Long Buu Huynh, Mercer University College of Pharmacy
Osteoporosis, or “porous bone”, is a bone disease characterized by a loss of bone mass and change in bone structure. There are no symptoms since osteoporosis is a silent condition. Risk factors that can cause osteoporosis are lifestyle choices, certain diseases, medications, and age.  Romosozumab is a medication used to help increase bone formation and decrease bone resorption. Alendronate is classified as an antiresorptive agent and used as first-line therapy for osteoporosis. The aim of this study is to investigate the effectiveness of romosozumab followed by alendronate compared with alendronate alone in postmenopausal women with osteoporosis and a previous fracture. 
|Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis |
|Design||Multicenter, international, randomized, double-blind trial; N= 4,093|
|Objective||To investigate effectiveness between romosozumab and alendronate in reduction of the risk of fracture in women patients with osteoporosis and previous fracture|
|Study Groups||Alendronate (n=2,047); romosozumab (n=2,046)|
|Methods||Women with the use of an interactive voice-response system were assigned randomly in a ratio of 1:1.
Women received monthly romosozumab (210 mg subcutaneously) or received weekly alendronate (70 mg orally) for 12 months.
Inclusion criteria: Ambulatory postmenopausal women (age of 55-90) with (1) a bone mineral density (BMD) T score of -2.5 or less at the tip or femoral neck; or (2) one or more moderate or severe vertebral fractures; or (3) two or more mild vertebral fracture; or (4) BMD T score of -2.0 or less at the total tip or femoral neck; or (5) either two or more or severe vertebral fractures or a proximal femur fracture sustained 3 to 24 month before randomization.
Exclusion criteria: (1) Women who did not meet inclusion criteria; (2) Inability to take alendronate tablets orally or contraindications to alendronate (GFR < 35 mL/1.73 m2 body surface area (BSA)
|Primary Outcome Measure||Cumulative incidence of new vertebral fracture at 24 months and of clinical fracture (non- vertebral and symptomatic vertebral fracture) at the time of the primary analysis|
|Baseline Characteristics||Demographic characteristics of the patients at baseline.*|
|Characteristic||Alendronate (n=2,047) †||Romosozumab (n=2,046) †|
|Age – yr||74.2 ± 7.5||74.4 ±
|Age ≥ 75 yr – no. (%)||1,071 (52.3)||1073 (52.4)|
|Ethnic group – no. (%)‡|
|Hispanic||662 (32.3)||631 (30.8)|
|Non Hispanic||1,385 (67.7)||1,415 (69.2)|
|Geographic region – no. (%)§|
|Central or Eastern Europe or Middle East||798 (39.0)||835 (40.8)|
|Latin America||727 (35.5)||674 (32.9)|
|Western Europe, Australia, Or New Zealand||264 (12.9)||269 (13.1)|
|Asia-pacific or South Africa||216 (10.6)||213 (10.4)|
|North America||42 (2.1)||55 (2.7)|
|Body mass index||25.36 ± 4.42||25.46 ± 4.41|
|Plus–minus values are means ±SD. There were no significant between-group differences at baseline. Percentages may not total 100 because of rounding. β-CTX denotes β-isomer of C-terminal telopeptide of type I collagen, IQR interquartile range, and P1NP procollagen type 1 N-terminal propeptide.
† Shown is the number of patients who were randomly assigned to the 12-month double-blind period of the trial.
‡ Ethnic group was reported by the patient.
§ The countries included within the respective regions are shown in the Supplementary Appendix.
|Results||Clinical characteristics of the patients at baseline|
|Characteristic||Alendronate (n=2,047)†||Romosozumab (n=2,046)†|
|Bone mineral density T score|
|Previous osteoporotic fracture at ≥45 yr of age — no. (%)||2,029 (99.1)||2,022 (98.8)
|Prevalent vertebral fracture — no. (%)||1,964 (95.9)
|Grade of most severe vertebral fracture‖|
|Mild||73 (3.6)||68 (3.3)|
|Moderate||570 (27.8)||532 (26.0)|
|Severe||1,321 (64.5)||1,369 (66.9)|
|Previous nonvertebral fracture at ≥45 yr of age — no. (%)||770 (37.6)||767 (37.5)|
|Previous hip fracture — no. (%)**||179 (8.7)||175 (8.6)|
Median serum β-CTX (IQR) — ng/liter‡‡
|Median serum P1NP (IQR) — μg/liter‡‡||44.7 (32.7–64.4)||50.6 (37.5–64.7)|
|Median 25-hydroxyvitamin D (IQR) — ng/ml||27.6 (24.0–34.2)||28.4 (24.0–34.8)|
|¶ The body-mass index is the weight in kilograms divided by the square of the height in meters.
‖ The grade of the most severe vertebral fracture was assessed with the use of the Genant grading scale (see the Supplementary Appendix).
** Previous hip fracture excludes pathologic or high-trauma hip fracture.
†† The score on the Fracture Risk Assessment Tool (FRAX),2 developed by the World Health Organization (www.shef.ac .uk/frax/), indicates the 10-year probability of major osteoporotic fracture, expressed as a percentage and calculated with bone mineral density.
‡‡ Data shown are for the 266 patients (128 in the alendronate group and 138 in the romosozumab group) who enrolled in the biomarker subs
|Adverse Events||Common Adverse Events|
|12-month double blind period|
|Alendronate (n=2,014)||Romosozumab (n=2,040)|
|Back pain||228 (11.3)||186 (9.1)|
|Nasopharyngitis||218 (10.8)||213 (10.4)|
|Serious Adverse Events|
|Cardiac ischemic event||6 (0.3)||16 (0.8)|
|Cerebrovascular event||7 (0.3)||16 (0.8)|
|Heart failure||8 (0.4)||4 (0.2)|
|Death||12 (0.6)||17 (0.8)|
|Noncoronary revascularization||5 (0.2)||3 (0.1)|
|Peripheral vascular ischemic event not requiring revascularization||2 (< 0.1)||0|
|Percentage that Discontinued due to Adverse Events: N/A|
|Study Author Conclusions||Treatment with romosozumab followed by alendronate in postmenopausal women with osteoporosis of high risk fracture yielded lower risk of fracture significantly than alendronate alone.|
This study demonstrates therapy with romosozumab followed by alendronate significantly reduces the risk of fractures in one year than with alendronate alone in postmenopausal women with osteoporosis. The evidence further demonstrates a reduction in the frequency of hip fractures with romosozumab followed by alendronate in women who have had a previous hip fracture when compared to alendronate therapy alone.
 Osteoporosis. American College of Rheumatology. https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Osteoporosis. March 2017. Accessed October 16, 2017.
 Saag KG, Peterson J, Brandi ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 2017;377:1417-27.