Relationship between sex hormone binding globulin and blood coagulation in women on postmenopausal hormone treatment.

: Postmenopausal hormone therapy increases the risk of venous thrombosis. Sex hormone binding globulin (SHBG) is a suggested marker of 'total estrogenicity'. The study objective was to evaluate the impact of hormone therapy on SHBG and the association with coagulation variables. The study populations comprised 202 healthy postmenopausal women randomized to treatment with low-dose or conventional-dose hormone therapy, tibolone or raloxifene (RET-study) and 140 women with a history of venous thrombosis randomized to conventional-dose hormone therapy or placebo (EVTET-study). SHBG was determined in serum collected at baseline and after 12 weeks. In healthy women, conventional-dose hormone therapy increased SHBG with mean 9.7 (95% confidence interval 4.8-14.5) nmol/l, low-dose hormone therapy by mean 5.9 (0.4-11.5) nmol/l, raloxifene by mean 7.2 (3.9-10.4) nmol/l, while tibolone reduced SHBG with mean -25.1 (-29.9 to -20.4) nmol/l. SHBG correlated with protein S, tissue factor pathway inhibitor (TFPI) and protein C at baseline, and with protein S and TFPI after 12 weeks, but the change in SHBG from baseline to 12 weeks was only associated with the change in activated protein C (APC) resistance. In women with a history of venous thrombosis, the mean increase in SHBG was 13.6 (8.4-18.9) nmol/l in the conventional-dose hormone therapy group, with no change in the placebo group. Baseline SHBG was higher among women who developed recurrent venous thrombosis on conventional-dose hormone therapy. SHBG correlated with several coagulation inhibitors, but the change in SHBG induced by postmenopausal hormone therapy was only associated with the change in APC resistance.

Randomized trial of hemiarthroplasty versus internal fixation for femoral neck fractures: no differences at 6 years.

BACKGROUND: Hemiarthroplasty has been shown superior to internal fixation for displaced femoral neck fractures (FNF) in the first 2 years. However, there are unanswered questions about the performance of hemiarthroplasty over the longer term compared with internal fixation. QUESTIONS/PURPOSES: We sought to compare hemiarthroplasty with internal fixation in terms of (1) outcomes scores for pain, hip function, and quality of life at a minimum of 5 years after surgery in a randomized trial. A secondary purpose was to compare (2) patient survival and (3) frequency of reoperation in the two groups. METHODS: A total of 222 consecutive patients older than 60 years, including those cognitively impaired, with FNF were randomized to either internal fixation with two parallel screws or bipolar hemiarthroplasty. At a minimum followup of 4.9 years (mean, 5.9 years; range, 4.9-7.2 years), 68 of the 70 surviving patients were examined by a study nurse and study physiotherapist blinded to initial treatment. Questionnaires on hip function (Harris hip score), quality of life (Eq5D), and activity of daily living function (Barthel ADL) were administered. The Barthel ADL index score was split into good function (score 95 or 100) and reduced function (score below 95). RESULTS: The mean survival of the groups was similar with 66.4% (73 of 110) of the patients undergoing hemiarthroplasty and 70.5% (79 of 112) of the patients undergoing internal fixation having died since surgery (p = 0.51). Only 12 of 31 living patients in the internal fixation group had retained their native hips at a mean of 6 years. Between 2 and 6 years, there were two new major reoperations (both in the internal fixation group, for avascular necrosis and deep wound infection). The mean Harris hip score was 66 (SD 19) and 67 (SD 20) in the internal fixation and hemiarthroplasty groups, respectively (p = 0.96). The mean Eq5D index was 0.50 (SD 0.40) in the internal fixation group and 0.34 (SD 0.36) in the hemiarthroplasty group (p = 0.10). Function in terms of ADLs was comparable between the groups; of the patients in the internal fixation group, 42% reported good function on the Barthel ADL index, and the corresponding number in the hemiarthroplasty group was 51% (p = 0.44). CONCLUSIONS: Hemiarthroplasty has predictable and good long-term results after FNF and is the treatment of choice compared with internal fixation. Further studies will evaluate if total hip arthroplasty has advantages over hemiarthroplasty in patients with fracture with long life expectancy.

Secular reduction of excess mortality in hip fracture patients >85 years.

BACKGROUND: More than 20% of the hip fracture patients die within the first year after the incident. Few data are available on the trends in mortality following a hip fracture. The present aim was to study changes in excess mortality after hip fracture from 1978/79 up to 1996/97. METHODS: Data on 5180 hip fracture patients aged ≥ 50 years, identified in three earlier, well validated, incidence studies from Oslo were used. The studies took place in the two years periods 1978-79 and 1989-89 and in a one year period from 1st of May 1996 to 30th of April 1997. The study was designed as a historic cohort study. Exposure was sustaining a hip fracture in the registration periods. Outcome was death of all causes. Age- and sex-specific one year-mortality rates were provided by Statistics Norway. Standardized mortality ratios (SMR) were calculated for the three cohorts for each sex and age-group, for the 0-6 months, 6-12 months, 0-1 year, 1-5 years and 5-10 years intervals after fracture. To assess the duration of the excess mortality in hip fracture patients, time-framed Kaplan-Meier curves for consecutive 5-years intervals were conducted for the hip fracture patients and the corresponding background population. Only patients still alive at the start of the time interval were included. One sample log rank tests were used to test for statistical significance. RESULTS: The one-year SMR ranged from 3.64 (2.82 - 4.61) to 4.53 (3.67 - 5.54) in men and from 2.78 (2.39 - 3.19) to 3.60 (3.19 - 4.05) in women. In the 0-6 months interval a reduction in SMR from 1978/79 to 1996/97 was observed in women aged ≥85 years. The duration of excess mortality ranged from two years in men ≥85 years to more than ten years in men and women aged 65-84 years. CONCLUSION: Excess mortality among hip fracture patients remains high. Over the decades, a reduced excess mortality was mainly seen in the oldest patients, suggesting that specific efforts intending to improve prevention and treatment of osteoporosis and osteoporotic fractures in the youngest elderly are required.

Changes in the vitamin D endocrine system and bone turnover after oral vitamin D3 supplementation in healthy adults: results of a randomised trial.

BACKGROUND: There is uncertainty as to which intake of vitamin D is needed to suppress PTH and maintain normal bone metabolism throughout winter at northern latitudes. We aimed to investigate whether four weeks' daily supplementation with 10 µg vitamin D3 from fish oil produced a greater change in serum vitamin D metabolites, parathyroid hormone, and bone turnover in healthy adults compared with solid multivitamin tablets. Furthermore, it was studied whether age, gender, ethnic background, body mass index, or serum concentrations at baseline predicted the magnitude of change in these parameters. METHODS: Healthy adults aged 19-48 years living in Oslo, Norway (59°N) were randomised to receive a daily dose of 10 µg vitamin D3 given as fish oil capsules or multivitamin tablets during four weeks in late winter. Serum samples from baseline and after 28 days were analysed for 25-hydroxyvitamin D (s-25(OH)D), 1,25-dihydroxyvitamin D (s-1,25(OH)2D), intact parathyroid hormone (s-iPTH), and osteoclast-specific tartrate-resistant acid phosphatase 5b (s-TRACP). Fifty-five eligible participants completed the intervention (74% of those randomised). RESULTS: S-25(OH)D increased by mean 34.1 (SD 13.1) nmol/l, p < 0.001; s-iPTH decreased by mean 1.2 (SD 2.5) pmol/l, p = 0.001; s-1,25(OH)2D increased by mean 13 (SD 48) pmol/l, p = 0.057; and s-TRACP increased by mean 0.38 (SD 0.33) U/l, p < 0.001. For all these parameters, there was no difference between fish oil and multivitamin formulation. Baseline concentrations were the only independent predictors of changes in biochemical parameters. CONCLUSIONS: Four weeks of daily supplementation with 10 µg vitamin D3 decreased mean s-iPTH and increased s-TRACP concentration, and this did not differ by mode of administration. Our results suggest an increased bone resorption following vitamin D supplementation in young individuals, despite a decrease in parathyroid hormone levels. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01482689.

[The treatment of femoral neck fractures]. / Behandling av lårhalsbrudd.

BACKGROUND: About 5000 people fracture their femoral neck every year in Norway. Mean age is about 83 years and about 3/4 are women. For more than 50 years the alternatives have been internal fixation or arthroplasty. In Norway, the tradition has been internal fixation. Recent studies, however, support the use of arthroplasty. The article provides a review on the treatment of femoral neck fractures. MATERIAL AND METHODS: The article is based on literature identified through a non-systematic search in Medline. RESULTS: Internal fixation has a higher risk of treatment failure (30 - 40 % in displaced fractures) than arthroplasty (less than 10 %). In elderly patients with displaced fractures, arthroplasty provides better hip function than internal fixation. Most patients should be treated with hemiarthroplasty, but total hip arthroplasty may give better function in the healthiest and fittest of the elderly patients. In patients younger than 60 - 65 years, internal fixation should be attempted, even though the failure rate is about 30 %. Undisplaced fractures should be treated with internal fixation, irrespective of age. The risk of treatment failure is about 10 %. INTERPRETATION: Elderly patients with displaced femoral neck fractures should be treated with arthroplasty, usually hemiarthroplasty. Osteosynthesis should normally be reserved for undisplaced fractures and fractures in young and otherwise healthy patients.

Vitamin D status in Sri Lankans living in Sri Lanka and Norway.

Vitamin D deficiency is common in non-Western immigrant groups living in Western countries. A comparison of vitamin D status in individuals who have emigrated and individuals who remain in their country of origin is needed in order to provide information about the effect of moving to northern latitudes. A total of 196 participants aged 30-60 years in a cross-sectional population-based study in Kandy, Sri Lanka (latitude 7 degrees north) and 242 Sri Lankans aged 31-60 years participating in a cross-sectional population-based study in Oslo, Norway (latitude 60 degrees north) were included in the analysis. All serum samples were analysed for serum 25-hydroxyvitamin D (s-25(OH)D) in the same laboratory. Sri Lankans living in Norway had substantially lower s-25(OH)D (mean 31.5 nmol/l) compared with those living in Sri Lanka (mean 54.2 nmol/l), and the prevalence of s-25(OH)D < 25 nmol/l was 9.3 times higher (95 % CI 4.4, 19.6) in Norway compared with Sri Lanka. In Sri Lanka there was a clear seasonal variation with the lowest s-25(OH)D levels in August-September and the highest levels in November-December. We conclude that vitamin D status among Sri Lankans living in Kandy, Sri Lanka was considerably higher than that among Sri Lankans living in Oslo, Norway. The low vitamin D status commonly observed in non-Western immigrant groups living at northern latitudes should not be regarded as normal levels for these groups. However, also in Sri Lanka we found a profound seasonal variation with the lowest levels in August and September after the Monsoon.

A randomised comparison of increase in serum 25-hydroxyvitamin D concentration after 4 weeks of daily oral intake of 10 microg cholecalciferol from multivitamin tablets or fish oil capsules in healthy young adults.

Many types of vitamin supplements are available on the market, but little is known about whether cholecalciferol obtained from fat-containing capsules differs in bioavailability from that of solid tablets. Our objective was to test whether 4 weeks of daily supplementation with 10 mug cholecalciferol given as a fish oil capsule produces a larger increase in serum 25-hydroxyvitamin D (s-25(OH)D) concentration compared with the same dose of cholecalciferol given as a multivitamin tablet. A total of seventy-four healthy subjects aged 19-49 years were initially included and fifty-five of these completed the study and fulfilled the inclusion criteria. After completing a self-administered questionnaire about diet and sunshine exposure and having a non-fasting venous blood sample drawn, participants were randomised to receive daily multivitamin tablets (n 28) or fish oil capsules (n 27), each containing equal doses of cholecalciferol. A second blood sample was drawn after 28 d. Mean baseline s-25(OH)D was 40.3 (sd 22.0) nmol/l in the multivitamin group and 48.5 (24.8) nmol/l in the fish oil group. When controlling for baseline s-25(OH)D, mean 4-week increase in s-25(OH)D was 35.8 (95 % CI 30.9, 40.8) nmol/l in the multivitamin group and 32.3 (95 % CI 27.3, 37.4) nmol/l in the fish oil group; the mean difference was 3.5 (95 % CI - 3.6, 10.6) nmol/l (P = 0.33). The results were unaltered by statistical adjustment for BMI, ethnic background, age and sex. We conclude that fish oil capsules and multivitamin tablets containing 10 microg cholecalciferol administered over a 4-week period produced a similar mean increase in s-25(OH)D concentration.