Chester Clinic

 

Osteo-1202 353.357

Osteoporos Int (2002) 13:353–357ß 2002 International Osteoporosis Foundation and National Osteoporosis Foundation Skeletal Status in Children, Adolescents and Young Adults with End-Stage Renal Failure Treated with Hemo- or Peritoneal Dialysis W. Pluskiewicz1, P. Adamczyk2, B. Drozdzowska3, K. Szprynger2, M. Szczepanska2, Z. Halaba4 andD. Karasek11Department and Clinic of Internal Diseases, Diabetology and Nephrology – Metabolic Bone Diseases Unit, 2Dialysis Division,Department of Pediatrics, Clinic of Nephrology, Endocrinology and Metabolic Disorders of Childhood, and 3Department andChair of Pathomorphology, Silesian School of Medicine in Katowice, Poland; and 4Outpatient Medical Care, Zabrze, Poland Abstract. The skeletal status in 30 children, adolescents strongly affected by ESRF. Both QUS and BMD and young adults (18 females, 12 males) with end-stage measurements show an ability to express skeletal renal failure (ESRF) aged 9-23 years (mean 15.8 + 3.6 changes in a similar manner, though the QUS parameter years) was evaluated using measurements of bone seems to be more sensitive at revealing changes due to mineral density (BMD, g/cm2) at the spine and total renal failure.
body (TB) (Lunar DPX-L, USA), quantitative ultrasound(QUS) of the hand phalanges (DBM Sonic 1200, IGEA, Keywords: Adolescents; Bone mineral density; Chil- Italy) and laboratory investigations (parathyroid hor- dren; End-stage renal failure; Quantitative ultrasound; mone, serum total and ionized calcium, serum phos- phate). Eleven subjects were treated with hemodialysisand 19 with peritoneal dialysis. The mean value of theamplitude-dependent speed of sound (Ad-SoS, m/s)measured by QUS was significantly decreased incomparison with the value obtained in a group of 686 age-matched controls (1942
74 m/s vs 2050
77 m/s,p<0.0001). BMD measurements were also decreased in Renal osteodystrophy is one of the most important comparison with mean values for the healthy population complications of chronic renal failure, and bone loss is (Z-scores for spine 71.47, and for TB 71.53). Duration frequently seen already in the early phase of the disease of dialysis correlated significantly with spine-BMD, TB- [1]. Renal osteodystrophy may result in considerable BMD and Ad-SoS (r = 70.37, r = 70.45, r = 70.55, morbidity for patients with end-stage renal failure respectively, p<0.05), while duration of ESRF did not (ESRF). Bone biopsy with tetracycline labeling is still have such an influence. Laboratory investigations did not considered the ‘gold standard' for the assessment of correlate with skeletal parameters. Ad-SoS correlated renal osteodystrophy [2,3]. Bone biopsy, being an significantly with spine-BMD (r = 0.45, p<0.05) and TB- invasive method, can not be widely used for assessing BMD (r = 0.56, p<0.01). Both QUS and BMD values the skeletal status in subjects with ESRF. Lately, bone correlated significantly with Tanner stages (r ranged mineral density (BMD) measurements have more often from 0.59 to 0.69, p<0.001) and did not increase with been applied for the diagnosis of renal osteodystrophy age except for correlation between age and TB-BMD. In [4–6]. More recently, quantitative ultrasound (QUS) conclusion, skeletal status in the population studied is methods were introduced for the diagnosis of skeletalchanges due to ESRF [4,7–11]. QUS measurements can Correspondence and offprint requests to: Wojciech Pluskiewicz, be performed in several sites of the skeleton, the most MD, Head of Metabolic Bone Diseases Unit, 3 Maja 13/15 Street, 41- common being the calcaneus. In 1992 a new ultrasound 800 Zabrze, Poland. Tel/fax: +48 32 2718110. e-mail: [email protected] (US) technology was developed for measurements of the W. Pluskiewicz et al.
hand phalanges (DBM Sonic 1200, IGEA, Carpi, Italy).
The control group for QUS examinations was In some studies [4,7,8] these measurements allowed the recruited randomly from pupils of local schools and detection of skeletal alterations in ESRF.
students of the Silesian School of Medicine. Prior to and The aim of the present study was the evaluation of during the evaluation there were no factors in the skeletal status in children, adolescents and young adults controls known to affect bone metabolism (either with ESRF using BMD measurements, QUS of the hand medications or diseases). The controls were selected phalanges and laboratory investigations.
from a group of 1010 subjects and matched with thepatients for age and gender. It was not possible to obtaina control group comparable with the patients with regard Subjects and Methods to weight and height because the patients in ESRF had amean body size much lower than the normal, healthy population. The local ethics committee gave itspermission for the study protocol.
The study group consisted of 30 patients (18 females, 12males) and 686 controls (423 females, 263 males). Theclinical characteristics of the patients and controls are given in Table 1. The population studied included allsubjects (children, adolescents, young adults) with ESRF Skeletal status was assessed by dual-energy X-ray from the Silesian region of Poland with about 4 million absorptiometry (DXA) examinations of the spine BMD inhabitants. Eleven patients were treated with regular (spine-BMD, g/cm2) and total body BMD (TB-BMD, hemodialysis, receiving two or three dialysis sessions per g/cm2) using a DPX-L densitometer (Lunar, Madison, week; the duration of hemodialysis was 6–15 h per WI) and by US measurements of the proximal hand week. Nineteen patients were on peritoneal dialysis (18 phalanges using a DBM Sonic 1200 (IGEA, Carpi, on automatic peritoneal dialysis and 1 on continuous Italy). Comparison between BMD values in patients and ambulatory peritoneal dialysis). The average duration of in the normal, healthy population was provided using Z- renal replacement therapy was 3.1 + 2.5 years, and the scores. All DXA measurements were done by the same mean time since the diagnosis of chronic renal failure operator. The coefficient of variation (CV % = SD/mean (CRF) was 6.2 + 4.1 years. All subjects remained on 6 100%) for BMD measurements was 1.1% for spine- drug therapy for CRF receiving calcium carbonate, 1a- BMD and 0.6% for TB-BMD.
hydroxycholecalciferol and erythropoietin. Ten subjects The US unit consists of two probes mounted on an received corticosteroid therapy: 5 patients before the electronic caliper: one emitter and one receiver. The study, and 5 during the study. The mean duration of this latter records the US energy after it has crossed the treatment was 60 months (range 2–169 months), and the phalanx. We determined the amplitude-dependent speed dose was 0.5–1 mg of prednisone per 1 kg of body of sound (Ad-SoS, m/s) in the distal metaphyses of the weight daily. The reasons for CRF were: chronic proximal phalanges of the second through fifth fingers of pyelonephritis in 11 patients, chronic glomerulonephritis the dominant hand. As was previously shown, no in 6, lupus nephritis in 2, polycystic kidney disease in 2, statistically significant differences between measure- rapidly progressive glomerulonephritis, familial nephro- ments of the extremity with and without a fistula exist nophthisis, bilateral renal hypoplasia, Wegener's gran- [5]. Speed of sound in bone tissue was calculated ulomatosis, amyloidosis, congenital nephrotic syndrome considering the first signal with an amplitude of 2 mV at and toxic injury in 1 each, and unknown causes in 2.
the receiving probe; thus, the measured speed of sound is Sexual maturity was assessed using Tanner stages. There amplitude-dependent. Acoustic coupling was achieved were 5 subjects without any symptoms of puberty, 4 in using a standard US gel. All measurements were done by Tanner stage I, 3 in Tanner stage II, 3 in Tanner's stage the same operator. The CV% was 0.64%.
III, 9 in Tanner stage IV and 5 in Tanner stage V. No The following laboratory tests were performed: serum past fractures were noted in the dialysis patients.
intact parathyroid hormone (i-PTH), phosphorus andtotal and ionized calcium serum concentrations. All Table 1. Clinical characteristic of patients and controls blood samples were taken just before hemodialysis, or inthe morning in the patients treated with peritoneal Patients (n = 30)a Controls (n = 686)b Duration of CRF (years) Duration of dialysis (years) All calculations of means and standard deviations (SDs) as well as linear correlations were done using theStatistica program run on an IBM PC. Correlations Values are mean + SD.
between Tanner stages and skeletal values were CRF, chronic renal failure.
a.Eighteen females, 12 males.
performed using the Spearman rank correlation test.
b.Four hundred and twenty-three females, 263 males.
Because of the small size of the population studied we Skeletal Status in End-Stage Renal Failure did not calculate statistical relationships separately for cant correlation with Ad-SoS (r = 70.29, p = 0.13).
gender and for the type of dialysis; all analyses were Skeletal measurements were also correlated with the performed for whole group. Statistical significance was duration of renal failure, duration of dialysis, age, achieved with p<0.05.
weight, height and Tanner stages. These data arepresented in Table 3. All three bone parameterscorrelated negatively and significantly with duration of dialysis, though the Ad-SoS value was affected morethan the BMD values. Duration of CRF did not correlate Table 2 shows the results of bone measurements and with Ad-SoS and BMD of the spine and TB. Age laboratory data in patients. BMD of the spine and total correlated significantly and positively with TB-BMD, body are expressed in grams per square centimeter and while spine-BMD and Ad-SoS showed a weaker, Z-scores. Such data allow comparison of our results with nonsignificant positive relationship with age. In the normal values for age and gender.
controls, Ad-SoS correlated significantly with age Ad-SoS was significantly lower in the dialysis patients (r = 0.73, p<0.0001). Weight, height and data expressing in comparison with controls (1942 + 74 m/s vs 2050 + sexual maturation assessed by Tanner stages correlated 77 m/s, p<0.0001). Also BMD values were decreased in significantly with all three skeletal parameters in dialysis comparison with the normal healthy population (Z-score for spine-BMD was 71.47 and for TB-BMD was71.53). Ad-SoS correlated significantly with spine-BMD (r = 0.45, p<0.05) and TB-BMD (r = 0.56, p<0.01), and spine- and TB-BMDs correlated with eachother (r = 0.81, p<0.0001). The mean value of i-PTH was The study has shown the serious abnormalities of increased in the dialysis patients, while serum total and skeletal status in the population studied. To our ionized calcium, and phosphate, were in the normal knowledge no studies using BMD and QUS measure- range. Correlations of skeletal measurements with ments in persons with ESRF aged less than 17 years have laboratory data were calculated and no significant previously been published. Generally, there is a relationships were obtained except for the correlation significantly greater number of adults than young between ionized calcium and spine-BMD (r = 70.37, subjects with ESRF treated with dialysis. In 1998 in p = 0.05). i-PTH showed a weak, negative, nonsignifi- the whole of Poland 6878 persons were on dialysis [12].
Among them 242 subjects were younger than 20 years.
Table 2. Results for skeletal and laboratory measurements in patients This means that our group constitutes of about 12% of with end-stage renal failure Polish dialysis patients (we had only 2 subjects olderthan 20 years). Because of the lack of other data it is not possible to compare current results with other studies performed in subjects of a comparable age. Results of QUS measurements in our study were compared with data for a large sample of the control group and have shown that skeletal status in our subjects is strongly affected by the disease. The difference between Ad-SoS Total serum calcium (mmol/l) in patients and controls was 108 m/s and this difference Ionized serum calcium (mmol/l) expressed in standard deviations is 1.45 (calculated as Phosphorus (mmol/l) 108 m/s; 74 m/s is the SD value in the dialysis patients),which is very close to the Z-scores obtained for spine- Values are mean + SD.
TB, total body; Ad-SoS, amplitude-dependent speed of sound; i-PTH, and TB-BMDs in our population. In the study by Rico et intact parathyroid hormone.
al. [8] performed with a DBM Sonic, a difference Table 3. Correlations between skeletal parameters and age, body size, durations of chronic renal failure and dialysis, and Tanner stages Values are correlation coefficients (r), with p values in parentheses. CRF, chronic renal failure; TB, total body; Ad-SoS, amplitude-dependentspeed of sound.
NS, not significant.
W. Pluskiewicz et al.
between hemodialyzed patients and controls expressed some DXA evaluations were done (hand, ultradistal in Z-scores was about 1. In another study investigating radius, radial shaft) in a group of adults with ESRF.
Correlations between US and BMD measurements were hemodialysis patients the difference between the value higher (r = 0.46–0.68) than in our study (r = 0.45–0.55), for healthy controls and patients was 119 m/s. If the which can probably be explained by the similar cortical/ latter value were expressed as a Z-score it would be trabecular ratio in sites measured in this study. The 71.4, which is very close to our data. A greater duration of dialysis correlated with QUS (r = 70.41) reduction in Z-score was observed by Foldes et al. [11] and BMD values (r = 70.35 to 70.53), which is very for speed of sound at the tibia (72.0), which can close to our data, and duration of renal failure probably be explained by the fact that cortical bone is significantly affected both US and BMD values, which more sensitive to the influence of an increase in i-PTH was not observed in the current study. Some differences were noted in the comparison of current relationships Also important information is provided by the between i-PTH and skeletal parameters; we did not comparison of age-related increase in Ad-SoS in the find such connections, while in Przedlacki et al.'s study dialysis patients with the same relationships in controls.
i-PTH correlated significantly with Ad-SoS in men (r = In subjects with ESRF Ad-SoS did not increase 70.54), and with DXA of the hand (r = 70.38) and significantly with age, while in controls this correlation radial shaft (r = 70.49). In the study by Przedlacki et al.
is significant (r = 0.73, p<0.0001). This means that we ionized calcium correlated significantly with Ad-SoS can expect the peak value of Ad-SoS in a patient with only, while in the current study only spine-BMD was ESRF to be lower than in healthy, control subjects.
correlated significantly with serum ionized calcium. The Correlations between age and BMD measurements lack of significant correlations between i-PTH and provide a similar result. Only TB-BMD increased skeletal parameters may suggest that hyperparathyroid- significantly with age in our subjects. In the study by ism associated with a high level of i-PTH has no marked Sabatier et al. [13] performed in a large population of influence on bone status in our patients. A similar 574 persons aged 10–24 years, spine BMD correlated observation is derived from the study in which no significantly with age (r = 0.49). Even stronger relation- correlation between i-PTH and bone osteopenia was ships were reported by Bonjour et al. [14] who obtained, found [16]. Another study showed that BMD of the total in a population of 207 young subjects aged 9–18 years, body and arm were inversely correlated with i-PTH [17].
correlations of spine BMD with age of 0.78 for males The limitations of our study were: (1) the lack of and 0.8 for females, and 0.63–0.87 and 0.7–0.84, analyses performed separately for gender and type of respectively for hip BMD. Our nonsignificant correlation dialysis, due to the relatively small sample size, and (2) of spine-BMD with age (r = 0.33) is weaker than those the cross-sectional design. Despite these limitations it obtained in these other studies. We did not find any study can be concluded that skeletal status in the population presenting a correlation between TB-BMD and age, so studied is strongly affected by ESRF. Both QUS and direct comparison is not possible. Only Zanchetta et al.
BMD measurements show an ability to express skeletal [15] in a study performed in a cohort of 900 subjects changes in a similar manner, though the QUS parameter aged 2–20 years assessed whole body mineral content. In seems to be more sensitive to changes due to renal this study, however, no exact value of correlation failure because of a stronger negative relationship between age and whole body mineral content was between Ad-SoS and duration of dialysis.
presented, despite the fact that this relationship wassignificant. On the basis of our data we suspect thatneither spinal nor total body peak BMD in subjects with ESRF will reach the level attained in a normal, healthypopulation. This may result in increased fracture risk in 1. Llach F, Bover J. Renal osteodystrophy. In: Brenner BM, Rector FC, editors. The kidney. 5th ed. Philadelphia: Saunders, this population in the future. These observations concerning BMD are very similar to those obtained for 2. Malluche HH, Sawaya BP, Faugere MC. Dialysis: current status, our US parameter.
contemporary limitations and future challenges. Kidney Int Correlations between skeletal and laboratory measure- ments did not show any significant relationships, but the 3. Fletcher S, Jones RG, Rayner HC, Harnden P, Hordon LD, Aaron JE, et al. Assessment of renal osteodystrophy in dialysis patients: correlation coefficient between Ad-SoS and i-PTH use of bone alkaline phosphatase, bone mineral density and (r = 70.29) is almost the same as that obtained in the parathyroid ultrasound in comparison with bone histology.
study by Montagnani et al. [7], who noted r = 70.28 with p<0.05. Probably the smaller size of our group 4. Przedlacki J, Pluskiewicz W, Wieliczko M, et al. Quantitative ultrasound of hand phalanges and dual-energy X-ray absorptio- prevented the correlation reaching significance. A metry of forearm and hand in patients with end-stage renal failure slightly stronger significant inverse correlation was treated with dialysis. Osteoporos Int 1999;10:1–6.
noted by Foldes et al. [11] between tibial SOS and i- 5. Taal MW, Masud T, Green D, Cassidy MJD. Risk factors for PTH (r = 70.39, p<0.01).
reduced bone density in haemodialysis patients. Nephrol Dial It is interesting to compare the current data with 6. Gabay C, Ruedin P, Slosman D, Bonjour JP, Leski M, Rizzoli R.
results obtained by Przedlacki et al. [4]. In this study the Bone mineral density in patients with end-stage renal failure. Am same device for US measurements was used, and also J Nephrol 1993;13:115–23.
Skeletal Status in End-Stage Renal Failure 7. Montagnani A, Gonelli S, Cepollaro Ch, et al. Quantitative Poland – 1998. Gdansk: Akademia Medyczna w Gdansku, 1999 ultrasound in the assessment of skeletal status in uremic patients.
(in Polish).
J Clin Densitom 1999;2:389–95.
13. Sabatier JP, Guaydier-Souquieres G, Laroche D, et al. Bone 8. Rico H, Aguado F, Revilla M, Villa LF, Martin J. Ultrasound mineral acquisition during adolescence and early adulthood: a bone velocity and metacarpal radiogrammetry in hemodialyzed study in 574 healthy females 10–24 years of age. Osteoporos Int patients. Miner Electrolyte Metab 1994;20:103–6.
9. Taal MW, Cassidy MJD, Pearson D, Green D, Masud T.
14. Bonjour JP, Theintz G, Buchs B, Slosman D, Rizzoli R. Critical Usefulness of quantitative heel ultrasound compared with dual- years and stages of puberty for spinal and femoral bone mass energy X-ray absorptiometry in determining bone mineral density accumulation during adolescence. J Clin Endocrinol Metab in chronic haemodialysis patients. Nephrol Dial Transplant 15. Zanchetta JR, Plotkin H, Alvarez Filguiera ML. Bone mass in 10. Kaan P, Gaul P, Wandel E, Renschin G, Beyer J. Apparente phalangeale Ultraschall-Transmissions-Geschwindigkeit und per- children: normative values for 2–20-year-old population. Bone Nieren- und Hochdruckkrankheiten 1995;24:389–92.
16. Lechleitner P, Dienstl A, Watfach C, Riccabona G, Koenig P, 11. Foldes AJ, Arnon E, Popovtzer MM. Reduced speed of sound in Dittrich P. Doppel-photonen-absorptiometrie bei Renalerosteo- tibial bone of haemodialysed patients: association with serum pathie. Wien Klin Wochenschr 1990;102:136–40.
PTH level. Nephrol Dial Transplant 1996;11:1318–21.
17. Asaka M, Iida H, Entani C, et al. Total and regional bone mineral 12. Puka J, Rutkowski B, Liberek T, Lao M., Rowinski W, density by dual photon absorptiometry in patients on maintenance Bautembach S. Report on the renal replacement therapy in hemodialysis. Clin Nephrol 1992;38:149–53.
Received for publication 12 July 2001 Accepted in revised form 8 November 2001

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