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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2017  |  Volume : 28  |  Issue : 3  |  Page : 538-544
Prevalence of osteoporosis in patients with chronic kidney disease (stages 3–5) in comparison with age- and sex-matched controls: A study from Kashmir Valley Tertiary Care Center


Department of Nephrology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India

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Date of Web Publication18-May-2017
 

   Abstract 

Chronic kidney disease (CKD) is associated with a range of metabolic bone diseases. Fracture rates are higher in CKD patients than age-matched controls throughout all the five stages of CKD. Dialysis patients have 4 times as many hip fractures as expected for their age. CKD forms an independent risk factor for osteoporosis, even in the absence of traditional risk factors. This study was carried out at the nephrology unit in a tertiary care center of Kashmir to know the prevalence of osteoporosis in CKD patients having glomerular filtration rate (GFR) <60 mL/min (stages 3–5). Among the 151 cases studied, the average estimated GFR was 16.78 ± 10.714 mL/min. There were 98 males (64.9%) and 53 females (35.1%). Their mean age was 51.01 ± 14.138 years. Osteoporosis based on femoral neck T-Score was seen in 31 patients (31.6%) while 43 patients (28.5%) had osteoporosis at L1, L2 lumbar vertebrae. The prevalence of osteoporosis based on femoral neck T-Score as well as osteopenia was highest in stage-5 CKD. In our study, the body mass index (BMI) had a positive correlation with osteoporosis; low BMI patients were at higher risk for osteoporosis (P = 0.014). In the Kashmir valley, the prevalence of osteoporosis was 31.8% in CKD patients against 22% in controls. Thus, CKD forms an important risk factor for osteoporosis even in the absence of traditional risk factors. We recommend early screening, detection, and management of osteoporosis to reduce the burden of morbidity and mortality in this subset of patients.

How to cite this article:
Najar M S, Mir MM, Muzamil M. Prevalence of osteoporosis in patients with chronic kidney disease (stages 3–5) in comparison with age- and sex-matched controls: A study from Kashmir Valley Tertiary Care Center. Saudi J Kidney Dis Transpl 2017;28:538-44

How to cite this URL:
Najar M S, Mir MM, Muzamil M. Prevalence of osteoporosis in patients with chronic kidney disease (stages 3–5) in comparison with age- and sex-matched controls: A study from Kashmir Valley Tertiary Care Center. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Nov 15];28:538-44. Available from: http://www.sjkdt.org/text.asp?2017/28/3/538/206439

   Introduction Top


Chronic kidney disease (CKD) is defined as kidney damage or glomerular filtration rate (GFR) of <60 mL/min/1.73 m2 for three months or more, regardless of the cause. CKD is associated with a range of different meta bolic bone diseases.[1],[2] Aging itself is associa ted with both reductions in GFR and increased prevalence of osteoporotic fractures.[3],[4] There is a growing body of literature which suggests that patients with CKD, who do not yet require renal replacement therapy, are also at an increased risk of fragility fracture.[4],[5],[6] This association was stronger than several tradi tional risk factors for fracture including age, gender, race, body weight, and bone mineral density (BMD) measured at the hip by dual- energy X-ray absorptiometry (DEXA).[6] End- stage renal disease (ESRD) is characterized by several metabolic and hormonal abnormalities, including decreased renal synthesis of 1,25 (OH)2D3, hyperphosphatemia, hypocalcemia, increased secretion of parathormone (PTH), chronic metabolic acidosis, premature hypo- gonadism, more recently recognized 25(OH) Vitamin D deficiency, and impairment of mineralization of osteoid.[7],[8]

Measurement of BMD by DEXA is an accep table method in predicting fracture risk in patients with CKD stages 3–5. Osteoporosis is traditionally diagnosed by low BMD on DEXA (T-score of -2.5 or lower) or low trauma fractures. In patients with early CKD (stage 1 to early stage 3), fractures are far more likely due to osteoporosis than specific form of CKD-mineral bone disease. In addi tion to osteoporosis, adynamic and osteo- myelitic forms of renal bone disease are also prevalent in CKD stages 3–5.[9],[10],[11] At present, double tetracycline-labeled quantitative bone histomorphometry is one of the best diagnostic tests. Similarly, trans-iliac crest bone biopsy is the gold standard to diagnose renal osteo- dystrophy (ROD) and osteoporosis in patients with significant kidney dysfunction; however, it has limited availability.[12] Bone biopsies pro vide evidence of the underlying pathophysio- logy as well as the measurements of bone turnover, mineralization, and volume scoring.[9]

Given the high prevalence of both osteopo rosis and CKD in older adults, it is of the utmost public health relevance to be able to assess fracture risk in this population.[3],[4] The increased risk of fracture noted in patients with predialysis CKD may be because of abnor malities in Vitamin D metabolism, parathyroid function, and calcium-phosphate balance, which may result in full-blown ROD long before kidney function deteriorates to the level of ESRD.[13] Serum levels of 1,25(OH)2 Vitamin D decline in a linear fashion. Moreover, approximately 40% of patients with estimated GFR (eGFR) between 40 and 49 mL/min had elevated serum PTH levels.[14] As elevated PTH levels are catabolic for cortical bone, these biochemical alterations could cause deterio ration in cortical architecture, leading to re duced cortical density and increased cortical porosity much earlier in the course of CKD than previously thought.[15] The lumbar spine and proximal femur comprise substantial amounts of both cortical and trabecular bones. DEXA provides a composite measurement of the cortical and trabecular compartment. Hence, DEXA is an established clinical tool for iden tifying patients with and without prevalent fractures and for identifying those who are at an increased risk of incident fracture.[16]


   Methodology Top


This is a prospective, hospital-based study, with age- and sex-matched controls, carried out in the department of nephrology at a ter tiary care center of Kashmir, India. All pa tients who attended the nephrology clinic or were admitted in the concerned ward with CKD stages 3–5, who were not on any renal replacement therapy, or those detected to have CKD stages 3–5 for the first time, were enrolled as cases from August 2013 to May 2015. The stages of CKD are described by the GFR, ranging from stage 1 with GFR >90 mL/min/1.73 m2 with risk factors, stage-2 with GFR = 90 mL/min/1.73 m2 with evidence of renal injury, stage 3 with GFR of 30–59 mL/ min/1.73 m2, stage 4 with GFR of 15–29 mL/ min/1.73 m2, and stage-5 with GFR <15 mL/ min/1.73 m2 (the level at which dialysis or transplantation may be necessary). All patients in the age group of >18 years to 65 years pre- dialysis (CKD stages 3–5) along with age- and sex-matched controls were included in the study.

Patients on renal replacement (hemodialysis or continuous ambulatory peritoneal dialysis), renal transplant recipients, patients on steroids, patients who were on anti-resorptive drugs (bisphosphonates), contraceptives, calcitonin, and pregnant woman were excluded from the study. Criteria for controls were framed accordingly.

After obtaining proper consent, a detailed history of related risk factors (smoking, hyper- tension, diabetes, steroid intake, and surgical menopause) was obtained from all cases and their medical records were checked. They were examined, and baseline investigations including kidney function tests, serum calcium levels, serum phosphorus levels, liver function tests, complete blood count, and lipid profile were performed.

All patients included in the study had eGFR <60 mL/min calculated using the Equation from the Modification of Diet in Renal Disease study[2] and were staged as per guidelines of the National Kidney Disease Outcomes Quality Initiative.[1] Cases were subjected to DEXA Scan (GE Lunar-1 Co. Prototype). The same methodology was carried out for the controls before subjecting them for DEXA scan. The DEXA definition of osteoporosis and the bone mass criteria followed for its diagnosis were adopted from the World Health Organization (WHO) definition of osteoporosis (1994).[17] The T-score was used for the evaluation of BMD and for the definition of different stages of BMD according to the WHO definition of osteoporosis as follows. T-score was taken at femoral neck and LI, L2 spine.

  • T-Score of ≤ −2.5 standard deviation (SD)
  • T-score of −1 SD to −2.5 SD is taken as osteopenia
  • T-score of > -1 SD is taken as normal.



   Statistical Analysis Top


Data obtained were subjected to statistical analysis. Pearson’s Chi-square test and Fisher’s exact test were used to analyze the data. Conti- nuous variables were analyzed by ANOVA technique. The statistical software Statistical Package for Social Science (SPSS) version 20.0 (SPSS Inc., Chicago, IL, USA) was used for analysis. P <0.05 was considered statisti- cally significant.


   Results Top


Of the 151 patients enrolled, there were 98 males (64.9%) and 53 females (35.1%). The age of the patients ranged from 21 to 65 years, with a mean of 51.01 ± 14.138 years. All the patients were known cases of CKD (diagnosed or first time evaluated) and were admitted or followed up in the nephrology clinic. The ave- rage eGFR of the study patients was 16.78 ± 10.714 mL/min. There were 15 cases with CKD stage 3 (10%), 63 with CKD stage 4 (41.3%), and 73 had CKD stage 5 (48.7%). The average BMD at the femoral neck in the study cases was 0.88 ± 0.085 g/m2, while BMD at LI, L2 spine was 0.96 ± 0.087 g/m2. With a mean T-Score of -1.13 ± 1.802 at the femoral neck, 48 patients (31.8%) had osteoporosis (T-Score < 24.5%) 37 ,(2.5?) had osteopenia, i.e., T-Score between 1? and 2.5?, and 66 (43.7%) fulfilled the criteria for normal BMD with T-Score up to -1 ([Table 1] and [Figure 1]). The mean T-Score at LI, L2 spine was -1.29 ± 1.492; 43 study cases (28.5%) were qualified for osteoporosis with T-Score < -2.5 at LI, L2, 57 patients (36.4%) had osteopenia and 51 (33.1%) had T-Score within normal range ([Table 2] and [Figure 2]). Of the 98 male patients enrolled as controls, osteopo- rosis based on femoral neck T-Score was seen in 31 patients (31.6%), osteopenia in 28 pa- tients (28.6%), and 39 patients (39.80%) had normal T-Score. Among the 53 female controls, 17 (32%) had osteoporosis, nine (17%) had osteopenia, and 27 (51%) had T-Score within normal range. Among cases, males formed a significant majority with osteoporosis; among 48 cases, 31 (64.6%) were male and 17 (35.4%) were female (P = 0.098). Among 98 male controls, osteoporosis based on L1, L2 T- Score was seen in 28 controls (28.6%), osteopenia in 41 controls (41.8%), and 29 (29.6%) controls had T-score within normal limits. Among 53 female cases, osteoporosis was seen in 15 cases (28.3%), osteopenia in 15 (28.3%) cases, and 23 cases (43.4%) had T- Score within normal limits. Again, no significant difference in percentile distribution of osteoporosis at L1, L2 was seen among males and females (28.6% vs. 28.3%). Among 43 cases having osteopo-rosis based on L1, L2 T-Score, 28 (65%) were male and 15 (35%) were female. Again, a majority of osteoporosis cases were male when compared to female (P = 0.043). In general, the prevalence of osteo porosis differed only slightly when the two sites were compared for both sexes (31.6% vs. 28.6% for males and 32% vs. 28.3% for females). However, the prevalence of osteo- penia at L1, L2 was significantly higher in both sexes than at femur neck (41.8% vs. 28.6 for males and 28.3% vs. 17% for females). The prevalence of osteoporosis based on femoral neck T-Score was highest in stage 5 CKD with 44 cases (91.6%) out of 48 belo nging to this stage. Similarly, the prevalence of osteopenia was highest in CKD stage 5; 20 cases (54%). Similarly, the prevalence of osteoporosis based on L1, L2 T-Score was highest in stage 5 CKD, seen in 81.6% of cases. Furthermore, the prevalence of osteo- penia was highest in CKD stage 5 seen in 46.5% of the patients. Of all osteoporotic indi viduals (cases and subjects taken together), 48 (70.6%) had CKD and only 20 (29.4%) did not have CKD [Table 2]. Statistically significant difference with P = 0.012 was found between the two groups. The data from our study show that CKD is an important risk factor for osteo porosis, and the prevalence of CKD increases with the severity of CKD.
Table 1: Stages of chronic kidney disease and distribution of osteoporosis in the study patients (femoral neck).

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Table 2: Stages of chronic kidney disease and distribution of osteoporosis (L1, L2 vertebra).

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Figure 1: T-score/femoral neck T-Score distribution among cases.

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Figure 2: T-score/osteoporosis distribution based on L1/L2 spine among cases.

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   Discussion Top


Aggarwal et al[18] noted reduced BMD early in the course of CKD as estimated by DEXA and increased fracture risk that worsened with the progression of CKD. In our study, we found that the prevalence of osteoporosis was higher in CKD patients than that in non-CKD con trols (P = 0.012). There was an increased pre valence of osteoporosis with the progression of CKD. Similarly, Hamdy et al[19] performed a study in which they found that 75% of patients with predialysis CKD had abnormal bone histology (74% of osteitis fibrosa, 19% of mixed bone disease, 1% of osteomalacia, 1% of aluminum bone disease, and 5% of adyna- mic bone disease). In this report, it was note worthy that creatinine clearances ranged from 15 to 50 mL/min, and none had clinical, bioch emical, or radiographic evidence of bone di sease. On similar lines, Nickolas et al[20] found a significant association between hip fracture and moderate-to-severe degrees of CKD, parti cularly in younger individuals, which was independent of traditional risk factors for hip fracture. An eGFR <60 mL/min was associated with a significant 2-fold increase in the like lihood of reporting a previous hip fracture. In younger participants (aged 50–74 years), the prevalence of CKD was approximately 3-fold higher in those with a history of hip fracture versus in those without a history of hip frac ture (19.0% vs. 6.2%, respectively; P = 0.04). However, Kinsella et al[21] noted that moderate CKD in women was associated with occur rence of fracture, but whether this is indepen dent of osteoporosis was not clear. They conducted a retrospective, cross-sectional study of 1702 female patients referred for DEXA scanning. The eGFR in mL/min/1.73 m2 by Modification of Diet in Renal Disease was calculated within one year (median interval of 4 weeks) of the DEXA scan. The indepen dent association of self-reported fracture occur rence with eGFR category was assessed using multivariate logistic regression. Mean age (SD) was 61.7 years and mean eGFR (SD) was 68.8. The percentages of patients with an eGFR of 75–89, 60–74, 30–59, and <30 were 34%, 45%, 20%, and 0.8%, respectively. Forty-seven percent had osteoporosis. Mean T-scores for the above eGFR categories were -2.2, -2.3, -2.5, and -3.0, respectively (P trend <0.001). Osteoporosis was significantly associated with eGFR on univariate analysis but not following adjustment for age.

In our study, eGFR and body mass index (BMI) had positive correlation with BMD. Patients having low eGFR and low BMI pa tients were at higher risk for osteoporosis (P = 0.014). Among patients with BMI <18.5,[4] osteoporosis at femur was present in two patients (50%). Among patients with BMI >25, osteoporosis was seen in 12 cases (40%). Marwaha et al[22] observed that BMD correlated positively with BMI and negatively with PTH levels. No correlation was observed with serum 25(OH) D levels.
Table 3: Prevalence of osteoporosis in patients with and without chronic kidney disease.

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In this study, the prevalence of osteoporosis based on femoral neck T-Score was highest in stage 5 CKD as was the prevalence of osteo- penia. Myong et al[23] studied the relationship between BMD and moderate-to-severe CKD among the general population in Korea. After adjustment for all variables, multiple regres sion analysis showed that BMD in the femur neck, total femur, and lumbar spine was posi tively associated with eGFR in both males and females. An additional analysis showed that CKD was also significantly associated with osteoporosis in both males and females. Ensrud et al[7] studied the relationship between renal function and risk of hip and vertebral fractures in older women. In their case-cohort study, they studied a cohort of 9704 women 65 years or older to compare baseline renal func tion (eGFR). Women with a reduced eGFR were at an increased risk of trochanteric hip fracture. Renal function was not independently associated with the risk of vertebral fracture. They concluded that older women with mode rate renal dysfunction are at an increased risk of hip fracture.


   Conclusion Top


This study was carried out to know the preva lence of osteoporosis in patients with CKD stages 3–5 (GFR <60 mL/min). In our study, CKD was associated with a high prevalence of osteoporosis. CKD formed an important risk factor for osteoporosis on univariate analysis. There was an increase in the prevalence of osteoporosis in CKD from stages 3–5. We recommend proper screening for the early detection and management of osteoporosis in CKD patients to reduce the burden of morbi dity and mortality in this subset of patients.

Conflict of interest: None declared.

 
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Levey AS, Eckardt KU, Tsukamoto Y, et al. Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005;67:2089-100.  Back to cited text no. 2
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Dukas L, Schacht E, Stähelin HB. In elderly men and women treated for osteoporosis a low creatinine clearance of <65 ml/min is a risk factor for falls and fractures. Osteoporos Int 2005;16:1683-90.  Back to cited text no. 5
    
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Nickolas TL, McMahon DJ, Shane E. Relationship between moderate to severe kidney disease and hip fracture in the United States. J Am Soc Nephrol 2006;17:3223-32.  Back to cited text no. 6
    
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Lindberg JS, Moe SM. Osteoporosis in end- state renal disease. Semin Nephrol 1999;19: 115-22.  Back to cited text no. 7
    
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Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int 2009; Suppl 113: S115-9.  Back to cited text no. 9
    
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Miller PD. The role of bone biopsy in patients with chronic renal failure. Clin J Am Soc Nephrol 2008;3 Suppl 3:S140-50.  Back to cited text no. 12
    
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Ureña P, Bernard-Poenaru O, Ostertag A, et al. Bone mineral density, biochemical markers and skeletal fractures in haemodialysiss patients. Nephrol Dial Transplant 2003;18: 2325-31.  Back to cited text no. 13
    
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Leonard MB. A structural approach to skeletal fragility in chronic kidney disease. Semin Nephrol 2009;29:133–43. '  Back to cited text no. 14
    
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Parfitt AM. A structural approach to renal bone disease. J Bone Miner Res 1998;13:1213-20.  Back to cited text no. 15
    
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Malluche HH, Ritz E, Lange HP, et al. Bone histology in incipient and advanced renal failure. Kidney Int 1976;9:355-62.  Back to cited text no. 16
    
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Aggarwal HK, Jain D, Yadav S, Kaverappa V. Bone mineral density in patients with pre- dialysis chronic kidney disease. Ren Fail 2013; 35:1105-11.  Back to cited text no. 18
    
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Hamdy NA, Kanis JA, Beneton MN, et al. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure. BMJ 1995;310:358-63.  Back to cited text no. 19
    
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Nickolas TL, Leonard MB, Shane E. Chronic kidney disease and bone fracture: A growing concern. Kidney Int 2008;74:721-31.  Back to cited text no. 20
    
21.
Kinsella S, Chavrimootoo S, Molloy MG, Eustace JA. Moderate chronic kidney disease in women is associated with fracture occurrence independently of osteoporosis. Nephron Clin Pract 2010;116:c256-62.  Back to cited text no. 21
    
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Marwaha RK, Tandon N, Garg MK, et al. Bone health in healthy Indian population aged 50 years and above. Osteoporos Int 2011 ;22: 2829-36.  Back to cited text no. 22
    
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Myong JP, Kim HR, Koo JW, Park CY. Relationship between bone mineral density and moderate to severe chronic kidney disease among general population in Korea. J Korean Med Sci 2013;28:569-74.  Back to cited text no. 23
    

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Correspondence Address:
Mohamad Muzzafer Mir
Department of Nephrology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir
India
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DOI: 10.4103/1319-2442.206439

PMID: 28540890

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