1 in 2 Women Over the Age of 50 Will Have a Fracture Related to Osteoporosis in Their Lifetime1

Osteoporotic fracture in postmenopausal women is a significant public health issue.1

Estimated Yearly Incidence of Osteoporotic Fractures and Other Serious Conditions2-5

Only 24% of women who suffered an osteoporotic fracture received treatment during the following year.6**

In women, a prior osteoporotic fracture increases the relative risk of a subsequent hip fracture by 77%.7††

** Fracture sites: hip, vertebrae, or wrist. Data are drawn from a retrospective database study from 7 health maintenance organizations.
†† Compared to women without a prior fracture.

The Risk of Fracture Increases Substantially with Advanced Age8

Incidence of Fracture with Age8

Adapted from Harvey N, et al. In: Rosen CJ, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 7th ed. Washington, DC: American Society for Bone and Mineral Research; 2008:198-203.

In a separate study estimating the 10-year probability of osteoporotic fracture, the risk of hip fracture was tripled in women aged 75 compared with women at 65 years of age.9

Prolia® (denosumab) may be an appropriate treatment option for patients with postmenopausal osteoporosis at high risk for fracture, including those with:10

  • A history of osteoporotic fracture
  • Multiple risk factors for fracture, where advanced age may be one of the risk factors

Indications

Prolia® (denosumab) 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, nonvertebral, and hip fractures.

Prolia® is indicated for treatment to increase bone mass in men 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.

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. 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, pruritis, 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, clinical monitoring of calcium and mineral levels is highly recommended. 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 should be considered prior to treatment in patients with risk factors for ONJ. Good oral hygiene practices should be maintained during treatment with 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 anti-resorptive 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.

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

Prolia® Postmarketing Active Safety Surveillance Program: The surveillance program is available to collect information from prescribers on specific adverse events. Please see www.proliasafety.com or call 1-800-772-6436 for more information.

References

1. US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: Department of Health and Human Services, Office of the Surgeon General; 2004. 2. Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22:465-475. 3. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics 2012 update: a report from the American Heart Association. Circulation. 2012;125:e2-220. 4. American Cancer Society. Cancer Facts & Figures 2012. Atlanta: American Cancer Society; 2012. 5. Watts NB, Bilezikian JP, Camacho PM, et al. 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. 6. Andrade SE, Majumdar SR, Chan KA, et al. Low frequency of treatment of osteoporosis among postmenopausal women following a fracture. Arch Intern Med. 2003;163:2052-2057. 7. Kanis JA, Johnell O, De Laet C, et al. A meta-analysis of previous fracture and subsequent fracture risk. Bone. 2004; 35:375 382. 8. Harvey N, Dennison E, Cooper C. Epidemiology of osteoporotic fractures. In: Rosen CJ, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 7th ed. Washington, DC: American Society for Bone and Mineral Research; 2008:198-203. 9. Kanis JA, Johnell O, Oden A, Dawson A, De Laet C, Jonsson B. Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int. 2001;12:989-995. 10. Prolia® (denosumab) prescribing information, Amgen.
Indication

Prolia® (denosumab) is indicated for:

  • 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.
Important Safety Information

Prolia® (denosumab) is contraindicated in patients with hypocalcemia, women who are pregnant, and patients with a history of systemic hypersensitivity to any component of the product. Patients receiving Prolia® should not receive XGEVA®. Clinically significant hypersensitivity including anaphylaxis has been reported with Prolia®. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of Prolia®. Hypocalcemia may worsen with the use of Prolia®, especially in patients with severe renal impairment. Adequately supplement all patients with calcium and vitamin D. Serious infections leading to hospitalization, dermatologic adverse reactions, ONJ, and atypical femoral fractures have been reported in patients receiving Prolia®. Monitor for consequences of suppression of bone turnover.



1 in 2 Women Over the Age of 50 Will Have a Fracture Related to Osteoporosis in Their Lifetime1

Osteoporotic fracture in postmenopausal women is a significant public health issue.1

Estimated Yearly Incidence of Osteoporotic Fractures and Other Serious Conditions2-5

Only 24% of women who suffered an osteoporotic fracture received treatment during the following year.6**

In women, a prior osteoporotic fracture increases the relative risk of a subsequent hip fracture by 77%.7††

** Fracture sites: hip, vertebrae, or wrist. Data are drawn from a retrospective database study from 7 health maintenance organizations.
†† Compared to women without a prior fracture.

The Risk of Fracture Increases Substantially with Advanced Age8

Incidence of Fracture with Age8

Adapted from Harvey N, et al. In: Rosen CJ, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 7th ed. Washington, DC: American Society for Bone and Mineral Research; 2008:198-203.

In a separate study estimating the 10-year probability of osteoporotic fracture, the risk of hip fracture was tripled in women aged 75 compared with women at 65 years of age.9

Prolia® (denosumab) may be an appropriate treatment option for patients with postmenopausal osteoporosis at high risk for fracture, including those with:10

  • A history of osteoporotic fracture
  • Multiple risk factors for fracture, where advanced age may be one of the risk factors

Indications

Prolia® (denosumab) 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, nonvertebral, and hip fractures.

Prolia® is indicated for treatment to increase bone mass in men 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.

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. 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, pruritis, 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, clinical monitoring of calcium and mineral levels is highly recommended. 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 should be considered prior to treatment in patients with risk factors for ONJ. Good oral hygiene practices should be maintained during treatment with 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 anti-resorptive 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.

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

Prolia® Postmarketing Active Safety Surveillance Program: The surveillance program is available to collect information from prescribers on specific adverse events. Please see www.proliasafety.com or call 1-800-772-6436 for more information.

References

1. US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: Department of Health and Human Services, Office of the Surgeon General; 2004. 2. Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22:465-475. 3. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics 2012 update: a report from the American Heart Association. Circulation. 2012;125:e2-220. 4. American Cancer Society. Cancer Facts & Figures 2012. Atlanta: American Cancer Society; 2012. 5. Watts NB, Bilezikian JP, Camacho PM, et al. 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. 6. Andrade SE, Majumdar SR, Chan KA, et al. Low frequency of treatment of osteoporosis among postmenopausal women following a fracture. Arch Intern Med. 2003;163:2052-2057. 7. Kanis JA, Johnell O, De Laet C, et al. A meta-analysis of previous fracture and subsequent fracture risk. Bone. 2004; 35:375 382. 8. Harvey N, Dennison E, Cooper C. Epidemiology of osteoporotic fractures. In: Rosen CJ, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 7th ed. Washington, DC: American Society for Bone and Mineral Research; 2008:198-203. 9. Kanis JA, Johnell O, Oden A, Dawson A, De Laet C, Jonsson B. Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int. 2001;12:989-995. 10. Prolia® (denosumab) prescribing information, Amgen.