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      State of the art in osteoporosis risk assessment and treatment

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          Abstract

          Background

          Osteoporosis constitutes a major public health problem, through its association with age-related fractures, particularly of the hip, vertebrae, distal forearm, and humerus. Over recent decades, it has evolved from being viewed as an inevitable consequence of ageing, to being recognised as a serious and eminently treatable disease.

          Materials and methods

          In this article, we review the literature pertaining to the epidemiology of osteoporosis, associated health burden, approaches to risk assessment and treatment.

          Results

          Although there is some evidence that fracture incidence has reached a plateau, or even started to decline, in the developed world, an ageing population and adoption of westernised lifestyles in transitioning populations is leading to an increasing burden of osteoporosis across the world. Whilst the clinical definition of osteoporosis has been based solely on bone mineral density, the prediction of fracture at the individual level has been improved by consideration of clinical risk factors in tools such as FRAX ®, derived from a greater understanding of the epidemiology of osteoporosis. Such advances in approaches to primary and secondary prevention of fractures, coupled with elucidation of the underlying biology, and the development of a range of highly effective antiosteoporosis medications, have enabled a step change in our ability to prevent osteoporosis-related fractures. However, there remains a substantial disparity between the number of individuals at high fracture risk and number treated globally.

          Conclusion

          Urgent work is needed at the level of health care systems, national and international policy, and in communication with patients and public, to ensure that all patients who should receive treatment for osteoporosis actually do so.

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          Most cited references75

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          Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.

          Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-microg and 40-microg parathyroid hormone groups; the respective relative risks of fracture in the 20-microg and 40-microg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46, respectively [95 percent confidence intervals, 0.25 to 0.88 and 0.25 to 0.861). As compared with placebo, the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points. Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo. Parathyroid hormone had only minor side effects (occasional nausea and headache). Treatment of postmenopausal osteoporosis with parathyroid hormone (1-34) decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated. The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects.
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            Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research.

            Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exposure to these drugs. In this report, we review studies on the epidemiology, pathogenesis, and medical management of AFFs, published since 2010. This newer evidence suggests that AFFs are stress or insufficiency fractures. The original case definition was revised to highlight radiographic features that distinguish AFFs from ordinary osteoporotic femoral diaphyseal fractures and to provide guidance on the importance of their transverse orientation. The requirement that fractures be noncomminuted was relaxed to include minimal comminution. The periosteal stress reaction at the fracture site was changed from a minor to a major feature. The association with specific diseases and drug exposures was removed from the minor features, because it was considered that these associations should be sought rather than be included in the case definition. Studies with radiographic review consistently report significant associations between AFFs and BP use, although the strength of associations and magnitude of effect vary. Although the relative risk of patients with AFFs taking BPs is high, the absolute risk of AFFs in patients on BPs is low, ranging from 3.2 to 50 cases per 100,000 person-years. However, long-term use may be associated with higher risk (∼100 per 100,000 person-years). BPs localize in areas that are developing stress fractures; suppression of targeted intracortical remodeling at the site of an AFF could impair the processes by which stress fractures normally heal. When BPs are stopped, risk of an AFF may decline. Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs.
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              European guidance for the diagnosis and management of osteoporosis in postmenopausal women

              Summary Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk of fractures due to osteoporosis. Introduction The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2008. This manuscript updates these in a European setting. Methods Systematic literature reviews. Results The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk, general and pharmacological management of osteoporosis, monitoring of treatment, assessment of fracture risk, case finding strategies, investigation of patients and health economics of treatment. Conclusions A platform is provided on which specific guidelines can be developed for national use.
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                Author and article information

                Contributors
                +44 23 8077 7624 , nch@mrc.soton.ac.uk
                Journal
                J Endocrinol Invest
                J. Endocrinol. Invest
                Journal of Endocrinological Investigation
                Springer International Publishing (Cham )
                0391-4097
                1720-8386
                12 April 2019
                12 April 2019
                2019
                : 42
                : 10
                : 1149-1164
                Affiliations
                [1 ]MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD UK
                [2 ]GRID grid.430506.4, NIHR Southampton Nutrition Biomedical Research Centre, , University of Southampton and University Hospital Southampton NHS Foundation Trust, ; Southampton, UK
                [3 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, NIHR Oxford Biomedical Research Centre, , University of Oxford, ; Oxford, UK
                Article
                1041
                10.1007/s40618-019-01041-6
                6751157
                30980341
                996cc71e-546d-4cd3-bfe3-4cbe8c9cb5df
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 28 February 2019
                : 22 March 2019
                Categories
                Review Article
                Custom metadata
                © Italian Society of Endocrinology (SIE) 2019

                osteoporosis,epidemiology,risk,frax,fracture,prevention
                osteoporosis, epidemiology, risk, frax, fracture, prevention

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