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"textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">The present study is a summary of the clinical practice guidelines on postmenopausal, glucocorticoid and male osteoporosis of the Spanish Society for Research on Bone and Mineral Metabolism (SEIOMM), performed using the methodology of evidence-based medicine. This study focuses particular attention on the problems of treating osteoporosis that have arisen in recent years, such as so-called therapeutic holidays, sequential treatment, controlling the therapeutic response and risk fracture assessment. The levels of evidence reached have been translated into grades of recommendation and are summarized in <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>. The complete version is freely available at the SEIOMM website (<a href="http://www.seiomm.org/">www.seiomm.org</a>). All committee members have expressly declared any potential conflicts of interest in the preparation of the guide.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Risk factors for fracture</span><p id="par0010" class="elsevierStylePara elsevierViewall">There are numerous factors related to the risk of bone fractures. The main risk factors are sex, age, bone mineral density (BMD), a personal history of fracture due to frailty, a first-degree family history of fracture due to frailty and low body weight (body mass index [BMI]<span class="elsevierStyleHsp" style=""></span><20<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>). Other known risk factors are various diseases and treatments (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">1,2</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion</span>: Clinical assessment combined with BMD measurement is an effective method for assessing the risk of fracture (grade A recommendation).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Bone densitometry</span><p id="par0020" class="elsevierStylePara elsevierViewall">Among the various techniques available, dual energy X-ray absorptiometry (DXA), which measures BMD, is the commonly used procedure for determining the risk of fracture.<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">3</span></a> The results are expressed in terms of T-score, which is the number of standard deviations (SD) by which the BMD value differs from that of the healthy youth population (20–29 years). The World Health Organization (WHO) has stated that a diagnosis of osteoporosis should be made when BMD is ≤−2.5<span class="elsevierStyleHsp" style=""></span>T.<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">4,5</span></a> The WHO later clarified that this value should correspond to a measurement performed in the femoral neck and using the NHANES III study as reference.<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">6</span></a> The International Society for Clinical Densitometry,<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">7</span></a> however, considers that the diagnosis can be established when this value of −2.5<span class="elsevierStyleHsp" style=""></span>T is found in any of the following three locations: lumbar spine, total hip or femoral neck. The WHO also defined the conditions of normality, osteopenia (low bone mass) and established or severe osteoporosis (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion:</span> The measurement of BMD in the proximal femur and lumbar spine using DXA is a useful test for assessing the risk of fracture (grade A recommendation).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Bone remodeling markers</span><p id="par0030" class="elsevierStylePara elsevierViewall">Bone remodeling markers provide information on bone turnover dynamics. Bone formation markers include osteocalcin, bone alkaline phosphatase and type <span class="elsevierStyleSmallCaps">I</span> procollagen carboxy-terminal and amino-terminal propeptides (PICP and P1NP). Bone resorption markers include type <span class="elsevierStyleSmallCaps">I</span> collagen carboxy-terminal and amino-terminal telopeptides (CTX in blood and urine, and NTX in urine) and tartrate-resistant acid phosphatase 5b (TRACP 5b). Various international organizations such as the International Federation of Clinical Chemistry have recommended the use of P1NP (formation) and s-CTX (resorption) for clinical studies.<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Bone markers are not useful for diagnosing osteoporosis, although they do help assess the risk of fracture.<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">9</span></a> Their change with treatment is useful for assessing the response to the treatment (level of evidence 2a).<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">10</span></a> The change should be greater than the value of the so-called minimum significant change, calculated at 20–25% for P1NP, 30% for CTX and 37–54% for NTX.</p><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion:</span> Systematic measurement of bone markers to diagnose patients with osteoporosis is not recommended but can be helpful in managing the therapeutic response (grade B recommendation).</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conventional radiology</span><p id="par0045" class="elsevierStylePara elsevierViewall">Conventional radiology is not a sensitive or specific method for assessing changes in bone mass.<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">5</span></a> However, the procedure is essential for identifying fractures. For the vertebrae, the diagnosis requires a reduction of at least 20–25% in vertebral body height (see the Genant method<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">11</span></a> in the complete version of the guidelines). Slight reductions can be confused with deformities of other origins (osteoarthritis).<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion:</span> Conventional radiology should be indicated to detect vertebral fractures but should not be used as a method for assessing bone mass for the diagnosis of osteoporosis (grade A recommendation).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Study protocol</span><p id="par0055" class="elsevierStylePara elsevierViewall">The study of female patients with osteoporosis should include a hemogram and a reading of elementary biochemical parameters. It is advisable to measure 25-hydroxy vitamin D (25OHD) and thyrotropin levels and perform a proteinogram. It is useful to quantify 24<span class="elsevierStyleHsp" style=""></span>h urinary calcium (hypocalciuria indicates a lack of supply or malabsorption; hypercalciuria contraindicates the administration of calcium). The advisability of measuring parathyroid hormone (PTH) levels and bone remodeling markers is debated. Patients should undergo both a BMD measurement and spinal radiography. If specific diseases are suspected as the cause of the osteoporosis (e.g., hypercortisolism, celiac disease), appropriate studies should be performed.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Risk prediction tools</span><p id="par0060" class="elsevierStylePara elsevierViewall">Various scales have been developed to assess the risk of experiencing densitometric osteoporosis and osteoporotic fractures. The scales for assessing the risk of densitometric osteoporosis do not include BMD, although the tools are useful for deciding when to perform this test.<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">13</span></a> These tools have similar abilities to predict low BMD. The easiest of the tools (the Osteoporosis Self-Assessment Tool [OST])<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">14,15</span></a> includes only age and weight, factors present in all of the other tools. To directly assess the risk of fractures, other tools have been developed, such as the Fracture Risk Assessment Tool (FRAX),<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">16</span></a> the Garvan Medical Research Institute tool<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">17</span></a> and the QFracture Index.<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">18</span></a> The three tools have similar discriminatory capacity and offer moderate performance.<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">19,20</span></a> FRAX is also designed to decide when to perform a BMD reading. Unfortunately, its adaptation to Spain has been inadequate<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">21</span></a> and it should therefore not be used.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Therapeutic decision</span><p id="par0065" class="elsevierStylePara elsevierViewall">There is no one international consensus as to when treatment should start for osteoporosis. SEIOMM considers that the following female patients should be treated:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">(1)</span><p id="par0070" class="elsevierStylePara elsevierViewall">Those who have a fracture due to frailty or a BMD<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>−2.5<span class="elsevierStyleHsp" style=""></span>T in the lumbar spine, femoral neck or total hip.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">(2)</span><p id="par0075" class="elsevierStylePara elsevierViewall">Those with osteopenia (particularly if the T is ≤−2.0) who also have factors strongly associated with a risk of fracture (e.g., hypogonadism, BMI<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>20, a family history of fractures, smoking and alcoholism, rheumatoid arthritis, type I diabetes and certain treatments such as antiestrogens).</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">(3)</span><p id="par0080" class="elsevierStylePara elsevierViewall">Those on glucocorticoid therapy.</p></li></ul></p><p id="par0085" class="elsevierStylePara elsevierViewall">Regardless of the previously mentioned standards, SEIOMM states that there are three conditions in which treatment is at the discretion of each physician:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">(a)</span><p id="par0090" class="elsevierStylePara elsevierViewall">Young women (50–60 years) with T values <−3<span class="elsevierStyleHsp" style=""></span>T.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">(b)</span><p id="par0095" class="elsevierStylePara elsevierViewall">Young women with distal radius fractures who have some other risk factor, especially if there are questions concerning the intensity of the trauma.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">(c)</span><p id="par0100" class="elsevierStylePara elsevierViewall">Women with grade 1 vertebral deformities, which are not always easy to interpret as fractures.</p></li></ul></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Performing densitometry</span><p id="par0105" class="elsevierStylePara elsevierViewall">There are no universally accepted criteria for its indication. The procedure should be considered when there are risk factors strongly associated with osteoporosis or fractures. FRAX is employed in other countries for this purpose, but the inadequate Spanish version precludes its use in Spain and, in any case, records a low number of factors. The criteria list is very long. We therefore establish only a general classification:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">(a)</span><p id="par0110" class="elsevierStylePara elsevierViewall">Diseases and treatments frequently associated with osteoporosis (e.g., rheumatoid arthritis, early menopause, hyperparathyroidism, corticosteroids, antiestrogens).</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">(b)</span><p id="par0115" class="elsevierStylePara elsevierViewall">Diseases whose association with osteoporosis or osteoporotic fracture depends on their severity (e.g., type 1 diabetes and poorly controlled hyperthyroidism, malabsorption).</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">(c)</span><p id="par0120" class="elsevierStylePara elsevierViewall">Other criteria, especially if 2 of them are met: age >65 years, BMI<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>, hereditary component, alcoholism/smoking.</p></li></ul></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Treatment</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Nonpharmacological interventions</span><p id="par0125" class="elsevierStylePara elsevierViewall">Patients should be advised to engage in physical activity, stop smoking and avoid excessive alcohol consumption. Preventing falls is important.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Calcium and vitamin D</span><p id="par0130" class="elsevierStylePara elsevierViewall">Patients treated with antiresorptive or anabolic drugs should take an appropriate amount of calcium and vitamin D (grade A recommendation).<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">22–26</span></a> Serum 25OHD levels should be above 20<span class="elsevierStyleHsp" style=""></span>ng/mL and preferably above 30<span class="elsevierStyleHsp" style=""></span>ng/mL.<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">27,28</span></a> The recommended daily dose of vitamin D is 800–1000<span class="elsevierStyleHsp" style=""></span>IU/d (its fortnightly or monthly equivalent may also be administered). The administration of large quantities of vitamin D in a single dose is not recommended (e.g., 500,000<span class="elsevierStyleHsp" style=""></span>IU/year<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">29</span></a>). In terms of calcium, the daily intake should be 1000–1200<span class="elsevierStyleHsp" style=""></span>mg/d. Achieving this amount through diet is preferable; however, if this is not possible, supplements should be added.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Calcitonin</span><p id="par0135" class="elsevierStylePara elsevierViewall">Its extended use is associated with an increased risk of cancer and is therefore not recommended.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Thiazides</span><p id="par0140" class="elsevierStylePara elsevierViewall">There are no data justifying their use in treating osteoporosis.<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">30</span></a> Their use may be considered in patients with hypercalciuria.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Estrogen therapy</span><p id="par0145" class="elsevierStylePara elsevierViewall">Effective in preventing osteoporotic fractures (level of evidence 2a). Its secondary effects have meant that it is not recommended for osteoporosis, except for women with a high risk of fracture who have no other therapeutic option.<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">31,32</span></a> For women who are treated with estrogens due to presenting a climacteric syndrome, estrogens may be considered appropriate for treating the osteoporosis.</p><p id="par0150" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion:</span> Estrogen therapy is not recommended for treating postmenopausal osteoporosis (grade A recommendation).</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Selective estrogen receptor modulators</span><p id="par0155" class="elsevierStylePara elsevierViewall">Raloxifene<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">33</span></a> (level of evidence 1a) and bazedoxifene<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">34</span></a> (level of evidence 2b) are useful for reducing vertebral fractures (by approximately 40%) but not nonvertebral fractures. Its main complication is an increased risk of deep vein thrombosis.</p><p id="par0160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion:</span> Selective estrogen receptor modulators (SERMs) are indicated for treating osteoporosis by reducing vertebral fractures (grade A recommendation).</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Tibolone</span><p id="par0165" class="elsevierStylePara elsevierViewall">Tibolone reduces fractures (level of evidence 1b), but its use is not recommended due to the risk of stroke (grade A recommendation).<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Phytoestrogens and isoflavones</span><p id="par0170" class="elsevierStylePara elsevierViewall">Isoflavones can have a favorable effect on BMD, but they are not recommended for treating osteoporosis due to a lack of data on their efficacy in fractures (grade A recommendation).</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Bisphosphonates</span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Etidronate</span><p id="par0175" class="elsevierStylePara elsevierViewall">Reduces vertebral fractures by approximately 40% but not nonvertebral fractures (level of evidence 1a) (grade A recommendation).<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">36</span></a> The drug has fallen into disuse.</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Alendronate</span><p id="par0180" class="elsevierStylePara elsevierViewall">At a dosage of 70<span class="elsevierStyleHsp" style=""></span>mg/week, alendronate decreases vertebral, nonvertebral and hip fractures by approximately 45%, 25–30% and 45–55%, respectively (level of evidence 1a).<a class="elsevierStyleCrossRefs" href="#bib0585"><span class="elsevierStyleSup">37,38</span></a> According to an extension study, patients for whom treatment is discontinued after 5 years have a greater risk of clinical vertebral fractures in the following 5 years than those who continue with the treatment.<a class="elsevierStyleCrossRefs" href="#bib0595"><span class="elsevierStyleSup">39,40</span></a> The risk of fracture, including nonvertebral, increases with increasing age and lower BMD in the femoral neck when discontinuing treatment.<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">41</span></a> Alendronate is usually well tolerated, with adverse effects<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">42</span></a> that have been reported with the other bisphosphonates in <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>.</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion:</span> By reducing vertebral, nonvertebral and hip fractures, alendronate has a grade A recommendation for treating osteoporosis.</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Risedronate</span><p id="par0190" class="elsevierStylePara elsevierViewall">Weekly doses of 35<span class="elsevierStyleHsp" style=""></span>mg decrease vertebral, nonvertebral and hip fractures by approximately 40%, 20% and 25%, respectively (level of evidence 1a).<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">44</span></a> The administration of 75<span class="elsevierStyleHsp" style=""></span>mg for two consecutive days a month is also effective.<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">45</span></a> Risedronate is well tolerated.</p><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion:</span> By reducing vertebral, nonvertebral and hip fractures, risedronate has a grade A recommendation for treating osteoporosis.</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Ibandronate</span><p id="par0200" class="elsevierStylePara elsevierViewall">This drug may be administered orally once a month (150<span class="elsevierStyleHsp" style=""></span>mg) or every 3 months intravenously (3<span class="elsevierStyleHsp" style=""></span>mg). Ibandronate decreases the risk of vertebral fracture by approximately 60%,<a class="elsevierStyleCrossRefs" href="#bib0630"><span class="elsevierStyleSup">46,47</span></a> but does not decrease nonvertebral fractures (level of evidence 1b).</p><p id="par0205" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion:</span> Ibandronate has a grade A recommendation for reducing vertebral fractures.</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Zoledronate</span><p id="par0210" class="elsevierStylePara elsevierViewall">At a dosage of 5<span class="elsevierStyleHsp" style=""></span>mg/y, zoledronate decreases vertebral, nonvertebral and hip fractures by approximately 70%, 25% and 40%, respectively (level of evidence 1b).<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">48</span></a> Women who, after 3 years of treatment, continued with the treatment for another 3 years have a vertebral fracture rate below 50% compared with those who discontinued the treatment.<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">49</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion:</span> By reducing vertebral, nonvertebral and hip fractures, risedronate has a grade A recommendation for treating osteoporosis.</p></span></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Denosumab</span><p id="par0220" class="elsevierStylePara elsevierViewall">This drug decreases the risk of vertebral, nonvertebral and hip fractures by 70%, 20% and 40%, respectively (level of evidence 1b).<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">50</span></a> A <span class="elsevierStyleItalic">post hoc</span> analysis indicated that its efficacy in reducing hip fractures was 62% greater when used at an age older than 75 years<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">51</span></a> than when used below this age (level of evidence 2b). In the 24 months following the discontinuation of the drug, a loss of the gained bone mass is observed, with subsequent stabilization at baseline values<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">52</span></a> (level of evidence 1b). Discontinuation also causes an increase in bone turnover markers to values greater than baseline, which subsequently return to normal.<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">52</span></a> When administered to patients who have previously undergone treatment with alendronate, an increase in the intensity of the antiresorptive effect is observed (level of evidence 1b).<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">53</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Denosumab is generally well tolerated, although a slight increase in the incidence of infections has been reported.<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">54</span></a> Cases of maxillary osteonecrosis and atypical femoral fractures have been reported, although the incidence rates have been low. The drug may be administered to patients with renal failure, but patients should be monitored for the possible onset of hypocalcemia (ensure an appropriate supply of calcium and vitamin D).</p><p id="par0230" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion:</span> By reducing vertebral, nonvertebral and hip fractures, denosumab has a grade A recommendation for treating osteoporosis.</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Strontium ranelate</span><p id="par0235" class="elsevierStylePara elsevierViewall">The drug reduces the incidence of vertebral and nonvertebral fractures by approximately 40% and 16%, respectively (level of evidence 1a).<a class="elsevierStyleCrossRefs" href="#bib0675"><span class="elsevierStyleSup">55,56</span></a> A <span class="elsevierStyleItalic">post hoc</span> analysis indicated that the drug reduces the incidence of hip fractures (36%) in high-risk patients (level of evidence 2b). The drug markedly increases BMD; however, part of the increase (up to 50%) is due to the absorption of radiation by the strontium deposited in the bone.</p><p id="par0240" class="elsevierStylePara elsevierViewall">The drug occasionally causes severe skin reactions. The drug increases the incidence of vascular problems, both venous (deep vein thrombosis) and arterial (myocardial infarction). The latter of these conditions means that the drug's indication is limited to patients with severe osteoporosis for whom there is no other therapeutic alternative, in the absence of poorly controlled arterial hypertension, a history of ischemic heart disease, peripheral arterial disease or cerebrovascular disease.<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">57</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion:</span> Strontium ranelate is effective in reducing vertebral and nonvertebral fractures (grade A recommendation), but its use is restricted to patients with a high risk of fracture and with no risk of cardiovascular disease.</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">PTH 1-34 (teriparatide)</span><p id="par0250" class="elsevierStylePara elsevierViewall">This drug decreases the risk of vertebral and nonvertebral fractures by 65% and 50%, respectively (level of evidence 1a).<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">58</span></a> This is the only available bone formation drug. The drug has not been studied in trials designed to assess its effect on hip fractures. It is administered in a daily subcutaneous injection for 2 years. The benefits achieved with the drug decrease after its discontinuation if it is not followed by the administration of an antiresorptive drug (level of evidence 2b).<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">59</span></a> Its tolerance is good. PTH (1-84) is still not commercially available.</p><p id="par0255" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Conclusion:</span> Teriparatide reduces fractures, both vertebral and nonvertebral (grade A recommendation).</p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Vertebroplasty and kyphoplasty</span><p id="par0260" class="elsevierStylePara elsevierViewall">These procedures are not recommended for patients with asymptomatic vertebral fractures or mild pain or in those with more than 1 year of progression. The procedures may be considered for patients with fractures of less than 6 weeks of progression and intense pain despite medical treatment and for those patients with fractures of 6 weeks to 1 year of progression and persistent pain that respond poorly to analgesics, if they present edema in magnetic resonance imaging. They can also be of use for patients who are contraindicated or have poor tolerance of analgesics. Given the cost-benefit ratio, vertebroplasty is generally preferable to kyphoplasty (grade B recommendation).</p></span></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Managing the therapeutic response</span><p id="par0265" class="elsevierStylePara elsevierViewall">Changing the treatment due to a possible inadequate response may be considered in the following circumstances<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">60</span></a>: (a) development of two successive fractures and (b) two of the following three factors coinciding: development of a new fracture, a reduction in BMD greater than the minimum significant change and a reduction in bone turnover markers lower than the minimum significant change (grade D recommendation).</p><p id="par0270" class="elsevierStylePara elsevierViewall">Before changing the therapy, the following conditions should be considered as possible causes of the inadequate response: (a) lack of vitamin D, (b) secondary forms of osteoporosis, (c) inadequate compliance, (d) tendency to fall, (e) defects in the measurement techniques, both BMD and remodeling markers, and (f) the presence of severe bone deterioration, which leads to an expectation of new fractures even though the drug is still active.</p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Treatment duration (grade D recommendation)</span><p id="par0275" class="elsevierStylePara elsevierViewall">Treatment should last as long as necessary to decrease the risk of fractures to acceptable levels.<a class="elsevierStyleCrossRefs" href="#bib0705"><span class="elsevierStyleSup">61–63</span></a> Although there is no one official definition of what is considered an acceptable level, it has been suggested that a BMD<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>−2.5<span class="elsevierStyleHsp" style=""></span>T in patients with no fractures or >−2<span class="elsevierStyleHsp" style=""></span>T in patients with 1 previous fracture (more than 3–5 years) could be an acceptable level. If the fracture is recent (less than 3–5 years), the situation is considered at risk, even if the BMD is above −2<span class="elsevierStyleHsp" style=""></span>T.</p><p id="par0280" class="elsevierStylePara elsevierViewall">The achievement of objectives should be assessed every 3–5 years. If the goals are considered achieved, the treatment may be discontinued in the manner as described later in this document. Otherwise, treatment should be continued. In this case, if a number of years have passed (approx. 6 for zoledronate and approx. 10 for alendronate, risedronate and denosumab) and it is deemed advisable to change to a drug with a different mechanism of action due to the risk of developing an atypical femoral fracture then teriparatide or, if necessary (and possible), strontium ranelate should be used.</p><p id="par0285" class="elsevierStylePara elsevierViewall">If the decision is made to discontinue treatment, then the increased risk of fracture this entails should be taken into account. This risk is small with bisphosphonates, which remain bound to the bone and can therefore be discontinued, leaving the patient untreated for a few years. The discontinuation of denosumab is followed by increased bone turnover. A mild antiresorptive agent (a SERM or a single injection of a half dose of zoledronate) should therefore be administered, at least temporarily.</p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Change of drug due to apparent lack of response (grade D recommendation)</span><p id="par0290" class="elsevierStylePara elsevierViewall">If the reason for the change is an apparent lack of response, it is advisable<a class="elsevierStyleCrossRefs" href="#bib0700"><span class="elsevierStyleSup">60,64</span></a> to (a) choose a drug that is considered to have a greater capacity to reduce fractures, (b) change an antiresorptive agent for a bone formation agent or (c) change an oral drug for an injectable one.</p></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Clinical decision algorithms</span><p id="par0295" class="elsevierStylePara elsevierViewall">The following therapeutic scenarios should be considered for selecting the drug (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>):<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">•</span><p id="par0300" class="elsevierStylePara elsevierViewall">A patient with a high vertebral fracture risk (equivalent to two or more vertebral fractures). The recommended treatment is teriparatide for 24 months, followed by a bisphosphonate or denosumab. If one does not wish to use teriparatide, one of the latter can be administered from the start.</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">•</span><p id="par0305" class="elsevierStylePara elsevierViewall">A young patient with a moderate risk of vertebral fracture and a low risk of hip fracture (no history of fractures and densitometric osteoporosis values exclusively in the spine). It is advisable to administer a SERM. This recommendation is reinforced by reports of atypical hip fracture as a long-term complication of bisphosphonates and denosumab, whose use should be delayed. Additionally, the use of a SERM overcomes problems related to dental manipulation. Alternatively, if one does not wish to use a SERM, alendronate or risedronate may be administered.</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">•</span><p id="par0310" class="elsevierStylePara elsevierViewall">A patient with other risk conditions. There are 4 drugs for this situation: alendronate, risedronate, zoledronate and denosumab. The first two are less expensive and are administered orally (zoledronate, although available as a generic, costs more due to the need for intravenous administration). The last two are administered by injection (intravenous in the case of zoledronate and subcutaneously for denosumab). The selection between the first two and the last two should be made based on the presence or absence of a number of factors that can be labeled as a whole as “restrictive factors for administering oral bisphosphonates,” such as oral intolerance, polypharmacy (comorbidity), lack of adherence or advanced age. The fewer of these factors that are present, the more advisable it is to use alendronate or risedronate; the more of these factors that are present, the more zoledronate or denosumab are advisable. The presence of a high risk of hip fractures, which is common in the elderly, can be another reason for preferring denosumab, which has been shown to be highly effective in preventing this fracture in those older than 75 years. Other circumstances that make the selection of denosumab advisable are a lack of availability of an outpatient center and a GFR<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>30–35<span class="elsevierStyleHsp" style=""></span>mL/min.</p></li></ul></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0315" class="elsevierStylePara elsevierViewall">As second-line drugs for all situations, we have ibandronate, strontium ranelate and SERMs.</p><p id="par0320" class="elsevierStylePara elsevierViewall">Finally, the concept of sequential treatment refers to conditions defined by predictable changes in the drug to be employed. <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows a sequential treatment algorithm.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Male osteoporosis</span><p id="par0325" class="elsevierStylePara elsevierViewall">The available evidence concerning treatment for male osteoporosis is scarce. The primary objective of most studies has been BMD. The results for BMD in men are similar to those observed in women, which leads us to believe that its efficacy is probably similar in terms of fractures. For this reason, it is worth establishing a drug strategy for men that is similar to that for women: (a) risedronate<a class="elsevierStyleCrossRefs" href="#bib0725"><span class="elsevierStyleSup">65,66</span></a> or alendronate<a class="elsevierStyleCrossRefs" href="#bib0735"><span class="elsevierStyleSup">67,68</span></a> (although the latter is not approved in Spain for treating male osteoporosis) for patients with no restrictive criteria for oral administration, according to the reports on postmenopausal osteoporosis; (b) zoledronate<a class="elsevierStyleCrossRefs" href="#bib0745"><span class="elsevierStyleSup">69,70</span></a> or denosumab<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">71</span></a> for patients with these criteria or more advanced age and therefore a greater risk of hip fractures; (c) teriparatide<a class="elsevierStyleCrossRefs" href="#bib0760"><span class="elsevierStyleSup">72,73</span></a> for osteoporosis with a high risk of vertebral fractures. Strontium ranelate<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">74</span></a> may be considered as a second-line drug, taking into account its limitations (grade D recommendation).</p><p id="par0330" class="elsevierStylePara elsevierViewall">The administration of calcium and vitamin D is recommended. Androgens are only justified if there is hypogonadism. Even in this case, one of the former drugs should probably be combined with androgens. When hypercalciuria is detected, the administration of thiazides should be assessed (grade D recommendation).</p></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Glucocorticoid-induced osteoporosis</span><p id="par0335" class="elsevierStylePara elsevierViewall">The drugs of choice are bisphosphonates.<a class="elsevierStyleCrossRefs" href="#bib0775"><span class="elsevierStyleSup">75–77</span></a> If the patient has several vertebral fractures, treatment with teriparatide is justified.<a class="elsevierStyleCrossRefs" href="#bib0790"><span class="elsevierStyleSup">78,79</span></a> Calcium and vitamin D should be administered. The active metabolites of vitamin D have a certain preventive action on bone loss, but there are no persuasive data on their effect in preventing fractures (grade A recommendation).<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">80</span></a></p><p id="par0340" class="elsevierStylePara elsevierViewall">Postmenopausal women and men older than 50 years who take daily doses of prednisone equal to or greater than 5<span class="elsevierStyleHsp" style=""></span>mg (or its equivalent) for more than 3 months should be treated. For premenopausal women and men younger than 50 years, treatment is indicated only if there are previous fractures, the BMD is very low or the corticosteroid dose is very high. Treatment should be maintained while the patient takes prednisone at the listed dosages. If this situation ceases but the patient meets the general criteria for undergoing antiosteoporotic treatment, this treatment should be maintained. For patients treated with corticosteroids, a densitometric checkup at shorter intervals than for patients with postmenopausal osteoporosis may be justified (grade D recommendation).</p></span><span id="sec0175" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Conflict of interests</span><p id="par0345" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>"
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2 => array:2 [
"identificador" => "sec0065"
"titulo" => "Calcitonin"
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4 => array:2 [
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"titulo" => "Bisphosphonates"
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"titulo" => "Etidronate"
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1 => array:2 [
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"titulo" => "PTH 1-34 (teriparatide)"
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"titulo" => "Vertebroplasty and kyphoplasty"
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"titulo" => "Managing the therapeutic response"
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"titulo" => "Change of drug due to apparent lack of response (grade D recommendation)"
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17 => array:2 [
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"titulo" => "Clinical decision algorithms"
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18 => array:2 [
"identificador" => "sec0165"
"titulo" => "Male osteoporosis"
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19 => array:2 [
"identificador" => "sec0170"
"titulo" => "Glucocorticoid-induced osteoporosis"
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"identificador" => "sec0175"
"titulo" => "Conflict of interests"
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"fechaRecibido" => "2015-05-31"
"fechaAceptado" => "2015-08-24"
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0 => array:4 [
"clase" => "keyword"
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1 => "Osteoporosis"
2 => "Postmenopause"
3 => "Corticosteroids"
4 => "Male"
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0 => array:4 [
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"palabras" => array:5 [
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"resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">These guidelines update issues covered in previous versions and introduce new ones that have arisen in recent years. The former refer mainly to the therapeutic developments that have been made during this time (zoledronate, denosumab, bazedoxifene), which have led to a change in the drug selection algorithm. The latter deal with therapeutic management, the description of new adverse effects (which have led to changes in therapeutic behavior patterns, as is the case with atypical fracture of the femur), treatment duration (with consideration for the so-called “therapeutic holidays”), the so-called sequential treatment and changes in treatment imposed by certain circumstances. A new algorithm has been introduced for sequential treatment. Attention has also been paid to vertebroplasty and kyphoplasty.</p></span>"
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"es" => array:2 [
"titulo" => "Resumen"
"resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La presente guía actualiza aspectos tratados en versiones anteriores, e introduce otros nuevos surgidos en los últimos años. Los primeros se refieren fundamentalmente a las novedades terapéuticas aparecidas en este tiempo (zoledronato, denosumab, bazedoxifeno), que han conducido a una modificación del algoritmo de elección del fármaco. Los segundos tienen que ver con el control terapéutico, la descripción de nuevos efectos secundarios (que han condicionado cambios en los patrones de conducta terapéutica, como es el caso de la fractura atípica de fémur), la duración del tratamiento (con la consideración de las denominadas «vacaciones terapéuticas»), los cambios de tratamiento que pueden imponer unas u otras circunstancias, y el denominado tratamiento secuencial. En relación con este último se ha introducido un nuevo algoritmo. También se han incluido consideraciones respecto a la vertebroplastia y la cifoplastia.</p></span>"
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"etiqueta" => "☆"
"nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: González-Macías J, del Pino-Montes J, Olmos JM, Nogués X, en nombre de la Comisión de Redacción de las Guías de Osteoporosis de la SEIOMM. Guías de práctica clínica en la osteoporosis posmenopáusica, glucocorticoidea y del varón. Sociedad Española de Investigación Ósea y del Metabolismo Mineral (3.ª versión actualizada 2014). Rev Clin Esp. 2015;215:515–526.</p>"
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"nota" => "<p class="elsevierStyleNotepara" id="npar0010">The names of the members of the Drafting Committee of osteoporosis guidelines are listed in <a class="elsevierStyleCrossRef" href="#sec0180">Anexo A</a>.</p>"
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"apendice" => "<p id="par0350" class="elsevierStylePara elsevierViewall">Josep Blanch Rubió, José Ramón Caeiro Rey, Jorge B. Cannata Andia, Antonio Cano Sánchez, Cristina Carbonell Abella, Luis Corral Gudino, Javier del Pino Montes, Luis del Río Barquero, Manuel Díaz Curiel, Bernardino Díaz López, Adolfo Díez Pérez, Alberto García Vadillo, Carlos Gómez Alonso, Jesús González Macías, Nuria Guañabens Gay, Federico Hawkins Carranza, Esteban Jódar Gimeno, Jorge Malouf Sierra, Ana Monegal Brancós, M. Jesús Moro Álvarez, Manuel Muñoz Torres, Xavier Nogués Solán, Joan Miquel Nolla Solé, José Manuel Olmos Martínez, Pilar Orozco López, Ramón Pérez Cano, José Luis Pérez Castrillón, Pilar Peris Bernal, J. Manuel Quesada Gómez, José Antonio Riancho Moral, Manuel Sosa Henríquez and Antonio Torrijos Eslava.</p> <p id="par0355" class="elsevierStylePara elsevierViewall">Methodology: Miguel Delgado.</p> <p id="par0360" class="elsevierStylePara elsevierViewall">Literature search: José Luis Hernández, María Rodríguez Sanz.</p>"
"etiqueta" => "Appendix A"
"identificador" => "sec0180"
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"en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Drug selection algorithm. Abbreviations: DS, digestive system; ALN, alendronate; Dmab, denosumab; BMD, bone mineral density; FN, femoral neck; RF, renal failure; PTH 1-34, teriparatide; SR, strontium ranelate; RIS, risedronate; SERMs, selective estrogen receptor modulators; ZOLE, zoledronate.</p>"
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"en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Sequential treatment algorithm. Abbreviations: DS, digestive system; ALN, alendronate; BPN, bisphosphonates; Dmab, denosumab; BMD, bone mineral density; RF, renal failure; PTH 1-34, teriparatide; SR, strontium ranelate; RIS, risedronate; SERMs, selective estrogen receptor modulators; ZOLE, zoledronate.</p>"
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"etiqueta" => "Table 1"
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"leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Abbreviation: RCT, randomized clinical trial.</p>"
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<table border="0" frame="\n
\t\t\t\t\tvoid\n
\t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Level \t\t\t\t\t\t\n
\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">1a</span> Systematic reviews of RCTs with homogeneity among the individual studies or several RCTs with similar results \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">1b</span> Individual RCT with narrow confidence interval \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">2a</span> Systematic review of cohort studies with homogeneity among the individual studies \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">2b</span> Individual cohort study or RCT of low quality \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">2c</span> “Results” research; ecological studies \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">3a</span> Systematic review of case-control studies with homogeneity among the individual studies \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">3b</span> Individual case-control study \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">4</span> Case series and low-quality cohort and case-control studies \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">5</span> Expert opinions without explicit critical assessment or based on physiology, basic research or “first principles” \t\t\t\t\t\t\n
\t\t\t\t</td></tr></tbody></table>
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0 => "xTab971647.png"
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"descripcion" => array:1 [
"en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Levels of evidence according to the Oxford Centre for evidence-based medicine for studies that assess therapy, prevention or damage.</p>"
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"identificador" => "tbl0010"
"etiqueta" => "Table 2"
"tipo" => "MULTIMEDIATABLA"
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"tabla" => array:1 [
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0 => array:2 [
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<table border="0" frame="\n
\t\t\t\t\tvoid\n
\t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendation \t\t\t\t\t\t\n
\t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study type \t\t\t\t\t\t\n
\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Consistent level 1 studies (randomized clinical trials). Consistency is defined as homogeneity (correlation) in the results of the various individual studies \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Consistent level 2 (cohort) or level 3 (case-control) studies or extrapolations of level 1 studies \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">C \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Level 4 studies (case series and low-quality cohort or case-control studies) or extrapolations of level 2 or level 3 studies \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Level 5 tests (expert opinions, inconclusive studies or inconsistency problems among them, whatever their level) \t\t\t\t\t\t\n
\t\t\t\t</td></tr></tbody></table>
"""
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0 => "xTab971643.png"
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"en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Levels of recommendation of the Oxford Centre for evidence-based medicine according to the levels of evidence.</p>"
]
]
4 => array:7 [
"identificador" => "tbl0015"
"etiqueta" => "Table 3"
"tipo" => "MULTIMEDIATABLA"
"mostrarFloat" => true
"mostrarDisplay" => false
"tabla" => array:1 [
"tablatextoimagen" => array:1 [
0 => array:2 [
"tabla" => array:1 [
0 => """
<table border="0" frame="\n
\t\t\t\t\tvoid\n
\t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">1. Factors associated with greater constancy</span> \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypogonadism \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Early menopause \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Amenorrhea \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anorexia nervosa \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Malabsorption \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rheumatoid arthritis \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diabetes (particularly type 1) \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Immobility \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Corticosteroids \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Aromatase inhibitors \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Gonadotropin-releasing hormone agonist \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">2. Factors associated with lower regularity</span> \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hyperparathyroidism \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hyperthyroidism \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Selective serotonin reuptake inhibitors \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Proton pump inhibitors \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anticonvulsants \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Calcium deficiency \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vitamin D deficiency \t\t\t\t\t\t\n
\t\t\t\t</td></tr></tbody></table>
"""
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0 => "xTab971645.png"
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"descripcion" => array:1 [
"en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Diseases and treatments that are risk factors for osteoporosis.</p>"
]
]
5 => array:7 [
"identificador" => "tbl0020"
"etiqueta" => "Table 4"
"tipo" => "MULTIMEDIATABLA"
"mostrarFloat" => true
"mostrarDisplay" => false
"tabla" => array:2 [
"leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: SD, standard deviation; BMD, bone mineral density; T-score, comparison with BMD value achieved in young reference population.</p>"
"tablatextoimagen" => array:1 [
0 => array:2 [
"tabla" => array:1 [
0 => """
<table border="0" frame="\n
\t\t\t\t\tvoid\n
\t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Diagnosis \t\t\t\t\t\t\n
\t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Criterion for BMD (T-score) \t\t\t\t\t\t\n
\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Normal \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BMD T<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>−1 SD \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Osteopenia or low bone mineral density \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BMD T<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>−1 and >−2.49 SD \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Osteoporosis \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>−2.5 SD \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe osteoporosis \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">BMD T<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>−2.5 SD<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>fracture \t\t\t\t\t\t\n
\t\t\t\t</td></tr></tbody></table>
"""
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0 => "xTab971646.png"
]
]
]
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"descripcion" => array:1 [
"en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">WHO Diagnostic Criteria for Osteoporosis.</p>"
]
]
6 => array:7 [
"identificador" => "tbl0025"
"etiqueta" => "Table 5"
"tipo" => "MULTIMEDIATABLA"
"mostrarFloat" => true
"mostrarDisplay" => false
"tabla" => array:2 [
"leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: NSAID, nonsteroidal anti-inflammatory drugs; ALN, alendronate; BP, bisphosphonates; FDA, Food and Drug Administration; GFR, glomerular filtration rate; IBAN, ibandronate; IV: intravenous; RIS, risedronate; ZOL, zoledronate.</p>"
"tablatextoimagen" => array:1 [
0 => array:2 [
"tabla" => array:1 [
0 => """
<table border="0" frame="\n
\t\t\t\t\tvoid\n
\t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type \t\t\t\t\t\t\n
\t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Comments \t\t\t\t\t\t\n
\t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommendations \t\t\t\t\t\t\n
\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Upper gastrointestinal tract \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reported with oral bisphosphonates (esophagitis and esophageal ulcers)An increase in the incidence of esophageal cancer has not been confirmed. \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Can be largely avoided if the drug is ingested properly (with a glass of water and remaining upright for the next 30 [ALN, RIS] or 60 [IBAN]<span class="elsevierStyleHsp" style=""></span>min). Oral BPs should be avoided for patients with upper gastrointestinal tract conditions (e.g., difficulty swallowing and Barrett's esophagus) \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute phase reaction \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Flu-like illness (malaise, myalgia, fever). Occurs mainly with IV BPs (25–35% of those who are treated with ZOL for the first time, decreasing in successive doses). Occurs at 24–36<span class="elsevierStyleHsp" style=""></span>h and generally disappears in 3 days. \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The administration of paracetamol (but not NSAIDs) is recommended. \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Atrial fibrillation \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Its association with BPs is debated. \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The FDA recommends that fear of its onset should not influence the prescription. \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Renal failure \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">For patients with normal GFR, IV BPs can promote the development of renal failure if not administered with caution. \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The excessively rapid administration of IV BPs (<15<span class="elsevierStyleHsp" style=""></span>min for ZOL) should be avoided, as well as the simultaneous use of potentially nephrotoxic agents (diuretic NSAIDs) and their use in dehydrated patients.Renal function should be assessed in the days following the administration of ZOL. BPs, both IV and oral, should be avoided if the GFR<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>30–35<span class="elsevierStyleHsp" style=""></span>mL/min \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypocalcemia \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IV BPs can cause hypocalcemia, especially when administered to patients with reduced GFR or vitamin D deficiency. \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinicians should ensure that vitamin D levels, calcemia and renal function are appropriate before administering BP intravenously.Calcemia should be assessed in the days following the administration of ZOL. \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Maxillary osteonecrosis \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Its risk is very low with oral BPs (1/1500–1/100,000 patients per year).<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">43</span></a> This disease is related to oral health status and dental operations \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Discontinuing BPs when faced with a dental operation is not recommended.The measurement of bone turnover markers is not recommended.If a patient with BP requires a dental operation, it should be performed, ensuring that the procedure is as noninvasive as possible.Patients with BPs should maintain good oral hygiene.Teriparatide could be useful for treating osteonecrosis. \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Atypical femur fractures \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Its incidence increases with the BP exposure time (high relative risk at 8–10 years of treatment, but low absolute risk) \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Requiring rest and, if necessary, surgery.The contralateral femur should be examined.Administering teriparatide may be considered for the treatment. \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Adverse ocular effects \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Various types of ocular inflammatory reactions have been reported with BPs. Can appear hours to years after the start of its administration (mean, 3 weeks). \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The use of BPs should be discontinued (progression is usually favorable) \t\t\t\t\t\t\n
\t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diffuse osteoarticular and muscle pain \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Is uncommon \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The use of BPs should be discontinued (the spontaneous progression is usually favorable) \t\t\t\t\t\t\n
\t\t\t\t</td></tr></tbody></table>
"""
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"en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Adverse effects of bisphosphonates.</p>"
]
]
]
"bibliografia" => array:2 [
"titulo" => "References"
"seccion" => array:1 [
0 => array:2 [
"identificador" => "bibs0005"
"bibliografiaReferencia" => array:80 [
0 => array:3 [
"identificador" => "bib0405"
"etiqueta" => "1"
"referencia" => array:1 [
0 => array:1 [
"referenciaCompleta" => "Office of the Surgeon General (US). Bone Health and Osteoporosis: A report of the surgeon general. Rockville (MD); Office of the surgeon general (US); 2004 [accessed 31.05.15]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK45513/."
]
]
]
1 => array:3 [
"identificador" => "bib0410"
"etiqueta" => "2"
"referencia" => array:1 [
0 => array:2 [
"contribucion" => array:1 [
0 => array:2 [
"titulo" => "Risk factors for falls among older adults: a review of the literature"
"autores" => array:1 [
0 => array:2 [
"etal" => false
"autores" => array:3 [
0 => "A.F. Ambrose"
1 => "G. Paul"
2 => "J.M. Hausdorff"
]
]
]
]
]
"host" => array:1 [
0 => array:2 [
"doi" => "10.1016/j.maturitas.2013.02.009"
"Revista" => array:6 [
"tituloSerie" => "Maturitas"
"fecha" => "2013"
"volumen" => "75"
"paginaInicial" => "51"
"paginaFinal" => "61"
"link" => array:1 [
0 => array:2 [
"url" => "https://www.ncbi.nlm.nih.gov/pubmed/23523272"
"web" => "Medline"
]
]
]
]
]
]
]
]
2 => array:3 [
"identificador" => "bib0415"
"etiqueta" => "3"
"referencia" => array:1 [
0 => array:2 [
"contribucion" => array:1 [
0 => array:2 [
"titulo" => "Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures"
"autores" => array:1 [
0 => array:2 [
"etal" => false
"autores" => array:3 [
0 => "D. Marshall"
1 => "O. Johnell"
2 => "H. Wedel"
]
]
]
]
]
"host" => array:1 [
0 => array:1 [
"Revista" => array:6 [
"tituloSerie" => "BMJ"
"fecha" => "1996"
"volumen" => "312"
"paginaInicial" => "1254"
"paginaFinal" => "1259"
"link" => array:1 [
0 => array:2 [
"url" => "https://www.ncbi.nlm.nih.gov/pubmed/8634613"
"web" => "Medline"
]
]
]
]
]
]
]
]
3 => array:3 [
"identificador" => "bib0420"
"etiqueta" => "4"
"referencia" => array:1 [
0 => array:1 [
"referenciaCompleta" => "Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. Geneva; World Health Organization (WHO Technical Report Series, No. 843); 1994."
]
]
]
4 => array:3 [
"identificador" => "bib0425"
"etiqueta" => "5"
"referencia" => array:1 [
0 => array:2 [
"contribucion" => array:1 [
0 => array:2 [
"titulo" => "The diagnosis of osteoporosis"
"autores" => array:1 [
0 => array:2 [
"etal" => false
"autores" => array:5 [
0 => "J.A. Kanis"
1 => "L.J. Melton 3rd."
2 => "C. Christiansen"
3 => "C.C. Johnston"
4 => "N. Khaltaev"
]
]
]
]
]
"host" => array:1 [
0 => array:2 [
"doi" => "10.1002/jbmr.5650090802"
"Revista" => array:6 [
"tituloSerie" => "J Bone Miner Res"
"fecha" => "1994"
"volumen" => "9"
"paginaInicial" => "1137"
"paginaFinal" => "1141"
"link" => array:1 [
0 => array:2 [
"url" => "https://www.ncbi.nlm.nih.gov/pubmed/7976495"
"web" => "Medline"
]
]
]
]
]
]
]
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