Serum leptin in dialysis renal osteodystrophy.
BACKGROUND
The hormone leptin is considered to have a role in the prevention of osteoporosis and probably acts on bone tissue through inhibition of osteoclasia. Its action has been attributed to interference in osteoprotegerin (OPG)/OPG-ligand equilibrium. Contradictory data also have been reported, casting doubts on the positive effect on bone mass of the hormone, at least in males. To date, the relation between serum leptin levels of dialysis patients and renal osteodystrophy, defined by histomorphometric and histodynamic parameters of bone, has not been studied.


METHODS
The study included 46 hemodialysis patients (32 men, 14 women; age, 57.2 +/- 11.4 years). A transiliac bone biopsy after double-tetracycline labeling was performed for histological, histomorphometric, and histodynamic studies. Blood samples were drawn for leptin, intact parathyroid hormone (PTH), whole PTH (PTH1-84), OPG, bone alkaline phosphatase, calcium, phosphate, 25-hydroxycholecalciferol, and calcitriol. Serum leptin was measured by means of a radioimmunoassay.


RESULTS
Eighteen patients had mixed osteodystrophy (MO); 17 patients, hyperparathyroidism; 9 patients, adynamic bone disease (ABD); and 2 patients, osteomalacia. Aluminum histochemistry results were positive in 1 patient with ABD and 1 patient with MO. A sex difference was found in serum leptin levels (48.9 +/- 38 ng/mL in women and 12.2 +/- 13.2 ng/mL in men; P < 0.0002). In the entire population, lnleptin correlated significantly with body mass index (BMI; P < 0.01). SD score (SDS) leptin (adjusted for BMI, sex, and age) correlated inversely with PTH1-84 level and osteoclastic surface (OcS/BS; P < 0.05) and had a borderline correlation with bone formation rate. Correlations between leptin levels and other parameters were enhanced in men. SDS leptin correlated inversely with OcS/BS (P < 0.01), osteoclastic number (P < 0.01), and mineral apposition rate (P < 0.01). In addition, SDS leptin had a borderline inverse correlation with osteoblast surface (P < 0.06) and significant correlation with OPG level (P < 0.05). No difference was found in serum leptin levels between histological groups.


CONCLUSIONS
The reported data confirm the finding of a positive relation between serum leptin level and BMI and greater levels in women compared with men. Serum leptin level is connected to bone resorption and also bone formation, both inversely related to serum leptin levels. The decrease in osteoclasia that accompanies increasing serum leptin levels does not seem to be related to an enhanced OPG effect because it was accompanied by decreased OPG levels. Low-turnover bone disease does not appear to be caused by increased serum leptin levels. The nature of the interrelation between serum leptin and PTH1-84 levels requires further study.
Department of Clinical Science, Second Medical Faculty, La Sapienza University, Rome, Italy. coen.gf@flashnet.it
Giorgio
G
Coen
Paola
P
Ballanti
Maria Stephanie
MS
Fischer
Alessandro
A
Balducci
Santo
S
Calabria
Luisa
L
Colamarco
Giacomo
G
Di Zazzo
Francesca
F
Lifrieri
Micaela
M
Manni
Daniela
D
Sardella
Italo
I
Nofroni
Ermanno
E
Bonucci
D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood* / Q000209:etiology / Q000473:pathology; D005260:Female; D006023:Glycoproteins; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010018:Osteomalacia / Q000097:blood; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000097:blood; D018160:Receptors, Cytoplasmic and Nuclear; D054411:Receptors, Leptin; D018124:Receptors, Tumor Necrosis Factor; D006435:Renal Dialysis / Q000009:adverse effects; D012737:Sex Factors; D013223:Statistics as Topic
D015415:Biomarkers; D006023:Glycoproteins; C515448:LEPR protein, human; D020738:Leptin; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D018160:Receptors, Cytoplasmic and Nuclear; D054411:Receptors, Leptin; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human