Daniel Sundh

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.

Association of Physical Activity with Trabecular Microstructure and Cortical Bone at Distal Tibia and Radius in Young Adult Men

CONTEXT The relationship between physical activity, trabecular microstructure, and cortical geometry in weight-bearing and non-weight-bearing bone has not previously been studied in men. OBJECTIVE The aim of this study was to investigate whether present (type and amount) and previous duration of physical activity were associated with trabecular microstructure and cortical cross-sectional area (CSA) in weight-bearing bone in young men. DESIGN AND SETTING This was a cross-sectional, population-based study. PARTICIPANTS Participants included a cohort of 829 Swedish men between 22.8 and 25.7 yr old (24.1 +/- 0.6 yr, mean +/- SD). MAIN OUTCOME MEASURES Several microstructural trabecular and cortical traits were assessed with high-resolution three-dimensional peripheral quantitative computed tomography at distal tibia and radius. A standardized questionnaire was used to collect information about physical activity amount (hours per year), duration (years), and type (strain score 0-3, based on ground reaction forces). RESULTS Men with the highest physical activity strain score had higher tibial trabecular bone volume fraction (13.9Delta%) and trabecular number (12.7%) than men with the lowest strain score (P < 0.001). Men in the group with the longest duration of physical activity had higher tibial cortical CSA (16.1%) than the sedentary men (P < 0.001). Inclusion of all physical activity variables in a linear regression model revealed that strain score independently predicted trabecular bone volume fraction, and trabecular number (P < 0.001) and that duration of previous physical activity independently predicted cortical CSA (P < 0.001) of the tibia. CONCLUSIONS In this large cohort of young men, the degree of mechanical loading due to type of physical activity was predominantly associated with trabecular microstructure, whereas duration of previous physical activity was mainly related to parameters reflecting cortical bone size in weight-bearing bone.

Exercise During Growth and Young Adulthood Is Independently Associated With Cortical Bone Size and Strength in Old Swedish Men

Previous studies have reported an association between exercise during youth and increased areal bone mineral density at old age. The primary aim of this study was to investigate if exercise during growth was independently associated with greater cortical bone size and whole bone strength in weight‐bearing bone in old men. The tibia and radius were measured using both peripheral quantitative computed tomography (pQCT) (XCT‐2000; Stratec) at the diaphysis and high‐resolution pQCT (HR‐pQCT) (XtremeCT; Scanco) at the metaphysis to obtain cortical bone geometry and finite element–derived bone strength in distal tibia and radius, in 597 men, 79.9 ± 3.4 (mean ± SD) years old. A self‐administered questionnaire was used to collect information about previous and current physical activity. In order to determine whether level of exercise during growth and young adulthood or level of current physical activity were independently associated with bone parameters in both tibia and radius, analysis of covariance (ANCOVA) analyses were used. Adjusting for covariates and current physical activity, we found that men in the group with the highest level of exercise early in life (regular exercise at a competitive level) had higher tibial cortical cross‐sectional area (CSA; 6.3%, p < 0.001) and periosteal circumference (PC; 1.6%, p = 0.011) at the diaphysis, and higher estimated bone strength (failure load: 7.5%, p < 0.001; and stiffness: 7.8%, p < 0.001) at the metaphysis than men in the subgroup with the lowest level of exercise during growth and young adulthood. Subjects in the group with the highest level of current physical activity had smaller tibial endosteal circumference (EC; 3.6%, p = 0.012) at the diaphysis than subjects with a lower current physical activity, when adjusting for covariates and level of exercise during growth and young adulthood. These findings indicate that exercise during growth can increase the cortical bone size via periosteal expansion, whereas exercise at old age may decrease endosteal bone loss in weight‐bearing bone in old men.

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.

Increased Cortical Porosity in Older Men With Fracture

Cortical porosity increases with age and affects bone strength, but its association with fracture in older men is unknown. The aim of this study was to investigate whether cortical porosity is associated with prevalent fractures in older men. A subsample of 456 men aged 80.2 ± 3.5 (mean ± SD) years, with available high‐resolution peripheral quantitative computed tomography measurements at the tibia from the 5‐year follow‐up exam, was drawn from the prospective MrOS Gothenburg study. Dual‐energy X‐ray absorptiometry was used to measure areal bone mineral density (aBMD). Data on physical activity, calcium intake, medications, diseases, and smoking were collected on questionnaires at the follow‐up exam. Of 87 men (19.1%) with fracture at or after age 50 years (all fracture group), 52 (11.4%) had had a self‐reported fracture before the baseline exam and 35 (7.7%) had had an X‐ray–verified fracture between baseline and follow‐up. Men in the all‐fracture group and in the X‐ray–verified group had 15.8% (13.2% ± 4.9% versus 11.4% ± 3.8%; p < 0.001) and 21.6% (14.1% ± 5.2% versus 11.6% ± 3.9%; p < 0.01) higher cortical porosity, respectively, than men in the nonfracture group. The independent associations between bone microstructure parameters and fracture were tested using multivariate logistic regression with age, height, weight, calcium intake, smoking, physical activity, medications, and diseases as covariates. Cortical porosity was independently associated with any fracture (reported or X‐ray–verified; OR per SD increase 1.49; 95% confidence interval (CI), 1.17 to 1.90) and with any X‐ray–verified fracture alone (OR 1.73; 95% CI, 1.23 to 2.42). Including aBMD (spine or hip, respectively) in the multivariate logistic regression above revealed that cortical porosity was associated with any fracture (OR 1.54; 95% CI, 1.17 to 2.01) and with X‐ray–verified fracture alone (OR 1.49; 95% CI, 1.00 to 2.22). Cortical porosity was associated with prevalence of fracture even after adjustment for aBMD.

Serum Estradiol Levels Are Inversely Associated With Cortical Porosity in Older Men

Context: The key role of serum estradiol (E2) for bone health in men is well established. The effect of serum sex steroids on bone microstructure, measured by high-resolution peripheral quantitative computed tomography, remains unknown in elderly men. Objective: The objective of the study was to examine the associations between serum sex steroids and bone microstructural parameters in older men. Methods: Trabecular and cortical bone microstructure at the tibia was measured by high-resolution peripheral quantitative computed tomography in 440 men (mean 80 y of age) participating in the population-based Osteoporotic Fractures in Men Sweden cohort. Serum levels of E2 and T were analyzed with mass spectrometry and free E2 and free T levels were calculated using law-of-mass-action equations. Results: Age-adjusted models demonstrated that E2 and free E2 but not T or free T associated significantly inversely with cortical porosity. The associations between E2 and free E2 and cortical porosity remained significant after further adjustment for height, weight, physical activity, calcium intake, and smoking. Models including both serum E2 and T demonstrated that E2 (standardized β = −.12, P < .05) but not T associated independently with cortical porosity. A similar independent association was found for free E2 (standardized β = −.12, P < .05) but not free T. Free E2 associated significantly with trabecular bone volume fraction in the age-adjusted models, but this association did not remain significant after further adjustment. Conclusions: Serum E2 levels associated inversely with cortical porosity in 80-year-old men. We propose that low serum E2 may reduce cortical bone strength, at least partly, by increasing cortical porosity and thereby increase fracture risk in older men.

Cortical bone area predicts incident fractures independently of areal bone mineral density in older men

Context: Areal bone mineral density (aBMD) measured using dual-energy X-ray absorptiometry (DXA) is used clinically to predict fracture but does not discriminate between trabecular and cortical bone assessment. Objective: This study aimed to investigate whether information on cortical and trabecular bone predict fracture risk independently of aBMD and clinical risk factors. Design and Participants: Cortical area, bone mass, porosity, and trabecular bone volume fraction (BVTV) were measured at the tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT) in 456 men (80.2 ± 3.5 years) recruited from the general population in Gothenburg, Sweden. aBMD was measured using DXA. Incident fractures (71 men) were X-ray verified. Associations were evaluated using Cox regression. Results: Cortical area [hazard ratio (HR) per standard deviation (SD) decrease, 2.05; 95% confidence interval (CI), 1.58 to 2.65], cortical bone mass (HR, 2.07; 95% CI, 1.58 to 2.70), and BVTV (HR, 1.62; 95% CI, 1.26 to 2.07), but not cortical porosity, were independently associated with fracture risk. These associations remained after adjustment for femoral neck aBMD and Fracture Risk Assessment risk factors (area: HR 1.96, 95% CI, 1.44 to 2.66; mass: HR 1.99, 95% CI, 1.45 to 2.74; BV/TV: HR 1.46, 95% CI, 1.09 to 1.96). After entering BV/TV and cortical area or bone mass simultaneously in the adjusted models, only the cortical parameters remained important predictors of fracture. Conclusion: HR-pQCT measurement of cortical area and mass might add clinically useful information for the evaluation of fracture risk.

Increased cortical porosity in women with hip fracture.

Hip fractures cause increased mortality and disability and consume enormous healthcare resources. Only 46% of hip fracture patients have osteoporosis at the total hip according to dual‐energy X‐ray absorptiometry (DXA) measurement. Cortical porosity increases with ageing and is believed to be important for bone strength.

Low serum vitamin D is associated with higher cortical porosity in elderly men

Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25‐hydroxyvitamin D has not been reported.

Current Physical Activity Is Independently Associated with Cortical Bone Size and Bone Strength in Elderly Swedish Women

Physical activity is believed to have the greatest effect on the skeleton if exerted early in life, but whether or not possible benefits of physical activity on bone microstructure or geometry remain at old age has not been investigated in women. The aim of this study was to investigate if physical activity during skeletal growth and young adulthood or at old age was associated with cortical geometry and trabecular microarchitecture in weight‐bearing and non–weight‐bearing bone, and areal bone mineral density (aBMD) in elderly women. In this population‐based cross‐sectional study 1013 women, 78.2 ± 1.6 (mean ± SD) years old, were included. Using high‐resolution 3D pQCT (XtremeCT), cortical cross‐sectional area (Ct.CSA), cortical thickness (Ct.Th), cortical periosteal perimeter (Ct.Pm), volumetric cortical bone density (D.Ct), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp) were measured at the distal (14% level) and ultra‐distal tibia and radius, respectively. aBMD was assessed using DXA (Hologic Discovery A) of the spine and hip. A standardized questionnaire was used to collect information about previous exercise and the Physical Activity Scale for the Elderly (PASE) was used for current physical activity. A linear regression model (including levels of exercise during skeletal growth and young adulthood [10 to 30 years of age], PASE score, and covariates) revealed that level of current physical activity was independently associated with Ct.CSA (β = 0.18, p < 0.001) and Ct.Th (β = 0.15, p < 0.001) at the distal tibia, Tb.Th (β = 0.11, p < 0.001) and BV/TV (β = 0.10, p = 0.001) at the ultra‐distal tibia, and total hip aBMD (β = 0.10, p < 0.001). Current physical activity was independently associated with cortical bone size, in terms of thicker cortex but not larger periosteal circumference, and higher bone strength at the distal tibia on elderly women, indicating that physical activity at old age may decrease cortical bone loss in weight‐bearing bone in elderly women.