International Journal of Biological & Medical Research

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1 Int J Biol Med Res. 201; 4(1): Int J Biol Med Res Volume, Issue 1, Jan BioMedSiDiret ubliations Contents lists available at BioMedSiDiret ubliations International Journal of Biologial & Medial Researh Journal homepage: International Journal of BIOLOGICAL AND MEDICAL RESEARCH Original Artile Bone Mineral Density In Chroni Kidney Disease atients a b d Lalithamma Akkupalli, G.aravathi, M.Somasundaram, J.Muni Radha a Tutor, Department of hysiology, Karpaga Vinayaga Institute of Medial Sienes & Researh Center, Chinnakolambakkam, Madhuranthagam, Kanhipuram-6008, T N, India. b rofessor & HOD, Department of hysiology, Sri Venkateshwara Institute of Medial Sienes, SVIMS University, Tirupati, A, India rofessor & HOD, Department of hysiology, Karpaga Vinayaga Institute of Medial Sienes & Researh Center, Chinnakolambakkam, Madhuranthagam, Kanhipuram-6008, TN, India. d Tutor, Department of hysiology, Rajiv Gandhi Institute of Medial Sienes, Ongole, Andhra radesh, India. A R T I C L E I N F O A B S T R A C T Keywords: Bone mineral density (BMD), Chroni kidney disease(ckd), Dialysis, Seondary hyperparathyroidism. Bakground: Metaboli bone disease is ommon in the ase of renal failure. The aim of this study is to ompare mineral hanges, hormonal hanges and bone mineral density in predialysis and post-dialysis renal failure patients. Hypothesis: Seondary hyperparathyroidism may be the ause for skeletal hanges in renal failure. Materials and Methods: 20 patients of both sexes, with hroni kidney disease formed the subjets of the present study. Studies are done in pre and post dialysis states. In this study bone mineral density is measured by dual energy X-ray absorptiometry and bone minerals are estimated by using standard lab tehniques. Results and Conlusion: The results of this study indiate no gross variation in both genders in all parameters. The serum alium levels (-0.07) are statistially dereased. In ontrast, serum phosphorus levels (-0.98) are raised but statistially not signifiant. arathyroid hormone levels (-0.50) are inreased but statistially not signifiant. Vitamin D levels (-0.02) are signifiantly inreased in post dialysis ompared to pre-dialysis subjets. Bone mineral density in lumbar spine (L1 to L4) T-Sore (-0.007), Z Sore (-0.009), nek of the femur T-Sore (<0.001), Z Sore (-0.008) statistially dereased. The forearm T-Sore (-0.97), Z Sore (-0.12) indiates small variation and statistially not signifiant. The mineral hanges are mainly due to inreased seretion of parathyroid hormone. Dialysis has no effet on in bone mineral density. There is skeletal resistane to parathyroid hormone, due to redution in number of hormone reeptors and dereased level of alitriol and loss of negative feedbak on parathyroid hormone seretion by alitriol. Copyright 2010 BioMedSiDiret ubliations IJBMR - ISSN: 0976:6685. All rights reserved. 1. Introdution Early diagnosis of skeletal hanges in hroni kidney disease may derease the risk of fratures. The advaned proedure is measuring bone density using DEXA(dual energy X-Ray absorptiometry).it is used to determine the amount of matter per ubi entimeter of bones. The development of seondary hyperparathyroidism in renal failure is assoiated with disturbanes of the endorine parathyroid hormone, vitamindaxis 7. In advane renal failure hyperparathyroidism progresses even in the presene of normoalemia or hyperalemia. Skeletal resistane to the alium mobilizing ation of TH, another fator responsible for maintenane of hyperparathyroidism in renal failure4. These hanges depend on several fators inluding 1, 25- (OH) 2 Vit-D status, type of nephropathy and individual dietary habits. In order to understand the auses of bone hanges in hroni kidney disease, the serum mineral ontent and hormone onentrations (TH, 1, 25-(OH) 2 Vit-D) are estimated. This may help in the prevention of bone fratures in hroni kidney disease patients. * Corresponding Author : Lalithamma Akkupalli Karpaga Vinayaga Institute of Medial Sienes & Researh Center, Madhuranthagam, Kanhipuram-6008, India. Copyright 2010 BioMedSiDiret ubliations. All rights reserved.

2 Lalithathamma Akkupalli et.al Int J Biol Med Res. 201; 4(1): Materials and Methods The institutional ethial ommittee's approval was obtained atients: The study was done in nephrology Department of Sri Venkateshwara Institute of Medial Sienes after obtaining permission from medial ethis ommittee of the institute. Studies were arried out in stages, 4 and 5 of 20 CKD patients aged between years, 10 males and 10 females attending Nephrology o.p for the past 6 months. The studies were done before dialysis and after dialysis of the patients. The dialysis patients were treated by onventional haemodialysis for 4-5 hours, two times a week. None of the patients had a past history of alohol or smoking. Aute renal failure ases, paediatri patients, patients with primary endorine abnormalities, diabetes mellitus, pulmonary tuberulosis and hypertension were exluded from this study. Biohemistry: Sample olletion: For estimation of serum alium, phosphorus, parathyroid hormone and vit-d the fasting blood sample was olleted into a lean tube allowed the blood to lot for at least 0 min at room temperature. Separated the serum by entrifugation and stored in a refrigerator and serum alium and phosphorus were assessed by using standard laboratory methods. 1, 25-(OH) 2, vit- D was measured by RIA (diasorin, atalog no: 68100E) and serum parathyroid hormone was measured by using N-tat arathyroid hormone S IRMA (Diasorin, atalog no.26100). Bone mineral density: Bone mineral density (BMD) of the lumbar spine, total hip and femoral nek were measured by using Dual energy X-ray absorptiometry (Disovery A, Hologi in.version USA). All Bone Mineral Density measurements were performed by the same experiened operator. Bone Mineral Density results were obtained in absolute values (g/m2), in T-sore and in Z- sore. T- sore is the number of standard deviations from the mean of a healthy adult population and is used to determine osteoporosis or osteopenia. Z-sore is the number of standard deviations from the mean of a healthy age and gender-mathed normal population, whih allows the omparison of Bone Mineral Density between patients of different age and gender. Osteoporosis was defined as a Bone Mineral Density T- sore at any site less than -2.5 and osteopenia as a Bone Mineral Density T-Sore between -1 and 2.5. The referene values were obtained from an Italian normal population. Statistial Analysis: Results were statistially analyzed by applying student test and alulated 'p' values. Results The results of this study indiate no gross variation in both genders of all parameters. The mean values of bone minerals and hormones for hroni kidney disease patients before and after dialysis are presented in the tables below. Serum alium (table- 1&graph-1) and vitamin D (table-2&graph-2) levels were signifiantly dereased in hroni kidney disease patients. hosphorus (table-1&graph-1) and parathyroid hormone (table- 2&graph-2) levels were signifiantly inreased in hroni kidney disease patients. In this study osteopenia was found in 50% in lumbar spine,.% in femur nek and forearm..% of the patients had osteoporosis in lumbar spine, forearm and nek of the femur. (table-&graph-). 2+ Table:-1: Comparison of SCa, SO 4, levels in Group I and Group II 2+ SCa (mg/dl) SO 4(mg/dl) Table:-2: Comparison of serum levels of TH and Vitamin D in Group I and I TH(pg/ml) VIT-D (ng/ml) Table:-: Comparison of BMD T and Z sores of LS, Hip and Forearm in Group I and II LS T-Sore LS Z-Sore Hip T-Sore Hip Z-Sore Fore arm T-Sore Fore arm Z-Sore I I ;NS 0.98;NS 0.50;NS 0.02;S I 0.007;S 0.009;S <0.001;S 0.008;S 0.97;NS 0.12;NS Graph:-1: Comparison of SCa +, SO, levels in Group I and 2 4 Group II

3 Lalithathamma Akkupalli et.al Int J Biol Med Res. 201; 4(1): Graph:-2: Comparision of serum levels of TH and Vit D in Group I and I Group:-: Comparison of BMD T and Z sores of LS, Hip and Forearm in Group I and II 4. Disussion Metaboli bone disease is ommon in the ourse of renal failure. It is observed in a number of studies that renal osteodystrophy is ommon in End Stage Renal Disease (ESRD) patients under dialysis treatment. It is the most ommon ause for mortality in End Stage Renal Disease. Seondary hyperparathyroidism is the main ause for renal osteodystrophy [8]. There is no gross variation in men and women of this study. It is observed that Serum alium is dereased in hroni kidney disease patients and the values are not muh altered in pre and post dialysis onditions. In ontrast Serum hosphorus levels are raised in hroni kidney disease patients and not muh hange is observed in post and pre onditions. The serum alium and phosphate levels are ontrolled by renal mehanisms. So damage of kidneys disturbs the alium and phosphate levels in serum. In these patients abnormalities in Glomerular filtration rate are also found (filtration rate <60 ml/min. In Last stages of hroni kidney disease serum alium levels derease and serum phosphate levels inrease. These hanges are mainly due to seondary hyperparathyroidism. These results are also supported by the studies of Hou SH et al [8]. The Serum Calium levels are dereased in this study beause Hypoalaemia is ommon but not invariably present in patients with advaned renal failure, and modest redutions in the onentration of serum alium may be noted in patients with mild renal insuffiieny. The hypoalaemia may be more pronouned in uremi patients with marked and widespread osteomalasia. In ontrast, the serum levels of alium may be normal or elevated in the patients with marked seondary hyperparathyroidism and generalized osteitis fibrosa. The levels of total, diffusible, and ionized alium are redued while those of omplexed alium are elevated. The perentages of diffusible and ionized frations are not different from normal. A diret relationship between the serum levels of ionized alium and the degree of redution in Glomerular filtration rate. The patients with marked dereases in the serum onentrations of ionized alium are those who have the lowest levels of Glomerular filtration rate. Aidosis may inrease the serum levels of ionized alium, but the relative ontribution of uremi aidosis to the values of ionized alium in patients with renal failure within to 5 minutes after initiation of regular hemodialysis, redialysis onentration of serum alium generally reahes levels between 9.0 and 10.0 mg/dl a rise in serum alium ours in patients with hypoalemia[12]. The serum phosphorus levels are inreased in this study beause the onentrations of serum phosphorus during the fasting state are usually normal or lower than normal in the early stages of renal failure. Hyperphosphatemia beomes apparent when Glomerular filtration rate falls below 20ml/min10.The serum phosphorus levels derease during dialysis seondary to its removal by dialyti proedure. Serum phosphorus onentration inreases during the interdialyti period, the rapidity of the rise depending on the dietary intake of phosphorus, the adherene to therapy with phosphate binding antaids, and the severity of seondary hyperparathyroidism. In the present study parathyroid hormone levels are inreased signifiantly and Vit-D levels are dereased in renal failure patients. These results are also supported by the study of Sanjay K Agarwal, et al., [1]. The mineral hanges are mainly due to inreased seretion of parathyroid hormone. arathyroid hormone seretion ours in response of hypoalaemia, hyperphosphatemia and 1, 25 Dihydroxy Cholialiferol defiieny. However Calium is more important in parathyroid hormone release and alitriol is important in inhibiting parathyroid hormone release. Aording to Dunstan, et al.,

4 Lalithathamma Akkupalli et.al Int J Biol Med Res. 201; 4(1): hyperparathyroidism develops even with normal alium levels or hyperalemia. This is independent of serum alium levels. While normal parathyroid glands have almost no proliferative ativity, uremia leads to hyperplasia of the parathyroids and to an inrease in the number of parathyroid hormone sereting ells in untreated uraemi, patients. A study by Menders et al [10] showed that there is a transition from simple hyperplasia to multinodular transformation and finally pseudoadenoma formation in ases with severe hyperparathyroidism. Another fator is skeletal resistane to the ation of parathyroid hormone to mobilize alium from bone. This depends on several fators inluding redution in the number of hormone reeptors and diminished levels of alitriol. In renal failure the synthesis of alitriol dereases due to destrution of renal parenhyma. This interrupts negative feedbak mehanism on parathyroid hormone seretion. Vitamin-D defiieny also develops in renal failure. Haemodialysis redues the serum alium and Vitamin D, due to loss in the dialysate. So loss of serum alium is prevented by higher amount of Calium in dialyzing fluid. Loss of Vitamin D metabolites lead to osteomalaia. This may be prevented by Vitamin D administration. Synthesis of interleukins is stimulated in dialysis. Interleukin-1 has bone resorbing ativity. The results of Bone Mineral Density testing are reported in omparison of ranges in s of the T-Sore and the Z-Sore. In the present study the Bone mineral density T and Z Sores are lower in post dialysis and re-dialysis Chroni kidney disease patients. Same results were seen in similar work by Ha SK et al(1996). Hormone that are important in bone remodeling, inluding parathyroid hormone, Vitamin D, estrogen, gluoortioids, interleukins, prostaglandins and the members of the TGF- super family of ytokines. One quality is impaired in Chroni Kidney Disease beause there is an inreased prevalene of hip frature in dialysis patients ompared with the general population in all age groups. Dialysis patients in their 40s have a relative risk of hip frature 80-fold that of age-and sex-mathed ontrols. Furthermore, a hip frature in a dialysis patient was assoiated with a doubling of the mortality rate observed in hip fratures in non-dialysis patients. In a multivariate analysis, the risk fators for hip frature inlude age, gender, and duration of dialysis and presene of peripheral vasular disease. Other analyses found rae, gender, duration of dialysis and low or very high arathyroid hormone levels as risk fators. These data, and advanes in other imaging modalities to a National Institutes of Health onsensus onferene to redefine osteoporosis as a skeletal disorder haraterized by ompromised bone strength that results in an inreased risk of frature. Bone strength reflets the integration of two main features. Bone density and bone quality. These quality fators inlude abnormal base turnover on remodeling and other indies of bone arhiteture suh as geometry, onnetivity, mineralization and ollagen ross linking[2]. These fators appear additive to bone mineral density as determinants of bone strength. 5. Conlusion The prolonged treatment with maintenane hemodialysis is assoiated with worsening of radiographi evidene of bone disease in most patients, irrespetive of the alium onentration in dialysate. Adequate ontrols of the serum levels of phosphorous within the normal range may possibly ameliorate or reverse this trend. The Bone mineral density T and Z sores are lower in patients in both before and after dialysis onditions. This study was onluded as the dialysis has no effet on skeletal hanges. It is observed that seondary hyperparathyroidism may be the ause for skeletal hanges in renal failure 6. Aknowledgment I a m e x t r e m e l y g r a t e f u l t o o u r D i r e t o r Dr.G.Subramanyam,D.M., SVIMS UNIVERSITY, Tirupati and Dean Dr.B.Vengamma, M.D., D.M. rofessor,head of the Department of Neurology,SVIMS UNIVERSITY,Tirupati for embling me to arryout this work suessfully. I express my sinere thanks to Dr.V.Sivakumar, M.D., D.M., rofessor and Head, Department of Nephrology SVIMS, Tirupati for having permitted me to arry out the study in the inpatients who were admitted in the Nephrology Unit. I am indebted to Dr.V.V.Sai Naresh,M.D., (Sr.Resident) Nephrology SVIMS for his help and ooperation in doing this work. 7. Referenes [1] Agarwal S.K.: Assessment of Renal Bone mineral Disorder in naïve CKD patients : A single entre prospetive study: Indian Journal of Nephrology. 2007: 17. [2] Cole RE. Improving linial deisions for women at risk of osteoporosis dueal femur bone mineral density testing. JAM osteopath Aso 2008:108(6): MD: [] Delmez, J. A. Tindira. C., Grons. :, Dusso, A: Windus, D. Wand slatopolsky. T. arathyroid hormone suppression by intravenous 1-25 dihydroxyvitamin D. A role for inreased sensitivity to alium. Journal of linial Investigation: 1989:8., [4] Dunstan.C.R.,et al.(1985a). The pathogenesis of renal osteoporosis:role of vitamin D,aluminum,parathyroid hormone,alium and phosphorus.quarterly Journal of Mediine [5] 4. Ersoy FF, passadakis S, Tam, memos ED, katopodis K, Ozener Akiek F, Camsari T, Ates K, Ataman R, Vlahojannis, JG, DombroSAN, utas C, AKpolat T, Bozfakioglu S, WUG, Karayaylal:I, Arinsoy T, stathkis C, yavuz M, Tsakiris JD, Dimitriodes CA, yilmaz ME, Gultekin M, karayalin B, yardimserver M, oreopoulos DG: Bone mineral density and its orrelation with linial and laboratory fators in hroni peritoneal dialysis patients. J Bone miner metab. 2006:24(1): MID: (pubmed: indexed for MEDLINE).

5 Lalithathamma Akkupalli et.al Int J Biol Med Res. 201; 4(1): [6] Godkar B. raful, Godkar. Darshan: Text book of medial laboratory Tehnology :1994: 2:16, 406. [7] Ha Sk, park CH, Seo JK, park SH, Karg SW, hoi KH, Lee Hy, Han Ds : Studies on bone markers and bone mineral density in patients with hroni renal failure : Yonsel med J ot : 7(5) : [8] Hou SH, Zhao, J. Ellman CF, Hu J, Criffin Z, Spiegel DM, Bourdeau JE: Calium and phosphorus fluxes during haemodialysis with low alium dialysate. Am J kidney Dis: 1991: Aug, 18(2): [8] Mario Coo, MD, and Heather Rush, MD: Inreased Inidene of Hip fratures in dialysis patients with low serum parathyroid hormone. Amerian Journal of kidney diseases. 2000: 6:6: [10] Murray R. L. Non protein Nitrogen ompounds, In linial hemistry; Theory, Analysis and o-relation Kaplan L. A. and pese A. J., Eds. C. V. Mosby, Toronto, 1984, [11] Sharon M. Moe, Stuart M. Sprague. Mineral bone disorder in hroni kidney disease. The kidney: Brenner: 2006:2:52: Copyright 2010 BioMedSiDiret ubliations IJBMR - ISSN: 0976:6685. All rights reserved.