Impact of osteoporotic fracture type and subsequent fracture on mortality: the Tromsø Study.

Less is known about the impact of non-hip non-vertebral fractures (NHNV) on early death. This study demonstrated increased risk of dying following hip and NHNV fractures which was further increased by a subsequent fracture. This highlights the importance of early intervention to prevent both initial and subsequent fractures and improve survival. INTRODUCTION: Osteoporotic fractures are a major health concern. Limited evidence exists on their impact on mortality in ageing populations. This study examined the contribution of initial fracture type and subsequent fracture on mortality in a Norwegian population that has one of the highest rates of fractures. METHODS: The Tromsø Study is a prospective population-based cohort in Norway. Women and men aged 50+ years were followed from 1994 to 2010. All incident hip and non-hip non-vertebral (NHNV) fractures were registered. NHNV fractures were classified as either proximal or distal. Information on self-reported co-morbidities, lifestyle factors, general health and education level was collected. Multivariable Cox models were used to quantify mortality risk with incident and subsequent fractures analysed as time-dependent variables. RESULTS: Of 5214 women and 4620 men, 1549 (30%) and 504 (11%) sustained a fracture, followed by 589 (38%) and 254 (51%) deaths over 10,523 and 2821 person-years, respectively. There were 403 (26%) subsequent fractures in women and 68 (13%) in men. Hip fracture was associated with a two-fold increase in mortality risk (HR 2.05, 95% CI 1.73-2.42 in women and 2.49, 95% CI 2.00-3.11 in men). Proximal NHNV fractures were associated with 49% and 81% increased mortality risk in women and men (HR 1.49, 95% CI 1.21-1.84 and 1.81, 95% CI 1.37-2.41), respectively. Distal NHNV fractures were not associated with mortality. Subsequent fracture was associated with 89% and 77% increased mortality risk in women and men (HR 1.89, 95% CI 1.52-2.35 and 1.77, 95% CI 1.16-2.71), respectively. CONCLUSION: Hip, proximal NHNV and subsequent fractures were significantly associated with increased mortality risk in the elderly, highlighting the importance of early intervention.

Determinants of trabecular bone score and prevalent vertebral fractures in women with fragility fractures: a cross-sectional sub-study of NoFRACT.

Determinants of trabecular bone score (TBS) and vertebral fractures assessed semiquantitatively (SQ1-SQ3) were studied in 496 women with fragility fractures. TBS was associated with age, parental hip fracture, alcohol intake and BMD, not SQ1-SQ3 fractures. SQ1-SQ3 fractures were associated with age, prior fractures, and lumbar spine BMD, but not TBS. INTRODUCTION: Trabecular bone score (TBS) and vertebral fractures assessed by semiquantitative method (SQ1-SQ3) seem to reflect different aspects of bone strength. We therefore sought to explore the determinants of and the associations between TBS and SQ1-SQ3 fractures. METHODS: This cross-sectional sub-study of the Norwegian Capture the Fracture Initiative included 496 women aged ≥ 50 years with fragility fractures. All responded to a questionnaire about risk factors for fracture, had bone mineral density (BMD) of femoral neck and/or lumbar spine assessed, TBS calculated, and 423 had SQ1-SQ3 fracture assessed. RESULTS: Mean (SD) age was 65.6 years (8.6), mean TBS 1.27 (0.10), and 33.3% exhibited SQ1-SQ3 fractures. In multiple variable analysis, higher age (ßper SD = - 0.26, 95% CI: - 0.36,- 0.15), parental hip fracture (ß = - 0.29, 95% CI: - 0.54,- 0.05), and daily alcohol intake (ß = - 0.43, 95% CI - 0.79, - 0.08) were associated with lower TBS. Higher BMD of femoral neck (ßper SD = 0.34, 95% CI 0.25-0.43) and lumbar spine (ßper SD = 0.40, 95% CI 0.31-0.48) were associated with higher TBS. In multivariable logistic regression analyses, age (ORper SD = 1.94, 95% CI 1.51-2.46) and prior fragility fractures (OR = 1.71, 95% CI 1.09-2.71) were positively associated with SQ1-SQ3 fractures, while lumbar spine BMD (ORper SD = 0.75 95% CI 0.60-0.95) was negatively associated with SQ1-SQ3 fractures. No association between TBS and SQ1-SQ3 fractures was found. CONCLUSION: Since TBS and SQ1-SQ3 fractures were not associated, they may act as independent risk factors, justifying the use of both in post-fracture risk assessment.

Grip strength in men and women aged 50-79 years is associated with non-vertebral osteoporotic fracture during 15 years follow-up: The Tromsø Study 1994-1995.

In 50-79-year-olds who participated in the Tromsø Study (1994-1995), the risk of non-vertebral osteoporotic fractures during 15 years follow-up increased by 22% in men and 9% in women per 1 SD lower grip strength. The strongest association was observed in men aged 50-64 years. INTRODUCTION: We aimed to explore whether low grip strength was associated with increased risk of non-vertebral osteoporotic fracture in the population-based Tromsø Study 1994-1995. METHODS: Grip strength (bar) was measured by a Martin Vigorimeter and fractures were retrieved from the X-ray archives at the University Hospital of North Norway between 1994 and 2010. At baseline, weight and height were measured, whereas information on the other covariates were obtained through self-reported questionnaires. Cox regression was used to estimate the hazard ratio (HR) of fracture in age- and gender-specific quintiles of grip-strength, and per 1 SD lower grip strength. Similar analyses were done solely for hip fractures. Adjustments were made for age, height, body mass index (BMI), marital status, education, smoking, physical activity, use of alcohol, self-perceived health, and self-reported diseases. RESULTS: In 2891 men and 4002 women aged 50-79 years, 1099 non-vertebral osteoporotic fractures-including 393 hip fractures-were sustained during the median 15 years follow-up. Risk of non-vertebral osteoporotic fracture increased with declining grip strength: hazard ratios per SD decline was 1.22 (95% CI 1.05-1.43) in men and 1.09 (95% CI 1.01-1.18) in women. HR for fracture in lower vs. upper quintile was 1.58 (95% CI 1.02-2.45) in men and 1.28 (95% CI 1.03-1.59) in women. The association was most pronounced in men aged 50-64 years with HR = 3.39 (95% CI 1.76-6.53) in the lower compared to the upper quintile. CONCLUSIONS: The risk of non-vertebral osteoporotic fracture increased with declining grip-strength in both genders, particularly in men aged 50-64 years.

Serum parathyroid hormone is associated with increased cortical porosity of the inner transitional zone at the proximal femur in postmenopausal women: the Tromsø Study.

Serum parathyroid hormone (PTH) was associated with increased bone turnover markers and cortical porosity of the inner transitional zone at the proximal femur. These results suggest that PTH through increased intracortical bone turnover leads to trabecularisation of inner cortical bone in postmenopausal women. INTRODUCTION: Vitamin D deficiency leads to secondary hyperparathyroidism and increased risk for fractures, whereas its association with cortical porosity is less clear. We tested (i) whether serum 25-hydroxyvitamin D (25(OH)D) and PTH were associated with cortical porosity and (ii) whether the associations of 25(OH)D) and PTH with fracture risk are dependent on cortical porosity. METHODS: This case-control study included 211 postmenopausal women, 54-94 years old, with prevalent fractures and 232 controls from the Tromsø Study. Serum 25(OH)D, PTH, and bone turnover markers (procollagen type I N-terminal propeptide [PINP] and C-terminal cross-linking telopeptide of type I collagen [CTX]) were measured. Femoral subtrochanteric cortical and trabecular parameters were quantified using computed tomography, and femoral neck areal bone mineral density (FN aBMD) was quantified using dual-energy X-ray absorptiometry. RESULTS: Compared with controls, fracture cases exhibited reduced serum 25(OH)D and increased PTH, PINP, and CTX, increased femoral subtrochanteric cortical porosity, and reduced cortical thickness and FN aBMD (all, p < 0.05). Serum 25(OH)D was not associated with cortical parameters (all, p > 0.10). PTH was associated with increased PINP, CTX, and cortical porosity of the inner transitional zone and reduced trabecular bone volume/tissue volume and FN aBMD (p ranging from 0.003 to 0.054). Decreasing 25(OH)D and increasing PTH were associated with increased odds for fractures, independent of age, height, weight, calcium supplementation, serum calcium, cortical porosity, and thickness. CONCLUSIONS: These data suggest that serum PTH, not 25(OH)D, is associated with increased intracortical bone turnover resulting in trabecularisation of the inner cortical bone; nevertheless, decreasing 25(OH)D) and increasing PTH are associated with fracture risk, independent of cortical porosity and thickness.

Measurement of cortical porosity of the proximal femur improves identification of women with nonvertebral fragility fractures.

UNLABELLED: We tested whether cortical porosity of the proximal femur measured using StrAx1.0 software provides additional information to areal bone mineral density (aBMD) or Fracture Risk Assessment Tool (FRAX) in differentiating women with and without fracture. Porosity was associated with fracture independent of aBMD and FRAX and identified additional women with fractures than by osteoporosis or FRAX thresholds. INTRODUCTION: Neither aBMD nor the FRAX captures cortical porosity, a major determinant of bone strength. We therefore tested whether combining porosity with aBMD or FRAX improves identification of women with fractures. METHODS: We quantified femoral neck (FN) aBMD using dual-energy X-ray absorptiometry, FRAX score, and femoral subtrochanteric cortical porosity using StrAx1.0 software in 211 postmenopausal women aged 54-94 years with nonvertebral fractures and 232 controls in Tromsø, Norway. Odds ratios (ORs) were calculated using logistic regression analysis. RESULTS: Women with fractures had lower FN aBMD, higher FRAX score, and higher cortical porosity than controls (all p < 0.001). Each standard deviation higher porosity was associated with fracture independent of FN aBMD (OR 1.39; 95% confidence interval 1.11-1.74) and FRAX score (OR 1.58; 1.27-1.97) in all women combined. Porosity was also associated with fracture independent of FRAX score in subgroups with normal FN aBMD (OR 1.88; 1.21-2.94), osteopenia (OR 1.40; 1.06-1.85), but not significantly in those with osteoporosis (OR 1.48; 0.68-3.23). Of the 211 fracture cases, only 18 women (9%) were identified using FN aBMD T-score < -2.5, 45 women (21%) using FRAX threshold >20%, whereas porosity >80th percentile identified 61 women (29%). Porosity identified 26% additional women with fractures than identified by the osteoporosis threshold and 21% additional women with fractures than by this FRAX threshold. CONCLUSIONS: Cortical porosity is a risk factor for fracture independent of aBMD and FRAX and improves identification of women with fracture.

Does recalled dieting increase the risk of non-vertebral osteoporotic fractures? The Tromsø Study.

UNLABELLED: The risk of non-vertebral osteoporotic fractures increased by increasing recalled amount of weight loss when dieting in women aged ≥ 46 years and in those with BMI < 25 kg/m(2) participating in the Tromsø Study (1994/1995-2009). The increased risk was present both in women with few and several episodes of recalled dieting. INTRODUCTION: The influence of repeated dieting on bone health is uncertain. This study aims to investigate whether recalled dieting is a risk factor for non-vertebral osteoporotic fractures. METHODS: In 1994/1995 weight and height were measured in all participants aged 25-69 years in the population-based Tromsø Study. Information about socioeconomic background, diseases and lifestyle factors was collected by questionnaires-including number of recalled dieting episodes and largest amount of weight loss when dieting. The participating 20,745 women and men were followed for 15 years, fractures were registered from X-ray archives and analysed by Cox's proportional hazards models. RESULTS: Among those who recalled dieting, 975 women and 364 men suffered a non-vertebral osteoporotic fracture during follow-up. Compared to women without recalled weight loss when dieting, women who reported their largest weight loss of 11 kg or more had a hazard ratio (HR) = 1.48 (95% CI 1.13-1.94) for osteoporotic fracture, adjusted for age, marital status, body mass index, height, education, physical activity, smoking, alcohol intake, history of cardiovascular disease and psychological distress. The increased risk was statistically significant only in women aged ≥ 46 years and in those with BMI < 25 kg/m(2). Women who recalled ≥ 11 dieting episodes had HR = 1.73 (CI 1.11-2.68) for osteoporotic fracture compared to those with no recalled episodes. Dieting was not associated with risk of fractures in men, but the number of fractures was low. CONCLUSIONS: The increased risk of non-vertebral osteoporotic fractures by recalled dieting in women indicates that maintenance of a stable weight may have beneficial effects on fracture risk.

Bone loss and the risk of non-vertebral fractures in women and men: the Tromsø study.

SUMMARY: We assessed the association between the rate of forearm bone loss and non-vertebral fracture. Bone loss at the distal forearm predicted fractures, independently of baseline BMD, but not independently of follow-up BMD in women. The BMD level where an individual ends up is the significant predictor of fracture risk. INTRODUCTION: Bone loss may predict fracture risk independently of baseline BMD. The influence of follow-up BMD on this prediction is unknown. The aim of this study was to assess the association between bone loss and fracture risk in both sexes in a prospective population-based study. METHODS: We included 1,208 postmenopausal women (50 to 74 years), and 1,336 men (55 to 74 years) from the Tromsø Study, who had repeated distal and ultra-distal forearm BMD measurements. Non-vertebral fractures were registered from 2001 to 2005. RESULTS: A total of 100 women and 46 men sustained fractures during the follow-up time. Independent of baseline BMD, the RR associated with distal site bone loss of 1 SD %/year was 1.23 (1.01-1.50) for low-trauma fractures (excluding hand, foot, skull & high-trauma) and 1.32 (1.07-1.62) for osteoporotic fractures (hip, wrist and shoulder). However, bone loss did not predict fracture after adjusting for follow-up BMD. The BMD level where an individual ends up became the significant predictor of fracture risk and not the rate of bone loss. Follow-up BMD at ultra-distal site was associated with low-trauma fractures in both sexes. While ultra-distal site BMD changes were not associated with fracture risk in both sexes. CONCLUSION: Bone loss at the distal forearm predicted non-vertebral fractures, independently of baseline BMD, but not independently of follow-up BMD, in women. The BMD level where an individual ends up is the significant predictor of fracture risk and not the rate of bone loss.

Anemia and the risk of non-vertebral fractures: the Tromsø Study.

UNLABELLED: In this longitudinal study of 5,286 persons, men with anemia had a 2.15 higher risk of non-vertebral fractures than men with high hemoglobin levels. Women with anemia had no increased fracture risk. INTRODUCTION: Low hemoglobin levels are associated with several risk factors for fractures such as low physical function, impaired cognition, and low bone mass. The aim of this population-based, prospective study was to examine whether anemia predicts non-vertebral fractures. METHODS: A total of 5,286 inhabitants from the municipality of Tromsø, Norway (2,511 men and 2,775 women), 55-74 years old at baseline, were followed for mean 8.3 years. Measurements of hemoglobin, mean corpuscular volume, height, weight, blood pressure, blood lipids, serum creatinine, and bone mineral density and questionnaire information concerning smoking and drinking habits, physical activity, prevalent diseases, and use of medication was collected before start of follow-up. Non-vertebral fractures were registered during follow-up. RESULTS: A total of 235 men and 641 women sustained a new non-vertebral fracture. One SD lower value of hemoglobin was associated with a 1.27 higher risk of fracture in men (p < 0.001, after multiple adjustments) and 1.08 (p = 0.07) in women. Men with anemia (hemoglobin levels <13 g/dL) had a 2.15 higher risk of non-vertebral fractures than men with high levels (15.2-18.8, g/dL) whereas women with anemia (hemoglobin levels <12 g/dL) had no increased fracture risk. CONCLUSION: Anemia is associated with non-vertebral fractures in men but not in women.

Validation of the use of Pap-stained vaginal smears for diagnosis of bacterial vaginosis.

Papanicolaou-stained cervicovaginal smears (Pap smears) are used to screen for cervical cancer. Since there is a lack of consensus in published reports respecting the efficacy of Pap-stained smears in BV diagnostics, there is a need to validate their use for diagnosis of BV. Slides from the international BV00 workshop were Pap stained and independently analyzed by four investigators under a phase-contrast microscope. All workshop slides--whether Pap-stained, Gram-stained or rehydrated air-dried smears--were scored according to the same Nugent classification. The diagnostic accuracy of Pap smears for diagnosis of BV had a sensitivity of 0.85 and a specificity of 0.92, with a positive and negative predictive value of 0.84 and 0.93, respectively. The interobserver weighted kappa index was 0.86 for Pap-stained smears compared to 0.81 for Gram-stained smears, and 0.70 for rehydrated air-dried smears using the mean Nugent score as the criterion standard. Provided that the samples are taken from equivalent locations (the vaginal fornix) and analyzed according to the same scoring criteria, there is no discernable difference in the diagnostic accuracy of the three smear-staining methods. The Pap-stained vaginal smears can be used as a wholly adequate alternative to Gram-stained smears for BV diagnosis.

An international study of the interobserver variation between interpretations of vaginal smear criteria of bacterial vaginosis.

An international workshop on vaginal smear-based diagnosis of bacterial vaginosis was organized where 13 investigators scoring 258 slides with smears from vaginal fluid. Interobserver reproducibility of interpretations of Nugent scores, Hay/Ison scores and wet smear scores for the diagnosis of bacterial vaginosis was shown to be high. Detailed analysis of individual scoring results however indicated that basic standards of quality control to ensure robust individual readings of slides must be adhered to.

[Occurrence of bacterial vaginosis among abortion seekers]. / Forekomst av bakteriell vaginose blant abortsøkere.

Bacterial vaginosis is the most common vaginal infection during the fertile period. The clinical diagnosis is based on three of Amsel's four criteria: thin, grey-white discharge, vaginal fluid pH above 4.5, a fishy odour on addition of 10% potassium hydroxide solution to the vaginal fluid, and the presence of clue cells on a saline wet mount. A probably more sensitive indicator of the diagnosis is based on Gram-stain, where the normal lactobacillus-dominated vaginal flora is changed to the lactobacillus deficient flora of bacterial vaginosis. The condition is probably associated with higher risk of complications in connection with pregnancy and gynaecological surgery. A prospective study of bacterial vaginosis based on microscopy of Gram-stained smears was conducted among 168 women applying for first trimester abortion. The prevalence of bacterial vaginosis was 24% and of Chlamydia trachomatis 8.4%. Four patients (10.3%) in the vaginosis group were treated with antibiotics for certain or suspected postabortal endometritis, as against six patients (5.4%) in the group without bacterial vaginosis.