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Biomedical subjects

K Akesson

Publications and source records attributed to K Akesson.

At least 19 recordsLinked to original sources
PubMed2006

Risk factors for fragility fracture in middle age. A prospective population-based study of 33,000 men and women.

The incidence of fragility fractures begins to increase in middle age. We investigated prospectively risk factors for low-energy fractures in men and women, and specifically for forearm, proximal humerus, vertebral, and ankle fractures. The population-based Malmö Preventive Project consists of 22,444 men and 10,902 women, mean age 44 and 50 years, respectively, at inclusion. Baseline assessment included multiple examinations and lifestyle information. Mean follow-up was 19 and 15 years for men and women, respectively, regarding incident fractures. Fractures were ascertained from radiographic files. At least one low-energy fracture occurred in 1,262 men and 1,257 women. In men, the risk factors most strongly associated with low-energy fractures were diabetes [relative risk (RR) 2.38, confidence interval (CI) 95% 1.65-3.42] and hospitalization for mental health problems (RR 1.92, CI 95% 1.47-2.51). Factors associated with mental health and lifestyle significantly increased the fracture risk in most of the specific fracture groups: hospitalizations for mental health problems (RR 2.28-3.38), poor appetite (RR 3.05-3.43), sleep disturbances (RR 1.72-2.95), poor self-rated health (RR 1.80-1.83), and smoking (RR 1.70-2.72). In women, the risk factors most strongly associated with low-energy fractures were diabetes (RR 1.87, CI 95% 1.26-2.79) and previous fracture (RR 2.00, CI 95% 1.56-2.58). High body mass index (BMI) significantly increased the risk of proximal humerus and ankle fractures (RR 1.21-1.33) while, by contrast, lowering the risk of forearm fractures (RR 0.88, CI 95% 0.81-0.96). Risk factors for fracture in middle-aged men and women are similar but with gender differences for forearm, vertebral, proximal humerus, and hip fracture whereas risk factors for ankle fractures differ to a certain extent. The risk-factor pattern indicates a generally impaired health status, with mental health problems as a major contributor to fracture risk, particularly in men.

Adult↗
PubMed2005

Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus.

Bone density, bone turnover and fracture susceptibility were evaluated in 1,132 randomly recruited women, all 75 years old. Seventy-four of the women had diabetes, while 1,058 women did not. Areal bone mineral density (aBMD) of the hip and lumbar spine was investigated by dual energy X-ray absorptiometry (DXA), and bone mass of the calcaneus was measured by ultrasound. Urinary deoxypyridinoline/creatinine (U-DPD/Crea) and serum C-terminal cross-linked telopeptide of type 1 collagen (S-CTX) were assessed as markers of bone resorption. Serum bone-specific alkaline phosphatase (S-bone ALP) and serum osteocalcin (S-OC) were assessed as markers of bone formation. Also, serum 25(OH) vitamin D and serum parathyroid hormone (S-PTH) were assessed. Fracture susceptibility was evaluated retrospectively and prospectively for up to 6.5 years. In diabetic women, the aBMD of the femoral neck was 11% higher (p<0.001), and BMD of the lumbar spine was 8% higher (p=0.002) than in non-diabetic women. There was no difference in bone mass by ultrasound of the calcaneus. Women with diabetes had higher BMD of the femoral neck (p<0.001) and lumbar spine (p=0.03) also after correction for differences in body weight. In diabetic women, U-DPD/Crea, S-CTX, and S-OC were decreased when compared with non-diabetic women (p=0.001 or less). After correction for covariance of body weight and plasma creatinine, S-CTX (p<0.001) and S-OC (p<0.001) were still lower in the diabetic women. Diabetic patients had hypovitaminosis D (p=0.008), a difference explained by differences in time spent outdoors and body weight. S-PTH did not differ between the groups. Women with diabetes had no more lifetime fractures (52%) than women without diabetic disease (57%), (p=0.31). This study shows that elderly women with diabetes and without severe renal insufficiency have high bone mass and low bone turnover. The high bone mass and low bone turnover is not likely to have a strong influence on fracture susceptibility.

Absorptiometry, Photon↗
PubMed2005

Association between 25-hydroxy vitamin D levels, physical activity, muscle strength and fractures in the prospective population-based OPRA Study of Elderly Women.

Vitamin D supplements have been used to prevent fractures. The effect may be mediated through increased bone mass, but also through reduced falling propensity. The aim of this study was to evaluate the association between 25-hydroxy vitamin D levels (25OHD), fall-associated variables (including tests of functional performance), and fracture in ambulatory women. At baseline 25OHD was measured in 986 women. Fall-associated variables were investigated at baseline. Fractures were recorded during a 3-year follow-up. Four percent of the women had 25OHD levels below 20 ng/ml (50 nmol/l), and 26% had 25OHD levels below 30 ng/ml (75 nmol/l). 25OHD correlated with gait speed (r =0.17, P <0.001), the Romberg balance test (r =0.14, P <0.001), self-estimated activity level (r =0.15, P <0.001), and thigh muscle strength (r =0.08, P =0.02). During the 3-year follow-up, 119 out of the 986 women sustained at least one fracture. The Cox proportional hazard ratio (HR) (95% confidence interval) for sustaining a fracture during the follow-up was 2.04 (1.04-4.04) for the group of women with 25OHD below 20 ng/ml, in which 9 out of 43 women sustained a fracture. Thirty-two of the 256 women with 25OHD levels below 30 ng/ml sustained a fracture during the follow-up, with a non-significant HR of 1.07 (1.07-1.61). This cohort of elderly, ambulatory women had a high mean 25OHD. A low 25OHD was associated with inferior physical activity level, gait speed and balance. A 25OHD level below 30 ng/ml was not associated with an increased risk of fractures in this study. However, a subgroup of women with 25OHD levels below 20 ng/ml had a tendency to an increased risk of fractures, which may be associated with an inferior physical activity and postural stability.

Accidental Falls↗
PubMed2005

Increased risk of diabetes among relatives of female insulin-treated patients diagnosed at 15-34 years of age.

AIMS: This study aimed to determine the risk of developing diabetes among relatives of patients diagnosed between 15 and 34 years of age who were treated with insulin. Our second aim was to determine whether there was a difference in risk of diabetes between relatives of male and female patients. METHODS: A questionnaire was sent to patients in the Diabetes Incidence Study in Sweden registry diagnosed between 1983 and 1993 to determine the presence of first-degree relatives with diabetes. RESULTS: In 3087 index patients treated with insulin, 17.8% (95% confidence interval 16.5, 19.2) had a first-degree relative (excluding offspring) treated with insulin, the frequency being higher in female (19.8%) than in male (16.5%, P = 0.018) patients. A total of 10.7% had a parent treated with insulin. The prevalence of insulin-treated diabetes was higher among parents of female (12.5%) than of male (9.5%), insulin-treated index patients (P = 0.0068). A similar difference was observed using life table analysis (P = 0.0025), which also showed that the risk by 63 years of age was 7.6% for parents of female and 4.9% for parents of male insulin-treated index patients. In insulin-treated index patients, 8.4% had a sibling with insulin-treated diabetes. CONCLUSIONS: We conclude that the risk for relatives of women with insulin-treated diabetes was higher than for relatives of insulin-treated male patients. We suggest that greater genetic susceptibility is required for females compared with males in the 15-34 age group in order to develop diabetes and hence females might carry more diabetes genes since more of their relatives also develop diabetes.

Adolescent↗
PubMed2004

Global core recommendations for a musculoskeletal undergraduate curriculum.

OBJECTIVE: To develop core recommendations for the learning outcomes of an undergraduate curriculum in musculoskeletal conditions for any parts of the globe. METHODS: Recommendations were developed by wide consultation with experts in orthopaedics, rheumatology, osteoporosis, and rehabilitation from all parts of the world who had interest and experience in these specialties, with the support of international and national societies. All possible knowledge, skills, and attitudes that might be of relevance to musculoskeletal conditions were initially considered and then reduced to those considered essential for all doctors. RESULTS: The recommendations focus on (a) basic skills to assess and diagnose musculoskeletal problems; (b) the competency to assess specific common or urgent musculoskeletal problems; (c) the theoretical background of the conditions and their management; and (d) the core knowledge necessary to support diagnosis and management, including basic sciences. At the end of the course, all students should be able to differentiate normal from abnormal locomotor symptoms in a patient, determine the relevant investigations and interpret the results, formulate a limited differential diagnosis, recognise the impact of the problem on the individual patient, and make an appropriate management plan. CONCLUSIONS: The recommendations set global standards for the minimum level of competence in managing patients with musculoskeletal problems. They define what all doctors should know when graduating from medical school, regardless of further specialisation. They are intended to form the basis of a curriculum for a musculoskeletal course and can be adapted for any medical school in any country throughout the world.

Clinical Competence↗
PubMed2003

Association of the collagen type 1 (COL1A 1) Sp1 binding site polymorphism to femoral neck bone mineral density and wrist fracture in 1044 elderly Swedish women.

Identification of risk factors for osteoporosis has been essential for understanding the development of osteoporosis and related fragility fractures. A polymorphism of the binding site for the transcription factor Sp1 of the collagen I alpha 1 gene (COLIA1) has shown an association to bone mass and fracture, but the findings have not been consistent, which may be related to population differences. The Sp1 polymorphism was determined in 1044 women, all 75 years old, participating in the population-based Osteoporosis Prospective Risk Assessment study in Malmö (OPRA). Bone mineral density, heel ultrasound and all previous fractures were registered. BMD was 2.7% lower in the femoral neck in women carrying at least one copy of the "s" allele ( P = 0.027). There was no difference in bone mass at any other site, weight, BMI or age at menopause. Women with a prevalent wrist fracture (n = 181) had an increased presence of the "s" allele. The odds ratio for prevalent wrist fracture was 2.73 (95% CI 1.1-6.8) for the ss homozygotes and 1.4 (95% CI 1.0-2.0) for the Ss heterozygotes when compared with the SS homozygotes. In conclusion, in this large and homogeneous cohort of 75-year-old Swedish women, there was an association among the Sp1 COLIA1 polymorphism, bone mass, and fracture. The presence of at least one copy of the "s" allele was associated with lower femoral neck BMD and previous wrist fracture and in addition, it was related to an increased risk for wrist fracture.

Aged↗
PubMed2003

Single nucleotide polymorphisms in the human gene for osteoprotegerin are not related to bone mineral density or fracture in elderly women.

Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor family, is a potent inhibitor of osteoclast activation and differentiation. In animal models OPG prevents bone loss, and in humans bone resorption can be reduced by injections of OPG. OPG may also play a role in cardiovascular disease since mice lacking the OPG gene display arterial calcification. In a screening effort of the OPG gene, we recently discovered a single nucleotide polymorphism in the promoter region of OPG (T950C), and reported an association with vascular morphology and function in 59 healthy individuals. Due to the pronounced effect of OPG on bone turnover, the present study was conducted to investigate whether OPG polymorphisms are also associated with bone mineral density or with fracture. The relationship between single nucleotide polymorphisms in the promoter region of OPG (T950C) and the first intron (C1217T), and bone mineral density, measured by DXA in the hip or spine or ultrasound of the heel, was investigated in the Malmö OPRA-study of 1044 women, all 75 years old. The possible relation to fracture incidence was also analyzed. Among the 858 and 864 individuals respectively, genotyped, no significant associations between the investigated single nucleotide polymorphisms and bone mineral density measurements (T950C P = 0.50-0.64, C1217T P = 0.51-1.00), quantitative ultrasound measurements of the calcaneus, or fractures (T950C P = 0.61-0.66, C1217T P = 0.14-0.33) were found. Thus, our results show that polymorphisms in the OPG gene, one of which has previously been found to be associated with cardiovascular morphology and function, are not associated with bone mineral density in elderly Swedish women.

Aged↗
PubMed2003

Influence of muscle strength, physical activity and weight on bone mass in a population-based sample of 1004 elderly women.

High physical activity level has been associated with high bone mass and low fracture risk and is therefore recommended to reduce fractures in old age. The aim of this study was to estimate the effect of potentially modifiable variables, such as physical activity, muscle strength, muscle mass and weight, on bone mass in elderly women. The influence of isometric thigh muscle strength, self-estimated activity level, body composition and weight on bone mineral density (dual energy X-ray absorptiometry; DXA) in total body, hip and spine was investigated. Subjects were 1004 women, all 75 years old, taking part in the Malmö Osteoporosis Prospective Risk Assessment (OPRA) study. Physical activity and muscle strength accounted for 1-6% of the variability in bone mass, whereas weight, and its closely associated variables lean mass and fat mass, to a much greater extent explained the bone mass variability. We found current body weight to be the variable with the most substantial influence on the total variability in bone mass (15-32% depending on skeletal site) in a forward stepwise regression model. Our findings suggest that in elderly women, the major fracture-preventive effect of physical activity is unlikely to be mediated through increased bone mass. Retaining or even increasing body weight is likely to be beneficial to the skeleton, but an excess body weight increase may have negative effects on health. Nevertheless, training in elderly women may have advantages by improving balance, co-ordination and mobility and therefore decreasing the risk of fractures.

Aged↗
PubMed2003

Effect of previous and present physical activity on bone mass in elderly women.

The importance of a physically active lifestyle as a preventive measure for maintaining bone mass is often stressed. The aim of this study was to evaluate the effect of everyday physical activity on bone mass from young adulthood to old age in 75-year-old women. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry technique in total body, hip (femoral neck and trochanter), and spine (LII-LIV) in a population-based cohort of 995 women, all 75 years old. Each woman responded to a questionnaire giving an estimate of the previous and present physical activity level at work and leisure time from youth and up to the present age of 75 years. No correlations were found between the different estimates of physical activity level and BMD. In a multiple regression analysis the different estimates of physical activity level did not have any combined effect on BMD in any of the skeletal regions measured; neither did the physical activity, previous or present, differ when the subgroup of women with a BMD in the highest quintile at all sites was compared with women with a BMD in the lowest quintile. The activity level in the various areas of life did not correlate to each other indicating that few women had chosen a generally active vs non-active lifestyle. A hypothetical positive effect on bone by one activity could therefore be diminished by another. The answer alternatives were mostly not normally distributed, which could also affect the results, making it difficult to identify women with extremely high or low physical activity level. In conclusion, the results from this study of randomly selected elderly women cannot confirm an effect of previous and present everyday physical activity on bone mass. Neither was it possible to find an effect of physical activity in those women with the highest BMD at all sites, suggesting that other factors are of greater importance for maintaining bone mass in elderly women.

Aged↗
PubMed2001

Role of biochemical markers in the management of osteoporosis.

Several serum and urine biochemical markers of bone resorption and formation have been developed. Biochemical bone markers have been used as intermediate end-points in all major studies of anti-osteoporotic therapies. Bone resorption markers, in particular, may add an independent, predictive value to the assessment of bone loss and fracture risk. There are also potential advantages in monitoring anti-osteoporotic treatment in the short-term in addition to bone densitometry, to rapidly identify non-responders to therapy, or non-compliance. Despite these recent advances, until now bone markers have simply been very useful research tools, with their clinical utility being limited by intra-individual and diurnal variability. However, the probability of the true bone mineral density response to hormone replacement therapy for the individual patient may be predicted using algorithms based on a spectrum of cut-off bone marker levels with varying false positive and negative rates. Thus, the transition of biochemical bone markers into everyday clinical practice may be rapidly approaching.

Biomarkers↗
PubMed2000

Bone loss following tibial osteotomy: a model for evaluating post-traumatic osteopenia.

The reduced bone mineral density (BMD) found in patients with fractures may, in part, follow rather than precede the fracture. We studied the magnitude and reversibility of bone loss in the 15 months following osteotomy in 21 men and 5 women with localized medial arthritis of the knee. BMD (mean +/- SD), measured using dual-energy X-ray absorptiometry, decreased by a maximum of 35 +/- 21% in the mid-diaphysis of the affected tibia at 9 months after surgery (p < 0.001). At 15 months, reversal of bone loss in non-fractured bones was incomplete; the remaining deficit was 20 +/- 27% relative to baseline (p < 0.001). Maximum bone loss occurred at 9 months at the total body (5 +/- 2%), spine (15 +/- 17%) and at Ward's triangle of the proximal femur of the unoperated limb (10 +/- 17%) (all p < 0.01). In summary, post-traumatic bone loss is region-specific with incomplete reversibility, at least after about 15 months. Deficits in BMD in cross-sectional studies of patients with fractures, held to be responsible for the bone fragility, may, in part, follow rather than precede the fracture.

Absorptiometry, Photon↗
PubMed1999

The proportion of carboxylated to total or intact osteocalcin in serum discriminates warfarin-treated patients from control subjects.

We assessed the serum concentration of gamma-carboxylated osteocalcin (OC), total OC, and full-length OC in a clinical setting of 37 patients on continuous warfarin treatment (international normalized ratio 2.0-3.8). A comparison was done with the results from 30 untreated age-matched controls. Four monoclonal antibodies, previously generated and characterized as to their ability to recognize different human OC forms and fragments, were used in three two-site immunofluorometric assays. The warfarin-treated patients had significantly lower levels of carboxylated OC 4.9 +/- 3.8 (+/- 1 SD) ng/ml compared with the controls 13.1 +/- 9.7 (p < 0.0001). There was no difference in the levels of total OC or full-length OC between the two groups of patients. A strong correlation was found between the serum concentration of carboxylated OC and total OC, both for the warfarin-treated patients (r = 0.98) and for the controls (r = 0.99). There was a distinct cut-off level at 0.80, in the quotient carboxylated OC/total OC, at which all warfarin-treated patients fell below and all controls above this level. Hence, the concentration or ratio of serum gamma-carboxylated OC in clinical settings such as warfarin-treated patients could be measured using two-site immunoassays.

Aged↗
PubMed1998

Effects of calcium depletion and repletion on serum insulin-like growth factor I and binding protein levels in weanling rats.

Previous studies in a weanling rat model indicated that dietary calcium depletion not only stimulated osteoclastic resorption but also inhibited bone formation. The present study sought to test whether the depletion-associated inhibition of bone formation is related to a reduction in serum insulin-like growth factor-I (IGF-I) and/or an increase in its binding proteins (IGFBPs). Twenty male weanling rats were divided into two weight-matched groups. The study group was subjected to a semisynthetic diet deficient in calcium (0.02% calcium) for 28 days, while the control group was pair-weighed on the same diet but containing 0.62% calcium. After the depletion phase, all rats were fed the same calcium-containing diet for an additional 14 days. Serum samples were obtained from each animal on a weekly basis and assayed for IGF-I and IGFBPs. During depletion, there was no statistically significant difference in serum IGF-I level between the study group and the control group. In contrast, the study group showed a statistically significant increase in several serum IGFBPs with apparent molecular size of 30-38 kD (IGFBP-3), 26-28 kD (IGFBP-1, -2, -5, and/or -6), and 24-25 kD (IGFBP-4), respectively, compared to the control group. There was no difference in nutritional intakes between the two groups of rats during depletion. During repletion, there was also no significant difference in serum IGF-I level between the control and study group. However, during the first 7 days of repletion, serum IGFBP-3 and the 26-28 kD IGFBP of the study group was significantly less than those of the control group, which then returned to the control level after 2 weeks of repletion. In summary: (1) calcium depletion in weanling rats increased several serum IGFBPs without an effect on IGF-I; and (2) calcium repletion induced an acute reduction in serum IGFBP-3. In conclusion, these findings represent the first evidence that the depletion-related inhibition of bone formation in the rat may be associated with an increase in several serum IGFBPs, which may act to inhibit the osteogenic actions of IGFs.

Animals↗
PubMed1998

Effects of short-term calcium depletion and repletion on biochemical markers of bone turnover in young adult women.

The skeletal responses to calcium depletion and repletion in rodents have been well characterized, but those in humans are poorly understood. The present study sought to evaluate the effects of short term dietary calcium depletion and repletion on biochemical markers of bone turnover in 15 young Caucasian women (age, 21-30 yr). The study contained 3 phases: 1) 5 days of a regular diet containing more than 800 mg/day calcium to establish baseline values (baseline phase), 2) 22 days of a restricted diet containing less than 300 mg/day calcium (depletion phase), and 3) 7 days of a normal diet containing more than 800 mg/day calcium (repletion phase). Serum and urine samples were obtained from each subject during the baseline phase; on the first, second, and last days of the depletion phase; and on the third and last days of the repletion phase. Serum levels of calcium, PTH, 1,25-dihydroxyvitamin D3, osteocalcin, and C-terminal type I procollagen peptide (PICP) and urinary levels of calcium and deoxypyridinoline were determined. Serum and urinary calcium levels were significantly reduced, and serum PTH and 1,25-dihydroxyvitamin D3 levels were markedly increased during depletion. These changes were completely reversed after 1 week of repletion. Depletion also rapidly and significantly increased the urinary deoxypyridinoline level, indicating increased bone resorption. The increase also returned rapidly to baseline upon repletion. Calcium depletion had contrasting effects on bone formation markers; whereas depletion significantly reduced the serum PICP level, it significantly increased serum osteocalcin level. Past histomorphometric studies in rodents indicated that the number of mature but inactive osteoblasts was increased during depletion despite an inhibition of bone formation. Thus, it is speculated that although the reduction in serum PICP reflected the depletion-associated inhibition of bone formation, the increase in serum osteocalcin could represent this depletion-related increase in osteoblast number. During repletion, serum osteocalcin remained elevated above baseline. PICP recovered from its depressed level and increased above baseline, a finding consistent with past histomorphometric findings of increased bone formation during repletion. In summary, this study confirms that 1) a short calcium depletion period produces calcium stress in young women, which leads to rapid stimulation of bone resorption and inhibition of bone formation; and 2) a subsequent calcium repletion period could lead to a compensatory increase in bone formation. In conclusion, the skeletal responses to calcium depletion/ repletion in young women may be similar to those in rodents.

Adult↗
PubMed1995

Assessment of biochemical markers of bone metabolism in relation to the occurrence of fracture: a retrospective and prospective population-based study of women.

We have in a population-based setting evaluated biochemical markers of bone metabolism in 328 women, aged 40-80 years, and related it to contents of bone mineral measurements and the retrospective and prospective presence of fracture. The participants were recruited from the city population files. Serum samples for analysis of osteocalcin (Oc), procollagen I carboxy-terminal extension peptide (PICP), and carboxy-terminal telopeptide of type I collagen (ICTP) were taken, and forearm bone mineral content (BMC) was measured by single photon absorptiometry (SPA). Fracture history was recorded, and the information was verified and supplemented from both radiologic and orthopedic files. Five years later the registration of fractures was repeated. At the initial investigation, Oc was 23% lower in women who had sustained a fracture (n = 37) within 6 years before measurement (6.3 +/- 3.6 microgram/l vs 8.2 +/- 4.2 microgram/l (p = 0.006)), after adjusting for age and BMC difference. PICP and ICTP were not different from values in the women without fracture. However, in women aged 70-80 years with a fracture sustained during the previous 6 years, PICP was lower (128 +/- 32 microgram/l vs 144 +/- 34 microgram/l, p = 0.046). Oc and ICTP were significantly correlated to age and BMC (Oc-age r = 0.36, Oc-BMC r = -0.31, ICTP-age r = 0.44, ICTP-BMC r = -0.24). The correlations of PICP were weaker. Prospectively, logistic regression gave an odds ratio (OR) of 1.8 (p = 0.015) for a low PICP and fracture susceptibility, at a change of 1 SD, independent of age and BMC. In the age bracket 70-80, the odds ratio was 2.4 (p = 0.036). The odds ratio for ICTP, independent of age and BMC, was 1.9 (P = 0.043) for 1 SD decrease and subsequent fracture risk. We concluded that women who had sustained at least one recent fracture had an altered bone turnover with decreased bone formation but an unaltered resorption. Women with retrospectively registered fractures also sustained subsequent fractures. A decrease from the mean of the collagen markers PICP and ICTP was associated with an increased risk for future fracture. Utilizing these biochemical markers of bone metabolism in a female population, PICP and ICTP had a similar influence on the risk of future fracture as forearm BMC (OR = 1.6, p = 0.03).

Adult↗