Oral Presentations, Invited Speakers

Abstracts P-50 to P-94

Posters will be on display throughout the symposium, but will be attended by their presenting authors as follows:

Odd numbers on Monday 12:15 - 14:00 and Wednesday 12:15 - 14:00
Even numbers on Tuesday 12:15 - 14:00 and Wednesday 12:15 - 14:00

Abstracts P-1 to P49     Abstracts P-95 to P-140
   

Osteocytes / Mechanical loading

 
P-50

CALCANEAL BONE MINERAL DENSITY IN ELITE PREADOLESCENT FEMALE SWIMMERS AND GYMNASTS

B. Durmaz¹*, B. Ozcaldiran², E. Kutlay²

¹School of Medicine, University of Ege, Izmir, Turkey

²School of Physical Education and Sport, University of Ege, Izmir, Turkey

Calcaneal bone mineral density (BMD) was compared between 10-14-yr-old female swimmers (SWM: N=13) with a history of swimming trainning (min. 12 hour/week for past 4 years) and gymnasts (GYM: N=12) with a history of high volume impact loading (min. 24 hour/week for past 4 years). Calcaneal BMD measures were determined by ultrasound bone densitometry (Sahara Clinical Bone Sonometer). BMD was normalized for height and body weight. GYM were significantly leaner (14.82±1.48 vs 15.85±2.11; means±SD) and had less body fat (8.92±0.73 vs 10.70±2.20 % body fat) than swimmers. Calcaneal BMD normalized for body weight was significantly greater in the GYM than SWM.

As would be expected, gymnasts spent significantly more time engaged in weight bearing activity than swimmers. Our study supports findings that weight-bearing activity is necessary to produce an increase in bone mass.

In conclusion, high volume impact loading was associated with greater (compared with swimmers) calcaneal BMD in pre-adolescent female gymnasts.

These results indicate that the effect on bones of participation in weight-bearing competitive sports begining early in life may be benefical.

[Programme]

 
P-51

BONE MINERAL DENSITY AND DIETARY INTAKE OF PRE- ADOLESCENT FEMALE SWIMMERS

B. Ozcaldiran¹*, B. Durmaz²

¹School of Physical Education and Sport, University of Ege, Izmir, Turkey

²School of Medicine, University of Ege, Izmir, Turkey

The purpose of this study was to compare the bone mineral density (BMD)of competitive female swimmers to age-, height- and weight- matched controls; and was to investigate the relationships between physical activity, dietary calcium and BMD.

23 Swimmers and 29 nonathletic controls aged 9-12 participated in the study. A 3- d dietary diary was completed by subjects for two weekdays and one weekend day. Completed diaries were analyzed using the Nutrient Analysis Program. BMD was obtain by DEXA.

There were statistically significant differences between groups for some dietary variables. Swimmers consumed much more daily intake of calcium, carbohydrate and protein than controls. Average total calorie intake was higher in the swimmers. BMD normalized for height and body weight was significantly greater in the swimmers. Also there was a positive correlation between calcium intake and BMD.

These results indicate that although the swimmers engaged in nonweight-bearing training, they have greater BMD. Dietary intake, especially calcium intake is important for bone mineral density in growing children.

[Programme]

 
P-52

CARTILAGE AND SUBCHONDRAL BONE INTERACTION IN NORMAL AND OSTEOARTHRITIC HUMAN KNEE JOINT: A HISTOLOGICAL AND HISTOMORPHOMETRICAL STUDY

J. Spanjol*, D. Bobinac, S. Zoricic, I. Kristofic, B. Vitkovic, I. Maric

Department of Anatomy, School of Medicine, University of Rijeka

The aim of this study was to determine the correlation between the morphological changes in articular cartilage and underlying subchondral bone in human knee joint. Tibial condyles were examined: 7 from autopsy specimen (average age 70,height 174 cm,weight 84 kg; equal gender distribution; articular cartilage macroscopically normal in appearance) and 8 from patients undergoing total endoprothesis surgery due to severe osteoarthritis (OA) (average age 66,height 170 cm, weight 75 kg, female). Articular cartilage and correspondent underlying subchondral bone specimens were taken at 8 constant points from both medial and lateral condyle using bone trephine. Specimens were washed in saline solution, decalcified in EDTA, embedded in paraffin and cut in serial slices (5 micro m) using Leica RM 2155 microtome. Tissue slices were stained with Safranin O and Toluidine blue. Human articular cartilage was histologically graded by the method of Mankin et al. for degenerative changes as well as the thickness of cartilage. Subchondral bone was studied histomorphometrically by image analysis (Sform, VAMS, Zagreb). The following static parameters were measured: BV/TV,BS/TV,Tb.Th.,Tb.Sp.,Tb.N.. The results of histomorphometrical study were divided into 3 groups according to the Mankin score: Mankin 0-6 (minimal changes), 7-9 (moderate changes) and 10-14 (severe changes). Such correlated results show that the Mankin score corresponds with the higher values of BV/TV and BS/TV. At the same time Tb.Th. was increased while Tb.Sp. was decreased. The cartilage thickness did not correspond to degenerative changes graded by the method of Mankin or to the subchondral bone architecture. Analysis of subchondral bone of the normal tibial condyles revealed lower values of BV/TV,BS/TV,Tb.Th and higher values of Tb.Sp., and Tb.N. when compared to the OA tibial condyles. Comparing results of morphometry of both normal condyles we determined that lateral condyle had greater bone volume of subchondral bone especially on the central part of the articular surface. In OA tibial condyles, the results were inversed; medial condyle was changed more strongly.

[Programme]

 
P-53

CALCANEAL BONE MASS AND MUSCLE STRENGTH IN FEMALE ATHLETES (SWIMMERS AND GYMNASTS)

B. Ozcaldiran¹*, B. Durmaz²

¹School of Physical Education and Sport, University of Ege, Izmir, Turkey

²School of Medicine, University of Ege, Izmir, Turkey

The purpose of this study was 1) to investigate the relationship between calcaneal bone mass and muscle strength and 2) to compare the effects of two different physical activity (weight-bearing versus non-weight bearing exercise as gymnastic and swimming) on calcaneal bone mass and ankle muscle strenth.

19 Swimmers and 21 gymnasts were enrolled the study. The participants were female Physical Education and Sport School Students, 18-21 years old, who had an athletic history of at least 10 years. Ultrasound parameters of the right heel was measured with the Sahara Clinical Bone Sonometer. Ankle muscle strength was evaluated with the isokinetic dynamometry.

Ankle muscle strength was positively correlated with ultrasound parameters. No significant difference in muscle strength was noted among the two groups. Calcaneal ultrasound parameters; BUA, SOS, QUI and BMD were higher (p<0.05)in the gymnasts than swimmers.

In conclusion;

1) Calcaneal bone mineral density was significantly higher in the gymnasts that performed weight bearing exercises than swimmers.

2) Although swimming is a non-weight bearing exercise, it can improve the muscle strength.

3) Swimming exercise had minimal effect on calcaneal bone mineral density.

[Programme]

 
Osteoporosis: pathophysiology and epidemiology

 
P-54

BONE MINERAL DENSITY AND BODY COMPOSITION ASSESSMENT IN CLINICAL PRACTICE

T. O. Chernova

Russian Endocrinology Research Centre, 24-1-387, Kirovogradsksya St, Moscow, Russia

During the past decades the implementation of bone densitometry in clinical practice made it possible to assess BMD in health and disease and to monitor the treatment.

PURPOSES: 1) To assess the clinical value of dual-femur acquisition in comparison with single-femur acquisition and the clinical value of spine densitometry in cases of bone deformities; 2) To assess the clinical significance of T- and Z-Scores

in comparing the clinical data of obese and normal patients; 3) To assess the perspectives of lateral morphometry in clinical practice; 4) To find the new modalities for clinical usage of body composition data.

METHODS: About 6000 patients were examined over the period of 4 years. We assessed all parameters of BMD and body composition using DEXA (Lunar Expert XL, USA).

CONCLUSIONS: 1) There were clinically insignificant differences between dominant and non-dominant proximal femur DEXA results. Dual-femur assessment is very important in special cases of problems with one femur or spine deformities and in cases of early diagnostics of osteopenia among risk population. The obtained data show that in cases of kyphosis, scoliosis, etc the spine acquisition has no clinical significance and is not acceptable for the therapy monitoring; 2) T-Score is important parameter, but Z-Score is more important in assessment of obese patients; 3) Lateral Morphometry (LM) is rather difficult for performance and assessment, it is necessary to assess it simultaneously with x-ray examinations or CT and LM may be useful for scientific research, but its usage for clinical practice is limited; 4) Body composition (BC) is a perspective research in the assessment and therapy monitoring of obesity along with the possible future implementation in the research of aging, insulin resistance and meno- and andropause treatment. The implementation of a new fan- beam densitometer (Prodigy) is promising due to unique possibilities of body composition assessment program.

[Programme]

 
P-55

FOREARM BONE MINERAL DENSITY AND URINARY CROSS- LINKED N-TELOPEPTIDES OF TYPE I COLLAGEN LEVELS IN PATIENTS WITH RHEUMATOID ARTHRITIS

J. Iwamoto¹*, T. Takeda¹, S. Ichimura²

¹Keio University, Tokyo, Japan

²National Defense Medical College, Saitama, Japan

The purpose of the present study was to compare the factors that affect forearm bone mineral density (BMD) and urinary cross-linked N-telopeptides of type I collagen (NTx) levels in patients with rheumatoid arthritis (RA). One hundred and eighty-four patients with RA and 185 sex- and age-matched controls were enrolled in the study: 71 men, 37-68 years of age (RA: 31, controls: 40), 129 premenopausal women, 30-48 years of age (RA: 67, controls: 62), and 169 postmenopausal women, 48-69 years of age (RA: 86, controls: 83). Forearm BMD was measured with a DXA (DTX-200, Osteometer, MediTech, CA, USA.), and urinary NTx levels were measured with enzyme-linked immunosorbent assay. The correlations of forearm BMD and urinary NTx levels with anatomic grade of the wrist, functional class, duration of disease, steroid use, health assessment questionnaire scores for the upper and lower extremities, the levels of serum c-reactive protein and rheumatoid factor, and erythrocyte sedimentation rate were examined by multiple regression analysis. Forearm BMD (g/cm²) was significantly lower and urinary NTx levels (nmol BCE/mmol Cr) were significantly higher in postmenopausal women with RA than in controls (BMD: 0.192±0.063 [mean±SD] vs 0.223±0.076, P<0.01; NTx: 76.2±27.3 vs 57.1±28.3, P<0.001). Urinary NTx levels were significantly higher in premenopausal women with RA than in controls (57.1±36.6 vs 42.3±21.3, P<0.01), although forearm BMD did not differ significantly between them. However, both forearm BMD and urinary NTx levels did not differ significantly between men with RA and controls. Multiple regression analysis showed that in postmenopausal women with RA, forearm BMD was negatively correlated with anatomic grade of the wrist (P<0.01), while urinary NTx levels were positively correlated with functional class and serum rheumatoid factor levels (both P<0.05). These findings suggest that forearm BMD loss in cases of RA may be apparent in women after menopause, and that it may be associated with disuse of the wrist, while increased urinary NTx levels may be associated with decreased general physical activity and increased disease activity.

[Programme]

 
P-56

NORMAL LEVEL OF P1NP IN PATIENTS WITH SUBCLINICAL HYPERTHYROIDISM AS A MARKER OF NORMAL BONE TURNOVER

S. Mirzaei^1,2*, M. Hahn¹, P. Knoll^1,2, G. Krotla³, K. Koriska³, H. Koehn^1,2

¹L. Boltzmann Institute of Nuclear Medicine, Wilhelminenspital, Vienna, Austria

²Wilhelminenspital, Vienna, Austria

³Kaiserin Elisabethspital, Vienna, Austria

There are differing reports in the literature on behalf of bone turnover in patients with subclinical Hyperthyroidism (suppressed TSH and peripheral normal thyroid hormone levels) or suppressed TSH (under treatment with thyroid hormone). The aim of this study was to compare the level of N-terminal pro-peptide of type 1 collagen (P1NP) in patients with different levels of thyroid function. 148 patients (119 f , 29 m, median age 57 y, age range : 17-87 y) of our outpatients were enrolled into the study. Patients with other systemic illnesses or systemic treatment with negative effect on bone metabolism were excluded. 19 out of 21 (14 f, 7 m) patients with elevated P1NP values had hyperthyroidism. Only two patients with elevated P1NP level had a subclinical hyperthyroidism. 60 out of the 127 patients with normal values of P1NP had a subclinical hyperthyroidism (n=35), suppressed TSH under treatment with thyroxin (n=15) , a slight hyperthyroid function (n=10) and the rest of the patients had an euthyroid function. In accordance with other studies it could be demonstrated that a hyperthyroidism is accompanied by a high bone turnover.

However, our findings suggest that subclinical hyperthyroidism is not associated with increased bone turnover.

[Programme]

 
P-57

DIFFERENCES IN LIFESTYLES AND ACTIVITY LEVELS IN AN ELDERLY POPULATION WITH AND WITHOUT MINIMAL TRAUMA FRACTURES

P. A. Turner¹*, G. A. Pryor²

¹School of Social Sciences, University of Teesside, Middlesbrough, UK

²Department of Orthopaedic Surgery, Peterborough Hospitals Trust, Peterborough, UK

BACKGROUND: Prevention of fragility fractures requires more than increased physical activity. Recent studies indicate that health benefits derive from social activities and that clinical depression is a risk factor for fragility fractures. This survey aimed to evaluate lifestyles, pursuits and barriers to activity in people aged 60-79 years, with and without recent minimal trauma fractures.

METHODS: A questionnaire administered during interview to 207 clients (26; 12.6% male; 181; 87.4% female), determined lifestyle behaviours in the three months preceding a fracture or interview. Interviews were conducted in the fracture clinic, the ward, or by telephone. The fracture group (Fg) comprised120 clients. The non- fracture group (NFg) (n-87), matched for race, age and gender was obtained from local GP lists. Exclusions: clients with neurological, severe cardiorespiratory or other disease related to inactivity or osteoporosis. Levels of activity were ranked using a 5- point scale.

RESULTS & DISCUSSION: TV viewing, shopping and reading emerged as dominant pursuits for all. As expected, physical activity levels for the Fg were significantly less than the NFg (p<0.01). However, more than a quarter (26%, 32/120) of the Fg had high activity levels. Multidimensional scaling differentiated between the Fg and NFg in social activities, participation in pursuits and reasons for changes in behaviours. For example, the Fg were more likely to have active, unskilled former occupations (50% v 75%) but were unlikely to drive (53% v 72%). The Fg were less likely to visit a library, have meals out or visit a pub (31% v 72%) or watch TV quiz shows (47% v 83%); but were more likely to have a recent bereavement (61% v 25%). Bereavement in this context included loss of a family pet, friends, children leaving home or loss of a spouse.

The picture that emerged in this study indicates that occupation, certain skills and recent bereavement may contribute to increased fracture risk. Bereavement can lead to reactive depression. Depression was recently identified as a predictor of functional decline in older women. Further research is required to both verify these findings and determine specific interventions that could best improve bone health and reduce fracture risk.

[Programme]

 
P-58

AN IMPROVED DIGITAL IMAGE PROCESSING ALGORITHM FOR VISUAL FRACTURE ASSESSMENT

C. C. Ruth, T. L. Kelly, E. von Stetton*, K. E. Wilson

Hologic, Inc., Bedford, USA

A new image processing algorithm, Image Pro^TM (Hologic, Inc.) has been developed to improve visualization of fractures in single energy spine images obtained on a bone densitometer. The algorithm has been applied to instant vertebral assessment (IVA) images obtained on a Hologic Delphi system. The algorithm improves endplate visualization by enhancing the high frequency component of the image.

Medical images often have a wide dynamic range and contain a vast range of frequency information not all of which is useful for diagnosis. Image Pro processing was developed to improve IVA images for fracture diagnosis. The image acquired in an IVA scan is single energy and covers the full spine. The intensity of x-rays which makes up the image varies significantly between the abdomen and the thorax. This low frequency variation masks the useful higher frequency information such as bone edges, and makes it difficult to view the full vertebrae at a single window and level setting. In radiography this problem is circumvented by taking two different exposures, one thorax and one abdomen, for a full spine exam. Image pro allows optimal visualization over the entire spine by enhancing the high frequencies while preserving the overall appearance of the image. Examples of IVA images are shown with and without Image Pro.

In conclusion, Image Pro digital image processing improves endplate visualization which may lead to improved fracture diagnosis.

[Programme]

 
P-59

ESTIMATED VOLUMETRIC BONE DENSITY IN HEALTHY MEN AND WOMEN IN CROATIA

S. Cvijetic¹*, M. Korsic²

¹Institute for Medical Research and Occupational Health, Zagreb, Croatia

²Department of Endocrinology, Clinical Hospital Center Rebro, Zagreb, Croatia

The aim of this study was to measure bone mineral density (BMD) in healthy Croatian people and see how age, height, weight and postmenopause associate with BMD and estimated volumetric bone density (BMAD).

The study included 526 healthy subjects (249 men and 277 women), aged 20 to 79 years. Anthropometric measurements included height, weight and body mass index (BMI). Bone mineral content (BMC) and areal density (BMD) were measured at the lumbar spine and proximal femur, using dual energy X-ray absorptiometry (DXA). The calculation of volumetric density relied on the formula: BMAD = BMD/vBA (BA=bone area). Association between densitometric parameters and age, height, weight and postmenopause was analyzed with multiple regression.

BMC and BMD decreased with age, especially in postmenopausal women. Bone area (BA) slightly increased with age in both sexes, and BMD loss after the age of 50 could be contributed to BA increase. To minimize the effect of bone size on bone density, volumetric density and areal density were regressed to age, anthropometry and postmenopause. Age and postmenopause were significantly associated with the spine and femoral BMD and BMAD. Furthermore, BMD showed a stronger association with height and weight than BMAD, in both regions.

Weaker association of body height and weight with BMAD than with BMD suggests that BMD depends on the bone size and body size and that the different BMD could be the consequence of the difference in that parameters.

[Programme]

 
P-60

CHANGE IN BONE MINERAL DENSITY IN PATIENTS WITH UROLITHIASIS: A FOLLOW-UP STUDY

A. Tucak¹*, S. Cvijetic², V. Babic Ivancic³, H. Milhofer Furedi⁴, J. Galic¹

¹Department of Urology, Clinical Hospital Osijek, Osijek, Croatia

²Institute for Medical Research and Occupational Health, Zagreb, Croatia

³Institute Rudjer Boskovic, Zagreb, Croatia

⁴Casali Institute of Applied Chemistry, The Hebrew University, Jerusalem, Israel

The purpose of this investigation was to assess the bone mineral content (BMC) and bone mineral density (BMD) over a period of one year in patients with urolithiasis and to determine the factors that could have influenced the changes in bone density during that period.

The patient group comprised 34 men, aged 41.2±7.9 years with recurrent urolithiasis. A wide spectrum of biochemical measurements was performed. Bone mineral density (g/cm²), bone mineral content (BMC) and bone area (BA) were measured twice over a period of one year, at the lumbar spine (L2-L4), femoral neck, Ward's triangle and trochanter, using dual energy absorptiometry. Patients' results were compared to those obtained from 30 healthy male controls of a comparable age group.

Nine patients were hypercalciuric, while most of other metabolic parameters were within the reference values. Bone mineral content and bone areas at all regions were lower in patients comparing to controls, but not significantly. The biggest annual reduction of BMD was noticed at the Ward's triangle (-5.70% in patients and -2.36% in controls), following with femoral neck (-4.06% patients, -2.03% controls) and trochanter (-3.06% patients, -1.39% controls). There was no significant decrease of the BMD of the spine. Analysing the influence of age, body mass index, metabolic parameters and dietary calcium intake on the annual reduction of bone density, we found that age, hyperuricosuria and calcium intake were significantly associated with the bone loss in that time period.

Bone mass reduction in patients with urolithiasis over a one year period did not differ significantly from that in controls and was mostly related to age, hyperuricosuria and calcium dietary restriction, but not to increased calcium excretion.

[Programme]

 
P-61

OSTEOPOROSIS IN PATIENTS WITH DEPRESSION

J. Menczel*, J. Y. Galfin, B. Shapira

Herzog Memorial Hospital, Herzog Hospital Institute of Osteoporosis and Department of Depression, Jerusalem, Israel

Osteoporosis is a major health problem affecting a large proportion of the population. In addition, depressive disorders are a very common health problem with the rate of incidence reaching between 10-25 percent for women and 5-12 percent for men.

Higher incidence of osteoporosis in patients with depression have been reported, but not confirmed by others. Twenty-five patients with major depression were examined and Bone Mineral Density (BMD) with a Lunar Prodigy Dual Photon Absorptionmeter (DEXA) were performed, BMD of lumbar spines and both hips were measured. Hamilton ratings were performed in all patients.

Of the 25 patients with major depression, 12 had definite osteoporosis (48 percent), and their BMD of the neck of femur ranged from t=-1.6 to -4.3, and L{2} to L{4} from -0.6 to -3.8. Only patients who had a t lower than -2.5, either of the neck of femur or L{2} to L{4} were included. Seven were females and five were men. Their ages ranged between 42 to 84 years.

Osteopenia, defined as a BMD measurement with a t of one of the sites between -1 to -2.5, was found in five patients. All five patients were females and their ages ranged from 26 to 73 years.

It can be deducted that 68 percent of the patients with major depression had a loss of bone mass greater than expected. Five who had a t lower than -2.5 were older 75 years. Each patient underwent an interview and risk factors for osteoporosis and fractures were recorded.

We have not matched a control group of the same age and sex, but the results were compared to prevalence figures published as well as to age-matched persons. A higher incidence of osteoporosis was found.

Patients with major depression suffer from falls and taking into consideration the higher prevalence of a low bone mass, preventive and therapeutic measures should be started to avoid fractures, especially of the neck of femur.

[Programme]

 
P-62

BONE MINERAL DENSITY AND MECHANICAL STRENGTH OF FEMUR IN FEMALE RATS CHRONICALLY EXPOSED TO CADMIUM

M. M. Brzoska¹*, J. Moniuszko-Jakoniuk¹, K. Majewska², S. Boczon³, R. Zadernowski²

¹Department of Toxicology, Medical Academy, Bialystok, Poland

²Chair of Food Plant Chemistry and Processing, University of Warmia and Mazury, Olsztyn, Poland

³Diagnostic Imaging Department, Provincial Sniadecki Hospital, Bialystok, Poland

Chronic cadmium exposure leads, among others, to bone lesion. For many years it has been thought that this heavy metal damages bone only at high exposure. But recently it has been hypothesized that cadmium may have lesional effect on bone at much lower levels of exposure than previously anticipated.

The study was designed to examine the effect of chronic (one year) cadmium treatment, corresponding to human environmental (5mg Cd/l of drinking water) and occupational (50mg Cd/l) exposure, on bone mineral density (BMD) and mechanical strength of femur in female rats.

The exposure to both cadmium levels resulted in a significant reduction in the femur BMD and decreased the bone mechanical strength. Femur mineral status significantly correlated with some parameters describing its mechanical properties.

Our results show that cadmium promotes demineralization and affects mechanical strength of bone, even at relatively low exposure. It can result in elevated fragility and increased risk of bone fractures.

[Programme]

 
P-63

OSTEOPOROSIS IN PATIENTS WITH ANKYLOSING SPONDYLITIS: COMPARISON OF SENSITIVITY OF HIP AND LUMBAR SPINE DXA-MEASUREMENTS

H. Franck*, T. Meurer

Center of Rheumatology, Oberammergau, Germany

Introduction: Patients with ankylosing spondylitis are wellknown to have osteoporosis to a certain degree. However, DXA-measurements are limited in the lumbar spine area by syndesmophyts.
The aim of our study was to evaluate the sensitivity of DXA-measurements of the hip, femoral neck (FN) and lumbar spine (LS) in patients with ankylosing spondylitis.

Methods: The lumbar spine and the hip was measured by DXA (Hologic 4500) in 258 patients with ankylosing spondylitis (mean age 49.7 years). All patients fulfilled the modified New York criteria of ankylosing spondylitis.

Results: There were far more patients with osteoporosis according to WHO-criteria measuring the femural neck than measuring lumbar spine (see table 1), only one patient was diagnosed as having osteoporosis by lumbar spine measurements, when

hip measurements was normal.
However 16 patients demonstrated with osteoporosis of the hip when measurements of the lumbar spine was normal (table 2).

Discussion: Our data show that DXA-measurements of the femural neck should be preferred in patients with ankylosing spondylitis in diagnosing osteoporosis.

[Programme]

 
P-64

THE PREDICTIVE VALUE OF BIOCHEMICAL MARKERS OF BONE TURNOVER AS PREDICTORS OF LOSS OF BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN

M. Díaz-Curiel¹*, J. Iborra², J. Farrerons³, J. Cannata⁴, A. Díez-Pérez⁵, J. González- Macias⁶, R. Pérez-Cano⁷, M. Queseda⁸, M. Sosa⁹

¹Fundación Jimenez Díaz, Madrid, Spain

²Novartis Farmacéutica, Spain

³Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

⁴Hospital Central de Asturias, Asturias, Spain

⁵Hospital del Mar, Barcelona, Spain

⁶Hospital Marques de Valdecilla, Santander, Spain

⁷Hospital Universitario Virgen de la Macarena, Sevilla, Spain

⁸Hospital Reina Sofia, Cordoba, Spain

⁹Hospital Universitario Insular de las Palmas, Gran Canarias, Spain

Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of bone mineral density (BMD). This study was designed to examine whether a single baseline bone marker could predict subsequent loss of BMD.

Patients and methods:Two hundred and eleven postmenopausal women were recruited from eight clinical research sites located in Spanish major geographical regions. We measured osteocalcin (OC) and bone alkaline phosphatase (BSAP), as markers of bone formation, and tartrate-resistant acid phosphatase (TRAP), Urinary collagen type I cross-linked C-telopeptide (CTx, CrossLaps) as markers of bone resorption. Lumbar spine and femoral neck BMD were measured at baseline and 6, 12, 18 and 24 months. The variables used were baseline data for the different markers and the percentage change from baseline for lumbar spine and femoral neck BMD. The baseline bone markers were categorised in low, normal, and high. High was defined as a value higher than the upper limit (mean +2SD). The percent change in BMD at 2 yr. was used to classify subjects as slow bone loss (<=1.4%), intermediate (between 1.4 and 2.7%) and fast bone loss patients (estimated annual bone loss >2.7%). A model of multiple regression was used to identify the clinical and biochemical parameters that allow to predict the fast loss of bone density.

Results:The mean age was 54.3 (±5.5) yr. Except with TRAP, there were no statistically significant relationships between the baseline values and subsequent bone loss. The initial bone turnover was balanced during all study period. Factors associated with higher annual bone loss in the spine were age (p=0.019; CI 95% -4.6 to -0.3), initial bone density (p<0.03 CI 95% -14.6 to -0.6) and TRAP (p=0.02; CI 95% -3 to -0.2). In the neck femoral, initial bone density (p=0.014; CI 95% -0.059 to 0.02) was the only factor associated with higher annual bone loss.

Conclusions:In this study, we have observed that baseline TRAP were significantly higher in those who lose bone mass faster to the 2 years. We have not observed any correlation between other bone markers and postmenopausal bone loss.

This study was supported by Novartis.

[Programme]

 
P-65

CLINICAL BONE DENSITOMETRIC EVALUATION OF THE MANDIBLE IN COMPLETE DENTURE WEARERS DEPENDENT ON SOME MORPHOMETRIC INDICES

D. Knezovic Zlataric*, A. Celebic

School of Dental Medicine, University of Zagreb, Croatia

The objective of this study was to determine whether the mandibular bone mineral density (BMD) is correlated with some mandibular morphometric indices on panoramic radiograph (PR). In a total of 72 dental PRs the following parameters were evaluated: MI = thickness of the mandibular cortex below the mental foramen, AI = thickness at the antegonion and GI = thickness at gonion and MCI = mandibular cortical index, based on the assessment of the 3 categories of cortical appearence due to resorptive changes. The study was conducted on 28 male patients (mean age 72.7; range 56 to 84 years) and 44 female patients (mean age 69.7; range 48 to 86 years). Using dental PRs and copper stepwedge, the mandibular BMD was investigated densitometrically. All the BMD values were expressed in equivalents of the actual stepwedge thickness. The results revealed significant positive correlation between AI, MI and GI and all the measured regions of interest (ROI) on the mandible, which comprised the density of cortical and trabecular bone together (p<0.05). The thickness of AI, MI and GI was not significantly correlated with the ROIs which comprised the density of cortical bone alone (p>0.05). MCI was significantly correlated with cortical bone density alone (p<0.05), while it was not significantly correlated with cortical and trabecular bone density together (p>0.05).

The use of morphometric indices and clinical bone densitometry on PRs may be helpful for general dental practitioners in the assessment of local quality of mandibular bone structure and osteopenia.

[Programme]

 
P-66

TRACKING SERUM 25 HYDROXY VITAMIN D (25-OHD) AND PARATHYROID HORMONE (PTH) IN HEALTHY ELDERLY WOMEN OVER A 1-YEAR PERIOD

J. Z. Ilich*, R. A. Brownbill, H. E. Mulrenan, L. Tamborini

School of Allied Health, University of Connecticut, Storrs, CT, USA

Low 25-OHD and elevated PTH, commonly thought to exist in elderly, may compromise their bone status. The objective of this study was to assess the relationship between the two, their possible effect on bone mass, and their changes after subjects have been supplemented with calcium (Ca) and vitamin D for 1 year.

Subjects included 117 healthy, postmenopausal women who were part of a larger study. Mean±SD for age, weight, and height was 68.8±7.1years, 68.2±11.0kg, 161.7±6.8cm, respectively. Bone mass of the whole body, forearm, spine, and hip was measured by DXA (Lunar). 25-OHD and PTH were analyzed by Nichols. Dietary intake was assessed by 3-day records and analyzed with Food Processor (ESHA).

Baseline values for 25-OHD and PTH were 52.8±12.8nmol/L and 61.9±16.3pmol/L, while those for dietary Ca and vitamin D were 871±371mg/day and 187±130 IU/day, respectively. Subjects were stratified into groups according to season and below and above 70 years. Participants in spring/summer groups were older, had higher Ca and vitamin D intakes (p<0.05), but there were no statistically significant differences in their 25-OHD or PTH compared to those in fall/winter groups. There was also no difference in 25-OHD or PTH levels across the two age groups. There was no relationship between 25-OHD and PTH and neither of them showed significant relationship with bone mass of measured skeletal sites. After baseline assessment, each subject was given 630mg/day Ca and 400 IU/day vitamin D (Citracal+D, Mission Pharmacal) and assessed 6 and 12 months later. Compliance with supplements was about 90% bringing total Ca and vitamin D intake to about 1400mg/day and 550 IU/day, respectively. Values for 25-OHD and PTH after 6 and 12 months were similar to their respective values at baseline (no statistical difference), there was no relationship between the two and no effect on bone mass.

We conclude that healthy elderly women might not necessarily be in danger of low 25-OHD and elevated PTH, as commonly thought. Although their intake of Ca and vitamin D was below recommendations at baseline, moderate supplementation did not make difference in serum values of 25-OHD and PTH after a year of follow-up.

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P-67

HISTOLOGIC VARIABILITY IN THE ILIAC CREST BIOPSY OF POSTMENOPAUSAL AND OSTEOPOROTIC WOMEN

P. Lozo¹*, D. Krpan², I. Brnic², A. Krvavica³, V. Kusec⁴

¹Health Centre Lozo, Zadar, Croatia

²General Hospital Sveti Duh, Zagreb, Croatia

³General Hospital Zadar, Zadar, Croatia

⁴Clinical Institute of Laboratory Diagnosis, Clinical Hospital Centre, Zagreb, Croatia

Postmenopausal osteoporosis is the commonest type of osteoporosis in clinical practice. At the cellular level osteoporosis is the consequence of imbalance or uncoupling of osteoblastic bone deposition and osteoclastic bone resorption. Histomorphometric studies have demonstrated considerable heterogeneity regarding the activity of bone cells and bone turnover in osteoporosis. It is well established that diagnosis for osteoporosis and fracture risk assessment are based on measurement of bone density. Association of bone histology characteristics and its impact on bone density remains to be elucidated and was addressed in this study. Forty-five postmenopausal women have undergone transiliac bone biopsy in the course of diagnostic procedures and the following static histomorphometric parameters were assessed by an optical grid: bone volume, osteoblast and osteoid surface, osteoid thickness and osteoclast surface. Bone mineral density (BMD) was measured by DEXA at the lumbar spine and hip. Published reference data for histomorphometric indices was used for comparison of the results. Data was analysed according to normal, osteopenic and osteoporotic BMD results and showed no difference for any of the histomorphometric parameters. A subgroup of patients with increased osteoclast and osteoblast/osteoid surface (14/45) was identified, among which those with reduced bone volume (4/45). BMD and T-scores for the lumbar spine and hip in these two subgroups were lower but not statistically significant in comparison to patients with normal histomorphometric parameters for bone volume, osteoclast, osteoblast and osteoid surfaces (8/45). These results support the existence on great histologic

variability of bone activity in the postmenopause and osteoporosis. Lack of association between single or several histomorphometric parameters, indicating rate of turnover, with BMD was probably a consequence of high variance and limited patient sample. In conclusion, evidence of increased bone cell activity with or without reduced bone volume might be encountered in postmenopausal women with normal and reduced bone mineral density.

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P-68

AGE RELATED CHANGES IN BONE MINERAL CONTENT, BONE MINERAL DENSITY AND ASH DENSITY OF THE VERTEBRAL BONE IN RELATION TO THE BONE VOLUME IN WOMEN

S. Zoricic¹*, O. Cvijanovic¹, I. Kristofic¹, D. Bobinac¹, Z. Crncevic-Orlic², I. Maric¹

¹Department of Anatomy, School of Medicine, University of Rijeka, Rijeka, Croatia

²Department for Endocrinology, Clinical Hospital Rijeka, Rijeka, Croatia

The aim of the present study was to determine the age-related changes in vertebral bone structure in women assessed by three different methods: dual energy X ray absorptiometry (DEXA), ash density analysis and bone histomorphometry. Furthermore, numerical ratios and correlations between measured bone parameters were calculated in order to establish true relations between them. The lumbar vertebral bodies without posterior element (L3) from normal female cases were collected during autopsy. The samples were divided into three age related groups of ages: 50-60, 60-70, and 70-80. The vertebral bodies without posterior elements, were carefully removed and cleaned from the surrounding tissue, washed in saline solution and frozen on -20 deg C until performing the measurement. Each specimen was placed in container filled with demineralized water and scanned with Hologic QDR 4500 C scanner in a vertical plane under constant conditions. The density calculations (BMC and BMD) were made with the scanning software in the default mode. Thereafter, 3 vertical bone cylinders were obtained from each specimen using bone trephine. Two cylinders were embedded undecalcified in MMA, cut on 5 microm thick slices, histomorphometrically stained with toluidin blue. Image analysis was performed using semiautomatic image analyzer (Sform, VAMS, Zagreb) and BV/TV was calculated. The third cylindrical bone specimen was ashed (580 deg C for 24 h) and weighed. Apparent ash density (AD) was calculated by dividing ash weight by the volume of the specimen. Calculating numerical relations between BMC, BMD, ash density and BV/TV showed constant ratios. These ratios did not significantly differ between different age groups. The results revealed that histomorphometrically calculated bone volume (BV/TV) was in accordance with the mineral content and density of the vertebral bone.

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P-69

AGE AND GENDER RELATED CHANGES IN BONE HISTOMORPHOMETRY IN FEMALES AND MALES

S. Zoricic*, I. Kristofic, O. Cvijanovic, D. Bobinac

Department of Anatomy, School of Medicine,University of Rijeka, Croatia

The aim of this study was: 1. to determine age related differences in vertebral bone structure assessed by histomorphometry in normal adult female and male population; 2. to evaluate gender related differences between the same parameters that reflect bone architecture quality. The material for this study comprised human lumbar vertebral bodies (L3) from normal female (N=20) and male (N=20) cadavers aged from 50 to 80 years. Vertical, 7 mm in diameter, cylinders were drilled in each vertebral specimen using bone trephine. Undecalcified bone samples were embedded in MMA, cut in 7 microm thick serial sections and stained with toluidine blue method. Histomorphometric analysis was performed using semiautomatic image analyzer (Issa, VAMS, Zagreb) and the following static bone parameters were calculated: trabecular bone volume (BV/ TV), bone surface density (BS/ TV), trabecular thickness (Tb.Th), number (Tb.N) and separation (Tb.S). Morphometric parameters were compared between different gender related groups using Student t test. The results of this study revealed severe alteration of the bone quality assessed by histomorphometrical parameters in both, female and male groups and in all age groups. Comparing to the normal values found in the literature, our findings showed 30 percent lower BV/TV in female and 25 percent lower BV/TV in male subjects. Comparing three correspondent age related groups between female and male, BV/TV, BS/TV, TbTh, TbN were significantly lower in females up to age 70. These differences were not present after that age and values of the bone histomorphometry became approximately equal in 70 to 80 years age group of both female and male subjects. Even though subjects investigated in this study were with no apparent bone and systemic disease, histomorphometrical study revealed severely altered bone structure, especially in female group.

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P-70

AMENORRHEA IN FEMALE ATHLETES IS A RISK FACTOR FOR OSTEOPOROSIS

T. Dusek*, M. Pecina, M. Loncar-Dusek, I. Bojanic

Department of Orthopaedic Surgery, School of Medicine, University of Zagreb, Croatia

The aim of this study was to estimate the influence of intensive training on menstrual cycles in female athletes. The questionnaire was used to determine the time of menarche, and the prevalence of primary and secondary amenorrhea and dysmenorrhea in 72 active female athletes from Zagreb (10 volleyball players, 18 basketball players, 10 ballet dancers, and 34 runners) aged between 15 and 21. The control group comprised of 96 girls of the same age not engaged in any sports activity. The prevalence of secondary amenorrhea was three times higher in athletes than in the control group (P=0.037). The prevalence of the primary amenorrhea was substantially higher in athletes than in the control group (6 of 72 vs. 0 of 96, p=0.014), whereas the prevalence of dysmenorrhea was twofold lower in athletes than in the control group (p<0.001). The highest prevalence of secondary amenorrhea was recorded in runners (14 of 31), particularly long-distance runners (11 of 17), whereas there was only one case of secondary amenorrhea among basketball players. Menarche was significantly delayed in athletes who started physical activities before the onset of menstruation (13.8±1.4 vs. 12.6±1.0 years, p<0.001). High intensity training before menarche postpones its onset. Type of training may be related to a significantly higher prevalence of secondary amenorrhea in runners than in basketball players. This work also presents a case of a female mid-distance runner with a well known trias of symptoms: anorexia, amenorrhea and osteoporosis which resulted in stress fracture occurrence on four localizations of the skeleton. Three stress fractures occurred during sports activities, whereas the fourth stress fracture occurred after sports activities stopped.

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P-71

DETERMINATION OF THE IN VIVO PRECISION OF SUNLIGHT OMNISENSE BONE SONOMETER IN ITALY

R. Mora*, L. Pedrotti, B. Bertani

Department of Orthopaedics and Traumatology, University of Pavia, Italy

Dual X-ray absorbiometry (DXA) is recognized as the 'gold-standard' for the diagnosis and treatment monitoring of osteoporosis. Quantitative ultrasound (QUS) methods are a potential alternative because they are inexpensive and do not expose to ionizing radiations.

Omnisense bone assessment (Sunlight Ultrasound Technologies, Rehovot, Israel), based on the measurement of the speed of an ultrasound wave propagating along the bone, is the first QUS device capable of measuring the SOS at many sites, such as proximal phalanx of the third digit of the hand, distal radius, fifth metatarsal and others.

Aim of this study was to determine the precision of the device, as measured by the Coefficient of Variation (CV) at the distal 1/3 Radius, proximal Phalanx III and Metatarsal V, and to compare the Omnisense CV to the CV obtained from DXA measurement at the hip joint.

15 females at the age of 45-60 (mean age: 54 years) were enrolled in the study. Each one was measured at the radius, third phalanx and fifth metatarsal with the Sunlight Omnisense, and at the hip joint (where the BMD of the neck, trochanter and Ward's was taken) with a DXA Hologic device (Hologic Inc., Waltham, Mass.).

The in vivo precision of the Omnisense, as measured by the CV, is extremely high (0.22 % at the radius, 0.36 % at the phalanx, 0.31 % at the metatarsal bone.

The in vivo precision of the DXA, as measured by the CV, was 1.75 % at the femoral neck, 1.05 % at the trochanter and 3.10 % at the Ward's.

Obtained results show that the Omnisense bone sonometer may represent a safe and available method for routinary assessment of skeletal health.

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P-72

INTESTINAL CALCIUM ABSORPTION AND BONE TURNOVER IN PRIMARY HYPERPARATHYROIDISM

V. Zikán*, J. J. Stepan

Department of Internal Medicine 3, Charles University, Faculty of Medicine, Prague, Czech Republic

Purpose: The purpose of this study was to assess the fractional intestinal calcium absorption (FCa) in patients with primary hyperparathyroidism (pHPT) and its relationship to calcium metabolism and bone remodeling.

Methods: The FCa was determined by using a ⁴⁵Ca, 3 h loading test. Biochemical markers of bone turnover: plasma type 1 collagen cross-linked C-telopeptide (betaCTx), plasma aminoterminal propeptide of type I procollagen (PINP), and plasma N-MID osteocalcin (OC), plasma intact parathormone (PTH), serum ionised calcium (iCa) and urinary calcium corrected for creatinine (UCa-Cr) were evaluated before and during 5 hours after the oral administration of calcium. Serum 1,25- dihydroxyvitamin D3 was evaluated at baseline. 15 patients with pHPT (13 postmenopausal women, aged 51-79 years and 2 men, aged 57 and 68 years) were included into the study.

Results: A significant positive correlation was found between FCa and serum 1,25- dihydroxyvitamin D3 (r²=0.76; p<0.0001) and between FCa and the change in serum concentration of iCa at 3 h after calcium load (r²=0.48; p<0.01). A significant negative correlation was found between the FCa and baseline plasma concentration of the markers of bone remodeling, betaCTx (r²=-0.46; p=0.01), OC (r²=- 0.40, P=0.01), PINP (r²=- 0.54; P<0.001), and iCa (r²=- 0.58; p<0.001), and PTH (r²=- 0.31; p<0.05). After calcium load, a significant correlation was found between the % change in PTH (at 1 h) and betaCTx (at 3 h) (r²=0.51, p<0.01), and between the % change in PTH (at 1 h) and UCa-Cr at 2 h (r²=0.53; p<0.01).

Conclusions: The data suggest that the low calcium absorption may contribute to bone loss in patients with pHPT.

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P-73

DIURNAL RHYTHM OF PLASMA 1,25-DIHYDROXYVITAMIN D AND VITAMIN D BINDING PROTEIN (DBP) IN POSTMENOPAUSAL WOMEN: RELATIONS TO PLASMA PTH AND CALCIUM- PHOSPHATE METABOLISM

L. Rejnmark^1,2*, A. L. Larsen³, P. Vestergaard¹, L. Heickendorff⁴, F. Andreasen², L. Mosekilde¹

¹Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital, Denmark

²Department of Clinical Pharmacology, Aarhus University, Denmark

³Department of Clinical Biochemistry, AKH, Aarhus University Hospital, Denmark

⁴Department of Clinical Biochemistry, Aarhus Amtssygehus, Aarhus University Hospital, Denmark

Objective: diurnal variations in plasma levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) have previously only been investigated in young individuals, and these studies have failed to demonstrate a diurnal rhythm. We studied whether plasma levels of 1,25(OH)2D and vitamin D binding protein (DBP) vary in a diurnal rhythm in postmenopausal women.

Methods: blood and urine were sampled with two- and 4-h intervals in order to assess diurnal variations in plasma levels of 1,25(OH)2D, DBP, and PTH, as well as in plasma levels and urinary excretion rates of calcium and phosphate. Additionally, the free 1,25(OH)2D index was calculated (the molar ratio of 1,25(OH)2D to DBP).

Results: plasma 1,25(OH)2D exhibited a diurnal rhythm (p<0.01) with a nadir in the morning (99±12pmol/l), followed by a rapid increase to a plateau at daytime (113±13pmol/l i.e., 14% above nadir level; p=0.005). A similar pattern of variation was found in plasma levels of DBP; peak levels 15% above nadir levels (p<0.01). The free 1,25(OH)2D index did not vary in a diurnal rhythm. PTH and plasma levels and urinary excretions of calcium and phosphate exhibited a diurnal pattern of variation.

The diurnal rhythm of DBP correlated to the rhythm of 1,25(OH)2D (r=0.47, p<0.01) and plasma albumin (r=0.76, p<0.01). Moreover, the rhythm of plasma calcium and PTH varied inversely (r=-0.36, p=0.02).

Conclusions: By the disclosure of a diurnal rhythm of total plasma 1,25(OH)2D, all major hormones and minerals related to calcium homeostasis now have been shown to exhibit diurnal variations. In clinical trials the diurnal variations of 1,25(OH)2D and DBP have to be considered i.e., blood sampling must be standardised according to time of day.

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P-74

REDUCED MINERALIZATION OF SV-HFO CELLS BY SERA FROM WOMEN WITH HIGH BONE MINERAL DENSITY

E. M. Colin*, M. van Driel, H. A. P. Pols, J. P. T. M. van Leeuwen

Erasmus University Medical Center, Rotterdam, The Netherlands

Aim: The risk of osteoporotic fractures is determined by both quantity and quality of bone. The elasticity of bone and thus its resistance to fracture is related to its degree of mineralisation. In the present study we analyzed whether there are differences in effects on osteoblast activity and mineralisation between serum from postmenopausal women with a very low and high bone mineral density (BMD).

Materials and methods: For this purpose sera of 21 women with a femoral neck BMD within the lowest quintile (<0.75 gram/cm²), and sera of 29 women with a femoral neck BMD within the highest quintile (>0.92 g/cm²) were tested. Serum and urine parameters for bone metabolism were measured. Human fetal osteoblast (SV- HFO) cells, that proceed through different stages of differentiation in culture, including extracellular matrix formation and mineralisation, were cultured in medium supplemented with the sera for 21 days. Mineralisation and alkaline phosphatase activity were measured at 21 days of differentiation.

Results: In vitro induction of calcium deposition in SV-HFO cells was significantly increased by sera of the low BMD group compared to sera of the high BMD group (0.18±0.04 nmol/microgram DNA) vs. 0.15±0.04 nmol/micrgram DNA, P=0.02). Alkaline phosphatase induction in SV-HFO cells by sera was similar in both groups. There were no differences in serum 1,25-dihydroxyvitamin D3 and parathyroid hormone levels between the two groups. Serum 17-beta-estradiol levels were significantly lower in women with a low BMD compared to women with a high BMD (17.0±4.6 pmol/l vs. 45.4±6.9 pmol/l, P<0.01), while the serum alkaline phosphatase activity and serum osteocalcin were increased in the low BMD compared with the high BMD group (55.0±2.5 U/ml vs. 48.6±1.7 U/ml, P<0.05 and 5.8±1.9 microgram/l vs. 4.7±1.8 microgram/l, P<0.05, respectively).

Conclusion: Serum from postmenopausal women with a high BMD and high estradiol level results in a reduced mineralisation as tested in our in vitro system. The current data suggest a new role for estradiol in bone homeostasis: i.e. control of the extent or set point of mineralisation, which potentially contributes to the quality of bone.

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P-75

INTERRELATIONS BETWEEN OSTEOPOROSIS, CARDIOVASCULAR DISEASE AND BREAST CANCER IN WOMEN: THE ROTTERDAM STUDY

M. van der Klift^1,2,3*, H. A. P. Pols^2,3, J. J. W. Coebergh³, J. C. M. Witteman³, A. Hofman³, C. E. D. H. de Laet^1,2

¹Institute for Medical Technology Assessment, Erasmus Medical Centre, Rotterdam, The Netherlands

²Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands

³Department of Epidemiology & Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands

Osteoporosis, cardiovascular disease and breast cancer are common diseases in elderly women, and estrogen exposure may be an important etiological factor in all these diseases. Bone mineral density (BMD) is considered a marker for long term estrogen exposure. We hypothesised that low BMD, reflecting low estrogen exposure throughout life would be associated with increased atherosclerosis and myocardial infarction (MI) risk, whereas a high BMD would be associated with increased breast cancer risk. As estrogens act more strongly on trabecular bone, results may differ for femoral neck (FN) and lumbar spine (LS) BMD.

We studied this in 3374 women aged 55 years or over from the Rotterdam Study, a prospective population-based cohort study with data on BMD available. At baseline, both LS and FN BMD was measured by DXA (Lunar DPX-L). Z-scores of BMD were calculated and divided into tertiles. Information on potential confounders was gathered. The presence of peripheral arterial disease (PAD), defined as an ankle-arm index at or below 0.9 at baseline was used as a measure of atherosclerosis. All MI cases were reported by general practitioners in the research area and coded and validated by trained research physicians. The Rotterdam Cancer Registry provided information on incident cancer. Logistic regression was used for PAD analyses, and Cox' proportional hazards models were used for all other analyses.

Follow-up time on average was 6.4 years. Overall, low FN BMD was associated with increased risk of PAD (OR 1.3 [1.0-1.7]), but also with a decreased risk of MI, (HR 0.5 [0.2-0.9]). In women with a high FN BMD, also a slight, non-significant risk reduction for MI was observed (HR 0.7 [0.4-1.3]). No clear association between FN BMD and breast cancer was observed. In contrast, high LS BMD was associated with increased MI and breast cancer risk, even though only the latter was statistically significant (HR 2.1 [1.1-3.7]).

The results of this study show that high LS BMD is strongly associated with increased breast cancer risk. No association between PAD and LS BMD was observed. The association between BMD, atherosclerosis and MI, however, is unlikely to be explained by estrogen exposure alone.

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P-76

DIETARY CALCIUM INTAKE AND PREVALENCE OF VERTEBRAL DEFORMITY IN SAMPLE OF ELDERLY URBAN CROATIAN POPULATION

S. Grazio

Department for Rheumatology, Physical Medicine and Rehabilitation University Hospital 'Sestre Milosrdnice' - Zagreb, Croatia

The aim of the study was to determine the role of calcium intake through nutritional consumption of milk and other milk products currently and in three time periods during life (until 25 years, 25-50 years and 50 years and over) and to relate the results to vertebral deformities in a sample of elderly population of Zagreb. Each of 425 recruited individuals (269 women and 156 men) completed interviewer administered questionnaire and had lateral thoracolumbar radiography performed according to the standard protocol. The morphometric measurements of vertebral height were used to determine the occurrence of vertebral deformity according to the method described by McCloskey et al. Adding numbers of days in which each subject in the last week eat milk products we obtained score ranging from 0-28. As the distribution of results was uneven we arbitrarily divided subjects to groups ( group I = score 0-10 and group II = score 11 and over). There was no difference between these two groups by age, related to sex, women had greater current consumption of milk products. There was an increased risk of finding vertebral deformity in women appertaining to group I (OR = 3,10, 95 percent CI = 1,20-7,97), but not for men (OR = 0,93, 95 percent CI = 0,37-2,35), or for both sexes (OR = 1,89, 95 percent CI = 0,99- 3,63). There was a statistically significant difference in frequency of drinking milk in the period of 25-50 years of life (women being again more frequent consumers), but not during other periods of life. There was no correlation in frequency of milk

consumption and prevalence of vertebral deformity in any of the periods of life, separately for men and women and taken together. To estimate milk consumption throughout the whole life we added the figures for all three periods of life, getting the score ranging from 3-12. Dividing the subjects into two groups (group I = score 3-7, group II = score 8-12) we found no increased risk of vertebral deformity in those who have been drinking less milk (OR = 1,43, 95 percent CI = 0,77-2,66). In conclusion we found that the relationship between milk consumption and vertebral deformity is inconsistent and therefore other confounding factors could have influenced the results.

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P-77

BONE FORMATION MARKERS IN OSTEOPENIC AND OSTEOPOROTIC POSTMENOPAUSAL WOMEN

I. Cs Toth, J. C. Dumon, S. DiRomana, N. Kheddoumi, H. Cheblal, J. J. Body*

Laboratories of Endocrinology, Bone Diseases and Clinical Chemistry, and Supportive Care Clinic, Inst. J. Bordet, Univ. Libre de Bruxelles, Brussels, Belgium

We have measured in 197 postmenopausal women (median age 59 years, range 40- 82) total Alk Phos, its bone isoenzyme (BAP, Hybritech) and intact osteocalcin (BGP, Biosource). Of these 197 patients, 95 were osteopenic and 102 osteoporotic. None of them took HRT nor was treated for osteoporosis. There was a significant correlation between BAP and BGP levels in osteopenic (rs=0.41; P=0.002) and in osteoporotic women (rs=0.34; P=0.01). Normal values were determined in 122 healthy premenopausal (PreMP). The means±SEM values are tabulated below. Values were significantly (P<0.0001) different in the three groups for all markers, BAP and BGP levels were higher in osteoporotic than in osteopenic women (P<0.01) but this is not the case for Alk Phos. The upper limit of normal (=97.5th percentile in PreMP women) was 104 mU/ml for Alk Phos, 14 microg/l for BAP, and 15 ng/ml for BGP. In osteopenic women, Alk Phos levels were elevated in 23% of the cases, BAP in 21% and BGP in 40% (P=0.007). In osteoporotic women, Alk Phos levels were elevated in 17%, BAP in 34% and BGP in 46% (P<0.001). The percentages of increased values were higher in osteoporotic versus osteopenic patients for BAP (P<0.05) but not for BGP levels. Along the same line, T scores were higher for BGP (2.3±0.3) than for BAP (1.7±0.2) and Alk Phos (1.1±0.2) (P<0.0003). In summary, we have shown in osteopenic and osteoporotic patients that BGP was more sensitive than BAP and Alk Phos, whether in terms of percentages of increased values or T scores as compared to PreMP women. However, BAP distinguished better than BGP osteopenic from osteoporotic women.

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P-78

SERUM ACTIVITY OF TYPE 5B ACP AND BIOCHEMICAL MARKERS OF TYPE I COLLAGEN DEGRADATION IN OSTEOPOROTIC MEN WITH KLINEFELTER'S SYNDROME TREATED WITH AN INTRAVENOUS IBANDRONATE

J. J. Stepan¹*, P. Burckhardt²

¹Dept. of Internal Medicine 3, Charles University Faculty of Medicine, Prague, Czech Republic

²Département de Médecine Interne, University, Lausanne, Switzerland

Effects of treatment and withdrawal of ibandronate was studied in 13 patients with Klinefelter's syndrome. The diagnosis of Klinefelter's syndrome was confirmed by cytogenetical analysis. The average age of the patients was 55.8 yr. (50-64 yr.), height 178.2±5.3 cm, and weight 86.1±14.1 kg. Median serum testosterone concentration (1.1; 0.6-3.2 ng/ml) was significantly (p<0.01) decreased compared to normal values. Mean BMD T-score at the lumbar spine, femoral neck and total body (DPX-L bone densitometer, Lunar, WI) was -2.60±1.08, -1.40±0.94, and -1.70±1.06. The patients were treated for 2 years with intravenous ibandronate (2 mg every three months) and followed again when untreated for 1 year. After 6 month of treatment, serum type 5b ACP (solid immunofixed enzyme activity assay, SBA, Finland) decreased by 44% and serum CTX (Osteometer, Denmark) by 44%; urinary free DPD, NTX and CTX decreased by 35%, 42%, and 65%, respectively (all p<0.05). Treatment for 2 years with iv ibandronate increased significantly BMD at the spine, hip, and total body (p<0.01); patients had gained 10.06±4.29%, at the lumbar spine, 6.71±5.46% at the femoral neck, and 5.00±2.35% at the total body (mean±SD). One year after withdrawal of the treatment, the rate of bone loss (2.06±3.17% at the lumbar spine; 4.31±3.83% at the femoral neck, and 0.12±2.40% at the total body) resumed above the pretreatment rate (1.34±0.77% at the lumbar spine, 0.90±0.32% at the femoral neck and 0.64±0.32% at the total body). One year after withdrawal of the treatment, activity of serum type 5b ACP returned to pretreatment levels while serum CTX doubled as compared with values on the second year of treatment. Conclusion: The results indicate that type 5b ACP in the serum reflects number of osteoclasts rather their activity. The enzyme can be used as a valuable adjunct to markers of degradation of type I collagen in assessment of mechanism of action of drugs and for monitoring treatments.

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P-79

EFFECT OF CALCIUM SUPPLEMENTATION IN SUCKLINGS ON BONE MINERAL DENSITY IN ADOLESCENT RATS

M. Saric*, V. M. Varnai, M. Piasek, M. Blanusa, D. Juresa, M. M. Saric, S. Cvijetic Avdagic, K. Kostial

Institute for Medical Research and Occupational Health, Zagreb, Croatia

Importance of adequate calcium intake on formation of bone mass has been proved for children and teenagers, but the effect of calcium supplementation during infancy is yet to be established. An increase in peak bone mass by calcium supplementation during skeletal formation may contribute to osteoporosis prevention.

We evaluated the effect of calcium supplementation in suckling rats on bone calcium content and essential element concentrations immediately after supplementation period and on bone mineral density (BMD) at the age of 2 months. Forty-eight female suckling rats (Wistar) were artificially fed on cow's milk or on cow's milk supplemented with 6% calcium (as Ca-hydrogen phosphate) to increase the daily calcium intake about 3 times above control values. Treatment lasted 7 hr a day for nine consecutive days, from day 6 through 14 after birth. At the end of supplementation period, 18 sucklings (9 non-supplemented and 9 calcium- supplemented) were killed and calcium concentration in the carcass (whole body after removal of the organs, total gastrointestinal tract, and skin) was analysed by atomic absorption spectrometry. Calcium supplementation was associated with an increase in carcass calcium concentration by about 17% compared to non-supplemented pups. Growth and concentrations of trace essential elements in carcass and organs were not affected. Other 30 suckling rats (15 non-supplemented and 15 calcium-supplemented) weaned on feed with marginal calcium (0.33%) and were fed on the same test diet during 7 weeks. At the end of this period, total body BMD was measured in 2-month- old rats by densitometry using dual energy X-ray absorptiometry (Lunar DPX, Madison, WI, USA) in ketamine and xylazine anesthesia. No difference was found between groups in relation to calcium supplementation during the suckling period.

These results confirm findings from our previous investigation in which calcium supplementation during the suckling period had no effect on BMD in 3-month-old female rats fed on either 1% or 0.45% calcium diet. It is concluded that calcium supplementation during the suckling period increases the calcium concentration in bones, but it has no influence on bone mineral density in adolescence, even under condition of marginal calcium intake.

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P-80

A MULTICENTER STUDY FOR THE EVALUATION OF PHALANGEAL QUANTITATIVE ULTRASOUND TECHNIQUE IN HUNGARY

V. Ferencz¹*, S. Meszaros¹, E. Toth¹, E. Csupor¹, F. Terlizzi³, E. V. McCloskey², C. Horvath¹

¹1st Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary

²WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK

³IGEA, Carpi, Italy

Introduction: The suitability of quantitative bone ultrasound has been addressed in many studies over the past some years. It is particularly important in multicenter trials establishing stability of instruments and determining differences that can occur among devices.

Methods: 17 DBM Sonic Bone Profiler devices (IGEA, Carpi, Italy) had been calibrated by same operator using a composite phantom developed by IGEA. The phantom was measured 12 times on each instrument and the precision error (CV%) was calculated for separate devices and for the whole group. Some more tests checking the zero position, the span and the amplitude were also done.

Results: The mean CV% and the range for the amplitude-dependent speed of sound (AD-SoS) was found as 0.2% (0.12-0.28) in the whole group with an inter-instrument CV% of 0.35%. Calibration of 14 devices was within the acceptable range (2580±25.8 m/s) for AD-SoS. The excluded 3 devices need recalibration followed by a re-evaluation of performance tests.

Conclusion: The results confirm the usefulness of the cross-calibration as a basic process in multicenter work using quantitative ultrasound of the bone. DBM Sonic Bone Profiler devices show a very low precision error. However, cross-calibration can reveal the need of service and recalibration if a number of devices are used. We suggest to repeat this process in regular time during multicenter trials.

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P-81

URGENT NEED FOR AN ACTION AGAINST OSTEOPOROSIS IN AFRICA

M. R. D. Zebaze¹*, L. M. Ebah², C. W. Djeumen², T. J. B. Echouffo³

¹Mfou District Hospital, Yaoundé, Cameroon

²University Teaching Hospital, Yaoundé, Cameroon

³Bafang District Hospital, Bafang, Cameroon

Osteoporosis is a well recognised public health problem in developed countries and efforts are currently made to reduce its economical and social impact. In Africa, there is a perpetuation of a certain myth of its scarcity or even absence. Because of this,no preventive or curative measures are currently taken. However, we reported in a previous study that osteoporosis is the third cause of admission for fractures in Cameroon and that fractures incidence are substantials and much higher than previously thought and may be increasing dramatically. It also appears following recent studies that lack of awareness of osteoporosis among African physicians might be contributing to the under-estimation of the disease. Thus osteoporosis is a growing public health problem in Africa. We therefore call for an urgent need to tackle the upcoming osteoporosis problem in this part of the world.

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P-82

COLLAGEN AND BONE CHARACTERISTICS IN ADULT PATIENTS WITH CONGENITAL HIP DYSPLASIA

C. M. Bonelli¹, D. Walter¹, A. Fahrleitner¹, J. C. Piswanger-Sölkner¹, H. Dobnig¹, W. Linhart², T. Reitinger², R. Windhager³, G. Leb¹, B. Obermayer-Pietsch¹*

¹Dept. of Internal Medicine, Karl-Franzens-University Graz, Austria

²Dept. of Pediatric Surgery, Karl-Franzens-University Graz, Austria

³Dept. of Orthopedic Surgery, Karl-Franzens-University Graz, Austria

BACKGROUND: Congenital hip dysplasia (CHD) is one of the most frequent congenital malformations of the skeleton. In Austria, every 10th women may be affected. Recently, we reported on significantly decreased BMD at the hip in adult patients with conservatively treated CHD (JBMR 15, 2000). In the present study, we investigated bone mineral density (BMD), parameters of connective tissue, bone and collagen metabolism and joint laxity in a large group of adult female CHD patients.

METHODS: Using medical records, 150 premenopausal women with a history of conservatively treated CHD were identified and invited to a clinical examination including connective tissue and joint laxity parameters, past medical history, DEXA measurements at the spine and both hips (Hologic 4000 plus) and bone ultrasound measurements at the radius, proximal phalanx and calcaneus (Sunlight, Lunar) and compared to 249 age matched controls. Biochemical characteristics included osteocalcin (OC), crosslaps (sCTX), 25(OH)vitamin D3, calcium, phosphate, alkaline phosphatase, aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal cross- linked telopeptide of type I collagen (ICTP). Patients with secondary causes of osteoporosis were excluded.

RESULTS: In CHD patients, BMD at the hip (neck, ward) was again significantly decreased as compared to controls (p=0.01, p=0.04, respectively) despite a normal lumbar BMD. OC, sCTX and PINP levels were significantly elevated in CHD patients (p=0.0001, p=0.03, and p=0.03 respectively). Furthermore, the incidence of hernias, joint laxity and peripheral bone fractures was significantly increased in CHD patients (p=0.0009, p=0.02, p=0.03, respectively) as compared to controls.

DISCUSSION: Decreased femoral BMD may increase the risk for hip fractures in adult women with conservatively treated CHD. However, disturbances of collagen and bone metabolism in these patients suggest a more general disorder of bone and connective tissue affecting a large part of the (female) population. Therefore, characterisation of CHD pathophysiology and a careful follow-up of CHD patients may contribute to further insights in causes and prevention of bone disease in these patients.

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P-83

DIFFERENTIAL DIAGNOSTICS OF INHERITED CONNECTIVE TISSUE DISEASES

V. Vyskocil^1,2*, J. Varvarovska², K. Koudela³, B. Kreuzberg⁴

¹Department of Bone Disease, Department of Medicine II, Charles University Hospital, Plzen, Czech Republic

²Department of Pediatric, Charles University Hospital, Plzen, Czech Republic

³Department of Orthopaedic Surgery, Charles University Hospital, Plzen, Czech Republic

⁴Department of Radiology, Charles University Hospital, Plzen, Czech Republic

The authors followed 350 patients with connective tissue diseases from 1996 to 2000. The reason for that choice is genetic relationship of collagen defect.

Complete clinical, radiological and biochemical examinations (including 50 items) were finished in 200 patients from initial number of 350 patients. The studied groups consisted of 45 patients with osteogenesis imperfecta (OI), 30 children with Ehlers Danlos syndrome (ED) and 45 patients with Marfan syndrome (MS) and 35 with familiar joint hyperelasticity. 21 cases were concluded as other diagnosis and in 24 cases no diagnosis was found due to different obstacles. Authors tried to apply the criteria combination for OI, MS and ED so that the validity of particular criteria could be evaluated and then used in diagnostic difficulties among the studied diseases.

The patients were examined physically first with stress to the single criteria in OI besides blue sclerae, number of fractures, time of the first fracture, classification according to Sillence, dentinogenesis imperfecta including some specific radiograph symptoms. In Marfan syndrome the authors followed not only MCP index but also the trunk deformity, echocardiography, ophthalmological examination and the index between arms span and body height, eventually the ratio between trunk and limbs.

In ED the authors followed joint hyperelasticity, especially of knee and elbow and vascular eventually organ complications such as pneumothorax and intestinal perforation.

Conclusions:

1. Patients with MF have significantly higher height, arms span and ratio between trunk and limbs.

2. Patients with ED have significantly lower incidence of scoliosis than patients with OI or MF.

3. Patients with OI have the lowest bone mineral density BMD, age of the first fracture and even level of PICP related to age.

4. Combination of densitometry, markers of bone metabolism and anthropometry can differentiate distinct groups of inherited connective tissue diseases.

5. Response to antiresorptive therapy can be used in differential diagnosis of those diseases.

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P-84

HIERARCHIAL INTEGRATION OF THE SKELETAL SYSTEM: A PLURALISTIC APPROACH TO A MULTI-FACTORIAL DISEASE - OSTEOPOROSIS

L. Klein

School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA

Hierarchial integration of the musculoskeletal system (Cells & Materials 7: 245, 247-57, 1997) has produced new insights into the sensing, communication, and signaling that occurs within and between systems, organs, tissues, cells and nuclei. Additional integration of the nervous and vascular systems permits complex sensing and communications of mechanical, metabolic, and nutritional stresses of bones and connective tissues within and among the various joints and bones of the body. The recent focus of research activities is on fundamental and applied aspects of bone mass, structure, metabolic turnover, and biological conservation in complex multi-systems. New insights for the significance of absolute bone mass (a "gold standard"), metabolic turnover, conservation and redistribution of mass are leading to absolute measurements of bone mass, hormonal mechanisms of metabolic turnover in bone from young mature and old species. Estrogen appears to be a biological integrator with its receptors interacting at both cellular and nuclear membranes from various cells.

New experimental designs and methods yield new quantitative approaches for analysis and unambiguous interpretation of complex biological systems that interact in situ. The skeletal system is very complex because it interacts with many other systems and organs such as muscle, nerve, vascular, renal, gastrointestinal, respiratory and brain. In addition, bones of the skeletal system are heterogeneous in structure and activity at all levels of organization, i.e. species, system, organs (bone), regions, tissues, and cells.

The presence of efficient conservation in situ of bone mineral mass (calcium and phosphorus) in whole animals (man including) requires specific experimental methods for observing and measuring quantitatively absolute bone mass and metabolic turnover. Current experimental methods usually observe and measure small parts of bone for concentraion and density of bone mass and turnover. This latter approach often leads to incomplete data and misinterpretation. Pluralistically all levels of data are important because all data are important.

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P-85

ABSOLUTE BONE WEIGHT OF WHOLE BONES: A "GOLD STANDARD" FOR BONE MASS

L. Klein*, C. L. Nash

School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA

A distinction needs to be made between absolute data and relative data in biology and medicine (Table 3, L. Klein, Cells & Materials 7: 245-57, 1997). Absolute bone mass is the "gold standard" because mass comes directly from physical weighing of each whole bone which represents a single intact anatomic unit. The weight of a dry, defatted bone is the absolute bone mass for a given bone and is the sum of mineral, matrix, and a small amout of cartilage.

In contrast, most radiological measurements are a relative index of bone mass such as bone mineral density which are presented as gm/cm², gm/cm³ or ash weight/unit volume. Physically, there is a distinct conceptual difference between absolute mass and relative mass. Biologically, changes in primary and secondary mineralization occur over time which complicate the accuracy of measuring bone mineral density.

The bones are from Hamann-Todd collection of the Cleveland Museum of Natural History and were obtained from human skeletons devoid of skeletal disease and/or generalized wasting. Eight appendicular bones (cranium, humerus, radius, ulna, clavicle, femur, tibia, fibula) and eight axial bones (scapula, pelvis, innominate, sacrum, ribs, cervical vertebra, thoracic vertebra, and lumbar vertebra) were studied at each decade from 10 to 93 years of age. Prior to accurate weighing, the bones were defatted, dried, and then compared as a function of age. The peak bone mass for females was at 20-29 years old and for males at 30-39 years old which are designated as the baseline (100%).

Our results demonstrated that the female bones from 20 to 90 years of age showed larger losses of mass by 90 years ranging from 23% in cervical vertebra to 49% in fibula. In comparison, the males showed much smaller losses of bone mass by 90 years ranging from 6% in cervical vertebra to 16% in humerus. Starting from the fourth decade, male bones showed small significant losses of bone (2-3%). In contrast, the female bones showed larger linear losses (11-12%) starting in the third decade. These data showed a surprising heterogeneity in the rates of bone loss for both male and female bones.

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P-86

ASSOCIATIONS BETWEEN QUANTITATIVE ULTRASOUND OF FINGER PHALANGES AND FAILURE LOADS OF SPINE AND FEMUR IN VITRO

R. Barkmann¹*, E-M. Lochmueller², F. Eckstein³, V. Kuhn³, C-C. Glueer¹

¹Medizinische Physik, Klinik für Diagnostische Radiologie, UK-Kiel, Germany

²Universitätsfrauenklinik, LMU München, Germany

³Musculoskeletal Research Group, Institute of Anatomy, LMU München, Germany

Although site matched bone density measurements of spine and femur are best suited to predict fracture risk on these sites, peripheral measurements offer some advantages in terms of costs, portability and radiation dose. We determined in an in vitro study correlations between Quantitative Ultrasound (QUS) measurements on finger phalanges and failure loads of spine and femur, in comparison with DXA on spine, femur and radius.

QUS measurements were performed on the third phalanx with excised soft tissue in medio-lateral and superio-inferior direction using a DBMSonic 1200 (Igea, Italy). Standard parameters are AD-SoS, UBPI and BTT. The performance of AD-SoS and UBPI depends on the value of a fixed trigger level, which is optimised for in vivo measurements but cannot be applied on measurements on formalin-fixed bones in vitro. Instead, we used a recently developed parameter (cAD-SoS) which strongly correlates (R=0.95) with the standard parameter AD-SoS, but does not depend on a fixed trigger level. nSOS is a new velocity parameter which strongly correlates with the cortical cross-sectional area of the phalanx. DXA measurements of LS 3, femur neck and distal radius were performed using a DPX-L (GE-Lunar, WI).

Significant correlations at p<0.01 could be found between all QUS and DXA parameters and all failure loads. Site matched DXA yielded the highest correlations (R=0.74 - 0.82). Lower correlations could be observed for DXA of the radius (R=0.53 to 0.62) and QUS of the phalanges (R=0.4 - 0.66). Best non site matched correlation was between nSOS and failure load of the femur (R=0.66, vertical loading).

QUS of finger phalanges is associated with failure loads of spine and femur with correlations somewhat lower than site matched DXA but similar to DXA of the radius. New QUS parameters might improve these correlations.

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P-87

EFFECTS OF THE BODY MASS INDEX AND AMENORRHOEA ON BONE MINERAL DENSITY

C. M. Francucci*, T. Mancini, A. Camilletti, L. Riccialdelli, B. Cola, F. Massi, M. Boscaro

Division of Endocrinology, Department of Internal Medicine, University of Ancona, Italy

The pathogenesis of osteoporosis is complex and many risk factors are involved. In order to select the patients at higher risk of osteoporosis, different questionnaires have been used. The questionnaire we have been using aims especially to look for conditions such as amenorrhoea, hyperthyroidism and hypercortisolism, which are well known risk factors for the osteoporosis.

In this study we have evaluated the effects of these risk factors and of the body mass (BMI) on bone mineral density (BMD) in 766 women who were referred to our centre to perform a Dual-Energy X-rays Absorptiometry (DPX Lunar V 3.61, Madison, Wisconsin).

These women presented a mean age ±SD of 46.2±2.5 (range 40-49 years), a mean BMI±SD of 25±4.4 and didn't present any other risk factors.

A positive correlation between BMI and BMD was observed (r=0.4 and P<0.001).

The patients were subsequently divided in four categories depending on risk factors (amenorrhoea, hypercortisolism, hyperthyroidism and controls). All groups did not differ for age and BMI.

We observed that amenorrhoic patients presented BMD significantly lower versus both hyperthyroid and controls (** p<0.001).

In conclusion our data show that underweight and amenorrhoic women have the lowest BMD. Amenorrhea is an important osteoporosis risk factor, independently of the weight.

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P-88

EFFECTS OF RISK FACTORS ON THE VERTEBRAL MINERAL DENSITY

T. Mancini, A. Camilletti, E. Biondi, P. Rutigliano, F. Massi, C. M. Francucci*, M. Boscaro

Division of Endocrinology, Department of Internal Medicine, University of Ancona, Italy

Many risk factors contribute to the pathogenesis of osteoporosis. Typical examples include lifestyle and constitutional factors, low body mass, low levels of physical activity, prolonged immobility, alcohol abuse, estradiol deficiency, long term corticosteroid use and hyperthyroidism. Many studies have shown that these factors predict low bone mass at any skeletal site.

Between 4.040 women (mean age±SD 55.2±10.1, BMI 25.8±5.1 and BMD 1.070±0.1g/cm²) arrived at our center, at the first time from 1996 to 2000, to effect a Dual-Energy X-ray Absorptiometry (DXA) for bone mineral density evaluation, we have selected 775 women with a middle age of 46.2±2.5 that are the whole group of patients with an age range of 40 to 49 years. Since these women had a significant reduction of spinal BMD at lumbar spine (L2-L4) vs 715 healthy women with the same range of age of DPX Lunar V 3.61 (mean BMD±SD 1.149±0.15g/cm² vs 1.170±0.12g/cm²; p=<0.001), we have excluded 283 women that had a history of amenorrhea (n. 217), hypercortisolism (n.30), hyperthyroidism (n.25), renal illnesses (n.9) and hyperparathyroidism (n.2). The others 492 women (without no other osteoporosis risk factors referred to us) had a bone mass like controls of DPX Lunar V 3.61 (mean BMD±SD 1.170±0.1g/cm² vs 1.170±0.12g/cm²; p=0.8). Even if the women with hypercortisolism had a bone mass reduced vs controls, only the patients with amenorrhea had a significantly lower BMD vs 492 healthy women and vs controls of DPX Lunar V 3.61 (mean BMD±SD 1.099±0.14g/cm² vs 1.170±0.1g/cm² vs 1.170±0.12; p=<0.001).

Our data show that amenorrhea is an osteoporosis risk factor more important than endogenous or iatrogenic hypercortisolism, that hyperthyroidism don't give rise to significant reduction of bone mass at vertebral level and that healthy women of middle Italy (Adriatic coast) and controls of DPX Lunar V 3.61 have the same BMD at lumbar spine.

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P-89

AXIAL AND LOCAL TIBIAL BONE MINERAL DENSITY IN MENOPAUSAL WOMEN WITH OSTEARTHRITIS

E. Jodar¹*, J. M. Padrino², G. Martinez¹, S. Azriel¹, F. Hawkins¹

¹Dept of Endocrinology, University Hospital 12 de Octubre, Madrid, Spain

²Dept of Rheumatology, University Hospital 12 de Octubre, Madrid, Spain

A negative association between osteoporosis (OP) and osteoarthritis (OA) has been described. OA has been related to an increased subcondral bone mineral density (BMD). Our aim was to assess axial (lumbar spine [LS] and fenoral neck [FN]) and local tibial (tibial spine [TS] and internal condylus [IC]) BMD in menopausal women with spinal or knee OA.

Patients & methods: 90 consecutive menopausal women, aged 50-70 years, were studied. 12 women did not show OA and were used to calculate local tibial z-scores (TS and IC). 78 patients showed mild to moderate spinal and/or knee OA. BMD was measured by DXA (Hologic QDR1000w). Bone turnover markers (BGP, total and bone ALP, NTx & Pyr) and calciotrophic hormones were also measured (PTHi, 25(OH)D, IGF-I and estradiol).

Results: Control and OA groups were comparable in age, weight, years since menopause, calciotrophic hormones and bone markers except for BGP, lower in OA patients (p=0.003). Local tibial BMD was increased in OA patients (z-score): IC: 0.711±1.789; TS: 0.722±0.946 (p<0.003 vs 0). Local tibial and axial BMD correlated closely, and local tibial BMD correlated with radiographic rating scale of OA (RxSc). 40 women (51.3%) showed densitometric OP. In the multivariate analysis, IC BMD was related to FN BMD, RxSc, estradiol and PTH (R: 0.872; adjusted R2: 0.693); TS BMD was, in turn, related to FN BMD and estradiol (R: 0.629; adjusted R2: 0.335).

Conclusions: Local tibial BMD is increased in menopausal women with mild-to- moderate spinal and/or knee OA and is related to radiographic rating scale. The prevalence of OP in these women is very high. Local tibial BMD and femoral neck BMD are closely related.

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P-90

PRECISION OF BONE MINERAL MEASUREMENT BY DUAL ENERGY X-RAY ABSORPTIOMETRY

M. R. Salamat

Department of Medical Physics and Medical Engineering, Isfahan University of Medical Sciences, Isfahan, Iran

There are several methodologies available for bone mineral measurement. Dual energy x-ray absorptiometry (DXA) has an overall advantage in terms such as precision and radiation exposure. It is a well-established method and has the potential of multi-site measurement. Although DXA is widely used to assess bone mineral of the spine and hip, little use of the technique has been made to investigate other sites of the body. Therefore, appropriate methods were developed to measure the hand, os calcis and tibia. Precisions of the methods were assessed. A Hologic QDR-1000W DXA system was used for the investigations.

Hand bone mineral measurement is of particular interest in rheumatoid arthritis patients (RA). A hand phantom which provided a convenient means of evaluating various protocols and assessing long term precision was developed and used for the investigations. The conventional protocols differ in factors such as scan speed, linearity, tissue depth dependence and precision. Therefore, a new protocol was evaluated for the precision.

A technique was developed for the assessment of os calcis. An os calcis phantom was constructed and used to assess precision and the effect of size of region of interest (ROI) on precision. In-vitro precise (CV=0.4%) and linear measurements were achieved independent of the size of ROI and soft tissue. Two different ways of subject positioning and two ROIs for the measurements were established, using a group of subjects. In-vivo precise measurements (CV<1.1%) were achieved for both ROIs.

A method was developed for the assessment of the various sections of the lower leg (tibia/fibula). Measurements were linear and soft tissue independent. Precise measurements (CV<1.4%) were achieved for the proximal and total lower leg. The rotation of the legs showed the least effect on BMD measurement of the proximal lower leg.

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P-91

ULTRASOUND DETERMINATION OF OSTEOPOROSIS PREVENTION

Z. C. Orlic¹*, K. D. Bozic²

¹Internal Clinic, University of Rijeka, Croatia

²Health Center Pula, Croatia

People who live in the sunshine part of Croatia, in Istria, were characterised as a low milk intake population forty years ago. Today there is no heavy industry, and the standard of living is much higher than in those days. Milk as the major calcium source was thought to be the main reason of low bone mass.

Clinicians can identify accurately, non-invasively and inexpensively, patients with low bone mass nowadays. So, we have done ultrasound examination of calcaneus to evaluate bone mass in l0% of the Istrian population.

Our investigation shows that the prevalence of osteoporosis is 27% in the whole population, 35% in women past menopause, but also 20% in men and l0% in premenopausal women. Osteopenia was detected 35% in the whole population and 37% in postmenopausal women, as well as 30% in men and in 30% premenopausal women. In 35% of whole population, and in 37% postmenopausal women, as well as in 30% of man and in 33% of premenopausal women.

Our findings of such low bone mass in people in Istria indicate urgent need for better evaluation of skeletal status in that population.

It will be interesting to correlate nutrition habits, genetic and physical factors in those people, which all can point out ethiological priorities in pathogenesis of primary osteoporosis.

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P-92

SECONDARY OSTEOPOROSIS IN PATIENT WITH ADULT CELIAC DISEASE

B. M. Sincic B.¹, Z. C. Orlic¹*, D. Krpan², D. J. Erzen¹

¹Internal Clinic, University of Rijeka

²Internal Clinic, Clinical Hospital 'Sveti Duh' Zagreb,Croatia

Bowel diseases are frequently associated with bone loss.

We have analyzed a fifty two year old woman who came to the clinic with the illness history of diarrhea, loss of weight and old fracture of fourth left metacarpal bone.

Routine laboratory test indicated malapsorption problems. Results of D-xylosa test, lipid absorption test, endomisial antibodies and jejunal biopsy confirmed the diagnosis of celiac disease.

After the specific diet treatment she slowly gained weight, but body mass index (BMI) did not rise more than 20 kg/m2.

After she was complaining of back pain, X-ray examination and bone densitometry were done.

Low bone mineral density (BMD) values indicated osteoporosis.

Biochemical markers of bone resorption confirmed an active resorption phase of bone remodeling. Parathyroid hormone (PTH) was twice the normal values. Bone biopsy and hystomorphometry established the diagnosis of hyperparathyroidism.

After three months of treatment with biosposphonates (alendronate), vitamin D and calcium supplementation, bone markers were elevated and the patient complained less of back pain.

The findings of the present case report suggest that patients with malapsorption syndrome are at high risk for bone loss. Further studies are needed to evaluate the efficacy of specific antiresorptive therapies and clinical utility of biochemical markers of bone turnover in predicting therapeutic response in these patients.

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P-93

EVALUATION OF BONE MASS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

B. M. Sincic, Z. C. Orlic*, D. Stimac, B. Radakovic, D. J. Erzen

Internal Clinic, University of Rijeka, Croatia

A low bone mineral density (BMD) has been reported in patients with inflammatory bowel diseases (IBD). The prevalence of osteoporosis seems to be higher in patients with Crohn's disease (CD) than in those with ulcerative colitis (UC), whereas the prevalence of osteopenia was found to be similar by most studies. Factors associated with bone loss in IBD are the inflammatory activity, corticosteroid use, duration of disease, male sex, low body-mass index, inactivity, hypogonadism, and in CD smoking and surgical resection.

The purpose of the present study was to determine the prevalence of osteopenia and osteoporosis in IBD patients, and to test the influence of clinical variables (age, sex, disease duration, corticosteroid use) on the bone mineral density (BMD).

Fifty eight patients with IBD entered the study. BMD was measured by dual- energy X-ray absorptiometry (DEXA). Overall prevalence of osteopenia and osteoporosis was 42% and 30%, respectively. We found no difference between CD and UC patients. There was also no significant difference regarding clinical variables between patients with normal and low BMD. When patients with CD were analyzed separately, we found statistically significant negative correlation (with correction for age, sex body mass index and corticosteroid use) between BMD and the duration of disease (r=0.58, p=0.002).

We conclude that the IBD patients have well defined osteopenia and osteoporosis, the degree of which is not different in CD and UC. Duration of the disease seems to be the only phenomenon related to the low bone mass.

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P-94

CONTRIBUTION TO THE PREVENTION OF OSTEOPOROSIS IN POSTMENOPAUSAL WOMAN IN REGION OF THE REPUBLIC OF CROATIA - CROATIAN LITTORAL

D. J. Erzen, Z. C. Orlic*

Internal Clinic, University of Rijeka, Croatia

The aim of the study was to evaluate the effects of hormonal replacement therapy, calcitonin and bisphosphonates on bone mass of postmenopausal women in region of the Republic of Croatia - Croatian Littoral. We have analysed 122 women of control group (the postmenopausal women who did not receive the therapy for osteoporosis) and 79 women who received therapy for osteoporosis during the period of 12 month (33 women hormonal replacement therapy, 32 women calcitonin and 14 women bisphosphonates).

In these women we measured bone mass density (BMD) of lumbal spine using densitometer MBC-lab 23 wich works on the principle of dual photon absorbtiometry utilizing gamma rays of the element gadolinium Gd 153. Laboratory measurements include routine tests and electrolite values in serum and urine and OH proline in urine specimens.

Hormonal replacement therapy prevents futher rapid loss of bone density that occurs in the first five years of menopause, during the period of 12 months and significantly increases bone mass of spine - about 2% Salmoncalcitonin 100 IU given intranasaly prevents bone loss in the spine in established osteoporosis and increases bone mass in a small percentage - about 1%. Cyclical etidronate therapy did not change BMD values. All of the patients have the calcium supplementation of 1000 mg daily and 600 UI vitamin D.

Hormonal replacement therapy and calcitonin have expected effect on increase of the bone mass. In the group treated with cyclic etidronate, we have poor results because it was a small group with small initial bone mass. For the better evaluation of these results in this group, it is necessary to have more patients and a longer period for the therapy.

To be more effective, all treatments should be started early, before serious bone loss has occurred.

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