Bone mineral density, biochemical markers and skeletal fractures in haemodialysis patients

Pablo Ureña1,3,5, Oana Bernard-Poenaru2, Agnès Ostertag3, Claude Baudoin3, Martine Cohen-Solal3, Tom Cantor4 and Marie Christine de Vernejoul3

1Service de Néphrologie-Dialyse, Clinique de l’Orangerie, Aubervilliers, France, 2Service Central de Biophysique, Laboratoire de Biologie Endocrinienne, Hôpital Lariboisière, Paris, France, 3INSERM Unité 349, Hôpital Lariboisière, Paris, France, 4Scantibodies Laboratory, Inc., Santee, CA, USA and 5Service de Physiologie et Explorations Fonctionnelles, Hôpital Bichat, Paris, France

Correspondence and offprint requests to: Prof. Marie-Christine de Vernejoul, INSERM Unité 349, Hôpital Lariboisière, 2, rue Ambroise Paré, F-75010 Paris, France. Email: christine.devernejoul{at}inserm.lrb.ap-hop-paris.fr



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. End-stage renal disease is often associated with altered bone metabolism.

Methods. In order to investigate the determinant factors of bone mineral density (BMD) and the risk factors of fractures, we studied 70 patients; 26 women (23 post-menopausal) and 44 men, (mean±SD) aged 60.5±14.3 years, treated by standard haemodialysis (HD) for 6.4±6.8 years. Main circulating bone biochemical markers were assessed and BMD was measured with a Lunar DPX densitometer at five sites. BMD results are expressed as a function of age and gender (Z-score).

Results. Mean Z-score was markedly decreased at the mid-radius (-2.75±1.23) whereas it was normal at the femoral neck (-0.42±1.13) and lumbar spine (0.02±2.13), and total body (-0.62±1.53). Time on HD was negatively correlated to the Z-score at the mid-radius and total body but not at the other sites. Serum intact parathyroid hormone (iPTH), whole PTH or cyclase activating PTH (CAP) and bone-specific alkaline phosphatase concentrations were negatively correlated with Z-scores at all sites. Twenty-one out of 70 patients had sustained a total of 27 fractures since the beginning of dialysis therapy (seven ribs, seven ankles, six vertebrae, three humerus, two wrists and two hips). They had a total body Z-score significantly lower than that of patients without fractures, -1.34±1.54 vs -0.37±1.46, respectively (P<0.031); however, their Z-scores at the other sites were not different. They were on HD for longer time, 10.4±9.5 vs 5.0±5.1, respectively (P<0.003), and the relative risk of skeletal fractures was 6.4 times greater after 10 years of HD. The seven patients with rib fractures had a decreased Z-score at most of the sites but not at the mid-radius. Rib fractures but no other fractures were associated with markedly decreased body weight, fat mass and serum leptin levels.

Conclusions. In conclusion, the Z-score at the mid-radius was decreased in HD patients and correlated with high serum PTH but not with fractures. Bone fractures were associated with the time passed on HD and with a low total body Z-score. Rib fractures were frequent and associated with a poor nutritional state.

Keywords: bone-specific alkaline phosphatase; leptin; parathyroid hormone; renal osteodystrophy; secondary hyperparathyroidism



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Chronic renal failure is often associated with alterations in calcium and phosphate metabolism. Once haemodialysis (HD) has begun, bone histological signs of secondary hyperparathyroidism can be found in >50% of the patients. However, clinical evidence of low bone turnover or adynamic bone disease can be seen in as many as one-third of these patients. Other less frequent bone diseases such as osteomalacia, aluminum-related bone disease, fluorosis, strontium overload or mixed bone diseases can be observed in the rest of the patients [1]. In addition, because of their advanced age, post-menopausal status in women, sedentary lifestyle, nutritional state, history of prior renal transplantation and treatment including steroids, these patients may also be expected to be at high risk for developing osteoporosis [2].

These different manifestations of the renal osteodystrophy can roughly be suspected on the basis of plasma intact parathyroid hormone (iPTH) levels [3] and the serum concentration of several biochemical markers of bone metabolism such as bone-specific alkaline phosphatase (bAP) and collagen breakdown products [4]. However, the only way to precisely diagnose them is by histological analysis of a tetracyclin double-labelled bone biopsy [5]. Moreover, neither the use of biochemical markers, nor the use of bone biopsy can predict the rate of bone loss and the risk of skeletal fracture in these patients.

During the last decade, bone mineral density (BMD) has been demonstrated to be effective for the surveillance of bone loss and the prediction of osteoporotic fractures in menopausal women [6,7]. However, its use in the evaluation of renal osteodystrophy has been a matter of debate and this in spite of the use of reliable techniques such as dual-energy X-ray absorptiometry (DEXA) or quantitative computerized tomodensitometry (QCT). Indeed, it has been impossible to separate the different types of renal-related bone diseases by these methods. Nonetheless, independent of the type of bone turnover, most of the dialysis patients show some degree of osteopenia and increased risk of fragility fractures [2,810]. The incidence of spontaneous skeletal fracture has been shown to be three to four times greater in dialysis patients than in the normal population [9].

The aim of the present cross-sectional study was to investigate the determinant factors of BMD, the incidence of skeletal fractures, and to see whether BMD and bone biochemical markers could predict the risks of these fractures in 70 adult Caucasian HD patients.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Patients
Seventy adult uraemic patients, all Caucasian, 26 females and 44 males (23 out of the 26 women were post-menopausal), on maintenance HD were included into the present cross-sectional study after their informed consent. All the patients were treated in the dialysis centre of the Clinique de l’Orangerie. Their mean (±SD) age was 60.5±14.3 years (range 21–87 years). Mean duration of HD treatment was 6.4±6.8 years. All the patients were treated by conventional HD 4–5 h, three times a week, using hollow fibre dialysers, either hemophane (GFS-20, Gambro) or cellulosic (TCA 170, Baxter), against a dialysis bath containing 32–36 mmol/l of bicarbonate, 0.85 mmol/l of magnesium, 1.50 (nine patients) to 1.75 mmol/l of calcium, and 2–3 mmol/l of potassium. The mean Kt/V for the group of patients was 1.47±0.27. Their residual creatinine clearance was <3 ml/min and all patients were oligo-anuric (<= 200 ml/24 h). Underlying nephropathy types were: six nephrosclerosis, eight interstitial nephropathy, nine polycystic kidney disease, 16 chronic glomerulonephritis, six congenital nephropathy, 10 diabetic nephropathy, one tuberculosis and 14 of unknown etiology. At the moment of the evaluation none of the patients, in particular the post-menopausal women, was receiving or had received within the 12 months previous to the study, oestrogen, calcitonin, bisphosphonate or PTH. Only two patients were receiving <5 mg/day of corticoids for ß2-microglobulin amyloid arthropathy, 25 patients received vitamin D derivatives either orally or intravenously, 55 patients were receiving between 0.5 and 3 g/day of calcium carbonate. Seven patients have had a previous kidney transplantation. There was no clinical or biological evidence for other bone disease such as osteomalcia, aluminum-related bone disease, and Paget’s disease.

Skeletal fractures
Skeletal fractures experienced by the patients after the onset of HD were recorded by patient interview and medical record retrieval, namely, standard radiographs, computerized tomography and Tc99-bone scintigraphy. Two or more rib fractures occurring at the same time were considered as a single event. In order to detect spontaneous and asymptomatic vertebral fractures, a standard set of antero-posterior and lateral radiographs of the dorsal and lumbar spine were obtained. Vertebral fracture was assessed according to radiological criteria described previously by McCloskey et al. [11]. These included ratios of antero-posterior, central-posterior and posterior-predicted posterior vertebral heights from T4 to L5.

Biochemistry
Pre-dialysis blood sampling was performed after a 12-h fast. Plasma calcium was determined using atomic absorption spectrometry, plasma phosphorus using a Technicon Auto Analyzer. Plasma iPTH was measured using a commercial radioimmunometric assay for intact human PTH 1-84 (Allegro Intact PTH, Nichols Institute, San Juan Capistrano, CA). This iPTH assay detects both 1-84 PTH and probably the described PTH inhibitor 7-84 PTH fragment [12]. The range of normal values was between 10 and 70 pg/ml. Plasma whole PTH (wPTH or CAP) was measured using a commercial radioimmunometric assay for whole human PTH 1-84 (Scantibodies Laboratories, CA) without any cross-reactivity with 7-84 PTH [13]. Normal values range from 5 to 50 pg/ml. Cyclase inactive PTH (CIP) was obtained by subtracting wPTH from iPTH and reflects the inhibitory action of PTH [3,12].

Plasma total alkaline phosphatase, albumin, ß2-microglobulin and pre-albumin were measured by a routine clinical chemistry automated method. Plasma bAP was measured using a radioimmunometric assay (Tandem-R, Ostase) provided by Hybritech Europe S.A., Belgium. The mean ± SD value obtained in normal adult individuals was 11.8±4.3 ng/ml (normal range 4.0–25.0 ng/ml). Plasma vitamin D and 1,25(OH)2D3 were measured by radiocompetition assays as described previously [14,15]. Normal values for plasma vitamin D were 10–40 ng/ml and for 1,25(OH)2D3, 20–60 pg/ml. Serum cross-laps levels were measured using an ELISA from Osteometer, Biotech, Denmark. Normal values were 1.74±0.74 nmol/l in pre-menopausal women and 3.01±1.55 nmol/l in post-menopausal women. Serum leptin levels were measured using a radioimmunoassay, Linco kit, San Charles, MO. Normal values, in normal adult subjects with a body mass index between 18 and 25, were for women 3.7–11.1 ng/ml and for men 2.0–5.6 ng/ml.

BMD
BMD was measured with DEXA (Lunar DPX densitometer) from Lunar Corporation, Madison, WI. All the BMD measurements were performed by the same experienced operator. The densitometer was calibrated everyday with a standard phantom specimen. The following sites were examined: the total body; LS, vertebrae L2–L4; the FN; MRa and trochanter. Scans were performed at the two forearms but only the results at the non-dominant forearm were considered with the exception in the case of arterio-vein fistula influence (only three cases). BMD results were obtained in absolute values (g/cm2), in T-score and in Z-score. Z-score is the number of standard deviations from the mean of a healthy age- and gender-matched normal population, which allows the comparison of BMD between patients of different age and gender. T-score is the number of standard deviations from the mean of a healthy young adult population (20–40 years old); it is used for the definition of osteopenia (between -1.0 and -2.5 T-score) and osteoporosis (less than -2.5 T-score) [16]. The reference values were obtained from a French normal population aged between 20 and 89 years issued from several centres and provided by Lunar France.

Statistical analysis
All results are given as the means ± standard deviations (SD). Statistical analysis was performed using Wilcoxon sign rank test. The correlations were tested using Pearson’s product moment (two-sided). We analysed the fracture rate after the onset of HD using Cox model adjusted on weight, total body Z-score and duration of HD. The excess of risk along the time after HD was estimated by the Risk ratio. Results were considered to be significant at the 5% critical level (P < 0.05). Significance levels are indicated in table and figure legends. All statistical calculations were carried out with StatView 4.5 (Abacus Concepts, Berkely, CA) software and SPLUS 4.5 (version 2000, MathSoft, Inc., Seattle, WA) software.



   Results
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Demographic and biochemical data
Table 1 depicts the demographic and biochemical data for the 70 HD patients. As expected with the decline in the renal function, the mean plasma concentration of iPTH, wPTH, CIP, ß2-microglobulin, cross-laps and leptin were greater than the highest value of the normal ranges. The 10, 25, 50, 75 and 90 percentiles for the dialysis duration were 1.0, 1.8, 3.7, 8.6 and 15.3 years, respectively. For the serum iPTH the values were 29, 65, 171, 469 and 776 pg/ml, respectively, and for the serum bAP the values were 4.2, 7.4, 11.9, 18.6 and 15.3 ng/ml, respectively.


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Table 1. Demographic and circulating biochemical parameters in the 70 patients

 
Bone densitometric data
The results show that when the group of HD patients was compared with a healthy age- and gender-matched population, the BMD expressed as Z-score was significantly decreased only at the mid-radius (-2.75±1.23) whereas it was comparable and not statistically significant from zero at the femoral neck (-0.42±1.13), lumbar spine (0.02±2.13), total body (-0.62±1.53) and trochanter (-0.25±1.46) (Figure 1). The mean Z-scores did not differ at any site according to the gender, the calcium concentration in the dialysis bath, the history of previous renal transplantation or parathyroidectomy and the treatment or not by vitamin D.



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Fig. 1. Mean ± SD BMD values, expressed as Z-score, the number of standard deviation from the mean of a healthy age- and gender-matched population, at each skeletal site for the 70 HD patients.

 
The prevalence of osteoporosis (T-score lower than -2.50) was 17, 47, 80 and 29% at the lumbar spine, femoral neck, mid-radius and total body, respectively. Normal T-scores were found in 23% of the patients at the lumbar spine, 10% at the femoral neck, 1% at the mid-radius and 29% at the total body. At this last site, nine patients showed a T-score >2.00. These patients did not have history of oxalosis, fluorosis, osteopetrosis or other sclerosing bone disease. It should be stressed that only one young and recently dialysed patient had a normal BMD at the mid-radius.

Total body weight and body mass index (BMI) were strong determinants of the Z-score at all the measured sites. There was also a direct correlation between fat mass and all the BMD sites. The lean mass did not correlate with the Z-score at the total body and lumbar spine (Table 2). The time passed on HD was negatively correlated to the Z-score at the mid-radius and total body but not at the other sites (Table 2).


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Table 2. Correlations between Z-scores and anthropometric and circulating biochemical parameters

 
Serum iPTH and bAP concentrations were negatively correlated to Z-scores at all sites. Whole PTH was also negatively correlated to Z-score at most of the sites with the exception of total body. However, CIP concentration, which is thought to reflect the level of PTH inhibitor, only negatively correlated with the Z-score at the lumbar spine. Eleven patients out of the 70 patients, considered as having a high bone remodelling (iPTH >250 pg/ml and bAP >20 ng/ml) did not show lower Z-scores at any site except the mid-radius. They did not show an increased incidence of bone fracture compared with patients without high bone remodelling. Serum cross-laps concentration, which is a marker of bone resorption rate, was negatively correlated with the Z-score at the mid-radius, whereas, it did not correlate with Z-score at other sites. Plasma levels of 25OHD3 and 1,25-OH2D3 did not correlate to Z-scores at any site.

As expected, serum leptin levels were positively correlated with total body weight (r = 0.32, P < 0.01) and especially with fat mass (r = 0.75, P < 0.0001) and BMI (r = 0.51, P < 0.0001). Serum leptin also directly correlated with the Z-score of total body (Table 2) and with the Z-score at lumbar spine but not at the femoral neck and the mid-radius.

Fractures
Twenty-one out of 70 patients had sustained a total of 27 fractures after the initiation of HD therapy (seven ribs, seven ankles, six vertebrae, three humerus, two wrists and two hips), most of these fractures were spontaneous or after small trauma. More than one fracture occurred in four patients. Patients with bone fractures were on HD for longer time than patients without, 10.4±9.5 vs 5.0±5.1, respectively (P < 0.003) (Table 3). The age, body weight and plasma concentrations of iPTH, wPTH, bAP, cross-laps and leptin were comparable in the two groups (Table 3). They had a total body Z-score significantly lower than that of patients without fractures, -1.34±1.54 vs -0.37±1.46, respectively (P < 0.02); however, their Z-scores at the other sites were not different. When analysing all the potential risk factors for skeletal fractures in the Cox model, only one variable, the time spent on HD, was a significant predictor. Moreover, the relative risk of skeletal fractures was not increased during the first 3 years of HD therapy, but progressively increased subsequently. The exact timing of the fracture could not be determined for the six patients with vertebral fractures and also for two additional patients with peripheral fractures. Therefore, we excluded these eight patients from the analysis and studied 13 fractured patients and 49 patients without fracture. Among the 27 patients dialysed for <3 years there was no fracture case whereas in patients dialysed for >3 years there was 13 patients who had sustained a fracture and 30 who were not fractured. The ratio was not significantly different and there was no significant increased risk of fracture after 3 years on dialysis. Among the 36 patients dialysed for <5 years three patients sustained a fracture and 10 among the 26 patients dialysed for >5 years. The ratio was different and the increase in risk fracture was 4.7. Among the 50 patients dialysed for <10 years five had a fracture whereas among the 12 dialysed for >10 years there was eight patients with a fracture; therefore, the increase in risk was 6.4 after 10 years of dialysis. In a separate analysis, we did not find a difference between women and men and the risks of bone fractures. Of note, in the group of patients without skeletal fractures, only 25% of them had osteoporosis, as defined by the WHO, with a total body T-score lower than -2.5 SD whereas in the group of patients with bone fractures this percentage reached 57%. Thus, as in the normal population, osteoporosis increase the risk of skeletal fractures in HD patients.


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Table 3. Comparison of demographic, circulating biochemical and densitometric parameters in patients with and without skeletal fractures

 
The five patients with vertebral fractures had a statistically significant lower Z-score at the total body (-2.14±0.85 vs -0.36±0.16) and femoral neck (-1.34±0.25 vs -0.16±0.13), respectively, but not at the mid-radius. These patients had also spent more time on HD than the non-fractured patients, 15.2±9.5 vs 5.4±5.7 years, respectively (P<0.001).

The seven patients with rib fractures had a significantly lower Z-score at the total body, femoral neck and lumbar spine when compared with the group of patients without fracture but they did not differ at the mid-radius Z-score (Table 4). Rib fractures but no other fractures were associated with markedly decreased total body weight, BMI, fat mass and serum leptin levels (Table 4). They had also spent more time in HD (Table 4). Plasma vitamin D3 levels in these seven patients could be considered as low but they were comparable with those of patients without fractures: 12.7±5.8 vs 10.3±6.7 ng/ml, respectively.


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Table 4. Comparison of demographic, circulating biochemical, and densitometric parameters in patients with rib fractures and patients without fractures

 
Three out of the seven patients with a previous history of renal transplantation presented one or two skeletal fractures. The low number of these patients did not allow us to make any comparison with not transplanted patients concerning the frequency and the prevalence of skeletal fractures.



   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
The present study demonstrated that BMD, as assessed by Z-score, was significantly decreased only at the mid-radius and not at four other skeletal sites in 70 HD patients. The mid-radius Z-score was inversely correlated with serum iPTH and wPTH concentrations; however, the decreased mid-radius Z-score was not predictive of bone fractures. Bone fractures were associated with the time spent on HD and with decreased total body Z-score. Rib fractures were frequent and occurred in patients with anthropometric and biochemical signs of poor nutritional state.

The effect of the treatment for end-stage renal disease on bone density and on the incidence and risk of skeletal fractures has rarely been investigated. To date, most of the work has been focused on pre-dialysis, HD and kidney transplanted patients and scarce or no information is available for patients on peritoneal dialysis [17], haemofiltration, haemodiafiltration and nocturnal or daily HD. In pre-dialysis patients, the prevalence of osteoporosis has been reported as 19, 26 and 33% at the lumbar spine, femoral neck and mid-radius, respectively [18,19]. However, it is unknown whether the incidence of bone fracture is increased in these patients.

In dialysis patients, the prevalence of osteoporosis is quite variable and depends on several factors including the type of device used for the bone measurement (ultrasound, DEXA or QCT), the skeletal site measured, and the age, gender and ethnic group. Nonetheless, regardless of the methods, most of the studies are in concordance with a reduced BMD in HD patients, which appears to be more pronounced than in peritoneal dialysis patients [17]. Indeed, the prevalence of osteoporosis in HD patients has been estimated to be 50% at the mid-radius [10], 16–19% at the femoral neck [2], 13–29% at the lumbar spine [2,9,10] and ~50% at the total body [9]. Our findings confirm and extend these results. However, it should be stressed that the mean Z-score was not significantly different between HD and normal subjects at all sites, with the exception of mid-radius. In addition, when compared with what is reported in normal subjects of the same age, we found a dramatically high prevalence of osteoporosis at the mid radius (80%) and at the femoral neck (47%) in our patients.

This is in accord with the statement that bone loss in renal osteodystrophy is site specific and shows a marked difference in the pattern of bone loss, some patients have a gradual or no bone loss at all, whereas others show rapid bone losses specially associated with high levels of PTH and alkaline phosphatases [20]. The preferential loss of BMD at the mid-radius is also in accord with the statement that in secondary as in primary hyperparathyroidism there is relatively greater loss of cortical rather than cancellous bone throughout the skeleton, in contrast to post-menopausal osteoporosis where the loss is mainly due to cancellous bone from the axial skeleton [8,21]. The fact that serum concentrations of iPTH, wPTH, bAP and cross-laps inversely correlated with the Z-score at the mid-radius, and that patients considered as having high bone remodelling (iPTH >250 pg/ml and bAP >20 ng/ml) did not show lower Z-scores at any site excepted the mid-radius, suggests that secondary hyperparathyroidism is the main factor responsible for the cortical bone loss [21]. Furthermore, serum iPTH and wPTH also inversely correlated with Z-score at the other sites. Of note, the time spent on HD was also a determinant factor of BMD at the mid-radius, which may imply that other factors, besides a high serum bioactive PTH, might be involved in the cortical bone loss including age, heparin, anaemia and many nutritional and lifestyle abnormalities. Regarding the different PTH measurements performed in the present study, very little or no additional information was obtained from the wPTH, CAP and CIP values. However, the use of these parameters as biochemical bone markers in dialysis patients requires further exploration. Similarly, no correlation was observed between either vitamin D or calcitriol and biochemical parameters.

The clinical relevance of the decreased BMD at the mid-radius still remains a matter of debate. In the present study, it did not predict patients with bone fractures. Likewise, the mean Z-score at lumbar spine and femoral neck did not distinguish fractured from not fractured patients. The only bone density parameter predicting skeletal fractures was the total body BMD, both the T-score and Z-score, which was significantly reduced. When analysing all the potential risk factors for skeletal fractures in the logistic regression model, only one variable, the time spent on HD, was a significant predictor. The relative risk of skeletal fractures increased 6.4 times after 10 years of dialysis. The age, body weight and serum concentrations of iPTH, wPTH, bAP, cross-laps and leptin were comparable between patients with and without fractures. Moreover, the fact that these biochemical parameters were of limited predictive value of bone fracture implies that further studies, with bone histology, are needed to know whether the type of renal osteodystrophy determines the risk of bone fracture.

Skeletal fractures were frequent, variable and different from those of osteoporotic patients [22]. Indeed, only five patients had vertebral fractures and two patients had hip fractures. The other fractures were at the sites unusually seen in osteoporotic patients such as rib, ankle and humerus. The prevalence of vertebral fracture was 7%, which is lower than the 20% reported previously in HD patients by Atsumi et al. [9]. A decreased Z-score at the total body and femoral neck, but not at the mid-radius, could distinguish patients with vertebral fractures from those without. The percentage of patients with WHO defined osteoporosis, total body T-score lower than -2.5 SD, was twice greater in the group of patients exhibiting skeletal fractures (57%) than in those without (25%). Thus, as in the normal population, osteoporosis increases the risk of skeletal fractures in HD patients. The incidence of hip fracture has been demonstrated to be 3–4-fold greater in dialysis patients than in the normal population [8]. In our series there was only a small number of patients with hip fracture (2.8%), which is probably due to their relative younger age.

Seven patients (10%) had sustained one or several rib fractures, either spontaneously or after a mild trauma. Such a high frequency of rib fractures has been suggested previously; however, precise data from controlled prospective studies are still lacking [10]. Patients with rib fractures had a BMD at the total body, femoral neck and lumbar spine significantly lower than that of patients without fractures. However, the two groups of patients did not differ at the mid-radius BMD. Rib fractures also occurred in patients with anthropometric and biochemical signs of poor nutritional state, as evidenced by a markedly decreased total body weight, BMI, fat mass and serum leptin levels. To the best of our knowledge, this is the first observation demonstrating that serum leptin levels are decreased in HD patients with skeletal fractures, and that leptin levels are directly correlated with the total body BMD, total body weight, BMI and fat mass in these patients [23,24]. This suggests that, besides its role in the regulation of fat mass, body weight and gonadal function [23], leptin could also be a modulator of bone mineral mass; however, this hypothesis requires further evaluation in HD patients.

In conclusion, the Z-score at the mid-radius was decreased in HD patients and correlated with high serum levels of bioactive PTH but not with fractures. Bone fractures were associated with the time passed on HD and with a low total body Z-score. Rib fractures were frequent and associated with poor nutritional state. From a practical point of view, we think that BMD at the total body should be currently measured because it is a good indicator of the increased risk of bone fracture in HD patients treated for >3 years.



   Acknowledgments
 
We gratefully acknowledge the contribution of the nursing staff Ms A. Guignan and J. Beurier, for their technical support.

Conflict of interest statement. None declared.



   References
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

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Received for publication: 20. 2.03
Accepted in revised form: 10. 6.03