The aim of this study was to identify and evaluate laboratory parameters associated with normal bone mineral density (BMD) and to test if -308 tumour necrosis factor (TNF) alpha gene promoter polymorphisms could influence BMD. We performed a comparative cross-sectional study of four main groups: young healthy individuals (20-30 years); subjects aged 50 years or over with normal BMD; osteoporotic subjects aged 50 years or over; osteoporotic women with active rheumatoid arthritis. Variables assessed included anthropometric features, diet intake, lifestyle, calcium-phosphorus balance, markers of bone turnover, sexual hormones, hormones related with body mass and growth, cytokines involved in inflammation and bone turnover, and -308 TNF alpha gene promoter polymorphisms. One hundred fifty-nine subjects were evaluated. Across the four groups, zinc serum levels were higher in men as compared to women. In addition, zinc serum levels were also higher in individuals with normal BMD as compared to osteoporotic subjects. Serum calcium levels were higher in normal BMD group. On the other hand, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were significantly higher in normal bone mass postmenopausal women and men as compared to age-matched osteoporotic groups. Finally, leptin was significantly lower in men, after correcting these results for body mass index values. The remaining variables assessed had a similar distribution among the different studied groups. In our population, low serum levels of leptin and high serum levels of zinc, calcium, FSH, and LH were associated with a higher BMD.