| Abstract|| |
To evaluate renal osteodystrophy (ROD), bone biopsies were performed in 57 patients with end-stage renal failure (ESRF) on dialysis, 46 on hemodialysis (HD) and 11 on peritoneal dialysis (PD). There were 29 males (mean age of 42 years) and 28 females (mean age of 39 years). Relevant presenting clinical features were pruritis in 46 cases, bone pains in 32, acute pseudogout in three, bone deformities in two, conjunctiva! calcification in two, cutaneous calcification in two, and corneal calcification in one. The mean value of predialysis blood investigations were as follows: urea 33.9 mmol/L, creatinine 913 umol/L, bicarbonate 18 mmol/L, calcium 2.36 mmol/L, albumin 40 g/L, phosphorus 1.69 mmol/L, alkaline phosphatase 178 U/L, parathyroid hormone 543 pmol/L, magnesium 1.06 mmol/L and aluminum 1.81 mmol/L. Skeletal survey showed no changes in 24 patients (42%), hyperparathyroid cystic changes of bones in seven, osteoporosis as the predominant features in seven, mixed picture of ROD in 12, subperiosteal resorption of the metacarpals in two, osteosclerosis (Rugger Jersey Spine) in two and osteomalacia in two patients. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN). All patients had low BMD (both LS and FN). Bone biopsy (BBX) revealed mixed picture in 30 cases, predominantly secondary hyperparathyroid changes in 10, mild hyperparathyroid changes in five, predominant osteoporosis in three, osteomalacia in four, aplastic (adynamic) bone in four, and aluminum deposition in one. All of the patients who showed evidence of bone involvement on BBX had abnormal BMD suggesting that BMD is a good non-invasive screening test for ROD but indiscriminative for the type of bone disease. BBX still remains the diagnostic tool to differentiate and classify different types of bone disease.
|How to cite this article:|
Mitwalli AH. Spectrum of Renal Osteodystrophy in Dialysis Patients at a Tertiary Hospital, Riyadh, Saudi Arabia. Saudi J Kidney Dis Transpl 1998;9:128-33
|How to cite this URL:|
Mitwalli AH. Spectrum of Renal Osteodystrophy in Dialysis Patients at a Tertiary Hospital, Riyadh, Saudi Arabia. Saudi J Kidney Dis Transpl [serial online] 1998 [cited 2019 Jul 18];9:128-33. Available from: http://www.sjkdt.org/text.asp?1998/9/2/128/39284
| Introduction|| |
Renal replacement therapy has increased the survival of patients with end-stage renal disease (ESRD). Long-term abnormalities such as those of bone and mineral metabolism have, therefore, become more apparent and they now account for significant morbidity and mortality among these patients , . Renal bone disease starts early in the course of chronic renal failure (CRF), so that by the time the glomerular filtration rate (GFR) falls to 50% of the normal value, about 50% of the patients show abnormal bone histology  . Few of these patients are symptomatic, and the diagnosis of bone disease by biochemical parameters and skeletal surveys are relatively poor predictors of the type and severity of bone disease  . Recently, however, development of intact parathyroid hormone (PTH) molecule assay by radio immunoassay and dual photon absorptiometry have been shown to contribute better towards identification and classification of bone disease , . This study was done to evaluate the efficacy of these non-invasive methods in diagnosing renal osteodystrophy (ROD) and in predicting bone disease among Saudi patients with ESRD who were on either herno or peritoneal dialysis. It also aims to compare the results of non-invasive techniques and bone biopsy (BBX) considered to be the gold standard for diagnosis of various forms of ROD.
| Methods and Materials|| |
The study was carried out between June 1992 and June 1994 at the Security Forces Hospital (SFH), Riyadh, Saudi Arabia. Fiftyseven Saudi ESRD patients who were on dialysis (HD or PD) for at least six months were included in this study. Females with oophorectomy were excluded. All patients were non-bedridden adults. All hemodialysis patients were on bicarbonate-bath dialysis. All patients were on calcium carbonate 1,500 - 3,000 mg/day and Vit D3 0.25 - 2 µgm/day, and none of the patients was on aluminum hydroxide AI(OH)3. The following biochemical parameters were measured in all the patients: serum calcium (Ca++), phosphate (Po4--)> magnesium (Mg++), alkaline phosphatase (Alk Ph), albumin (Alb), urea, creatinine (Cr), and bicarbonate (HCO3-)
The value of Ca++ was corrected for serum albumin level by the formula described by Kleinman and co-workers . All the reported values represent the mean for three consecutive predialysis measurements. Plasma intact PTH and aluminum (Al) levels were analyzed in the JS pathology laboratories JSPS in London, U.K. The radiological studies carried out included: skull, limbs, pelvis, lumbosacrai spine and hands radiography, and the signs looked for were subcortical erosions, osteopenia, osteosclerosis, osteomalacia (looser zones), soft tissue calcifications and pathological fractures. Dual photon-bone mineral densito-metry (BMD) of both femoral neck (FN) and lumbarspine (LS) were done for all patients. All patients had bone biopsy from the iliac crest (right or left) after oral tetracycline labeling using 500 mg twice a day orally given on day 1, 2, 13, 14. The biopsy was obtained, after written consent from the patients, by using (Vilaghy-Zellerman) needle. Two pieces 610 mm transiliac bone biopsy were taken.
Specimens were fixed in 70% alcohol. The tissues were processed and stained using Vonkossa, Massou/Goldner trichrome toluiden blue, aluminum and solochrome azurine stains and also examined by fluorescent microscopy at JSPS laboratory. Detailed morphometry included: trabecular bone volume, osteoid, bone resorption indices (eroded surface and osteoclast surface) and bone formation indices (osteoid surface, active osteoid surface, calcification rate).
For statistical analysis Student's T-test, chi-square and Fisher's exact test were used.
| Results|| |
A total of 57 dialysis patients (HD and PD) were studied, 46 (80.7%) were on HD and 11 (19.3%) on PD. There were 29 (50.9%) males with a mean age of 42 years and a range age of 16-78 years, and 28(49.1%)) females with a mean age of 39 years and an age range of 14-65 years. The mean duration on HD was 22 months with a range of 6-96 months and the mean duration on PD was 27.6 months with a range of 6-42 months. The causes of ESRD were glomerulo-nephritis in 18 patients; diabetes mellitus in 11; chronic pyelonephritis in 8; hypertension in 6; polycystic kidney disease in two; and one with each of the following: obstructive uropathy, SLE3 analgesic nephropathy and tuberculosis of kidney. In eight patients the etiology remained undetermined.
The frequency of the different clinical symptoms in the studied patients were; Pruritis 46 (80.7%), bone pain 32 (56.1%), soft tissue calcification 12 (21.1%), fractures 9 (15.8%), pseudogout 3 (5.3%), and bone deformities 2 (3.5%).
The mean predialysis values of BUN, creatinine, bicarbonate, calcium, and phosphorrus were 33.9 mmol/L, 913 umol/L, 18 mmol/L, 2.34 mmol/L and 1.69 mmol/L respectively. The mean values of alkaline phosphatase, PTH, magnesium and aluminum were 178 U/L, 543 pmol/L, 1.06 mmol/L and 1.81 mmol/L respectively. All the patients had low bone mineral density on dual photon absorptiometry, compared to the normal value for matched age and sex as per values established for the Saudi population . These are recorded in our hospital as the following mean±S.D. values and were both statistically significant: Lumbarspine (LS) 0.92 ± 0.17 for male (normal value for matched age 1.142 ± 0.096, p value = 0.004) and 0.69 ±0.31 for female patients (normal value for matched age 1.143 ± 0.105, p value = 0.002). However, the measurements at the femoral neck were not statistically significant: 1.02 ± 0.12 for male (normal value for matched age 1.143 ± 0.105, p value - 0.29) and 0.92 ± 0.29 for female patients (normal value for matched age 0.956 ± 0.100, p value = 0.30).
The radiological changes showed no pathological changes in 24 patients (42.1%). However, 22 patients (38.6%) had changes compatible with secondary hyperparathyroidism which included subperiosteal erosion and cyst formation. Osteoporosis was the underlying radiological bone disease in seven patients (12.3%). Osteomalacia was recognized in four patients two of whom had pseudo fractures (losers zones).
The histological changes found on bone biopsy (BBX) showed that mixed picture is the most common finding in 30 patients (52.6%), followed by changes of secondary hyperparathyroidism in 10 patients (17.5%). Mild hyperparathyroid changes were seen in five patients (8.8%). Osteomalacia was found only in four of the patients (7.0%), three of the patients (5.3%) had changes compatible with osteoporosis and only one patient had AL deposition. There were four patients (7.0%) with aplastic (adynamic) bone, ah1 of whom were diabetics and three were on PD and none of them was on A1(OH)3 [Table - 1].
Though the patients on peritoneal dialysis were few in number (11 patients vs 46 on HD), the only significant difference was in the frequency of aplastic (adynamic) bone disease, which was observed in 27.3% of patients receiving PD vs 2.2% in HD patients with overall prevalence of 7.0% when all patients were grouped together. The rest of bone lesions had similar frequencies. All four patients with adynamic (aplastic) bone had diabetes as the cause of ESRD and all of them were older than 50 years of age and had low PTH level.
Correlation between serum PTH and hone histology
[Table - 1] shows the correlation between the histological patterns and the serum PTH levels. Three patients with serum PTH of < 100 pmol/L had aplastic bone disease. No other bone lesion was seen in the group with PTH of less than 100 pmol/L. Conversely high turnover bone disease (hyperparathyroidism and mixed type) was found in patients with elevated PTH levels.
Correlation between BMD and bone histology
All patients had low BMD values of 1 to 3 standard deviations below the normal values for those matched for age and sex. However, there was no correlation between results of BMD and the different types of the histological changes.
| Discussion|| |
The effect of current practices of dialysis, such as inclusion of older age group and diabetic patients, the availability of active Vit D; the awareness of Al toxicity and the use of CaCo3 as a phosphate binder all have impacted on patterns of ROD. Our study shows that about 70% of the study patients had high turnover bone disease: (mixed lesion 52.6% or hyperparathyroidism as seen in 17.5% of the cases). This was different from the findings of Hutchison, et al who quoted mixed lesion 13% and hyperparathyroidism 50% respectively  , but if considered collectively as a group of high turnover bone diseases then the total percentage would be 63%, which is in agreement with our study. The high prevalence of secondary hyperparathyroidism may be related to noncompliance of patients in taking phosphate binders in our region. Alternatively, it may be an indicator of Vit D3 deficiency for a long time before dialysis is started. It may, therefore, be a future practice to use active Vit D3 in the course of CRF once the GFR falls below 50% to prevent such severe form of metabolic bone disease  . Smith et al  reported that 15% of their patients had osteomalacia and Llach et al  reported that 25% of their patients had osteomalacia. In our study, however, the prevalence of osteomalacia was 7% of the patients. The apparently low prevalence in our patients may be due to lack of exposure to Al intoxication  . Aplastic lesions without Al intoxication, however, still remains a diagnostic challenge and in such patients associated hypercalcemia and low PTH levels could help in differentiating the two conditions  . Aplastic or adynamic bone disease without Al intoxication was seen in 7% of our study patients, which may reflect a much lower prevalence in contrast to previously reported prevalence of 27%, but is in agreement with Llach et al  and comparable to Coen, et al  . Sub-clinical levels of AL intoxications could be a reason for low turnover aplastic lesion. This was not noted in our patients bone biopsies. This is in agreement with others , . Only one patient in our study had Al deposition (1.8%) with high PTH levels (284 pmol/L). This low prevalence of Al-related bone disease is much lower than other studies  and is probably largely due to avoidance of the use of aluminum hydroxide Al(0H)3. Regarding modality of dialysis influencing the pattern of ROD, we studied only a small number of patients on PD in whom 27% had low turnover adynamic bone disease compared to 2.2% on HD. The mechanism described for this is probably the more sustained and higher calcium level associated with PD  , which could be due to over treatment  . The other possible reason for the increased prevalence of low turnover adynamic bone disease in PD patients may be due to the older age and diabetic etiology as noted by other authors ,,.
To exactly define the pattern of ROD, bone biopsy remains the gold standard  . We tried to correlate bone histology with PTH levels, dual photon absorptiometry and skeletal survey. High PTH levels (more than 400) was associated with high turnover bone disease (either mixed or secondary hyperparathyroidism) and lower levels (below 100) with adynamic bone disease. Intermediate results were found in mild cases, with considerable overlap.
Radiological changes appear late in the course of ROD and X-ray techniques focus on cortical bone while the early abnormalities of ROD appear in cancellous bone , .
In this study, comparison between radiological findings and biochemical and hormonal parameters showed statistically insignificant correlations similar to previous reports , . Also there was no strong correlation between the radiological findings and the histological changes similar to previous reports  .
Our study showed that all of the patients studied had abnormal BMD results when compared to healthy age- and sex-matched individuals, as stated by El-Desouki  . This disagrees with other studies where BMD results were low only in 65% of the cases of ROD  but is in agreement with Mazess et al  , where all the ROD patients in their study were significantly below 20% of normal. This suggests that dual photon can detect changes of bone mineralization defect much earlier than conventional radiology as noted by Wahner et al  . Unfortunately BMD remains quite non-specific for the type of bone disease, though it may indicate the severity of bone mass  . It seems, at best, that BMD is a good adjunct methodology to screen the patients initially. There was no correlation at all with histological diagnosis, which still remains as the only available tool of accurate classification of renal bone disease.
| Acknowledgment|| |
We thank Ms Miriam Gozo Culanding who gave excellent secretarial assistance in preparing this manuscript. Also we extend our thanks to the nurses in the dialysis unit of Security Forces Hospital, particularly Sister Lora Corpuz, who helped in this study.
| References|| |
|1.||Coburn JW, Slatopolsky E. Vit. D, PTH and renal osteodystrophy in Brenner BM ed. The kidney. W.B. Saunders 1986;39:1657. |
|2.||Malluche H, Faugere MC. Renal bone disease 1990: an unmet challenge for the nephrologist. Kidney hit 1990;38:193-211. |
|3.||Avioli L, The renal osteodystrophy in the kidney: edited by Brcncs B, Rector FC Philadelphia,WB Saunders 1986; 1542-80. |
|4.||Adams J, Chen S, Adams P, Isherwood I. Measurement of trabecular bone mineral by dualenergy computed tomography. J Comp Assit Tongor 1982;6:601-7. |
|5.||Genant HK, Block JE, Steiger P, Glueer CC, Ettinger B, Harris ST. Appropriate use of bone densitometry. Radiology 1989;170:817-22. [PUBMED] [FULLTEXT]|
|6.||Kleinman KS, Coburn JW. Amyloid syndrome associated with hemodialysis. Kidney Int1989;35:567-75. [PUBMED] |
|7.||El-Desouki M. Bone mineral density of the spine and femur in the normal Saudi population.Saudi Med J 1995;16(l):30-5. |
|8.||Hutchison AJ, Whitehouse RW, Boulton HF, et al. Correlation of bone histology with parathyroid hormone, vitamin D3, and radiology in end-stage renal disease. Kidney Int 1993;44:1071-7. [PUBMED] |
|9.||Malluche HH, Ritz E, Lange HP, et al. Bone histology in incipient and advanced renal failure. Kidney Int 1976;9:355-62. [PUBMED] |
|10.||Smith AJ, Faugere MC, Abreo K, Fanti P, Julian B, Malluche HH. Aluminumrelated bone disease in mild and advanced renal failure: evidence for high prevalence and morbidity and studies on etiology and diagnosis. Am J Nephrol 1986;6:275-83. |
|11.||Llach F, Felsenfeld AJ, Coleman MD, et al. The natural course of dialysis osteomalacia. Kidney Int 1986;18:S74-9. |
|12.||Coen G, Mazzaferro S, Ballanti P, etal.Renal bone disease in 76 patients with varying degrees of predialysis chronic renal failure: a cross-sectional study. Nephrol Dial Transplant 1996;! 1(50):813-9. |
|13.||Moriniere P, Cohen-solal M, Belbrik S, et al. Disappearance of aluminic bone disease in long term asymptomatic dialysis population restricting A1(OH)3 intake: emergence of an idiopathic adynamic bone disease not related to aluminum" Nephron 1989;53:93-101. |
|14.||Cohen-solal ME, Sebert JL, Boudailliez B, et al. Non aluminic adynamic bone disease in non-dialyzed uremic patients: a new type of osteopathy due to overtreatment? Bone 1992;13:1-5. [PUBMED] [FULLTEXT]|
|15.||Mortan AR, Hercz G. Hypercalcemia in dialysis patients comparison of diagnostic methods. Dial Transplant 1991;661-694. |
|16.||Delmez JA. The spectrum of renal osteodystrophy in peritoneal dialysis patients. Perit Dial Int 1996;16(l):24-5. |
|17.||Ritz E, Krempien B, Mehls O, Malluche H. Skeletal abnormalities in chronic renal insufficiency before and during maintenance hemodialysis. Kidney Int 1973;4:116-27. [PUBMED] |
|18.||Van Ypersle de Strihou C, Jadoul M, Malghem J, et al. Effect of dialysis membrane and patients age on signs of dialysis related amyloidosis. Kidney Int 1991;39(5):1012-9. |
|19.||Eastwood JB, Bordier PJ, de-WardenerHE. Some biochemical, histological, radiological and clinical features of renal osteodystrophy. Kidney Int I973;4:128-40. |
|20.||Owen JP, Pamell AP, Keir MJ, et al. Critical analysis of the use of skeletal surveys in patients with chronic renal failure. ClinRadiol 1988;39:578-82. |
|21.||Huraib S, Souqiyyeh MZ. Aswad S, AlSwailem AR. Pattern of renal osteodystrophy in hemodialysis patients in Saudi Arabia. Nephrol Dial Transplant 1993;8:603-8. |
|22.||Mazess RB, Peppier WW, Chesney RW, et al. Total body and regional bone mineral by dual-photon absorptiometry in metabolic bone disease. Calcif Tissue Int 1984;36(1):813. |
|23.||Wahner HW, Dunn WL, Riggs BL. Noninvasive bone mineral measurements. SeminNuclMed 1983;13:282-9. |
|24.||Alberts C, van-der-Schoot JB, BusemannSokole E. Bone scintigraphy and densitometry in symptomatic haemodialysis bone dise |
Ahmed H Mitwalli
Department of Medicine, King Khalid University Hospital, P.O. Box 2925, Riyadh 11461
[Table - 1]