Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis

Introduction: Osteoporosis is a highly prevalent skeletal disorder characterized by compromised bone strength, usually related to decreased bone mass and microstructural alterations of bone tissue, predisposing a person to an increased risk of fracture. As other prevalent disorders, osteoporosis is the result of a complex interplay of genetic and acquired factors. Areas covered: We provide an update of recent studies aimed at identifying the clinical and genetic factors that influence the response to drugs used to treat osteoporosis, as well as those determining the risk of two intriguing adverse effects of antiresorptives: osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). Expert opinion: Several clinical factors have been suggested to increase the risk of a poor drug response, such as advanced age and frailty. Candidate gene studies suggest that some common polymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for bisphosphonates, also influence the response to antiresorptives. However, they await for replication in large independent cohorts of patients. Similarly, some genetic and acquired factors may influence the risk of ONJ and AFF. Preliminary data suggest that the risk of suffering these adverse effects may have a polygenic basis

Serum 25-hydroxyvitamin D, parathyroid hormone, calcium intake, and bone mineral density in Spanish adults

Summary Vitamin D insufficiency is very common among Spanish community-dwelling adult subjects. A threshold of serum 25(OH)D around 30 ng/ml would be necessary for the prevention of secondary hyperparathyroidism and hip bone loss in our population, regardless of the dairy calcium ingestion. Introduction This study aims to assess 25-hydroxyvitamin D?25(OH)D?status in Spanish adult subjects and to analyze its relationships with serum PTH levels, calcium intake, and bone mineral density (BMD). Methods A total of 1811 individuals (1154 postmenopausal women and 657 men) aged 44?93 years participated in the study. Serum 25(OH)D, intact parathyroid hormone (PTH), aminoterminal propeptide of type I collagen (P1NP), and Cterminal telopeptide of type I collagen (?-CTX) levels were measured by electrochemiluminescence. BMD was determined by dual x-ray absorptiometry (DXA) at lumbar spine, femoral neck, and total hip. Results Serum 25(OH)D levels were below 10, 20, and 30 ng/ml in 5, 40, and 83%of participants, respectively. There was a significant seasonal difference in mean serum 25(OH)D, with higher levels in summer?autumn. In multivariate analysis, 25(OH)D levels were negatively correlated with age, serum PTH and creatinine, body mass index, smoking, alcohol intake, and a number of chronic diseases, but positively with dairy calcium intake. The magnitude of the difference in serum PTH according to 25(OH)D quartiles was not influenced by calcium intake. A threshold of serum 25(OH)D around 30 ng/ml was observed for serum PTH and hip BMD. Conclusions Vitamin D insufficiency is very common among Spanish community-dwelling adult subjects. A threshold of serum 25(OH)D around 30 ng/ml would be necessary for the prevention of secondary hyperparathyroidism and hip bone loss in our population, regardless of the dairy calcium ingestion. Programs to improve vitamin D status may be required in our country

Thai Osteoporosis Foundation (TOPF) position statements on management of osteoporosis

The adjusted incidence rate of hip fracture in Thailand has increased more than 31% from 1997 to 2006. Mortality and morbidity after hip fracture are also high. One year mortality after a hip fracture has increased from 18% in 1999 to 21% in 2007. The Thai Osteoporosis Foundation (TOPF) developed the first Clinical Practice Guideline (CPG) in 2002 and keeps updating the CPG since then. This latest version of the CPG is our attempt to provide comprehensive positional statement on the diagnosis, prevention and treatment of osteoporosis in Thailand. The study group who revised this position statement contains experts from the TOPF, Four Royal Colleges of Thailand, includes the Orthopaedic Surgeons, Gynecologists and Obstetricians, Physiatrists, Radiologists and 2 Associations of Endocrinologists and Rheumatologists which have involved in the management of patients with osteoporosis