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Title: Osteoporosis and vertebral fractures in ankylosing spondylitis: Current concepts and therapeutic challenges
Author: Gonzalez-Lopez, L.
Gamez-Nava, J.I.
De La Cerda-Trujillo, L.F.
Rocha-Munoz, A.D.
Zavaleta-Muniz, S.A.
Issue Date: 2013
Abstract: Osteoporosis is a frequent complication of ankylosing spondylitis (AS), with a prevalence from 19% to 62% dependent upon general factors (age, gender, smoking status), biomechanical aspects, specific character-istics of the disease (such as, a longer disease duration, presence of syndesmophytes, severe extra-articular manifestations or involvement of peripheral joints), and finally, factors related to the pro-inflammatory process with an increased in resorption by osteoclasts associated with the stimuli induced by cytokines. Differences in osteoporosis frequencies are observed when it is evaluated exclusively in the axial skeleton or when it is included the forearm in the measurement of bone mineral density (BMD). Vertebral fractures are relevant complications of osteoporosis in AS, with a prevalence varying from 16 to 32%, although these fractures are frequently misdiagnosed in the clinical practice, observed as an unexpected finding in radiographic studies. More recent diagnostic methods to detect vertebral fractures include vertebral morphometry measured with dual photon X-ray absorption (DXA), with a prevalence of osteoporotic fractures in thoracic and lumbar spine of 19%, whereas, in our center vertebral fractures in have been identified in 32%. Interestingly, a high proportion of patients with osteoporotic vertebral fractures have a normal BMD measurement in their lumbar spine being related to the presence of syndesmophytes that act as an artifact for overestimating the BMD in the lumbar spine. Osteoporotic vertebral fractures are associated with a decrease in the global functional capacity and impairment in spine mobility. A multiplicity of cytokines and other molecules participate in the genesis of osteoporosis in AS and constitute potential targets for present and future therapeutic strategies. TNF-α and interleukin-6 (IL-6) are related to a decrease in BMD in early stages of AS whereas, a decrease in serum levels of sclerostin and Dikkoppf (DKK) have been associated with syndesmophytes and the inhibition of bone mass formation. Several adipokines, including leptin and adiponectin, have been related to abnormalities in BMD in other diseases but their contribution to osteoporosis associated with AS has not yet been evaluated. Bone remodeling markers, such as type I collagen N-terminal propeptide (PINP), have been related to disease duration or age, whereas, markers of bone resorption seem to be related to low BMD, although their predictive value for the development of vertebral fractures is still unclear. Treatment with anti-TNF inhibitors is associated with an increase in BMD and an improvement in serum levels of bone remodeling markers. Since there is not enough evidence to consider that the use of anti-TNF inhibitors constitutes a sufficient strategy to decrease the risk of vertebral fractures in AS patients with osteoporosis, the addition of other therapies are therefore required including vitamin D, calcium supple-ments, antiresorptive therapy with biphosphonates or teriparatide in AS with osteoporosis or with a high risk for osteoporotic fractures. Some biphosphonates such as pamidronate offer benefits in some clinical manifestations, improving axial symptoms and peripheral arthritis. In summary, osteoporosis and vertebral fractures in AS are an exciting research area for evaluation of new therapeutic strategies oriented towards prevention and treatment of this relevant complication in AS. © 2013 Nova Science Publishers, Inc.
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