Romosozumab-aqqg (Evenity) [Medicare]

Number: 0954m

Medicare Part B Step Therapy Criteria

For Medicare Advantage plans that do not offer prescription drug coverage (MA)

Evenity, for the indication listed below:

  • Treatment of osteoporosis

Is not covered for new starts, unless the member meets ANY of the following:

  1. Inadequate response to a trial of Prolia (denosumab)
  2. Intolerable adverse event with Prolia (denosumab)
  3. Prolia (denosumab) is contraindicated for the member.

For Medicare Advantage plans that offer prescription drug coverage (MAPD)

Evenity, for the indication listed below:

  • Treatment of osteoporosis

Is not covered for new starts, unless the member meets ANY of the following:

  1. Inadequate response to a trial of Forteo (teriparatide injection)
  2. Intolerable adverse event to Forteo (teriparatide injection)
  3. Forteo (teriparatide injection) is contraindicated for the member.

Policy

Note: REQUIRES PRECERTIFICATION. Precertification of Evenity (romosozumab-aqqg) is required of all Aetna participating providers and members in applicable plan designs. For precertification of Evenity, call (866) 752-7021 (Commercial), (866) 503-0857 (Medicare), or fax (866) 267-3277.

Aetna considers romosozumab-aqqg (Evenity) medically necessary for members with post-menopausal osteoporosis when any of the following criteria are met:

  • Member has a history of fragility fractures; or

  • Member has a pre-treatment T-score less than or equal to -2.5 or member has osteopenia (i.e., pre-treatment T-score greater than -2.5 and less than -1) with a high pre-treatment FRAX fracture probability (See Appendix B) and meets any of the following criteria:

    • Member has indicators of higher fracture risk (e.g., advanced age, frailty, glucocorticoid use, very low T-scores [less than or equal to -3.5], or increased fall risk); or
    • Member has failed prior treatment with or is intolerant to previous injectable osteoporosis therapy (e.g., zoledronic acid [Reclast], teriparatide [Forteo, Bonsity], denosumab [Prolia]); or
    • Member has had an oral bisphosphonate trial of at least 1-year duration or there is a clinical reason to avoid treatment with an oral bisphosphonate (See Appendix A).

Aetna considers Evenity (romosozumab-aqqg) medically necessary for all members (including new members) requesting authorization for continuation of therapy who meet all initial selection criteria and have received less than 12 monthly doses of Evenity.

Aetna considers monthly injection of romosozumab-aqqg (Evenity) not medically necessary for members who have had a myocardial infarction or stroke within the preceding year. 

Dosing Recommendations

Evenity (romosozumab-aqqg) is available as 105 mg/1.17 mL solution in a single-use prefilled syringe. A full dose of Evenity requires two single-use prefilled syringes. Evenity should be administered by a healthcare provider. 

The recommended dose of Evenity is 210 mg administered monthly as a subcutaneous injection in the abdomen, thigh or upper arm. Treatment duration for Evenity is 12 monthly doses, as the anablolic effect of Evenity wanes after 12 monthly doses of therapy. If osteoporosis therapy remains warranted, continued therapy with an anti-resorptive agent should be considered.

Source: Amgen, 2019

Background

Approximately 10 million Americans (80 % of them women) suffer from osteoporosis, which may lead to an increased risk of spine, wrist, and hip fractures. For post-menopausal women, age, personal or family history of fracture, Asian or Hispanic heritage, smoking, and cortisone use have been associated with significantly increased likelihood of osteoporosis; while higher body mass index (BMI), African American heritage, estrogen or diuretic use, and exercise have been associated with significantly decreased likelihood of osteoporosis (Siris et al, 2001). Furthermore, Wu and colleagues (2002) reported that any fracture (unrelated to motor vehicle accidents) sustained between the ages of 20 and 50 years is associated with increased risk of fractures after the age of 50 years in women. Although osteoporosis is usually considered a disease of women, up to 20 % of vertebral fractures and 30 % of hip fractures occur in men. Risk factors for osteoporotic fractures in men include low BMI, smoking, high alcohol consumption, corticosteroid therapy, physical inactivity, and diseases that predispose to low bone mass (Eastell et al, 1998). However, the exact mechanism of bone loss remains unknown in primary male osteoporosis (Legrand et al, 2001). 

Bone mineral density (BMD) is useful in the diagnosis of osteoporosis. It is usually provided as the T score -- the number of standard deviations (SDs) the BMD falls below or above the mean value in a reference population (young, healthy adults). The World Health Organization (WHO) osteoporosis diagnostic classification assessment (1994) defines osteoporosis as a T score of 2.5 or more SDs below the mean (i.e., less than -2.5). Osteopenia is defined as a T score of -1.0 to -2.5 and a T score of -1.0 or higher is considered normal. It should be noted that a male database should be used for diagnosing osteoporosis in men.

In 2008, a World Health Organization (WHO) task force introduced the Fracture Risk Assessment Tool (FRAX), which provides a fracture risk assessment by estimating the 10-year probability of hip fracture or major osteoporotic fractures combined (hip, spine, shoulder, or wrist) for an untreated patient using femoral neck BMD and easily obtainable clinical risk factors for fracture.

Past guidelines have recommended non-pharmacologic interventions to reduce bone loss in postmenopausal women include lifestyle measures such as adequate calcium and vitamin D, exercise, smoking cessation, counseling on fall prevention, and avoidance of heavy alcohol prior to pharmacologic interventions. In general, 1200 mg of elemental calcium daily, total diet plus supplement, and 800 international units of vitamin D daily are advised (Rosen 2019). In addition to lifestyle measures, patients at high risk for fracture should receive pharmacologic therapy. Oral bisphosphonates are considered as first-line pharmacologic therapy in postmenopausal women with a history of fragility fracture or with osteoporosis based upon bone mineral density (BMD) measurement (T-score ≤-2.5). Alendronate (Fosamax) and risedronate (Actonel) have been the most extensively studied bisphosphonates under clinical trials conditions. Both drugs can lower the risk of vertebral and hip fractures by 25 to 50 %. However, there may be clinical reasons to avoid oral bisphosphonate therapy, which may include esophageal disorders, an inability to follow the dosing requirements (e.g., stay upright for at least 30 to 60 minutes), or chronic kidney disease (CKD) (estimated glomerular filtration [eGFR] rate <30 mL/min). Oral bisphosphonates should also be avoided after certain types of bariatric surgery in which surgical anastomoses are present in the GI tract (e.g., Roux-en-Y gastric bypass). Alternatives for initial therapy in patients with contraindications or intolerance to oral bisphosphonates include intravenous (IV) bisphosphonates (unless the contraindication is CKD), denosumab (Prolia), teriparatide (Forteo)/abaloparatide (Tymlos) (except in CKD), and raloxifene (Evista), a selective estrogen receptor modulator (SERM).

The 2010 guidelines from the American Association of Clinical Endocrinologists (Watts 2010) recommended teriparatide for patients with very high fracture risk or patients in whom bisphosphonate therapy has failed. They state that teriparatide is contraindicated in patients at increased risk of osteosarcoma (those with Paget disease of bone, open epiphyses, a history of irradiation involving the skeleton, or an unexplained elevation of alkaline phosphatase level of skeletal origin). Teriparatide should also not be administered to patients with primary or any form of secondary untreated or unresolved hyperparathyroidism. 

In the 2016 update of the American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis (Camacho 2016), the document states approved agents with efficacy to reduce hip, nonvertebral, and spine fractures including alendronate, risedronate, zoledronic acid, and denosumab are appropriate as initial therapy for most patients at high risk of fracture. Teriparatide, denosumab, or zoledronic acid should be considered for patients unable to use oral therapy and as initial therapy for patients at especially high fracture risk. Also, raloxifene or ibandronate may be appropriate initial therapy in some cases where patients requiring drugs with spine-specific efficacy.

In 2019, the Endocrine Society released guidelines on the pharmacologic treatment of osteoporosis in postmenopausal women, which were cosponsored by the European Society of Endocrinology. The document provides recommendations for the treatment and management of osteoporosis in postmenopausal women and emphasizes assessment after being on treatments to see if further treatment is necessary. The guidelines continue to recommend starting with lifestyle and nutritional optimization for bone health, especially calcium and vitamin D, for all postmenopausal women, along with an assessment of 10-year fracture risk according to country-specific guidelines. As before, bisphosphonates and denosumab are still advised as first-line therapies. For women who have been on bisphosphonates for 3 to 5 years, fracture risk should be assessed and women with a low-to-moderate risk of fracture should be prescribed a "bisphosphonate holiday". However, in patients with very severe osteoporosis, multiple fractures, and/or very low bone density, the Endocrine Society recommends anabolic treatments (e.g., teriparatide (Forteo) or abaloparatide (Tymlos) as first-line therapy.

On April 09, 2019, the U.S. Food and Drug Administration (FDA) approved Evenity (romosozumab-aqqg) subcutaneous injection, a sclerostin inhibitor for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. Evenity is a monoclonal antibody that increases bone formation and, to a lesser extent, decreases bone resorption. Sclerostin is produced by osteocytes and inhibits bone formation. In animal models and a phase I trial in healthy adults, inhibiting sclerostin through the administration of a sclerostin monoclonal antibody increased bone mass (Padhi 2011; Ominsky 2010; Li 2009). One dose of Evenity consists of two injections, one immediately following the other, given once a month by a health care professional. The bone forming effect of Evenity wanes after 12 doses so more than 12 doses should not be used. If osteoporosis therapy is needed after the 12 doses, patients should begin an osteoporosis treatment that reduces bone breakdown.

The safety and efficacy of Evenity were demonstrated in two clinical trials involving a total of more than 11,000 women with postmenopausal osteoporosis. In the first trial, one year of treatment with Evenity lowered the risk of a new fracture in the spine (vertebral fracture) by 73% compared to placebo. This benefit was maintained over the second year of the trial when Evenity was followed by one year of denosumab (another osteoporosis therapy) compared to placebo followed by denosumab. In the second trial, one year of treatment with Evenity followed by one year of alendronate (another osteoporosis therapy) reduced the risk of a new vertebral fracture by 50% compared to two years of alendronate alone. Evenity followed by alendronate also reduced the risk of fractures in other bones (non-vertebral fractures) compared to alendronate alone.

In the first trial (FRActure study in postmenopausal woMen with ostEoporosis (FRAME) Clinical Trial; NCT01575834), Cosman et al 2016 state romosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. The author enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck. Patients were randomly assigned to receive subcutaneous injections of 210 mg romosozumab or placebo monthly for 12 months; thereafter, patients in each group received denosumab 60 mg for 12 months, administered subcutaneously every 6 months. The co-primary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months. Secondary end points included clinical (a composite of non-vertebral and symptomatic vertebral) and non-vertebral fractures. At 12 months, new vertebral fractures had occurred in 16 of 3321 patients (0.5%) in the romosozumab group, as compared with 59 of 3322 (1.8%) in the placebo group (representing a 73% lower risk with romosozumab; P<0.001). Clinical fractures had occurred in 58 of 3589 patients (1.6%) in the romosozumab group, as compared with 90 of 3591 (2.5%) in the placebo group (a 36% lower risk with romosozumab; P=0.008). The reduction in non-vertebral fractures was not significantly different between romosozumab (56 of 3589 patients or 1.6% of patients) and the placebo group (75 of 3591 or 2.1% of patients), P=0.10. At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3325 patients] in the romosozumab group vs. 2.5% [84 of 3327] in the placebo group, a 75% lower risk with romosozumab; P<0.001). Adverse events, including instances of hyperostosis, cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and two cases of osteonecrosis of the jaw were observed in the romosozumab group. The authors concluded that in postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year.

In the FRAME trial, one year of romosozumab increased spine and hip BMD by 13% and 7%, respectively, and reduced vertebral and clinical fractures with persistent fracture risk reduction upon transition to denosumab over 24 months. Two years after the publication of the FRAME study, Cosman et al (2018) further characterize the BMD gains with romosozumab by quantifying the percentages of patients who responded at varying magnitudes; report the mean T-score changes from baseline over the 2-year study and contrast these results with the long-term BMD gains seen with denosumab during Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) and its Extension studies; and assess fracture incidence rates in year 2, when all patients received denosumab. Among 7180 patients (n = 3591 placebo, n = 3589 romosozumab), most romosozumab-treated patients experienced ≥3% gains in BMD from baseline at month 12 (spine, 96%; hip, 78%) compared with placebo (spine, 22%; hip, 16%). For romosozumab patients, mean absolute T-score increases at the spine and hip were 0.88 and 0.32, respectively, at 12 months (placebo: 0.03 and 0.01) and 1.11 and 0.45 at 24 months (placebo-to-denosumab: 0.38 and 0.17), with the 2-year gains approximating the effect of 7 years of continuous denosumab administration. Patients receiving romosozumab versus placebo in year 1 had significantly fewer vertebral fractures in year 2 (81% relative reduction; p < 0.001), with fewer fractures consistently observed across other fracture categories. The data support the clinical benefit of rebuilding the skeletal foundation with romosozumab before transitioning to anti-resorptive therapy.

Subsequent to the initial FRAME trial, Cosman et al (2018) conducted a post-hoc analysis for the role of regional background fracture risk on non-vertebral outcome. In the initial FRAME study, 1 year of the bone-forming agent romosozumab significantly reduced new vertebral and clinical fracture risk versus placebo. Non-vertebral fracture risk was not significantly reduced in the overall population, influenced by a low placebo-group fracture rate, observed particularly in the highest-enrolling region of Latin America. In year 1 of FRAME, postmenopausal women with a T-score of -2.5 to -3.5 at the total hip or femoral neck were randomized to subcutaneous romosozumab 210 mg or placebo once monthly for 12 months. Of 7180 randomized women, 43% were from Latin America, largely Colombia and Brazil. Pre-specified analyses assessed fracture risk reductions by geographic regions. A significant treatment-by-geographic region interaction for the clinical (p = 0.029) and non-vertebral fracture (p = 0.042) endpoints led to further characterization of the Latin American population and comparison with the remaining study population, grouped post hoc as rest-of-world. Non-vertebral fracture efficacy in the overall population was also assessed by baseline fracture risk using the Fracture Risk Assessment Tool (FRAX). Romosozumab significantly and consistently reduced new vertebral fracture risk in Latin America (70% reduction; p = 0.014) and rest-of-world (74% reduction; p < 0.001). For non-vertebral fracture, risk reductions were observed in rest-of-world (42% reduction; p = 0.012), with no treatment effect observed in Latin America, where background non-vertebral fracture risk was low (1.2% in the placebo group). Consistent with this finding, in the overall population, greater reductions in non-vertebral fracture risk were observed among women with higher FRAX scores. These findings suggest that fracture risk assessment should consider regional factors in addition to classical risk factors, such as bone mineral density. In women at high risk for fracture, romosozumab reduced non-vertebral fracture risk within 1 year.

In the second trial submitted for FDA approval (Active-Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk (ARCH); NCT01631214), Saag et al (2017) enrolled 4093 postmenopausal women with osteoporosis and a fragility fracture and randomly assigned them in a 1:1 ratio to receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) in a blinded fashion for 12 months, followed by open-label alendronate in both groups. The primary end points were the cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture (non-vertebral and symptomatic vertebral fracture) at the time of the primary analysis (after clinical fractures had been confirmed in ≥330 patients). Secondary end points included the incidences of non-vertebral and hip fracture at the time of the primary analysis. Serious cardiovascular adverse events, osteonecrosis of the jaw, and atypical femoral fractures were adjudicated. Over a period of 24 months, a 48% lower risk of new vertebral fractures was observed in the romosozumab-to-alendronate group (6.2% [127 of 2046 patients]) than in the alendronate-to-alendronate group (11.9% [243 of 2047 patients]) (P<0.001). Clinical fractures occurred in 198 of 2046 patients (9.7%) in the romosozumab-to-alendronate group versus 266 of 2047 patients (13.0%) in the alendronate-to-alendronate group, representing a 27% lower risk with romosozumab (P<0.001). The risk of non-vertebral fractures was lower by 19% in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group (178 of 2046 patients [8.7%] vs. 217 of 2047 patients [10.6%]; P=0.04), and the risk of hip fracture was lower by 38% (41 of 2046 patients [2.0%] vs. 66 of 2047 patients [3.2%]; P=0.02). Overall adverse events and serious adverse events were balanced between the two groups. During year 1, positively adjudicated serious cardiovascular adverse events were observed more often with romosozumab than with alendronate (50 of 2040 patients [2.5%] vs. 38 of 2014 patients [1.9%]). During the open-label alendronate period, adjudicated events of osteonecrosis of the jaw (1 event each in the romosozumab-to-alendronate and alendronate-to-alendronate groups) and atypical femoral fracture (2 events and 4 events, respectively) were observed. The authors concluded that in postmenopausal women with osteoporosis who were at high risk for fracture, romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone.

The skeletal effects of romosozumab have also been compared with teriparatide in a randomized, open label phase 3 study by Langdahl et al (2017; NCT01796301). The authors state previous bisphosphonate treatment attenuates the bone-forming effect of teriparatide. The authors compared the effects of 12 months of romosozumab (AMG 785), a sclerostin monoclonal antibody, versus teriparatide on bone mineral density (BMD) in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy. This randomized, phase 3, open-label, active-controlled study was done at 46 sites in North America, Latin America, and Europe. Women (aged ≥55 to ≤90 years) with postmenopausal osteoporosis who had taken an oral bisphosphonate for at least 3 years before screening and alendronate the year before screening; an area BMD T score of -2·5 or lower at the total hip, femoral neck, or lumbar spine; and a history of fracture were enrolled. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous romosozumab (210 mg once monthly) or subcutaneous teriparatide (20 μg once daily). The primary endpoint was percentage change from baseline in areal BMD by dual-energy x-ray absorptiometry at the total hip through month 12 (mean of months 6 and 12), which used a linear mixed effects model for repeated measures and represented the mean treatment effect at months 6 and 12. All randomized patients with a baseline measurement and at least one post-baseline measurement were included in the efficacy analysis. Between Jan 31, 2013, and April 29, 2014, 436 patients were randomly assigned to romosozumab (n=218) or teriparatide (n=218). 206 patients in the romosozumab group and 209 in the teriparatide group were included in the primary efficacy analysis. Through 12 months, the mean percentage change from baseline in total hip areal BMD was 2·6% (95% CI 2·2 to 3·0) in the romosozumab group and -0·6% (-1·0 to -0·2) in the teriparatide group; difference 3·2% (95% CI 2·7 to 3·8; p<0·0001). The frequency of adverse events was generally balanced between treatment groups. The most frequently reported adverse events were nasopharyngitis (28 [13%] of 218 in the romosozumab group vs 22 [10%] of 214 in the teriparatide group), hypercalcaemia (two [<1%] vs 22 [10%]), and arthralgia (22 [10%] vs 13 [6%]). Serious adverse events were reported in 17 (8%) patients on romosozumab and in 23 (11%) on teriparatide; none were judged treatment related. There were six (3%) patients in the romosozumab group compared with 12 (6%) in the teriparatide group with adverse events leading to investigational product withdrawal. The authors concluded that transition to a bone-forming agent is common practice in patients treated with bisphosphonates, such as those who fracture while on therapy. In such patients, romosozumab led to gains in hip BMD that were not observed with teriparatide. These data could inform clinical decisions for patients at high risk of fracture.

Evenity increased the risk of cardiovascular death, heart attack and stroke in the alendronate trial, but not in the placebo trial. Therefore, Evenity contains a boxed warning on its labeling stating that it may increase the risk of heart attack, stroke and cardiovascular death and should not be used in patients who have had a heart attack or stroke within the previous year. Health care professionals should also consider whether the benefits of Evenity outweigh its risks in those with other risk factors for heart disease and should discontinue Evenity in any patient who experiences a heart attack or stroke during treatment.

According to the FDA-approved labeling, romosozumab-aqqg (Evenity) is contraindicated in any of the following individuals:

  • Hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating therapy with Evenity
  • A history of systemic hypersensitivity to romosozumab or to any component of the product formulation. Reactions have included angioedema, erythema multiforme .

Appendix

Appendix A: Clinical reasons to avoid oral bisphosphonate therapy

  • Esophageal abnormality that delays emptying such as stricture of achalasia
  • Active upper gastrointestinal problem (e.g., dysphagia, gastritis, duodenitis, erosive esophagitis, ulcers)
  • Inability to stand or sit upright for at least 30 to 60 minutes
  • Inability to take at least 30 to 60 minutes before first food, drink, or medication of the day
  • Renal insufficiency (creatinine clearance <35 mL/min)
  • History of intolerance to an oral bisphosphonate.

Appendix B: WHO Fracture Risk Assessment Tool

  • High FRAX fracture probability: 10 year major osteoporotic fracture risk ≥ 20% or hip fracture risk ≥ 3%.
  • 10-year probability; calculation tool available at: FRAX Fracture Risk Assessment Tool
  • The estimated risk score generated with FRAX should be multiplied by 1.15 for major osteoporotic fracture and 1.2 for hip fracture if glucocorticoid treatment is greater than 7.5 mg (prednisone equivalent) per day.
Table: CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :

Other CPT codes related to the CPB:

96372 Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular

HCPCS codes covered if selection criteria are met:

J3111 Injection, romosozumab-aqqg, 1 mg

Other HCPCS codes related to the CPB:

J0897 Injection, denosumab, 1 mg
J3110 Injection, teriparatide, 10 mcg
J3489 Injection, zoledronic acid, 1 mg

ICD-10 codes covered if selection criteria are met:

M80.00xA - M80.08xS Age-related osteoporosis with current pathological fracture
M81.0 Age-related osteoporosis without current pathological fracture

The above policy is based on the following references:

  1. ACOG Practice Bulletin Number 129: Osteoporosis. Obstet Gynecol. 2012;120(3):718-734.
  2. Amgen Inc. Evenity (romosozumab-aqqg) injection, for subcutaneous use. Prescribing Information. Thousand Oaks, CA: Amgen; revised December 2019.
  3. Camacho PM, Petak SM, Binkley N, et al. American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis - 2016. Endocr Pract. 2016;22(Suppl 4):1-42.
  4. Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016;375(16):1532-1543.
  5. 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(7):1219-1226.
  6. Cosman F, Crittenden DB, Ferrari S, et al. Romosozumab FRAME Study: A Post Hoc Analysis of the Role of Regional Background Fracture Risk on Nonvertebral Fracture Outcome. J Bone Miner Res. 2018;33(8):1407-1416.
  7. Cosman F, de Beur SJ, LeBoff MS, et al. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10): 2359-2381.
  8. Eastell R, Boyle IT, Compston J, et al. Management of male osteoporosis: Report of the UK Consensus Group. QJM. 1998;91(2):71-92.
  9. 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(5):1595-1622.
  10. Ensrud KE, Crandall CJ. Osteoporosis. Ann Intern Med 2017;167(03):ITC17–ITC32
  11. Fink HA, Gordon G, Buckley L, et al. 2017 American College of Rheumatology Guidelines for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res. 2017;69:1521-1537.
  12. FRAX® WHO fracture risk assessment tool. © World Health Organization Collaborating Centre for Metabolic Bone Diseases: University of Sheffield, UK. Available at: https://www.sheffield.ac.uk/FRAX/. Accessed April 10, 2019.
  13. Jeremiah MP, Unwin BK, Greenwald MH, et al. Diagnosis and management of osteoporosis. Am Fam Physician. 2015;92(4):261-268.
  14. 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(10102):1585-1594.
  15. Legrand E, Hedde C, Gallois Y, et al. Osteoporosis in men: A potential role for the sex hormone binding globulin. Bone. 2001;29(1):90-95.
  16. Li X, Ominsky MS, Warmington KS, et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009;24(4):578-88.
  17. McClung MR. Romosozumab for the treatment of osteoporosis. Osteoporos Sarcopenia. 2018;4(1):11–15.
  18. National Institute for Health and Care Excellence. Osteoporosis Overview. Last updated February 2018. Available at: http://pathways.nice.org.uk/pathways/osteoporosis. Accessed April 10, 2019.
  19. Ominsky MS, Vlasseros F, Jolette J, et al. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res. 2010;25(5):948-59.
  20. Padhi D, Jang G, Stouch B, et al. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011;26(1):19-26.
  21. Rosen HN, Drezner MK. Overview of the management of osteoporosis in postmenopausal women. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed April 2019.
  22. Saag KG, Petersen J, Brandi ML, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017;377(15):1417-1427.
  23. Siris ES, Miller PD, Barrett-Connor E, et al. Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: Results from the National Osteoporosis Risk Assessment. JAMA. 2001;286(22):2815-2822.
  24. Treatment to prevent osteoporotic fractures: an update. Department of Health and Human Services, Agency for Healthcare Research and Quality. 2012; Publication No. 12-EHC023-EF. Available at https://www.effectivehealthcare.ahrq.gov/lbd.cfm.
  25. Tucker ME. New Guidelines Address Osteoporosis Treatment Postmenopause.  Medscape Medical News. New York, NY: WebMD Inc.; March 25, 2019. 
  26. U.S. Food and Drug Administration (FDA). Evenity (romosozumab-aqqg) injection, for subcutanous use. Prescribing Information. Reference ID: 4416809. Rockville, MD: FDA; revised April 2019.
  27. U.S. Food and Drug Administration (FDA). FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture. FDA News Release. Silver Spring, MD: FDA; April 09, 2019.
  28. Watts NB, Bilezikian JP, Camacho PM, et al; AACE Osteoporosis Task Force. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2010;16 Suppl 3:1-37.
  29. World Health Organization (WHO). Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Report of a WHO study group. WHO Technical Report Series 843. Geneva, Switzerland: WHO; 1994.
  30. Wu F, Mason B, Horne A, et al. Fractures between the ages of 20 and 50 years increase women's risk of subsequent fractures. Arch Intern Med. 2002;162(1):33-36.