Bisphosphonates’ implementation in trauma management: a method of bone healing facilitation

This issue seems acute as despite new achievements in surgical technique and implementation of new implants for bone and joint surgery, the percentage of nonunion remains high. The association between bone healing andenvironmental factors, sedentary lifestyle, imbalanced diet is well established and has been demonstrated in a number of previous studies [1, 2]. As a result, new methods of bone healing both surgical and pharmacological are necessary to improve the current situation [2, 3]. At the present time there are several ways for bone healing facilitation: active forms of Calcium with Ergocalciferol, Platelet-rich blood plasma (PRP), ultrasonic shockwave therapy and many others [3, 4, 5]. Every method has its own advantages alongside with disadvantages. The application of bisphosphonates (BP) for bone healing has not been completely examined in clinical practice yet. On the other hand, the biological activity of bisphosphonates is well established and fairly predictable which is particularly significant for prognosis and management of thethe adverse effects [6, 7]. Experimental researches of BP application for bone healing, performed on animal models, revealed positive clinical results of fracture closure [7].

The objective of the research is to analyse the experimental practice of BP implementation for bone healing facilitation.

Materials and methods . The design of the research is prospective, non-randomized, controlled study. All participants were the patients of both sexes who had undergone surgical treatment at the Orthopedic Departments in the city of Voronezh. The age of the patients was from 21 to 40. All the patients signed informed consent before the beginning of theresearch. The patients were divided in two groups: group I (case) which consisted of the patients receiving BP therapy and group II (control) which consisted of the patients receiving non-BP therapy. Patients of both groups during bone healing process were given Calcemine, a calcium containing drug, in standard doze. The patients of group I were given Alendronic acid in tablets alongside with Calcemine. The blood samples were taken from patients for bone resorption markers: Osteocalcine (OC) and beta-Crosslaps (bCL). The timing for blood sample taking was similar for all the patients for both groups: on day 1 after surgery, a month after surgery and in 3 months after surgery. Meanwhile, patients were asked about compliance and possible adverse effects during all thetime of the Re-search.At the final point all the data has been statistically processed and conclusions were made.

Results. The initial blood sample in both groups had similar results: the blood level of OC and bCL was virtually identical. The level of OC 21,2±1,2 ng/ml in core group and 20,3±0,9 ng/ml in the control one. For bCL the results were 0,71±0,15 ng/l and 0,68± 0,16 ng/l respectively. In-group differences were statistically not significant (p>0,05) . In a month differences started to differ: the level of OC in core and control groups: 30,11±1,2 ng/ml and 24,14 ±1,1 ng/ml. The level of bCL was: 0,78±0,08 ng/l and 0,88±0,05 respectively. In-groups differencies were statistically significant (p<0,05). In three months results were: OCin core and control groups: 27,2±2,2 ng/ml and 21,3±1,8 ng/ml. The level of bCLwas: 0,525±0,07 ng/l and 0,619± 0,05 ng/l respectively. In-groups differencies were statistically significant (p<0,05). The level of OC became higher, what can be explained because of increased bone formation via osteoblastic hyperfunction. Vice versa, the level of bCL became lower beause of osteoblastic suppression, especially in core group. The higher level of OC and lower level of bCLmay be explained with pharmacological effect of Alendronic acid- suppression of bone resorption via osteoclastic apoptosis.

When estimating final results, in control group 4 cases of delayed bone healing were recorded. On the other hand, the core group had no cases of delayed healing. So our team has made a conclusion that elevating of bone healing results could be achieved via moderate suppression of bone resorption. After the Research it may be stated, that the normalization of bone healing can be achieved with bisphosphonates, especially Alendronic acid. During three months of investigation, it was stated that in core group the level of osteocalcin was higher, but the level of betaCrosslaps was lower, which can be a symptom of better growth process in bone tissue. When examining final results, there were no cases of delayed bone healing in core group. So to say, the implementation of Alendronic acid for bone healing may be a good idea to achieve better results in general. However, good trauma management on previous stages remains crucial in all cases.

Conclusion . According to the obtained results, BP admission appears as the effective way of bone healing promotion. Clinical safety of these drugs, which has been approved in rheumatology, poses a possibility of their implementation in Traumatology and Orthopedics. Suppression of osteoclastic apoptosis leads to less bone turnover what accelerates bone healing then. The implementation of BP in different clinical cases, however, remains a topic of further investigations.