Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 102 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 


 
Table of Contents   
ORIGINAL ARTICLE  
Year : 2013  |  Volume : 24  |  Issue : 1  |  Page : 41-47
Relationship between serum leptin levels and bone mineral density and bone metabolic markers in patients on hemodialysis


1 Department of Nephrology, Imam Khomeini Hospital Complex, Tehran University of Medical Science, Tehran, Iran
2 Department of Endocrinology, Imam Khomeini Hospital Complex, Tehran University of Medical Science, Tehran, Iran
3 Research Development Center, Imam Khomeini Hospital Complex, Tehran University of Medical Science, Tehran, Iran

Click here for correspondence address and email

Date of Web Publication22-Jan-2013
 

   Abstract 

Leptin is the protein product of the obesity gene, which is produced in fat tissue. It was originally thought to be involved only in the regulation of food intake and energy balance. We aimed to investigate the relationship of serum leptin levels with bone mineral density (BMD) and biochemical markers of bone turnover in patients on hemodialysis (HD). This study included 72 patients (43 males and 29 females), whose mean age was 55.1 ± 11.4 years, mean body mass index was 23.13 ± 2.75 kg/m 2 and mean duration on HD was 5 ± 3.4 years. The BMD values were calculated using dual-energy X-ray absorptiometry (DEXA) at the femoral neck and lumbar spine. Blood samples were taken for leptin, intact parathyroid hormone (I-PTH), bone alkaline phosphatase (BAP), calcium (Ca), phosphate (P) and albumin. The leptin levels were higher in females than in males (22.3 ± 19.6 vs 20.8 ± 23), but this difference was not significant. The serum leptin level had a strong positive correlation with Ca levels in the female patients (r = 0.659 and P = 0.01) and a negative correlation with albumin levels (r = -0.461 and P = 0.01). No correlation was found with age, BMI, duration on dialysis, BMD and serum levels of PTH, BAP and P for the entire patient group or either gender separately. The serum leptin level was significantly lower in females with PTH >300 pg/mL when compared with patients with PTH = 100-300 pg/mL (86 ± 85 vs 47 ± 48) (P = 0.011).Women with BAP <300 IU/L had significantly higher serum leptin than those with BAP 300-600 IU/L (P = 0.024). Women with Ca <8.5 mg/dL had significantly lower serum leptin levels compared with those with Ca levels of 8.5-10.5 mg/dL (P = 0.011). There was no significant difference between the two genders among variables such as age, BMI, duration on dialysis, serum leptin, I-PTH, Ca, P, BAP, albumin and BMD of the femoral neck and lumbar spine.

How to cite this article:
Ahmadi F, Salari S, Maziar S, Esfahanian F, Khazaeipour Z, Ranjbarnovin N. Relationship between serum leptin levels and bone mineral density and bone metabolic markers in patients on hemodialysis. Saudi J Kidney Dis Transpl 2013;24:41-7

How to cite this URL:
Ahmadi F, Salari S, Maziar S, Esfahanian F, Khazaeipour Z, Ranjbarnovin N. Relationship between serum leptin levels and bone mineral density and bone metabolic markers in patients on hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2014 Oct 20];24:41-7. Available from: http://www.sjkdt.org/text.asp?2013/24/1/41/106238

   Introduction Top


Leptin is a polypeptidic hormone produced by the white adipocyte under the control of the adiposity gene. [1] This hormone has been initially considered as an anti-obesity hormone by its action on the hypothalamic center, through the OBRb receptor, which suppresses appetite and increases basal metabolism. [2] However, leptin receptors have been identified in many pepheral tissues, including the skeleton. [3]

Because leptin is a small peptide, it is cleared by the kidney. Therefore, serum leptin concentrations are increased in patients with chronic renal failure and in those undergoing dialysis, [4] thereby causing a decrease in the bone mineral density (BMD). [5]

However, in vitro studies suggest that leptin has osteogenic effects mediated by its recaptors in osteoblasts, osteoclasts and chondrocytes, with resulting increased bone mineralization. [6],[7],[8] It has been suggested that because leptin is produced and secreted systemically, the direct peripheral positive effects may over-ride the negative central effects of leptin on bone. [8],[9] Thus, the relationship of leptin concentration and bone density in humans is still uncertain. [10],[11] There are very few available data about the correlation between leptin and BMD in patients on hemodialysis (HD). Some studies have found that leptin was associated with higher BMD [12],[13],[14] and decreased bone resorption, [14],[15],[16],[17] while others have reported a negative association with BMD [18],[19],[20],[21] and bone formation, [22] or no association with BMD, [10],[16],[17],[23],[24],[25],[26],[27],[28] bone loss [29] or bone turnover. [23],[24],[29]

In this study, we aimed to examine the relationship of serum leptin with BMD as well as biochemical markers of bone turnover in patients on HD.


   Material and Methods Top


Patients

This study was a cross-sectional survey that was performed between March 2005 and March 2006 on patients undergoing HD in dialysis centers at the Imam Khomeini and Amir Alam Hospital, Tehran, Iran. Seventy-two patients were included in this study. All the patients were treated by conventional HD for 3-4 h, three-times a week, using hollow fiber dialyzers, either hemophane (GFS-20, Gambro) or polysulfone, against a dialysis bath containing 32-36 mmol/L of bicarbonate, 0.85 mmol/L of magnesium, 1.50 mmol/L of calcium and 2 mmol/L of potassium.

All participants agreed to have their BMD measured in addition to the serum biochemistry evaluation.

Patients with diabetes mellitus and hepatic disorders, those who had undergone surgical parathyroidectomy and patients on bisphosphonate, beta blockers and aluminum hydroxide therapy were excluded.

All participants gave written consent. The study was approved by the Local Ethics Committee.

Assays

In all patients, weight and height were measured by the standard technique after HD. BMI was calculated as body weight (kg) divided by height in meters squared (m 2 ). Pre-dialysis blood sampling was performed after a 12-h fast and was sent to the hospital laboratory. The levels of serum leptin were analyzed by enzyme-linked immunoadsorbent assay (ELISA) using the Diagnostic Biochem Canada Direct ELISA kit. Normal values were 2-40 ng/mL in premenopausal women, 2-70 ng/mL in postmenopausal women and 0.5-15 ng/mL in men.

The following parameters were assessed: albumin, calcium (Ca), phosphorus (P) and bone alkaline phosphatase (BAP) using standard laboratory methods; levels of intact-parathyroid hormone (I-PTH) were measured by the Electro Chemi Luminescence Immuno Assay (ECLIA) method using Roche Elecsys PTH kits. The normal range was 15-65 pg/mL.

Dual X-ray absorptiometry

BMD at the lumbar spine (L1 - L4) and femoral neck area were measured by dual-energy x-ray absorptiometry (DEXA) using a lunar densitometer. BMD was automatically calculated from the bone area and expressed absolutely in g/cm 2 . The results are given by T-scores (number of standard deviations from the mean BMD for young sex-matched normal controls) and Z-scores (number of standard deviations from the mean BMD for age and sex-matched normal controls).


   Statistical Analysis Top


Statistical analysis was performed using SPSS 11.5 software. Quantitative results have been expressed as mean ± SD. T-test or the Mann-Whitney U test was used to compare quantitative variables in the two qualitative groups and ANOVA or the Kruskal Wallis test was used in more than two groups. Pearson test and Spearman's rho test were used to assess the correlation of the two quantitative variables. P-values <0.05 were considered as statistically significant.


   Results Top


The study subjects included 72 HD patients, of whom 29 (40.3%) were female and 43 (59.7%) were male. The demographic and biochemical data, measured in all the patients, are shown in [Table 1]. The cause of kidney disease in the study patients included: polycystic kidney disease in one patient, glomerulonephritis in five patients, hypertensive nephropathy in 35 patients and unknown etiology in 31 patients. None of the patients had diabetic nephropathy.
Table 1: Demographic features and biochemical markers in the study patients (mean ± SD).

Click here to view


There was no significant difference between the two genders among variables such as age, BMI, duration on dialysis, serum leptin, I-PTH, Ca, P, BAP, albumin as well as BMD of the femur neck and lumbar spine.

The leptin levels were higher in women compared with the levels in men (22.3 ± 19.6 vs 20.8 ± 23), but this difference was not significant. The correlation between serum leptin levels and other variables in the entire study group and in both genders are shown in [Table 2].
Table 2: Correlation between serum leptin levels and variables in patients.

Click here to view


Analysis showed that serum leptin levels had a positive correlation with the serum Ca levels (Spearman's rho test r = 0.659 and P = 0.01) and a negative correlation with the serum albumin levels only in women (r = -0.461 and P = 0.01). There was no correlation between serum leptin levels and age, BMI, duration on dialysis, BMD and serum levels of I-PTH, BAP and P for the entire patient group or for each gender separately [Table 3].
Table 3: Serum leptin levels in patient groups based on clinical and serum biochemistry characteristics (P-value).

Click here to view


The serum leptin levels were significantly lower in women with PTH >300 pg/mL when compared with patients whose PTH was between 100 and 300 pg/mL (86 ± 85 vs 47 ± 48) (Mann-Whitney test, P = 0.011). Similarly, women with BAP <300 IU/L had significantly higher serum leptin levels in comparison with those with BAP between 300 and 600 IU/L (Mann-Whitney test, P = 0.024). Also, women with Ca levels <8.5 mg/dL had significantly lower serum leptin levels than those with Ca between 8.5 and 10.5 mg/dL (Mann-Whitney test, P = 0.011).

There was no significant correlation between leptin levels and etiology of ESRD. Among the study patients, only five (6.9%) had received corticosteroids earlier. The serum leptin levels were significantly higher in female patients who had a history of having received corticosteroid therapy (Mann-Whitney test, P = 0.053).


   Discussion Top


Our results showed that leptin levels were higher (20.8 ± 23 ng/dL) in males (normal value 0.5-15 ng/dL), while the level was in the normal range in women (22.3 ± 19.6 ng/mL; normal, 2-70 ng/mL). Yilmaz et al [30] showed that the serum leptin levels were higher by more than two-fold in women than in men.

The BMD Z- and T-scores were higher in men than in women at all sites, but the differences were not significant. In an earlier study, it was found that the BMD Z-score was higher in women than in men at all sites; the difference at the neck of the femur was statistically significant. [31]

In this study, the duration on dialysis was longer in women (5.3 ± 3.3 vs 4.9 ± 3.5 years) (the difference was not statistically significant). This finding was similar to the findings of Ghazali et al, [31] and Yilmaz et al. [30]

In the present study, we found a positive correlation between leptin levels and serum Ca, although the BMD did not show any correlation with leptin levels. These findings show that leptin levels do not have a direct impact on bone mass in HD patients, although leptin has an influence on Ca levels; this is perhaps due to the osteogenic effects of leptin in osteoblasts, osteoclasts and chondrocytes. [6],[7],[8] Małyszko et al,[32] in their study, have reported that BMD and bone metabolism are not related to leptin levels in patients on HD and peritoneal dialysis. Two recent studies have reported an inverse relationship between leptin, bone mass and PTH in HD patients. [33],[34]

Results of some other studies are contradictory to the findings of our study; two studies found that leptin levels directly correlated with the BMD, total body weight, BMI and fat mass in HD patients with skeletal fractures. [35],[36] In the study of Ghazali et al, [31] there was a positive link between BMD and serum leptin levels in chronic HD patients, which persisted after adjustment for BMI, PTH concentration and dialysis duration.

Some previous studies surveyed the role of serum leptin levels on BMD in selected samples of men and women. Weiss et al [37] reported that leptin predicted higher BMD levels independent of age and BMI in women, but not in men. Some other studies have supported the current findings in women. [10],[11],[12] In addition, Pasco et al [10] recently reported that in non-obese Australian women, there was a positive correlation between bone mass and serum leptin levels, which was independent of body weight and fat mass. Two studies in men found an inverse association, [14],[17],[20] while four others reported no such association. [4],[18],[20],[27] The absence of correlation between serum leptin levels and bone density in our study and in other studies may be caused by leptin resistance. [30],[38],[39] We also found no correlation between serum leptin and serum I-PTH levels. Kokot et al [40] suggested that PTH could have a negative effect on serum leptin concentration in HD patients.

As reported by Yilmaz et al, [30] BAP had no correlation with leptin. This is in accordance with the findings of the Mayo Clinic Cohort, [14] and some other studies, [31],[33],[34] and suggests that leptin might be implicated in low bone turnover.

Sato et al [20] found that there was an inverse correlation between serum leptin concentrations and biochemical markers of bone formation in 221 Japanese men. Ducy et al [5] demonstrated an inhibitory effect of leptin on bone formation in mice.

Our results are similar to the results of Merabet et al, [39] who showed that there was no association between leptin accumulation and duration on HD.

In conclusion, our study shows that serum leptin concentrations did not have any correlation with BMD and markers of bone formation. However, serum leptin levels showed a positive correlation with calcium levels.

 
   References Top

1.Ahima RS, Flier JS. Leptin Annu Rev Physiol 2000;62:413-37.  Back to cited text no. 1
    
2.Cinti S, Frederich RC, Zingaretti MC, De Matteis R, Flier JS, Lowell BB. Immunohistochemical localization of leptin and uncoupling protein in white and brown adipose tissue. Endocrinology 1997;138:797-804.  Back to cited text no. 2
[PUBMED]    
3.Whipple T, Sharkey N, Demers L, Williams N. Leptin and the skeleton. Clin Endocrinol 2002; 57:701-11.  Back to cited text no. 3
[PUBMED]    
4.Lindberg JS, Moe SM. Osteoporosis in end-stage renal disease. Semin Nephrol 1999;19: 115-22.  Back to cited text no. 4
[PUBMED]    
5.Yilmaz A, Nur N, Turgut B. Leptin and bone mineral density in haemodialysis patients. Ann Acad Med Singapore 2009;38:374-4.  Back to cited text no. 5
[PUBMED]    
6.Reseland JE, Syversen U, Bakke I, et al. Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization. J Bone Miner Res 2001; 16:1426-33.  Back to cited text no. 6
[PUBMED]    
7.Thomas T, Gori F, Khosla S, Jensen MD, Burguera B, Riggs BL. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology 1999;140:1630-8.  Back to cited text no. 7
[PUBMED]    
8.Cornish J, Callon KE, Bava U, et al. Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol 2002;175:405-15.  Back to cited text no. 8
[PUBMED]    
9.Reid IR, Comish J. Direct actions of leptin on bone remodeling. Calcif Tissue Int 2004;74: 313-6.   Back to cited text no. 9
[PUBMED]    
10.Ruhl CE, Everhart JE. Relationship of serum leptin concentration with bone mineral density in the United States population. J Bone Miner Res 2002;17:1896-903.  Back to cited text no. 10
[PUBMED]    
11.Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: A central control of bone mass. Cell 2000;100:197-207.  Back to cited text no. 11
[PUBMED]    
12.Pasco JA, Henry MJ, Kotowicz MA, et al. Serum leptin levels are associated with bone mass in nonobese women. J Clin Endocrinol Metab. 2001 May;86(5):1884-7.  Back to cited text no. 12
    
13.Yamauchi M, Sugimoto T, Yamaguchi T, et al. Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women. Clin Endocrinol (Oxf). 2001 Sep;55(3):341-7.  Back to cited text no. 13
    
14.Blain H, Vuillemin A, Guillemin F, et al. Serum leptin level is a predictor of bone mineral density in postmenopausal women. J Clin Endocrinol Metab. 2002 Mar;87(3):1030-5.  Back to cited text no. 14
    
15.Schett G, Kiechl S, Bonora E, et al. Serum leptin level and the risk of nontraumatic fracture. Am J Med 2004;117:952-6.   Back to cited text no. 15
[PUBMED]    
16.Thomas T, Burguera B, Melton LJ 3rd, et al. Role of serum leptin, insulin, and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women. Bone 2001;29:114-20.  Back to cited text no. 16
[PUBMED]    
17.Roux C, Arabi A, Porcher R, Garnero P. Serum leptin as a determinant of bone resorption in healthy postmenopausal women. Bone 2003;33:847-52.  Back to cited text no. 17
[PUBMED]    
18.Blum M, Harris SS, Must A, et al. Leptin, body composition and bone mineral density in premenopausal women. Calcif Tissue Int 2003;73:27-32.  Back to cited text no. 18
[PUBMED]    
19.Morberg CM, Tetens I, Black E, et al. Leptin And bone mineral density: A cross-sectional study in obese and nonobese men, J Clin Endocrinol Metab 2003;88:5795-800.  Back to cited text no. 19
    
20.Sun AJ, Jing T, Heymsfield SB, Phillips GB. Relationship of leptin and sex hormones to bone mineral density in men. Acta Diabetol 2003;40 Suppl 1:S101-5.  Back to cited text no. 20
[PUBMED]    
21.Kontogianni MD, Dafni UG, Routsias JG, Skopouli FN. Blood leptin and adiponectin as possible mediators of the relation between fat mass and BMD in perimenopausal women. J Bone Miner Res 2004;19:546-51.   Back to cited text no. 21
[PUBMED]    
22.Sato M, Takeda N, Sarui H, et al. Association between serum leptin concentrations and bone mineral density, and biochemical markers of bone turnover in adult men. J Clin Endocrinol Metab 2001;86:5273-6.  Back to cited text no. 22
    
23.Iwamoto I, Douchi T, Kosha S, Murakami M, Fujino T, Nagata Y. Relationships between serum leptin level and regional bone mineral density, bone metabolic markers in healthy women. Acta Obstet Gynecol Scand 2000;79: 1060-4.  Back to cited text no. 23
[PUBMED]    
24.Martini G, Valenti R, Giovani S, Franci B, Campagna S, Nuti R. Influence of insulin-like growth factor-1 and leptin on bone mass in healthy postmenopausal women. Bone 2001; 28:113-7.  Back to cited text no. 24
[PUBMED]    
25.Thomas T, Burguera B. Is leptin the link between fat and bone mass? J Bone Miner Res 2002;17:1563-9.  Back to cited text no. 25
[PUBMED]    
26.Scariano JK, Garry PJ, Montoya GD, Chandani AK, Wilson JM, Baumgartner RN. Serum leptin levels, bone mineral density and osteoblast alkaline phosphatase activity in elderly men and women. Mech Ageing Dev 2003;124: 281-6.  Back to cited text no. 26
[PUBMED]    
27.Zoico E, Zamboni M, Adami S, et al. Relationship between leptin levels and bone mineral density in the elderly. Clin Endocrinol 2003; 59:97-103.  Back to cited text no. 27
[PUBMED]    
28.Abou Samra R, Baba NH, Torbay N, Dib L, El-Hajj Fuleihan G. High plasma leptin is not associated with higher bone mineral density in insulin-resistant premenopausal obese women. J Clin Endocrinol Metab 2005;90:2588-94.  Back to cited text no. 28
[PUBMED]    
29.Dennison EM, Syddall HE, Fall CH, et al. Plasma leptin concentration and change in bone density among elderly men and women: The Hertfordshire Cohort Study. Calcif Tissue Int 2004;74:401-6.  Back to cited text no. 29
[PUBMED]    
30.Ghazali A, Grados F, Oprisiu R, et al. Bone mineral density directly correlates with elevated serum leptin in haemodialysis patients. Nephrol Dial Transplant 2003;18:1882-90.  Back to cited text no. 30
[PUBMED]    
31.Malyszko J, Malyszko JS, Bondyra Z, Wolczyñski S, Lebkowska U, My?liwiec M. Bone mineral density and bone metabolism are not related to leptin in hemodialyzed and peritoneally dialyzed uremic patients. Med Sci Monit 2004;10 Suppl 3:115-9.  Back to cited text no. 31
    
32.Coen G, Ballanti P, Fischer MS, et al. Serum leptin in dialysis renal osteodystrophy. Am J Kidney Dis 2003;42:1036-42.  Back to cited text no. 32
[PUBMED]    
33.Mallamaci F, Tripepi G, Zoccali C. Leptin in end stage renal disease (ESRD): A link between fat mass, bone and the cardiovascular system. J Nephrol 2005;18:464-8.   Back to cited text no. 33
    
34.Spiegelman BM, Flier JS. Adipogenesis and obesity: Rounding out the big picture. Cell 1996;87:377-89.   Back to cited text no. 34
[PUBMED]    
35.Fontán MP, Rodríguez-Carmona A, Cordido F, García-Buela J. Hyperleptinemia in uremic patients undergoing conservative management, peritoneal dialysis, and hemodialysis: A comparative analysis. Am J Kidney Dis 1999; 34:824-31.  Back to cited text no. 35
    
36.Weiss LA, Barrett-Connor E, von Mühlen D, Clark P. Leptin predicts BMD and bone resorption in older women but not older men: The Rancho Bernardo study. J Bone Miner Res 2006;21:758-64.  Back to cited text no. 36
    
37.Fleet JC. Leptin and bone: Does the brain control bone biology? Nutr Rev 2000;58:209-11.   Back to cited text no. 37
    
38.Merabet E, Dagogo-Jack S, Coyne DW, et al. Increased plasma leptin concentration in end-stage renal disease. J Clin Endocrinol Metab 1997;82:847-50.  Back to cited text no. 38
    
39.Kokot F, Chudek J, Karkoszka H, Adamczak M, Wiecek A, Klimek D. Does PTH influence leptin concentration in haemodialysed uraemic patients? Nephron 1999;82:372-3.  Back to cited text no. 39
    
40.Parhami F, Tintut Y, Ballard A, Fogelman AM, Demer LL. Leptin enhances the calcification of vascular cells: Artery wall as a target of leptin. Circ Res 2001;88:954-60.  Back to cited text no. 40
    

Top
Correspondence Address:
Neda Ranjbarnovin
Research Development Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Keshavarz bulvar, Tehran
Iran
Login to access the Email id


DOI: 10.4103/1319-2442.106238

PMID: 23354190

Get Permissions




 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
   
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
   Introduction
   Material and Methods
   Statistical Analysis
   Results
   Discussion
    References
    Article Tables
 

 Article Access Statistics
    Viewed1183    
    Printed31    
    Emailed0    
    PDF Downloaded387    
    Comments [Add]    

Recommend this journal