Changes of Bone Turnover Markers in Long Bone Nonunions Treated with a Regenerative Approach

Abstract

In this clinical trial, we investigated if biochemical bone turnover markers (BTM) changed according to the progression of bone healing induced by autologous expanded MSC combined with a biphasic calcium phosphate in patients with delayed union or nonunion of long bone fractures. Bone formation markers, bone resorption markers, and osteoclast regulatory proteins were measured by enzymatic immunoassay before surgery and after 6, 12, and 24 weeks. A satisfactory bone healing was obtained in 23 out of 24 patients. Nine subjects reached a good consolidation already at 12 weeks, and they were considered as the “early consolidation” group. We found that bone-specific alkaline phosphatase (BAP), C-terminal propeptide of type I procollagen (PICP), and beta crosslaps collagen (CTX) changed after the regenerative treatment, BAP and CTX correlated to the imaging results collected at 12 and 24 weeks, and BAP variation along the healing course differed in patients who had an “early consolidation.” A remarkable decrease in BAP and PICP was observed at all time points in a single patient who experienced a treatment failure, but the predictive value of BTM changes cannot be determined. Our findings suggest that BTM are promising tools for monitoring cell therapy efficacy in bone nonunions, but studies with larger patient numbers are required to confirm these preliminary results.

Serial Monitoring of Serum Bone Specific Alkaline Phosphatase (Bap) Levels Following Intramedullary Fixation of Tibial Shaft Fractures

“…Levels reached baseline by 24 weeks. Further a remarkable decrease in BAP was observed at all time points in a single patient who experienced atreatment failure (Granchi et al, 2017).…”

“…BAP is found in the plasma membrane of osteoblasts (Gothlin and Ericsson, 1973). A crossreactivity of approximately 15% between liver and bone ALP can affect measurements in individuals with high liver ALP (Granchi et al, 2017). Patients with liver disease or deranged liver function tests were excluded from the study.…”

Chondrogenic and BMP-4 primings confer osteogenesis potential to human cord blood mesenchymal stromal cells delivered with biphasic calcium phosphate ceramics

“…Interestingly, it was observed that MSX2, which has been shown to suppress ALP transcription at the promoter level and to antagonize osteoblast differentiation 32,33 , was up-regulated in CBMSCs compared www.nature.com/scientificreports/ www.nature.com/scientificreports/ to BMSCs. Since ALP has been shown to be a marker of bone healing in patients 7 , this may represent an important difference between the two MSC sources in terms of their osteogenesis. Intriguingly, CBMSC ALP gene expression was rescued by chondrogenic priming and in vitro culture on BCP biomaterial.…”

Bioceramics and bone healing

“…This strategy is particularly suited to complex skeletal injuries lacking sufficient osteogenic potential. Although significant progress has been made in this field in recent years and several clinical studies are under way both in Europe and the United States, 76 a better understanding of the role of each of the components and the interactions amongst them remains to be reached. In particular, the development of scaffolds that are able not only to support cell attachment and growth, but to also provide the adequate temporary niche to the cells and instruct them in the right direction, may represent a significant step forward for the efficacy of this therapeutic approach.…”