Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis

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. [1] 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. [2]

Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis [2]
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)

Duration Two years
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 ±

7.5

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)†
Body-mass index¶ 25.36±4.42 25.46±4.41
Bone mineral density T score
Lumbar spine –2.99±1.24 –2.94±1.25
Total hip –2.81±0.67 –2.78±0.68
Femoral neck –2.90±0.50 –2.89±0.49
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)

 

1,969 (96.2)

 

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)
FRAX score††

Median serum β-CTX (IQR) — ng/liter‡‡

20.0±10.1

230.0 (137.0–388.0)

20.2±10.2

2,76.0 (166.0–407.0)

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.

References

[1] Osteoporosis. American College of Rheumatology. https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Osteoporosis. March 2017. Accessed October 16, 2017.

[2] 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.

 

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