ABSTRACT
BACKGROUND: Postmenopausal osteoporosis is a multifactorial disease. Genetic factors play an essential role in contributing to bone mineral density (BMD) variability, which ranges from 60 to 85%. Alendronate is used as the first line of pharmacological treatment for osteoporosis; however, some patients do not respond adequately to therapy with alendronate. AIM: The aim of this work was to investigate the influence of combinations of potential risk alleles (genetic profiles) associated with response to anti-osteoporotic treatment in postmenopausal women with primary osteoporosis. METHODS: A total of 82 postmenopausal women with primary osteoporosis receiving alendronate (70 mg administered orally per week) for one year were observed. The bone mineral density (BMD; g/cm2) of the femoral neck and lumbar spine was measured. According to BMD change, patients were divided into two groups: responders and non-responders to alendronate therapy. Polymorphic variants in CYP19, ESR1, IL-6, PTHR1, TGFß, OPG and RANKL genes were determined and profiles were generated from the combination of risk alleles. RESULTS: A total of 56 subjects were responders to alendronate and 26 subjects were non-responders. Carriers of the G-C-G-C profile (constructed from rs700518, rs1800795, rs2073618 and rs3102735) were predisposed to response to alendronate treatment (p = 0.001). CONCLUSIONS: Our findings highlight the importance of the identified profiles for the pharmacogenetics of alendronate therapy in osteoporosis.
Subject(s)
Bone Density Conservation Agents , Osteoporosis , Humans , Female , Alendronate/therapeutic use , Bone Density Conservation Agents/adverse effects , Retrospective Studies , Postmenopause/genetics , Osteoporosis/drug therapy , Lumbar VertebraeABSTRACT
BACKGROUND: There is a possibility that excess body fat affects bone mass gain and may compromise skeletal health in obese children. The purpose of the study was to identify the relationship between bone mineral density (BMD) and body composition in normal weight, overweight and obese children. METHODS: This was a cross-sectional study of 6- to 11-year-old children who attended the hospital's outpatient clinic. They were apparently healthy and had no history of prematurity, low birth weight, or chronic diseases. Body mass index (BMI) was used to identify subjects as normal weight, overweight or obese. BMD and body composition were assessed by dual energy X-ray absorptiometry. The BMD values (total and lumbar spine) were compared between normal weight, overweight and obese children. Correlation coefficients were calculated, and multivariate models were performed. RESULTS: Forty-nine children were included: 16 with normal weight, 15 that were overweight and 18 with obesity; the mean age was 8.4 ± 1.7 years. All the participants had a normal BMD (> - 2 SD). BMD was higher in obese children and had a positive correlation with total and trunk lean mass in the three study groups (p < 0.001). In obese children, an inverse correlation of lumbar spine BMD (Z score) with total and trunk fat mass (p < 0.05) was identified. In the multivariate models (with the whole group), the total lean mass was the only significant variable that explained BMD variability. CONCLUSIONS: BMD in obese children was higher than that in normal weight children, which is explained by their greater lean mass and not by excess body fat. In obese children, a higher fat mass was related to a lower lumbar spine BMD. Lean mass had a direct correlation with BMD in the three study groups and was the most important predictor of BMD, reflecting the importance of strengthening the muscular system through performing physical activity and practicing a healthy lifestyle.
