. 2016 Apr 13;22(4):284–297. doi: 10.1089/ten.teb.2015.0357

Table 1.

The Adverse Effects of BMP-2 in Clinical and Preclinical Models

Clinical side effects associated with BMP-2
Side effect	Main findings	References
Inflammatory complications	Cervical spine swelling	^{65,69,145–148}
	Seroma formation	^{65,66,149–154}
Radiculopathy	Nerve root compression/postoperative radiculitis	^{48,55,67,152,155–158}
Ectopic bone	Neuroforaminal and soft tissue ectopic bone and bone cyst formation	^48,158–163
Osteoclast activation, osteolysis, and subsidence	Vertebral and nonvertebral bone resorption	^{41,48,55,60,61,156,164–170}
	Graft subsidence	^{41,60,61,166,171}
Urogenital events	Retrograde ejaculation	^76,172–175
	Bladder retention	^172,175
Wound complications	Hematoma	^{9,79,80,146,152,176,177}
	Wound dehiscence	^{9,13,79,152,176}
	Infection	^{9,48,79,80,151,152,16}

Preclinical side effects with BMP-2 (in vitro and in vivo)
Side effect	Main findings	References
Induction of inflammation	Increase in IL-1β, IL-6, IL-10, IL-17, IL-18, TNF-α	^{102,105,123,178–180}
Osteoclast activation	Potentiation of nuclear factor-kβ ligand and induction of RANKL	^{104,181–184}
	Upregulation of PPARγ pathway and repression of Wnt signaling pathways	¹⁸⁵
Induction of adipogenesis and bone cyst formation	Dose-dependent induction of PPARγ expression	^{64,102,178,186–188}

BMP, bone morphogenetic protein-2; IL, interleukin; PPARγ, peroxisome proliferator-activated receptor gamma; RANKL, receptor activator of nuclear kappa-B ligand; TNF-α, tumor necrosis factor-α.