The topic of the last two posts (Part One and Part Two) has been the recent publication of three-year milestone data of a clinical study investigating the safety and feasibility of treating lumbar degenerative disc disease with an autologous injection of bone marrow concentrate (BMC). The three-year milestone publication naturally follows the previous publication of the one-year and two-year milestone results. For transparency, I want to mention that I am a co-author on the three publications. I also am not trying to tell physicians how to practice medicine when it comes to the limited, non-surgical options available for treating painful, degenerative disc disease.
Take a look at the two previous posts for background on the clinical study of BMC intra-discal treatment for pain associated with degenerative disc disease. Both Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) were used to track pain and functionality of the patients, so data for both metrics were plotted over the three years in the most recent paper. Figure 1 shows a bar chart of VAS and ODI for all surviving patients over the three-year interval. Both VAS and ODI averaged results of the 20 study subjects remaining active at the three-year milestone were statistically significantly different at all post-treatment time points (3, 6 12, 24 and 36 months) compared to the pre-treatment averaged results.
Where the paper really gets interesting to me, as a scientist, is in the tracking of VAS and ODI with respect to the cellularity of each of the BMC preparations used to treat study subjects’ degenerative disc pathology three-years before. Unlike almost all publications in the orthopedic regenerative medicine area, the Pettine clinical study involved a detailed analysis of each of the BMC samples injected into the patients at time 0. Both CFU-F assays and flow cytometry were performed on an aliquot of each BMC preparation sent to my ex-employer’s research laboratory. Consequently, it was possible to estimate the mesenchymal stem cell (MSC) content from the CFU-F assay and to estimate the number of CD34+ cells present (which is a marker for HSCs, if appropriate negative CD markers are used in the CD marker panel, and they were).
Figures 3a and 3b show the results out to three-years for ODI and VAS for two sub-populations of the surviving patients based on a cutoff of 2,000 CFU-Fs per mL of injectate. I briefly reviewed the origins of the 2,000 CFU-F cutoff in the last post (AABBCC). The patients surviving to three-years who had >2,000 CFU-F/mL of injectate showed a much lower averaged value for both ODI and VAS compared to the patients with <2,000 CFU-F/mL of injectate, which was statistically significantly different between the two sub-populations for both the VAS and ODI metrics. But there was a curious bump in the reported values of both VAS and ODI at the 1-year milestone. My only thought is that the three patients who would progress to a surgical outcome during the second-year of the study were beginning to feel more pain prior to the one-year milestone, but stuck it out into the second-year. Or, since these are small data sets, it just could be a random fluctuation in the data.
The other two panels in Figure 3 show the ODI (Fig. 3c) and VAS (Fig. 3d) results for three levels of CD34+ cells: <1 million CD34+ cells per mL of injectate; 1-2 million CD34+ cells; and >2 million CD34+ cells. I will point out that since there are only 20 patients being tracked over the three-year period, it is possible after dividing them into three sub-populations that one or two patients could have a big impact on the averaged values recorded. But, hey, it was only intended to be a pilot study on treating degenerative disc disease.
I will conclude my review of the three-year milestone clinical outcomes, along with a consideration of the role that a placebo effect could play in the recorded data, in the next post. I wouldn’t lose any sleep over the chance that the results are due to a placebo effect.