One leg standing time predicts fracture risk in older women independent of clinical risk factors and BMD.

In women of ages 75-80 years, a low one leg standing time (OLST) was associated with an increased risk of incident fractures, independently of bone mineral density and clinical risk factors. OLST contributed substantially to fracture probability, indicating that the test should be considered when evaluating fracture risk in older women. INTRODUCTION: Physical function and risk of falls are important risk factors for fracture. A few previous studies have suggested that a one leg standing time (OLST) less than 10 s predicts fracture risk, but the impact of OLST, in addition to known clinical risk factors, for fracture probability is unknown. The aim of this study was to determine the independent contribution of OLST to fracture probability in older women. METHODS: The Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study of 3028 women 75-80 years old, recruited from the greater Gothenburg area in Sweden. At baseline, information on risk factors was collected using questionnaires, bone mineral density was measured with dual-energy X-ray absorptiometry (DXA), and OLST was performed. RESULTS: During a median follow-up of 3.6 years (IQR 1.5 years), X-ray-verified incident fractures were identified using health records. OLST was available in 2405 women. OLST less than 10 s was associated with an increased risk for incident hip fracture (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) [1.49-6.10]), major osteoporotic fracture (HR 95% CI 1.76 [1.34-1.46]), and nonvertebral fracture (HR 95% CI 1.61 [1.26-2.05]) in Cox regression analyses adjusted for age, height, and weight. Depending on BMD, the 4-year fracture probability increased by a factor of 1.3 to 1.5 in a 75-year-old woman with a low OLST (<10 s). CONCLUSION: A low OLST has a substantial impact on fracture probability and should be considered when evaluating fracture risk in older women.

The timed up and go test predicts fracture risk in older women independently of clinical risk factors and bone mineral density.

The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. In older women, TUG time predicts the risk of major osteoporotic fracture and hip fracture independently of clinical risk factors and bone mineral density, and has a substantial impact on fracture probabilities. INTRODUCTION: The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. A slow TUG has been associated with an increased fracture risk, but it is unclear whether the association is independent of clinical risk factors and bone mineral density (BMD). The aim of this study was to investigate if TUG time was associated with fracture risk independently of clinical risk factors and BMD and to determine its impact on fracture probabilities in older women. METHODS: A standardized questionnaire was used to assess information regarding clinical risk factors in the large population-based SUPERB study of 3028 older women (75-80 years). At baseline, the TUG test was performed and BMD measured with DXA. The association between TUG time and the risk of hip fracture and major osteoporotic fracture (MOF) was examined using an extension of Poisson regression. RESULTS: Fracture incidence increased steeply with increasing TUG time up to 12 s and subsequently started to level off. A slow TUG time was therefore defined as TUG > 12 s, a cutoff level then used in Cox models to study the association between slow TUG and fracture risk. A slow TUG time was associated with an increased risk of fracture (MOF 2.39 [1.80-3.18] and hip fracture 2.96 [1.62-5.40]). These associations were slightly attenuated but remained significant after adjustment for clinical risk factors and femoral neck BMD. Depending on BMD, the 4-year fracture probability of MOF increased by a factor of 1.5-1.9 in a 75-year-old woman with slow TUG (> 12 s). CONCLUSION: The TUG time predicts the risk of MOF and hip fracture independently of clinical risk factors and BMD and has a substantial impact on fracture probabilities, indicating that inclusion of the TUG test in patient evaluation should be considered in order to improve fracture prediction in older women.

Decreased physical health-related quality of life-a persisting state for older women with clinical vertebral fracture.

In a population-based study of older Swedish women, we investigated if clinical vertebral fracture was associated with lower health-related quality of life (HRQoL) and determined whether the association remained over time. Clinical vertebral fracture was associated with lower HRQoL and the effect persisted for up to 18.9 years. INTRODUCTION: Vertebral fractures are often associated with back pain and reduced physical function, which might result in isolation and depression. As a result, women with vertebral fractures often have lower health-related quality of life (HRQoL), but during what time frame the decrease lingers is unclear. Therefore, the aim of this study was to investigate if clinical vertebral fracture and hip fracture were associated with lower HRQoL and to determine whether the associations remained over time. METHODS: Vertebral fracture assessments (VFA) were performed using dual-energy X-ray absorptiometry. Data regarding prior fractures, medications, medical history, and physical activity was collected using a questionnaire. Self-rated physical HRQoL was assessed using the 12-Item Short-Form Health Survey (SF-12). Women with clinical vertebral fractures were divided into tertiles according to time since fracture onset and their HRQoL was compared with non-fractured women. RESULTS: In a population-based cross-sectional study of 3028 women aged 77.8 ± 1.63 (mean ± SD), a total of 130 (4.3%) women reported at least one clinical vertebral fracture. Women with a clinical vertebral fracture, divided into tertiles (T1-T3) depending on time since the fracture occurred, had lower HRQoL (T1: 36.3 ± 10.8; T2: 41.0 ± 9.94; and T3:41.6 ± 11.4) than women without fracture (46.2 ± 10.6; p < 0.001). Using linear regression analysis, clinical vertebral fracture was associated with reduced physical HRQoL for up to 18.9 years, independently of covariates (age, height, weight, smoking, prior stroke, mental HRQoL, grip strength, and lumbar spine BMD). CONCLUSIONS: Clinical vertebral fracture was associated with lower self-rated physical HRQoL, for up to 18.9 years after time of fracture.

Extensive undertreatment of osteoporosis in older Swedish women.

In a population-based study of older Swedish women, we investigated the proportion of women treated with osteoporosis medication in relation to the proportion of women eligible for treatment according to national guidelines. We found that only a minority (22%) of those eligible for treatment were prescribed osteoporosis medication. INTRODUCTION: Fracture rates increase markedly in old age and the incidence of hip fracture in Swedish women is among the highest in the world. Although effective pharmacological treatment is available, treatment rates remain low. Limited data are available regarding treatment rates in relation to fracture risk in a population-based setting in older women. Therefore, we aimed to investigate the proportion of older women eligible for treatment according to Swedish Osteoporosis Society (SvOS) guidelines. METHODS: A population-based study was performed in Gothenburg in 3028 older women (77.8 ± 1.6 years [mean ± SD]). Bone mineral density of the spine and hip was measured with dual-energy X-ray absorptiometry. Clinical risk factors for fracture and data regarding osteoporosis medication was collected with self-administered questionnaires. Logistic regression was used to evaluate whether the 10-year probability of sustaining a major osteoporotic fracture (FRAX-score) or its components predicted treatment with osteoporosis medication. RESULTS: For the 2983 women with complete data, 1107 (37%) women were eligible for treatment using SvOS criteria. The proportion of these women receiving treatment was 21.8%. For women eligible for treatment according to SvOS guidelines, strong predictors for receiving osteoporosis medication were glucocorticoid treatment (odds ratio (95% CI) 2.88 (1.80-4.59)) and prior fracture (2.58 (1.84-3.61)). CONCLUSION: This study demonstrates that a substantial proportion of older Swedish women should be considered for osteoporosis medication given their high fracture risk, but that only a minority receives treatment.

Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial.

BACKGROUND: The importance of the gut microbiome for bone metabolism in mice has recently been demonstrated, but no studies are available in humans. Lactobacillus reuteri ATCCPTA 6475 (L. reuteri 6475) has been reported to increase bone mineral density (BMD) in mice but its effect on the human skeleton is unknown. The objective of this trial was to investigate if L. reuteri 6475 affects bone loss in older women with low BMD. METHODS: In this double-blind, placebo-controlled study, women from the population who were 75 to 80 years old and had low BMD were randomized to orally receive 1010 colony-forming units of L. reuteri 6475 daily or placebo. The predefined primary end-point was relative change after 12 months in tibia total volumetric BMD (vBMD). RESULTS: Ninety women were included and 70 completed the study. L. reuteri 6475 reduced loss of total vBMD compared to placebo both in the intention-to-treat (ITT) analysis [-0.83% (95% confidence interval [CI], -1.47 to -0.19%) vs. -1.85% (95% CI, -2.64 to -1.07%); mean difference 1.02% (95% CI, 0.02-2.03)] and per protocol analysis [-0.93% (95% CI, -1.45 to -0.40) vs. -1.86% (95% CI, -2.35 to -1.36); mean difference 0.93% (95% CI, 0.21-1.65)]. In general, similar but smaller effects were observed in the secondary bone variable outcomes, but these differences did not reach statistical significance in the ITT population. Adverse events did not differ between groups. CONCLUSIONS: Supplementation with L. reuteri 6475 should be further explored as a novel approach to prevent age-associated bone loss and osteoporosis.

Increased cortical porosity in women with hip fracture.

BACKGROUND: 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. OBJECTIVE: To investigate whether older women with hip fracture have higher cortical porosity than controls, and if so whether this difference is independent of clinical risk factors and areal bone mineral density (aBMD). METHODS: From an ongoing population-based study, we identified 46 women with a prevalent X-ray-verified hip fracture and 361 control subjects without any fractures. aBMD was measured with DXA. High-resolution peripheral quantitative computed tomography was used to measure bone microstructure at the standard (ultradistal) site and at 14% (distal) of the tibial length. RESULTS: Women with a previous hip fracture had lower aBMD at the femoral neck (-11.8%) and total hip (-14.6%) as well as higher cortical porosity at the ultradistal (32.1%) and distal (29.3%) tibia compared with controls. In multivariable logistic regression analysis, with adjustment for covariates (age, height, weight, smoking, calcium intake, physical activity, walk time, oral glucocorticoids, parental hip fracture, rheumatoid arthritis, previous fall, current bisphosphonate treatment and femoral neck aBMD), cortical porosity at the ultradistal [odds ratio per standard deviation increase (95% confidence interval) 2.61 (1.77-3.85)] and distal [1.57 (1.12-2.20)] sites was associated with prevalent hip fracture. CONCLUSION: Cortical porosity was associated with prevalent hip fracture in older women independently of femoral neck aBMD and clinical risk factors.

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

BACKGROUND: 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. OBJECTIVE: To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men. METHODS: A population-based cohort of 444 elderly men (mean ± SD age 80.2 ± 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay. RESULTS: Mean cortical porosity at the distal tibia was 14.7% higher (12.5 ± 4.3% vs. 10.9 ± 4.1%, P < 0.05) whilst cortical volumetric BMD, area, trabecular bone volume fraction and femoral neck areal BMD were lower in men in the lowest quartile of vitamin D levels compared to the highest. In men with vitamin D deficiency (<25 nmol L-1 ) or insufficiency [25-49 nmol L-1 , in combination with an elevated serum level of parathyroid hormone (>6.8 pmol L-1 )], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P < 0.01). A linear regression model including age, weight, height, daily calcium intake, physical activity, smoking vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized ß = -0.110, R2 = 1.1%, P = 0.024), area (ß = 0.123, R2 = 1.4%, P = 0.007) and cortical volumetric BMD (ß = 0.125, R2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (ß = 0.102, R2 = 0.9%, P = 0.04). CONCLUSION: Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry.

Bone material strength is associated with areal BMD but not with prevalent fractures in older women.

UNLABELLED: Reference point indentation is a novel method to assess bone material strength index (BMSi) in vivo. We found that BMSi at the mid-tibia was weakly associated with spine and hip areal bone mineral density but not with prevalent fracture in a population-based cohort of 211 older women. INTRODUCTION: Reference point indentation is a novel method to assess BMSi in vivo. Lower BMSi has been observed in patients with prior fracture than in controls, but no association between BMSi and areal bone mineral density (aBMD) has been found. Population-based association studies and prospective studies with BMSi and fractures are lacking. We hypothesized that BMSi would be associated with prevalent fractures in older Swedish women. The aim was to investigate the associations between BMSi, aBMD, and prevalent fracture in older women. METHODS: Two hundred eleven women, mean age 78.3 ± 1.1 years, were included in this cross-sectional, population-based study. BMSi was assessed using the OsteoProbe device at the mid-tibia. Areal BMD of the hip, spine, and non-dominant radius was measured using dual-energy X-ray absorptiometry (DXA). Fracture history was retrieved using questionnaires, and vertebral fractures were identified using vertebral fracture assessment (VFA) by DXA. RESULTS: One hundred ninety-eight previous fractures in 109 subjects were reported. A total of 106 women had a vertebral fracture, of which 58 women had moderate or severe fractures. An inverse correlation between BMSi and weight (r = -0.14, p = 0.04) was seen, and BMSi differed according to operator (ANOVA p < 0.01). Adjusting for weight and operator in a linear regression model, we found that BMSi was positively associated with aBMD of the total hip (ß = 0.14, p = 0.04), non-dominant radius (ß = 0.17, p = 0.02), and lumbar spine (L1-L4) (ß = 0.14, p < 0.05). Using logistic regression, we could not find any association in crude or adjusted BMSi (for age, weight, height, walking speed, calcium intake, smoking, bisphosphonate and glucocorticoid use, and operator) with prevalent fractures. CONCLUSION: We conclude that BMSi is associated with aBMD but not with prevalent fracture in a population-based cohort of 211 older women.

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.