Advertisement
JOGC

Guideline No. 422g: Menopause and Osteoporosis

      ABSTRACT

      Objective

      Provide strategies for improving the care of perimenopausal and postmenopausal women based on the most recent published evidence.

      Target Population

      Perimenopausal and postmenopausal women.

      Benefits, Harms, and Costs

      Target population will benefit from the most recent published scientific evidence provided via the information from their health care provider. No harms or costs are involved with this information since women will have the opportunity to choose among the different therapeutic options for the management of the symptoms and morbidities associated with menopause, including the option to choose no treatment.

      Evidence

      Databases consulted were PubMed, MEDLINE, and the Cochrane Library for the years 2002–2020, and MeSH search terms were specific for each topic developed through the 7 chapters.

      Validation Methods

      The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations).

      Intended Audience

      physicians, including gynaecologists, obstetricians, family physicians, internists, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; pharmacists; medical trainees, including medical students, residents, fellows; and other providers of health care for the target population.

      SUMMARY STATEMENTS

      • 1
        Secondary causes of bone loss should be excluded before confirming the presence of postmenopausal osteoporosis (moderate).
      • 2
        The Fracture Risk Assessment Tool (FRAX) can be used to evaluate 10-year fracture risk (high). Alternatively, the Canadian Association of Radiologists and Osteoporosis Canada (CAROC) assessment tool may be used to evaluate the 10-year fracture risk (moderate).
      • 3
        Ensure patients with postmenopausal osteoporosis receive a calcium-enriched diet (1200 mg elemental calcium daily) and adequate vitamin D supplementation, aiming for a 25-hydroxyvitamin D level of 75–125 nmol/L (30–50 ng/mL) (high).
      • 4
        Health care providers should treat all patients with osteoporosis at intermediate risk with a 10%–20% risk of major osteoporotic fracture over the next 10 years with pharmacologic therapy (high).
      • 5
        Health care providers should treat all patients at high risk of fracture (with a ≥20% risk of MOF or ≥3% risk of hip fracture over the next 10 years with pharmacologic therapy (high).
      • 6
        Health care providers should treat all patients at very high fracture risk (recent fracture within the past 12 months or multiple fragility fractures or major osteoporotic fracture risk >30% or hip fracture risk >4.5%) preferably with an anabolic agent followed by an antiresorptive agent (moderate).
      • 7
        Patients taking bisphosphonates should be considered for a bisphosphonate drug holiday after 5 years of bisphosphonate therapy, if the fracture risk is intermediate and femoral neck T-score is better than –2.5 and in the absence of prior fragility fracture (moderate).
      • 8
        Atypical femoral fractures are associated with long-term bisphosphonate therapy and are uncommon. It is important to ask about thigh or groin pain in patients on antiresorptive therapy and the antiresorptive therapy should be stopped in the presence of an atypical femoral fracture (moderate).
      • 9
        Osteonecrosis of the jaw is a rare complication of antiresorptive therapy, and the incidence seen in patients prescribed antiresorptive therapy ranges from 1 in 10 000 to 1 in 100 000 patient-years (high).
      • 10
        Romosozumab, teriparatide, or denosumab should not be stopped without replacing these agents with an antiresorptive agent in order to prevent declines in bone mineral density and bone strength following cessation of drug therapy. (high).

      RECOMMENDATIONS

      • 1
        All adults ≥65 years should be screened for increased fracture risk by clinical evaluation and bone mineral density assessment. Community-based screening in older women may be effective in reducing the incidence of hip fracture (conditional, moderate).
      • 2
        In postmenopausal women <65 years, evaluate fracture risk clinically without bone mineral density assessment (FRAX without bone mineral density). A bone mineral density assessment should be considered for patients with diseases or drugs associated with an increased risk of fracture or in the presence of a prior fragility fracture (conditional, low). If the FRAX score for MOF without bone mineral density is >10%, a bone mineral density assessment should also be considered.
      • 3
        All patients with osteoporosis should be treated. After a fragility fracture, the risk of a subsequent fracture is highest in the next 12–24 months (imminent fracture risk). Pharmacologic therapy should be initiated after a fragility fracture without delay. (strong, high).
      • 4
        Bisphosphonates may be offered to patients with osteoporosis at an intermediate risk of fracture in the absence of contraindications, ideally for up to 5 years (strong, high). Fracture risk should be revaluated after 3 to 5 years of bisphosphonate therapy, and a drug holiday should be considered (strong, moderate).
      • 5
        Denosumab may be offered for up to 10 years in patients at high or very high risk of fracture in the presence of a normal serum calcium (adjusted for albumin or ionized calcium), normal vitamin D, and estimated glomerular filtration rate (eGFR) >15 mL/min/1.73 m2. If denosumab is discontinued, it should be replaced with an alternative treatment option (strong, high).
      • 6
        Romosozumab may be offered to those at high or very high risk of fracture for up to 1 year (strong, high). After 1 year of therapy, romosozumab should be followed by an antiresorptive agent (strong, moderate). Romosozumab is contraindicated in the presence of a recent myocardial infarction or stroke or for patients with a high risk for major adverse cardiovascular events.
      • 7
        Teriparatide or abaloparatide (for up to 2 years)  may be offered to patients with a high or very high risk of fracture and should be followed by an antiresorptive agent (strong, high). Teriparatide and abaloparatide are not advised in patients with a history of cancer, radiation exposure, hypercalcemia, or hyperparathyroidism.
      • 8
        Raloxifene or bazedoxifene may be offered to postmenopausal women with an intermediate risk of fracture who are at increased risk of breast cancer and at low risk of thromboembolic disease (conditional, ungraded).
      • 9
        Menopausal hormone therapy may be given to postmenopausal women experiencing menopausal symptoms at low, intermediate, or high fracture risk if they are under the age of 60 years, with no history of breast cancer or thromboembolic disease and at a low risk of cerebrovascular or cardiovascular disease (conditional, moderate).
      • 10
        A daily weight-bearing exercise program, as well as a calcium-enriched diet with adequate vitamin D supplementation, are advised (strong, high). Limitation of alcohol intake and smoking cessation should also be emphasized (strong, moderate).

      Keywords

      ABBREVIATIONS:

      AFF: (atypical femoral fracture), BMD: (bone mineral density), CAROC: (Canadian Association of Radiologists and Osteoporosis Canada assessment tool), DXA: (dual-energy X-ray absorptiometry), eGFR: (estimated glomerular filtration rate), FN: (femoral neck), FRAX: (Fracture Risk Assessment Tool), MACE (major adverse cardiovascular events), MHT: (menopausal hormone therapy), MOF: (major osteoporotic fracture), PTH: (parathyroid hormone), TBS: (trabecular bone score)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Obstetrics and Gynaecology Canada
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      REFERENCES

        • Hopkins RB
        • Burke N
        • Von Keyserlingk C
        • et al.
        The current economic burden of illness of osteoporosis in Canada.
        Osteoporos Int. 2016; 27: 3023-3032
        • Bessette L
        • Ste-Marie LG
        • Jean S
        • et al.
        The care gap in diagnosis and treatment of women with a fragility fracture.
        Osteoporosis Int. 2008; 19: 79-86
        • Khan A
        • Fortier M
        Menopause and Oseteoporosis Working Group. Osteoporosis in menopause.
        J Obstet Gynaecol Can. 2014; 36: 839-840
        • Camacho PM
        • Petak SM
        • Binkley N
        • et al.
        American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2020 update.
        Endocr Pract. 2020; 26: 1-46
        • Eastell R
        • Rosen CJ
        • Black DM
        • et al.
        Pharmacological management of osteoporosis in postmenopausal women: An Endocrine Society* clinical practice guideline.
        J Clin Endocrinol Metab. 2019; 104: 1595-1622
        • Shoback D
        • Rosen CJ
        • Black DM
        • et al.
        Pharmacological management of osteoporosis in postmenopausal women: An endocrine society guideline update.
        J Clin Endocrinol Metab. 2020; 105: 587-594
        • Shepstone L
        • Lenaghan E
        • Cooper C
        • et al.
        Screening in the community to reduce fractures in older women (SCOOP): A randomised controlled trial.
        Lancet. 2018; 391: 741-747
        • Rubin KH
        • Rothmann MJ
        • Holmberg T
        • et al.
        Effectiveness of a two-step population-based osteoporosis screening program using FRAX: The randomized risk-stratified osteoporosis strategy evaluation (ROSE) study.
        Osteoporosis Int. 2018; 29: 567-578
        • Merlijn T
        • Swart KM
        • Schoor NM
        • et al.
        The effect of a screening and treatment program for the prevention of fractures in older women: A randomized pragmatic trial.
        J Bone Miner Res. 2019; 34: 1993-2000
        • Viswanathan M
        • Reddy S
        • Berkman N
        • et al.
        Screening to prevent osteoporotic fractures.
        JAMA. 2018; 319: 2532
        • Kanis JA
        • McCloskey E
        • Johansson H
        • et al.
        FRAX® with and without bone mineral density.
        Calcif Tissue Int. 2012; 90: 1-13
        • Kanis JA
        • Johansson H
        • Oden A
        • et al.
        Worldwide uptake of FRAX.
        Arch Osteoporos. 2014; 9: 166
        • Leslie WD
        • Majumdar SR
        • Lix LM
        • et al.
        High fracture probability with FRAX usually indicates densitometric osteoporosis: Implications for clinical practice.
        Osteoporosis Int. 2012; 23: 391-397
        • Nguyen ND
        • Frost SA
        • Center JR
        • et al.
        Development of prognostic nomograms for individualizing 5-year and 10-year fracture risks.
        Osteoporosis Int. 2008; 19: 1431-1444
        • Ahmed LA
        • Nguyen ND
        • Bjørnerem Å
        • et al.
        External validation of the garvan nomograms for predicting absolute fracture risk: The tromsø study.
        PLoS ONE. 2014; 9e107695
        • Crandall CJ
        • Larson J
        • LaCroix A
        • et al.
        Predicting fracture risk in younger postmenopausal women: Comparison of the garvan and FRAX risk calculators in the women's health initiative study.
        J Gen Intern Med. 2019; 34: 235-242
        • Hoff M
        • Meyer HE
        • Skurtveit S
        • et al.
        Validation of FRAX and the impact of self-reported falls among elderly in a general population: The HUNT study.
        Norway. Osteoporos Int. 2017; 28: 2935-2944
        • Sambrook PN
        • Cameron ID
        • Chen JS
        • et al.
        Influence of fall related factors and bone strength on fracture risk in the frail elderly.
        Osteoporos Int. 2007; 18: 603-610
        • Mccloskey EV
        • Odén A
        • Harvey NC
        • et al.
        A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX.
        J Bone Miner Res. 2016; 31: 940-948
        • Su Y
        • Leung J
        • Hans D
        • et al.
        The added value of trabecular bone score to FRAX® to predict major osteoporotic fractures for clinical use in Chinese older people: The Mr. OS and Ms. OS cohort study in Hong Kong.
        Osteoporosis International. 2017; 28: 111-117
        • Leslie WD
        • Lix LM.
        Simplified 10-year absolute fracture risk assessment: A comparison of men and women.
        J Clin Densitom. 2010; 13: 141-146
        • Kendler DL
        • Marin F
        • Zerbini CAF
        • et al.
        Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial.
        Lancet. 2018 Jan 20; 391: 230-240
        • Saag KG
        • Petersen J
        • Brandi ML
        • et al.
        Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis.
        N Engl J Med. 2017 Oct 12; 377: 1417-1427
        • Deloumeau A
        • Moltó A
        • Roux C
        • Briot K.
        Determinants of short term fracture risk in patients with a recent history of low-trauma non-vertebral fracture.
        Bone. 2017 Dec; 105: 287-291
        • Lyles KW
        • Colón-Emeric CS
        • Magaziner JS
        • et al.
        Zoledronic acid and clinical fractures and mortality after hip fracture.
        N Engl J Med. 2007; 357: 1799-1809
        • Black DM
        • Schwartz AV
        • Ensrud KE
        • et al.
        Effects of continuing or stopping alendronate after 5 years of treatment.
        JAMA. 2006; 296: 2927
        • Paggiosi MA
        • Peel N
        • McCloskey E
        • et al.
        Comparison of the effects of three oral bisphosphonate therapies on the peripheral skeleton in postmenopausal osteoporosis: The TRIO study.
        Osteoporosis Int. 2014; 25: 2729-2741
        • Adler RA
        • El-Hajj Fuleihan G
        • Bauer DC
        • et al.
        Managing osteoporosis in patients on long-term bisphosphonate treatment: Report of a task force of the American Society for Bone and Mineral Research.
        J Bone Miner Res. 2016; 31: 16-35
        • Bone HG
        • Wagman RB
        • Brandi ML
        • et al.
        10 years of denosumab treatment in postmenopausal women with osteoporosis: Results from the phase 3 randomised FREEDOM trial and open-label extension.
        Lancet Diabetes Endocrinol. 2017; 5: 513-523
        • Black DM
        • Rosen CJ.
        Postmenopausal osteoporosis.
        N Engl J Med. 2016; 374: 254-262
        • Black DM
        • Bauer DC
        • Schwartz AV
        • et al.
        Continuing bisphosphonate treatment for osteoporosis — For whom and for how long?.
        N Engl J Med. 2012; 366: 2051-2053
        • Iqbal SM
        • Qamar I
        • Zhi C
        • et al.
        Role of bisphosphonate therapy in patients with osteopenia: A systemic review.
        Cureus. 2019;
        • Reid IR
        • Horne AM
        • Mihov B
        • et al.
        Fracture prevention with zoledronate in older women with osteopenia.
        N Engl J Med. 2018; 379: 2407-2416
        • Pols HAP
        • Felsenberg D
        • Hanley DA
        • et al.
        Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: Results of the fosit study.
        Osteoporosis Int. 1999; 9: 461-468
        • Cummings SR.
        Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures:results from the fracture intervention trial.
        JAMA. 1998; 280: 2077
        • Siris ES
        • Simon JA
        • Barton IP
        • et al.
        Effects of risedronate on fracture risk in postmenopausal women with osteopenia.
        Osteoporosis Int. 2008; 19: 681-686
        • Adams AL
        • Adams JL
        • Raebel MA
        • et al.
        Bisphosphonate drug holiday and fracture risk: A population-based cohort study.
        J Bone Miner Res. 2018; 33: 1252-1259
        • Naylor KE
        • Jacques RM
        • Paggiosi M
        • et al.
        Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: The TRIO study.
        Osteoporosis Int. 2016; 27: 21-31
        • Boonen S
        • Lips P
        • Bouillon R
        • et al.
        Need for additional calcium to reduce the risk of hip fracture with vitamin D supplementation: Evidence from a comparative metaanalysis of randomized controlled trials.
        J Clin Endocrinol Metab. 2007; 92: 1415-1423
        • Weaver CM
        • Alexander DD
        • Boushey CJ
        • et al.
        Calcium plus vitamin D supplementation and risk of fractures: An updated meta-analysis from the National Osteoporosis Foundation.
        Osteoporosis Int. 2016; 27: 367-376
        • Jackson RD
        • Lacroix AZ
        • Gass M
        • et al.
        Calcium plus vitamin d supplementation and the risk of fractures.
        N Engl JMed. 2006; 354: 669-683
        • Kanis JA
        • Johansson H
        • Johnell O
        • et al.
        Alcohol intake as a risk factor for fracture.
        Osteoporos Int. 2005; 16: 737-742
        • Kanis JA
        • Johnell O
        • Oden A
        • et al.
        Smoking and fracture risk: a meta-analysis.
        Osteoporos Int. 2005; 16: 155-162
        • Kelley GA
        • Kelley KS
        • Kohrt WM.
        Effects of ground and joint reaction force exercise on lumbar spine and femoral neck bone mineral density in postmenopausal women: a meta-analysis of randomized controlled trials.
        BMC Musculoskelet Disord. 2012; 13: 177
        • Kelley GA
        • Kelley KS
        • Tran ZV.
        Exercise and lumbar spine bone mineral density in postmenopausal women: a meta-analysis of individual patient data.
        J Gerontol A Biol Sci Med Sci. 2002 Sep; 57: M599-M604
        • Bischoff-Ferrari HA
        • Dietrich T
        • Orav EJ
        • et al.
        Positive association between 25-hydroxy vitamin d levels and bone mineral density: A population-based study of younger and older adults.
        Am J Med. 2004; 116: 634-639
        • Holick MF
        • Siris ES
        • Binkley N
        • et al.
        Prevalence of vitamin D inadequacy among postmenopausal north american women receiving osteoporosis therapy.
        J Clin EndocrinolMetab. 2005; 90: 3215-3224
        • Carmel AS
        • Shieh A
        • Bang H
        • et al.
        The 25(OH)D level needed to maintain a favorable bisphosphonate response is ≥33 ng/mL.
        Osteoporosis Int. 2012; 23: 2479-2487
        • Hansen KE
        • Johnson RE
        • Chambers KR
        • et al.
        Treatment of vitamin D insufficiency in postmenopausal women.
        JAMA Intern Med. 2015; 175: 1612
        • Sanders KM
        • Stuart AL
        • Williamson EJ
        • et al.
        Annual high-dose oral vitamin D and falls and fractures in older women.
        JAMA. 2010; 303: 1815
        • Hanley DA
        • Cranney A
        • Jones G
        • et al.
        Vitamin D in adult health and disease: A review and guideline statement from Osteoporosis Canada.
        CMAJ. 2010; 182: E610-E6E8
        • Rizzoli R
        • Stevenson JC
        • Bauer JM
        • et al.
        The role of dietary protein and vitamin D in maintaining musculoskeletal health in postmenopausal women: A consensus statement from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).
        Maturitas. 2014; 79: 122-132
        • Vestergaard P
        • Schwartz K
        • Pinholt EM
        • et al.
        Gastric and esophagus events before and during treatment of osteoporosis.
        Calcif Tissue Int. 2010; 86: 110-115
        • Evenepoel P
        • Cunningham J
        • Ferrari S
        • et al.
        European consensus statement on the diagnosis and management of osteoporosis in chronic kidney disease stages G4–G5d.
        Nephrol DialTransplant. 2021; 36: 42-59
        • Black DM
        • Reid IR
        • Boonen S
        • et al.
        The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: A randomized extension to the horizon-pivotal fracture trial (PFT).
        J Bone Miner Res. 2012; 27: 243-254
        • Cosman F
        • Cauley JA
        • Eastell R
        • et al.
        Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: When is it reasonable to discontinue treatment?.
        J Clin Endocrinol Metab. 2014; 99: 4546-4554
        • Jamal SA
        • Ljunggren Ö
        • Stehman-Breen C
        • et al.
        Effects of denosumab on fracture and bone mineral density by level of kidney function.
        J Bone Miner Res. 2011; 26: 1829-1835
        • Block GA
        • Bone HG
        • Fang L
        • et al.
        A single-dose study of denosumab in patients with various degrees of renal impairment.
        J Bone Miner Res. 2012; 27: 1471-1479
        • Cummings SR
        • Ferrari S
        • Eastell R
        • et al.
        Vertebral fractures after discontinuation of denosumab: A post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension.
        J Bone Miner Res. 2018; 33: 190-198
        • Tsourdi E
        • Langdahl B
        • Cohen-Solal M
        • et al.
        Discontinuation of denosumab therapy for osteoporosis: A systematic review and position statement by ECTS.
        Bone. 2017; 105: 11-17
        • Miller PD
        • Hattersley G
        • Riis BJ
        • et al.
        Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis.
        JAMA. 2016; 316: 722
        • Neer RM
        • Arnaud CD
        • Zanchetta JR
        • et al.
        Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.
        N Engl J Med. 2001; 344: 1434-1441
        • Eastell R
        • Nickelsen T
        • Marin F
        • et al.
        Sequential treatment of severe postmenopausal osteoporosis after teriparatide: Final results of the randomized, controlled European study of forsteo (EUROFORS)*.
        J Bone Miner Res. 2009; 24: 726-736
        • Cosman F
        • Miller PD
        • Williams GC
        • et al.
        Eighteen months of treatment with subcutaneous abaloparatide followed by 6 months of treatment with alendronate in postmenopausal women with osteoporosis: Results of the ACTIVExtend Trial.
        Mayo Clin Proc. 2017; 92: 200-210
        • Leder BZ
        • Tsai JN
        • Jiang LA
        • et al.
        Importance of prompt antiresorptive therapy in postmenopausal women discontinuing teriparatide or denosumab: The denosumab and teriparatide follow-up study (data-follow-up).
        Bone. 2017; 98: 54-58
        • Díez-Pérez A
        • Marin F
        • Eriksen EF
        • et al.
        Effects of teriparatide on hip and upper limb fractures in patients with osteoporosis: A systematic review and meta-analysis.
        Bone. 2019; 120: 1-8
        • Black DM
        • Bilezikian JP
        • Ensrud KE
        • et al.
        One year of alendronate after one year of parathyroid hormone (1–84) for osteoporosis.
        N Engl J Med. 2005; 353: 555-565
        • Leder BZ
        • Tsai JN
        • Uihlein AV
        • et al.
        Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): Extension of a randomised controlled trial.
        Lancet. 2015; 386: 1147-1155
        • Bone HG
        • Cosman F
        • Miller PD
        • et al.
        Activextend: 24 months of alendronate after 18 months of abaloparatide or placebo for postmenopausal osteoporosis.
        J Clin Endocrinol Metab. 2018; 103: 2949-2957
        • Cosman F
        • Crittenden DB
        • Ferrari S
        • et al.
        FRAME study: The foundation effect of building bone with 1 year of romosozumab leads to continued lower fracture risk after transition to denosumab.
        J Bone Miner Res. 2018; 33: 1219-1226
        • Cosman F
        • Crittenden DB
        • Adachi JD
        • et al.
        Romosozumab treatment in postmenopausal women with osteoporosis.
        N Engl J Med. 2016; 375: 1532-1543
        • Genant HK
        • Engelke K
        • Bolognese MA
        • et al.
        Effects of romosozumab compared with teriparatide on bone density and mass at the spine and hip in postmenopausal women with low bone mass.
        J Bone Miner Res. 2017; 32: 181-187
        • Langdahl BL
        • Libanati C
        • Crittenden DB
        • et al.
        Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: A randomised, open-label, phase 3 trial.
        Lancet. 2017; 390: 1585-1594
        • Ettinger B.
        Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial.
        JAMA. 1999; 282: 637
        • Ensrud KE
        • Stock JL
        • Barrett-Connor E
        • et al.
        Effects of raloxifene on fracture risk in postmenopausal women: The raloxifene use for the heart trial.
        J Bone Miner Res. 2007; 23: 112-120
        • Silverman SL
        • Chines AA
        • Kendler DL
        • et al.
        Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: Results of a 5-year, randomized, placebo-controlled study.
        Osteoporosis Int. 2012; 23: 351-363
        • Lindsay R
        • Gallagher JC
        • Kagan R
        • et al.
        Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women.
        Fertil Steril. 2009; 92: 1045-1052
        • Cuzick J
        • Sestak I
        • Bonanni B
        • et al.
        Selective oestrogen receptor modulators in prevention of breast cancer: An updated meta-analysis of individual participant data.
        Lancet. 2013; 381: 1827-1834
        • Barrett-Connor E
        • Mosca L
        • Collins P
        • et al.
        Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women.
        N Engl J Med. 2006; 355: 125-137
        • Palacios S
        • Silverman SL
        • de Villiers TJ
        • et al.
        A 7-year randomized, placebo-controlled trial assessing the long-term efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis: Effects on bone density and fracture.
        Menopause. 2015; 22: 806-813
        • Vogel VG.
        Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes:the nsabp study of tamoxifen and raloxifene (STAR) P-2 trial.
        JAMA. 2006; 295: 2727
        • Cauley JA.
        Effects of estrogen plus progestin on risk of fracture and bone mineral density: the women's health initiative randomized trial.
        JAMA. 2003; 290: 1729
        • Mosekilde L
        • Beck-Nielsen H
        • Sørensen OH
        • et al.
        Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women — results of the danish osteoporosis prevention study.
        Maturitas. 2000; 36: 181-193
        • Manson JE
        • Chlebowski RT
        • Stefanick ML
        • et al.
        Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the women's health initiative randomized trials.
        JAMA. 2013; 310: 1353
        • Shane E
        • Burr D
        • Abrahamsen B
        • et al.
        Atypical subtrochanteric and diaphyseal femoral fractures: Second report of a task force of the American Society for Bone and Mineral Research.
        J Bone Miner Res. 2014; 29: 1-23
        • Khan AA
        • Kaiser S.
        Atypical femoral fracture.
        CMAJ. 2017; 189 (E542-E)
        • Dell RM
        • Adams AL
        • Greene DF
        • et al.
        Incidence of atypical nontraumatic diaphyseal fractures of the femur.
        J Bone Miner Res. 2012; 27: 2544-2550
        • Khan AA
        • Leslie WD
        • Lentle B
        • et al.
        Atypical femoral fractures: A teaching perspective.
        Can Assoc Radiol J. 2015; 66: 102-107
        • Schilcher J
        • Michaëlsson K
        • Aspenberg P.
        Bisphosphonate use and atypical fractures of the femoral shaft.
        N Engl J Med. 2011; 364: 1728-1737
        • Watts NB
        • Aggers D
        • Mccarthy EF
        • et al.
        Responses to treatment with teriparatide in patients with atypical femur fractures previously treated with bisphosphonates.
        J Bone Miner Res. 2017; 32: 1027-1033
        • Chiang CY
        • Zebaze RMD
        • Ghasem-Zadeh A
        • et al.
        Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy.
        Bone. 2013; 52: 360-365
        • Miyakoshi N
        • Aizawa T
        • Sasaki S
        • et al.
        Healing of bisphosphonate-associated atypical femoral fractures in patients with osteoporosis: A comparison between treatment with and without teriparatide.
        J Bone Miner Metab. 2015; 33: 553-559
        • Khan AA
        • Morrison A
        • Hanley DA
        • et al.
        Diagnosis and management of osteonecrosis of the jaw: A systematic review and international consensus.
        J Bone Miner Res. 2015; 30: 3-23
        • Khan AA
        • Morrison A
        • Kendler DL
        • et al.
        Case-based review of osteonecrosis of the jaw (ONJ) and application of the international recommendations for management from the International Task Force on ONJ.
        J Clin Densitom. 2017; 20: 8-24