Increased Bone Material Strength Index Is Positively Associated With the Risk of Incident Osteoporotic Fractures in Older Swedish Women.

No previous studies have investigated the association between the bone material strength index (BMSi; an indicator of bone material properties obtained by microindentation) and the risk of incident fracture. The primary purpose of this prospective cohort study was to evaluate if BMSi is associated with incident osteoporotic fracture in older women and, secondarily, with prevalent fractures, anthropometric traits, or measurements of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). In a population-based cohort, 647 women aged 75 to 80 years underwent bone microindentation using the OsteoProbe device. Data on clinical risk factors (CRFs), prevalent fractures, and incident fractures were collected using questionnaires, medical records, and a regional X-ray archive. BMD and vertebral fracture assessment (VFA) were assessed by DXA (Hologic, Discovery A). Associations between BMSi, anthropometrics, BMD, and prevalent fractures were investigated using correlation and linear and logistic regression. Cox proportional hazards and competing risks analysis by Fine and Gray were used to study the association between BMSi and the risk of fracture and mortality. BMSi was weakly associated with age (r = -0.13, p < 0.001) and BMI (r = -0.21, p < 0.001) and with BMD of lumbar spine (ß = 0.09, p = 0.02) and total hip (ß = 0.08, p = 0.05), but only after adjustments. No significant associations were found between BMSi and prevalent fractures (self-reported and/or VFA identified, n = 332). During a median follow-up time of 6.0 years, 121 major osteoporotic fractures (MOF), 151 any fractures, and 50 deaths occurred. Increasing BMSi (per SD) was associated with increased risk of MOF (hazard ratio [HR] = 1.29, 95% confidence interval [CI] 1.07-1.56), any fracture (HR = 1.29, 95% CI 1.09-1.53), and mortality (HR = 1.44, 95% CI 1.07-1.93). The risk of fracture did not materially change with adjustment for confounders, CRFs, femoral neck BMD, or when considering the competing risk of death. In conclusion, unexpectedly increasing BMSi was associated with greater fracture risk. The clinical relevance and potential mechanisms of this finding require further study. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC 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.

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 (ß = -0.34,p < 0.001), Ct.Po (ß = 0.18, p = 0.01), and Ct.vBMD (ß = -0.32, p < 0.001). BMSi was independent of covariates associated with cortical porosity (ß = -0.14, p = 0.04) and cortical volumetric BMD (ß = 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.

Bone turnover markers predict bone mass development in young adult men: a five-year longitudinal study.

CONTEXT: Peak bone mass is an important factor for the lifetime risk of developing osteoporosis. Ways to predict bone development in young adulthood are lacking. Objective and Main Outcome Measures: The aim of this study was to investigate whether baseline measurements of bone turnover markers could predict bone development in early adulthood in men. DESIGN, SETTING, AND PARTICIPANTS: In total, 817 men (age at baseline, 18.9 ± 0.6 y; mean ± SD) from the population-based Gothenburg Osteoporosis and Obesity Determinants Study were included in this 5-year longitudinal study. Areal bone mineral density (aBMD) and bone mineral content (BMC) were measured using dual-energy x-ray absorptiometry, and volumetric BMD (vBMD) and cortical bone size were measured using peripheral quantitative computed tomography. Blood samples were collected at the baseline visit, and levels of osteocalcin (OC) and N-terminal telopeptide of type I collagen were analyzed. RESULTS: OC was a positive predictor of the increase in aBMD and BMC of the total body (R(2): aBMD, 6.6%; BMC, 4.9%), lumbar spine (R(2): aBMD, 5.4%; BMC, 5.7%), and radius (R(2): aBMD, 14.8%; BMC, 12.8%) between 19 and 24 years (P < .001). Men in the highest OC quartile at baseline (35.2 ± 4.4 ng/mL; mean ± SD) gained markedly more in radius cortical cross-sectional area (4.0 ± 4.3 vs 1.9 ± 2.9 mm(2)) and trabecular vBMD (11 ± 7 vs 3 ± 12 mg/mm(3)) than men in the lowest OC quartile at baseline (17.7 ± 2.3 ng/mL; mean ± SD) (P < .001). CONCLUSION: A high OC level at the age of 19 predicts a favorable development in BMD, BMC, and bone size between 19 and 24 years of age.

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.

Smoking is associated with impaired bone mass development in young adult men: a 5-year longitudinal study.

It has previously been shown that smoking is associated with reduced bone mass and increased fracture risk, but no longitudinal studies have been published investigating altered smoking behavior at the time of bone mass acquisition. The aim of this study was to investigate the development of bone density and geometry according to alterations in smoking behavior in a 5-year, longitudinal, population-based study of 833 young men, age 18 to 20 years (baseline). Furthermore, we aimed to examine the cross-sectional, associations between current smoking and parameters of trabecular microarchitecture of the radius and tibia, using high-resolution peripheral quantitative computed tomography (HR-pQCT), in young men aged 23 to 25 years (5-year follow-up). Men who had started to smoke since baseline had considerably smaller increases in areal bone mineral density (aBMD) at the total body (mean ± SD, 0.020 ± 0.047 mg/cm(2) versus 0.043 ± 0.040 mg/cm(2) , p < 0.01) and lumbar spine (0.027 ± 0.062 mg/cm(2) versus 0.052 ± 0.065 mg/cm(2) , p = 0.04), and substantially greater decreases in aBMD at the total hip (-0.055 ± 0.058 mg/cm(2) versus -0.021 ± 0.062 mg/cm(2) , p < 0.01) and femoral neck (-0.077 ± 0.059 mg/cm(2) versus -0.042 ± 0.070 mg/cm(2) , p < 0.01) than men who were nonsmokers at both the baseline and follow-up visits. At the tibia, subjects who had started to smoke had a smaller increment of the cortical cross-sectional area (CSA) than nonsmokers (8.1 ± 4.3 mm(2) versus 11.5 ± 8.9 mm(2) , p = 0.03), and a larger decrement of trabecular volumetric BMD (vBMD) than nonsmokers (-13.9 ± 20.5 mg/mm(3) versus -4.1 ± 13.9 mg/mm(3) , p < 0.001). In the cross-sectional analysis at follow-up (23-25 years of age), smokers had significantly lower trabecular vBMD at the tibia (7.0%, p < 0.01) due to reduced trabecular thickness (8.9%, p < 0.001), as assessed using HR-pQCT, than nonsmokers. In conclusion, this study is the first to report that men who start to smoke in young adulthood have poorer development of their aBMD at clinically important sites such as the spine and hip than nonsmokers, possibly due to augmented loss of trabecular density and impaired growth of cortical cross-sectional area.

Catch up in bone acquisition in young adult men with late normal puberty.

The aim of this study was to investigate the development of bone mineral density (BMD) and bone mineral content (BMC) in relation to peak height velocity (PHV), and to investigate whether late normal puberty was associated with remaining low BMD and BMC in early adulthood in men. In total, 501 men (mean ± SD, 18.9 ± 0.5 years of age at baseline) were included in this 5-year longitudinal study. Areal BMD (aBMD) and BMC, volumetric BMD (vBMD) and cortical bone size were measured using dual-energy X-ray absorptiometry (DXA) and pQCT. Detailed growth and weight charts were used to calculate age at PHV, an objective assessment of pubertal timing. Age at PHV was a strong positive predictor of the increase in aBMD and BMC of the total body (R(2) aBMD 11.7%; BMC 4.3%), radius (R(2) aBMD 23.5%; BMC 22.3%), and lumbar spine (R(2) aBMD 11.9%; BMC 10.5%) between 19 and 24 years (p < 0.001). Subjects were divided into three groups according to age at PHV (early, middle, and late). Men with late puberty gained markedly more in aBMD and BMC at the total body, radius, and lumbar spine, and lost less at the femoral neck (p < 0.001) than men with early puberty. At age 24 years, no significant differences in aBMD or BMC of the lumbar spine, femoral neck, or total body were observed, whereas a deficit of 4.2% in radius aBMD, but not in BMC, was seen for men with late versus early puberty (p < 0.001). pQCT measurements of the radius at follow-up demonstrated no significant differences in bone size, whereas cortical and trabecular vBMD were 0.7% (p < 0.001) and 4.8% (p < 0.05) lower in men with late versus early puberty. In conclusion, our results demonstrate that late puberty in males was associated with a substantial catch up in aBMD and BMC in young adulthood, leaving no deficits of the lumbar spine, femoral neck, or total body at age 24 years.

Cortical consolidation due to increased mineralization and endosteal contraction in young adult men: a five-year longitudinal study.

CONTEXT: Peak bone mass is an important factor in the lifetime risk of developing osteoporosis. Large, longitudinal studies investigating the age of attainment of site-specific peak bone mass are lacking. OBJECTIVE AND MAIN OUTCOME MEASURES: The main outcome measures were to determine the site-specific development of peak bone mass in appendicular and axial skeletal sites and in the trabecular and cortical bone compartments, using both dual x-ray absorptiometry and peripheral computed tomography. DESIGN, SETTING, AND POPULATION: In total, 833 men [aged 24.1 ± 0.6 yr (mean ± sd)] from the original population-based Gothenburg Osteoporosis and Obesity Determinants Study (n = 1068) were included in this follow-up examination at 61.2 ± 2.3 months. Areal bone mineral density (aBMD) was measured with dual x-ray absorptiometry, whereas cortical and trabecular volumetric bone mineral density and bone size were measured by peripheral computed tomography at baseline and at the 5-yr follow-up. RESULTS: During the 5-yr study period, aBMD of the total body, lumbar spine, and radius increased by 3.4, 4.2, and 7.8%, respectively, whereas a decrease in aBMD of the total hip of 1.9% was observed (P < 0.0001). Increments of 2.1 and 0.7% were seen for cortical volumetric bone mineral density of the radius and tibia, respectively (P < 0.0001), whereas cortical thickness increased by 3.8% at the radius and 6.5% at the tibia due to diminished endosteal circumference (radius 2.3% and tibia 4.6%, P < 0.0001). CONCLUSION: aBMD decreased at the hip but increased at the spine and radius, in which the increment was explained by continued mineralization and augmented cortical thickness due to endosteal contraction in men between ages 19 and 24 yr.

Trabecular volumetric bone mineral density is associated with previous fracture during childhood and adolescence in males: the GOOD study.

Areal bone mineral density (aBMD) measured with dual-energy X-ray absorptiometry (DXA) has been associated with fracture risk in children and adolescents, but it remains unclear whether this association is due to volumetric BMD (vBMD) of the cortical and/or trabecular bone compartments or bone size. The aim of this study was to determine whether vBMD or bone size was associated with X-ray-verified fractures in men during growth. In total, 1068 men (aged 18.9 +/- 0.6 years) were included in the population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) Study. Areal BMD was measured by DXA, whereas cortical and trabecular vBMD and bone size were measured by peripheral quantitative computerized tomography (pQCT). X-ray records were searched for fractures. Self-reported fractures in 77 men could not be confirmed in these records. These men were excluded, resulting in 991 included men, of which 304 men had an X-ray-verified fracture and 687 were nonfracture subjects. Growth charts were used to establish the age of peak height velocity (PHV, n = 600). Men with prevalent fractures had lower aBMD (lumbar spine 2.3%, p = .005; total femur 2.6%, p = .004, radius 2.1%, p < .001) at all measured sites than men without fracture. Using pQCT measurements, we found that men with a prevalent fracture had markedly lower trabecular vBMD (radius 6.6%, p = 7.5 x 10(-8); tibia 4.5%, p = 1.7 x 10(-7)) as well as a slightly lower cortical vBMD (radius 0.4%, p = .0012; tibia 0.3%, p = .015) but not reduced cortical cross-sectional area than men without fracture. Every SD decrease in trabecular vBMD of the radius and tibia was associated with 1.46 [radius 95% confidence interval (CI) 1.26-1.69; tibia 95% CI 1.26-1.68] times increased fracture prevalence. The peak fracture incidence coincided with the timing of PHV (+/-1 year). In conclusion, trabecular vBMD but not aBMD was independently associated with prevalent X-ray-verified fractures in young men. Further studies are needed to determine if assessment of trabecular vBMD could enhance prediction of fractures during growth in males.