log weight, bisphosphonates or glucocorticoid use, smoking, calcium intake, walking speed, and BMSi operator) and associated with BMSi (β = –0.34,p < 0.001), Ct.Po (β = 0.18, p = 0.01), and Ct.vBMD (β = –0.32, p < 0.001). BMSi was independent of covariates associated with cortical porosity (β = –0.14, p = 0.04) and cortical volumetric BMD (β = 0.21, p = 0.02) at the distal tibia, but these bone parameters could only explain 3.3% and 5.1% of the variation in BMSi, respectively. In conclusion, fat mass was independently and inversely associated with BMSi and Ct.vBMD, but positively associated with Ct.Po, indicating a possible adverse effect of adipose tissue on bone quality and bone microstructure. Local s.c. fat in tibia was most strongly associated with these bone traits, suggesting a local or paracrine, rather than systemic, negative effect of fat on bone. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR)

The prevalence of vertebral fractures is associated with reduced hip bone density and inferior peripheral appendicular volumetric bone density and structure in older women

Vertebral fractures (VFs) are among the most severe and prevalent osteoporotic fractures. Their association with bone microstructure have been investigated in several retrospective case‐control studies with spine radiography for diagnosis of VF. The aim of this population‐based cross‐sectional study of 1027 women aged 75 to 80 years was to investigate if prevalent VF, identified by vertebral fracture assessment (VFA) by dual‐energy X‐ray absorptiometry (DXA), was associated with appendicular volumetric bone density, structure, and bone material strength index (BMSi), independently of hip areal bone mineral density (aBMD). aBMD was measured using DXA (Discovery; Hologic); BMSi with microindentation (Osteoprobe); and bone geometry, volumetric BMD, and microstructure with high‐resolution peripheral quantitative computed tomography (HRpQCT) (XtremeCT; Scanco Medical AG). aBMD was lower (spine 3.2%, total hip [TH] 3.8%) at all sites in women with VF, but tibia BMSi did not differ significantly compared to women without VF. In multivariable adjusted logistic regression models, radius trabecular bone volume fraction and tibia cortical area (odds ratio [OR] 1.26; 95% confidence interval [CI], [1.06 to 1.49]; and OR 1.27 [95% CI, 1.08 to 1.49], respectively) were associated with VF prevalence, whereas BMSi and cortical porosity were not. The risk of having one, two, or more than two VFs was increased 1.27 (95% CI, 1.04 to 1.54), 1.83 (95% CI, 1.28 to 2.61), and 1.78 (95% CI, 1.03 to 3.09) times, respectively, for each SD decrease in TH aBMD. When including either cortical area, trabecular bone volume fraction or TBS in the model together with TH aBMD and covariates, only TH aBMD remained independently associated with presence of any VF. In conclusion, TH aBMD was consistently associated with prevalent VFA‐verified VF, whereas neither trabecular bone volume fraction, cortical area, cortical porosity, nor BMSi were independently associated with VF in older women. © 2017 American Society for Bone and Mineral Research

Type 2 diabetes mellitus is associated with better bone microarchitecture but lower bone material strength and poorer physical function in elderly women: A population-based study

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of fractures according to several studies. The underlying mechanisms remain unclear, although small case‐control studies indicate poor quality of the cortical bone. We have studied a population‐based sample of women aged 75 to 80 years in Gothenburg, randomly invited from the population register. Areal bone mineral density (aBMD) was measured by dual‐energy X‐ray absorptiometry (Hologic Discovery A), bone microarchitecture by high‐resolution peripheral quantitative computed tomography (HR‐pQCT; ExtremeCT from Scanco Medical AG), and reference point indentation was performed with Osteoprobe (Active Life Scientific). Women with T2DM (n = 99) had higher aBMD compared to controls (n = 954). Ultradistal tibial and radial trabecular bone volume fraction (+11% and +15%, respectively), distal cortical volumetric BMD (+1.6% and +1.7%), cortical area (+11.5% and +9.3%), and failure load (+7.7% and +12.9%) were higher in diabetics than in controls. Cortical porosity was lower (mean ± SD: 1.5% ± 1.1% versus 2.0% ± 1.7%, p = 0.001) in T2DM in the distal radius but not in the ultradistal radius or the tibia. Adjustment for covariates (age, body mass index, glucocorticoid treatment, smoking, physical activity, calcium intake, bone‐active drugs) eliminated the differences in aBMD but not in HR‐pQCT bone variables. However, bone material strength index (BMSi) by reference point indentation was lower in T2DM (74.6 ± 7.6 versus 78.2 ± 7.5, p < 0.01), also after adjustment, and women with T2DM performed clearly worse in measures of physical function (one leg standing: –26%, 30‐s chair‐stand test: –7%, timed up and go: +12%, walking speed: +8%; p < 0.05‐0.001) compared to controls. In conclusion, we observed a more favorable bone microarchitecture but no difference in adjusted aBMD in elderly women with T2DM in the population compared to nondiabetics. Reduced BMSi and impaired physical function may explain the increased fracture risk in T2DM. © 2016 American Society for Bone and Mineral Research