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      Italian association of clinical endocrinologists (AME) position statement: drug therapy of osteoporosis

      case-report

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          Abstract

          Treatment of osteoporosis is aimed to prevent fragility fractures and to stabilize or increase bone mineral density. Several drugs with different efficacy and safety profiles are available. The long-term therapeutic strategy should be planned, and the initial treatment should be selected according to the individual site-specific fracture risk and the need to give the maximal protection when the fracture risk is highest (i.e. in the late life). The present consensus focused on the strategies for the treatment of postmenopausal osteoporosis taking into consideration all the drugs available for this purpose. A short revision of the literature about treatment of secondary osteoporosis due both to androgen deprivation therapy for prostate cancer and to aromatase inhibitors for breast cancer was also performed. Also premenopausal females and males with osteoporosis are frequently seen in endocrine settings. Finally particular attention was paid to the tailoring of treatment as well as to its duration.

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          The online version of this article (doi:10.1007/s40618-016-0434-8) contains supplementary material, which is available to authorized users.

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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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            Osteoporosis prevention, diagnosis, and therapy.

            (2001)
            To clarify the factors associated with prevention, diagnosis, and treatment of osteoporosis, and to present the most recent information available in these areas. From March 27-29, 2000, a nonfederal, nonadvocate, 13-member panel was convened, representing the fields of internal medicine, family and community medicine, endocrinology, epidemiology, orthopedic surgery, gerontology, rheumatology, obstetrics and gynecology, preventive medicine, and cell biology. Thirty-two experts from these fields presented data to the panel and an audience of 699. Primary sponsors were the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institutes of Health Office of Medical Applications of Research. MEDLINE was searched for January 1995 through December 1999, and a bibliography of 2449 references provided to the panel. Experts prepared abstracts for presentations with relevant literature citations. Scientific evidence was given precedence over anecdotal experience. The panel, answering predefined questions, developed conclusions based on evidence presented in open forum and the literature. The panel composed a draft statement, which was read and circulated to the experts and the audience for public discussion. The panel resolved conflicts and released a revised statement at the end of the conference. The draft statement was posted on the Web on March 30, 2000, and updated with the panel's final revisions within a few weeks. Though prevalent in white postmenopausal women, osteoporosis occurs in all populations and at all ages and has significant physical, psychosocial, and financial consequences. Risks for osteoporosis (reflected by low bone mineral density [BMD]) and for fracture overlap but are not identical. More attention should be paid to skeletal health in persons with conditions associated with secondary osteoporosis. Clinical risk factors have an important but poorly validated role in determining who should have BMD measurement, in assessing fracture risk, and in determining who should be treated. Adequate calcium and vitamin D intake is crucial to develop optimal peak bone mass and to preserve bone mass throughout life. Supplementation with these 2 nutrients may be necessary in persons not achieving recommended dietary intake. Gonadal steroids are important determinants of peak and lifetime bone mass in men, women, and children. Regular exercise, especially resistance and high-impact activities, contributes to development of high peak bone mass and may reduce risk of falls in older persons. Assessment of bone mass, identification of fracture risk, and determination of who should be treated are the optimal goals when evaluating patients for osteoporosis. Fracture prevention is the primary treatment goal for patients with osteoporosis. Several treatments have been shown to reduce the risk of osteoporotic fractures, including those that enhance bone mass and reduce the risk or consequences of falls. Adults with vertebral, rib, hip, or distal forearm fractures should be evaluated for osteoporosis and given appropriate therapy.
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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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                Author and article information

                Contributors
                +39.432.552537 , vescini.fabio@aoud.sanita.fvg.it
                roberto.serena@libero.it
                abalestrieri@ausl-cesena.emr.it
                fbandeira@gmail.com
                stefaniabonadonna@endocrinologo.eu
                valentina.camozzi@unipd.it
                scassibba@hpg23.it
                robertocesareo@libero.it
                iacopo.chiodini@policlinico.mi.it
                cmfrancucci@libero.it
                laura.gianotti@unito.it
                grimaldi.franco@aoud.sanita.fvg.it
                rinaldo.guglielmi@gmail.com
                brunomadeo@hotmail.com
                claudio.marcocci@med.unipi.it
                A.Palermo@unicampus.it
                alscill@tin.it
                edda.vignali@tin.it
                rochira.vincenzo@unimore.it
                michele.zini@asmn.re.it
                Journal
                J Endocrinol Invest
                J. Endocrinol. Invest
                Journal of Endocrinological Investigation
                Springer International Publishing (Cham )
                0391-4097
                1720-8386
                11 March 2016
                11 March 2016
                2016
                : 39
                : 807-834
                Affiliations
                [1 ]Endocrinology and Metabolic Disease Unit, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, P.le S.M. della Misericordia, 15, 33100 Udine, Italy
                [2 ]Endocrinology Service, Galeazzi Institute IRCCS, Milan, Italy
                [3 ]Unit of Endocrinology and Diabetology, Department of Internal Medicine, M. Bufalini Hospital, Cesena, Italy
                [4 ]Division of Endocrinology, Diabetes and Bone Diseases, Agamenon Magalhães Hospital, University of Pernambuco Medical School, Recife, Brazil
                [5 ]Istituto Auxologico Italiano, Milan, Italy
                [6 ]Unit of Endocrinology, Department of Medicine, University of Padova, Padua, Italy
                [7 ]Endocrinology and Diabetology, Papa Giovanni XXIII Hospital, Bergamo, Italy
                [8 ]Endocrinology, S. Maria Goretti Hospital, Latina, Italy
                [9 ]Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
                [10 ]Post Acute and Long Term Care Department, I.N.R.C.A., Ancona, Italy
                [11 ]San Pier Damiano Hospital, Villa Maria Group Care and Research, Faenza, Ravenna Italy
                [12 ]Endocrinology and Metabolic Diseases, S. Croce e Carle Hospital, Cuneo, Italy
                [13 ]Endocrinology Unit, Regina Apostolorum Hospital, Albano Laziale, Rome Italy
                [14 ]Integrated Department of Medicine, Endocrinology and Metabolism, Geriatrics, University of Modena and Reggio Emilia, Modena, Italy
                [15 ]Endocrine Unit 2, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy
                [16 ]Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy
                [17 ]Endocrinology, Casa Sollievo della Sofferenza IRCCS, San Giovanni Rotondo, Italy
                [18 ]Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy
                [19 ]Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
                [20 ]Endocrinology Unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy
                Article
                434
                10.1007/s40618-016-0434-8
                4964748
                26969462
                3ffaa366-a798-43f8-8db3-68be1794da51
                © The Author(s) 2016

                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 September 2015
                : 22 January 2016
                Categories
                Consensus Statement
                Custom metadata
                © Italian Society of Endocrinology (SIE) 2016

                osteoporosis,fracture,treatment,bisphosphonates,teriparatide,strontium ranelate,denosumab,serms,adherence,side effects,non-responder,male osteoporosis,drug-induced osteoporosis,androgen deprivation,aromatase inhibitors,length of therapy

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