Table 3. The Effect of Prolia on the Incidence of Nonvertebral Fractures at Year 3 *
Event rates based on Kaplan-Meier estimates at 3 years.
†
Excluding those of the vertebrae (cervical, thoracic, and lumbar), skull, facial, mandible, metacarpus, and finger and toe phalanges.
‡
p-value = 0.01. 
 Proportion of Women With Fracture (%)* Absolute Risk Reduction (%)

(95% CI)  Relative Risk Reduction (%)

(95% CI) 
 Placebo

N = 3906

(%)  Prolia

N = 3902

(%) 
Nonvertebral fracture†  8.0 6.5 1.5 (0.3, 2.7) 20 (5, 33)‡ 

Effect on Bone Mineral Density (BMD)
Treatment with Prolia significantly increased BMD at all anatomic sites measured at 3 years. The treatment differences in BMD at 3 years were 8.8% at the lumbar spine, 6.4% at the total hip, and 5.2% at the femoral neck. Consistent effects on BMD were observed at the lumbar spine, regardless of baseline age, race, weight/body mass index (BMI), baseline BMD, and level of bone turnover.

After Prolia discontinuation, BMD returned to approximately baseline levels within 12 months.

Bone Histology and Histomorphometry
A total of 115 transiliac crest bone biopsy specimens were obtained from 92 postmenopausal women with osteoporosis at either month 24 and/or month 36 (53 specimens in Prolia group, 62 specimens in placebo group). Of the biopsies obtained, 115 (100%) were adequate for qualitative histology and 7 (6%) were adequate for full quantitative histomorphometry assessment.

Qualitative histology assessments showed normal architecture and quality with no evidence of mineralization defects, woven bone, or marrow fibrosis in patients treated with Prolia.

The presence of double tetracycline labeling in a biopsy specimen provides an indication of active bone remodeling, while the absence of tetracycline label suggests suppressed bone formation. In subjects treated with Prolia, 35% had no tetracycline label present at the month 24 biopsy and 38% had no tetracycline label present at the month 36 biopsy, while 100% of placebo-treated patients had double label present at both time points. When compared to placebo, treatment with Prolia resulted in virtually absent activation frequency and markedly reduced bone formation rates. However, the long-term consequences of this degree of suppression of bone remodeling are unknown.

16 HOW SUPPLIED/STORAGE AND HANDLING
Prolia is supplied in a single-use prefilled syringe with a safety guard or in a single-use vial. The grey needle cap on the single-use prefilled syringe contains dry natural rubber (a derivative of latex).

60 mg/1 mL in a single-use prefilled syringe 1 per carton NDC 55513-710-01
60 mg/1 mL in a single-use vial 1 per carton NDC 55513-720-01

Store Prolia in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton. Do not freeze. Prior to administration, Prolia may be allowed to reach room temperature (up to 25°C/77°F) in the original container. Once removed from the refrigerator, Prolia must not be exposed to temperatures above 25°C/77°F and must be used within 14 days. If not used within the 14 days, Prolia should be discarded. Do not use Prolia after the expiry date printed on the label.

Protect Prolia from direct light and heat.

Avoid vigorous shaking of Prolia.

17 PATIENT COUNSELING INFORM