|Year : 2022 | Volume
| Issue : 2 | Page : 137-143
The frequency of osteoporosis in patients with predialysis chronic renal failure and the factors affecting the development of osteoporosis
A Karatas1, E Erdem2, YK Arıcı3, E Canakci4, E Turkmen5, NT Turker6
1 Department of Internal Medicine, Division of Nephrology, Education and Research Hospital, Ordu University School of Medicine, Ordu, Turkey
2 Samsun Dialysis Clinic, Ondokuz Mayis University, School of Medicine, Samsun, Turkey
3 Department of Biostatistics and Medical Informatics, Ordu University, School of Medicine, Ordu, Turkey
4 Department of Anesthesiology and Reanimation, Education and Research Hospital, Ordu University, School of Medicine, Ordu, Turkey
5 Department of Internal Medicine, Division of Nephrology, Ondokuz Mayis University, School of Medicine, Samsun, Turkey
6 Department of Internal Medicine, Education and Research Hospital, Ordu University School of Medicine, Ordu, Turkey
|Date of Submission||04-Jun-2020|
|Date of Acceptance||23-Nov-2021|
|Date of Web Publication||16-Feb-2022|
Dr. A Karatas
Department of Internal Medicine, Division of Neprology, Education and Research Hospital, Ordu University, School of Medicine, Bucak Town, Nefs-i Bucak Street, Ordu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Osteoporosis is a common public health problem in chronic kidney patients. The risk factors for osteoporosis in patients with nondialysis CKD have not been fully investigated. It is not known exactly whether the risk factors of osteoporosis in the general population are also valid for the nondialysis CKD patients. Aims: This study aims to determine the frequency of osteoporosis and the risk factors for osteoporosis in nondialysis CKD patients. Patients and Methods: Our study was performed with 283 nondialysis stage 3-5 CKD patients. According to the BMD results, the patients were classified into groups as normal, osteopenia and osteoporosis according to World Health Organization criteria. Monocyte/high-density lipoprotein-cholesterol ratio (MHR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) were calculated individually for all cases. Results: According to our BMD results, 67 (24%) patients were found to have osteoporosis. In the osteoporosis patient group, compared to the normal BMD group, females were higher and the mean age was higher (P = 0.025, P = 0.028). Body mass index (BMI) and eGFR were lower in the osteoporosis group (P = 0.013). Parathyroid Hormone and Platelet-to-lymphocyte ratio in the patients in the osteoporosis group was higher than of those in the normal group (P = 0.026, P = 0.035). In the multivariate logistic regression analysis, advanced age, female gender, and low BMI were determined as independent risk factors for the development of osteoporosis in nondialysis CKD patients. Conclusion: Advanced age, female gender and low BMI are the risk factors for osteoporosis in nondialysis CKD patients. It may be a rational approach to measure BMD for the diagnosis of osteoporosis in nondialysis CKD patients who are elderly, female and have low BMI.
Keywords: Body mass index, nondialysis chronic kidney disease, osteoporosis, platelet-to-lymphocyte ratio
|How to cite this article:|
Karatas A, Erdem E, Arıcı Y K, Canakci E, Turkmen E, Turker N T. The frequency of osteoporosis in patients with predialysis chronic renal failure and the factors affecting the development of osteoporosis. Niger J Clin Pract 2022;25:137-43
|How to cite this URL:|
Karatas A, Erdem E, Arıcı Y K, Canakci E, Turkmen E, Turker N T. The frequency of osteoporosis in patients with predialysis chronic renal failure and the factors affecting the development of osteoporosis. Niger J Clin Pract [serial online] 2022 [cited 2022 Dec 2];25:137-43. Available from: https://www.njcponline.com/text.asp?2022/25/2/137/337760
| Introduction|| |
Ostoeporosis has been defined by the World Health Organization (WHO) as a bone fragility and an increased risk of fracture as a result of low bone mass and disruption in bone tissue. Bone disease in patients with nondialysis chronic kidney disease (CKD) is defined as mineral and bone disorder (MBD) and increases the risk of MBD fracture. Especially in CKD Stage 3-5 patients, the fact that CKD-induced MBD, and osteoporosis seen together in the non-CKD population, significantly increase the risk of fracture. Bone fractures have been shown to be more common in patients with nondialysis CKD compared to the general population. Increased fracture may be an important cause of morbidity and mortality in these patients.,
In estimating the risk of postmenopausal or age-related fractures in the general population, the bone mineral density (BMD) is used. BMD measurement has also been found to estimate the fracture risk in patients with nondialysis CKD. Kidney Disease: In the Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD guideline, BMD measurement was recommended for patients with nondialysis Stage 3-5 CKD if there is a risk factor for osteoporosis or if there is a CKD-MBD finding.
In general population, advanced age, female gender, postmenopausal status, low body mass index (BMI), decreased physical activity, vitamin d deficiency, anticonvulsants medications, hypogonadism, chronic heparin use and alcohol use can be shown as risk factors for osteoporosis. The risk factors for osteoporosis in patients with nondialysis CKD have not been fully investigated. It is not known exactly whether the risk factors of osteoporosis in the general population are also valid for the nondialysis CKD patients.
In some studies, various markers such as mean platelet volume (MPV), red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte to high-density lipoprotein cholesterol ratio (MHR) have been shown to be associated with diseases or disease progression.,,, There are also studies examining the relationship between osteoporosis patients and these markers in the general population.,, In nondialysis CKD patients, the relationship between low BMD and these markers is unknown.
In our study, we measured BMD to determine the frequency of osteoporosis in nondialysis CKD patients. According to the BMD result, we investigated the risk factors of osteoporosis in nondialysis CKD patients with osteoporosis. We also investigated whether markers such as MPV, RDW, NLR, PLR, MHR are the indicators of osteoporosis in nondialysis CKD patients.
| Methodology|| |
This present study was approved by the Ordu University local Clinical Research and Ethics Committee (Decision no: 2018/193, Date: 20.09.2018). Our study was designed cross-sectional and conducted with 283 nondialysis CKD patients who applied to the Nephrology outpatient clinic between January 2019 and July 2019. Patients with serum PTH levels above 800 pg/ml were considered to have severe hyperparathyroidism and these patients were excluded from the study. Those with severe primary hyperparathyroidism, immobilization, Parkinson's disease, multiple sclerosis, polio, amyotrophic lateral sclerosis, have a systemic disease were excluded from the study. None of the patients included in our study were using steroids. Patients using steroids to ensure group homogenization were excluded from the study. The diagnosis of nondialysis CKD was made in accordance with the KDIGO guideline. The estimated glomerular filtration rate (eGFR) value of the patients was calculated. The eGFR value was calculated with Chronic Kidney Disease Epidemiology Collaboration creatinine equation. The eGFR value of all patients was <60 ml/min/1.73 m2. The patients were Stage 3-5 patients according to the KDIGO guideline. Patients who received dialysis treatment were not included in the study. BMI was calculated in all patients (BMI = weight (kg)/height [m2]). BMI was classified as normal, overweight, obese, morbidly obese according WHO criteria. BMI in the range of 18.5-24.99 were considered normal, those between 25 and 29.99 were overweight, those between 30 and 39.99 were considered obese, those above 40 and above were considered morbid obese.
Blood samples were taken in the morning after 12 hours of fasting for the test results of the patients. The complete blood count was performed with the CELL-DYN RUBY (Abbott, IL, USA) device. Routine biochemical analyses (serum creatinine, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglyceride, C-reactive protein, uric acid, albumin, potassium, calcium) were studied with the COBAS c501 (Roche, Basel, Switzerland) module, and hormone analyses (folic acid, vitamin B12, 25-hydroxy vitamin D, Parathyroid hormone (PTH), ferritin were studied with the COBAS e 601 (Roche, Basel, Switzerland) device. Urine albumin to creatinine ratio (UACR) was studied with the morning urine sample. MHR, NLR, PLR ratios were calculated in all patients. Patients with malignancy, acute and chronic infection, hematological disease and inflammatory disease, and patients with a history of chronic glucocorticoid use were not included in the study.
BMD measurement was performed to all patients with the HOLOGIC SQ-15882 (Massachusetts, USA) device by Dual Energy X-Ray Absorptiometry (DEXA) method. Hip and Lumbar spine measurements were done bilaterally with DEXA. We looked at the total hip or femoral neck.
The recommended reference range was the National Health and Nutrition Examination Survey (NHANES) III reference database for femoral neck measurements in Caucasian women aged 20–29 years. Patients were classified according to T score. The T score ≥-1.0 was accepted as normal; as osteopenia from -1.0 to -2.5; ≤-2.5 was accepted as osteoporosis. Classification was made by taking the lowest T score from Lumbar Spine and femur T scores.
All study procedures were conducted in accordance with the Declaration of Helsinki. Voluntary consent was obtained from the subjects participated in the study.
In this study, all statistical analyses were performed using the SPSS v26 (IBM Inc., Chicago, IL, USA) statistical software. Data are indicated n (%) or means ± standard deviation (SD) and minimum-maximum values. The data were analyzed using one-way ANOVA followed by Tukey's post hoc test. Prior to the analysis, the Levene's and Kolmogorov-Smirnov test were performed in normal variance equality and normal distribution, respectively. The two-way Chi-square test was used to test for differences between frequencies of categorical variables. Multiple binary logistic regression was carried out to determine the variables associated with osteoporosis and to establish the diagnostic model. The odds ratio with 95% confidence interval was calculated for risk estimation of risk factors. The significance level for all statistical tests was set to 95% (P < 0.05).
| Results|| |
Study was performed with 283 nondialysis CKD patients. We had 120 (42.4%) female and 163 (57.6%) male patients. The mean age of the total patients was 66.9 ± 12.3 years (24-87 years). According to our bone mineral density results, 80 (28%) patients had normal BMD, while 136 (48%) patients had osteopenia and 67 (24%) patients had osteoporosis. Descriptive statistics and comparison of baseline characteristics the study groups as shown in [Table 1].
|Table 1: Descriptive statistics and comparison of baseline characteristics the study groups|
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T and Z scores, hip and lumbar densities of the cases according to the BMD measurement results are shown in [Table 2]. Descriptive statistics of BMD scores according to NHANES III reference database shown in [Table 2]
|Table 2: The descriptive statistics of BMD scores according to (NHANES) III referencedatabase|
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Compared to patients with normal BMD, females were more in the Osteoporosis group and the mean age was higher (P = 0.025, P = 0.028). BMI was found to be lower in the osteoporosis group (P = 0.025).
As shown in [Table 3],
|Table 3: The descriptive statistics and comparison of clinical parameters in the study groups|
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One-way ANOVA showed that eGFR showed statistically significant differences in intergroup (P = 0.013). The mean eGFR was found lower in patients with osteoporosis than the normal group (P < 0.05). According to one-way ANOVA, PTH and PLR also showed a statistically significant difference between groups (P = 0.026 and P = 0.035, respectively). While PTH and PLR did not show difference in the osteopenia group compared to the normal group (p > 0.05), it was high in the osteoporosis group compared to the normal group (P < 0.05). In addition, there was also no significant difference between osteopenia and osteoporosis groups in terms of PTH and PLR (p > 0.05). The lymphocyte ratio, which was determined to show a significant change compared to the groups by one-way ANOVA (P = 0.026), in the patients with osteoporosis was significantly lower than both normal and patients with osteopenia (P < 0.05). Albumin, ALP, 25-OH D, Uric acid, HGB, Ferritin, Ca, P, MHR, NLR, UACR, HbA1C, Glucose, RDW, MPV, Folate, B12, pH, pCO2, HCO3, WBC, CRP, Monocyte, Neutrofil and blood fats did not differ significantly compared to study groups (p > 0.05).
Multivariate logistic regression analysis was performed to determine the independent variables associated with the development of osteoporosis. eGFR was grouped to better reveal its effect on low BMD in the multivariate analysis [Table 4]. The patients were divided in 4 groups based on the e-GFR levels 45-59,9; 30-44,9; 15-29,9; <15. Advanced age, female gender, low BMI were identified as independent risk factors for the development of osteoporosis in nondialysis CKD patients (P = 0.001, P = 0.017 and P = 0.002, respectively). Although PTH was seen as a risk factor in the model (P = 0.048), the odds ratio (1.006) for this variable was very low. For this reason, its risk dimension could not be identified [Table 4].
|Table 4: The multivariate logistic regression analysis for osteoporosis risk factor prediction|
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The risk of osteoporosis in patients with BMI 18.5–24.99 kg/m2 was found to be approximately 19,73 times higher than patients with BMI >40 kg/m2. In addition, it was determined that females have 3.07 times higher risk of osteoporosis than males. Patients aged >60 years had a risk of osteoporosis 7.08 times higher than those aged ≤60 years [Table 4].
| Discussion|| |
The incidence of fracture increases as the CKD stage progresses. The incidence of fractures was found as 24, 2, 31,2 and 46,3 per 1000 person-years in CKD stages 3a, 3b, and 4 respectively., The fractures in CKD patients are more common than the general population. This is because the CKD-related bone and mineral metabolism changes in CKD patients are associated with osteoporosis risk factors seen in the non-CKD population. KDIGO guideline has recommended BMD measurement in patients with nondialysis stage 3-5 CKD if there is a risk factor for osteoporosis or if there is a finding of CKD-MBD. We detected osteoporosis in 24% of patients with nondialysis stage 3-5 whom we measured BMD. In our study, we investigated the risk factors of osteoporosis in nondialysis CKD patients and similar to the general population, we found advanced age, female gender, decreased BMI to be a risk factor for osteoporosis. In our osteoporosis patient group, there was an increase in PTH, PLR and a decrease in eGFR values compared to those with normal BMD. We have not detected PTH, PLR and eGFR as independent risk factors.
In a study conducted in USA, creatinine clearance has been calculated with the formula of Cockcroft and Gault in 13,831 individuals and BMD results have been evaluated. Osteoporosis has been found to be 26% and osteopenia has been found to be 47% in females over 20 years old with GFR ≤60 ml/min/1.73 m2. In males with GFR ≤60 ml/min/1.73 m2, osteoporosis has been found to be 10% and osteopenia has been found to be 46%. In the same study, osteoporosis has been found to be 1.4% in females with GFR >60 ml/min/1.73 m2 and 0.6% in males. Our study results were similar. We detected osteopenia in 48% of our patients with nondialysis CKD and osteoporosis in 24%. Of our patients with osteoporosis, 57% were female. We can say that osteoporosis is common in the nondialysis CKD patient group with GFR <60 ml/min/1.73 m2.
In our study, we determined advanced age and female gender as independent risk factors for osteoporosis in nondialysis CKD patients, just like the general population. In the literature, there are different results in different studies on this subject. There are studies that have not found age and gender related to BMD in nondialysis CKD patients, as well as studies that have detected decreased BMD in females and older age.,,
In our study, we showed that low BMI is an independent risk factor for osteoporosis in nondialysis CKD patients. The low BMI has been shown, in different studies, to be a risk factor for osteoporosis in nondialysis CKD.,,
It has been investigated in the general population whether markers such as MHR, NLR, PLR are related to osteoporosis. In postmenopausal females, PLR was associated with low BMD., Similarly, it has been reported that NLR may be an indicator of postmenopausal osteoporosis. In our study, when we looked at the relationship of these markers with osteoporosis in nondialysis CKD patients, the PLR value was higher in the osteoporosis patient group, however, we did not detect PLR as an independent variable for osteoporosis.
We found the PTH level to be higher in our osteoporosis patient group. In our further analysis, although the PTH result was statistically significant, we believe that it is not an independent risk factor for osteoporosis because the odd ratio is very low. For this reason, we did not detect it as an independent variable. There is a study which have found PTH value as predictor for total femur BMD in CKD stage 3-4 patients. In this study, similar to our results, serum 25-hydroxy vitamin D levels have not been found to be associated with BMD. Increased intact PTH level in older males has been found to cause more BMD loss, regardless of eGFR. There are also studies that have not found PTH related to BMD in nondialysis CKD patients. Similar to our study, Manghat et al. have determined the level of intact PTH as correlated with BMD in nondialysis CKD patients, however, they have not detected it as an independent variable. Manghat et al. have not found a correlation between 25-hydroxy vitamin D levels and BMD. Fidan et al. have not found a relationship between BMD and intact PTH and 25-hydroxy vitamin D levels in patients with nondialysis CKD.
In patients with nondialysis CKD, the risk of fracture increases as eGFR decreases., In CKD stages 3a and 3b, the risk of fractures have been found to be increased by 28% and 46% compared to stages 1 and 2. Different results have been found in studies showing relationship between eGFR and BMD in patients with nondialysis CKD. In our study, eGFR was lower in the osteoporosis patient group, however, we did not detect it as an independent variable. Fidan et al. have not found a relationship between eGFR and BMD in nondialysis patients. Although Manghat et al. have shown a correlation between eGFR and BMD in nondialysis CKD patients, they have not detected eGFR as an independent variable for BMD. In studies, when patients with eGFR <60 ml/min/1.73 m2 were compared with patients with normal renal function or early-stage CKD, the risk of fracture has been found to be increased. Further decrease in eGFR value in nondialysis stage 3-5 patients with eGFR <60 ml/min/1.73 m2 may not have an effect on BMD.
The limitations of our study, the sample size was small and cross-sectional. Another restrictive factor is that our study was conducted in a single region population. Another limitation of our study is that we do not have detailed information about the drug use affecting bone metabolism of our cases. New prospective studies on this subject will be carried out with larger scale, multicenter and drug use information, and will contribute positively to the solution of the issue.
In conclusion, osteoporosis is observed in a significant part, such as 24%, of CKD patients. Advanced age, female gender, low BMI were identified as independent risk factors for the development of osteoporosis in nondialysis CKD patients. While age is also a diagnostic criterion for osteoporosis, BMI has a low diagnostic value for osteoporosis. It may be a rational approach to measure BMD for the diagnosis of osteoporosis in nondialysis CKD patients who are elderly, female and have low BMI.
Compliance with ethical standards
This present study was approved by the Ordu University Local Clinical Research and Ethics Committee (Decision no: 2018/193, Date: 20.09.2018).
Written informed consent was obtained from patients who participated in this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]