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

Nephrol Dial Transplant (2003) 18: 2325–2331 DOI: 10.1093/ndt/gfg403 Original Article 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 1 Service 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 Abstract 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 bonespecific 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 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. 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 midradius 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 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 Nephrol Dial Transplant 18(11) ß ERA–EDTA 2003; all rights reserved 2326 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 [2,8–10]. 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 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 crosssectional 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 tuberculosi (...truncated)