Inter and Intravariability of BMPs in Commercially Available Demineralized Bone Matrix Products

Background Information: DBMs are commonly employed to augment available bone graft in spinal fusion procedures. Surgeons are presented with an ever-increasing variety of commercially available human Demineralized Bone Matrix product formulations (DBMs) from which to choose. Yet there is limited information on a DBM product’s osteoinductive efficacy, potency, and constancy.

Purpose: To evaluate relative quantities of known osteoinductive proteins among three different production lots of the same manufactured formulation (intra-product potency variability) as well as to compare differences among products (inter-product potency variability).

Methods: Two-step protein extraction procedures were used: 200mg of each DBM formulation was placed in 2ml of 4M guanidine hydrochloride in 0.5M sodium acetate at pH 5.8, 4°C for 7 days. The remaining DBM was extracted with 2ml of 4M GuHCL in 0.5M sodium acetate containing 0.5M EDTA at pH 5.8, 4°C for 7 days. Both protein extracts were dialyzed four times against distilled water at 4°C for 48 hours. The amount of BMP-2, BMP-4, and BMP-7 was determined using ELISA.

Results: The variability among different lots of the same DBM formulation (intra-product potency variability) was greater than the variability among different DBM product formulations (BMP-2 p<01 , BMP7 p<0.001). The amount of BMP-4 was undetectable. extraction efficiency BMP-2 and BMP-7 85-99%.

Conclusions: This in vitro assay suggests that there is greater variability in relative osteoinductive potency, as per quantities of BMPs, among three lots of a single DBM preparation than among different DBM product formulations. This variability undermines potential reliability that is fundamental to constancy and necessitates that a potency assay be completed for each production lot of DBM prior to human implantation.