Romosozumab for the treatment of postmenopausal women at high risk of fracture

Figures & data

Figure 1. Simplified schematic representation of sclerostin actions in bone cells. Sclerostin is secreted by osteocytes and binds to LRPs on osteoblasts, thereby inhibiting the Wnt signaling pathway and bone formation by degrading β-catenin. Sclerostin also upregulates RANKL synthesis in the osteocyte, which binds to the RANK receptor on osteoclasts, thereby stimulating osteoclastogenesis. Examples of up-regulators (a) and down-regulators (b) of sclerostin production are shown in the text boxes of the figure. Note the decrease of RANKL production by romosozumab in contrast to the increase by parathyroid hormone [48,52,53].

Table 1. Fracture risk reduction (RR) for VFs, non-VFs, clinical and Hip fractures in the ARCH study [34], which included postmenopausal women with a bone mineral density T score of – 2.5 or less at the total Hip or femoral neck and either one or more moderate or severe vertebral fractures or two or more mild vertebral fractures; or a bone mineral density T score of – 2.0 or less at the total Hip or femoral neck and either two or more moderate or severe vertebral fractures or a fracture of the proximal femur sustained 3–24 months before randomization.

	At 12 months			At 24 months (for VF) At 2.7 years (for other fractures in the primary analysis)
	ALN	ROMO	RR (95%CI) p-value	ALN-ALN	ROMO-ALN	RR (95%CI) p-value
Vertebral fracture	6.3%	4.0%	37% (15 to 53%) p = 0.003	11.9%	6.2%	48% (34 to 60%) p < 0.001
Non-vertebral fracture	4.6%	3.4%	26% (−1 to 46%) p = 0.06	10.6%	8.7%	19% (1 to 34%) p = 0.04
Clinical fracture	5.4%	3.9%	28% (4 to 46%) p < 0.05	13.0%	9.7%	27% (12 to 39%) p < 0.001
Hip fracture				3.2%	2.0%	38% (4 to 46%) p = 0.02

ALN: alendronate

ROMO: romosozumab

Box 1. Drug summary box

Drug name	Romosozumab
Phase	Launched
Indication	Osteoporosis in postmenopausal women at high risk of fracture
Mechanism of action	Sclerostin-inhibiting humanized monoclonal antibody
Route of administration	subcutaneously
Pivotal trials	FRAME: NCT01575834 ARCH: NCT01631214 BRIDGE: NCT02186171 STRUCTURE: NCT01796301

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