Is a daily supplementation with 40 microgram vitamin D3 sufficient? A randomised controlled trial.

PURPOSE: The effect of 40 µg (1,600 IU) per day of vitamin D(3) on serum 25-hydroxyvitamin D (25(OH)D) and markers of bone and mineral metabolism was evaluated. METHODS: This intervention study was designed as a double-blind randomised controlled trial. Forty-five community-dwelling subjects (32 females), age 55-84 years, at 58° North latitude were supplemented for 1 year with 40 µg vitamin D(3) plus 1,000 mg calcium per day, or with 1,000 mg calcium per day for controls. Safety parameters and 25(OH)D, intact parathyroid hormone (PTH), ionized calcium, bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase isoform 5b (TRACP5b) were measured over the study period. RESULTS: All subjects supplemented with vitamin D(3) reached a 25(OH)D level above 50 nmol/L. Mean (SD) serum 25(OH)D increased from 50.4 (13.5) nmol/L to 84.2 (17.5) nmol/L, range 55.0-125.0 nmol/L in the vitamin D(3) supplemented group and the corresponding levels for the control group were 47.3 (14.1) nmol/L and 45.7 (13.4) nmol/L, range 26.0-73.0 nmol/L. No serious adverse event was recorded and the highest 25(OH)D level reached, 125.0 nmol/L, is well below toxic levels. BALP and TRACP5b did not change significantly over the study period. CONCLUSIONS: This trial suggests that a daily supplementation with 40 µg vitamin D(3) is sufficient to secure a 25(OH)D level of 50 nmol/L. No side effects were observed in the study group.

A striving for independence: a qualitative study of women living with vertebral fracture.

BACKGROUND: Quantitative studies using generic and disease-specific health-related quality of life (HRQOL) questionnaires have shown that osteoporosis-related vertebral fractures have a significant negative effect on HRQOL, but there are only few studies that address what it means to live with vertebral fracture from a deeper experiential perspective. How HRQOL and daily life are affected several years after vertebral fracture and how women cope with this are more unclear. This study aimed to describe how HRQOL and daily life had been affected in women with vertebral fracture several years after diagnosis. METHODS: The study design was qualitative. Semi-structured interviews were conducted with ten Swedish women during 2008. Data were analysed using qualitative inductive content analysis. RESULTS: The findings of this study revealed three themes related to the influence on HRQOL and daily life: A threatened independence, i.e. back pain, anxiety, negative impact on self-image and consequences in daily life; Strategies for maintaining independence, i.e. coping, self-care and support; and The importance of maintaining independence, i.e. the ability to perform everyday activities, social interaction and having something meaningful to do. The women were striving for independence or maintaining their independence by trying to manage different types of symptoms and consequences in different ways. CONCLUSION: HRQOL and daily life were strongly affected in a negative way by the impact of the vertebral fracture. Information from this study may provide new knowledge and understanding of the women's experiences of living with vertebral fracture from an insider's point of view in order to obtain a deeper understanding of the women's everyday life. However, further evaluation is still needed in larger study groups.

Health-related quality of life after vertebral or hip fracture: a seven-year follow-up study.

BACKGROUND: The negative impact of vertebral and hip low-energy fractures on health-related quality-of-life (HRQOL) has been demonstrated previously, but few prospective long-term follow-up studies have been conducted. This study aims to (i) investigate the changes and long-term impact of vertebral or hip fracture and between fracture groups on HRQOL in postmenopausal women prospectively between two and seven years after the inclusion fracture, (ii) compare HRQOL results between fracture and reference groups and (iii) study the relationship between HRQOL and physical performance, spinal deformity index and bone mineral density at seven-year follow-up. METHODS: Ninety-one women examined two years after a low-energy vertebral or hip fracture were invited to a new examination seven years after the diagnosis. HRQOL was examined using the SF-36 questionnaire and was compared with an age and sex-matched reference group. Physical function was assessed using tests and questionnaires. Bone mineral density was measured. Radiographs of the spine were evaluated using the visual semiquantitative technique. A longitudinal and cross-sectional design was used in this study. Statistical analyses included descriptive statistics, Student's t-tests, ANCOVA, and partial correlation. RESULTS: Sixty-seven women participated. In the 42 women (mean age 75.8, SD 4.7) with vertebral fracture as inclusion fracture, bodily pain had deteriorated between two and seven years and might be explained by new fracture. Remaining pronounced reduction of HRQOL was seen in all domains except general health and mental health at seven-year follow-up in women with vertebral fractures compared to the reference group (p < 0.05). All 25 women (mean age 75.0, SD 4.7) with hip fracture as inclusion fracture had no significant changes in HRQOL between two and seven years and did not differ from the reference group regarding HRQOL after seven years. The vertebral group had significantly lower values for bodily pain, vitality, role-emotional function and mental health compared to the hip group. HRQOL showed a positive relationship between physical activity, static balance and handgrip strength. CONCLUSION: The long-term reduction of HRQOL in women with vertebral fracture emerged clearly in this study. The relationships between HRQOL and physical performance in women with vertebral and hip fracture raise questions for more research.

Weight loss, body fat mass, and leptin in Parkinson's disease.

Weight loss is a common problem in Parkinson's disease (PD), but the causative mechanisms behind this weight loss are unclear. We compared 26 PD patients with sex and age matched healthy controls. Examinations were repeated at baseline, after one and after two years. Body fat mass was measured by Dual X-ray Absorptiometry (DXA). Seventy three per cent of the PD patients lost body weight. Loss of body fat mass constituted a considerable part of the loss of body weight. In the patients who lost weight, serum leptin levels were lower than in those who did not lose weight. The relationship between low body fat mass and low leptin levels seems to be relevant, at least for female PD patients. It is reasonable to believe that low leptin levels in these patients could be secondary to the decreased body fat mass.

Preoperative tumor localization by means of venous sampling for fibroblast growth factor-23 in a patient with tumor-induced osteomalacia.

OBJECTIVE: To report on a novel strategy for tumor localization in a 62-year-old man with hypophosphatemic tumor-induced osteomalacia (TIO). METHODS: Repeated computed tomographic and magnetic resonance imaging scans failed to localize any tumor in a patient with adult-onset hypophosphatemic osteomalacia. Therefore, venous sampling for fibroblast growth factor-23 (FGF23)--a circulating hormone that has been identified as a causative factor for TIO--in major veins was conducted. Serum FGF23 was measured from collected samples by an intact FGF23 enzyme-linked immunosorbent assay. RESULTS: Venous sampling suggested a local increase in serum FGF23 in the left femoral vein; this finding prompted performance of octreotide scintigraphy restricted to the left leg. A tumor was located at the lateral condyle of the left femur, which was also confirmed by magnetic resonance imaging. Surgical resection of the tumor normalized the serum phosphorus and 1,25-dihydroxyvitamin D3 levels within 5 to 10 days, and FGF23 declined to normal levels within 24 hours. Histologic analysis supported the diagnosis of a soft-tissue giant cell tumor. CONCLUSION: Our study case demonstrates the diagnostic complexity and difficulties in localizing a small tumor in a patient with TIO. Venous sampling for FGF23 may be helpful in tumor localization in sporadic cases of hypophosphatemic osteomalacia, especially when noninvasive diagnostic techniques prove insufficient.

Clinical testing for mutations in the MEN1 gene in Sweden: a report on 200 unrelated cases.

CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) is a tumor syndrome of the parathyroid, endocrine pancreas, and anterior pituitary caused by mutations in the MEN1 gene on 11q13. OBJECTIVE: The goal of this study was to determine the MEN1 mutation spectrum and detection rate among Swedish patients and identify which patient categories should be tested for MEN1 mutations. DESIGN/SETTING/PATIENTS: DNA sequences and referral forms from patients referred to the Department of Clinical Genetics at Karolinska University Hospital, Sweden, for clinical MEN1 mutation screening were analyzed. The mutation status of 371 patients (including 200 probands) was ascertained, and the multiplex ligation-dependent probe amplification (MLPA) assay was evaluated for the detection of large deletions. MAIN OUTCOME MEASURE: The main outcome measure was MEN1 genotypes. RESULTS: Forty-eight of 200 index cases (24%) shared 40 different mutations (18 novel). A total of 69% of all mutations resulted in a truncated protein. Two large deletions were detected by MLPA. A total of 94% of all MEN1 families had a mutation in the coding region of the MEN1 gene. A total of 6% of sporadic cases had MEN1 mutations. There was no correlation between severe disease and mutation type or location. CONCLUSIONS: A total of 4% of all mutations were large deletions, and MLPA is now included in our standard MEN1 mutation screening. Individuals with at least one typical endocrine tumour and at least one of the following: 1) a first-degree relative with a major endocrine tumor; 2) an age of onset less than 30 yr; and/or 3) multiple pancreatic tumors/parathyroid hyperplasia were most likely to harbor a mutation; thus these patients should be screened for MEN1 mutations.

Women with low-energy fracture should be investigated for osteoporosis.

INTRODUCTION: Treatment of osteoporosis is becoming more effective, but methods to identify patients who are most suitable for investigation and treatment are still being debated. Should any type of fracture have higher priority for investigation of osteoporosis than any other? Is the number of previous fractures useful information? MATERIAL AND METHODS: We investigated 303 consecutive women patients between 55 and 75 years of age who had a newly diagnosed low-energy fracture. They answered a questionnaire on previous fractures which also dealt with risk factors. Bone mineral density (BMD) was measured at the hip, lumbar spine, and forearm. RESULTS: The distribution of fracture location was: distal forearm 56%, proximal humerus 12%, vertebra 18%, and hip 13%, all with similar age. Half of the subjects had had at least one previous fracture before the index fracture, 19% had had two previous fractures, and 6% had had three or more previous fractures. Patients with vertebral or hip fracture had lower BMD and had had more previous fractures than patients with forearm or humerus fractures. There was an inverse correlation between number of fractures and BMD. Osteoporosis was present in one-third of patients with forearm fracture, in one-half of those with hip or humerus fracture, and in two-thirds of those with vertebral fracture. INTERPRETATION: Vertebral fractures were the strongest marker of low BMD and forearm fractures the weakest. The number of previous fractures is helpful information for finding the most osteoporotic patient in terms of severity. Investigation of osteoporosis therefore seems warranted in every woman between the ages of 55 and 75 with a recent low-energy fracture, with highest priority being given to those with vertebral, hip, or multiple fractures.

Common biochemical markers of bone turnover predict future bone loss: a 5-year follow-up study.

BACKGROUND: Bone mineral density (BMD) is used to follow gain or loss of bone mass but cannot detect changes within a short period of time. Biochemical markers of bone turnover may be of value for prediction of individual bone loss. METHODS: We studied the relation between common inexpensive markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin (OC), urinary hydroxyproline (OHPr), and calcium (Ca)), BMD, age, and menopause in a combined cross-sectional and longitudinal design comprising 429 pre- and postmenopausal randomly selected women aged 21-79 years (mean 50 years). A follow-up was initiated after 5 years (including 192 of these women), which focused on changes in bone mass and the ability of these four common markers of bone turnover (sampled at baseline) to predict future bone loss. RESULTS: A marked increase was observed for all markers at the beginning of menopause. During the postmenopausal period ALP and Ca decreased to near premenopausal levels, while OC and OHPr remained high even 15 years after menopause. We also found inverse correlations at baseline between the bone markers and BMD, independent of the selected marker or skeletal site, r=-0.14 to -0.46, P<0.05. The correlations between ALP, OC, OHPr, and subsequent bone loss over 5 years, was significant for arm, r=-0.23 to -0.36, P<0.01. Baseline levels of all bone markers correlated significantly at group level with the 5-year follow-up of BMD for all sites. The ability of markers to predict individual bone loss was estimated by a multivariate regression model, which included baseline BMD, age, and body mass index as independent variables. ROC analysis showed a validity of approximately 76% for the forearm model, but was lower for the hip (55%) and lumbar spine (65%). CONCLUSIONS: These data show that the common inexpensive biochemical markers of bone turnover ALP, OC, OHPr, and Ca were related to the current bone mass and, moreover, provides information about future bone loss at the individual level. Future investigations should include an evaluation of the clinical relevance of markers of bone turnover in relation to fracture risk.

Is calcaneal stiffness more sensitive to physical activity than forearm bone mineral density? A population-based study of persons aged 20-79 years.

AIMS: The aim of this study was to investigate the associations between forearm bone mineral density (BMD), calcaneal stiffness, and physical activity levels in a normal population using different non-invasive methods. METHODS: The participants were invited to undergo bone measurements using single photon absorptiometry of the forearm and quantitative ultrasound (QUS) of the calcaneal bone, and also to complete a questionnaire. Physical activity levels were designated low, moderate, and high in the question on leisure-time activity. RESULTS: There were 956 participants included in the present study. Forearm BMD in the eighth age decade was 0.40 g/cm2 (95% CI 0.33-0.46 g/cm2) lower than in the third decade among women and 0.28 g/cm2 (95% CI 0.18-0.37 g/cm2) lower among men. The differences in calcaneal stiffness between the same age decades were 22.4 (95% CI 17.5-27.4) among women and 15.8 (95% CI 8.0-23.5) among men. The correlation between forearm BMD and calcaneal stiffness was 0.58 (95% CI 0.52-0.64) in women and 0.34 (95% CI 0.25-0.42) in men. Reported moderate and high leisure-time activity levels in both genders were associated with higher calcaneal stiffness but not with forearm BMD. CONCLUSIONS: The QUS may be used to measure the effect of present physical activity levels on calcaneal bone at the population level. Further longitudinal studies are warranted in order to determine the most appropriate non-invasive method in population-based studies.

Knowledge of osteoporosis in a Swedish municipality--a prospective study.

BACKGROUND: As a part of the Vadstena Osteoporosis Prevention Project, the knowledge of osteoporosis was examined before the intervention program started, after 5 and 10 years. METHODS: At baseline (in 1989) 15% of the population in two Swedish municipalities was randomly invited to the study. The participants in the study group were invited for examination by forearm bone densitometry and a questionnaire concerning lifestyle and risk factors for osteoporosis and also knowledge of osteoporosis, while the subjects in the control group were examined only by questionnaire. Follow-ups were made in 1994 and in 1999. Meanwhile education about osteoporosis was given to the study group, to the public, and to various professionals in the study community. RESULTS: There was a difference in the level of knowledge between the groups prior to the intervention. The rate of increment did not differ significantly between the groups for the study period. Previous participants had 0.58 higher score than new participants in the study group in 1994 (P = 0.031) and 0.76 higher score in 1999 (P < 0.001) regarding the total number of correct answers. The women in the study group had 0.63 higher score than the men in 1994 (P = 0.016) and 1.03 higher score in 1999 (P < 0.001) regarding the total number of correct answers. CONCLUSION: There was no significant effect of a general intervention program concerning the knowledge of osteoporosis in participants in the intervention area compared to the control area.