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{\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;13\\\/18\\\/24\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;13\\\/18\\\/24\u0022}],\u0022ac\u0022:{\u0022spmdc;13\\\/18\\\/24\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;13\\\/18\\\/24\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EBisphosphonates provide substantial protection against fractures and strong evidence shows this protection occurs early, within weeks or months of initiation of therapy, and the benefit persists, although does not increase, over time. Other management strategies for osteoporosis discussed in this article are combinations of drugs that further contribute to bone fragility, as well as prevention strategies such as calcium, vitamin D, and bisphosphonates.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EMetabolic Bone Disease\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EMetabolic Bone Disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EExclusive Article - For home page\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EBisphosphonates provide substantial protection against fractures and strong evidence shows this protection occurs early, within weeks or months of initiation of therapy, and the benefit persists, although does not increase, over time. The overall risk:benefit ratio of bisphosphonates is favorable at 10 years and especially to 5 years, according to Michael McClung, MD, Oregon Osteoporosis Center, Portland, Oregon, USA.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EVertebral fractures were reduced by 60% to 70%, and even in patients on long-term glucocorticoid therapy fractures were reduced by 70% by 1 year with bisphosphonates [McClung M et al. \u003Cem\u003EAm J Med\u003C\/em\u003E 2013]. Multiple vertebral fractures were reduced by 75% to 96%, hip fractures by 40% to 50%, and nonvertebral fractures by 20% to 35%.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe early benefit with the bisphosphonate risedronate in two different studies showed response as early as 6 to 12 months in nonvertebral and hip fractures, respectively [Harrington JT et al. \u003Cem\u003ECalcif Tissue Int\u003C\/em\u003E 2004; McClung MR et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2001]. An example of the persistent benefit with treatment, from the VERT-MN study with risedronate, is shown in \u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E. However, Dr. McClung noted that, while there does not appear to be improvement in Years 6 to 7, that does not mean that the bisphosphonate is not working. The benefits are persistent, but not necessarily progressive.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/18\/24\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Fracture Protection With Bisphosphonates Is Persistent\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1433019088\u0022 data-figure-caption=\u0022Fracture Protection With Bisphosphonates Is Persistent\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/18\/24\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/18\/24\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/18\/24\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13841\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-5\u0022 class=\u0022first-child\u0022\u003EFracture Protection With Bisphosphonates Is Persistent\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced from Harrington JT et al. Risedronate Rapidly Reduces the Risk for Nonvertebral Fractures in Women with Postmenopausal Osteoporosis. \u003Cem\u003ECalcif Tissue Int\u003C\/em\u003E 2004;74(2)129\u2013135. With permission from Springer-Verlag.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-6\u0022\u003EBisphosphonates are generally well tolerated and were very safe in randomized clinical trials. Some side effects that could be considered \u201cnuisance problems,\u201d said Dr. McClung, include upper gastrointestinal intolerance that was rarely seen in some 50 clinical trials but often limits acceptance and persistence of bisphosphonate treatment. Others are acute phase reaction after intravenous (IV) or high-dose oral therapy that is flu-like and short-lived; bone and muscle pain that was not seen in clinical trials and has an unknown incidence and cause; inflammatory eye problems, including uveitis and iritis; renal impairment and failure with IV therapy, that was not seen in clinical trials with careful attention to pretreatment renal function and volume status; and anaphylactic reaction that is rare with an unknown incidence [McClung M et al. \u003Cem\u003EAm J Med\u003C\/em\u003E 2013].\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EMajor safety concerns with bisphosphonates are atypical femoral fracture (AFF), atrial fibrillation, and esophageal cancer. The United States Food and Drug Administration (FDA) concluded there was no evidence for a link between bisphosphonates and atrial fibrillation, which was seen in only one of the two HORIZON studies with zoledronic acid [Black DM et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2007]. Although a series of cases of patients with esophageal cancer were reported [Wysowski DK. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009], most observational studies have reported no risk or decreased risk of esophageal cancer [McClung M et al. \u003Cem\u003EAm J Med\u003C\/em\u003E 2013; Cardwell CR et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2010]. One study reported an increased risk of esophageal cancer in patients with 10 or more prescriptions of oral bisphosphonates over 3 years, and the absolute risk was calculated to be 1 per 1000 population over 5 years [Green J et al. \u003Cem\u003EBMJ\u003C\/em\u003E 2010]. The FDA concluded there was no association between oral bisphosphonates and an increased risk of esophageal cancer. However, bisphosphonates should be avoided in patients with Barrett\u0027s esophagus.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003ERegarding AFF, in a Swedish cohort of nearly 12,800 women there was a suggestion of an increase in the absolute risk, (5 cases per 10,000 patient-years; OR, 1.3; 95% CI, 1.1 to 1.6) [Schilcher J et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011]. The risk of AFF is related to duration of bisphosphonate treatment. The risk of AFF decreased rapidly after drug withdrawal in this cohort, \u223c70% in each of the first 2 years (OR, 0.28; 95% CI, 0.21 to 0.38). In a cohort of 1,835,116 patients in the United States, the risk of duration-dependent AFF was 1.78 per 100,000 patient-years in the first 2 years of treatment and 113.1 per 100,000 patient-years during Years 8 to 9.9 of treatment [Dell RM et al. \u003Cem\u003EJ Bone Miner Res\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EIn patients with moderate fracture risk, a drug holiday of 1 to 3 years can be considered after 3 to 5 years of bisphosphonate treatment, because of its persistent protection, and the risk of AFF is reduced [Whitaker M et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2012]. However, in patients at high risk of spine fracture, continuing treatment through 10 years is justified.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003ERegarding calcium and vitamin D, a reasonable recommendation for their daily intake from food and supplements based on current evidence is 800 to 1200 mg and 800 to 2000 IU, respectively, stated Dr. McClung.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EMEDICATION-INDUCED OSTEOPOROSIS AND FRACTURES\u003C\/h2\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EMany common drugs prescribed by rheumatologists contribute to increased fracture risk (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). Mary Beth Humphrey, MD, PhD, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA, stated that more studies are needed to determine how combinations of these drugs further contribute to bone fragility, and that prevention strategies include calcium, vitamin D, and bisphosphonates are needed.\u003C\/p\u003E\n         \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/13843\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/13843\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13843\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-12\u0022 class=\u0022first-child\u0022\u003EDrugs Known to Increase Bone Fracture Risk\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EGlucocorticoid (GC) use is highest among older adults (3.5% of men aged \u226580 years; 2.7% of women aged 70 to 79 years), yet concomitant use of bisphosphonates in all patients taking a GC is low at only 8.6% [Overman RA et al. \u003Cem\u003EArthritis Care Res (Hoboken)\u003C\/em\u003E 2013]. The relative risk of hip and vertebral fracture with GC use is shown in \u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E.\u003C\/p\u003E\n         \u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/18\/24\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Risk of Hip and Vertebral Fracture With Glucocorticoid Use\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1433019088\u0022 data-figure-caption=\u0022Risk of Hip and Vertebral Fracture With Glucocorticoid Use\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/18\/24\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/18\/24\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/18\/24\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13842\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-14\u0022 class=\u0022first-child\u0022\u003ERisk of Hip and Vertebral Fracture With Glucocorticoid Use\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003En=244,000 cases and controls\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EReproduced with permission from MB Humphrey, MD, PhD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EThe American College of Rheumatology recommendations [Grossman JM et al. \u003Cem\u003EArthritis Care Res (Hoboken)\u003C\/em\u003E 2010] for postmenopausal women and men aged \u226550 taking a GC \u22653 months is bisphosphonate treatment for patients at low risk (World Health Organization Fracture Risk Assessment Score [FRAX] \u0026lt;10%) on prednisone \u22657.5 mg or moderate risk (FRAX 10% to 19%) on any GC dose, and a bisphosphonate or teriparatide for high-risk (FRAX \u0026gt;20%) patients on any GC dose. For premenopausal women with childbearing potential and men aged \u0026lt;50 years taking a GC for 1 to 3 months, there are insufficient data for a recommendation, and a bisphosphonate or teriparatide is recommended for patients taking prednisone \u0026gt;7.5 mg for \u0026gt;3 months. For premenopausal women without childbearing potential and men aged \u0026lt;50 years taking prednisone \u0026gt;5 mg for 1 to 3 months a bisphosphonate is recommended, and a bisphosphonate or teriparatide is recommended for any GC dose taken for \u0026gt;3 months.\u003C\/p\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EProton pump inhibitors have a modest relative risk of \u223c1.5 for fractures that is dose and duration dependent, which is further increased with concomitant GC use [Kwok CS et al \u003Cem\u003EBone\u003C\/em\u003E 2011; Pouwels S et al. \u003Cem\u003EOsteoporos Int\u003C\/em\u003E 2011]. Selective serotonin reuptake inhibitors were associated with a relative risk of 1.72 for fracture in a meta-analysis of 12 studies [Wu Q et al. \u003Cem\u003EOsteoporos Int\u003C\/em\u003E 2012].\u003C\/p\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EAnticonvulsant drugs are thought to increase vitamin D metabolism and alter calcium absorption, and directly inhibit osteoblasts \u003Cem\u003Ein vitro\u003C\/em\u003E. In one study of patients aged \u226550 years taking an antiepileptic drug, the adjusted OR ranged from 1.24 with clonazepam (95% CI, 1.05 to 1.47) to 1.91 with phenytoin (95% CI, 1.58 to 2.30) [Jett\u00e9 N et al. \u003Cem\u003EArch Neurol\u003C\/em\u003E 2011]. Valproic acid was not associated with an increased fracture risk (OR, 1.10; 95% CI, 0.70 to 1.72) in this study.\u003C\/p\u003E\n         \u003Cp id=\u0022p-18\u0022\u003EHeparin is associated with dose- and duration-dependent bone loss. The risk of osteoporosis was increased with long-term use of unfractionated heparin, with a fracture rate of 2% to 3%; vertebral fractures being most common. The risk of osteoporosis, although present, was substantially lower with low molecular weight heparin [Rajgopal R et al. \u003Cem\u003EThromb Res\u003C\/em\u003E 2008]. Warfarin was shown to be associated with increased fracture risk in a population-based retrospective cohort, with 12 months of treatment being an independent predictor of vertebral (p=0.009) and rib (p=0.02) fracture [Caraballo PJ et al. \u003Cem\u003EArch Intern Med\u003C\/em\u003E 1999].\u003C\/p\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EThiazolidinediones, used to treat type 2 diabetes and commonly seen in the rheumatology clinic, were shown to increase fracture risk in women but not men with long-term use in one meta-analysis [Loke YK et al. \u003Cem\u003ECMAJ\u003C\/em\u003E 2009]. At 4 years of treatment with a thiazolidinedione, treatment of \u223c50 to 100 patients induced one fracture [Dormuth CR et al. \u003Cem\u003EArch Intern Med\u003C\/em\u003E 2009]. Patients on multiple drugs may require coordination between the endocrinologist and rheumatologist.\u003C\/p\u003E\n         \u003Cp id=\u0022p-20\u0022\u003ECalcineurin inhibitors, including tacrolimus and cyclosporine, are associated with dose- and time-dependent bone loss, and \u223c46% of users will have a hip fracture compared with 20% of nonusers [Mazzantini M et al. \u003Cem\u003EClin Exp Rheumatol\u003C\/em\u003E 2007].\u003C\/p\u003E\n         \u003Cp id=\u0022p-21\u0022\u003EDr. Humphrey stated that additional studies are needed to determine how the combinations of these medications further contribute to bone fragility in patients.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/13\/18\/24.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzo6ip\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzo6ip\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzo6ip\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}