5 INDICATIONS

Prolia® is indicated for the treatment of postmenopausal women with osteoporosis 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. In postmenopausal women with osteoporosis, Prolia® reduces the incidence of vertebral, See More

PROLIA® IS THE ONLY FDA-APPROVED THERAPY FOR CANCER TREATMENT–INDUCED BONE LOSS (CTIBL) DUE TO HORMONE ABLATION THERAPY (CTIBL-HALT).1

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Prolia® Mechanism of Action

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Prolia® helps you treat patients at high risk for fracture with 5 indications

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When breast cancer metastasizes to a patient’s bones, another treatment is available

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How many of your patients on hormone ablation therapy for breast cancer are at high risk for fracture?

When your patients are losing bone mass due to treatment for breast cancer, help protect their bone health with Prolia®.1

Breast Cancer Treatment–induced Bone Loss Indication

Prolia® is indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.

Estrogen molecule for illustration purposes only.

In the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), denosumab is included as a treatment option to increase bone density and reduce risk of fractures in postmenopausal women on aromatase inhibitor therapy.2

National Comprehensive Cancer Network® (NCCN®) makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Among Women with Breast Cancer

Aromatase inhibitor therapy results in estrogen depletion, leading to bone loss and increased fracture risk.3

How does aromatase inhibitor (AI) therapy put women with breast cancer at high risk for fracture?

Fracture: Patients with breast cancer receiving aromatase inhibitor (AI) therapy are more likely to experience a fracture than those not receiving AI therapy5

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Data from a claims-based retrospective cohort study conducted from 1998 to 2005, involving patients with breast cancer, without bone metastases, and no previous osteoporosis, osteopenia, or fracture
claims, receiving AI therapy (n = 1,354) versus those
not receiving AI therapy (n = 11,014).5

CI = confidence interval; RR=relative risk.

Calcium and vitamin D supplementation alone may not be sufficient to prevent bone loss and fractures in patients receiving AI therapy4


How does AI therapy put women with breast cancer at high risk for fracture?

BMD: The most pronounced rate of bone loss at the lumbar spine, measured by BMD, occurs within the first year of AI therapy (-2.3%)6,7

Data from a randomized, double-blind, multicenter, prospective substudy performed within the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial assessing BMD changes at the lumbar spine and total hip in postmenopausal women with nonmetastatic breast cancer receiving anastrozole or tamoxifen therapy.6,7

Calcium and vitamin D supplementation alone may not be sufficient to prevent bone loss and fractures in patients receiving AI therapy4

See how a phase 3 BMD study assessed how Prolia® can protect against aromatase inhibitor–induced bone loss1,4

Prolia® was proven to protect against aromatase inhibitor–induced bone loss in a phase 3 study1,4

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Study design (CTIBL-HALT)1,4

A 2-year, randomized, multinational, double-blind, phase 3 study assessing the effects of Prolia® vs placebo on BMD

Women with nonmetastatic breast cancer receiving AI (N = 252)

†Patients were instructed to take 1,000 mg of calcium and 400 IU of vitamin D supplementation only.

Primary endpoint:

Percent change in: Lumbar spine BMD from baseline to 12 months

Exploratory endpoints:

Percent change in:

  • Lumbar spine BMD from baseline to 24 months
  • Total hip BMD from baseline to 24 months
  • Femoral neck BMD from baseline to 24 months

CTIBL-HALT = cancer treatment–induced bone loss due to hormone ablation therapy; SC = subcutaneous.

Prolia® increased BMD in patients on AI therapy for breast cancer in a pivotal trial1,4

Prolia® increased BMD in patients on AI therapy for breast cancer in a pivotal trial1,4

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Primary Endpoint: Significant increase (5.5%) in BMD at the lumbar spine compared with placebo at 12 months (p < 0.0001)1

Mean percent change in BMD at 12 months1,4

Mean Percent Change in Lumbar Spine BMD at 12 Months. See references below.


Exploratory Endpoints: Prolia® demonstrated a continued increase in BMD at key sites through 24 months1

Mean percent change in BMD at 24 months1,4

Mean Percent Change in Lumbar Spine BMD at 24 Months. See references below.

 

CI = confidence interval; CTIBL-HALT = cancer treatment–induced bone loss due to hormone ablation therapy.

Mean percent change in BMD at 24 months1,4

Mean Percent Change in Total Hip BMD at 24 Months. See references below.

CTIBL-HALT = cancer treatment–induced bone loss due to hormone ablation therapy.

Mean percent change in BMD at 24 months1,4

 Mean Percent Change in Femoral Neck BMD at 24 Months. See references below

CTIBL-HALT = cancer treatment–induced bone loss due to hormone ablation therapy.

Prolia® safety profile was established in a pivotal phase 3 trial over a 2-year period4

Prolia® safety and tolerability were evaluated in a pivotal phase 3 trial over a 2-year period4

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Safety: Prolia® safety and tolerability were evaluated in a pivotal trial in women with breast cancer and bone loss from AI therapy over a 2-year period4

The overall incidence of adverse events was similar between Prolia® and placebo (91% vs 90%, respectively).4

Adverse events ( 10% frequency in each treatment group)4

Placebo
(n = 120)
Prolia®
(n = 129)
Arthralgia 25.0% 24.0%
Pain in extremity 11.7% 14.7%
Back pain 12.5% 14.0%
Fatigue 14.2% 13.2%
  • Musculoskeletal pain has also been reported in clinical trials1
  • The percentage of patients who withdrew from the study due to adverse events was 0.8% and 4.2% for the Prolia® and placebo groups, respectively1
  • The incidence of serious adverse events was 14.7% in the Prolia® group and 9.2% in the placebo group1

CTIBL-HALT=cancer treatment–induced bone loss due to hormone ablation therapy.

Important Safety Information

Prolia® is contraindicated in patients with hypocalcemia, in women who are pregnant and in patients with a history of systemic hypersensitivity to any component of the product. Patients receiving Prolia® should not receive XGEVA®. Clinically significant hypersensitivity, hypocalcemia, osteonecrosis of the jaw, atypical femoral fracture, multiple vertebral fractures following the discontinuation of Prolia® treatment, serious infections, dermatologic adverse reactions, musculoskeletal pain, and suppression of bone turnover have been reported in patients receiving Prolia®. Prolia® may cause fetal harm. It is not known whether Prolia® is excreted in human milk.

Please see additional Important Safety Information below, as well as Prescribing Information.

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If you have a clinical inquiry or would like to report an adverse event related to Prolia®, please visit www.amgen.com.

Learn about the largest and longest study of fracture risk among women receiving AI therapy for nonmetastatic breast cancer3

Learn about the largest and longest study of fracture risk among women receiving AI therapy for nonmetastatic breast cancer3

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A phase III study evaluated fracture risk in over 3400 women with nonmetastatic breast cancer3

The Adjuvant Denosumab in Breast Cancer (ABCSG-18) trial: The largest study and longest follow-up evaluating fracture risk in postmenopausal* women receiving AI therapy for nonmetastatic breast cancer3

: ABCSG-18 Study Design Schematic.

Primary Endpoint

  • Time to first clinical fracture† 

Bone-related Secondary Endpoints

  • Percentage change in BMD in the total lumbar spine, total hip, and femoral neck from baseline to 36 months
  • Incidence of new vertebral fractures from baseline to 36 months
  • Incidence of new or worsening of pre-existing vertebral fractures from baseline to 36 months

Exploratory Endpoints

  • Percentage change in BMD in the total lumbar spine, total hip, and femoral neck from baseline to 12 and 24 months
  • Incidence of new vertebral fractures from baseline to 12 and 24 months
  • Incidence of new or worsening of vertebral fractures from baseline to 12 and 24 months

*Women were considered postmenopausal if they had a bilateral oophorectomy, were 60 years old, or were < 60 years old but had follicle-stimulating hormone (FSH) and estradiol levels in the postmenopausal range.3

†Clinically evident fractures—excluding the skull, face, fingers, and toes—with associated symptoms.3

ABCSG-18 was the first major study to evaluate high-risk postmenopausal women with a wide range of baseline characteristics, including T-scores, age, and tumor grades3

Baseline demographics between treatment groups3

Placebo every 6
months (n = 1709)
Prolia® 60 mg every
6 months (n = 1711)
Age group (years)
< 50 31 (2%) 34 (2%)
50-59 448 (26%) 473 (28%)
60-69 755 (44%) 782 (46%)
70-79 414 (24%) 372 (22%)
80 61 (4%) 50 (3%)
Tumor grade
G1 338 (20%) 365 (21%)
G2/Gx 1028 (60%) 1038 (61%)
G3 339 (20%) 303 (18%)
Unknown 4 (< 1%) 5 (< 1%)
Chemotherapy before randomization
None 1287 (75%) 1288 (75%)
Adjuvant 329 (19%) 338 (20%)
Neoadjuvant 93 (5%) 85 (5%)
Start of AI treatment
With denosumab/placebo 269 (16%) 270 (16%)
Before denosumab/placebo 1440 (84%) 1441 (84%)
Total lumbar spine BMD
T-score < -1.0 775 (45%) 773 (45%)
T-score -1.0 934 (55%) 938 (55%)

‡The protocol allowed administration of AI for up to 2 years prior to randomization. Median duration of AI therapy before randomization in 2881 patients was 1 month.3

Prolia® was proven to reduce fracture risk by half vs placebo (Primary Endpoint)3

Prolia® was proven to reduce fracture risk by half vs placebo (Primary Endpoint)3

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In women with nonmetastatic breast cancer being treated with an AI, Prolia® delayed the time to first clinical fracture by 50% compared to placebo3

Percentage risk of fracture based on Kaplan-Meier time-to-event analysis within each treatment group at 6-month intervals3

Percentage risk of fracture based on Kaplan-Meier time-to-event analysis within each treatment group at 6-month intervals. See reference below

The hazard ratio and p value were calculated from a Cox model including treatment groups as the independent variable and stratified by the randomization stratification factors. Error bars are 95% confidence intervals.

Prolia® reduced first clinical fracture rate at 7 years3

  • 11.1% in the Prolia® group vs 26.2% in the placebo group

Secondary Endpoints: Prolia® significantly reduced the incidence of new vertebral fractures3

Incidence of vertebral fractures at 36 months. See reference below

New vertebral fracture at 36 months

Incidence of vertebral fractures at 36 months. See reference below
Incidence of vertebral fractures at 36 months. See reference below

Prolia® was proven to increase BMD over time (Secondary and Exploratory Endpoints)3

Prolia® increased BMD over time (Secondary and Exploratory Endpoints)3

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Continued use of Prolia® was shown to significantly increase BMD in the lumbar spine, total hip, and femoral neck over a 3-year period in breast cancer patients taking AI therapy3

Mean recorded percentage changes in bone mineral density at total lumbar spine, total hip, and femoral neck for each treatment group at 12, 24, and 36 months3,*

BMD at Lumbar Spine, Total Hip, and Femoral Neck
BMD at Lumbar Spine, Total Hip, and Femoral Neck
BMD at Lumbar Spine, Total Hip, and Femoral Neck

Overall BMD increases observed in this study are consistent with the results in the pivotal trial in breast cancer patients on AI therapy3,4

*The pivotal trial in breast cancer patients on AI therapy demonstrated an increased difference in BMD from baseline at 12 months in lumbar spine (primary endpoint) and 24 months in lumbar spine, total hip, and femoral neck (exploratory endpoints) vs placebo.4

In the ABCSG-18 study, the incidence of adverse events or serious adverse events in the Prolia® and placebo groups were similar3

In the ABCSG-18 study, the incidence of adverse events or serious adverse events in the Prolia® and placebo groups were similar3

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All adverse events that occurred in more than 5% of all patients3

Adverse Events

Placebo every 6 months
[n = 1690]
Prolia® 60 mg every 6 months
[n = 1709]
Musculoskeletal and connective tissue disorders 801 (47%) 832 (49%)
Arthralgia 437 (26%) 435 (26%)
Back pain 145 (9%) 151 (9%)
Bone pain 110 (7%) 137 (8%)
Pain in extremity 85 (5%) 106 (6%)
Vascular disorders 394 (23%) 472 (28%)
Hot flush 230 (14%) 263 (15%)
Hypertension 93 (6%) 111 (7%)
General disorders and administration site conditions 244 (14%) 277 (16%)
Fatigue 98 (6%) 108 (6%)
Atypical fracture 0 0
ONJ* 0 0

*During the trial period, all potential cases of osteonecrosis of the jaw (ONJ) were adjudicated by an independent international expert panel. Thirty-one dental problems were assessed, but none were determined to meet the diagnostic criteria of ONJ.3

Serious adverse events included musculoskeletal and connective tissue disorders (eg, osteoarthritis, intervertebral disc protrusion); injury, poisoning, and procedural complications (eg, meniscus injury); nervous system disorders (eg, carpal tunnel syndrome); eye disorders (eg, cataract); and endocrine disorders (eg, goiter)3

warning message

If you have a clinical inquiry or would like to report an adverse event related to Prolia®, please visit www.amgen.com.

What dosing schedule should you follow for patients on Prolia®?

Prolia® is the only FDA-approved therapy for cancer treatment–induced bone loss (CTIBL) due to hormone ablation therapy (CTIBL-HALT).1

Be confident your Prolia® patients are receiving 6 months of therapy with each injection1

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Single-use prefilled 1 mL syringe

Single-use prefilled 1 mL syringe

The image above is for illustration purposes only and represents a snapshot in time. Actual dosing and duration of a particular patient's therapy should be based upon the product's approved labeling and the independent clinical decision of the provider.

Important Safety Information

Following discontinuation of Prolia® treatment, fracture risk increases, including the risk of multiple vertebral fractures. Evaluate an individual's benefit/risk before initiating treatment with Prolia®. If Prolia® treatment is discontinued, consider transitioning to an alternative antiresorptive therapy.

Prolia® is administered as 1 shot every 6 months1

  • 60 mg subcutaneous injection in the upper arm, upper thigh, or abdomen by a healthcare professional
    • – Pre-existing hypocalcemia must be corrected prior to initiating therapy with Prolia®
    • – Adequately supplement all patients with calcium and vitamin D
    • – Multiple vertebral fractures have been reported following Prolia® discontinuation
  • As a subcutaneous injection, Prolia® does not undergo first-pass metabolism8,9
  • May lessen patient pill burden

IMPORTANT SAFETY INFORMATION

Contraindications: Prolia® is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating Prolia®. Prolia® is contraindicated in women who are pregnant and may cause fetal harm. In women of reproductive potential, pregnancy testing should be performed prior to initiating treatment with Prolia®. Prolia® is contraindicated in patients with a history of systemic hypersensitivity to any component of the product. Reactions have included anaphylaxis, facial swelling and urticaria.

Same Active Ingredient: Prolia® contains the same active ingredient (denosumab) found in XGEVA®. Patients receiving Prolia® should not receive XGEVA®.

Hypersensitivity: Clinically significant hypersensitivity including anaphylaxis has been reported with Prolia®. Symptoms have included hypotension, dyspnea, throat tightness, facial and upper airway edema, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of Prolia®.

Hypocalcemia: Hypocalcemia may worsen with the use of Prolia®, especially in patients with severe renal impairment. In patients predisposed to hypocalcemia and disturbances of mineral metabolism, including treatment with other calcium-lowering drugs, clinical monitoring of calcium and mineral levels is highly recommended within 14 days of Prolia® injection. Concomitant use of calcimimetic drugs may worsen hypocalcemia risk and serum calcium should be closely monitored. Adequately supplement all patients with calcium and vitamin D.

Osteonecrosis of the Jaw (ONJ): ONJ, which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients receiving Prolia®. An oral exam should be performed by the prescriber prior to initiation of Prolia®. A dental examination with appropriate preventive dentistry is recommended prior to treatment in patients with risk factors for ONJ such as invasive dental procedures, diagnosis of cancer, concomitant therapies (e.g., chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid disorders. Good oral hygiene practices should be maintained during treatment with Prolia®. The risk of ONJ may increase with duration of exposure to Prolia®.

For patients requiring invasive dental procedures, clinical judgment should guide the management plan of each patient. Patients who are suspected of having or who develop ONJ should receive care by a dentist or an oral surgeon. Extensive dental surgery to treat ONJ may exacerbate the condition. Discontinuation of Prolia® should be considered based on individual benefit-risk assessment.

Atypical Femoral Fractures: Atypical low-energy, or low trauma fractures of the shaft have been reported in patients receiving Prolia®. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with antiresorptive agents.

During Prolia® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be evaluated to rule out an incomplete femur fracture. Interruption of Prolia® therapy should be considered, pending a risk/benefit assessment, on an individual basis.

Multiple Vertebral Fractures (MVF) Following Discontinuation of Prolia® Treatment: Following discontinuation of Prolia® treatment, fracture risk increases, including the risk of multiple vertebral fractures. New vertebral fractures occurred as early as 7 months (on average 19 months) after the last dose of Prolia®. Prior vertebral fracture was a predictor of multiple vertebral fractures after Prolia® discontinuation. Evaluate an individual's benefit/risk before initiating treatment with Prolia®. If Prolia® treatment is discontinued, consider transitioning to an alternative antiresorptive therapy.

Serious Infections: In a clinical trial (N=7808) in women with postmenopausal osteoporosis, serious infections leading to hospitalization were reported more frequently in the Prolia® group than in the placebo group. Serious skin infections, as well as infections of the abdomen, urinary tract and ear were more frequent in patients treated with Prolia®.

Endocarditis was also reported more frequently in Prolia®-treated patients. The incidence of opportunistic infections and the overall incidence of infections were similar between the treatment groups. Advise patients to seek prompt medical attention if they develop signs or symptoms of severe infection, including cellulitis.

Patients on concomitant immunosuppressant agents or with impaired immune systems may be at increased risk for serious infections. In patients who develop serious infections while on Prolia®, prescribers should assess the need for continued Prolia® therapy.

Dermatologic Adverse Reactions: In the same clinical trial in women with postmenopausal osteoporosis, epidermal and dermal adverse events such as dermatitis, eczema and rashes occurred at a significantly higher rate with Prolia® compared to placebo. Most of these events were not specific to the injection site. Consider discontinuing Prolia® if severe symptoms develop.

Musculoskeletal Pain: Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking Prolia®. Consider discontinuing use if severe symptoms develop.

Suppression of Bone Turnover: In clinical trials in women with postmenopausal osteoporosis, Prolia® resulted in significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry. The significance of these findings and the effect of long-term treatment are unknown. Monitor patients for these consequences, including ONJ, atypical fractures, and delayed fracture healing.

Adverse Reactions: The most common adverse reactions (>5% and more common than placebo) in women with postmenopausal osteoporosis are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. The most common adverse reactions (>5% and more common than placebo) in men with osteoporosis are back pain, arthralgia, and nasopharyngitis. Pancreatitis has been reported with Prolia®.

In women with postmenopausal osteoporosis, the overall incidence of new malignancies was 4.3% in the placebo group and 4.8% in the Prolia® group. In men with osteoporosis, new malignancies were reported in no patients in the placebo group and 4 (3.3%) patients in the Prolia® group. A causal relationship to drug exposure has not been established.

The most common adverse reactions (>3% and more common than active-control group) in patients with glucocorticoid-induced osteoporosis are back pain, hypertension, bronchitis, and headache.

The most common (per patient incidence 10%) adverse reactions reported with Prolia® in patients with bone loss receiving ADT for prostate cancer or adjuvant AI therapy for breast cancer are arthralgia and back pain. Pain in extremity and musculoskeletal pain have also been reported in clinical trials. Additionally, in Prolia®-treated men with nonmetastatic prostate cancer receiving ADT, a greater incidence of cataracts was observed.

Denosumab is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity.

Please see Prolia® full Prescribing Information, including Medication Guide

IMPORTANT SAFETY INFORMATION
Contraindications: Prolia® is contraindicated in patients with hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating Prolia®. Prolia® is contraindicated in women who are pregnant and may cause fetal harm. In women of reproductive potential, pregnancy testing should be performed prior to initiating treatment with Prolia®. Prolia® is contraindicated in patients with
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References: 1. Prolia® (denosumab) prescribing information, Amgen. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer Version 2.2019, 7/2/19. ©National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 22, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. 3. Gnant M, Pfeiler G, Dubsky PC, et al; on behalf of the Austrian Breast and Colorectal Cancer Study Group. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015;386(9992):433-443. 4. Ellis GK, Bone HG, Chlebowski R, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol. 2008;26:4875-4882. 5. Mincey BA, Duh MS, Thomas SK, et al. Risk of cancer treatment–associated bone loss and fractures among women with breast cancer receiving aromatase inhibitors. Clin Breast Cancer. 2006;7:127-132. 6. Eastell R, Adams JE, Coleman RE, et al. Effect of anastrozole on bone mineral density: 5-year results from the Anastrozole, Tamoxifen, Alone or in Combination Trial 18233230. J Clin Oncol. 2008;26:1051-1058. 7. Eastell R, Hannon RA, Cuzick J, et al, on behalf of the ATAC Trialists’ group. Effect of an aromatase inhibitor on BMD and bone turnover markers: 2-year results of the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial (18233230). J Bone Miner Res. 2006;21:1215-1223. 8. Turner PV, Brabb T, Pekow C, Vasbinder MA. Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci. 2011;50:600-613. 9. Burkiewicz JS, Scarpace SL, Bruce SP. Denosumab in osteoporosis and oncology. Ann Pharmacother. 2009;43:1445-1455.