leptin and Osteomalacia

Reduced bone mass and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Undoubtedly, genetics play an important role, but other factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid therapy in inflammatory bowel disease (IBD) and other lifestyle factors, such as smoking or being sedentary, may contribute to reduced bone mass. At a molecular level the proinflammatory cytokines that contribute to the intestinal immune response in IBD and probably also in coeliac disease are also known to enhance bone resorption. The discovery of the role of the receptor to activated NFkappaB (RANK) interaction with its ligand RANKL in orchestrating the balance between bone resorption and formation may link mucosal and systemic inflammation with bone remodelling, since RANK-RANKL are also involved in lymphopoiesis and T-cell apoptosis. Low circulating leptin in response to weight loss in any gastrointestinal disease may be an important factor in reducing bone mass. This report will summarize current concepts regarding gastrointestinal diseases (primarily IBD, coeliac disease and postgastrectomy states) and low bone mass and fracture.

Topics: Bone and Bones; Bone Density; Celiac Disease; Diagnosis, Differential; Gastrectomy; Gastrointestinal Diseases; Humans; Inflammatory Bowel Diseases; Leptin; Nutritional Status; Osteomalacia; Osteoporosis; Risk Factors; Vitamin D

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.. 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.. 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.. 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.

Topics: Aged; Biomarkers; Body Mass Index; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Glycoproteins; Humans; Hyperthyroidism; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Osteomalacia; Osteoprotegerin; Parathyroid Hormone; Receptors, Cytoplasmic and Nuclear; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Renal Dialysis; Sex Factors; Statistics as Topic