Bone supplement: proceedings of ECTS/IBMS Geneva 2005-06-20
Bone, 38, (2, Supplement 1), . (doi:10.1016/j.bone.2005.09.022).
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Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. At the age of 50 years, the remaining lifetime risk of at least one fracture of the hip, vertebral body, or distal forearm approaches 50% among the white female population and 20% among the white male population. The most frequent site of fracture is the thoracolumbar spine with prevalence rates of radiographic vertebral fracture estimated at around 25% among white women aged 50 years and over and 12% among white men of similar age. Vertebral fractures are the most common complication of osteoporosis and are associated with significant morbidity and frequently do not come to clinical attention, since, first, only one third of these fractures are associated with clinical signs, and, second, there is a high rate of failure in identifying vertebral fractures on X-rays  P.D. Delmas, L. Van de Langerijt and N.B. Watts, Underdiagnosis of vertebral fractures is a worldwide problem: the IMPACT Study, J. Bone Miner. Res. 20 (2005), pp. 557–563. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (46). Hip fractures are less frequent but are also associated with lasting disability, decreased quality of life, and a significant increase in morbidity.
Fracture incidence depends on two factors: bone strength and trauma . During the first three decades of life, fractures typically arise from high-energy trauma, such as road traffic accidents. Above the age of 64 years, around 90% of fractures result from a fall from standing height or less.
Osteoporosis and related fractures are a major health problem in the elderly population. Moreover, osteoporosis is associated with an ever-increasing financial burden on countries. There is a body of evidence showing a lack of awareness about osteoporosis and its treatment options among patients and physicians. Faced with this situation, the European Union has drawn up a plan of action for the prevention of osteoporotic fractures in the European Community. It is aimed at highlighting the key steps required to reduce the social and economic burden of osteoporosis .
Reduced bone strength is therefore an important, modifiable, determinant of fracture risk in the elderly. Bone mineral density (BMD) is a major determinant of bone strength. However, bone strength is determined by other aspects of bone structure including size, geometry, microarchitecture, and turnover. The two major causes of involutional bone loss are secondary hyperparathyroidism and reduced physical activity. In addition, estrogen deficiency predisposes to bone loss among women. Other important causes of bone loss include thinness, cigarette smoking, heavy alcohol consumption, drugs, and diseases that secondarily predispose to osteoporosis, and a family history of fracture. The use of these clinical risk factors, together with BMD measurement, as part of algorithms for the primary and secondary prevention of osteoporotic fracture is currently the subject of scrutiny by policy makers worldwide. A recent initiative proposes that effective targeting of pharmacological agents to prevent fracture might be made on the basis of algorithms using these risk predictors, to ascertain the 10-year absolute risk of fracture in an individual. The precise choice of intervention can then be determined by the cost-effectiveness of various agents in patients with the estimated absolute fracture probability.
Over the past 15 years, large double-blind, placebo-controlled trials have been performed in postmenopausal women with osteoporosis, with incident vertebral and nonvertebral fracture as a primary end point. These trials have confirmed that several agents are able to markedly reduce (by 30% to 50%) the risk of vertebral fracture. These include the bisphosphonates (etidronate, alendronate, risedronate), postmenopausal hormone replacement therapy, selective estrogen receptor modulators (raloxifene), and teriparatide. These studies also demonstrated that some agents are able to reduce the risk of hip and vertebral fractures (alendronate, risedronate). Strontium ranelate is a new antiosteoporotic agent that has recently received approval in the European Union for the treatment of postmenopausal osteoporosis to reduce the risk of vertebral and hip fractures . It is the first such agent that appears to simultaneously increase bone formation and decrease bone resorption. Results from a phase 3 clinical trial, carried out in postmenopausal women with prevalent vertebral fractures, showed that strontium ranelate significantly reduces the risk of new vertebral and new clinical vertebral fractures after 1 year and over 3 years . Results from a second large-scale phase 3 clinical trial, have shown that, over 3 years, strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women, as well as the risk of hip fracture in osteoporotic patients aged 74 years or more . In addition, this study also showed that strontium ranelate decreases the risk of vertebral fracture in patients without prevalent vertebral fracture over 3 years. In both these trials, BMD was significantly increased at the lumbar spine, femoral neck, and total hip. Strontium ranelate is well tolerated, particularly at the upper gastrointestinal level. Strontium ranelate will be useful in the first-line treatment of postmenopausal osteoporosis as well as in those intolerant to oral bisphosphonate therapy, those with a previous history of upper gastrointestinal disease, and the elderly.
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