Lone Jørgensen

Walking after stroke: Does it matter? Changes in Bone mineral density within the first 12 months after stroke. A longitudinal study

Abstract: Stroke patients have increased risk of hip fractures. Nearly all fractures occur on the hemiplegic side, and reduced bone mineral density (BMD) may be an important predisposing factor. The aim of this study was to investigate the degree of demineralization within the first year after stroke, and to elucidate a possible difference in patients with high versus low ambulatory levels. Forty acute stroke patients were followed (17 initially wheelchair-bound and 23 initially ambulatory). BMD was measured in the proximal femur bilaterally at a mean 6 days, 7 months and 1 year after stroke onset using dual-energy X-ray absorptiometry. Ambulatory status was independently associated with changes in BMD (p≤0.005) 1 year after stroke. The 17 initially wheelchair-bound patients had a significant 10% reduction in BMD at the paretic side and 5% reduction at the non-paretic side (p<0.001), while the 23 patients initially able to walk had a significant loss (3%) only at the paretic side (p = 0.01). The analysis also indicated that the major reduction in BMD took place within the first 7 months. Two months after stroke 12 of the wheelchair-bound patients had relearned to walk. At the paretic side the 1 year changes in BMD in the patients who stayed wheelchair-bound, the patients who relearned to walk within the first 2 months and the patients who were able to walk throughout the study were 13%, 8% and 3%, respectively, and a statistically significant trend with ambulatory level was found (p = 0.007). This study provides clear evidence that lack of mobility and weight-bearing early after stroke is an important factor for the greater bone loss in the paretic leg, but that relearning to walk within the first 2 months after stroke, even with the support of another person, may reduce the bone loss after immobilization.

Changes in muscle mass, fat mass, and bone mineral content in the legs after stroke: a 1 year prospective study

Demineralization and muscle atrophy, common among patients with hemiplegia, may be risk factors for future hip fracture. The aim of this longitudinal study was to investigate changes in lean (muscle) mass and bone mineral content (BMC) of the legs during the first year after stroke according to the patients ambulatory level. Twenty-five patients immobilized due to acute stroke were followed. BMC and lean mass of each leg were measured at a mean of 7 days, 2 months, 7 months, and 1 year after the stroke using dual-energy X-ray absorptiometry. Both BMC and lean mass had decreased significantly in the paretic leg (p < 0.05) at the 1 year evaluation and the loss was significantly greater on the paretic side compared with the nonparetic side (p < 0.001). Patients who had not relearned to walk at the 2 month evaluation (n = 12) lost 6% (p < 0.05) of their lean mass in the paretic leg during this time period, and this mass was not regained within the subsequent 10 months. In contrast, a significant 5% loss of lean mass found at 2 months on the nonparetic side was regained completely. With respect to the patients who relearned to walk within the first 2 months (n = 13) lean mass had increased by 5% after 1 year (p < 0.05) in the nonparetic leg, whereas no significant changes were found in the paretic leg during follow-up. Both groups of patients did, however, lose bone mineral in the paretic leg during the first year after stroke (9% and 6%, respectively, p < 0.05), but only the patients who were still unable to walk by 2 months had significant bone loss in the nonparetic leg also (3%, p < 0.05). Thus, lean muscle mass is rapidly lost and may be regained shortly after stroke, whereas loss of BMC appears difficult to prevent, especially on the paretic side. Regaining muscle mass may, however, slow the loss of bone mineral.

Bone Mineral Density in Acute Stroke Patients Low Bone Mineral Density May Predict First Stroke in Women

Background and Purpose— Osteoporosis and stroke share several risk factors, including age, smoking, low physical activity, and hypertension. Thus, low bone mineral density (BMD) and high stroke risk may be related. We examined the relationship between BMD and acute stroke in noninstitutionalized men and women aged ≥60 years. Methods— Sixty-three stroke patients (33 women and 30 men) and 188 control subjects from the general population were included. BMD was measured by using dual-energy x-ray absorptiometry at both proximal femurs. The measurements of the stroke patients were performed 6 days after the onset of stroke. Results— The BMD at the femoral neck in the female stroke patients was 8% lower than in the control subjects (P =0.007). In men, no difference in BMD between the stroke patients and their controls was found. Women with BMD values in the lowest quartile had a higher risk of stroke than women with BMD values in the highest quartile (OR 4.8), and the probability value for linear trend over the quartiles was statistically significant (P =0.003). The OR for stroke increased 1.9 per SD (0.13 g/cm2) reduction in BMD, and the association between low BMD and stroke in women remained significant when the analysis was adjusted for potential confounders. Conclusions— Female, but not male, stroke patients have lower BMD than population controls. Low BMD may predict stroke in women.

Ambulatory level and asymmetrical weight bearing after stroke affects bone loss in the upper and lower part of the femoral neck differently: bone adaptation after decreased mechanical loading

The aim of this 1-year prospective study of acute stroke patients was to determine the effects of walking and asymmetrical weight bearing on the loss of bone mineral in the upper and lower femoral neck. Forty patients were followed. Eight remained unable to walk, whereas 32 relearned to walk independently within 7 months (12 shortly after the stroke, 15 by 2 months, 5 by 7 months). Bone mineral density (BMD) was measured in the proximal femur within the first week after stroke and 1 year later; regional BMD changes were computed for the lower and upper femoral neck. The lower part of the femoral neck is mainly influenced by compressive stresses of the hip, the upper part by tensile stresses during walking. When comparing mean BMD loss in groups of patients according to when they relearned to walk, a statistically significant trend in BMD loss was found in the lower femoral neck on both the paretic and nonparetic sides (p < 0.01 and p = 0.01, respectively), whereas, for the upper femoral neck, no significant trend was seen (p >/= 0.1). In addition, the body weight distribution during standing was assessed by use of a force-plate in 38 patients who could stand independently at the 7 month evaluation. The only significant correlation between changes in BMD and asymmetrical weight bearing was found in the lower femoral neck on the paretic side (r = 0.6, p < 0.001). In conclusion, this study shows that the reduction in BMD in the femoral neck occurs mainly in the lower part of the neck and on the paretic side. The BMD loss depended on when or if the patients relearned to walk, but also on the amount of body weight born on the paretic leg. Thus, measuring the lower part of the femoral neck gives a better estimate of the impact of gait and weight bearing than measuring the total femoral neck.

Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial

Background: High vitamin D levels may reduce the risk of relapses and disease progression in multiple sclerosis. Methods: This 96-week randomised controlled trial was designed to assess the effect of vitamin D3 supplementation on bone mineral density in persons with multiple sclerosis. Supplementation with 20,000 IU vitamin D3 weekly raised median serum 25-hydroxy vitamin D (25[OH]D) to 121 nmol/L. The modified intention to treat analysis included 35 persons in the vitamin D3 group and 33 in the placebo group. Participants were age 21 to 50 years and fully ambulatory (median Expanded Disability Status Scale (EDSS) 2.5). We studied the effect of supplementing vitamin D3 on the exploratory outcomes annualised relapse rate (ARR), EDSS, multiple sclerosis functional composite (MSFC) components, grip strength, and fatigue. Results: After 96 weeks, there was no significant difference between groups in ARR (absolute difference 0.10, 95% CI -0.07 to 0.27; p = 0.25), EDSS (absolute difference -0.01, 95% CI -0.35 to 0.35; p = 0.97), MSFC components, grip strength, or fatigue. Conclusion: Supplementation with 20,000 IU vitamin D3 weekly did not result in beneficial effects on the measured multiple sclerosis-related outcomes. This study was not powered to address clinical outcomes, but none of the results were suggestive of an effect in this unselected population of fully ambulatory persons with multiple sclerosis.

Association of Albuminuria and Cancer Incidence

Albuminuria, which is associated with noncardiovascular mortality, might be a result of altered vascular permeability caused by cytokines and other tumor cell products. The aim of this population-based, longitudinal study was to examine whether elevated albumin-to-creatinine ratio (ACR) is associated with cancer incidence. A total of 5425 participants without diabetes or previous cancer in the Tromsø Study were followed; 590 had a first diagnosis of cancer during 10.3 yr of follow-up. The ACR at baseline significantly correlated with the incidence of cancer, even after adjustment for age, gender, body mass index, physical activity, and smoking (P < 0.001). Participants with ACR in the highest quintile were 8.3- and 2.4-fold more likely to receive a diagnosis of bladder cancer and lung cancer, respectively, compared with those with ACR in the lowest quintile after similar adjustments. It is concluded that albuminuria is associated with cancer incidence in individuals without a history of diabetes, macroalbuminuria, or previous cancer and that it might confer risks of varying magnitude for different types of cancer.

Serum osteoprotegerin is a predictor for incident cardiovascular disease and mortality in a general population: the Tromsø Study

Summary.  Background: Osteoprotegerin (OPG) concentration in serum is associated with the presence and severity of atherosclerosis. Objective: To investigate the association between serum osteoprotegerin and the risk of a future myocardial infarction, ischemic stroke and mortality in a general population. Patients/methods: OPG was measured in serum collected from 6265 subjects recruited from a general population without a prior myocardial infarction and ischemic stroke (the Tromsø Study). Incident myocardial infarction, ischemic stroke and mortality were registered during follow‐up. Cox regression models were used to estimate crude and adjusted hazard ratios and 95% confidence intervals (HR; 95% CI). Results: There were 575 myocardial infarctions, 284 ischemic strokes and 824 deaths (146 deaths as a result of ischemic heart disease, 78 deaths because of stroke and 600 deaths due to other causes) in the cohort during a median of 10.6 years of follow‐up. Serum OPG (per SD [1.13 ng mL−1] increase in OPG) was associated with an increased risk of a myocardial infarction (1.20; 1.11–1.31), ischemic stroke (1.32; 1.18–1.47), total mortality (1.34; 1.26–1.42), death because of ischemic heart disease, (1.35; 1.18–1.54), stroke (1.44; 1.19–1.75) and non‐vascular causes (1.31; 1.22–1.41) after adjustment for age, gender, current smoking, systolic blood pressure, body mass index, high density lipoprotein cholesterol, total cholesterol, creatinine, high sensitivity C‐reactive protein (CRP) and diabetes mellitus or HbA1c > 6.1%. No association was detected between OPG and incident hemorrhagic stroke (1.02; 0.73–1.43). Conclusions: Serum OPG was associated with future risk of myocardial infarction, ischemic stroke, total mortality, mortality of ischemic heart disease, stroke and of non‐vascular causes independent of traditional cardiovascular risk factors.

Glycated hemoglobin level is strongly related to the prevalence of carotid artery plaques with high echogenicity in nondiabetic individuals: the Tromsø study.

Background—High levels of HbA1c have been associated with increased mortality and an increased risk of atherosclerosis assessed as carotid intima-media thickness or plaque prevalence. In the present population-based study, we examined the association between HbA1c and plaque prevalence with emphasis on plaque echogenicity in subjects not diagnosed with diabetes. Methods and Results—HbA1c measurements and ultrasonography of the carotid artery were performed in 5960 subjects (3026 women, 2934 men) 25 to 84 years of age. Plaque morphology was categorized into 4 groups from low echogenicity (soft plaque) to strong echogenicity (hard plaque). HbA1c was categorized into 5 groups: <5.0%, 5.0% to 5.4%, 5.5% to 5.9%, 6.0% to 6.4% and >6.4%. Carotid plaque prevalence increased with increasing HbA1c level (P for linear trend=0.002). The OR for hard plaques versus no plaques was 5.8 in the highest HbA1c group (>6.4%) compared with subjects in the lowest group (<5.0%) after adjustment for several possible confounders. The risk of predominantly hard plaques was also significantly associated with HbA1c levels, although the ORs at each level were somewhat lower than for hard plaques. With respect to the risk of soft plaques versus no plaques, no statistically significant relationship with HbA1c levels was found. Conclusions—Metabolic changes reflected by HbA1c levels may contribute to the development of hard carotid artery plaques, even at modestly elevated levels.

A prospective study of sex steroids, sex hormone-binding globulin, and non-vertebral fractures in women and men : the Tromsø Study

OBJECTIVES As bone fragility is partly the result of sex hormone deficiency, we sought to determine whether circulating sex steroids or sex hormone-binding globulin (SHBG) predicts non-vertebral fractures. METHODS Forearm bone mineral density (BMD), total estradiol and testosterone, calculated free levels, and SHBG were measured in 1386 postmenopausal women and 1364 men aged 50-84 years at baseline in the Tromsø Study (1994-1995). Non-vertebral fractures were documented between 1994 and 2005. RESULTS During 8.4 years (range 0.01-10.4) of follow-up, 281 women and 105 men suffered non-vertebral fractures. For both sexes, fracture cases had lower BMD and higher SHBG, but sex steroids were not lower. Each standard deviation (s.d.) increase in SHBG increased non-vertebral fracture risk in women (hazards ratio (HR) 1.17; 95% confidence interval (CI) 1.03-1.33) and men (HR 1.26; 95% CI 1.03-1.54). After further adjustment for BMD, the risk was not statistically significant in women (HR 1.09; 95% CI 0.95-1.24) or men (HR 1.22; 95% CI 0.99-1.49). Each s.d. decrease in BMD increased fracture risk in women (HR 1.36; 95% CI 1.19-1.56) and men (HR 1.41; 95% CI 1.15-1.73). Fracture rates were highest in participants with SHBG in the highest tertile and BMD in the lowest tertile and were 37.9 and 17.0 per 1000 person-years in women and men respectively. However, in both sexes the combination of BMD and SHBG was no better predictor of fracture risk than BMD alone. Sex steroids were not associated with fracture risk. CONCLUSIONS Measurements of sex steroids or SHBG are unlikely to assist in decision making regarding fracture risk susceptibility.

Relation between serum osteoprotegerin and carotid intima media thickness in a general population - the Tromsø Study

Summary.  Background: Previous studies have reported conflicting results on the relation between serum osteoprotegerin (OPG) concentration and carotid intima media thickness (CIMT). Patients/methods: The present study was conducted to investigate the relations between OPG, risk factors for cardiovascular diseases (CVD) and carotid intima media thickness (CIMT) in a large cross‐sectional study including 6516 subjects aged 25–85 years who participated in a population‐based health survey. Results: CIMT increased significantly across tertiles of OPG after adjustment for traditional cardiovascular risk factors such as age, gender, smoking, total cholesterol, high‐density lipoprotein (HDL) cholesterol, C‐reactive protein (CRP), body mass index (BMI), systolic blood pressure, CVD and diabetes mellitus (P < 0.0001). There was a significant interaction between age and OPG (P = 0.026). The risk of being in the uppermost quartile of CIMT was reduced (OR 0.52, 95% CI 0.30–0.88) with each standard deviation (SD) higher level of OPG in subjects < 45 years (n = 444), whereas subjects ≥ 55 years of age (n = 4884) had an increased risk of being in the uppermost quartile of CIMT (OR 1.19, 95% CI 1.10–1.29) after adjustment for traditional CVD risk factors. Conclusions: Age has a differential impact on the association between OPG and CIMT in a general population. The present findings may suggest that increased serum OPG does not promote early atherosclerosis in younger subjects.