Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study.

We have previously shown that center- and sex-specific fall rates explained one-third of between-center variation in upper limb fractures across Europe. In this current analysis, our aim was to determine how much of the between-center variation in fractures could be attributed to repeated falling, bone mineral density (BMD), and other risk factors in individuals, and to compare the relative contributions of center-specific BMD vs. center-specific fall rates. A clinical history of fracture was assessed prospectively in 2451 men and 2919 women aged 50-80 from 20 centers participating in the European Prospective Osteoporosis Study (EPOS) using standardized questionnaires (mean follow-up = 3 years). Bone mineral density (BMD, femoral neck, trochanter, and/or spine) was measured in 2103 men and 2565 women at these centers. Cox regression was used to model the risk of incident fracture as a function of the person-specific covariates: age, BMD, personal fracture history (PFH), family hip fracture history (FAMHIP), time spent walking/cycling, number of 'all falls' and falls not causing fracture ('fracture-free') during follow-up, alcohol consumption, and body mass index. Center effects were modeled by inclusion of multiplicative gamma-distributed random effects, termed center-shared frailty (CSF), with mean 1 and finite variance theta (theta) acting on the hazard rate. The relative contributions of center-specific fall risk and center-specific BMD on the incidence of limb fractures were evaluated as components of CSF. In women, the risk of any incident nonspine fracture (n = 190) increased with age, PFH, FAMHIP, > or =1 h/day walking/cycling, and number of 'all falls' during follow-up (all P < 0.074). 'Fracture-free' falls (P = 0.726) and femoral neck BMD did not have a significant effect at the individual level, but there was a significant center-shared frailty effect (theta = 0.271, P = 0.001) that was reduced by 4% after adjusting for mean center BMD and reduced by 19% when adjusted for mean center fall rate. Femoral trochanter BMD was a significant determinant of lower limb fractures (n = 53, P = 0.014) and the center-shared frailty effect was significant for upper limb fractures (theta = 0.271, P = 0.011). This upper limb fracture center effect was unchanged after adjusting for mean center BMD but was reduced by 36% after adjusting for center mean fall rates. In men, risk of any nonspine fracture (n = 75) increased with PFH, fall during follow-up (P < 0.026), and with a decrease in trochanteric BMD [RR 1.38 (1.08, 1.79) per 1 SD decrease]. There was no center effect evident (theta = 0.081, P = 0.096). We conclude that BMD alone cannot be validly used to discriminate between the risk of upper limb fractures across populations without taking account of population-specific variations in fall risk and other factors. These variations might reflect shared environmental or possibly genetic factors that contribute quite substantially to the risk of upper limb fractures in women.

Determinants of the size of incident vertebral deformities in European men and women in the sixth to ninth decades of age: the European Prospective Osteoporosis Study (EPOS).

UNLABELLED: More severe vertebral fractures have more personal impact. In the European Prospective Osteoporosis Study, more severe vertebral collapse was predictable from prior fracture characteristics. Subjects with bi-concave or crush fractures at baseline had a 2-fold increase in incident fracture size and thus increased risk of a disabling future fracture. INTRODUCTION: According to Euler's buckling theory, loss of horizontal trabeculae in vertebrae increases the risk of fracture and suggests that the extent of vertebral collapse will be increased in proportion. We tested the hypothesis that the characteristics of a baseline deformity would influence the size of a subsequent deformity. METHODS: In 207 subjects participating in the European Prospective Osteoporosis Study who suffered an incident spine fracture in a previously normal vertebra, we estimated loss of volume (fracture size) from plane film images of all vertebral bodies that were classified as having a new fracture. The sum of the three vertebral heights (anterior, mid-body, and posterior) obtained at follow-up was subtracted from the sum of the same measures at baseline. Each of the summed height loss for vertebrae with a McCloskey-Kanis deformity on the second film was expressed as a percentage. RESULTS AND CONCLUSIONS: In univariate models, the numbers of baseline deformities and the clinical category of the most severe baseline deformity were each significantly associated with the size of the most severe incident fracture and with the cumulated sum of all vertebral height losses. In multivariate modeling, age and the clinical category of the baseline deformity (crush > bi-concave > uni-concave > wedge) were the strongest determinants of both more severe and cumulative height loss. Baseline biconcave and crush fractures were associated at follow-up with new fractures that were approximately twice as large as those seen with other types of deformity or who previously had undeformed spines. In conclusion, the characteristics of a baseline vertebral deformity determines statistically the magnitude of vertebral body volume lost when a subsequent fracture occurs. Because severity of fracture and number of fractures are determinants of impact, the results should improve prediction of the future personal impact of osteoporosis once a baseline prevalent deformity has been identified.

Incidence of vertebral fracture in europe: results from the European Prospective Osteoporosis Study (EPOS).

Vertebral fracture is one of the major adverse clinical consequences of osteoporosis; however, there are few data concerning the incidence of vertebral fracture in population samples of men and women. The aim of this study was to determine the incidence of vertebral fracture in European men and women. A total of 14,011 men and women aged 50 years and over were recruited from population-based registers in 29 European centers and had an interviewer-administered questionnaire and lateral spinal radiographs performed. The response rate for participation in the study was approximately 50%. Repeat spinal radiographs were performed a mean of 3.8 years following the baseline film. All films were evaluated morphometrically. The definition of a morphometric fracture was a vertebra in which there was evidence of a 20% (+4 mm) or more reduction in anterior, middle, or posterior vertebral height between films--plus the additional requirement that a vertebra satisfy criteria for a prevalent deformity (using the McCloskey-Kanis method) in the follow-up film. There were 3174 men, mean age 63.1 years, and 3,614 women, mean age 62.2 years, with paired duplicate spinal radiographs (48% of those originally recruited to the baseline survey). The age standardized incidence of morphometric fracture was 10.7/1,000 person years (pyr) in women and 5.7/1,000 pyr in men. The age-standardized incidence of vertebral fracture as assessed qualitatively by the radiologist was broadly similar-12.1/1,000 pyr and 6.8/1,000 pyr, respectively. The incidence increased markedly with age in both men and women. There was some evidence of geographic variation in fracture occurrence; rates were higher in Sweden than elsewhere in Europe. This is the first large population-based study to ascertain the incidence of vertebral fracture in men and women over 50 years of age across Europe. The data confirm the frequent occurrence of the disorder in men as well as in women and the rise in incidence with age.

Hip geometry, bone mineral distribution, and bone strength in European men and women: the EPOS study.

Hip geometry and bone mineral density (BMD) have been shown previously to relate, independently of each other, to risk of hip fracture. We used Lunar DPX "beta" versions of hip strength analysis (HSA) and hip axis length (HAL) software to analyze scans from ten representative age-stratified population samples in the European Prospective Osteoporosis Study (EPOS). All 1617 subjects were >50 years of age, and 1033 were women. The data were modeled with gender and center as categorical variables. The bone mineral density of the upper half of the femoral neck declined at a faster rate with age than that in the lower half. Femoral neck cross-sectional moment of inertia (CSMI), a measure of resistance to bending, showed no significant age reduction in either gender. However, height and weight effects on CSMI were significantly more beneficial in men than in women (0.002 < p < 0.012) and the weight effect appeared to be mediated by bone mineral content (BMC). Compressive stress (Cstress), defined as the stress in the femoral neck at its weakest cross section arising from a standardized fall, was higher in women. Although Cstress increased with body weight when BMC was held constant, in practice it fell through the association and statistical interaction of rising body weight with rising BMC. HAL, as expected, was strongly positively associated with male gender and also height (p < 0.0001). Hip strength-related indices were markedly center-dependent. Significant differences (p < 0.0001) were noted between the centers for all the variables investigated that related to hip geometry. Adjustment for femoral neck bone mineral content (totBMC) showed these center differences to account for >50% of center variation in hip strength, which remained highly significant (p < 0.0001). We conclude that there are substantial geographical differences in femoral neck geometry as well as in BMD. These geometric variations may contribute to the large variations in hip fracture risk across Europe. The effects of aging on hip strength need to be explored in longitudinal studies.

Falls explain between-center differences in the incidence of limb fracture across Europe.

There is important geographic variation in the occurrence of the major osteoporotic fractures across Europe. The aim of this study was to determine whether between-center variation in limb fracture rates across Europe could be explained by variation in the incidence of falls. Men and women, aged 50-79 years, were recruited from population-based registers in 30 European centers. Subjects were followed by postal questionnaire to ascertain the occurrence of incident fractures, and were also asked about the occurrence and number of recent falls. Self-reported fractures were confirmed, where possible, by review of the radiographs, medical record, or subject interview. The age- and gender-adjusted incidence of falls was calculated by center using Poisson regression. Poisson regression was also used to assess the extent to which between-center differences in the incidence of limb fractures could be explained by differences in the age- and gender-adjusted incidence of falls at those centers. In all, 6302 men (mean age 63.9 years) and 6761 women (mean age 63.1 years) completed at least one questionnaire concerning fractures and falls. During a median follow-up time of 3 years, 3647 falls were reported by men and 4783 by women. After adjusting for age and gender, there was evidence of significant between-center differences in the occurrence of falls. There was also between-center variation in the occurrence of upper limb, lower limb, and distal forearm fractures. Variation in the age- and gender-adjusted center-specific fall rates explained 24%, 14%, and 6% of the between-center variation in incidence of distal forearm and upper and lower limb fractures, respectively. Given the constraints inherent in such an analysis, in men and women aged 50-79 years, variation in fall rates could explain a significant proportion of the between-center variation in the incidence of limb fracture across Europe.

Reactivation of primary hypertrophic osteoarthropathy by bronchogenic carcinoma.

This paper reports 2 cases of primary hypertrophic osteoarthopathy (PHO) which evolved into secondary hypertrophic osteoarthopathy (SHO) under the influence of bronchogenic carcinoma. The patients had a clinical picture of primary hypertrophic osteoarthropathy but without any signs of disease activity until in the last several months when a malignant bronchopulmonary condition developed. This activated all the symptoms: joint swelling; enlarged fingers and distal forearms and legs; moist palms and soles; unpleasant odour of perspiration; and deeper folds of the forehead and nasolabial furrow. A bone scan showed increased accumulation of the radioisotope in specific regions of the skeleton. To our knowledge, no similar cases have been described in the literature.

The medical and surgical treatment of finger clubbing and hypertrophic osteoarthropathy. A blind study with colchicine and a surgical approach to finger clubbing reduction.

In fourteen patients affected with pachydermoperiostosis (PDP), or primary hypertrophic osteoarthropathy, the efficacy of colchicine (0.5 mg day for one month) versus placebo on the main clinical features of the disease (finger clubbing, arthritis and pachydermia) was evaluated. In addition, in one patient the usefulness of surgical reduction of clubbed fingertips was investigated. Colchicine did not demonstrate any appreciable effect on finger clubbing (expressed in degrees) or pachydermia, while an effect on arthralgia (as evaluated by the Ritchie Index and Pain Scale) was observed. The surgical treatment of clubbed fingertips failed to show a satisfactory and stable reduction of the fingertips; two months after surgery the nail matrix apparently produced new tissue, once again enlarging and deforming the finger. These results suggest that low dose colchicine cannot be considered the drug of first choice for the treatment of PDP, while higher dosages, although effective, are not tolerated because of the severe side effects. An effective medical and surgical treatment for PDP will be found only when the pathogenetic mechanisms of the disease are clarified.

Pachydermoperiostosis (primary hypertrophic osteoarthropathy): in vitro evidence for abnormal fibroblast proliferation.

Pachydermoperiostosis (PDP) is a disease characterized by the presence of pachydermia, periostosis and finger clubbing. Evidence that the skin and soft tissues are involved in the disease prompted the in vitro investigation of the behaviour of fibroblasts obtained from cutaneous biopsies of involved and apparently uninvolved PDP skin. PDP fibroblasts from affected skin demonstrated an abnormal proliferation, very rapid and tumultuous when compared to the growth of fibroblasts derived from apparently uninvolved skin and fibroblasts from the skin of healthy subjects. This characteristic was confirmed by the rate of thymidine incorporation, which was increased in PDP-affected fibroblasts (1152 dpm) compared to apparently non-PDP involved fibroblasts (273 dpm) and controls (262 dpm). Ultracentrifuged and non-centrifuged conditioned medium (CM) of fibroblasts affected or apparently not affected with PDP were used to evaluate the effect on the proliferation of healthy skin fibroblasts, compared to the effect of CM derived from healthy fibroblasts and from healthy fibroblasts incubated with 10% and 1% foetal calf serum. The CM of non-centrifuged PDP fibroblasts resulted in a statistically significant stimulation of fibroblast growth when compared to that expressed by ultracentrifuged PDP CM, healthy fibroblast CM and 10% stimulated CM. These data show that PDP fibroblasts maintain in vitro the capacity to proliferate at a higher rate than healthy fibroblasts and that in the CM residual cells and/or their debris may be present, inducing the abnormal growth of healthy fibroblasts. This evidence suggests that fibroblasts in PDP may play a role in the development of the disease.

The spectrum of dermatological symptoms of pachydermoperiostosis (primary hypertrophic osteoarthropathy): a genetic, cytogenetic and ultrastructural study.

Pachydermoperiostosis (PDP) is characterized by finger clubbing, periostosis and peculiar skin involvement (pachydermia, seborrhea and folliculitis). The aim of our work was to determine the occurrence of dermatological symptoms in patients with PDP and their relatives, and to study ultrastructural skin changes in the complete and incomplete forms of the disease. A genetic and cytogenetic study was performed in order to identify the mechanism of transmission, to discover possible links to other genetic and non-genetic diseases and to determine the chromosomal complement and eventual chromosomal anomalies. Pachydermia was the most frequent skin alteration together with seborrhea; folliculitis was present in five patients. In the relatives mild pachydermia was detected in 2 out of 26, while seborrhea was present in 6 subjects. Light microscopic observation showed acanthotic epidermis and endothelial hyperplasia in the dermis with partial occlusion of the lumen, lymphohistiocytic infiltrate, and thickening and packing of collagen fibers. Electron microscopy showed fibroblast activation with increased fibrillogenic activity as shown by hypertrophic Golgi complexes and rough endoplasmatic reticulum with cisternae filled with microfibrils. Endothelial cells partially or completely occluded the capillary lumen and presented an increased amount of Weibel Palade bodies. These data show that skin involvement in PDP is a prominent feature, that sometimes these symptoms may also be present in their relatives, and that endothelial and fibroblast activation is present in the skin. Unfortunately the cytogenetic study did not provide any information about possible karyotype abnormalities.

Primary hypertrophic osteoarthropathy: clinical, radiologic, and scintigraphic characteristics.

BACKGROUND: Our aim was to establish clinical and imaging characteristics of primary hypertrophic osteoarthropathy (PHO). METHODS: A group of 76 patients (71 men and 5 women) with primary hypertrophic osteoarthropathy was examined. Extensive history and status of the locomotor system were determined in all patients. Radiologic and scintigraphic examinations of the bones, thermography, capillaroscopy, gastroscopy, and histologic analysis were also performed. RESULTS: Family history was positive in all 55 patients (100%) summoned for a check-up. Finger clubbing of the hands and feet as well as positive Schamroth test were found in all patients, while hyperhydrosis was found in 65 (85.5%), seborrhea in 39 (51%), and involvement of the joints in 52 (68.5%) patients. Histologic analysis in 18 (23.7%) patients predominantly showed periarticular edema and moderate cellular activity. Periostosis of the long bones was also found in all patients, while scintigraphy, performed in 44 patients, was positive in 18 (33.5%) patients in the active phase of the disease. Thermography, performed in 10 patients, ranged from hypothermia to thermal amputation of feet and hands. Capillaroscopy of hands and feet in 47 (61.8%) patients showed changes in small blood vessels. Gastroscopy indicated abnormalities (ulcer and hypertrophic gastritis) in 21 patients (27.6%). CONCLUSIONS: PHO has special clinical and radiographic manifestations (finger clubbing and periostosis of the long bones) that are associated with some minor manifestations. Development of the disease is gradual (to 20 years) and requires a special diagnostic assessment.

Relationship of the functional status, duration of the disease and pain intensity and some psychological variables in patients with rheumatoid arthritis.

A sample of 61 patients with rheumatoid arthritis was studied to assess the interrelationship between depression, helplessness, functional abilities, pain intensity and duration of the disease. The following questionnaires were employed: Arthritis Helplessness Index (AHI), Epidemiological Studies Depression Scale (CES-D), and the Modified Health Assessment Questionnaire (MHAQ). The pain intensity level was assessed using the Visual Analogue Scale (VAS). Significant interrelationship of MHAQ with VAS and AHI was found as well as between AHI and CES-D and VAS and CES-D. A slight interrelationship between AHI and CES-D was also found. The results obtained from two groups of patients--one including patients with the disease lasting from 1 to 5, and the other extending over a period of 15 to 24 years--were compared. The second group manifested significantly greater difficulties in performing their everyday activities (MHAQ).

The prevalence of osteoarthrosis of the sacroiliac joints in an urban population.

Little attention has been paid to the sacroiliac joints especially with respect to the occurrence of degenerative changes. Two hundred thirty nine of the 1200 persons with rheumatic complaints were examined. In 186 of them osteoarthritis of the sacroiliac joints was found (78%). Among test subjects 51.6% suffered from the low back pain.

HLA antigens in Yugoslav population with rheumatoid arthritis.

The antigens of HLA-DR locus were determined in 127 patients with rheumatoid arthritis and in 175 healthy persons. The frequency of HLA-DR1 antigen was discovered in 45% of the patients and in 22.3% of the examinees from the control group (p less than 0.001). The relative risk is 2.84. 69% of the patients were seropositive. The HLA-DR4 antigen was found in 34% of the patients and in 21% of the healthy examinees (p less than 0.05). The relative risk is 1.91. The rheumatoid factor was determined in 70% of the patients with this antigen.

Radiologic changes of ischial tuberosity in ankylosing spondylitis.

The objective of the paper was to emphasize the meaning of involvement of ischial tuberosity in ankylosing spondylitis, enriching the clinical picture of the disease and pointing to ankylosing spondylitis, especially when sacroiliitis is absent or less developed. Radiologic examination of ischial tuberosity was performed in 68 patients with different developmental stages of ankylosing spondylitis. There were 66 (97%) men and two (3%) women, aged 30 to 56 years. Anteroposterior radiographs of the pelvis were performed in all patients and independently assessed by two radiologists. The radiologic changes of ischial tuberosity were classified into four stages: 1) stage of minimal changes, 2) stage of destructive changes, 3) stage of reconstructive changes, and 4) stage of ossification of tendon fibers in the form of rumpled tufts. Radiologic changes of enthesitis were found on ischial tuberosity in 31 patients (45.5%, p < 0.01). Stage 1 or minimal changes were found in two (6.5%); stage 2 or destructive changes in 13 (42.0%); stage 3 or reconstructive changes in 11 (35.5%) and stage 4 or "tufts phenomenon" in five (16.0%) patients. The classification of changes is useful for the assessment of disease range and progression as well as for the diagnosis when sacroiliitis is obscurely developed and other radiologic signs are not present.

[Is there a rheumatic fever?]. / Ima li reumatske vrucice?

In 1988, 11 patients with a suspicion to rheumatic fever (RF) or acute polyarthritis were admitted to the Department of Internal Medicine, University Hospital, "Dr. M. Stojanovic". Eight patients have been extensively treated together with a physiatrist, while one of them on an outpatient basis. Follow-up has been from 3 to 9 months. Rheumatic fever was diagnosed with a certainty in only one patient. Three have had the diagnoses of Reiter's syndrome and individually, of infectional, ankylosing and rheumatoid arthritis. One patient is still followed up because of the symptomatic diagnosis of partially cured oligoarthritis or recurrent RF. The numerical relation of established diagnoses for the followed up patients has been in accordance with the decrease in incidence of RF both in our country and the world some decades ago. The possible causes of frequent diagnoses of RF in adults and the necessity of careful evaluation of clinical and laboratory parameters and the need to follow-up unclear polyarthritis even when the patients are not hospitalized, until the definite diagnosis has not been made is stressed in this paper. Therefore, the administration of corticosteroids has to be avoided in these patients, except in special cases.

[Nonsteroidal antirheumatic agents and the gastrointestinal system]. / Nesteroidni antireumatici i gastrointestinalni sustav.

The antiinflammatory drugs are broadly used also in the treatment of inflammatory and degenerative rheumatic diseases relating to the treatment of extraarticular rheumatism. It has been held that they have an effect in rheumatic diseases even by means of the inhibition of prostaglandins synthesis. Later it was evidented that all drugs coming from that group cause a numerous side-effects particularly in gastrointestinal system, usually relating to those caming a strong inhibition of prostaglandin synthesis. Some of them cause a selective inhibition of prostaglandin synthesis especially in stomach and kidneys. The appearance of side-effects in gastrointestinal system with patients taking these drugs for a longer period of time could be prevented by a careful choice of their usage. It has been evidented that misoprostol strongly effect the prevention of stomach lesions and duodenum enabling so the usage of non-steroidal antiinflammatory drugs over a longer period of time.

[Pleuropulmonary changes in ankylosing spondylitis]. / Pleuropulmonalne promjene u ankilozantnom spondilitisu.

Pulmonary changes in 100 patients suffering from ankylosing spondylitis were studied. There were 85 men and 15 women with an average age of 48 years (range 29 to 72 years). The mean duration of the disease was 18 years (range 4 to 37 years). The highest percentage of patients (66%) was aged 40 to 60 years. Pleuropulmonary changes were found in 21% of cases. Of these, 11% were due to pulmonary and pleural tuberculosis and the remaining 19% to nonspecific inflammatory processes. Fibrobulous changes affecting the apical region of the lungs were found in one patient with rigid spine and thoracic cage 13 years after the onset of the disease.

[Double-blind study of the effect of tiaprofenic acid in comparison with indomethacin in patients with degenerative joint diseases]. / Dvostruko-slijepo ispitivanje ucinka tiaprofenske kiseline u usporedbi s indometacinom u bolesnika s degenerativnom bolesti zglobova.

The research of the effect and tolerance of tiaprophenic acid comprised 32 patients (10 male and 22 female) aged 53.7 years on average. 16 patients were treated by tiaprophenic acid and the other 16 by indomethacin. Among them 23 patients suffered from gonarthrosis and 9 patients from coxarthrosis. The tested subjective and objective parameters were markedly improved in 66.7% and less well in further 10.4% of patients (a total of 77% examinees). Side-effects were more various and developed more frequently in patients treated by indomethacin.

[The frequency of gout and other disorders of uric acid metabolism in Dalmatia in comparison with these disorders in Croatia]. / Ucestalost uloga i drugih poremecaja metabolizma mokracne kiseline u Dalmaciji u usporedbi s istim pojavama u unutrasnjosti Hrvatske.

According to the literature gout is more frequent in Dalmatia than in continental part of Croatia. Higher average values of uric acid in serum, prevalence of hyperuicaemia as well as uric nephrolithiasis are also seen more frequently in Dalmatia comparing to the continental Croatia. This is probably genetically determined and is connected with metabolic changes of uric acid. Relative isolation of population in Dalmatian where the part of immigrants from other regions since the war started was very small favoured these changes. In addition some exogenous factors contribute in clinical manifestation of uric acid metabolic disturbances. The most important among them are consumption of food rich in nucleoproteins and dehydration in summer period.

[Hypertrophic osteoarthropathy in hemiparesis]. / Hipertroficna osteoartropatija u hemiparezi.

A case of concomitant hypertrophic osteoarthropathy and hemiparesis is presented. The patient had several attacks of cerebrovascular insult with hemiparesis of both the left and right sides. After the last attack he developed clubbed fingers and later periostal reaction on the long bones. The case is interesting and rare, particularly as we have not found similar data in literature.