Stesura Seveso Archivio Italiano di Urologia e Andrologia 2015; 87, 162 ORIGINAL PAPER Effect of immobilization on urine calcium excretion in orthopedic patients with pelvic fracture treated by skin traction Ali Derakhshan 1, Nima Derakhshan 2, Hamid Namazi 3, Fariborz Ghaffarpasand 2 1 Nephrology Urology Research Center, 2 Neuroscience Research Center and 3 Department of Orthopedics - Shiraz University of Medical Sciences, Shiraz, Iran. Objectives: To determine the effects on urine calcium excretion of immobiliza- tion by skin traction in patients with pelvic fracture. Methods: In a prospective study, a consecutive series of patients with pelvic fracture treated by skin traction were enrolled. Serum (calcium, phosphorous, alkaline phos- phatase, sodium, potassium, uric acid, BUN, creatinine) and fasting urine calcium, creatinine, sodium, potassium and uric acid were checked within 48 hours of hospitaliza- tion and at 7, 14 and 21 days of immobilization and then after 3 months of mobilization. Trends in changes of vari- ables were recorded. Results: Fifty five patients were enrolled in this study; they were 45 (81.8%) males and 10 (18.2%) females with a mean age 19.4 ± 12.7 years. We found that serum levels of calcium (p = 0.004), phosphorous (p = 0.047) and alka- line phosphatase (p = 0.001) increased significantly during the 3 weeks of immobilization. In the same way, urine cal- cium/urine creatinine ratio increased significantly in the study period (p = 0.004). No symptomatic renal stone for- mation was observed during the study period. Conclusions: Immobilization even in short term causes hypercalciuria in orthopedic patients. Although it is tran- sient and improves with subsequent mobilization, it is needed to be considered specifically by the team caring for this group of patients. KEY WORDS: Hypercalciuria; Short term immobilization; Pelvic fracture; Skin traction. Submitted 2 September 2014; Accepted 31 October 2014 Summary No conflict of interest declared. immobilized (12, 13). Also the effect of immobilization on hypercalciuria and hypercalcemia at intermediate term has been studied (14). There are only few reports (mostly case reports) regarding the hypercalciuria in patients who are immobilized temporarily due to orthopedic fractures (15- 20). In this study, we have investigated the effect of short term immobilization on urinary calcium excretion and also on serum calcium and parathormone in patients who are immobilized with skin or skeletal traction for a pelvic fracture in orthopedic wards. PATIENTS AND METHOD Study population This was a prospective cross-sectional study being per- formed during a 1-year period from 2012 to 2013 in Chamran and Nemazi hospitals, both tertiary orthopedics healthcare centers affiliated with Shiraz University of Medical Sciences. The study protocol was approved by institutional review board (IRB) and ethics committee of Shiraz University of Medical Sciences. All the recruited patients provided their informed written consents before inclusion in the study. We consecutively included all the patients younger than 40 years of age with traumatic pelvic fractures who underwent skin traction and were immobi- lized. The age limit of 40 was selected to lower the risk of interaction of natural process of resorption induced by aging. Patients with metabolic bone disease, patients with primary or metastatic bone tumor, patients on steroid, cal- cium or vitamin D supplements, and patients with abnor- mal baseline serum or urinary calcium level were exclud- ed from the study. We also excluded those patients who were lost at follow-up during the initial 3 weeks of the study, those with renal insufficiency at any time during the study, those with urinary tract infection and any those tak- ing any medication interfering with urinary calcium excre- tion. All of the patients were in complete physical health before the accident which led to hospitalization. Study protocol All the patients underwent complete physical examination by attending physician and the findings were recorded in a DOI: 10.4081/aiua.2015.1.62 INTRODUCTION Hypercalciuria is the most common metabolic cause of renal stone in children and adults (1-4). Hypercalciuria is defined as urinary calcium excretion of more than 4 mg/kg in 24 hour urine or a calcium/creatinine ratio of 0.20 mg/mg in a random urine sample (5, 6). In addition to uri- nary stones, hypercalciuria can cause hematuria, dysuria, frequency, urgency and occasionally enuresis (7-11). Long term immobilization causes hypercalciuria and hypercalcemia in patients with meningomyelocele who are Derakhshan_Stesura Seveso 02/04/15 10:24 Pagina 62 63Archivio Italiano di Urologia e Andrologia 2015; 87, 1 Urine calcium excretion after immobilization data gathering form. We arbitrarily defined the short term immobilization as immobilization of less than 3 weeks. The first sampling was done within 48-hour of hospitalization. Serum levels of albumin, calcium (Ca), phosphorous (P), blood urea nitrogen (BUN), creatinine (Cr), sodium (Na), potassium (K) were measured. We also obtained spot urine sample to measure urine Ca, Cr, Na and K. The samples were tested with the same technique in the two university hospital laboratories. The tests were repeated on days 7, 14 and 21 of hospitalization (immobilization). Also, they were repeated 2 to 3 months after mobilization. In addition, parathormone (PTH) level was measured on day 21 day of admission and the sera were refrigerated; after collection of all PTH samples, it was examined in a special reference endocrine and metabolism laboratory. Statistical analysis All the data was analyzed using Statistical Package for Social Science (SPSS Inc., Chicago, USA) software for Window version 16.0. Frequency distribution of the vari- ables, means and standard deviations of the values were presented in tables and charts. The mean values were compared in different time intervals using repeated measure and paired t-test. Proportions were compared using Chi-square test. A 2-sided p-value less than 0.05 was considered statistically significant. RESULTS Fifty five patients were enrolled in this study; they were 45 (81.8%) males and 10 (18.2%) females with a mean age 19.4 ± 12.7 years. The baseline characteristics are summa- rized in Table 1. We found that serum levels of calcium increased significantly during the 3 weeks of immobiliza- tion (p = 0.004). In the same way, the serum level of phos- phorous increased significantly during 3 weeks of immo- bilization (p = 0.047). The serum levels of alkaline phos- phatase also increased during the study period (p = 0.001). However there was no significant difference in serum levels of BUN, creatinine and albumin after the 3 weeks of skin traction. The values for serum sodium and potassium were within normal limits throughout the study. The urine calcium/urine creatinine ratio increased in the study period significantly (p = 0.004) (Figure 1). After mobilization, we had the opportunity to check the urine calcium/urine creatinine ratio in 47 patients who had returned for follow-up visit 2 to 3 months after dis- charge from the hospital. The ratio after the 3 months was similar to the baseline (0.13 ± 0.04 vs. 0.13 ± 0.06; p = 0.381). Table 1. The baseline characteristics and changing trend of laboratory findings in 55 patients with pelvic fracture treated by skin traction. Baseline Day 7 Day 14 Day 21 p-value Serum Ca (mg/dL) 9.2 ± 0.74 9.3 ± 0.65 9.3 ± 0.85 10.1 ± 0.87 0.004 Serum P (mg/dL) 4.6 ± 1.2 4.5 ± 0.9 4.8 ± 1.3 5.0 ± 0.71 0.047 Urine Ca/Urine Cr 0.13 ± 0.06 0.17 ± 0.11 0.22±0.12 0.29 ± 0.17 0.001 BUN (mg/dL) 14.4 ± 4.5 14.1 ± 2.9 13.9 ± 3.6 13.8 ±5.9 0.186 Creatinine (mg/dL) 0.81 ± 0.28 0.79 ± 1.7 0.94 ± 0.84 0.93 ± 0.16 0.098 ALP (IU) 424.6 ± 316.2 448.6 ± 298.3 561.6 ± 181.6 575.3 ± 227.1 0.001 Albumin (g/dL) 4.1 ± 0.32 3.9 ± 0.14 4.0 ± 0.56 4.1 ± 0.32 0.783 ALP: Alkaline phosphatase; BUN: Blood Urea Nitrogen; Ca: Calcium; P: Phosphorous Figure 1. Calcium/creatinine ratio at baseline and throughout the study. Figure 2. Urine Ca/Cr ratio in patients < 20 years and 20-40 years. Derakhshan_Stesura Seveso 02/04/15 10:24 Pagina 63 Archivio Italiano di Urologia e Andrologia 2015; 87, 1 A. Derakhshan, N. Derakhshan, H. Namazi, F. Ghaffarpasand 64 Serum PTH was checked only once at the end of the 3rd week and it was 17.42 ± 10.04 ng/ml. The study popu- lation was then divided into 2 groups; 28 patients were between 2-20 years with a mean age of 8.8 ± 6.6 years and 27 were 21-40 years with the mean age of 30.3 ± 6.7 years (Figure 2). The above mentioned parameters were similar to the results in the whole group and no signifi- cant inter-group differences were observed. No sympto- matic renal stone formation was observed during the study period. DISCUSSION Hypercaciuria is the most common metabolic cause of renal stone in children and adults (1-4). Hypercalciuria may present with different signs and symptoms specifi- cally in children such as hematuria, abdominal pain, fre- quency, dysuria and occasionally enuresis (7-11). In a well-designed study by Zerwekh et al., the biochemical markers of bone turnover and calcium homeostasis were evaluated in normal volunteers subjected to 12 weeks of bed rest. They found a significant rise in biomarkers of the bone turn over, urine, and serum calcium (21). Hypercalciuria is a known consequence of long and inter- mediate term immobilization which leads to decreased bone mineral density. This entity has been studied in patients with stroke and long term immobilization and also in children with intermediate term immobilization with Legg-Calvé-Perthes disease and developmental dys- plasia of the hip joint (12-14). In this study, even after one week of immobilization in children with Legg-Calve- Perthes disease urine calcium increased 2.3 times as com- pared to the baseline value but this did not happen in children with developmental dysplasia of the hip who had never been ambulated before immobilization. Immobilization and associated hypercalciuria can lead to stone formation which has been reported even within a few days of immobilization in children (17). In this prospective study, the effect of short term immo- bilization in 55 orthopedic patients with pelvic fracture who were assigned for short term immobilization (skin traction) was studied. Even after the first week of immo- bilization, urine calcium excretion increased from the baseline level and the test was repeated in the 2nd and 3rd weeks of immobilization; we found higher levels of cal- cium/creatinine ratio but not significantly different from the first week value. This indicates that immobilization induces bone resorption and is associated to hypercalci- uria even after a few days. We had the opportunity to check urine calcium/creati- nine ratio 2-3 months after mobilization in the majority of our patients (number = 47); it had returned to previ- ous values in the majority of patients, 0.13 ± 0.04 (p = 0.38) with Pearson correlation = 0.846. This indi- cates that the effect of immobilization on urine calcium excretion is transient. Serum calcium was also checked simultaneously with urine calcium in the first, second and third week, although it was higher than the baseline level in the third week of immobilization but the P value didn't reach a statistically significant level (p = 0.057). Regarding the serum calcium level, we didn't reach the same conclu- sion as previous studies which were mostly case reports (12, 13, 16, 18, 22, 23). In some of these reports, the period of immobilization was more than that of our study. Our results regarding serum parameters were sim- ilar to the results of Korkes et al. (14) with almost no change in serum parameters in that study. Symptomatic stone formation was not seen in any case in our study as in those of Korkes F (14) and Andrews PI (18). In conclusion, immobilization even in short term causes hypercalciuria in orthopedic patients. Although it is tran- sient and improves with subsequent mobilization, it is needed to be considered specifically by the team caring for this group of patients. ACKNOWLEDGEMENTS We would like to thank the Vice Chancellor for Research for his financial support. The authors would also like to thank Dr. Nasrin Shokrpour for editorial assistance and Ms Rosta for statistical analysis at Center for Development of Clinical Research of Nemazi Hospital. We also thank the cooperation of Mrs. Oraghi (Nemazee Hospital Cast Room Nurse) and Mr. Mozaffari (Chamran Hospital Orthopedic Ward Nurse) in sample collection. REFERENCES 1. Monk RD, Bushinsky DA. Kidney stones. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR (eds) Williams textbook of endocrinology. WB Saunders, Philadelphia. 2011; 1350-1367. 2. Bushinsky DA, Coe FL, Moe OW. Nephrolithiasis. In: Brenner BM (ed) The kidney. WB Saunders, Philadelphia. 2012; 1455-1507. 3. Worcester EM, Coe FL. Calcium kidney stones. 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Human synthetic calcitonin therapy for hypercalcemia of immobilization. J Pediatr. 1995; 126:825-827. 23. Meythaler JM, Tuel SM, Cross LL. Successful treatment of immobilization hypercalcemia using calcitonin and etidronate. Arch Phys Med Rehabil. 1993; 74:316-9. Correspondence Ali Derakhshan, MD Professor of Pediatric Nephrology Nephrology Urology Research Center Shiraz University of Medical Sciences, Shiraz, Iran Nima Derakhshan, MD (Corresponding Author) nima_med83@yahoo.com Resident of Neurosurgery Neuroscience Research Center Shiraz University of Medical Sciences Chamran Hospital, Chamran Avenue, Shiraz, Iran Hamid Namazi, MD Associate Professor of Orthopedic Surgery Department of Orthopedics Shiraz University of Medical Sciences, Shiraz, Iran Fariborz Ghaffarpasand, MD Resident of Neurosurgery Neuroscience Research Center Shiraz University of Medical Sciences, Shiraz, Iran Derakhshan_Stesura Seveso 02/04/15 10:24 Pagina 65