Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians

• DOI: 10.7326/m15-1361
• Publication Date: 2017-05-11T16:57:48Z
• Authors: Amir Qaseem; Mary Ann Forciea; Robert M. McLean; Thomas D. Denberg
• Keywords: Haven; Guideline; Clinical Practice

Clinical Guidelines6 June 2017Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Practice Guideline Update From the American College PhysiciansFREEAmir Qaseem, MD, PhD, MHA, Mary Ann Forciea, Robert M. McLean, Thomas D. Denberg, for Guidelines Committee Physicians*Amir MHAFrom Physicians University Pennsylvania Health System, Philadelphia, Pennsylvania, Yale School Medicine, New Haven, Connecticut., MDFrom PhDFrom Physicians*Author, Article, Disclosure Informationhttps://doi.org/10.7326/M15-1361 SectionsSupplemental MaterialAboutVisual AbstractAbstractPDF ToolsAdd favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail AbstractThis article has been corrected. The original version (PDF) is appended this as a Supplement.AbstractDescription:This guideline updates 2008 (ACP) recommendations on treatment low bone density osteoporosis prevent fractures men women. This endorsed by Academy Family Physicians.Methods:The ACP based these systematic review randomized controlled trials; reviews; large observational studies (for adverse events); case reports rare events) that were published between 2 January 2005 3 2011. was updated July 2016 using machine-learning method, limited update October done. outcomes evaluated events. focuses comparative benefits risks short- long-term pharmacologic treatments density, including pharmaceutical prescriptions, calcium, vitamin D, estrogen. Evidence graded according GRADE (Grading Recommendations Assessment, Development Evaluation) system.Target Audience Patient Population:The target audience includes all clinicians. patient population women with osteoporosis.Recommendation 1:ACP recommends clinicians offer alendronate, risedronate, zoledronic acid, denosumab reduce risk hip vertebral who have known osteoporosis. (Grade: strong recommendation; high-quality evidence)Recommendation 2:ACP treat osteoporotic therapy 5 years. weak low-quality 3:ACP bisphosphonates fracture clinically recognized 4:ACP against monitoring during 5-year period 5:ACP menopausal estrogen plus progestogen raloxifene moderate-quality 6:ACP should make decision whether osteopenic 65 years age older are at high discussion preferences, profile, benefits, harms, costs medications. evidence)Osteoporosis systemic skeletal disease characterized decreasing mass microarchitectural deterioration tissue leads an increased fragility ( 1). Although can be present any bone, hip, spine, wrist most likely affected. found estimated 200 million people worldwide 2), 54 United States 3). Approximately 50% Americans than 50 4). economic impact health care system $25.3 billion per year 2025 3).Risk factors include (but not to) increasing age, female sex, postmenopause women, hypogonadism premature ovarian failure, body weight, history parental fracture, ethnic background (white persons higher black persons), previous clinical morphometric due minimal trauma (that is, fracture), rheumatoid arthritis, current smoking, alcohol intake (3 more drinks daily), mineral (BMD), D deficiency, calcium intake, hyperkyphosis, falling, immobilization 5). Another factor use certain medications, commonly implicated being glucocorticoids, anticoagulants, anticonvulsants, aromatase inhibitors, cancer chemotherapeutic drugs, gonadotropin-releasing hormone agonists 5).Osteoporosis diagnosed occurrence fracture. In patients without often BMD. Dual-energy x-ray absorptiometry (DXA) gold standard test diagnosing Results DXA scored SDs from young, healthy norm (usually female) reported T scores. For example, score –2 indicates BMD below norm. international reference description postmenopausal aged femoral neck 2.5 SD young adult mean 2). measured imperfect predictor risk, identifying less one half go fracture.Bone also classified Z score, number above expected patient's sex. –2.0 lower defined either "low chronological age" "below range age," those "within 6). Risk scores combine testing results, such FRAX (the World Organization Fracture Assessment Tool), used predict among density.Pharmacologic (alendronate, ibandronate, acid), peptide hormones (teriparatide [the 1,3,4 amino acid fragment parathyroid hormone] calcitonin), (in form therapy) selective receptor modulators (SERMs) (raloxifene women). Most aim resorption. Denosumab (a new biologic agent), dietary supplemental treatment. Bazedoxifene, SERM, recently approved U.S. Food Drug Administration (FDA) conjugated prevention osteoporosis.Guideline Focus Target PopulationThis presents additional available evidence treatments, medications agents, since publication guideline, replaces 7). Several therapies included excluded update, calcitonin, which no longer widely treatment, both etidronate pamidronate, neither FDA-approved One biologic, denosumab, human monoclonal antibody FDA osteoporosis, added guideline. Different may affect various parts differently. These sponsored Agency Healthcare Research Quality (AHRQ) 6, 8). Physicians.MethodsSystematic Review EvidenceThe conducted AHRQ's Southern California Evidence-based Center–RAND Corporation. Appendix 1 summarizes methods review, details 8).Reviewers searched databases method searches, once 2014 then specifically bisphosphonates, through 12 9). shows search methodology update. Reviewers did drug bazedoxifene 2013 26 2016. tables identified Tables 2.Appendix Table 1. Randomized, Controlled Trials Identified UpdateAppendix 2. Post hoc Subgroup Analyses Follow-up Studies UpdateGrading Developing RecommendationsThis developed ACP's (CGC) development process, paper 10). CGC accompanying 8), full report 6), when reporting Recommendations, 1).Table Grading System*Peer ReviewThe AHRQ peer-reviewed posted Web site public comments. journal. journal online comments Regents Governors, represent physician members national level.Comparative Benefits Treatment Versus Placebo Reducing Patients With OsteoporosisBisphosphonatesHigh-quality showed alendronate 11–42- 43–45), risedronate 34–36, 42, 46–77- 78), 79–85), vertebral, nonvertebral, compared placebo High-quality ibandronate reduces radiographic fractures, although insufficient determine effect 38, 86–94). Moderate-quality 95).DenosumabHigh-quality 96–108). Japanese trial its 1-year open-label extension study prevalent protected 101, 109).TeriparatideHigh-quality teriparatide nonvertebral 34, 110–120).SERMsHigh-quality women; however, it statistically significantly decrease 121–127).Bazedoxifene combination estrogens (20 mg, 0.45 mg estrogen). find trials (RCTs) had primary outcomes.Estrogen Therapy Postmenopausal WomenModerate-quality difference reduced established 40, 41, 123, 128–130). differs associated 7, 131). focused opposed newer data, osteoporosis.Calcium Vitamin DModerate-quality overall alone uncertain. 132–157), adherence low. Data efficacy reducing mixed, uncertain 129, 134–139, 142–144, 146, 148, 149, 152, 158–189- 190–209).Physical ActivityEvidence conclusively show physical activity 210–218). There effectiveness other interventions.Comparative Within Among Classes OsteoporosisEvidence superiority medication over another, within same class classes, 21, 29, 40–42, 130, 139, 156, 175, 199, 201, 208, 219–234). Network meta-analyses addressing lack head-to-head comparisons drugs mostly significant differences 235–239).Benefits Reduction Individuals RisksBone Mineral DensityModerate-quality post analysis RCT 240).FRAX AssessmentModerate-quality interaction assessed relative 75 241).Prior (Prevention vs. Treatment)Evidence because conflicting results 240, 242–244). benefited 245).AgeHigh-quality least effective they younger 246–249).SexEvidence regarding men, few relevant 28, 50–52, 82, 90, 136, 157, 166). Two RCTs D3 elderly but 136). reduction treated intramuscular injection ergocalciferol, whereas 166).Race/EthnicityHigh-quality placebo, decreases Asian 250), consistent findings studies.Glucocorticoid TreatmentModerate-quality taking glucocorticoids 30, 219).Renal InsufficiencyEvidence assessing renal function raloxifene, preventing 251–254).Harms Pharmacologic FracturesBisphosphonatesLow-quality atypical subtrochanteric issued warning 255). suggests event related duration, rate 1.78 100 000 8 256).Low-quality osteonecrosis jaw, side 257–282).The atrial fibrillation; there 126, 283–288). recent double-blind HORIZON-PFT fibrillation 9 versus 6 incidence arrhythmia (14.1% 4.2%; P = 0.02) 85). incident acute myocardial infarction (hazard ratio [HR], 1.38 [95% CI, 1.08 1.77], after cardiovascular for) median 3.6 follow-up 289). population-based cohort events, (adjusted HR, 1.55 [CI, 1.04 2.39]) congestive heart failure 1.65 1.36 1.99]) 290). contrast, meta-analysis concluded association oral intravenous bisphosphonate total stroke, infarction, death 287).High-quality mild upper gastrointestinal symptoms 83, 291–303), network 304).High-quality hypocalcemia (odds [OR], 7.22 1.81 42.7]) 81, 305). influenza-like (OR, 6.39 5.76 7.09]) 79, 306–308). secondary uveitis (1.1% 0.5% 2.1%]) episcleritis (0.1% 0.0% 0.7%]) 309).Ibandronate myalgias, cramps, limb pain 2.25 1.57 3.29]) 92, 310), effects 1.45 1.14 1.86]) 81), arthritis arthralgias 2.82 2.32 3.45]), headaches 3.18 2.57 3.97]), 12.1 516]).Evidence associate 292, 311–326).DenosumabHigh-quality 1.74 1.29 2.38]) 43, 327). infection (risk [RR], 1.26 1.01 1.57]) 328). small slight increase bacterial cellulitis (1.3% 0.6%), serious 1.5%) 109). rash/eczema 1.96 1.46 2.66]) 96, 97). FREEDOM (Fracture Evaluation every Months) confirmed events jaw 100).TeriparatideHigh-quality 3.26 3.78]) 113, 117, 329, 330), headache 1.27 1.69]) 331), hypercalcemia 12.9 10.5 16]) 116, 331, 332). Other 2.36 2.01 2.77]) hypercalciuria 2.44 2.08 2.86]) 254). cases osteosarcoma first 4 voluntary Forteo Registry safety 333), postmarketing series encompassing cases, before diagnosis 334).SERMsHigh-quality hot flashes 1.58 1.35 1.84]) 122, 335–340) thromboembolic 1.63 1.98]) 336, 341–346). Raloxifene pulmonary embolism 1.82 1.16 2.92) 341, 345, 347) cerebrovascular 1.56 342, 348–350). comparing surveillance (aged <75 y) ≥75 351).Estrogen WomenHigh-quality Women's Initiative accidents venous 352). subsequent assessment breast decreased discontinued 353). progestin invasive cancer, node-positive tumors, deaths 354).Calcium DAlthough data suggested supplementation 355). 356).Monitoring OsteoporosisThere how monitor do need regular 357–368). 365) only 10% normal mildly (T > –1.49) develop 15 years; moderate osteopenia –1.50 –1.99) advanced –2.49) year. improvement prediction major baseline 357). Overall several 358–363) even if increase.Duration TherapyLow-quality appropriate duration uncertain, high-risk benefit 242, 369–371). cumulative continuing 10 (18.9% 19%) 240). –2.5 worse stopping (11.1% 5.3%) 242). continued receive 369).The Figure provides summary considerations.Figure. Summary women.BMD density; dual-energy absorptiometry; Tool; GI gastrointestinal. Download figure PowerPoint Future ResearchMost treating further research needed men. directly needed.RecommendationsRecommendation 1: evidence)High-quality ≤ experienced fractures) beneficial loss initial fractures. Some acid) agent well clinical, fractures.Both symptoms. rash eczema. Bisphosphonates jaw. fibrillation, some Zoledronic hypocalcemia, symptoms, arthralgias, headache, uveitis.When prescribing discuss importance adherence. Factors poor inconvenience absence underlying disease, comorbid conditions, socioeconomic status.Although shown types; therefore, recommended first-line thromboembolism. Calcitonin, considered guideline.Calcium supplements regimens, regimens unclear. majority gave many D; agents considered. However, dosages carefully considered, excess dosing 221, 372–377). 355), demonstrated kidney stones 137).Recommendation 2: evidence)Although direct therapy, up Continuing reassessing therapy. (242) preexisting