Jan A. Falch

Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: Results from 394 patients in the Oslo County rheumatoid arthritis register

OBJECTIVE To examine the bone mineral density (BMD), frequency of osteoporosis, and risk factors for BMD reduction in a representative population of female rheumatoid arthritis (RA) patients ages 20-70 years. METHODS BMD in the femoral neck, total hip, and spine L2-4 (anterior-posterior view) was measured in 394 RA patients recruited from a validated county RA register (completeness 85%) comprising 721 women ages 20-70 years. BMD was measured with dual-energy x-ray absorptiometry, and age-specific values were compared with pooled values from a European/US population of healthy subjects free from earlier fractures, chronic diseases, and medications influencing bone metabolism. A multiple linear regression model was used to determine individual predictors of BMD. RESULTS No statistically significant differences were found in demographic, disease activity, disease severity, or health status parameters between the RA register patients in whom BMD was measured and the remaining register patients. Femoral neck BMD was significantly reduced by 4.2% in the age group 50-59 years, and by 5.0% in those ages 60-70 years. For BMD in the total hip, the significant reductions were 3.7%, 6.0%, and 8.5% in the age groups 40-49 years, 50-59 years, and 60-70 years, respectively. No significant reduction in spine L2-4 BMD was found. A 2-fold increased frequency of osteoporosis was observed in all 4 age groups of RA patients compared with the reference population, ranging from 0% to 28.6% in the femoral neck, 0% to 29.9% in the total hip, and 1.8% to 31.5% in the spine. Predictors of reduced BMD were as follows: at the femoral neck, older age, low body weight, current use of corticosteroids, greater physical disability (as measured by the modified Health Assessment Questionnaire [M-HAQ]), and presence of rheumatoid factor; at the total hip, older age, low weight, current use of corticosteroids, and higher M-HAQ disability score; and at the lumbar spine, older age, low weight, and current use of corticosteroids. CONCLUSION Register-based prevalence data on BMD reduction in female RA patients ages 20-70 years are presented for the first time in this report, which demonstrates a 2-fold increase in osteoporosis in this representative population.

Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial.

Randomized controlled trials have shown that a combination of vitamin D and calcium can prevent fragility fractures in the elderly. Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known. We studied if an intervention with 10 μg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double‐blinded randomized controlled trial. Residents from 51 nursing homes were allocated randomly to receive 5 ml of ordinary cod liver oil (n = 569) or 5 ml of cod liver oil where vitamin D was removed (n = 575). During the study period of 2 years, fractures and deaths were registered, and the principal analysis was performed on the intention‐to‐treat basis. Biochemical markers were measured at baseline and after 1 year in a subsample. Forty‐seven persons in the control group and 50 persons in the vitamin D group suffered a hip fracture. The corresponding figures for all nonvertebral fractures were 76 persons (control group) and 69 persons (vitamin D group). There was no difference in the incidence of hip fracture (p = 0.66, log‐rank test), or in the incidence of all nonvertebral fractures (p = 0.60, log‐rank test) in the vitamin D group compared with the control group. Compared with the control group, persons in the vitamin D group increased their serum 25‐hydroxyvitamin D concentration with 22 nmol/liter (p = 0.001). In conclusion, we found that an intervention with 10 μg of vitamin D3 alone produced no fracture‐preventing effect in a nursing home population of frail elderly people.

Factors Associated with Mortality after Hip Fracture

Abstract: There is a well-known excess mortality subsequent to hip fracture, which is probably restricted to subgroups of hip fracture patients with reduced health status. We studied the association between risk factors and death in 248 hip fracture patients and 248 controls originally enrolled in a population-based case–control study. This cohort was followed for 3 1/2 years with respect to total mortality. A markedly increased mortality was found in hip fracture patients passing a mental status test at a low score [relative risk (RR) = 2.3, 95% confidence interval (CI) 1.4-3.7], in hip fracture patients reporting two or more selected chronic diseases (RR = 3.3, 95% CI 1.8–6.1), in hip fracture patients not walking outdoors before the fracture (RR = 3.2, 95% CI 2.0–5.1) and in hip fracture patients in the lower half of handgrip strength distribution (RR = 2.3, 95% CI 1.6–3.4), all compared with the control group. In contrast, hip fracture patients without these risk factors did not have increased mortality compared with the control group. This study suggests that otherwise healthy and fit patients do not have increased mortality subsequent to hip fracture. The excess mortality is restricted to persons with reduced mental status, reduced somatic health and low physical ability. Special attention should be paid to patients with such risk factors in the treatment and rehabilitation period.

Epidemiology of hip fractures in Norway

During the 2-year period 1978-1979, a total of 2109 hip fractures (of the proximal end of the femur) occurred in Oslo. The age- and sex-specific annual incidence was the highest ever reported. A previous hip fracture had occurred in 13 per cent of the women and 6.8 per cent of the men. In 1979, a total of 5920 hip fractures was reported in Norway. Compared with Oslo, all other counties had a lower incidence. The number of fractures in Oslo was five times greater in 1982 compared with 1950. This increase cannot be explained only by the increasing number of elderly persons.

Glucocorticoid replacement therapy and pharmacogenetics in Addison's disease: effects on bone.

UNLABELLED Context Patients with primary adrenal insufficiency (Addisons disease) receive more glucococorticoids than the normal endogenous production, raising concern about adverse effects on bone. OBJECTIVE To determine i) the effects of glucocorticoid replacement therapy on bone, and ii) the impact of glucocorticoid pharmacogenetics. DESIGN, SETTING AND PARTICIPANTS A cross-sectional study of two large Addisons cohorts from Norway (n=187) and from UK and New Zealand (n=105). MAIN OUTCOME MEASURES Bone mineral density (BMD) was measured; the Z-scores represent comparison with a reference population. Blood samples from 187 Norwegian patients were analysed for bone markers and common polymorphisms in genes that have been associated with glucocorticoid sensitivity. RESULTS Femoral neck BMD Z-scores were significantly reduced in the patients (Norway: mean -0.28 (95% confidence intervals (CI) -0.42, -0.16); UK and New Zealand: -0.21 (95% CI -0.36, -0.06)). Lumbar spine Z-scores were reduced (Norway: -0.17 (-0.36, +0.01); UK and New Zealand: -0.57 (-0.78, -0.37)), and significantly lower in males compared with females (P=0.02). The common P-glycoprotein (ABCB1) polymorphism C3435T was significantly associated with total BMD (CC and CT>TT P=0.015), with a similar trend at the hip and spine. CONCLUSIONS BMD at the femoral neck and lumbar spine is reduced in Addisons disease, indicating undesirable effects of the replacement therapy. The findings lend support to the recommendations that 15-25 mg hydrocortisone daily is more appropriate than the higher conventional doses. A common polymorphism in the efflux transporter P-glycoprotein is associated with reduced bone mass and might confer susceptibility to glucocorticoid induced osteoporosis.

Body composition in patients with inflammatory bowel disease: a population-based study

OBJECTIVES:Weight loss and nutritional depletion are common features of inflammatory bowel disease. Our aim was to assess body composition in patients with Crohns disease (CD) and ulcerative colitis (UC) and to evaluate possible differences between the patient groups and healthy subjects.METHODS:A total of 60 patients with CD, 60 patients with UC, and 60 healthy subjects were investigated. Each group consisted of 24 men and 36 women. Body composition was measured by dual x-ray absorptiometry and Z scores were obtained by comparison to age- and sex-matched normal values.RESULTS:Bone mineral content and lean body mass were significantly lower in patients with CD compared with patients with UC and healthy subjects. The body composition of CD men was more strongly affected than that of women. UC patients had significantly higher fat mass and body mass index than patients with CD and healthy subjects. There was no difference in the percentage of fat mass between the two patient groups. Corticosteroid treatment and smoking had a negative impact on bone mineral content and lean body mass in CD patients independently of each other.CONCLUSIONS:CD was associated with disturbances in body composition: both bone mineral content and lean body mass were significantly reduced, especially in men with CD. Corticosteroid therapy and smoking had a significant influence on body composition in patients with CD. When studying the effects of inflammatory bowel disease on body composition and nutritional status, patients with CD and UC should be evaluated separately.

Reduced bone mineral density in male rheumatoid arthritis patients: Frequencies and associations with demographic and disease variables in ninety-four patients in the Oslo county rheumatoid arthritis register

OBJECTIVE To examine reductions in bone mineral density (BMD) and factors associated with reduced BMD in 94 male rheumatoid arthritis (RA) registry patients ages 20-70 years. METHODS Dual-energy x-ray absorptiometry was used to measure BMD in the anteroposterior lumbar spine at L2-LA, the femoral neck, and the total hip, and clinical data were collected. The patients were recruited from a validated county RA registry (completeness 85%) comprising 192 men ages 20-70 years. Age-specific BMD values were compared with a pooled healthy European/United States population. Bivariate and multivariate analyses were performed to determine demographic and disease-related associations with BMD and reduced bone mass (Z score of < or =1 SD below the mean value in controls). RESULTS A statistically significant BMD reduction was found only for the oldest age group (60-70 years): 5.2% reduction in the femoral neck and 6.9% in the total hip. No BMD reduction was found at L2-L4. The proportions (95% confidence intervals) of RA patients with Z scores of < or =1 SD below control (16% expected) were 30.9% (21.6-40.2) for L2-L4, 30.8% (95% CI 21.3-40.3) for the femoral neck, and 33.0% (95% CI 23.3-42.7) for the total hip. Disease activity and severity measures were, in general, not associated with BMD or reduced bone mass. CONCLUSION A 2-fold statistically significant increased frequency of patients with reduced bone mass (Z score of < or =1 SD below control; 16% expected) was found for both the spine and the hip. The only significant reduction in BMD by age group was for the hip in patients who were ages 60-70 years, with no reduction in L2-LA BMD. Multivariate analyses did not reveal consistent associations between reduced BMD and demographic or disease variables.

Self reported non-vertebral fractures in rheumatoid arthritis and population based controls: incidence and relationship with bone mineral density and clinical variables

Objective: To compare the incidence of self reported non-vertebral fractures after RA diagnosis between female patients with RA and control subjects, and to explore possible associations between non-vertebral fractures and bone mineral density (BMD), disease, and demographic factors. Methods: 249 women (mean age 63.0 years) recruited from a county register of patients with RA and population controls (n = 249) randomly selected after matching for age, sex, and residential area were studied. Data on previous non-vertebral fractures were obtained from a detailed questionnaire, and BMD was measured at the hip and spine. Results: 53 (21.3%) patients with RA had had 67 fractures after RA diagnosis, the corresponding numbers for controls were 50 (20.1%) and 60 (odds ratio (OR) for paired variables for overall fracture history 1.09, 95% CI 0.67 to 1.77). The overall fracture rates per 100 patient-years were 1.62 and 1.45, respectively, but self reported hip fractures were increased in RA (10 v 2, OR 9.0, 95% CI 1.2 to 394.5). Patients with a positive fracture history had longer disease duration, were more likely to have at least one deformed joint, and had lower age and weight adjusted BMD than those with no fracture history. In logistic regression analysis, fracture history was independently related to BMD only. Conclusions: With the probable exception of hip fractures, non-vertebral fractures do not seem to be a substantial burden in RA. Similar independent relationships between levels of BMD and fracture history were found in patients with RA and in population based controls.

More postoperative femoral fractures with the Gamma nail than the sliding screw plate in the treatment of trochanteric fractures

Despite several studies showing a higher incidence of peri-implant femoral fractures with the Gamma nail than with a sliding screw plate (SSP), the Gamma nail has remained the standard implant for trochanteric fractures in many hospitals. We recorded 921 trochanteric fractures in the city of Oslo during 2 years and compared the reoperation frequency in patients treated with the Gamma nail (n 379) and SSP (n 542). The distribution of age and gender in the two treatment groups was the same. 65 patients were reoperated on, several of them more than once. The only significant difference between the two surgical methods in complications leading to a reoperation was the frequency of femoral shaft fractures. 17 of the patients treated with the Gamma nail had a new femoral fracture postoperatively, compared to 3 of those with a SSP. The relative risk of another femoral fracture after surgery was 12 (95% CI: 2.7-52) if the surgical device was a Gamma nail compared to a SSP.The Gamma nail therefore can not be recommended as the standard implant for trochanteric fractures.

Body height, body mass index, and fatal hip fractures: 16 years' follow-up of 674,000 Norwegian women and men

We studied the relations between body height, body mass index (BMI), and fatal hip fractures prospectively in a large, representative population. During the years 1963–1975, a nationwide compulsory mass x-ray examination including standardized height and weight measurements took place in Norway covering all persons age 15 years and older. In the study presented here, we selected women (N = 357,807) and men (N = 316,041) age 50–89 years at screening. We matched the file to the national death register containing causes of death throughout 1991; we defined cases as persons with hip fracture mentioned on their death certificates. During an average follow-up of 16.4 years, we identified a total of 6,087 fatal hip fractures in the study population. There was a distinct inverse relation between BMI and fatal hip fracture, with an age-adjusted relative risk (RR) in the three highest vs the low quartile of 0.68 [95% confidence interval (CI) = 0.63–0.72] in women and 0.57 (95% CI = 0.52–0.62) in men. The risk of fatal hip fractures increased slightly with increasing body height [RR = 1.10 (95% CI = 1.04–1.16) in women and RR = 1.08 (95% CI = 1.01–1.16) in men per 10-cm increase in body height]. This study indicates that low BMI is an important risk factor for fatal hip fractures and that body height has a weak, positive association.